Publications by authors named "Si-Yang Wang"

48 Publications

Metal-Free Photosynthesis of Alkylated Benzimidazo[2,1-]isoquinoline-6(5)-ones and Indolo[2,1-]isoquinolin-6(5)-ones in PEG-200.

J Org Chem 2021 Jul 23;86(13):9055-9066. Epub 2021 Jun 23.

Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.

A visible-light-induced decarboxylation reaction was developed for the synthesis of alkylated benzimidazo[2,1-]isoquinoline-6(5)-ones and indolo[2,1-]isoquinolin-6(5)-ones under metal-free conditions. Impressively, metal catalysts and traditionally volatile organic solvents could be effectively avoided.
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http://dx.doi.org/10.1021/acs.joc.1c01022DOI Listing
July 2021

Identification of Potential Gene and MicroRNA Biomarkers of Acute Kidney Injury.

Biomed Res Int 2021 8;2021:8834578. Epub 2021 Jan 8.

Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China.

Acute kidney injury (AKI) is a disease that seriously endangers human health. At present, AKI lacks effective treatment methods, so it is particularly important to find effective treatment measures and targets. Bioinformatics analysis has become an important method to identify significant processes of disease occurrence and development. In this study, we analyzed the public expression profile with bioinformatics analysis to identify differentially expressed genes (DEGs) in two types of common AKI models (ischemia-reperfusion injury and cisplatin). DEGs were predicted in four commonly used microRNA databases, and it was found that miR-466 and miR-709 may play important roles in AKI. Then, we found key nodes through protein-protein interaction (PPI) network analysis and subnetwork analysis. Finally, by detecting the expression levels in the renal tissues of the two established AKI models, we found that Myc, Mcm5, E2f1, Oip5, Mdm2, E2f8, miR-466, and miR-709 may be important genes and miRNAs in the process of AKI damage repair. The findings of our study reveal some candidate genes, miRNAs, and pathways potentially involved in the molecular mechanisms of AKI. These data improve the current understanding of AKI and provide new insight for AKI research and treatment.
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http://dx.doi.org/10.1155/2021/8834578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810567PMC
May 2021

Method used to establish a large animal model of drug-induced acute kidney injury.

Exp Biol Med (Maywood) 2021 Apr 19;246(8):986-995. Epub 2021 Jan 19.

Department of Nephrology, the First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China.

Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.
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http://dx.doi.org/10.1177/1535370220981756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024500PMC
April 2021

A deep-learning-based prognostic nomogram integrating microscopic digital pathology and macroscopic magnetic resonance images in nasopharyngeal carcinoma: a multi-cohort study.

Ther Adv Med Oncol 2020 14;12:1758835920971416. Epub 2020 Dec 14.

Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, P. R. China.

Background: To explore the prognostic value of radiomics-based and digital pathology-based imaging biomarkers from macroscopic magnetic resonance imaging (MRI) and microscopic whole-slide images for patients with nasopharyngeal carcinoma (NPC).

Methods: We recruited 220 NPC patients and divided them into training ( = 132), internal test ( = 44), and external test ( = 44) cohorts. The primary endpoint was failure-free survival (FFS). Radiomic features were extracted from pretreatment MRI and selected and integrated into a radiomic signature. The histopathological signature was extracted from whole-slide images of biopsy specimens using an end-to-end deep-learning method. Incorporating two signatures and independent clinical factors, a multi-scale nomogram was constructed. We also tested the correlation between the key imaging features and genetic alternations in an independent cohort of 16 patients (biological test cohort).

Results: Both radiomic and histopathologic signatures presented significant associations with treatment failure in the three cohorts (C-index: 0.689-0.779, all  < 0.050). The multi-scale nomogram showed a consistent significant improvement for predicting treatment failure compared with the clinical model in the training (C-index: 0.817 0.730,  < 0.050), internal test (C-index: 0.828 0.602,  < 0.050) and external test (C-index: 0.834 0.679,  < 0.050) cohorts. Furthermore, patients were stratified successfully into two groups with distinguishable prognosis (log-rank  < 0.0010) using our nomogram. We also found that two texture features were related to the genetic alternations of chromatin remodeling pathways in another independent cohort.

Conclusion: The multi-scale imaging features showed a complementary value in prognostic prediction and may improve individualized treatment in NPC.
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http://dx.doi.org/10.1177/1758835920971416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739087PMC
December 2020

Therapeutic effect of intravenous sodium thiosulfate for uremic pruritus in hemodialysis patients.

Ren Fail 2020 Nov;42(1):987-993

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Objectives: This study aimed to compare the efficacy of intravenous sodium thiosulfate (IV STS) with that of loratadine in the treatment of uremic pruritus in hemodialysis (HD) patients.

Methods: This retrospective study included 44 HD patients with pruritus aged over 18 years between June 2018 and January 2020 at the Aerospace Center Hospital of China. Twenty-four HD patients received 3.2 g IV STS treatment three times per week at the end of each HD session for 8 weeks. Twenty HD patients received loratadine (10 mg/day) for 8 weeks. Pruritus intensity was measured using a visual analog scale (VAS) and the detailed pruritus score (DPS) at three time points. The safety of STS was evaluated according to adverse event symptoms and biological variable changes.

Results: There was no significant difference between the STS and loratadine groups in age, sex, characteristics of pruritus, or other clinical variables before treatment. After 8 weeks of treatment, the VAS score (7.07 ± 2.56 and 2.67 ± 2.01) and DPS (30.72 ± 4.81 and 8.04 ± 2.86) decreased significantly in the STS group ( < 0.05). The mean decrease in VAS score (6.89 ± 1.98 and 6.34 ± 2.35) and DPS (28.90 ± 3.24 and 26.92 ± 2.41) in the loratadine group was not statistically significant ( > 0.05). There were no morbidities or mortalities associated with the use of either drug. All biological variables remained stable after therapy.

Conclusions: STS can improve uremic pruritus in HD patients. However, literature on the subject remains lacking. Close monitoring for adverse effects is advised.
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http://dx.doi.org/10.1080/0886022X.2020.1822867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534216PMC
November 2020

Vitamin D affects the neutrophil-to-lymphocyte ratio in patients with type 2 diabetes mellitus.

J Diabetes Investig 2021 Feb 2;12(2):254-265. Epub 2020 Aug 2.

Department of Geriatrics, Shanghai Xuhui Central Hospital, Shanghai, China.

Aims/introduction: Chronic inflammation is an underlying feature of type 2 diabetes mellitus. Hypovitaminosis D is associated with type 2 diabetes mellitus, but whether it contributes to chronic inflammation is unclear. We examined the effects of vitamin D on various immune markers to evaluate its contribution to systemic inflammation in type 2 diabetes mellitus.

Materials And Methods: We retrospectively analyzed data from type 2 diabetes mellitus patients, people with prediabetes and control patients without diabetes (n = 9,746). Demographic and clinical variables were evaluated using descriptive statistics and generalized linear regression. A stratified analysis based on total serum vitamin D was also carried out.

Results: Neutrophil count was a significant predictor of 1,5-anhydroglucitol and glycated hemoglobin (HbA1c) in patients with prediabetes (1,5-anhydroglucitol: β = -0.719, P < 0.001 and HbA1c: β = -0.006, P = 0.002) and patients with diabetes (1,5-anhydroglucitol: β = 0.207, P = 0.004 and HbA1c: β = -0.067, P = 0.010). Lymphocyte count was a significant predictor of HbA1c in patients without diabetes (β = 0.056, P < 0.001) and patients with prediabetes (β = 0.038, P < 0.001). The neutrophil-to-lymphocyte ratio (NLR) was a significant predictor of HbA1c in patients without diabetes (β = -0.001, P = 0.032). No immune markers differed significantly based on vitamin D level among patients without diabetes (P> 0.05 for all). Among patients with prediabetes, those who were vitamin D-deficient had the highest NLR (P = 0.040). Among patients with diabetes, those who were vitamin D-deficient had the highest neutrophil count (P = 0.001), lowest lymphocyte count (P = 0.016) and highest NLR (P < 0.001).

Conclusions: The NLR is strongly influenced by serum vitamin D level. Given the high prevalence of hypovitaminosis D and elevated NLR among chronic disease patients and the elderly, our results suggest that clinical interpretation of NLR as a predictive marker of type 2 diabetes mellitus-related inflammation should consider vitamin D level, age and pre-existing morbidity.
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http://dx.doi.org/10.1111/jdi.13338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858138PMC
February 2021

miRNAs in stem cell-derived extracellular vesicles for acute kidney injury treatment: comprehensive review of preclinical studies.

Stem Cell Res Ther 2019 09 3;10(1):281. Epub 2019 Sep 3.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, 100853, China.

Stem cell therapy has been applied in many fields. Basic and clinical studies on stem cell therapy for acute kidney injury (AKI) have been conducted. Stem cells have been found to exert renal protection through a variety of mechanisms, such as regulating the immune system and secreting growth factors, cytokines, and extracellular vesicles (EVs). Among them, EVs are considered to be important mediators for stem cell protection because they contain various biological components, including microRNAs (miRNAs). miRNAs are a class of small RNAs that function in posttranscriptional gene regulation. A number of studies have confirmed that miRNAs in stem cell-derived EVs can protect from AKI. miRNAs can enter the injured renal tissue through EVs released from stem cells, thereby exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenesis effects on AKI. However, the stem cell sources and AKI models used in these studies have differed. This article will summarize the miRNAs that play a role in kidney protection in stem cell EVs and clarifies the treatment characteristics and mechanisms of different miRNAs. This may provide a reference for clinical practice for acute and chronic kidney diseases.
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http://dx.doi.org/10.1186/s13287-019-1371-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724288PMC
September 2019

Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial.

J Cancer 2019 2;10(14):3214-3223. Epub 2019 Jun 2.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng Road East, Guangzhou 510060, China.

: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. : Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. : A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. : Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.
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http://dx.doi.org/10.7150/jca.30123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603389PMC
June 2019

The prevalence of depression and the association between depression and kidney function and health-related quality of life in elderly patients with chronic kidney disease: a multicenter cross-sectional study.

Clin Interv Aging 2019 15;14:905-913. Epub 2019 May 15.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, People's Republic of China.

The prevalence of depression and the relationship between depression and kidney function and health-related quality of life (HRQOL) are not well understood in elderly patients with predialysis chronic kidney disease (CKD). This study aimed to evaluate the prevalence of depression and the association between depression and kidney function and HRQOL. In this cross-sectional study, 1079 elderly participants with CKD were recruited at 32 clinical centers located within 26 cities throughout 24 provinces in China. Demographic information and laboratory analyses were collected. Symptoms of depression were assessed using the 15-item Geriatric Depression Scale (GDS-15). HRQOL was evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36) instrument. The prevalence of depression was 23.0%. The estimated glomerular filtration rate (eGFR) was negatively correlated with the GDS score whether it was treated as a categorical variable (r=-0.097, =0.001) or as a continuous variable (r=-0.100, =0.001). Marital status, education level, history of CVD and diabetes, CKD stage and proteinuria confirmed to be independent and significant predictors of depression in patients with CKD. Compared with CKD 1-2 patients, we observed an increase of 0.541 and 4.171 in the odds for developing depression in patients CKD 4 (odds ratio [OR] =1.541; =0.031) and CKD 5 (odds ratio [OR] =5.171; <0.001), respectively. We observed negative and significant correlations with the GDS score for the following components: PCS (r=-0.370, <0.001), MCS (r=-0.412, <0.001), burden of kidney disease (r=-0.403, <0.001), symptoms and problems of kidney disease (r=-0.360, <0.001) and effects of kidney disease (r=-0.355, <0.001). Depression was an independent and significant predictor of all the subcomponents of the HRQOL. The prevalence of depression in elderly patients with CKD was high and was negatively correlated with kidney function. Depression had a major negative impact on HRQOL.
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http://dx.doi.org/10.2147/CIA.S203186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526925PMC
September 2019

Methionine restriction delays senescence and suppresses the senescence-associated secretory phenotype in the kidney through endogenous hydrogen sulfide.

Cell Cycle 2019 07 5;18(14):1573-1587. Epub 2019 Jun 5.

a Department of Nephrology, Chinese PLA General Hospital , Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases , Beijing , China.

Aging is a risk factor for various acute and chronic kidney injuries. Kidney aging is accompanied by the secretion of growth factors, proteases, and inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). These factors accelerate the aging process and senescence-associated changes. Delaying kidney senescence may prevent acute and chronic kidney injury. Methionine restriction (MR) was found to be an effective intervention for delaying senescence. However, the mechanism of MR remains unclear. In this study, we investigated the effect of MR on the survival rate and renal aging of C57BL/6 mice and examined the relevant mechanisms. MR increased the survival rate and decreased the levels of senescence markers in the aging kidney. Both in vivo and in vitro, MR upregulated the transsulfuration pathway to increase HS production, downregulated senescence markers and the SASP, and activated AMPK. The ability of MR to delay aging was reduced when AMPK was inhibited. These results suggest that MR may slow animal aging and kidney senescence through HS production and AMPK pathway activation. : DR: diet restriction; MR: methionine restriction; SASP: senescence-associated secretory phenotype; AL: ad libitum; CKD, chronic kidney disease; AKI: acute kidney disease; TSP: transsulfuration pathway; CGL: cystathionine g-lyase; HS: hydrogen sulfide; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; IS: indoxyl sulfate; CC: compound C.
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http://dx.doi.org/10.1080/15384101.2019.1618124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619995PMC
July 2019

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

N Engl J Med 2019 09 31;381(12):1124-1135. Epub 2019 May 31.

From the Departments of Radiation Oncology (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), Medical Oncology (Y.-H.L.), and Nasopharyngeal Carcinoma (H.-Y.M.) and the Clinical Trials Center (Y.G.), Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), and the Department of Radiation Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University (X.-C.W., Q.-F.S.), Guangzhou, the Cancer Center, Tongji Hospital Affiliated to Tongji Medical College (G.-Q.H., G.-X.L.), and the Cancer Center, Union Hospital, Tongji Medical College (K.-Y.Y., J.H.), Huazhong University of Science and Technology, Wuhan, the Department of Radiation Oncology, First People's Hospital of Foshan, Foshan (N.Z., S.-Q.L.), the Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning (X.-D.Z., L.L.), the Department of Head and Neck Oncology, Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital, Guiyang (F.J., J.-H.L.), the Department of Radiation Oncology, XiJing Hospital of Fourth Military Medical University, Xi'an (M.S., J.Z.), the Cancer Center (Z.-B.C.), and the Department of Head and Neck Oncology (S.-Y.W., Q.-D.L.), Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, the Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou (Y.T., L.Z.), the Department of Radiation Oncology, Peking University Cancer Hospital, Beijing (Yan Sun, B.-M.Z.), and the Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang (J.-G.L., Y.X.) - all in China; and the Divisions of Radiation Oncology and Medical Sciences, National Cancer Center Singapore, and the Oncology Academic Program, Duke-National University of Singapore Medical School - both in Singapore (M.L.K.C.).

Background: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.

Methods: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety.

Results: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group.

Conclusions: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).
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http://dx.doi.org/10.1056/NEJMoa1905287DOI Listing
September 2019

Do all patients with advanced N-stage nasopharyngeal carcinoma benefit from the addition of induction chemotherapy to concurrent chemoradiotherapy?

Ther Adv Med Oncol 2019 21;11:1758835919833863. Epub 2019 Mar 21.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, Guangdong Province, China.

Background: The aim of this study was to evaluate the benefits from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in N2-3 nasopharyngeal carcinoma (NPC).

Methods: A total of 3089 patients with nonmetastatic NPC, staged as N2-3 were retrospectively reviewed. IC contained cisplatin (80 mg/m) with 5-fluorouracil (800 mg/m/day over 120 h), or cisplatin (80 mg/m) with docetaxel (80 mg/m), or cisplatin (60 mg/m) with 5-fluorouracil (600 mg/m over 120 h), and docetaxel (60 mg/m) administered at 3-week intervals for two or three cycles. Concurrent chemotherapy consisted of cisplatin (80 or 100 mg/m) given in weeks 1, 4, and 7 of radiotherapy, or cisplatin (40 mg/m) given weekly during radiotherapy. Overall, three well-matched risk groups (low, intermediate, and high risk) were created using propensity score matching, and IC plus CCRT was compared with CCRT in each risk group. Our primary endpoint was distant metastasis-free survival (DMFS).

Results: A nomogram for DMFS was established with good prognostic accuracy (C-index, 0.69; 95% confidence interval, 0.64-0.73). The survival curves for low, intermediate, and high-risk groups stratified by the nomogram were significantly different between all three risk groups, with corresponding 5-year DMFS rates of 90.7%, 79.4%, and 64.9%, respectively ( < 0.001). IC plus CCRT was significantly associated with superior DMFS as compared with CCRT alone (69.5% 56.7%, = 0.004) in the high-risk group. However, no significant difference between IC plus CCRT and CCRT was observed ( = 0.831 and 0.608, respectively) in the intermediate and low-risk groups.

Conclusions: Our findings can help accurately guide the treatment of individual patients with advanced N-stage NPC.
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http://dx.doi.org/10.1177/1758835919833863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431774PMC
March 2019

Phase II Study of a Bi-Weekly Chemotherapy Regimen of Combined Liposomal Paclitaxel and Nedaplatin for the Treatment of Advanced Squamous Cell Lung Cancer.

Transl Oncol 2019 Apr 27;12(4):656-660. Epub 2019 Feb 27.

Department of Medical Oncology, The Fifth Affiliated Hospital of Sun-Yat-Sen University, Zhuhai, Guangdong Province, People's Republic of China. Electronic address:

The platinum-based, two-drug, 3-week regimen is currently the main first-line chemotherapy program for the treatment of advanced squamous cell lung cancer. The aim of this phase II clinical study was to evaluate the efficacy and adverse events of the bi-weekly program of liposomal paclitaxel combined with nedaplatin as a first-line treatment for advanced squamous cell lung cancer. A total of 52 cases of advanced squamous cell lung cancer were included in this phase II clinical trial. Patients received intravenous infusion of liposomal paclitaxel (100 mg/m) and nedaplatin (50 mg/m) on days 1 and 15 of a 4-week cycle. Each patient received two to six cycles of chemotherapy, consistent with the regimen of combined liposomal paclitaxel and nedaplatin. The total effective rate of this chemotherapy program was 37.5%. The median progression-free survival time was 8.5 months (95% confidence interval: 7.8-9.2). The median survival time was 16 months (95% confidence interval: 14.1-17.9). The main adverse event was myelosuppression. Grade 3 leukopenia was noted in seven patients (13.5%), and no grade 4 leukopenia was observed. Grade 3 anemia was noted in four patients (7.7%), and no grade 4 anemia was observed. In addition, no grade 2 or higher thrombocytopenia and no grade 3 or 4 non-bone marrow toxicity was detected. The bi-weekly program of liposomal paclitaxel combined with nedaplatin is effective for the treatment of advanced squamous cell lung cancer, with high safety and few adverse events. However, additional studies are warranted to confirm these results. The trial was registered under the number ChiCTR-OIN-17011423.
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http://dx.doi.org/10.1016/j.tranon.2019.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395851PMC
April 2019

Prognostic value of neutrophil-to-lymphocyte ratio in advanced nasopharyngeal carcinoma: a large institution-based cohort study from an endemic area.

BMC Cancer 2019 Jan 8;19(1):37. Epub 2019 Jan 8.

Department of Radiation Oncology, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, People's Republic of China.

Background: Findings remain unclear whether neutrophil-to-lymphocyte ratio (NLR) detrimentally affects advanced nasopharyngeal carcinoma (NPC) prognosis. We aim to evaluate the prognostic value of NLR in patients with NPC based on a large-scale cohort from an endemic area.

Methods: We selected patients retrospectively from a cohort examining long-term cancer outcomes following diagnosis. Neutrophil counts and lymphocyte counts were assessed prior to treatment. Kaplan-Meier method and log-rank test were used to calculate and compare survival outcomes. Additionally, Cox proportional hazards model was utilized to carry out univariate and multivariate analyses.

Results: Between October 2009 and August 2012, we enrolled 1550 consecutive NPC patients staged II-IVB. The median value of NLR was 2.27 (interquartile range [IQR], 1.71-3.12). Determined by operating characteristic curve using overall survival (OS) as an endpoint, the cutoff value for NLR was 2.50. At 5 years, NLR > 2.50 was associated with inferior OS (90.3% vs 82.5%; P < 0.001), distant metastasis-free survival (DMFS, 89.4% vs 85.0%; P = 0.014), and progression-free survival (PFS, 80.9% vs 76.5%; P = 0.031) than NLR ≤2.50. In multivariate analysis, NLR was found to be a significant prognostic factor for OS (HR, 1.72; 95% CI, 131-2.24; P < 0.001), DMFS (HR, 1.45; 95% CI, 1.10-1.92; P = 0.009), and PFS (HR, 1.29; 95% CI, 1.04-1.59; P = 0.021).

Conclusion: Pretreatment NLR independently affects survival. Our findings suggest that NLR measurements will be of great clinical significance in the management of NPC.
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http://dx.doi.org/10.1186/s12885-018-5236-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325732PMC
January 2019

Survival impact of radiotherapy interruption in nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A big-data intelligence platform-based analysis.

Radiother Oncol 2019 03 14;132:178-187. Epub 2018 Nov 14.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, PR China. Electronic address:

Purpose: To evaluate the effect of radiotherapy interruption (RTI) in patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT).

Patients And Methods: A total of 7826 patients using the well-established big-data intelligence platform were identified. Computer-generated random numbers were used to assign these patients into a training cohort (n = 3913 patients) and an internal validation cohort (n = 3913 patients). RTI was defined as the difference between radiation treatment time and planned radiation time (assuming a Monday start). Survival analysis was performed using the Kaplan-Meier method for survival, and log-rank test to evaluate difference. Optimal RTI threshold was identified using the recursive partitioning analyses (RPAs). Multivariate analysis was performed using the Weibull model. The primary endpoint was overall survival (OS).

Results: The optimal threshold of RTI with respect to OS in the training cohort was 6.5 d based on RPAs. Therefore, a uniform threshold of 7 d (<7 vs. ≥7 d) was selected to classify both training and validation cohorts into high and low RTI groups for survival analysis. RTI of ≥7 d showed significant detrimental effects on OS in both training (5-y OS, 82.4% vs 86.5%; P = 0.001) and validation cohorts (5-y OS, 85.2% vs 86.7%; P = 0.013) than those patients with RTI of <7 d. Consistent with results of the univariate analysis, RTI of ≥7 d was found to be an independent unfavorable prognostic factor for OS in both training (HR, 1.49; 95% CI, 1.14-1.95; P = 0.003) and validation cohort (HR, 1.37; 95% CI, 1.07-1.65; P = 0.031). Subgroup analysis showed that RTI of ≥7 d had significant adverse effects on prognosis of NPC patients receiving IMRT, regardless of TNM stage and chemotherapy (P < 0.05 for all).

Conclusions: In the IMRT era, RTI independently influences survival. Raising RTI ≥ 7 d was consistently unfavorable for NPC survival. Medical practitioners must remind patients on the importance of minimizing RT interruptions.
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http://dx.doi.org/10.1016/j.radonc.2018.10.018DOI Listing
March 2019

Energy restriction in renal protection.

Br J Nutr 2018 11;120(10):1149-1158

Energy restriction (ER) has been widely studied as a novel intervention, and its ability to prolong life has been fully demonstrated. For example, ER can significantly extend the lifespans of model flies, worms, rodents and other mammals. The role of ER in renal protection has also been elucidated. In preclinical studies, adjusting total energy intake or consumption of specific nutrients has prophylactic or therapeutic effects on ageing-related kidney disease and acute and chronic kidney injury. Amino acid restriction has gradually attracted attention. ER mimetics have also been studied in depth. The protective mechanisms of ER and ER mimetics for renal injury include increasing AMP-activated protein kinase and sirtuin type 1 (Sirt1) levels and autophagy and reducing mammalian target of rapamycin, inflammation and oxidative stress. However, the renal protective effect of ER has mostly been investigated in rodent models, and the role of ER in patients cannot be determined due to the lack of large randomised controlled trials. To protect the kidney, the mechanism of ER must be thoroughly researched, and more accurate diet or drug interventions need to be identified.
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http://dx.doi.org/10.1017/S0007114518002684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316363PMC
November 2018

The characteristics and risk factors for cisplatin-induced acute kidney injury in the elderly.

Ther Clin Risk Manag 2018 25;14:1279-1285. Epub 2018 Jul 25.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Disease, Beijing, China,

Objectives: The most serious adverse reaction of cisplatin is acute kidney injury (AKI). Cisplatin-induced acute kidney injury (CIA) has no specific preventive measures. This study aims to explore the characteristics and risk factors for CIA in the elderly and to identify potential methods to reduce CIA.

Materials And Methods: Patients ≥18 years old, with primary tumors, who received initial cisplatin chemotherapy and whose serum creatinine (SCr) values were measured within 2 weeks pre- and postcisplatin treatment and who had complete medical records, were selected from a single center from January 1, 2013 to December 31, 2015. The exclusion criteria included radiotherapy or surgery, recurrent tumors, previous cisplatin treatment, lack of any SCr values before or after cisplatin therapy, and incomplete medical records.

Results: Out of a total of 527 patients, 349 were elderly. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use (9.2%) was more prevalent in the elderly than in younger patients (2.8%, = 0.007). The dosage of cisplatin treatment was lower in the elderly, but the incidence of CIA (9.46%) was higher in the elderly than in younger patients (3.37%). There were significant differences in the SCr levels, estimated glomerular filtration rate, ACEI/ARB use, and whether a single application of cisplatin was administered, between the elderly AKI group and the non-AKI group. Multivariable analysis showed that administration of a single application of cisplatin (OR 2.853, 95% CI: 1.229, 6.621, = 0.015) and ACEI/ARB use (OR 3.398, 95% CI: 1.352, 8.545, = 0.009) were predictive factors for developing CIA in the elderly.

Conclusion: The incidence of CIA in the elderly was higher than in younger patients. ACEI/ ARB usage and administration of a single application of cisplatin were independent risk factors for CIA in the elderly.
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http://dx.doi.org/10.2147/TCRM.S165531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065555PMC
July 2018

Comparing treatment outcomes of concurrent chemoradiotherapy with or without nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma.

Cancer Biol Ther 2018 6;19(12):1102-1107. Epub 2018 Aug 6.

a Department of Radiation Oncology, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy , Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology , Guangzhou , Guangdong Province , P.R. China.

: The benefits of additional use of nimotuzumab (NTZ) in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is largely unclear. We aim to compare LA-NPC treatment outcomes in patients that received CCRT with nimotuzumab (NTZ) to patients that received CCRT only. : Between October 2009 and January 2012, 31 previously untreated and newly diagnosed LA-NPC patients were administered CCRT (3 cycles of 100 mg/m cisplatin every third week with intensity-modulated radiotherapy) plus NTZ according to an IRB-approved institutional research protocol. A well-balanced cohort of 62 patients who received CCRT alone was created by matching each patient who received CCRT plus NTZ via propensity-matched analysis in a 2:1 ratio. : Compared with CCRT only, CCRT plus NTZ was significantly associated with superior overall survival (5-year OS; 96.8% vs. 82.3%; = 0.001), superior distant metastasis-free survival (5-year DMFS; 90.3% vs. 80.6%, = 0.012) and superior progression-free survival (5-year PFS; 83.9% vs. 71.0%, = 0.006). In multivariate analysis, the inclusion of NTZ to CCRT was confirmed to be a favorable factor for OS (HR, 0.31; 95% CI, 0.02-0.71; = 0.027), DMFS (HR, 0.45; 95% CI, 0.13-0.77; = 0.034), and PFS (HR, 0.38; 95% CI, 0.11-0.89; = 0.041). In addition, no significant differences in hematology parameters, dermatitis, nausea, vomiting, xerostomia, nephrotoxicity or neurotoxicity were found between the two arms (all  > 0.05). : The inclusion of NTZ to CCRT is more effective for long-term survival among LA-NPC patients than CCRT only.
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http://dx.doi.org/10.1080/15384047.2018.1491501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301798PMC
August 2018

The detrimental effects of radiotherapy interruption on local control after concurrent chemoradiotherapy for advanced T-stage nasopharyngeal carcinoma: an observational, prospective analysis.

BMC Cancer 2018 Jul 16;18(1):740. Epub 2018 Jul 16.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong Province, People's Republic of China.

Background: Previous studies have reported radiotherapy interruption (RTI) is associated with poor local control in two-dimensional radiotherapy (2DRT) era. However, it remains unclear whether RTI still affects local control for advanced T stage (T3-4) in the intensity-modulated radiation therapy (IMRT) era. We aim to evaluate whether RTI affects local control for T3-4 NPC treated with definitive IMRT.

Methods: In this observational prospective study, 447 T3-4 NPC patients treated with IMRT plus concurrent chemotherapy were included. All patients completed the planned radiotherapy course, and RTI was defined as the actual time taken to finish the prescribed course of radiotherapy minus the planned radiotherapy time. Receiver operating characteristic (ROC) curve was used for determined the cutoff point of RTI. The effects of RTI on local control were analyzed in multivariate analysis.

Results: At 5 years, the local relapse-free survival (LRFS) and overall survival (OS) rates were 93.7 and 85.7%, respectively. The cutoff RTI for LRFS was 5.5 days by ROC curve. Compared to patients with RTI >  5 days, patients with RTI ≤ 5 days had a significantly lower rate of LRFS (97% vs. 83%; P < 0.001). In multivariate analysis, RTI was a risk factor independently associated with LRFS (HR = 9.64, 95% CI, 4.10-22.65), but not for OS (HR = 1.09, 95% CI, 0.84-1.64).

Conclusions: The current analysis demonstrates a significant correlation between prolonged RTI and local control in NPC, even when concurrent chemotherapy is used. We consider that attention to RTI seems to be warranted for patients with advanced T-stage NPC in the era of IMRT.
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http://dx.doi.org/10.1186/s12885-018-4495-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048841PMC
July 2018

Prognostic Value of Circulating Lipoprotein in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

Cell Physiol Biochem 2018 16;48(1):285-292. Epub 2018 Jul 16.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Background/aims: Lipoproteins have been reported to be associated with prognosis in various cancers; however, the prognostic value of lipoproteins in patients with nasopharyngeal carcinoma (NPC) remains largely unknown. We aim to asses the role of circulating lipoproteins in locoregionally advanced NPC patients.

Methods: Between October 2009 and August 2012, a total of 1,081 patients with stage III-IVB NPC were included in the analysis. Circulating high-density lipoprotein (HDL) and low-density lipoprotein (LDL) are the two key lipoproteins, which were measured at baseline. Receiver operating characteristic (ROC) curve analysis was used to evaluate different cut-off points for lipoproteins. Actuarial rates were performed using Kaplan-Meier methods and the log-rank test.

Results: The cutoff points of HDL, LDL, and LDL/HDL ratio were 1.17 mmol/L, 3.75 mmol/L, and 2.73, respectively. At 5 years, high HDL (> 1.17 mmol/L) was significantly associated with better overall survival (OS, 86.6% vs. 78.9%; P=0.004), distant metastasis-free survival (DMFS, 86.9% vs. 80.8%; P=0.004), locoregional relapse-free survival (LRFS, 90.8% vs. 85.4%; P=0.010), and progression-free survival (PFS, 79.1% vs. 70.2%; P= 0.001) than low HDL (≤1.17 mmol/L). In contrast, high LDL (> 3.75 mmol/L) tend to be inferior OS (79.1% vs. 84.9%; P= 0.016) in compassion with low LDL (≤3.75 mmol/L). Likewise, patients with high LDL/HDL ratio (> 2.73) tend to be inferior OS (79.3% vs. 86.9%; P=0.001), DMFS (81.9% vs. 86.5%; P=0.030), and PFS (72.6% vs. 77.8%; P= 0.034) than those of low LDL/HDL ratio (≤2.73). In multivariate analysis, baseline HDL was found to be a significant prognostic factor for LRFS (HR= 0.65; 95% CI, 0.45-0.93; P= 0.019) and PFS (HR=0.75; 95% CI, 0.58-0.98; P= 0.034).

Conclusions: Circulating HDL is significantly associated with treatment outcomes in patients with locoregionally advanced NPC. We suggest that HDL measurements will be of great clinical significance in the management of NPC.
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http://dx.doi.org/10.1159/000491728DOI Listing
September 2018

Dose Escalation of Lobaplatin Concurrent with IMRT for the Treatment of Stage III-IVb NPC: A Phase I Clinical Trial.

Transl Oncol 2018 Aug 29;11(4):1007-1011. Epub 2018 Jun 29.

Department of Medical Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519001, Guangdong Province, PR China. Electronic address:

The maximum tolerated dose (MTD) of lobaplatin as a single agent chemotherapy concurrent with intensity-modulated radiotherapy (IMRT) in Asian population with nasopharyngeal carcinoma (NPC) remains unclear. From June 2016 to December 2017, 17 patients diagnosed with stage III-IVb NPC from an Asian population were prospectively enrolled. Patients were administered lobaplatin with 25-50 mg/m escalation of dosage on day 1. Every 21 days (days 1, 22, and 43) during radiotherapy, cycles were repeated. We administered radiotherapy as 2.12-2.27 Gy per fraction with five daily fractions each week for 6 to 7 weeks. The evaluation of lobaplatin-related toxic effects was based on the Common Terminology Criteria for Adverse Events version 4.0. During the weekly treatment period, complete blood counts and biochemistry were performed. Dose-limiting toxicities (DLTs) were determined by the following events during any cycle in which lobaplatin was administered. Each dose group consisted of at least three cases. We proceeded to the subsequent dose group in the absence of DLT with a dose increment of 5 mg/m until DLT occurred. Periods from 1 week prior to the chemotherapy initiation to 3 weeks after the last chemotherapy were defined as DLT observation periods. MTD was determined by the dose that was immediately below the dose that produced DLT. After analysis, DLT occurred in three patients, including a group with two of three patients in 45 mg/m lobaplatin and another group with one of five patients in 40 mg/m lobaplatin. No grade 3-4 toxicity was observed in patients treated with lobaplatin <40 mg/m. The tumor response rate at 12 weeks after treatment was 100%. In summary, lobaplatin concurrent with IMRT was active in stage III-IVb NPC, and the MTD for the lobaplatin as single-agent chemotherapy was 40 mg/m when combined with IMRT in an Asian population. This trial is registered with ClinicalTrials.gov, number NCT03188497.
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http://dx.doi.org/10.1016/j.tranon.2018.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039884PMC
August 2018

Pentraxin-3 in Thrombolytic Therapy for Acute Ischemic Stroke: No Relation with Curative Effect and Prognosis.

Med Sci Monit 2018 Jun 27;24:4427-4432. Epub 2018 Jun 27.

Stroke Center, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).

BACKGROUND Pentraxin-3 (PTX3) is considered a high quality inflammatory marker of the severity and prognosis of several diseases, however, the value of PTX3 in thrombolytic therapy for acute ischemic stroke remains unclear and PTX3 is still controversial in evaluating the prognosis of stroke patients. In this study, we investigated the association of PTX3 with thrombolytic therapy in patients with acute ischemic stroke. MATERIAL AND METHODS Forty-seven stroke patients who received thrombolytic therapy within 4.5 hours after symptom onset were enrolled consecutively between July 2016 and June 2017. All the patients underwent multiphase CTA (computerized tomography angiography) or CT perfusion before thrombolysis with no indication for endovascular treatment. Initial and 24 hours of National Institute of Health Stroke Scale (NIHSS) scores and serum PTX3 level, stroke risk factors and predictors, and mRS (modified Rankin scale) at 3 months were collected prospectively. Predictors of thrombolytic therapy effect and long-term prognosis were investigated by univariate and multivariate logistic regression. RESULTS The 24 hour NIHSS score and the treatment time was associated with symptom improvement, while the PTX3 level had no association with neurological improvement and prognosis in stroke patients receiving thrombolytic therapy. CONCLUSIONS PTX3 is not suitable to serve as an indicator of thrombolytic efficacy and had no association with long-term prognosis in stroke patients receiving thrombolytic therapy.
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http://dx.doi.org/10.12659/MSM.909015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052828PMC
June 2018

Prognostic value of serum bilirubin in southern Chinese patients with advanced nasopharyngeal carcinoma.

Clin Chim Acta 2018 Sep 31;484:314-319. Epub 2018 May 31.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.. Electronic address:

Background: We evaluated the prognostic value of serum bilirubin in advanced nasopharyngeal carcinoma (NPC) patients.

Methods: Seven-hundred fifty-nine advanced NPC patients treated with definitive chemoradiotherapy were retrospectively analyzed. Serum indirect bilirubin (IBIL) and direct bilirubin (DBIL) were measured before treatment. To evaluate different cutoff points for serum bilirubin, we utilized ROC curves. The Kaplan-Meier method and log-rank test were adopted to calculate and compare survival outcomes. Cox proportional hazard models were used to perform univariate and multivariate analyses.

Results: At 5 y, IBIL >7.15 μmol/l were significantly associated with superior progression-free survival (PFS, 83.6% vs 70.3%; P < .001), overall survival (OS, 88.6% vs 80.5%; P = .012), distant metastasis-free survival (DMFS, 90.3% vs 82.8%; P = .006), and locoregional relapse-free survival (LRFS, 92.1% vs 86.4%; P = .048) than IBIL ≤7.15 μmol/l. Similarly, patients with DBIL >2.65 μmol/l had better prognosis across all outcomes than those of patients with DBIL ≤2.65 μmol/l (all P < .05), except no difference was observed in LRFS (90.5% vs. 87.3%, P = .195). Multivariate analyses showed that IBIL >7.15 μmol/l was an independent protective prognostic factor for PFS (HR, 0.57; 95% CI, 0.40-0.81; P = .002), OS (HR, 0.67; 95% CI, 0.43-0.92; P = .041), and DMFS (HR, 0.63; 95% CI, 0.40-0.98; P = .034); while serum DBIL only remained significant for PFS (HR, 0.63; 95% CI, 0.44-0.89; P = .009).

Conclusions: Pretreatment IBIL and DBIL are potentially independent prognostic factors for patients with advanced NPC.
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http://dx.doi.org/10.1016/j.cca.2018.05.058DOI Listing
September 2018

An enzymatic mechanism for balancing the stoichiometry of nitrogen and phosphorus in a shallow Chinese eutrophic lake.

Sci Total Environ 2018 Jul 7;630:1071-1077. Epub 2018 Mar 7.

Key Laboratory of Algal Biology, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, the Chinese Academy of Sciences, NO.7 Donghu South Road, Wuhan 430072, China. Electronic address:

The over-enrichment of lake waters with nitrogen (N) and phosphorus (P) has become a serious environmental problem, but modes of change in stoichiometry and enzymatic regeneration along trophic gradients are largely unknown. Seasonal variations in the kinetics of extracellular aminopeptidase (LAP) and alkaline phosphatase (AP), together with the composition of phytoplankton and concentrations of N and P, were examined from Jun 2013 to September 2014 in a Chinese shallow lake in which two basins had contrasting trophic states. The turbid basin had a significantly higher concentration of chlorophyll a and lower ratios of N to P. In parallel, the turnover time of organic N mediated by LAP (T) was significantly shorter, and its maximum velocity (V) was significantly higher compared to those in the clear basin. Considering data from both basins, there were linear decreases in N/P and the ratios between dissolved inorganic N and total N with an increasing trophic state index, coupled with a significantly positive relationship between N/P and T. Additionally, with decreasing TN/TP, the Michaelis constant (K) of the AP increased linearly, reducing the efficiency of P regeneration. In contrast, the K value of LAP decreased, and V increased, which enhanced N mineralization by simultaneously increasing the reaction velocity and improving the affinity for substrate. Additionally, the K value of LAP was significantly related to that of AP and the ammonium concentration. Thus, substrate affinity acted as a key factor modifying the pathways of enzymatic degradation of organic N and P according to their stoichiometry in the water column. Phytoplankton composition was directly linked to T. Overall, this study seemed to be the first to connect a stoichiometric shift of N and P with kinetics of extracellular enzymes responsible for their regeneration along trophic gradients, presenting an additional pathway to overcome nitrogen deficiency in eutrophic lakes.
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http://dx.doi.org/10.1016/j.scitotenv.2018.02.297DOI Listing
July 2018

Characteristics of and risk factors for death in elderly patients with acute kidney injury: a multicentre retrospective study in China.

Postgrad Med J 2018 May 7;94(1111):249-253. Epub 2018 Mar 7.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Purpose Of The Study: The incidence of acute kidney injury (AKI) with a poor prognosis in the elderly has been increasing each year. This study aimed to investigate the clinical characteristics of and risk factors for death from AKI in the elderly and help improve prognosis.

Study Design: This study was a retrospective cohort study based on data from adult patients (≥18 years old) admitted to 15 hospitals in China between 1 January 2009 and 31 December 2011. The characteristics of AKI in the elderly were compared with those in younger patients.

Results: In elderly patients with AKI, rates of hypertension, cardiovascular disease and multiple organ dysfunction syndrome (MODS) were higher than in younger patients (44.2% vs 31.2%, 16.1% vs 4.6% and 20.9% vs 16.9%, respectively), the length of ICU stay was longer (3.8 days vs 2.7 days, P=0.019) and renal biopsy (1.0% vs 7.13%, P<0.001) and dialysis (9.6% vs 19.2%, P<0.001) were performed less. Hospital-acquired (HA) AKI was more common than community-acquired (CA) AKI (60.3% vs 39.7%), while the most common cause of AKI was pre-renal (53.5%). Multiple logistic regression analysis showed that age (OR 1.041, 95% CI 1.023 to 1.059), cardiovascular disease (OR 1.980, 95% CI 1.402 to 2.797), cancer (OR 2.302, 95% CI 1.654 to 3.203), MODS (OR 3.023, 95% CI 1.627 to 5.620) and mechanical ventilation (OR 2.408, 95% CI 1.187 to 4.887) were significant risk factors for death.

Conclusions: HA-AKI and pre-renal AKI were more common in the elderly. Age, cardiovascular disease, cancer, MODS and mechanical ventilation were independent risk factors for death in the elderly with AKI.
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http://dx.doi.org/10.1136/postgradmedj-2017-135455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931240PMC
May 2018

The Characteristics and Survival Outcomes in Patients Aged 70 Years and Older with Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era.

Cancer Res Treat 2019 Jan 6;51(1):34-42. Epub 2018 Feb 6.

State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.

Purpose: We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era.

Methods And Materials: From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses.

Results: For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05).

Conclusion: Our findings suggest IMRT +/- chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.
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http://dx.doi.org/10.4143/crt.2017.551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333982PMC
January 2019

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein-Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma.

Chin J Cancer 2017 12 29;36(1):98. Epub 2017 Dec 29.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.

Background: According to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system, over 50% of patients with nasopharyngeal carcinoma (NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node (GTVnd) and pretreatment serum copy number of Epstein-Barr virus (EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.

Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic (ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.

Results: The 5-year distant metastasis-free survival (DMFS) rates for patients with GTVnd > 18.9 vs. ≤ 18.9 mL were 82.2% vs. 93.2% (P < 0.001), and for patients with EBV DNA copy number > 4000 vs. ≤ 4000 copies/mL were 83.5% vs. 93.9% (P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis (both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-, moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1, 87.4, and 73.8%, respectively (P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification (hazard ratio [HR], 4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).

Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.
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http://dx.doi.org/10.1186/s40880-017-0264-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747160PMC
December 2017

Clinical Study of Intracranial and Extracranial Atherosclerotic Stenosis in Spontaneous Intracerebral Hemorrhage Patients.

J Stroke Cerebrovasc Dis 2018 Feb 8;27(2):286-290. Epub 2017 Dec 8.

Stroke Center, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Background And Purpose: Nowadays, researchers had begun to focus on the use of antiplatelet and statins in patients with spontaneous intracerebral hemorrhage (sICH), but atherosclerosis treatment remains uncertain in these patients. We aimed to investigate the incidence and characteristics of intracranial and extracranial atherosclerotic stenosis in these patients and analyze its related risk factors.

Methods: Intracranial and extracranial arteries of consecutive patients with sICH were studied retrospectively with computed tomography angiography of head and neck. The risk factors, severity, and distribution of atherosclerotic stenosis were examined and analyzed.

Results: We included 226 patients with sICH, of whom 110 patients (48.7%) had atherosclerotic stenosis. Of the patients, 57 (51.8%) had intracranial stenosis and 75 (68.2%) had multiple stenosis. A total of 1870 vessels were examined and 287 vessels (15.3%) had atherosclerotic stenosis, of which 217 cases (75.6%) were mild stenosis. Intracranial and extracranial atherosclerosis was more likely to be found in patients with advanced age (P < .001), diabetes mellitus (P = .008), non-deep hemorrhage (P = .011).

Conclusions: Atherosclerotic stenosis is common in patients with sICH, and is characterized by mild stenosis and the involvement of multiple sites. The stenosis of the vertebrobasilar system is relatively severe. Advanced age, diabetes mellitus, and non-deep bleeding are its related risks.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.08.011DOI Listing
February 2018

Efficacy and safety of pemetrexed and nedaplatin followed by pemetrexed maintenance therapy in advanced lung adenocarcinoma.

Cancer Manag Res 2017 20;9:671-677. Epub 2017 Nov 20.

Department of Medical Oncology, The Fifth Affiliated Hospital of Sun-Yat-Sen University, Zhuhai, Guangdong, People's Republic of China.

Objective: To evaluate the efficacy and safety of pemetrexed and nedaplatin followed by pemetrexed maintenance therapy in advanced lung adenocarcinoma.

Methods: A total of 53 advanced lung adenocarcinoma patients hospitalized between July 2013 and June 2016 with a performance status ≤2 were enrolled in this study. All patients received 4-6 cycles of combination chemotherapy comprising pemetrexed (500 mg/m dL) and nedaplatin (80 mg/m dL). Each chemotherapy cycle consisted of 21 days. After the efficacy of the combination chemotherapy was assessed, patients with stable disease, partial remission, or complete remission received pemetrexed maintenance therapy (500 mg/m dL) until disease progression or intolerable side effects occurred. Each pemetrexed maintenance therapy cycle was 28 days.

Results: After completion of the pemetrexed and nedaplatin combination chemotherapy, 26 (49.1%), 15 (28.3%), and 12 (22.6%) patients exhibited partial remission, stable disease, and progressive disease, respectively. Complete remission was not achieved in any patient. Therefore, the response and disease control percentages were 49.1% and 77.4%, respectively. A total of 38 patients were further administered pemetrexed maintenance chemotherapy for an average of 9.8 cycles. The median progression-free survival and overall survival of the 38 patients receiving the pemetrexed maintenance therapy were 9.3 (95% confidence interval: 8.6-10) months and 16.3 (95% confidence interval: 14.5-18.2) months, respectively. The major adverse effects included bone marrow suppression and gastrointestinal reactions, which were well tolerated.

Conclusions: Combination chemotherapy based on pemetrexed and nedaplatin is effective for the treatment of advanced lung adenocarcinoma with a high tolerance by patients. In addition, pemetrexed maintenance therapy of advanced lung adenocarcinoma is safe and effective for the treatment of advanced lung adenocarcinoma following pemetrexed and nedaplatin combination chemotherapy.
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http://dx.doi.org/10.2147/CMAR.S150975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700764PMC
November 2017

Prognostic value of primary gross tumor volume and standardized uptake value of F-FDG in PET/CT for distant metastasis in locoregionally advanced nasopharyngeal carcinoma.

Tumour Biol 2017 Jul;39(7):1010428317717843

2 Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.

Distant metastasis has become the predominant model of treatment failures in patients with locoregionally advanced nasopharyngeal carcinoma. Effort should therefore be made to stratify locoregionally advanced nasopharyngeal carcinoma patients into different groups based on the risk of metastasis to improve prognosis and tailor individualized treatments. This study aims to assess the value of primary gross tumor volume and the maximum standardized uptake value for predicting distant metastasis-free survival of patients with locoregionally advanced nasopharyngeal carcinoma. A total of 294 locoregionally advanced nasopharyngeal carcinoma patients who were identified from prospectively maintained database and underwent fluor-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging before treatment were included. The maximum standardized uptake value was recorded for the primary tumor (SUVmax-P) and neck lymph nodes (SUVmax-N). Computed tomography-derived primary gross tumor volume was measured using the summation-of-area technique. At 5 years, the distant metastasis-free survival rate was 83.7%. The cut-off of the SUVmax-P, SUVmax-N, and primary gross tumor volume for distant metastasis-free survival was 8.95, 5.75, and 31.3 mL, respectively, by receiver operating characteristic curve. In univariate analysis, only SUVmax-N (hazard ratio: 7.01; 95% confidence interval: 1.70-28.87; p < 0.01) and clinical stage (hazard ratio: 3.03; 95% confidence interval: 1.67-5.47; p = 0.007) were confirmed as independent predictors of distant metastasis-free survival. A prognostic model was derived by SUVmax-N and clinical stage: low risk (SUVmax-N < 5.75 regardless of clinical stage), medium risk (stage III and SUVmax-N ≥ 5.75), and high risk (stage IV and SUVmax-N ≥ 5.75). Multivariate analysis revealed that SUVmax-N and the prognostic model remained independent prognostic factors for distant metastasis-free survival (p = 0.023 and p < 0.001, respectively), but the clinical stage became insignificant (p = 0.133). Furthermore, the adjusted hazard ratios for the prognostic model were higher than SUVmax-N (hazard ratio = 6.27 vs 5.21, respectively). In summary, compared with SUVmax-P, SUVmax-N may be a better predictor of distant metastasis-free survival for patients with locoregionally advanced nasopharyngeal carcinoma. Combining SUVmax-N with clinical stage gives a more precise picture in predicting distant metastasis.
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http://dx.doi.org/10.1177/1010428317717843DOI Listing
July 2017