Publications by authors named "Na Shen"

181 Publications

ASO Visual Abstract: Longitudinal Assessment of Quality of Life Following Molecular Testing for Indeterminate Thyroid Nodules.

Ann Surg Oncol 2021 Jul 22. Epub 2021 Jul 22.

Section of Endocrine Surgery, Department of Surgery, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA.

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http://dx.doi.org/10.1245/s10434-021-10418-yDOI Listing
July 2021

Vitamin D status in Mainland of China: A systematic review and meta-analysis.

EClinicalMedicine 2021 Aug 14;38:101017. Epub 2021 Jul 14.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, HUST, Wuhan, China.

Background: Low vitamin D (VitD) status is becoming a global health issue. Previous heterogenous results are urging a meta-analysis to delineate a panorama of VitD conditions in the general population in Mainland of China.

Methods: We performed a systematic review and meta-analysis by searching PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, WanFang, and VIP databases up to June 4, 2021. The inclusion criteria were as follows: (1) original articles or dissertations focused on VitD status of people in Mainland of China; and (2) studies were population-based, cross-sectional, or longitudinal cohort with baseline data. The outcomes were serum 25(OH)D concentration and the prevalence of low VitD status. Low VitD status included VitD deficiency (< 30 nmol/L) and VitD inadequacy (< 50 nmol/L). Data were estimated by Hierarchical Bayesian methods. All included studies were cross-sectional or longitudinal cohort studies about VitD status of people in Mainland of China. (Registration: PROSPERO CRD42021226130).

Findings: A total of 105 eligible studies including 234,519 subjects were included. In adults, the overall mean 25(OH)D concentration was 44.3 nmol/L (95% Credible Interval [CrI]: 39.8-48.7). The pooled prevalence of VitD deficiency and inadequacy was 20.7% (95% CrI: 11.9-32.9) and 63.2% (95% CrI: 53.5-72.3), respectively. In children and adolescents, the overall mean 25(OH)D concentration was 52.2 nmol/L (95% CrI: 46.7-57.5). The pooled prevalence of VitD deficiency and inadequacy was 23.0% (95% CrI: 8.9-44.3) and 46.8% (95% CrI: 37.2-56.6), respectively. Specially, we identified that the prevalence of VitD inadequacy increased with age in populations with age ≤ 18 years and ≥ 60 years.

Interpretation: Low VitD status is prominent in general population of Mainland of China, especially for adults.

Funding: National Major Scientific and Technological Special Project for "Significant New Drugs Development" (2017ZX09304022).
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http://dx.doi.org/10.1016/j.eclinm.2021.101017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283334PMC
August 2021

Longitudinal Assessment of Quality of Life Following Molecular Testing for Indeterminate Thyroid Nodules.

Ann Surg Oncol 2021 Jul 22. Epub 2021 Jul 22.

Section of Endocrine Surgery, Department of Surgery, University of California Los Angeles David Geffen School of Medicine, 10833 Le Conte Ave. 72-227 CHS, Los Angeles, CA, 90095, USA.

Background: Molecular testing can refine the risk of malignancy in cytologically indeterminate thyroid nodules and can reduce the need for diagnostic thyroidectomy. However, quality of life (QOL) in patients mananged with molecular testing is not well studied.

Objective: We aimed to assess the QOL of patients undergoing surveillance after a benign molecular test result, or thyroidectomy after a suspicious molecular test result.

Methods: This prospective longitudinal follow-up of the Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules randomized trial utilized the Thyroid-Related Patient-Reported Outcome, 39-item version (ThyPro-39) to assess the QOL of patients with indeterminate cytology on thyroid fine needle aspiration (FNA) biopsy. All patients underwent molecular testing at the time of initial FNA. A mixed-effect model was used to determine changes in QOL over time.

Results: Of 252 eligible patients, 174 completed the assessment (69% response rate). Molecular test results included 72% (n = 124) benign and 28% (n = 50) suspicious. ThyPro-39 scores of benign molecular test patients were unchanged from baseline (following initial FNA and molecular test results) to 18 months of ultrasound surveillance. Baseline symptoms of goiter, anxiety, and depression were more severe for patients with suspicious compared with benign molecular test results. At a median of 8 months after thyroidectomy, suspicious molecular test patients reported improved symptoms of goiter, anxiety, and depression.

Conclusion: A benign molecular test provides sustained QOL throughout ultrasound surveillance, without worsening anxiety or depression relating to the risk of malignancy. Definitive surgery results in improvement of QOL in patients with suspicious molecular tests.
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http://dx.doi.org/10.1245/s10434-021-10375-6DOI Listing
July 2021

Long non-coding RNA HOTAIR/microRNA-761 sponge regulates PPME1 and further influences cell biological functions in thyroid carcinoma.

Laryngoscope Investig Otolaryngol 2021 Jun 26;6(3):438-445. Epub 2021 May 26.

Department of General Surgery Jiading District Central Hospital Affiliated to Shanghai University of Medicine & Health Sciences Shanghai China.

Background: Most well-differentiated thyroid carcinomas display good therapeutic outcomes, but there are still some patients who are not sensitive to the general treatments lose their treatment opportunities. Thus, it is important to understand the molecular mechanisms that cause thyroid carcinoma, so as to find effective diagnostic and therapeutic targets.

Aim Of The Study: To explore the role of homeobox transcript antisense RNA (HOTAIR) in thyroid carcinoma through protein phosphatase methylesterase 1 (PPME1) by sponging microRNA 761 (miR-761).

Methods: The regulation network amongst HOTAIR, miR-761 and PPME1 was predicted by online sources. RT-PCR was conducted to evaluate the expression of HOTAIR and miR-761 in tumor tissues. Clinical data was collected and analyzed by Chi-square test. Cell apoptosis and proliferation was evaluated using three types of cancer cells (HTh-7, CAL-62, BCPAP) after treated with si-HOTAIR and miR-761inhibitor. The binding site among HOTAIR, miR-761 and PPME1 was verified by dual luciferase reporter assay. PPME1 expression was measured after HOTAIR and miR-761 were suppressed by western blot. Survival time was measured in nude mice using log-rank test.

Results: HOTAIR was expressed to a significantly greater extent than miR-761 in thyroid tumor tissues ( < .001). miR-761 and PPME1 were negatively correlated (coef = -1.91,  < .001). HOTAIR competitively binds to miR-761 and miR-761 directly targets PPME1. HOTAIR was highly correlated with TNM (  = 5.797,  = .016), tumor size (  = 7.955,  = .005) and lymphatic metastasis (  = 6.0,  = .014). HOTAIR promoted cell proliferation and inhibited cell apoptosis, whereas miR-761 did not. HOTAIR elevated and miR-761 suppressed PPME1 expression. HOTAIR expression appears to affect the survival time in vivo.

Conclusion: HOTAIR regulated thyroid cancer cells by binding to miR-761 through PPME1.
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http://dx.doi.org/10.1002/lio2.593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223458PMC
June 2021

Bisphenol A exposure, interaction with genetic variants and colorectal cancer via mediating oxidative stress biomarkers.

Environ Pollut 2021 Jun 23;287:117630. Epub 2021 Jun 23.

Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Bisphenol A (BPA) may induce oxidative stress as well as the toxicity of colon cancer cells. We hypothesized that BPA exposure and interactions with genetic variants might be associated with colorectal cancer (CRC) risk, and the association might be partly mediated by oxidative stress. We measured urinary BPA and three oxidative stress markers [8-iso-prostaglandinF (8-isoPGF), 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in 275 new CRC cases and 538 healthy controls. A set of 25 genetic variations in 12 candidate DNA repair genes and 5 metabolic enzyme genes were genotyped by Sequenom MassARRAY approach. In multivariable logistic regression, significant positive associations of CRC risk with BPA, 8-OHdG and HNE-MA were observed. Additionally, 8-OHdG, HNE-MA and 8-isoPGF were significantly positively associated with BPA (P < 0.05). The mediation analysis showed BPA-associated HNE-MA significantly mediated 11.81% of the effect of BPA on CRC risk. Moreover, BPA was found to interact with ERCC5 rs17655 and rs2296147 (both P < 0.05) to increase CRC risk. In brief, our results suggested BPA was associated with CRC risk and the positive association of BPA with CRC risk might be partly mediated by the oxidative stress HNE-MA. BPA might interact with ERCC5 rs17655 and rs2296147 to increase CRC risk.
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http://dx.doi.org/10.1016/j.envpol.2021.117630DOI Listing
June 2021

rs641738 Is Not Associated With the Risk of Hepatocellular Carcinoma or Persistent Hepatitis B Infection.

Front Oncol 2021 25;11:639438. Epub 2021 May 25.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: A hot genetic variant, rs641738 within the and , was recently reported to be associated with several liver diseases. However, the results remain controversial. Therefore, this study aimed to explore the role of rs641738 in the risk of hepatocellular carcinoma (HCC) and persistent hepatitis B virus (HBV) infection.

Methods: We first conducted a case-control study that included 779 HCC cases and 1412 cancer-free controls. Controls consisted of 678 persistent HBV carriers and 734 spontaneously recovered subjects. The gene variant rs641738 was genotyped using the MassARRAY platform. The results were analyzed in five genetic models using multivariate logistic regression analyses. Next, we performed a systematic review and meta-analysis to further explore the role of this variant in HCC risk.

Results: The results suggested no association between rs641738 and HCC risk in most genetic models (all > 0.05). Although a marginally significant association was observed in TT . CC ( = 0.037) and the recessive models ( = 0.044). The meta-analysis of 2135 HCC cases and 4388 controls supported that this variant was not related to HCC risk, even in the TT . CC and recessive models. We also determined that this variant did not influence persistent HBV infection.

Conclusion: Our work highlights that rs641738 is not associated with the risk of HCC or persistent HBV infection. This study provides some clues to identify the "truth" of potential disease-related genetic factors in the post-genome era.
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http://dx.doi.org/10.3389/fonc.2021.639438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185222PMC
May 2021

Berberine Attenuates Cerebral Ischemia-Reperfusion Injury Induced Neuronal Apoptosis by Down-Regulating the CNPY2 Signaling Pathway.

Front Pharmacol 2021 28;12:609693. Epub 2021 Apr 28.

Department of Central Laboratory, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, Tianjin, China.

Berberine (BBR) has a neuroprotective effect against ischemic stroke, but its specific protective mechanism has not been clearly elaborated. This study explored the effect of BBR on the canopy FGF signaling regulator 2 (CNPY2) signaling pathway in the ischemic penumbra of rats. The model of cerebral ischemia-reperfusion injury (CIRI) was established by the thread embolization method, and BBR was gastrically perfused for 48 h or 24 h before operation and 6 h after operation. The rats were randomly divided into four groups: the Sham group, BBR group, CIRI group, and CIRI + BBR group. After 2 h of ischemia, followed by 24 h of reperfusion, we confirmed the neurologic dysfunction and apoptosis induced by CIRI in rats ( < 0.05). In the ischemic penumbra, the expression levels of CNPY2-regulated endoplasmic reticulum stress-induced apoptosis proteins (CNPY2, glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), C/EBP homologous protein (CHOP), and Caspase-3) were significantly increased, but these levels were decreased after BBR treatment ( < 0.05). To further verify the inhibitory effect of BBR on CIRI-induced neuronal apoptosis, we added an endoplasmic reticulum-specific agonist and a PERK inhibitor to the treatment. BBR was shown to significantly inhibit the expression of apoptotic proteins induced by endoplasmic reticulum stress agonist, while the PERK inhibitor partially reversed the ability of BBR to inhibit apoptotic protein ( < 0.05). These results confirm that berberine may inhibit CIRI-induced neuronal apoptosis by downregulating the CNPY2 signaling pathway, thereby exerting a neuroprotective effect.
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http://dx.doi.org/10.3389/fphar.2021.609693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113774PMC
April 2021

Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101.

Theranostics 2021 3;11(12):5955-5969. Epub 2021 Apr 3.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

Anti-programmed cell death protein 1 (PD-1) therapy has shown promising efficacy in hepatocellular carcinoma (HCC), but its response rates in advanced HCC are lower than 20%. A critical reason for this is the imbalance between CD8 T cells and tumor burden. Here, a novel concept of vascular disruption and normalization dependent on a polymeric vascular disrupting agent (VDA) poly (-glutamic acid)--methoxy poly (ethylene glycol)/combretastatin A4 (CA4-NPs) + a vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) inhibitor DC101 is applied to improve anti-PD-1 therapy, wherein CA4-NPs reduce tumor burden and DC101 simultaneously increases the number of intratumoral CD8 T cells, successfully regulating the abovementioned imbalance in an H22 tumor model. Blood vessel density, tumor cell proliferation, and necrosis were evaluated to reveal the effects on reducing tumor burden by CA4-NP treatment. Pericyte coverage of blood vessels, tumor blood vessel perfusion, tumor hypoxia, and intratumoral immune cells were examined to verify their role in vascular normalization and immune cell homing of DC101. Furthermore, the effects of CA4-NPs + DC101 on reducing tumor burden and increasing the number of immune cells were studied. Finally, tumor suppression, intratumoral CD8 T cell activation, and the synergistic effects of anti-PD-1 combined with CA4-NPs + DC101 were verified. The tumor inhibition rate of anti-PD-1 antibody combined with CA4-NPs + DC101 reached 86.4%, which was significantly higher than that of anti-PD-1 (16.8%) alone. Importantly, the Q value reflecting the synergy between CA4-NPs + DC101 and anti-PD-1 was 1.24, demonstrating a strong synergistic effect. Furthermore, CA4-NPs + DC101 improved anti-PD-1 therapy by increasing the number of intratumoral CD8 T cells (anti-PD-1, 0.31% vs triple drug combination, 1.18%). These results reveal a novel approach to enhance anti-PD-1 therapy with VDAs + VEGF/VEGFR2 inhibitors in HCC.
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http://dx.doi.org/10.7150/thno.58164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058708PMC
July 2021

Predictive Classification System for Low Back Pain Based on Unsupervised Clustering.

Global Spine J 2021 Apr 26:21925682211001813. Epub 2021 Apr 26.

Department of Orthopedics, Shanghai 92323Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Study Design: Retrospective study.

Objective: Lumbar magnetic resonance imaging (MRI) findings are believed to be associated with low back pain (LBP). This study sought to develop a new predictive classification system for low back pain.

Method: Normal subjects with repeated lumbar MRI scans were retrospectively enrolled. A new classification system, based on the radiological features on MRI, was developed using an unsupervised clustering method.

Results: One hundred and fifty-nine subjects were included. Three distinguishable clusters were identified with unsupervised clustering that were significantly correlated with LBP ( = .017). The incidence of LBP was highest in cluster 3 (57.14%), nearly twice the incidence in cluster 1 (30.11%). There were obvious differences in the sagittal parameters among the 3 clusters. Cluster 3 had the smallest intervertebral height. Based on follow-up findings, 27% of subjects changed clusters. More subjects changed from cluster 1 to clusters 2 or 3 (14.5%) than changed from cluster 2 or cluster 3 to cluster 1 (5%). Participation in sport was more frequent in subjects who changed from cluster 3 to cluster 1.

Conclusion: Using an unsupervised clustering method, we developed a new classification system comprising 3 clusters, which were significantly correlated with LBP. The prediction of LBP is independent of age and better than that based on individual sagittal parameters derived from MRI. A change in cluster during follow-up may partially predict lumbar degeneration. This study provides a new system for the prediction of LBP that should be useful for its diagnosis and treatment.
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http://dx.doi.org/10.1177/21925682211001813DOI Listing
April 2021

Harnessing Big Data to Optimize an Algorithm for Rapid Diagnosis of Pulmonary Tuberculosis in a Real-World Setting.

Front Cell Infect Microbiol 2021 18;11:650163. Epub 2021 Mar 18.

Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.

Background: The prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting.

Methods: 28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.. We analyzed specimen types' effect on these assays' performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections.

Results: Sputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB/Xpert and 6/7 of AFB/Xpert cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB or Xpert. However, T-SPOT (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of -specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT. assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB/Xpert patients.

Conclusions: Concurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOT and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB/Xpert patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers' decisions regarding prevention and control of TB in a high burden setting.
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http://dx.doi.org/10.3389/fcimb.2021.650163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012509PMC
July 2021

Synergistic Therapy for Cervical Cancer by Codelivery of Cisplatin and JQ1 Inhibiting Plk1-Mutant Trp53 Axis.

Nano Lett 2021 03 11;21(6):2412-2421. Epub 2021 Mar 11.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

JQ1, a specific inhibitor of bromodomain-containing protein 4 (BRD4), could have great potential in the treatment of cervical cancer. However, its clinical application is limited by its short plasma half-life and limited antitumor efficacy. In this work, cisplatin (CDDP) was first utilized as the stabilizer and cooperator in the nanosystem (mPEG--P(Glu--Phe)-CDDP/JQ1, called PGP-CDDP/JQ1) to break through the efficiency limitation of JQ1. The PGP-CDDP/JQ1 had a combination index (CI) of 0.21, exerting a strong cytotoxic synergistic effect. experiments revealed that PGP-CDDP/JQ1 had a significantly higher tumor inhibition effect (tumor inhibition rate: 85% vs 14%) and plasma stability of JQ1 (area under the curve (AUC): 335.97 vs 16.88 μg × h/mL) than free JQ1. The mechanism underling the synergism of JQ1 with CDDP in PGP-CDDP/JQ1 was uncovered to be inhibiting Plk1-mutant Trp53 axis. Thus, this study provides an optional method for improving the clinical application of JQ1 in cervical cancer.
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http://dx.doi.org/10.1021/acs.nanolett.0c04402DOI Listing
March 2021

Construction of a Risk Prediction Model for Subsequent Bloodstream Infection in Intestinal Carriers of Carbapenem-Resistant Enterobacteriaceae: A Retrospective Study in Hematology Department and Intensive Care Unit.

Infect Drug Resist 2021 2;14:815-824. Epub 2021 Mar 2.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People's Republic of China.

Background: To establish a risk prediction model for carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in intestinal carriers.

Methods: CRE screenings were performed every two weeks in hematology department and intensive care unit (ICU). Patients with positive CRE rectal swab screening were identified using electronic medical records from 15 May 2018 to 31 December 2019. Intestinal carriers who developed CRE BSI were compared with those who did not develop CRE infection. A 1:1 matched case-control study was conducted. The control group was selected by stratified random sampling based on the department to ensure that all the departments were represented. Univariate logistic analysis, multivariate logistic analysis and stepwise regression analysis were carried on a variety of patient factors and microbial factors.

Results: A total of 42 cases were included. Multivariate analysis showed that gastrointestinal injury (OR 86.819, 95% CI 2.584-2916.592, =0.013), tigecycline exposure (OR 14.991, 95% CI 1.816-123.737, =0.012) and carbapenem resistance score (OR 11.236, 95% CI 1.811-69.700, =0.009) were independent risk factors for CRE BSI in intestinal carriers (<0.050). They were included in the Logistic regression model to predict BSI. According to receiver operating characteristic (ROC) curve analysis, the cut-off value of the model was 0.722, and the sensitivity, specificity and area under the curve (AUC) were 90.5%, 85.7% and 0.921, respectively.

Conclusion: The risk prediction model based on gastrointestinal injury, tigecycline exposure and carbapenem resistance score of colonizing strain can effectively predict CRE BSI in patients with CRE colonization. Early CRE screening and detection for inpatients in key departments may promote early warning and reduce the risk of nosocomial infection of CRE.
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http://dx.doi.org/10.2147/IDR.S286401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936666PMC
March 2021

Cisplatin nanoparticles boost abscopal effect of radiation plus anti-PD1 therapy.

Biomater Sci 2021 Apr 3;9(8):3019-3027. Epub 2021 Mar 3.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

The abscopal effect of radiation therapy (RT) is clinically significant but occurs rarely. Although anti-programmed cell death protein 1 antibody (anti-PD1) is likely to enhance the abscopal effect in patients receiving RT, the incidence rate remains less than 30%. One major limitation is the paucity of CD8 T cells within non-irradiated tumors. Here, cisplatin (CDDP) loaded poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) are confirmed to increase CD8 T cells within non-irradiated tumors and boost the abscopal effect of RT plus anti-PD1, and more strongly than CDDP. Compared to RT and RT + CDDP, RT + CDDP-NPs induced greater immunogenic cell death (ICD) with enhanced proportion of Calreticulin Lewis lung cancer (LLC) cells (16.47%, 20.53% and 27.03%), along with which more CD8 T cells were infiltrated into CDDP-NP treated irradiated tumors in the unilateral LLC tumor model. In the bilateral LLC tumor model, RT + CDDP-NPs significantly induced more chemokine (C-X-C motif) ligand 10 (CXCL10) secretion (36.3, 44.19 and 56.37 pg mL), which corresponded to greater CD8 T cell infiltration in the non-irradiated tumors (0.19%, 0.20% and 0.72%). Finally, compared to RT + anti-PD1 and RT + anti-PD1 + CDDP, RT + anti-PD1 + CDDP-NPs significantly inhibited the growth of non-irradiated tumors more forcefully, as indicated by the respective tumor volumes of 1141, 1146 and 585 mm. This is the first study to show that CDDP-NPs can amplify RT-induced immune activation and break through the efficiency limitation of the RT plus anti-PD1 induced abscopal effect.
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http://dx.doi.org/10.1039/d1bm00112dDOI Listing
April 2021

A folate receptor 3 SNP promotes mitochondria-induced clonogenicity of CML leukemia cells: Implications for treatment free remission.

Clin Transl Med 2021 02;11(2):e317

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1002/ctm2.317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862584PMC
February 2021

Lung metastases in newly diagnosed hypopharyngeal cancer: a population-based study.

Eur Arch Otorhinolaryngol 2021 Feb 18. Epub 2021 Feb 18.

Department of Otolaryngology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Purpose: Current population-based estimates of the incidence and prognosis of lung metastases of hypopharyngeal cancer are lacking. The purpose of the study is to characterize the incidence proportions and survival probability of patients with hypopharyngeal cancer and lung metastases.

Materials And Methods: We identified 2714 adult patients diagnosed with hypopharyngeal cancer between 2010 and 2014 for whom the status of lung metastases was known from the SEER database. Multivariable logistic and Cox regression models were performed to identify the risk factors associated with the presence of lung metastases at diagnosis and 5-year all-cause mortality, respectively.

Results: We identified 128 patients with lung metastases at the time of diagnosis of hypopharyngeal cancer. Females were less likely to have lung metastases. Incidences of lung metastases were higher among patients with histological grade III/IV. For each 10 mm increase in tumor size, the odds of having lung metastases increased by 6.6%. Patients with lung metastases had a shorter survival time.

Conclusion: Our study provides insight into the epidemiology of lung metastases in patients with hypopharyngeal cancer. When the tumor is diagnosed, we should pay close attention to the sex, race, tumor size and histological grade to quickly detect the distant metastases.
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http://dx.doi.org/10.1007/s00405-021-06675-yDOI Listing
February 2021

Self-Amplifying Nanotherapeutic Drugs Homing to Tumors in a Manner of Chain Reaction.

Adv Mater 2021 Feb 31;33(7):e2002094. Epub 2020 Dec 31.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

Active tumor-targeting drug delivery has great potency in cancer therapy. However, the targeting efficiency of traditional active tumor-targeting nanotherapeutic drugs is limited by the scarcity of their accessible targets/receptors in tumors. Here, a novel self-amplifying tumor-targeting strategy with a chain reaction mechanism is developed. A coagulation targeting peptide (GNQEQVSPLTLLKXC, termed A15)-decorated poly(L-glutamic acid)-graft-maleimide poly(ethylene glycol)/combretastatin A4 conjugate (A15-PLG-CA4) is prepared to obtain a self-amplifying nanotherapeutic platform homing to tumors. After administration to tumor-bearing mice, A15-PLG-CA4 starts a chain reaction cycle consisting of intratumoral hemorrhage, target FXIIIa amplification, blood clot binding, and CA4 release in tumors. In this way, A15-PLG-CA4 increases the level of its accessible targets (FXIIIa) in a manner of chain reaction. The FXIIIa activity at 8 h is 4.1-fold more than the one at 0 h in the C26 tumors treated with A15-PLG-CA4. The total CA4 concentration at 24 h is 2.9-fold more than the control. A15-PLG-CA4 shows a significantly higher antitumor effect against large C26 tumors (≈500 mm ) thanks to the remarkable tumor-targeting ability compared with the control. Therefore, this report highlights the potential of the self-amplifying tumor-targeting strategy in the development of next generation active tumor-targeting nanotherapeutic drugs for tumor therapy.
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http://dx.doi.org/10.1002/adma.202002094DOI Listing
February 2021

Importance of early detection of juvenile polyposis syndrome: A case report and literature review.

Medicine (Baltimore) 2020 Dec;99(50):e23494

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Rationale: Juvenile polyposis syndrome (JPS) is a rare genetic gastrointestinal disorder with hidden and variable clinical features. Early detection is crucial for good prognosis.

Patient Concerns: A 20-year-old female went to hospital for fever, and was unexpectedly diagnosed as JPS during treatment. She reported no clinical signs or family history of JPS.

Diagnosis: Blood routine examination on hospital admission suggested a moderate anemia. Bone marrow cytology and leukemia fusion gene test were performed to rule out leukemia. Other examinations including ultrasound and computed tomography were also conducted for differential diagnosis. Further electronic colonoscopy identified more than 20 pedicle polyps located at her ileocecum and rectum. Mutation analysis detected a novel de novo pathogenic variant, c.910C>T (p.Gln304Ter) within bone morphogenetic protein receptor type 1A gene, establishing the diagnosis of JPS.

Interventions: The patient was treated with endoscopic interventions. We also provided a genetic counseling for this family.

Outcomes: The patient's polyps were removed, some of which already had adenomatous changes. The patient received surveillance of hereditary colorectal cancer according to guidelines.

Lessons: Variable features and lack of family history probably lead to a great underestimation of potential JPS population. It is recommended to perform genetic testing by a multigene panel in individuals who have suspected symptoms of polyposis.
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http://dx.doi.org/10.1097/MD.0000000000023494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738017PMC
December 2020

Normal activated partial thromboplastin time in Chinese patients with mild hemophilia B.

Hematology 2020 Dec;25(1):484-488

Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Objectives: Hemophilia B (HB, OMIM: 300746) is one of the most common bleeding disorders with an X-linked recessive inheritance pattern, caused by the deficiency of coagulation factor IX (FIX). FIX is encoded by the gene located on Xq27.1. Diagnosis of HB is primarily suspected by prolonged activated partial thromboplastin time (APTT), decreased FIX activity (FIX:C) or genetic test of the gene. We herein described a Chinese family with patients of mild HB.

Methods: Sanger sequencing of the gene was applied to identify mutation. Coagulation tests were performed.

Results: The proband was a 5-year-old boy. He suffered prolonged bleeding after tonsillectomy recently and circumcision last year as well. His grandfather experienced prolonged bleeding after gastric surgery. Both patients showed normal APTT, though they had significantly decreased FIX:C. Sanger sequencing of the gene revealed a novel hemizygous c.639C > A (p.Asn213Lys) missense mutation in both patients. The proband's mother carried heterozygous mutation. This mutation was located in the activation peptide domain of FIX.

Conclusion: In conclusion, we confirmed that APTT could be normal in mild HB patients. Highly sensitive APTT for mild HB and molecular genetic test could confirm the diagnosis of mild HB.
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http://dx.doi.org/10.1080/16078454.2020.1853403DOI Listing
December 2020

FXIIIa substrate peptide decorated BLZ945 nanoparticles for specifically remodeling tumor immunity.

Biomater Sci 2020 Oct 11;8(20):5666-5676. Epub 2020 Sep 11.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

Combretastatin A4 nanoparticles (CA4-NPs), which notably inhibit tumor growth, were found to cause tumor regrowth due to the intratumoral enrichment of M2-type macrophages after treatment. Since BLZ945, an inhibitor of CSF-1 receptor (CSF-1R), depletes and inhibits the proliferation of M2-type macrophages, it has the potential to relieve the immunosuppressive microenvironment and improve anti-tumor therapy of CA4-NPs. However, CSF-1R exists widely, not only in macrophages, and BLZ945 could cause potential hepatotoxicity. It is necessary to establish a tumor-targeting drug delivery system to reduce the off-target and side effects of BLZ945. In this study, FXIIIa substrate peptide A15 decorated BLZ945 nanoparticles (A15-BLZ-NPs) were developed, in which, BLZ945-poly(d,l-lactide) (BLZ945-PLA), produced by ring-opening polymerization, was encapsulated in poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA), and A15 was decorated on the surface PEG segment. A15-BLZ-NPs could crosslink with fibrin through elevated FXIIIa and specifically target intratumoral coagulation spots induced by CA4-NPs. In vivo studies showed that CA4-NPs induced enhanced distribution of BLZ945 in tumors, as the BLZ945 content was 3.75-fold in the CA4-NP + A15-BLZ-NP group compared to that of A15-BLZ-NP single treatment. Meanwhile, compared to the CA4-NP group, the combination treatment significantly reduced the proportion of M2-type macrophages (from 64.4% to 24.5%) and enriched cytotoxic T lymphocytes (from 1.5% to 18.9%) in tumors, suggesting that A15-BLZ-NPs remodeled and activated tumor immunity after CA4-NP treatment. Furthermore, the combined treatment effectively improved the tumor inhibition rate to 73.4%, which was significantly higher than that of CA4-NP (15.5%) or A15-BLZ-NP (23.9%) single treatment. This work established a novel combination strategy for anti-tumor therapy.
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http://dx.doi.org/10.1039/d0bm00713gDOI Listing
October 2020

The Influence of Cochlear Implant-Based Electric Stimulation on the Electrophysiological Characteristics of Cultured Spiral Ganglion Neurons.

Neural Plast 2020 6;2020:3108490. Epub 2020 Sep 6.

ENT Institute and Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Background: Cochlear implant-based electrical stimulation may be an important reason to induce the residual hearing loss after cochlear implantation. In our previous study, we found that charge-balanced biphasic electrical stimulation inhibited the neurite growth of spiral ganglion neurons (SGNs) and decreased Schwann cell density in vitro. In this study, we want to know whether cochlear implant-based electrical stimulation can induce the change of electrical activity in cultured SGNs.

Methods: Spiral ganglion neuron electrical stimulation in vitro model is established using the devices delivering cochlear implant-based electrical stimulation. After 48 h treatment by 50 A or 100 A electrical stimulation, the action potential (AP) and voltage depended calcium current ( ) of SGNs are recorded using whole-cell electrophysiological method.

Results: The results show that the of SGNs is decreased significantly in 50 A and 100 A electrical stimulation groups. The reversal potential of is nearly +80 mV in control SGN, but the reversal potential decreases to +50 mV in 50 A and 100 A electrical stimulation groups. Interestingly, the AP amplitude, the AP latency, and the AP duration of SGNs have no statistically significant differences in all three groups.

Conclusion: Our study suggests cochlear implant-based electrical stimulation only significantly inhibit the of cultured SGNs but has no effect on the firing of AP, and the relation of inhibition and SGN damage induced by electrical stimulation and its mechanism needs to be further studied.
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http://dx.doi.org/10.1155/2020/3108490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490630PMC
September 2020

Expression of hypoxia-inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors.

Brain Behav 2020 08 12;10(8):e01718. Epub 2020 Jun 12.

Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: It has been indicated that abnormal glucose metabolism mediated by hypoxia-inducible factor 1α (HIF-1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL).

Objective: To investigate the protein levels of HIF-1α, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in PCNSL and whether their levels are associated with prognostic factors.

Methods: Expression of HIF-1α, GLUT1, and HK2 in 39 tumor tissues was evaluated by immunohistochemical stainning. The correlation of the expression of HIF-1α with the protein level of GLUT1 and HK2 was investigated. In addition, the association between these protein expression levels and clinical parameters and prognosis was analyzed.

Results: In the tumor specimens of PCNSL, positive stainings of HIF-1α, GLUT1, and HK2 were in 23 patients (58.97%), 25 patients (64.1%), and 26 patients (66.67%), respectively, which were associated with the expression level of lactic dehydrogenase (LDH), but not with age, gender, number of lesion, ECOG score, or deep structure. The expression of HIF-1α was positively correlated with the expression of GLUT1 (p < .01, r = .749) and HK2 (p < .01, r = .787). Univariate analysis showed that upregulated GLUT1 was unfavorable predictors of progression-free survival (PFS) in PCNSL. The results of Cox proportional hazards model showed GLUT1 was significantly associated with shorter PFS (hazard ration: 5.65; 95% confidence interval: 1.23-25.84; p = .026).

Conclusions: This study indicated that there was a hypoxic microenvironment and HIF-1α was involved in the regulation of glycolysis pathway in PCNSL. GLUT1 might be a potential marker for shorter PFS in PCNSL.
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http://dx.doi.org/10.1002/brb3.1718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428508PMC
August 2020

Nonreceptor protein tyrosine phosphatases (NRPTPs) gene family associates with the risk of hepatocellular carcinoma in a Chinese hepatitis B virus-related subjects.

Mol Carcinog 2020 08 2;59(8):980-988. Epub 2020 Jun 2.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Nonreceptor protein tyrosine phosphatases (NRPTPs) are reported to be associated with several human cancers, but their roles in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. Here, we integrated bioinformatics tools, population association analyses, and biological assays to systematically screen for potentially functional single nucleotide polymorphisms (SNPs) within the 17 NRPTPs genes and evaluate the effects of candidate SNPs on the risk of HCC or persistent HBV infection. A total of 790 HBV-related HCC cases and 1454 cancer-free controls were enrolled. Controls included 711 HBV persistent carriers and 743 spontaneously recovered subjects. Results demonstrated that PTPN4 rs9308777 (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.06-1.49, P = .009) and PTPN12 rs350050 (OR = 1.26, 95% CI = 1.10-1.45, P = .001), were significantly associated with HCC risk, but not with persistent HBV infection risk. The cumulative risk effect of these two SNPs was more significantly increased the susceptibility to HCC (OR = 1.27, 95% CI = 1.14-1.41, P = 2.40 × 10 ). Subsequent biological assays further revealed the potential pathogenesis that PTPN4 rs9308777 might decrease the gene expression, and PTPN12 rs3750050 might promote cell proliferation by attenuating PTPN12's inhibitory activity on EGFR/ERK pathway. In summary, our integrative study highlights that PTPN4 and PTPN12 are significantly associated with HBV-related HCC risk, but do not influence persistent HBV infection. These findings shed light on the importance of the synergistic effects of regulatory and missense variants on the risk for HCC, and provide data to support personalized cancer medicine in the future.
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http://dx.doi.org/10.1002/mc.23228DOI Listing
August 2020

Characteristics and diagnosis rate of 5630 subjects receiving SARS-CoV-2 nucleic acid tests from Wuhan, China.

JCI Insight 2020 05 21;5(10). Epub 2020 May 21.

BACKGROUNDThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a novel viral pneumonia (COVID-19), which is rapidly spreading throughout the world. The positive result of nucleic acid test is a golden criterion to confirm SARS-CoV-2 infection, but the detection features remain unclear.METHODSWe performed a retrospective analysis in 5630 high-risk individuals receiving SARS-CoV-2 nucleic acid tests in Wuhan, China, and investigated their characteristics and diagnosis rates.RESULTSThe overall diagnosis rate was 34.7% (1952/5630). Male (P = 0.025) and older populations (P = 2.525 × 10-39) were at significantly higher risk of SARS-CoV-2 infection. People were generally susceptible, and most cases concentrated in people of 30-79 years. Furthermore, we investigated the association between diagnosis rate and the amount of testing in 501 subjects. Results revealed a 1.27-fold improvement (from 27.9% to 35.5%) of diagnosis rate from testing once to twice (P = 5.847 × 10-9) and a 1.43-fold improvement (from 27.9% to 39.9%) from testing once to 3 times (P = 7.797 × 10-14). More than 3 testing administrations was not helpful for further improvement. However, this improvement was not observed in subjects with pneumonia (P = 0.097).CONCLUSIONAll populations are susceptible to SARS-CoV-2 infection, and male and older-aged populations are at significantly higher risk. Increasing the amount of testing could significantly improve diagnosis rates, except for subjects with pneumonia. It is recommended to test twice in those high-risk individuals whose results are negative the first time, and performing 3 tests is better, if possible.FUNDINGThis work was supported by National Mega Project on Major Infectious Disease Prevention (no. 2017ZX10103005-007) and National Key Research and Development Program of China (no. 2018YFE0204500).
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http://dx.doi.org/10.1172/jci.insight.137662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259521PMC
May 2020

Urinary bisphenol A and its interaction with ESR1 genetic polymorphism associated with non-small cell lung cancer: findings from a case-control study in Chinese population.

Chemosphere 2020 Sep 19;254:126835. Epub 2020 Apr 19.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Bisphenol A (BPA), a well-known endocrine disruptor, was reported to promote migration and invasion of lung cancer cells, but findings in human study is absent. A case-control study in Chinese population was conducted to evaluate the association between BPA exposure and non-small cell lung cancer (NSCLC), and explore the interaction between BPA exposure and estrogen-related genetic polymorphism on NSCLC. BPA concentrations were measured in urine samples using an UHPLC-MS method and rs2046210 in estrogen receptor α (ESR1) gene was genotyped by TaqMan genotyping system. Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association analyses. As a result, 615 NSCLC cases and 615 healthy controls were enrolled from Wuhan, central China. The mean age was 58.0 (SD: 7.9) years old for controls and 59.2 (SD: 8.8) years old for cancer cases. The creatinine-adjusted BPA levels were significantly higher in NSCLC cases than that in healthy controls (median: 0.97 vs 0.73 μg/L, P < 0.001). Exposure to high levels of BPA was significantly associated with NSCLC (adjusted OR = 1.91, 95%CI: 1.39-2.62, P < 0.001 for the highest quartile). We also observed a shallow concave dose-response relationship about the overall association between BPA and NSCLC. Moreover, interaction analyses showed that BPA exposure interacted multiplicatively with rs2046210, with a marginal P value (P = 0.049), to contribute to NSCLC. In conclusion, exposure to high levels BPA may be associated with NSCLC and the relationship may be modified by genetic polymorphism in ESR1.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126835DOI Listing
September 2020

Correction: An eximious and affordable GSH stimulus-responsive poly(α-lipoic acid) nanocarrier bonding combretastatin A4 for tumor therapy.

Biomater Sci 2020 05 23;8(10):2977. Epub 2020 Apr 23.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.

Correction for 'An eximious and affordable GSH stimulus-responsive poly(α-lipoic acid) nanocarrier bonding combretastatin A4 for tumor therapy' by Zhilin Liu et al., Biomater. Sci., 2019, 7, 2803-2811.
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http://dx.doi.org/10.1039/d0bm90037kDOI Listing
May 2020

Clinical characteristics of 80 hospitalized frontline medical workers infected with COVID-19 in Wuhan, China.

J Hosp Infect 2020 Apr 14. Epub 2020 Apr 14.

Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China. Electronic address:

More than 1,000 medical workers have been infected with COVID-19 in China. The 80 hospitalized patients included 57 SARS-CoV-2 confirmed and 23 clinically diagnosed. The median age was 39 years, 49 (61.25%) were women, and one patient died. The most common symptoms at onset were fever (65, 81.25%), cough (47, 58.75%), fatigue (28, 35%), myalgia (19, 23.75%), expectoration (19, 23.75%), and diarrhea (15, 18.75%). Patients of frontline medical workers at a single-center hospital showed some unique clinical and laboratory findings compared with other patients in Wuhan and outside of Wuhan. This study provides our experience for other frontline medical workers.
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http://dx.doi.org/10.1016/j.jhin.2020.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194674PMC
April 2020

Ruxolitinib add-on in corticosteroid-refractory graft--host disease after allogeneic stem cell transplantation: Results from a retrospective study on 38 Chinese patients.

World J Clin Cases 2020 Mar;8(6):1065-1073

Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.

Background: Graft--host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation. Some patients have steroid-refractory (SR) GVHD.

Aim: To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.

Methods: We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered 5-10 mg/d depending on disease severity, patient status, and the use of anti-fungal drugs. Overall response rate, time to best response, malignancy relapse rate, infection rate, and treatment-related adverse events were assessed.

Results: The analysis included 10 patients with SR-aGVHD (grade III/IV, = 9) and 28 patients with SR-cGVHD (moderate/severe, = 24). For the SR-aGVHD and SR-cGVHD groups, respectively: Median number of previous GVHD therapies was 2 (range: 1-3) and 2 (1-4); median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo; median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo; and overall response rate was 100% (complete response: 80%) and 82.1% (complete response: 10.7%) with a response observed in all GVHD-affected organs. The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0% and 10.7%, respectively. Reactivation rates for cytomegalovirus, Epstein-Barr virus, and varicella-zoster virus, respectively, were 30.0%, 10.0%, and 0% for the SR-aGVHD group and 0%, 14.3%, and 7.1% for the SR-cGVHD group.

Conclusion: Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.
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http://dx.doi.org/10.12998/wjcc.v8.i6.1065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103980PMC
March 2020

CDC25B is associated with the risk of hepatocellular carcinoma, but not related to persistent infection of hepatitis B virus in a Chinese population.

Mol Biol Rep 2020 May 4;47(5):3361-3368. Epub 2020 Apr 4.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The cell division cycle 25 (CDC25) gene members, including CDC25A, CDC25B and CDC25C, are reported to be associated with several human cancers. Here, we aim to investigate the association of functional polymorphisms of CDC25 gene family with the risk of hepatocellular carcinoma (HCC) and persistent infection of Hepatitis B virus (HBV) in a Chinese HBV-related population. First, we used bioinformatics tools to systematically screen functional polymorphisms within CDC25 gene family. Second, we evaluated the effects of candidate polymorphisms by recruiting 790 HCC cases, 709 persistent HBV carriers (PHC), and 741 subjects with HBV natural clearance (SHNC). MassARRAY platform was used for genotyping. At last, we conducted functional prediction and assay to further explore the pathogenic mechanism of the identified polymorphism. Our results demonstrated that CDC25B rs2295348 played a protective role in HCC risk in a HBV-related Chinese population (adjusted odds ratio [OR] = 0.77, 95% confidence interval [CI] 0.65-0.93, P = 0.006). It showed a more significantly reduced HCC risk in the SHNC population (adjusted OR = 0.73, 95% CI 0.59-0.89, P = 0.002). However, we did not observe the association between CDC25B rs2295348 and the risk of persistent HBV infection. Further functional prediction and assay demonstrated that the mutant A allele of CDC25B rs2295348 might significantly decrease gene expression to modify the HCC risk. Our results suggest that CDC25B rs2295348 may confer a protective effect on HCC risk in a HBV-related Chinese population, but do not influence the susceptibility to persistent HBV infection.
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http://dx.doi.org/10.1007/s11033-020-05408-4DOI Listing
May 2020

Congenital fibrinogen disorder caused by digenic mutations of the and genes.

Hematology 2020 Dec;25(1):145-148

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Congenital fibrinogen disorders (CFDs) are caused by monoallelic or biallelic mutations in , , and genes. Quantitative CFDs include afibrinogenemia and hypofibrinogenemia, while qualitative CFDs consist of dysfibrinogenemia and hypodysfibrinogenemia. Hypofibrinogenemia and dysfibrinogenemia are autosomal dominant disorders while afibrinogenemia is a recessive one. We aimed to perform genetic diagnosis of a Chinese patient with CFD. DNA was extracted from peripheral blood mononuclear cells (PBMCs) and targeted next generation sequencing (NGS) was applied using amplicon-based panel (www.ampliseq.com) targeting all exons and splice sites of , , and genes. Identified mutations were confirmed by Sanger sequencing. We have identified a novel heterozygous c.560_561delTG (p.Val187GlufsTer2) frameshift deletion and a novel heterozygous c.190T > G (p.Cys64Gly) missense mutations in a Chinese patient with CFD. This is the first report of digenic variants causing CFD, and these findings may improve understanding of the genetic architecture of CFD.
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http://dx.doi.org/10.1080/16078454.2020.1746109DOI Listing
December 2020

Discovery and comparison of serum biomarkers for diabetes mellitus and metabolic syndrome based on UPLC-Q-TOF/MS.

Clin Biochem 2020 Aug 16;82:40-50. Epub 2020 Mar 16.

Department of Cardiology, Tianjin 4th Center Hospital, Tianjin 300140, China; Tianjin Fourth Central Hospital, Tianjin 300140, China. Electronic address:

Introduction: Diabetes mellitus (DM) and metabolic syndrome (MetS) are systemic metabolic disorders, which have risk factors for diabetic cardiovascular and cerebral microvascular disease. It is very important to screen the metabolic biomarkers between DM and MetS patients, which can make patients benefit to a greater extent and prevent the occurrence of disease in advance.

Objectives: Diabetes mellitus (DM) and metabolic syndrome are a complex, chronic illness with a pronounced impact on the quality of life of many people. However, understanding the metabolic changes in patients and identifying high-risk individuals is crucial for prevention and disease management strategies.

Methods: In this study, a nontargeted metabolomics approach based on UPLC-Q-TOF/MS was used to find the differential metabolites in serum samples from patients with DM and MetS.

Results: Metabonomic analysis reveals metabolic differences between DM and HC with significant differences more than 60 metabolites. While, more than 65 metabolites have significant differences between MetS and HC. The independent disturbed pathway in the DM group was the FoxO signaling pathway. The independent disturbed pathways in the MetS group were the alpha-linolenic acid metabolism, glycerophospholipid metabolism and pyrimidine metabolism. The independent disturbed metabolites and the logistic regression result showed that betaine, alpha-linolenic acid, d-mannose, l-glutamine and methylmalonic acid can be used as a combinatorial biomarker to distinguish DM from healthy control. L-isoleucine, l-glutamine, PC(16:0/16:0), alpha-d-glucose, ketoisocaproic acid, d-mannose, uridine can be used as a combinatorial biomarker in MetS.

Conclusion: Our findings, on one hand, provide critical insight into the pathological mechanism of DM and MetS. On the other hand, supply a combinatorial biomarker to aid the diagnosis of diseases in clinical usage.
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http://dx.doi.org/10.1016/j.clinbiochem.2020.03.007DOI Listing
August 2020
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