Publications by authors named "Xiao-Bo Li"

195 Publications

[Lignans with inhibitory effect on 5α-reductase from Urtica cannabina].

Zhongguo Zhong Yao Za Zhi 2021 Aug;46(15):3846-3852

School of Pharmacy, Shanghai Jiao Tong University Shanghai 200240, China.

The lignans in Urtica cannabina were isolated by preparative HPLC, silica, and ODS column chromatographies, and identified by NMR and HR-MS. The inhibitory activities on 5α-reductase were evaluated in vitro. As a result, ten secolignans,(2R,4S)-2,4-bis(3-methoxyl-4-hydroxyphenyl)-3-butoxypropanol(1), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone(2), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(3), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(trans urticol, 4), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone-3-O-β-D-glucopyranoside(5), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(6), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(trans-urticol-7-O-β-D-glucopyranoside, 7), cycloolivil-4-O-β-D-glucopyranoside(8), isolariciresinol-4'-O-β-D-glucopyranoside(9), and olivil-4'-O-β-D-glucopyranoside(10), together with a polyphenol [α-viniferin(11)], were isolated from U. cannabina for the first time. Compound 1 was a new lignan. Compound 7 was potent in inhibiting 5α-reductase.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210519.201DOI Listing
August 2021

Diagnostic endoscopic submucosal dissection in the diagnosis of biopsy-missed gastric mucosa-associated lymphoid tissue lymphoma.

J Dig Dis 2021 Aug 17. Epub 2021 Aug 17.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.

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http://dx.doi.org/10.1111/1751-2980.13042DOI Listing
August 2021

An integrated machine learning framework for a discriminative analysis of schizophrenia using multi-biological data.

Sci Rep 2021 Jul 19;11(1):14636. Epub 2021 Jul 19.

Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou, 510006, Guangdong, China.

Finding effective and objective biomarkers to inform the diagnosis of schizophrenia is of great importance yet remains challenging. Relatively little work has been conducted on multi-biological data for the diagnosis of schizophrenia. In this cross-sectional study, we extracted multiple features from three types of biological data, including gut microbiota data, blood data, and electroencephalogram data. Then, an integrated framework of machine learning consisting of five classifiers, three feature selection algorithms, and four cross validation methods was used to discriminate patients with schizophrenia from healthy controls. Our results show that the support vector machine classifier without feature selection using the input features of multi-biological data achieved the best performance, with an accuracy of 91.7% and an AUC of 96.5% (p < 0.05). These results indicate that multi-biological data showed better discriminative capacity for patients with schizophrenia than single biological data. The top 5% discriminative features selected from the optimal model include the gut microbiota features (Lactobacillus, Haemophilus, and Prevotella), the blood features (superoxide dismutase level, monocyte-lymphocyte ratio, and neutrophil count), and the electroencephalogram features (nodal local efficiency, nodal efficiency, and nodal shortest path length in the temporal and frontal-parietal brain areas). The proposed integrated framework may be helpful for understanding the pathophysiology of schizophrenia and developing biomarkers for schizophrenia using multi-biological data.
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http://dx.doi.org/10.1038/s41598-021-94007-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290033PMC
July 2021

Theoretical Insights into the Reduction Mechanism of Np(VI) with Phenylhydrazine.

J Phys Chem A 2021 Jul 8;125(28):6180-6188. Epub 2021 Jul 8.

Laboratory of Nuclear Energy Chemistry, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

Effectively adjusting and controlling the valence state of neptunium from the spent fuel reprocessing process is essential to separating neptunium. Hydrazine and its derivatives as free-salt reductants have been experimentally demonstrated to effectively reduce Np(VI) to Np(V). We have theoretically investigated the reduction mechanisms of Np(VI) with hydrazine and three derivatives (HOCHNH, CHNH, and CHONH) in previous works. Herein, we further explored the reduction reaction of Np(VI) with phenylhydrazine (CHNH) including the free radical ion mechanism and the free radical mechanism. Potential energy profiles (PEPs) indicate that the rate-determining step of both mechanisms is the first stage. Moreover, for the free radical ion mechanism, phenylhydrazine possesses better reduction ability to Np(VI) compared to HOCHNH, CHNH, and CHONH, which falls completely in line with the experimental results. Additionally, the analyses of the quantum theory of atoms in molecules (QTAIM), natural bond orbitals (NBOs), electron localization function (ELF), and localized molecular orbitals (LMOs) have been put forward to elucidate the bonding evolution for the structures of the reaction pathways. This work offers insights into the reduction mechanism of Np(VI) with phenylhydrazine from the theory point of view and contributes to design more high-efficiency reductants for the separation of U/Np and Np/Pu in spent fuel reprocessing.
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http://dx.doi.org/10.1021/acs.jpca.1c04198DOI Listing
July 2021

Long- and short-term outcomes of early gastric cancer after endoscopic resection: a retrospective study from China.

Endosc Int Open 2021 Jul 21;9(7):E1086-E1096. Epub 2021 Jun 21.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.

 The aim of the study was to evaluate short- and long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in China because no study has yet been conducted to confirm its effectiveness in EGC in China.  A total of 570 EGC samples from 537 patients were collected for evaluation of en bloc, complete, and curative resection using ESD. Data from 302 patients with at least 3 years of active follow-up were collected for analysis of recurrence of EGC and occurrence of metachronous GC (MGC). Short- and long-outcomes of mixed-type and pure differentiated EGC were also compared. En bloc resection rates of 96.0 %, 98.7 %, and 95.2 %, complete resection rates of 91.2 %, 96.6 % and 90.8 %, and curative resection rates of 83.0 %, 96.2 % and 88.2 % were achieved in all EGCs included in the study, those with absolute indication, and those with expanded indication, respectively. As a long-term outcome, recurrence was observed in 1.3 % of patients, 3-year and 5-year recurrence rates being 0.7 % and 1.2 %, respectively. Thirteen patients (4.3 %) exhibited MGCs during follow-up, all of which were resected in a second ESD.  The effectiveness of ESD for EGC in China was confirmed, with satisfactory short- and long-term outcomes. With scheduled follow-up, the outcomes for mixed-type EGC can be similar to those for pure differentiated EGC after complete resection without development of lymphovascular invasion.
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http://dx.doi.org/10.1055/a-1381-7013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216778PMC
July 2021

Neo-adjuvant radiation therapy provides a survival advantage in T3-T4 nodal positive gastric and gastroesophageal junction adenocarcinoma: a SEER database analysis.

BMC Cancer 2021 Jul 3;21(1):771. Epub 2021 Jul 3.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.

Background: Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs.

Methods: We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (TN, TN, TN, and TN).

Results: Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in TN subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66-0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P <  0.001), but not in diffuse type (P = 0.11) for TN patients. In the multivariate competing risk model, NRT still showed survival advantage only in T N patients (subdistribution HR: 0.77; 95% CI: 0.64-0.93; P = 0.006), but not in other subgroups.

Conclusions: NRT might benefit resectable gastric and GEJ cancer patients of T3-4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.
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http://dx.doi.org/10.1186/s12885-021-08534-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254219PMC
July 2021

Patterns of Lymph Node Metastasis in Patients With T1/T2 Gastroduodenal Neuroendocrine Neoplasms: Implications for Endoscopic Treatment.

Front Endocrinol (Lausanne) 2021 28;12:658392. Epub 2021 May 28.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Guidelines have differed in their opinion regarding the indications for endoscopic resection of gastric-neuroendocrine neoplasms (g-NENs) and duodenal-NENs (d-NENs). We examined the association between size and lymph node metastasis (LNM) to identify candidates most suitable for endoscopic resection. We identified 706 patients with T1/T2 g-NENs and 621 patients with T1/T2 d-NENs from the SEER database. The prevalence of LNM and risk factors associated with LNM were analyzed. LNM was present in 8.1% of patients with gastroduodenal neuroendocrine tumors (NETs) and 31.6% of patients with neuroendocrine carcinomas (NECs). Multivariate logistic regression indicated that tumor size >10mm, greater invasion depth, and poor differentiation were independently associated with LNM. In addition, the percentage of g-NETs invading submucosa with LNM increased with tumor size (≤10 mm,3.9%;11-20 mm,8.6%;>20 mm,16.1%). However, in contrast to the low LNM risk in patients with small g-NETs (≤10 mm), we found that LNM rate exceeded 5% even for patients with small submucosal-infiltrating d-NETs. Among patients with nodal-negative g-NETs, the cause specific survival (CSS) was similar for those who received surgical resection and endoscopic resection. Among patients with d-NETs, the CSS was better for those who received endoscopic resection. In conclusion, patients with d-NETs had a higher probability of LNM than those with g-NETs. Endoscopic resection can be utilized for curative treatment of submucosa-infiltrating g-NETs and intramucosal d-NETs when the size is 10 mm or less. These results reinforce the need to search for LNM in lesions that are larger than 10 mm.
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http://dx.doi.org/10.3389/fendo.2021.658392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194267PMC
May 2021

The Short-term Effects of Temperature on Infectious Diarrhea among Children under 5 Years Old in Jiangsu, China: A Time-series Study (2015-2019).

Curr Med Sci 2021 Apr 20;41(2):211-218. Epub 2021 Apr 20.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.

The association between meteorological factors and infectious diarrhea has been widely studied in many countries. However, investigation among children under 5 years old in Jiangsu, China remains quite limited. Data including infectious diarrhea cases among children under five years old and daily meteorological indexes in Jiangsu, China from 2015 to 2019 were collected. The lag-effects up to 21 days of daily maximum temperature (Tmax) on infectious diarrhea were explored using a quasi-Poisson regression with a distributed lag non-linear model (DLNM) approach. The cases number of infectious diarrhea was significantly associated with seasonal variation of meteorological factors, and the burden of disease mainly occurred among children aged 0-2 years old. Moreover, when the reference value was set at 16.7°C, Tmax had a significant lag-effect on cases of infectious diarrhea among children under 5 years old in Jiangsu Province, which was increased remarkably in cold weather with the highest risk at 8°C. The results of DLNM analysis implicated that the lag-effect of Tmax varied among the 13 cities in Jiangsu and had significant differences in 8 cities. The highest risk of Tmax was presented at 5 lag days in Huaian with a maximum RR of 1.18 (95% CI: 1.09, 1.29). Suzhou which had the highest number of diarrhea cases (15830 cases), had a maximum RR of 1.04 (95% CI:1.03, 1.05) on lag 15 days. Tmax is a considerable indicator to predict the epidemic of infectious diarrhea among 13 cities in Jiangsu, which reminds us that in cold seasons, more preventive strategies and measures should be done to prevent infectious diarrhea.
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http://dx.doi.org/10.1007/s11596-021-2338-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056199PMC
April 2021

Specific epigenetic age acceleration patterns among four molecular subtypes of gastric cancer and their prognostic value.

Epigenomics 2021 May 20;13(10):767-778. Epub 2021 Apr 20.

Division of Gastroenterology & Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

To determine the association of the methylation age (Horvath epigenetic clock) of gastric cancer (GC) tissues with molecular subtypes and patient survival. Multivariate regression models were used to determine the association of methylation age acceleration (AA) with the clinical and molecular characteristics of 333 GC patients. Relative to the chromosomal instability subtype, the epigenetic AA was 49.8 (95% CI: 42.7-56.9) years for Epstein-Barr virus, 16.1 (10.6-21.6) years for microsatellite instability, and 6.05 (0.1-11.1) years for genomic stability subtype. GC patients with accelerated aging of tumor tissues had better outcomes (adjusted hazard ratio: 3.13; p = 0.03). Differentially methylated probes in patients with accelerated and decelerated methylation aging enriched in pathways including BMP signaling, HMGB1 signaling, STAT3 signaling and human embryonic stem cell pluripotency. Our results highlight the prognostic value of epigenetic AA in GC and suggest that epigenetic AA is also an indicator of molecular subtype in GC.
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http://dx.doi.org/10.2217/epi-2020-0290DOI Listing
May 2021

Divergent Alterations of Structural-Functional Connectivity Couplings in First-episode and Chronic Schizophrenia Patients.

Neuroscience 2021 04 13;460:1-12. Epub 2021 Feb 13.

Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou 510006, China; The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Huiai Hospital, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Diagnosis and Rehabilitation of Dementia, Guangzhou 510500, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Healthcare Devices, Guangzhou 510500, China; Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan. Electronic address:

Emerging evidence suggests that the coupling relating the structural connectivity (SC) of the brain to its functional connectivity (FC) exhibits remarkable changes during development, normal aging, and diseases. Although altered structural-functional connectivity couplings (SC-FC couplings) have been previously reported in schizophrenia patients, the alterations in SC-FC couplings of different illness stages of schizophrenia (SZ) remain largely unknown. In this study, we collected structural and resting-state functional MRI data from 73 normal controls (NCs), 61 first-episode (FeSZ) and 78 chronic (CSZ) schizophrenia patients. Positive and negative syndrome scale (PANSS) scores were assessed for all patients. Structural and functional brain networks were constructed using gray matter volume (GMV) and resting-state magnetic resonance imaging (rs-fMRI) time series measurements. At the connectivity level, the CSZ patients showed significantly increased SC-FC coupling strength compared with the FeSZ patients. At the node strength level, significant decreased SC-FC coupling strength was observed in the FeSZ patients compared to that of the NCs, and the coupling strength was positively correlated with negative PANSS scores. These results demonstrated divergent alterations of SC-FC couplings in FeSZ and CSZ patients. Our findings provide new insight into the neuropathological mechanisms underlying the developmental course of SZ.
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http://dx.doi.org/10.1016/j.neuroscience.2021.02.008DOI Listing
April 2021

Bone marrow mesenchymal stem cell transplantation downregulates plasma level and the microglia expression of transforming growth factor β1 in the acute phase of cerebral cortex ischemia.

Chronic Dis Transl Med 2020 Dec 1;6(4):270-280. Epub 2020 Jul 1.

Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical School of Yangzhou University, Yangzhou, Jiangsu 225001, China.

Background: Both bone marrow mesenchymal stem cell (BM-MSC) and transforming growth factor-β1 (TGF-β1) have a strong anti-inflammatory capacity in stroke. But their relationship has not been well addressed. In this study, we investigated how intravenous BM-MSC transplantation in rats effected the expression of TGF-β1 48 h post cerebral ischemia, and we analyzed the main cells that produce TGF-β1.

Methods: We used a distal middle cerebral artery occlusion (dMCAO) model in twenty Sprague-Dawley (SD) rats. The rats were randomly divided into two groups: the ischemic control group and the postischemic BM-MSC transplantation group. One hour after the dMCAO model was established, the rats were injected in the tail vein with either 1 ml saline or 1 × 10 BM-MSCs suspended in 1 ml saline. ELISAs were used to detect TGF-β1 content in the brain infarct core area, striatum and the plasma at 48 h after cerebral infarction. Immunofluorescent staining of brain tissue sections for TGF-β1, Iba-1, CD68 and NeuN was performed to determine the number and the proportion of double stained cells and to detect possible TGF-β1 producing cells in the brain tissue.

Results: Forty-eight hours after ischemia, the TGF-β1 content in the infarcted area of the BM-MSC transplantation group (23.94 ± 4.48 pg/ml) was significantly lower than it was in the ischemic control group (34.18 ± 4.32 pg/ml) (F = 13.534,  = 0.006). The TGF-β1 content in the rat plasma in the BM-MSC transplantation group (75.91 ± 12.53 pg/ml) was significantly lower than it was in the ischemic control group (131.18 ± 16.07 pg/ml) (F = 36.779,  = 0.0002), suggesting that after transplantation of BM-MSCs, TGF-β1 levels in the plasma decreased, but there was no significant change in the striatum area. Immunofluorescence staining showed that the total number of nucleated cells (1037.67 ± 222.16 cells/mm) in the infarcted area after transplantation was significantly higher than that in the ischemic control group (391.67 ± 69.50 cells/mm) (F = 92.421,  < 0.01); the number of TGF-β1 cells after transplantation (35.00 ± 13.66 cells/mm) was significantly reduced in comparison to that in the ischemic control group (72.33 ± 32.08 cells/mm) (F = 37.680,  < 0.01). The number of TGF-β1/Iba-1 microglia cells in the transplantation group (3.67 ± 3.17 cells/mm) was significantly reduced in comparison to that of the ischemic control group (13.67 ± 5.52 cells/mm) (F = 29.641,  < 0.01). The proportion of TGF-β1/Iba-1 microglia cells out of all Iba-1 microglia cells after transplantation (4.38 ± 3.18%) was significantly decreased compared with that in the ischemic control group (12.81 ± 4.86%) (F = 28.125,  < 0.01).

Conclusions: Iba-1 microglia is one of the main cell types that express TGF-β1. Intravenous transplantation of BM-MSCs does not cooperate with TGF-β1 cells in immune-regulation, but reduces the TGF-β1 content in the infarcted area and in the plasma at 48 h after cerebral infarction.
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http://dx.doi.org/10.1016/j.cdtm.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729118PMC
December 2020

Association between positivity of serum autoantibodies and liver disease severity in patients with biopsy-proven NAFLD.

Nutr Metab Cardiovasc Dis 2021 02 13;31(2):552-560. Epub 2020 Oct 13.

NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China. Electronic address:

Background And Aims: Some previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD.

Methods And Results: A total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77-11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30-7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3-F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype.

Conclusions: Serum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.
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http://dx.doi.org/10.1016/j.numecd.2020.10.004DOI Listing
February 2021

lncRNA VIM‑AS1 promotes cell proliferation, metastasis and epithelial‑mesenchymal transition by activating the Wnt/β‑catenin pathway in gastric cancer.

Mol Med Rep 2020 Dec 11;22(6):4567-4578. Epub 2020 Oct 11.

Yulin Cancer Diagnosis and Treatment Center, The First Hospital of Yulin, Yulin, Shaanxi 719000, P.R. China.

The present study aimed to explore the biological functions and molecular mechanisms of the long non‑coding RNA VIM antisense RNA 1 (VIM‑AS1) in gastric cancer (GC). The expression of VIM‑AS1 was analyzed in tissues from patients with GC and GC cell lines by reverse transcription‑quantitative (RT‑q)PCR. The relationship between VIM‑AS1 expression and overall survival time of patients with GC was also assessed. To determine the biological functions of VIM‑AS1, Cell Counting Kit‑8 assay, colony formation assay, flow cytometry, wound healing assay and Transwell assay were employed. The targeting relationship among VIM‑AS1, microRNA (miR)‑8052 and frizzled 1 (FZD1) was verified by the dual luciferase reporter gene assay. The underlying molecular mechanism of VIM‑AS1 on GC was determined by RT‑qPCR and western blotting. In addition, tumor formation was detected in nude mice. The results of the present study demonstrated that VIM‑AS1 was highly expressed in GC tissues and cells. In addition, VIM‑AS1 expression was demonstrated to be closely related to the prognosis of patients with GC. Notably, silencing VIM‑AS1 inhibited the proliferation, migration and invasion, and enhanced apoptosis of AGS and HGC‑27 cells. Silencing VIM‑AS1 significantly increased the protein expression levels of cleaved caspase‑3, Bax and E‑cadherin, but decreased the protein expression levels of Bcl‑2, N‑cadherin, vimentin, matrix metalloproteinase (MMP)‑2, MMP‑9, β‑catenin, cyclin D1, C‑myc and FZD1. Additionally, silencing VIM‑AS1 inhibited tumor growth in nude mice. Cumulatively, the present study demonstrated that VIM‑AS1 may promote cell proliferation, migration, invasion and epithelial‑mesenchymal transition by regulating FDZ1 and activating the Wnt/β‑catenin pathway in GC.
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http://dx.doi.org/10.3892/mmr.2020.11577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646824PMC
December 2020

Qualitative Transcriptional Signature for the Pathological Diagnosis of Pancreatic Cancer.

Front Mol Biosci 2020 23;7:569842. Epub 2020 Sep 23.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

It is currently difficult for pathologists to diagnose pancreatic cancer (PC) using biopsy specimens because samples may have been from an incorrect site or contain an insufficient amount of tissue. Thus, there is a need to develop a platform-independent molecular classifier that accurately distinguishes benign pancreatic lesions from PC. Here, we developed a robust qualitative messenger RNA signature based on within-sample relative expression orderings (REOs) of genes to discriminate both PC tissues and cancer-adjacent normal tissues from non-PC pancreatitis and healthy pancreatic tissues. A signature comprising 12 gene pairs and 17 genes was built in the training datasets and validated in microarray and RNA-sequencing datasets from biopsy samples and surgically resected samples. Analysis of 1,007 PC tissues and 257 non-tumor samples from nine databases indicated that the geometric mean of sensitivity and specificity was 96.7%, and the area under receiver operating characteristic curve was 0.978 (95% confidence interval, 0.947-0.994). For 20 specimens obtained from endoscopic biopsy, the signature had a diagnostic accuracy of 100%. The REO-based signature described here can aid in the molecular diagnosis of PC and may facilitate objective differentiation between benign and malignant pancreatic lesions.
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http://dx.doi.org/10.3389/fmolb.2020.569842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538791PMC
September 2020

Chemotherapy-based split stereotactic body radiation therapy for borderline resectable and locally advanced pancreatic cancer: study protocol of a prospective, single-arm phase II trial.

BMJ Open 2020 11 5;10(11):e039900. Epub 2020 Nov 5.

Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China

Introduction: The question of how to administer adequate chemotherapy to synchronise stereotactic body radiation therapy (SBRT) treatment strategy to maximise the benefits of neoadjuvant therapy for the improved prognosis of patients with borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer is a challenging and debatable issue. No studies have yet evaluated the efficacy of split-course SBRT as the neoadjuvant chemoradiotherapy regimen. We aimed to study whether neoadjuvant chemotherapy plus split-course SBRT results in better outcomes in BRPC and LAPC patients.

Methods And Analysis: Treatment-naïve patients with radiographically confirmed BRPC or LAPC, supporting biopsy results and no severe comorbidities will be enrolled. They will be treated with nab-paclitaxel plus gemcitabine (nab-P+Gem) chemotherapy plus split-course SBRT, followed by an investigator's choice of continuation of treatment with nab-P+Gem or surgery. nab-P+Gem chemotherapy will commence on day 1 for each of six cycles: nab-paclitaxel 125 mg/m intravenous infusion over approximately 30-45 min, followed by gemcitabine 1000 mg/m intravenous infusion over about 30 min on days 1 and 15 of each 28-day cycle. During the first and second cycles of chemotherapy, SBRT will be given as a single irradiation of 10 Gy four times (days 2 and 16 of each 28-day cycle). The primary endpoint is progression-free survival; while the secondary outcomes are the time to treatment failure, disease control rate, overall response rate, overall survival, R0 resection rate and incidence of adverse effects.

Ethics And Dissemination: The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (No. 2019YF015-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality.

Trial Registration Number: NCT04289792.
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http://dx.doi.org/10.1136/bmjopen-2020-039900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646341PMC
November 2020

Discovery of a novel EGFR ligand DPBA that degrades EGFR and suppresses EGFR-positive NSCLC growth.

Signal Transduct Target Ther 2020 10 9;5(1):214. Epub 2020 Oct 9.

College of Pharmacy, Jinan University, Guangzhou, China.

Epidermal growth factor receptor (EGFR) activation plays a pivotal role in EGFR-driven non-small cell lung cancer (NSCLC) and is considered as a key target of molecular targeted therapy. EGFR tyrosine kinase inhibitors (TKIs) have been canonically used in NSCLC treatment. However, prevalent innate and acquired resistances and EGFR kinase-independent pro-survival properties limit the clinical efficacy of EGFR TKIs. Therefore, the discovery of novel EGFR degraders is a promising approach towards improving therapeutic efficacy and overcoming drug resistance. Here, we identified a 23-hydroxybetulinic acid derivative, namely DPBA, as a novel EGFR small-molecule ligand. It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant NSCLC by degrading EGFR. Mechanistic studies disclosed that DPBA binds to the EGFR extracellular domain at sites differing from those of EGF and EGFR. DPBA did not induce EGFR dimerization, phosphorylation, and ubiquitination, but it significantly promoted EGFR degradation and repressed downstream survival pathways. Further analyses showed that DPBA induced clathrin-independent EGFR endocytosis mediated by flotillin-dependent lipid rafts and unaffected by EGFR TKIs. Activation of the early and late endosome markers rab5 and rab7 but not the recycling endosome marker rab11 was involved in DPBA-induced EGFR lysosomal degradation. The present study offers a new EGFR ligand for EGFR pharmacological degradation and proposes it as a potential treatment for EGFR-positive NSCLC, particularly NSCLC with innate or acquired EGFR TKI resistance. DPBA can also serve as a chemical probe in the studies on EGFR trafficking and degradation.
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http://dx.doi.org/10.1038/s41392-020-00251-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544691PMC
October 2020

Natural products as potent inhibitors of hypoxia-inducible factor-1α in cancer therapy.

Chin J Nat Med 2020 Sep;18(9):696-703

College of Pharmacy, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou 510632, China. Electronic address:

Hypoxia is a prominent feature of tumors. Hypoxia-inducible factor-1α (HIF-1α), a major subunit of HIF-1, is overexpressed in hypoxic tumor tissues and activates the transcription of many oncogenes. Accumulating evidence has demonstrated that HIF-1α promotes tumor angiogenesis, metastasis, metabolism, and immune evasion. Natural products are an important source of antitumor drugs and numerous studies have highlighted the crucial role of these agents in modulating HIF-1α. The present review describes the role of HIF-1α in tumor progression, summarizes natural products used as HIF-1α inhibitors, and discusses the potential of developing natural products as HIF-1α inhibitors for the treatment of cancer.
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http://dx.doi.org/10.1016/S1875-5364(20)60008-5DOI Listing
September 2020

Clinical and genetic features of transthyretin-related familial amyloid polyneuropathy in China.

Chin Med J (Engl) 2020 Nov;133(21):2616-2618

Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.

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http://dx.doi.org/10.1097/CM9.0000000000001094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722615PMC
November 2020

Marital status, an independent predictor for survival of gastric neuroendocrine neoplasm patients: a SEER database analysis.

BMC Endocr Disord 2020 Jul 23;20(1):111. Epub 2020 Jul 23.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.

Background: Marital status proves to be an independent prognostic factor in a variety of cancers. However, its prognostic impact on gastric neuroendocrine neoplasms (G-NEN) has not been investigated.

Methods: We identified 3947 G-NEN patients from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, propensity scores for marital status were used to match 506 unmarried patients with 506 married patients. We used Kaplan-Meier method and multivariate Cox regression to analyse the association between marital status and the overall survival (OS) and G-NEN cause-specific survival (CSS) before matching and after matching.

Results: Married patients enjoyed better OS and CSS, compared with divorced/separated, single, and widowed patients. Multivariate Cox regression analysis indicated that unmarried status was associated with higher mortality hazards for both OS and CSS among G-NEN patients. Additionally, widowed individuals had the highest risks of overall (adjusted hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.35-1.81, P < 0.001) and cancer-specific mortality (adjusted HR: 1.33, 95% CI: 1.05-1.68, P = 0.02) compared to other unmarried groups in both males and females. Furthermore, unmarried status remained an independent prognostic and risk factor for both OS (HR 1.51, 95% CI 1.19-1.90, P = 0.001) and CSS (HR 1.50, 95% CI 1.10-2.05, P = 0.01) in 1:1 propensity score-matched analysis.

Conclusion: Marital status was an independent prognostic factor for G-NEN. Meanwhile, widowed patients with G-NEN had the highest risk of death compared with single, married, and divorced/separated patients.
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http://dx.doi.org/10.1186/s12902-020-00565-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376955PMC
July 2020

Theoretical Study on the Reduction Mechanism of Np(VI) by Hydrazine Derivatives.

J Phys Chem A 2020 May 29;124(19):3720-3729. Epub 2020 Apr 29.

Laboratory of Nuclear Energy Chemistry, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

The key to effective separation of neptunium from the spent fuel reprocessing process is to adjust and control its valence state. Hydrazine and its derivatives have been experimentally confirmed to be effective salt-free reductants for reducing Np(VI) to Np(V). We theoretically studied the reduction reactions of Np(VI) with three hydrazine derivatives (2-hydroxyethyl hydrazine (HOCHNH), methyl hydrazine (CHNH), and formyl hydrazide (CHONH)) and obtained the free radical ion mechanism and the free radical mechanism. Their potential energy profiles (PEPs) suggest that the free radical mechanism is the most probable reaction. Based on the energy barrier of the free radical ion mechanism, the trend of the reduction ability of the three hydrazine derivatives is HOCHNH > CHNH > CHONH, which is in excellent agreement with the experimental results. Lastly, the analyses of natural bond orbitals (NBOs), quantum theory of atoms-in-molecules (QTAIM), and electron localization function (ELF) have been carried out to explore the bonding evolution of the structures along the reaction pathways. This work provides an insight into the reduction mechanism of Np(VI) with hydrazine derivatives from the theoretical perspective and helps to design more effective reductants for the separation of U/Np and Np/Pu in spent fuel reprocessing.
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http://dx.doi.org/10.1021/acs.jpca.0c01504DOI Listing
May 2020

Poorly differentiated is more significant than signet ring cell component for lymph node metastasis in mixed-type early gastric cancer: a retrospective study from a large-volume hospital.

Surg Endosc 2021 04 10;35(4):1558-1565. Epub 2020 Apr 10.

Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Objective: The purpose of this study was to explore the role of different undifferentiated components in the lymph node metastasis (LNM) of early mixed gastric cancer.

Methods: A total of 1596 patients with EGC who underwent gastrectomy were divided into four types: pure differentiated (PD), pure poorly differentiated (Poorly D), pure signet ring cell carcinoma (SRC), and mixed. Mixed type was classified into four subtypes: differentiated-predominant type mixed with poorly differentiated component (MD-P), poorly differentiated-predominant type mixed with differentiated component (MP-D), differentiated-predominant type mixed with SRC component (MD-S), and poorly differentiated-predominant type mixed with SRC component (MP-S). We analyzed the clinicopathological differences between all types and the rates of LNM of patients fulfilling endoscopic submucosal dissection (ESD) criteria.

Results: LNM was more common in mixed (21.9%) than in PD (7.5%, P < 0.001) or SRC (11.3%, P < 0.001). When analyzed the subgroups of mixed type, LNM was more frequent in MD-P (15.4%) than in PD (7.5%, P = 0.003). LNM in MD-S (7.4%, P = 1.000) was not higher than in PD. MP-S (24.5%) showed a higher rate of LNM than SRC (11.3%, P < 0.001) rather than Poorly-D (22.7%, P = 0.681). For lesions satisfying ESD criteria, MD-S (0%, P = 1.000), and MD-P (5.9%, P = 0.12) did not have higher rates of LNM than PD (1.4%).

Conclusion: The presence of poorly differentiated component but not SRC increases the LNM rate of mixed type. ESD is recommended for the treatment of MD-S and MD-P consistent with ESD criteria.
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http://dx.doi.org/10.1007/s00464-020-07532-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940273PMC
April 2021

Prognosis of colorectal cancer patients is associated with the novel log odds of positive lymph nodes scheme: derivation and external validation.

J Cancer 2020 16;11(7):1702-1711. Epub 2020 Jan 16.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.

To construct proper and externally validate cut-off points for log odds of positive lymph nodes scheme (LODDS) staging scheme in colorectal cancer (CRC). The X-tile approach was used to find the cut-off points for the novel LODDS staging scheme in 240,898 patients from the Surveillance, Epidemiology and End Results (SEER) database and externally validated in 1,878 from the international multicenter cohort. Kaplan-Meier plot and multivariate Cox proportional hazard models were performed to investigate the role of the novel LODDS classification. The prognostic cut-off values were determined as -2.18, and -0.23 (< 0.001). Patients had 5-year cancer-specific survival rates of 83.8%, 57.4% and 24.4% with increasing LODDS (< 0.001) in the SEER database. Five-year overall survival rates were 77.2%, 55.0% and 26.7% with increasing LODDS (< 0.001) in the external international multicenter cohort. Multivariate survival analysis identified both the LODDS classification, the patient's age, the T category, the M status, and the tumor grade as independent prognostic factors in both two independent databases. The analyses of the subgroup of patients stratified by tumor location (colon or rectum), number of retrieved lymph node (< 12 or ≥ 12), TNM stage III, lymph node-negative also confirmed the LODDS as independent prognostic factors (< 0.001) in both two independent databases. The novel LODDS classification was an independent prognostic factor for patients with CRCs and should be calculated for additional risk group stratification with pN scheme.
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http://dx.doi.org/10.7150/jca.38180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052858PMC
January 2020

Young-Onset Early Colorectal Cancer Had Similar Relative Survival to but Better Overall Survival Than Conventional Early Colorectal Cancer: A Large Population-Based Study.

Front Oncol 2020 27;10:96. Epub 2020 Feb 27.

Key Laboratory of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, Ministry of Health, School of Medicine, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.

There existed limited evidence about prognosis of young-onset early colorectal cancer (ECRC). In the present study, we aimed to compare prognosis between patients with young-onset ECRCs and patients with conventional ECRCs. Patients with surgically resected, histologically diagnosed ECRCs were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Young-onset ECRC was defined as ECRC occurring in patients aged <50 years. Five-years relative survival was calculated at the time of diagnosed year and linear regression was performed to analyze the association between 5-years relative survival and age. The multivariate Cox regression, multivariate competing risk model, and propensity score matching (PSM) and univariate analysis weighted by the inverse probability of treatment weight (IPTW) were used to compare overall survival (OS) between young-onset ECRCs and conventional ECRCs. A total of 51,197 ECRCs were retrieved from SEER database, including 4,634 young-onset ECRCs and 46,563 conventional ECRCs. Five-years relative survival was found to be moderately associated with different age groups ( = -0.725, = 0.0034). Patients with young-onset ECRCs (96.7%) had similar 5-years relative survival compared with conventional ECRCs (96.3%). However, multivariate Cox regression [HR (hazard ratio), 0.18; 95% CI: 0.16-0.20; < 0.001] showed better OS in young-onset ECRCs. After PSM, we still found favored prognosis for young-onset ECRCs under univariate Cox regression (HR, 0.18; 95% CI: 0.16-0.21; < 0.001). Similar results could also be found in the univariate Cox regression weighted by IPTW (HR, 0.17; 95% CI: 0.17-0.18; < 0.001). Patients with young-onset ECRCs had similar relative survival but better OS compared with conventional ECRCs.
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http://dx.doi.org/10.3389/fonc.2020.00096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056900PMC
February 2020

Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications.

Cancer Immunol Immunother 2020 Jun 25;69(6):1057-1069. Epub 2020 Feb 25.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai, 200001, China.

Background: Immunotherapy could trigger durable response in advanced gastric cancer, but it only benefits a minority of patients. We aimed to propose a robust molecular classification of gastric cancer microenvironment to identify ideal candidates for tailoring effective immunotherapy.

Methods: A training cohort of 375 gastric cancer samples with RNA sequencing data was analysed. We virtually microdissected tumour, stromal, and immune cell gene expression patterns employing a non-negative matrix factorization algorithm. These expression patterns were annotated using immune- and stromal-related gene signatures. Validation of immunogenomic classification was performed across six microarray datasets of 1406 samples.

Results: We found approximately half of gastric cancer samples to have higher immune cell infiltrates, PD-L1 expression, markers of cytolytic activity, and fewer copy number aberrations (all P < 0.05). We termed this group of tumours the Immune Class, which incorporated two components, namely Immune Activation and Immunosuppressive Subtype, according to immunosuppressive or activated microenvironment. Immune Activation Subtype was associated with improved survival in multivariate survival analysis and shared similar genomic characteristics with responders of anti-PD-1 therapy. Immunosuppressive Subtype featured high immune infiltration, stromal enrichment, and transforming growth factor (TGF)-β signalling pathway activation and correlated with non-responsiveness signature of checkpoint blockade therapy, which might be suitable for anti-PD-L1 and anti-TGF-β combined therapy.

Conclusions: We proposed and independently validated three reproducible immune molecular subtypes of gastric cancer, which may provide implications for patient selection of immunotherapy.
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http://dx.doi.org/10.1007/s00262-020-02525-8DOI Listing
June 2020

Feasibility of using narrow band imaging international colorectal endoscopic classification for diagnosing colorectal neoplasia in China: A multicenter pilot observational study.

J Dig Dis 2020 Feb;21(2):88-97

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: We aimed to investigate whether Chinese endoscopists without narrow-band imaging (NBI) experiences could achieve high accuracy in the real-time diagnosis of colorectal polyps using NBI International Colorectal Endoscopic (NICE) classification after web-based training.

Methods: Altogether 15 endoscopists from five centers with no NBI experiences followed a short, web-based training program on the NICE classification and took web-based test. Their performances were compared with 15 matched experienced endoscopists with no NBI experience who received no NBI training. These 15 trained endoscopists then made real-time diagnoses of colorectal neoplasia. A logistic regression was used to assess potential predictors of diagnostic performance.

Results: Compared with those who received no training, trained endoscopists achieved comparable overall accuracy (85.3% vs 83.1%, P = 0.408) and accuracy at a high-confidence level (87.0% vs 86.0%, P = 0.670), but had a higher confidence rate (86.1% vs 83.7%, P = 0.004) for the diagnosis of neoplasia. Real-time diagnostic accuracy, sensitivity and specificity were 94.3% (95% confidence interval [CI] 91.5%-96.2%), 96.2% (95% CI 93.4%-97.9%) and 85.3% (95% CI 74.8%-92.1%) at high-confidence level. The high-confidence level was the strongest predictor of real-time diagnostic accuracy (odds ratio 12.66, P < 0.001).

Conclusions: Web-based training can improve the confidence level of endoscopists in accurately diagnosing colorectal polyps using the NICE classification. Chinese endoscopists can achieve high accuracy in diagnosing colorectal neoplasia at a high confidence level (ClinicalTrials ID: NCT02033980).
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http://dx.doi.org/10.1111/1751-2980.12841DOI Listing
February 2020

[Comprehensive mass spectrum analysis of two flavone-6,8-C-di-glycosides and its application by high resolution electrospray ionization tandem mass spectroscopy in both negative and positive ion modes].

Zhongguo Zhong Yao Za Zhi 2019 Nov;44(22):4880-4887

School of Pharmacy,Shanghai Jiao Tong University Shanghai 200240,China.

The tandem mass spectrum of apigenin-6,8-C-di-glucoside( 1) and apigenin-6-C-glucose-8-C-rhamnoside( 2) were obtained by high resolution electrospray ionization mass spectrometry( HR-ESI-MS/MS) in both positive and negative ion modes. The elemental composition of each ion was determined according to its accurate mass-to-charge,hence,the fragmentation pathways of each compound were proposed in both negative and positive ion modes. Comprehensive analysis of each ion and its proposed fragmentation pathways of the two compounds was initially conducted in both negative and positive ion mode HR-ESI-MS/MS to explore the diagnostic ions for flavone-6,8-C-di-glycosides and the characteristic ions for each compound and their cleavage rules. The results showed that a family of fragmentation ions with m/z 353,325,311,297 in ESI(-)-MS and m/z 355,325,307,295 in ESI( +)-MS could be the diagnostic ions of flavone-6,8-C-di-glycoside,and characteristic neutral loss could be assigned to glycosyl substitution,for example,neutral losses of C_4H_8O_4( 120),C_3H_6O_3( 90),C_2H_4O_2( 60) for glucoside substitution while neutral losses of C_4H_8O_3(104),C_3H_6O_2( 74),C_2H_4O( 44) for rhamnoside substitution. Furthermore,only one H_2O loss from mother ion( [M-H]-) was observed for 1 & 2 in ESI(-)-MS while five to six H2 O loss from mother ion( [M+H]+) was observed for 1 & 2 in ESI( +)-MS to produce a family of ions by subsequent loss of H_2O,which could be applied for glucosyl difference. The flavone-6,8-C-di-glycosides in both ESI( +)-MS and ESI(-)-MS showed the cleavage similarity at sugar substitutions. However,there were much more differences by the fragmentation pathways and neutral losses between ESI( +)-MS and ESI(-)-MS as following,hyperconjugation ions by subsequent loss of H_2O from precursor ions of flavone-6,8-C-di-glycosides in ESI( +)-MS were not observed in ESI(-)-MS; the subsequent neutral loss of CH_2O in ESI( +)-MS were rarely observed in ESI(-)-MS; the loss of CO only happen at C-ring of flavone ESI( +)-MS other than glycosyl position in ESI(-)-MS; the C4-chain neutral loss of flavone-6,8-C-di-glycosides happened at 8-C-glycosyl position other than at 6-C-glycosyl position. The above cleavage rules and diagnostic ions of ESI( +)-MS were successfully applied for the structure identification of 4 flavone-6 C,8 C-diglycosides from the stem extract of Dendrobium officinale as vicenin Ⅱ,vicenin Ⅰ,isoschaftoside,schaftoside as well as one flavone-O-glysoside named rutin,which were supported by ESI(-)-MS data as well.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190823.201DOI Listing
November 2019

Survival-Associated Alternative Messenger RNA Splicing Signatures in Pancreatic Ductal Adenocarcinoma: A Study Based on RNA-Sequencing Data.

DNA Cell Biol 2019 Nov 4;38(11):1207-1222. Epub 2019 Sep 4.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China.

Multiple studies have shown that cancer-specific alternative splicing (AS) alterations are associated with clinical outcome. In this study, we aimed to profile prognostic AS signatures for pancreatic ductal adenocarcinoma (PDAC). We integrated the percent-spliced-in (PSI) data of AS in 140 PDAC patients based on the Cancer Genome Atlas (TCGA) dataset. We identified overall survival (OS)-associated AS events using univariate Cox regression analysis. Then, prognostic AS signatures were constructed for OS and chemoresistance prediction using the least absolute shrinkage and selection operator (LASSO) method. We also analyzed splicing factors (SFs) regulatory networks by Pearson's correlation. We detected 677 OS-related AS events in 485 genes by profiling 10,354 AS events obtained from 140 PDAC patients. Gene functional enrichment analysis demonstrated the pathways enriched by survival-associated AS. The AS signatures constructed with significant survival-associated AS events revealed high performance in predicting PDAC survival and gemcitabine chemoresistance. The area under the receiver operator characteristic curve was 0.937 in training cohort and 0.748 in validation cohort at 2000 days of OS. Furthermore, we identified prognostic SFs (e.g., ESRP1 and HNRNPC) to build the AS regulatory network. We constructed AS signatures for OS and gemcitabine chemoresistance in PDAC patients, which may provide clues for further experiment-based mechanism study.
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http://dx.doi.org/10.1089/dna.2019.4862DOI Listing
November 2019

Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors.

Eur J Med Chem 2019 Aug 29;175:357-372. Epub 2019 Apr 29.

Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Science, Institute of Drug Discovery and Development, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China. Electronic address:

Lysine-specific demethylase 1 (LSD1), demethylase against mono- and di - methylated histone3 lysine 4, has emerged as a promising target in oncology. More specifically, it has been demonstrated as a key promoter in acute myeloid leukemia (AML), and several LSD1 inhibitors have already entered into clinical trials for the treatment of AML. In this paper, a series of new indole derivatives were designed and synthesized based on a lead compound obtained by a high-throughput screening with our in-house compound library. Among the synthetic compounds, 9e was characterized as a potent LSD1 inhibitor with an IC of 1.230 μM and can inhibit the proliferation of THP-1 cells effectively. And most importantly, this is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. Hence, the discovery of 9e may serve as a proof of concept work for AML treatment.
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http://dx.doi.org/10.1016/j.ejmech.2019.04.065DOI Listing
August 2019

Research of Biological Dose Conversion Platform Based on a Modified Linear Quadratic Model.

Dose Response 2019 Jan-Mar;17(1):1559325819828623. Epub 2019 Mar 28.

Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.

The study aimed to develop a novel dose conversion platform by improving linear-quadratic (LQ) model to more accurately describe radiation response for high fraction/acute doses. This article modified the LQ model via piecewise fitting the biological dose curve using different fractionated dose and optimizing the consistency between mathematical model and experimental data to gain a more reasonable transform. That mathematical development of the LQ model further amended certain deviations of various cell curves with high doses and implied the rationality of the present model at low dose range. The modified biologically effective dose model that solved the dilemma of inaccurate LQ model had been used in comparing between hypofractionated and conventional fractioned dose. It has been verified that the calculated values are similar in the treatment of same efficacy, no matter what α/β is, and provided a more rational explanation for significant differences among various hypofractionations. The equivalent uniform dose based on the subsection function could represent arbitrary inhomogeneous dose distributions including high-dose fractions, providing a foundation for the implementation of detailed evaluation of different cell dose effects.
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http://dx.doi.org/10.1177/1559325819828623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440057PMC
March 2019

Utility of a standardized training program for endoscopic diagnosis of early gastrointestinal neoplasia.

Endosc Int Open 2019 Apr 21;7(4):E452-E458. Epub 2019 Mar 21.

Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.

 Image enhanced endoscopy (IEE) allows endoscopists to improve recognition and characterization of gastrointestinal neoplasia. The Asian Novel Bio-Imaging and Intervention Group (ANBIG) conducted a standardized training program in endoscopic diagnosis and treatment of early gastrointestinal cancers in Asia. We embarked on a study to investigate the effect of this module on endoscopic diagnosis of early gastrointestinal neoplasia.  This prospectively collected database was from workshops conducted on training for endoscopic diagnosis of early gastrointestinal neoplasia. All workshops were conducted in a standardized format, which included a pretest, a learning phase consisting of didactic lectures, case discussion, and live demonstration followed by a post-test to assess knowledge gained. The pretest and post-training tests were standardized questions addressing four domains, including basic knowledge of imaging and diagnosis of esophageal, gastric, and colonic neoplasia.  From November 2013 to November 2016, 41 ANBIG workshops were conducted in 13 countries. A total of 1863 delegates and 40 faculty participated in these workshops. Of the delegates, 627 completed both tests. There was a significant improvement after training in all domains of the tests. There was a trend in general lack of knowledge across all domains for delegates from "low" healthcare cost countries before training. All delegates demonstrated significant improvement in knowledge of all domains after the workshop irrespective of whether they were from "high" or "low" healthcare cost per capita countries.  A standardized teaching program on IEE improved the diagnostic ability and quality of endoscopists in recognizing early gastrointestinal neoplasia in Asia.
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http://dx.doi.org/10.1055/a-0854-3525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428678PMC
April 2019
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