BACKGROUND & AIMS:Autoimmune hepatitis (AIH) is a chronic progressive inflammatory liver disease, with its incidence increasing continuously worldwide. The mechanisms underlying the regulation of immune tolerance in AIH remain largely unknown. This study investigated a novel regulatory pathway of regulatory T cell/T helper 17 (Treg/Th17) balance involving the ubiquitin-conjugating enzyme E2O (UBE2O) and underlying mechanisms. METHODS:UBE2O expression was analyzed in patients and mice with AIH. In vivo UBE2O overexpression in a chronic AIH model and naïve CD4+ T differentiation induction assays were used to investigate the exact role of UBE2O in AIH. Liver samples were assessed by histology, immunochemistry, immunoblot, flow cytometry, and enzyme-linked immunosorbant assays. Mass spectrometry, co-immunoprecipitation, cytokine microarray, and site-specific mutation experiments were utilized to elucidate underlying molecular mechanisms. RESULTS:We detected a reduction of UBE2O expression in livers of patients and mice with AIH. Low expression of UBE2O indicated severe liver inflammatory injury. Hepatic UBE2O overexpression experiments demonstrated that UBE2O alleviated hepatic injury, inflammation, and fibrosis, and restored Treg/Th17 balance in experimental AIH. Mechanistically, UBE2O was found to interact with and promote ubiquitination degradation of YBX1 at lysine 135 (K135), leading to the reduction of interleukin-6 transcription and secretion in hepatocytes, thus rewiring naïve CD4+ T cells differentiation into Tregs. Furthermore, YBX1 partially reversed the protective effects of UBE2O overexpression in AIH. CONCLUSIONS:Our study revealed a previously unrecognized hepatocellular UBE2O/YBX1/interleukin-6 axis in AIH that primes hepatocytes to restore immune tolerance. Targeting UBE2O might provide a promising therapeutic target for AIH by linking posttranslational modification and hepatic immune tolerance.

Lenvatinib, as a multi-kinase inhibitor, has been approved as a first-line drug for patients with advanced hepatocellular carcinoma (HCC). Gasdermin E (GSDME)-mediated pyroptosis, a form of programmed cell death, can be induced by chemotherapy drugs or certain kinase inhibitors. However, the role of Lenvatinib in inducing pyroptosis in HCC warrants further investigation. Phase contrast microscopy, LDH assays, and gain- and loss-of-function strategies were used to evaluate Lenvatinib-induced pyroptosis in HCC cells. GSDME palmitoylation was assessed via the acyl-biotin exchange method. In vivo, a subcutaneous HCC xenograft model in nude mice were established to assess the effects of interfering with GSDME on the sensitivity of HCC to Lenvatinib. Lenvatinib induced pyroptosis in HCC cells in a dose- and time-dependent manner. Additionally, Lenvatinib promoted GSDME cleavage, with upregulation of GSDME enhancing pyroptosis and downregulation reducing this effect. The ABE method revealed that GSDME is palmitoylated, and Lenvatinib increased its palmitoylation, promoting plasma membrane localization and enhancing protein stability. Inhibition of GSDME palmitoylation by 2-BP blocked Lenvatinib-induced pyroptosis. In vivo, upregulation of GSDME increased HCC sensitivity to Lenvatinib and inhibited tumor growth. Lenvatinib induces pyroptosis in HCC by promoting the palmitoylation of GSDME, enhancing its localization to the plasma membrane and increasing its protein stability. Interfering with GSDME, both in vitro and in vivo, affects Lenvatinib-induced pyroptosis, thereby altering the therapeutic sensitivity of HCC to Lenvatinib. Targeting GSDME palmitoylation represents a potential therapeutic strategy for HCC, as it enhances Lenvatinib-induced pyroptosis and improves the therapeutic response.

BACKGROUND:High-dose dual therapy (HDDT) is an emerging and promising therapeutic regime for Helicobacter pylori (H. pylori) eradication. However, the pharmacokinetics of the components of HDDT, amoxicillin and proton pump inhibitor, are likely to be affected by body size. In this study, we aimed to find out the impact of body size on the efficacy of HDDT. METHODS:We collected the medical data of 385 treatment-naive patients infected with H. pylori who received HDDT (esomeprazole 20 mg and amoxicillin 750 mg four times daily) for 14 days from July 2020 to December 2021. The associations among the eradication efficacy, adverse events, and variables (sex, age, height, body weight, body mass index (BMI), body surface area (BSA), smoking, drinking, etc.) were analyzed respectively in our study. Among these factors, continuous variables were classified into categorical variables using the cut-off values which were calculated by receiver operating characteristic analysis. RESULTS:The eradication rate of HDDT was 89.9%. There were 55 (14.3%) patients who occurred adverse events during the treatment. Patients with height <170.5 cm, body weight <60.5 kg, BMI <20.55 kg/m2 , BSA <1.69 m2 had a higher eradication rate (92.1% vs. 84.0%, 93.1% vs. 86.8%, 96.0% vs. 87.8%, 93.4% vs. 84.8%, all p < .05). The multivariate analysis showed that BSA ≥1.69 m2 (OR 2.53, 95% CI: 1.28-4.99, p = .007) was the only independent predictor of eradication failure. CONCLUSION:HDDT could achieve better eradication efficacy in patients with small BSA. Clinicians should be aware of the impact of BSA on the H. pylori eradication rate and pay more attention to patients with large BSA.

A growing body of epidemiological evidence suggests that nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for chronic kidney disease (CKD), but the regulatory mechanism linking NAFLD and CKD remains unclear. Our previous studies have shown that overexpression of PDE4D in mouse liver is sufficient for NAFLD, but little is known about its role in kidney injury. Here, liver-specific PDE4D conditional knockout (LKO) mice, adeno-associated virus 8 (AAV8)-mediated gene transfer of PDE4D and the PDE4 inhibitor roflumilast were used to assess the involvement of hepatic PDE4D in NAFLD-associated renal injury. We found that mice fed a high-fat diet (HFD) for 16 weeks developed hepatic steatosis and kidney injury, with an associated increase in hepatic PDE4D but no changes in renal PDE4D. Furthermore, liver-specific knockout of PDE4D or pharmacological inhibition of PDE4 with roflumilast ameliorated hepatic steatosis and kidney injury in HFD-fed diabetic mice. Correspondingly, overexpression of hepatic PDE4D resulted in significant renal damage. Mechanistically, highly expressed PDE4D in fatty liver promoted the production and secretion of TGF-β1 into blood, which triggered kidney injury by activating SMADs and subsequent collagen deposition. Our findings revealed PDE4D might act as a critical mediator between NAFLD and associated kidney injury and indicated PDE4 inhibitor roflumilast as a potential therapeutic strategy for NAFLD-associated CKD.

Aim: Different researches showed controversial results about the 'off-hours effect' in nonvariceal upper gastrointestinal bleeding (NVUGIB). Materials & methods: A total of 301 patients with NVUGIB were divided into regular-hours group and off-hours group based on when they received endoscopic hemostasis, and the relationship of the clinical outcomes with off-hours endoscopic hemostasis was evaluated. Results: Patients who received off-hours endoscopy were sicker and more likely to experience worse clinical outcomes. Off-hours endoscopic hemostasis was a significant predictor of the composite outcome in higher-risk patients (adjusted OR: 4.63; 95% CI: 1.35-15.90). However, it did not associate with the outcomes in lower-risk patients. Conclusion: Off-hours effect may affect outcomes of higher-risk NVUGIB patients receiving endoscopic hemostasis (GBS ≥12).

目的:比较分析非静脉曲张性上消化道出血(NVUGIB)床边急诊内镜与择期内镜治疗的临床特点和疗效.方法:回顾性收集304例NVUGIB并接受内镜止血治疗患者的病例资料,其中接受床边急诊内镜的152例患者纳入急诊内镜组,接受择期内镜止血的152例患者纳入择期内镜组,比较分析2组患者的一般情况、病情严重程度、疗效等.结果:2组患者的一般情况、病因构成、止血方式无明显差异(P均＞0.05),与择期内镜组比较,急诊内镜组患者血红蛋白量和血小板计数低,凝血时间延长,AIMS65评分及内镜前Rockall(pRS)评分较高(P均＜0.01),输血率高(60.4％vs 47.4％,P＜0.01),输血量多(P＜0.01),再出血率高(12.2％vs 3.9％,P＜0.01),住院时间更长(P＜0.01).2组患者止血成功率都在80％以上,并发症发生率和死亡率无明显统计学差异(P＞0.05).结论:对于NVUGIB患者,需行床边急诊内镜止血者失血情况严重,凝血功能差,其输血量、再出血率、住院时间均较高或较长,但死亡率与择期内镜止血治疗者相近.

含铋剂的四联治疗是目前国内外共识推荐根除幽门螺杆菌( H. pylori)感染的一线治疗方案，但其仍有用药品种多、不良反应率高、治疗成本高等局限性，因此，二联治疗又重新引起关注。标准剂量阿莫西林和质子泵抑制剂(PPI)二联治疗在早期的探索中未能取得令人满意的结果，但大剂量二联治疗的多项临床研究均取得了令人满意的根除率，其不良反应较含铋剂四联治疗少，患者依从性较高，且治疗成本更低。本文综述大剂量阿莫西林和PPI二联治疗方案对 H. pylori的根除效果及其作用机制研究进展，并介绍含新型抑酸剂的二联治疗方案的应用现状。

Background Radioresistance is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure. Previous studies have focused on the deficits in cellular apoptosis as a mechanism for radioresistance; however, additional potential death modes involved in modulating radiosensitivity of NPC have not been explored. Methods Pyroptosis was assessed by phase-contrast imaging, LDH release assays, live cell imaging, and Western blotting. In vitro and in vivo assays were used to investigate the function of gasdermin E (GSDME) and ovarian tumor family deubiquitinase 4 (OTUD4). NPC tissues were analyzed using Western blotting, immunohistochemistry, and real-time PCR. The molecular mechanism was determined using immunoprecipitation assays and mass spectrometry. Results Live cell imaging revealed that 40—75% of irradiation-induced dead NPC cells were pyroptotic cells. Furthermore, irradiation-induced pyroptosis is triggered by GSDME, which are cleaved by activated caspase-3 in the intrinsic mitochondrial pathway. Additionally, GSDME was significantly downregulated in radioresistant NPC specimens. Low GSDME expression was a predictor of worse prognosis and conferred NPC radioresistance both in vitro and in vivo. Mechanistically, OTUD4 deubiquitinated and stabilized GSDME, enhancing radiosensitivity of NPC cells by promoting pyroptosis. Clinically, OTUD4 was significantly correlated with GSDME in NPC biopsies, and patients with low expression of both OTUD4 and GSDME suffered the worst radiotherapy response and survival. Conclusions GSDME-dependent pyroptosis is a critical determinant of radiosensitivity in NPC, and is modulated by OTUD4 via deubiquitinating and stabilizing GSDME. These findings reveal a promising novel direction to investigate radioresistance and suggest potential therapeutic targets for sensitizing NPC to radiotherapy.

Objective The role of urgent endoscopy in nonvariceal upper gastrointestinal hemorrhage (NVUGIH) remains controversial. We designed a retrospective study to compare the outcomes between urgent endoscopy (within 12 h) and non-urgent endoscopy for patients with NVUGIH. Methods A total of 540 hospitalized patients with NVUGIH were included in our study. Patients who received endoscopy within 12 h or after 12 h were divided into two groups, the urgent and non-urgent endoscopy groups, respectively. The clinical outcomes including rebleeding, mortality, endoscopic re-intervention, need for emergency surgery and interventional radiotherapy were compared between the groups. Patients with Glasgow-Blatchford scores (GBS) <12 and ≥12 were defined as the lower- and high-risk groups, respectively, and the predictors of rebleeding and mortality in both groups were analyzed individually. Results Patients with NVUGIH in the urgent endoscopy group had a higher rate of rebleeding (27.6% vs. 16.9%, P =0.003) and blood transfusion (73.2% vs. 55.5%, P <0.001) than those in the non-urgent endoscopy group, while the mortality and the length of hospitalization were not significantly different between the groups ( P >0.05). For lower-risk patients, urgent endoscopy was independently associated with a higher likelihood of rebleeding (adjusted OR: 1.73, 95% CI: 1.03–2.88), while it was not associated with in-hospital mortality. However, the urgent need for endoscopy was not associated with rebleeding and inhospital mortality in high-risk patients. Conclusion Endoscopy within 12 h did not provide any advantage in the outcomes of patients with NVUGIH, and may even lead to an increased rebleeding rate in lower-risk patients.

Abstract Background Protein arginine methylation has emerged a pivotal role in cancer progression. However, the role of protein arginine methyltransferase 3 (PRMT3) in hepatocellular carcinoma (HCC) remains unknown. Methods The expression pattern of PRMT3 in HCC was analysed using quantitative real‐time‐polymerase chain reaction (qRT‐PCR), Western blotting and immunohistochemistry assays. Loss‐ and gain‐of‐function experiments were carried out to determine the oncogenic role of PRMT3 in HCC. Glucose consumption and lactate production assays, seahorse bioscience, mass spectrometry, co‐immunoprecipitation, metabonomic analysis and site‐specific mutation experiments were used to explore the underlying molecular mechanisms. Furthermore, a xenograft mouse model was established to investigate the effects of PRMT3 and its inhibitor, SGC707, treatment on tumour growth in vivo. Results The expression of PRMT3 was significantly upregulated in HCC, with high expression of which correlated with poor prognosis. PRMT3 knockdown led to the decrease in proliferation, glycolysis of HCC cells and tumour growth, whilst its overexpression showed opposite results. The catalytic activity of PRMT3 was important in mediating these biological processes. Mechanistically, our data showed that PRMT3 interacted with and mediated asymmetric dimethylarginine (ADMA) modification of lactate dehydrogenase A (LDHA) at arginine 112 (R112). Compared with LDHA‐wild‐type (LDHA‐WT) cells, LDHA‐R112K‐mutant‐expressing HCC cells exhibited a decrease in lactate dehydrogenase (LDH) activity, HCC cell glycolysis and proliferation. Furthermore, the administration of SGC707, a selective inhibitor of PRMT3, disrupted the PRMT3‐mediated LDHA methylation and abolished PRMT3‐induced HCC glycolysis and tumour growth. Conclusions Our results suggested a novel oncogenic role of PRMT3 in HCC, and it could be a promising therapeutic target for HCC by linking post‐translational modification and cancer metabolism.

Background: Epigenetic dysregulation participates in the initiation and progression of hepatocellular carcinoma (HCC). Bromodomain-containing protein 9 (BRD9) can identify acetylated lysine residues, contributing to several cancers. The function and molecular mechanism of BRD9 in HCC remain poorly understood. Methods: BRD9 levels in tissues and cells of HCC and normal liver were evaluated using bioinformatic analysis, real-time PCR, and western blot. BRD9's association with clinical outcomes was investigated via survival analyses. Biological behaviors and pathways related to BRD9 were predicted using gene set enrichment analysis. BRD9's role in proliferation was verified via cell counting kit 8, colony formation, and 5-Ethynyl-2'-deoxyuridine assays. Its role in the cell cycle and apoptosis was assessed using flow cytometry. The role of BRD9 in vivo was investigated using xenograft tumor models. A rescue assay was performed to investigate the molecular mechanism of BRD9. Results: BRD9 was markedly upregulated in HCC and higher BRD9 expression was associated with higher grade, advanced stage, greater tumor size, and poorer prognosis. BRD9 overexpression enhanced cell proliferation, cell cycle progress, but impeded cell apoptosis. BRD9 downregulation had the opposite effects. In vivo, BRD9 promoted xenograft tumor growth. Mechanistically, BRD9 activated Wnt/beta-catenin signaling, obstruction of which abrogated BRD9-mediated tumorigenesis. Conclusion: Increased BRD9 in HCC correlated with poor prognosis, which functioned via activating Wnt/beta-catenin signaling. Thus, BRD9 might be a promising biomarker and therapeutic target for patients with HCC.

Long noncoding RNAs (lncRNAs) have been identified to play increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. LncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is demonstrated to decrease in several cancers. However, it is still unknown whether lncRNA NBR2 is involved in hepatocellular carcinoma and autophagy. We found that HCC cases with lower NBR2 expression had significantly worse overall survival than those with higher NBR2 expression in advanced patients. And the expression of NBR2 was negatively correlated with the degree of malignancy of HCC cell lines and differentiation of hepatocellular carcinoma. Besides, NBR2 inhibited the proliferation, invasion, and migration of liver cancer cells. We further found that NBR2 repressed cytoprotective autophagy to restrain HCC cell proliferation. Moreover, NBR2 inhibited Beclin 1-dependent autophagy through ERK and JNK pathways. Taken together, NBR2 suppressed autophagy-induced cell proliferation at least partly through ERK and JNK pathways. These data indicated that NBR2 served as a tumor suppressor gene in hepatocellular carcinoma. The current study provides a novel insight and treatment strategy for hepatocellular carcinoma.

Background: Increasing evidence has implicated that lncRNAs (long non-coding RNAs) play significant roles in carcinogenesis and progression of HCC (hepatocellular carcinoma). LINC01503 is a new lncRNA related to several tumors. Nonetheless, its role in HCC still remains unclear. Methods: The expression levels of LINC01503 in HCC, normal liver tissues as well as HCC cell lines were evaluated by TCGA (The Cancer Genome Atlas) and real-time PCR assay, respectively. The relationship between LINC01503 levels and the prognosis of patients with HCC was evaluated using Kaplan-Meier survival analysis. Then the potential biological functions and pathways related to LINC01503 were investigated by GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, and GSEA v4.0.1 software was employed. Furthermore, the influence of LINC01503 on the proliferation and apoptosis of HCC cells was confirmed using CCK8 assay, flow cytometry, and clone formation assay in cell experiments. Also the pro-tumor effect of LINC01503 was verified by mice xenograft experiment in vivo. In addition, the functional pathway of LINC01503 was proved by western blot and rescue experiments. Results: LINC01503 was highly expressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage, and poor prognosis of HCC patients. Silencing LINC01503 with shRNA significantly restrained the proliferation of MHCC-97H HCC cells and strengthened the apoptosis, while up-regulation of LINC01503 in Huh7 HCC cells contributed to the contrary effects. Besides, LINC01503 promoted tumor growth of nude mice transplanted with liver cancer cells. Mechanistically, MAPK/ERK signaling pathway was activated by LINC01503, inhibition of which could alleviate the pro-tumor effect of LINC01503, consistent with the forecast of GSEA (Gene Set Enrichment Analysis). Conclusion: LINC01503 is highly expressed in HCC and promotes the progression of HCC via MAPK/ERK pathway, which maybe a new potential biomarker and therapeutic target for HCC.

Bladder cancer is one of the most commonly diagnosed tumors and is results from the accumulation of somatic mutations in the DNA. Tumor mutation burden (TMB) has been associated with cancer immunotherapeutic response. In this study, we attempted to explore the correlation between TMB and cancer prognosis. Identify the different expressed genes and immune cell infiltration signatures between low and high TMB group. Mutation data, gene expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high and low TMB groups, allowing differentially expressed genes (DEGs) to be identified. Functional enrichment and protein-protein interaction (PPI) network analysis were used to identify the functions of the DEGs. And immune cell infiltration signatures were evaluated by CIBERSORT algorithm. These results shown that high TMB was significantly associated with prognosis. We obtained a list of TMB related genes which may influence the infiltrations of immune cells. We also found a higher proportion of CD8 T cells, CD4 T cells and NK cells in the high TMB group. Our data suggest that higher TMB tends to promote the infiltrations of T cells and NK cells and patients with higher TMB may achieve a more favorable prognosis in bladder cancer.

Objective:To study the manifestations of digestive system of hospitalized patients with coronavirus disease 2019 (COVID-19) in Wuhan, China, and to provide a reference for disease control and treatment.Methods:The data of hospitalized patients with COVID-19 in the Sino-French Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 27 to February 14, 2020 were retrospectively analyzed, which included general information, positive rate of nucleic acid test, severity of disease, incubation period, initial symptoms and manifestations of digestive system. The general information, positive rate of nucleic acid detection, and manifestations of digestive system were compared between critical patients who required non-invasive or invasive assisted ventilation (critical group) and non-critical patients without assisted ventilation (non-critical group). Continuous corrected Chi-square test and independent sample median Chi-square test were used for statistical analysis.Results:Among the 305 patients, there were 146 males (47.9%) and 159 females (52.1%), and the median age was 57 years old. Nucleic acid assay of nasopharyngeal swabs or pharyngeal swabs were positive in 84.1% (228/271) patients including 46 patients (15.1%) of critical group and 259 patients (84.9%) of non-critical group. The incubation period was one to fifteen days, and the median period was six days. The initial symptoms were mainly fever (81.1%, 163/201), cough (39.3%, 79/201), fatigue (54.7%, 110/201), and loss of appetite (50.2%, 101/201). In one to ten days after the disease onset, 79.1% (159/201) of patients developed gastrointestinal symptoms including nausea (29.4%, 59/201), vomiting (15.9%, 32/201), or abdominal pain (6.0%, 12/201). 49.5% (146/295) of patients had diarrhea, with a median time of 3.3 days, (3.3±1.6) times per day, and a duration of (4.1±2.5) days. After excluding possible drug-related diarrhea, the incidence of diarrhea was still 22.2%. Only 6.9% (4/58) of patients had positive fecal leukocytes or fecal occult blood test. Alanine aminotrans ferase (ALT), aspartate aminotransferase (AST), or total bilirubin (TBil) increased in 39.1% (119/304) of patients on admission. Patients with ALT or AST ≥ 80 U/L only accounted for 7.9% (24/304) and 6.3% (19/304), respectively. About 2.0% (6/304) of patients also had increased TBil level, and the average level was (37.4±21.1) μmol/L. The median age of critical group was older than that of non-critical group (65 years vs. 56 years), the proportion of patients with abnormal liver function and slightly increased AST (40-<80 U/L) on admission of critical group were both higher than those of non-critical group (67.4% (31/46) vs. 34.1% (88/258) and 47.8% (22/46) vs. 21.7% (56/228)), and the differences were statistically significant ( χ2=5.885, 18.154 and 15.723; all P <0.05). There were no significant differences in the proportion of males (58.7% (27/46) vs. 45.9% (119/259)), the positive rate of nucleic acid test (94.6% (35/37) vs. 82.5% (193/234)), the percentage of patients with gastrointestinal symptoms (85.0% (17/20) vs. 78.5% (142/181)), the incidence of diarrhea (44.7% (17/38) vs. 50.2% (129/257)) and the proportion of patients with abnormal TBil level on admission (6.5% (3/46) vs. 1.2% (3/258)) (all P>0.05). Conclusions:The manifestation of digestive system of hospitalized COVID-19 patients in Wuhan is significant, the proportion of patients with diarrhea and abnormal aminotransferase level is high. And on admission the proportion of patients with abnormal liver function of critical group is higher than that of non-critical group, which will provide reference for the prevention and treatment of COVID-19.

Objective@#To study the manifestations of digestive system of hospitalized patients with novel coronavirus pneumonia (NCP) in Wuhan, China, and to provide reference for disease control and treatment.@*Methods@#The data of hospitalized patients with NCP in the Sino-French Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology was retrospectively analyzed, which included general information, nucleic acid test, severity degree of disease, incubation period, initial symptoms and manifestations of digestive system. The general information, positive rate of nucleic acid detection, and manifestations of digestive system were compared between critical patients who required non-invasive or invasive assisted ventilation (critical group) and non-critical patients without assisted ventilation (non-critical group). Continuous corrected chi-square test and independent sample median test were performed for statistical analysis.@*Results@#Among the 305 patients there were 146 males (47.9%) and 159 females (52.1%), median age 57 years old. Nucleic acid assay of nasopharynx swab or pharynx swab of 84.1% (228/271) patients were positive. Forty-six patients (15.1%) were in critical group and 259 patients (84.9%) were in non-critical group. The incubation period was one to fifteen days, and the median period was six days. The initial symptoms mainly were fever (81.1%, 163/201), cough (39.3%, 79/201), fatigue (54.7%, 110/201), and loss of appetite (50.2%, 101/201). In one to ten days after the disease onset, 79.1% (159/201) of patients developed gastrointestinal symptoms including nausea (29.4%, 59/201), vomiting (15.9%, 32/201), or abdominal pain (6.0%, 12/201). 49.5% (146/295) of patients had diarrhea, median time was 3.3 days, (3.3±1.6) times per day, and a duration of (4.1±2.5) days. Excluding possible drug-related diarrhea, the incidence of diarrhea still was 22.2%. Only 6.9% (4/58) of patients were found leukocytes or fecal occult blood positive in regular stool test. ALT, AST, or bilirubin increased in 39.1% (119/304) of patients at admission. Patients with ALT or AST ≥ 80 U/L only accounted for 7.9% (24/304) and 6.3% (19/304), respectively. About 2.0% (6/304) of patients also had increased bilirubin level, average level was (37.4 ± 21.1) μmol/L. The median age of critical group was older than that of non-critical group (65.5 years vs. 56 years), at admission the rates of abnormal liver function test abnormal and slightly increased AST (40~80 U/L) of critical group were both higher than those of non-critical group (67.4% (31/46) vs. 34.1% (88/258) and 47.8% (22/46) vs. 21.7% (56/228)), and the differences were statistically significant (x2=5.885, 18.154 and 15.723;all P 0.05).@*Conclusions@#The manifestation of digestive system of hospitalized NCP patients in Wuhan is significant, the ratio of patients with diarrhea and abnormal aminotransferase level is high. And at admission the rate of patients with abnormal liver function rate of critical group is higher than that of non-critical group, which will provide reference for the prevention and treatment of NCP.

Background: An emerging outbreak of COVID-19 has rapidly caused global pandemic. Few studies were reported on the incidence and role of influenza virus co-infection on COVID-19. Methods: 273 hospitalized patients with COVID-19 and tests of influenza A/B virus were enrolled from February to March 2020 in Wuhan, China. Data on baseline characteristics, clinical manifestations and outcomes, laboratory findings were collected and analysed. Findings: The incidence of influenza virus co-infection in patients with COVID-19 was 55·3% (151/273), with 48·5% (133/273) of influenza A and 6·6% (18/273) of influenza B, respectively. Influenza virus co-infection was significantly more common in non-critical group (60·5%, 115/190) than critical group (43·4%, 36/83; p=0·01). The fatality of COVID-19 in influenza group was 9·9% (15/151), while it was 23·8% (29/122) in non-influenza group (p=0·01). Accordingly, the incidence of critical type was higher in influenza group (p=0·01). Cox regression analysis revealed that co-infection with influenza virus had significant reduction of fatality than non-influenza group (OR 0·470, p<0·05). Other fatality indicators included age (p=0·02), sex (OR 3·626, p=0·00), and low lymphocytes (OR 2·368, p=0·04). Interpretation: There is a high incidence of influenza virus co-infection in patients with COVID-19 in Wuhan, China. It seems like co-infection with influenza virus acts as a protective factor for COVID-19. The relationship between SARS-nCoV-2 and influenza virus co-infection warrants further studies. Funding Statement: This study was supported by National Natural Science Foundation of China Grant (No. 81800493). Declaration of Interests: All authors have no conflicts of interest to declare. Ethics Approval Statement: The procedure was approved by the Institutional Ethics Board of Tongji Medical College. The follow-up was up to March 22, 2020.

目的:探讨学员轮流演示点评方法在胃镜教学中的应用价值.方法:以消化内镜培训基地胃镜初学人员51名为研究对象,采用回顾性队列研究方法,根据学员初学胃镜时所接受的教学方法分为对照组(采用传统教学法)和实验组(采用学员轮流演示点评法).通过问卷形式调查二组学员在本中心初学胃镜情况,以评价两种胃镜教学方法的培训效果.结果:实验组学员在术前准备和揣摩、注意操作细节、操作规范、观察全面、进步速度、学员满意度等方面均优于对照组,差异有统计学意义(P＜0.01).结论:学员轮流演示点评教学相对于传统胃镜教学,有利于提高教学效果,学员满意度更高,值得进一步探索和推广.

Primary cilia are organelles protruding from cell surface into environment that function in regulating cell cycle and modulating cilia-related signal. Primary ciliogenesis and autophagy play important roles in tumorigenesis. However, the functions and interactions between primary cilia and autophagy in hepatocellular carcinoma (HCC) have not been reported yet. Here, we aimed to investigate the relationship and function of primary cilia and autophagy in HCC. In vitro, we showed that serum starvation stimuli could trigger primary ciliogenesis in HCC cells. Blockage of primary ciliogenesis by IFT88 silencing enhanced the proliferation, migration, and invasion ability of HCC cells. In addition, inhibition of primary cilia could positively regulate autophagy. However, the proliferation, migration, and invasion ability which were promoted by IFT88 silencing could be partly reversed by inhibition of autophagy. In vivo, interference of primary cilia led to acceleration of tumor growth and increase of autophagic flux in xenograft HCC mouse models. Moreover, IFT88 high expression or ATG7 low expression in HCC tissues was correlated with longer survival time indicated by the Cancer Genome Atlas (TCGA) analysis. In conclusion, our study demonstrated that blockage of primary ciliogenesis by IFT88 silencing had protumor effects through induction of autophagy in HCC. These findings define a newly recognized role of primary cilia and autophagy in HCC.