A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians′ awareness of opportunistic virus reactivation during anti-tumor treatment.

Objective To explore the potential pathogenic genes of intestinal metaplasia.Methods Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January,2022 to June,2022,and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study.All the participants underwent gastroscopy and pathological examination,and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes(DEGs).The biological functions of the DEGs were analyzed using bioinformatics analysis,and qRT-PCR was used to validate the results.Results Transcriptomic sequencing identified a total of 1373 DEGs,including 827 upregulated and 546 downregulated ones.The top 6 upregulated genes(AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2),ranked based on their significance and average expression level,were selected for validation,and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia(P<0.05).Conclusion AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2 participate in the occurrence and development of intestinal metaplasia,and may serve as potential biomarkers for diagnosing intestinal metaplasia.

Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Objective to explore the use of performance management as a lever in public hospitals to achieve quality improvement,efficiency enhancement,and high-quality development under the dual influences of na-tional civil service examination and Diagnosis-Related Groups(DRGs)payment policy reform.Methods A questionnaire survey was conducted to summarize the current situation and problems of performance assessment in public hospitals in China.Based on the identified problems,an upgraded performance management system was proposed,and key indicators were selected through a case study in a specific hospital.Results An empirical study in a specific hospital demonstrated the positive effects of the upgraded performance management system on hospital management improvement.Conclusion Public hospitals should establish a long-term mechanism for performance management,focusing on organizational positioning,indicator design,management levers,and talent development,to continuously support high-quality development.

Objective To explore the potential pathogenic genes of intestinal metaplasia.Methods Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January,2022 to June,2022,and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study.All the participants underwent gastroscopy and pathological examination,and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes(DEGs).The biological functions of the DEGs were analyzed using bioinformatics analysis,and qRT-PCR was used to validate the results.Results Transcriptomic sequencing identified a total of 1373 DEGs,including 827 upregulated and 546 downregulated ones.The top 6 upregulated genes(AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2),ranked based on their significance and average expression level,were selected for validation,and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia(P<0.05).Conclusion AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2 participate in the occurrence and development of intestinal metaplasia,and may serve as potential biomarkers for diagnosing intestinal metaplasia.

Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

Objective:To explore the clinical and histopathologic features of lupus nephritis (LN) patients with positive antineutrophil cytoplasmic antibody (ANCA), so as to provide more theoretical basis to recognize and treat this disease.Methods:Clinical data of biopsy-proven LN patients with ANCA test in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2002 to September 11, 2020 were collected and analyzed retrospectively. The difference of clinical data, laboratory examination, and pathological examination of renal biopsy between ANCA-positive group and ANCA-negative group. The clinicopathological characteristics between different ANCA serotypes were compared.Results:A total of 1 304 patients with LN confirmed by renal biopsy and ANCA test results were enrolled. Eighty ANCA-positive patients from 1 304 LN patients were screened. There are 55(68.8%) ANCA-positive LN patients with positive anti-myeloperoxidase antibodies (MPO). There were 14(17.5%) ANCA-positive LN patients with positive anti-proteinase 3 antibodies (PR3), and 11(13.8%) ANCA-positive patients with double positive antibodies of MPO and PR3. ANCA-positive LN patients had significantly higher serum creatinine [135.5(68.0, 361.8) μmol/L vs 88.0(64.0, 165.0) μmol/L, P=0.004] and blood urea nitrogen [12.35(6.35, 21.18) mmol/L vs 8.60 (5.50, 15.70) mmol/L, P=0.026] as well as lower estimated glomerular filtration rate [45.70(13.83, 84.10) ml·min -1·(1.73 m 2) -1 vs 66.75(38.43, 96.22) ml·min -1·(1.73 m 2) -1, P=0.001] than ANCA-negative patients (stratified sampling of 160 patients). ANCA-positive LN patients had higher chronicity index than ANCA-negative LN patients [3(2, 7) vs 2(0, 5), P=0.006]. There were statistically significant difference in hemoglobin, serum creatinine and estimated glomerular filtration rate among ANCA-positive group, ANCA-negative group, and MPO-ANCA and PR3-ANCA double positive group. MPO-ANCA and PR3-ANCA double positive LN patients had the lowest hemoglobin and estimated glomerular filtration rate, and highest serum creatinine among the three groups (all P<0.05). Conclusions:ANCA-positive LN patients have worse renal function and higher renal histological chronicity index than ANCA-negative LN patients, especially for patients with double positive MPO-ANCA and PR3-ANCA. More stringent monitoring and therapy may be needed in this subgroup of LN patients.

Excessive theta (θ) frequency oscillation and synchronization in the basal ganglia (BG) has been reported in elderly parkinsonian patients and animal models of levodopa (L-dopa)-induced dyskinesia (LID), particularly the θ oscillation recorded during periods when L-dopa is withdrawn (the off L-dopa state). To gain insight into processes underlying this activity, we explored the relationship between primary motor cortex (M1) oscillatory activity and BG output in LID. We recorded local field potentials in the substantia nigra pars reticulata (SNr) and M1 of awake, inattentive resting rats before and after L-dopa priming in Sham control, Parkinson disease model, and LID model groups. We found that chronic L-dopa increased θ synchronization and information flow between the SNr and M1 in off L-dopa state LID rats, with a SNr-to-M1 flow directionality. Compared with the on state, θ oscillational activity (θ synchronization and information flow) during the off state were more closely associated with abnormal involuntary movements. Our findings indicate that θ oscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1 θ oscillation may participate in the induction of dyskinesia.

Objective: To explore the most economically feasible cervical cancer screening strategies in urban China. Methods: A series of Markov models were constructed to evaluate health and economic outcomes of different screening strategies. There were 24 screening strategies including four screening methods: liquid-based cytology (LBC), human papillomavirus (HPV) DNA genotyping, HPV DNA genotyping with LBC triage (HPV DNA+ LBC), HPV DNA genotyping and LBC co-testing (HPV DNA-LBC), along with three intervals (every 1, 3 or 5 years) and two starting age for screening (30 or 35 years old) were compared. Models parameters were obtained from a cervical cancer screening study in urban China and literature reviews. Results: The cumulative incidence and mortality risk of cervical cancer declined over 69% and 82% respectively for each screening strategy as compared with the no screening scenario. LBC every five years starting from 35 years old strategy cost the least (RMB 690 per capita) and could save life years compared with no screening. The cost effectiveness ratios of 24 strategies ranged from -10 903 to 117 992 RMB per life year saved. All strategies were cost-effective compared to no screening. In the incremental cost-effectiveness analysis, LBC every 5 years starting from 30 strategy, HPV DNA genotyping every 3 years starting from 30 strategy, LBC every 3 years starting from 30 strategy and LBC every year starting from 30 strategy were dominant strategies. Conclusions Screening can effectively prevent cervical cancer. In urban Chinese areas with insufficient socioeconomic resources, LBC every 5 years from 35 years old strategy is recommended. In relatively more affluent areas, LBC every 5 years from 30 years old strategy, LBC every 3 years from 30 years old strategy, HPV DNA genotyping every 3 years from 30 years old strategy, and LBC every year from 30 years old strategy are recommended successively.