Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Objective To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T(UBE2T)on radiosensitivity of hepatocellular carcinoma(HCC).Methods Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector,and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay.The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice,and tumor growth following irradiation were recorded.The xenografts were collected for analyzing infiltration of CD4+T cells and regulatory T cells(Tregs)using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting.The correlations of UBE2T expression with immune cell infiltration,glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database,and the results were verified in a co-culture system of Hepa1-6 cells and Tregs.Results UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models(especially in C57BL/6 mice).CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells,T follicular helper cells,M2 macrophages,monocytes,lymphocytes and Tregs in HCC.The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA,and irradiation increased infiltration of CD4+T cells and Tregs in the tumor microenvironment.Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration.GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC.In the cell co-culture system,UBE2T overexpression significantly enhanced lactate production,proliferation and immunosuppressive functions of Tregs.Conclusion A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.

Objective To investigate the effect of Danggui Shaoyao powder on apoptosis of cochlear spiral ganglion cells of age-related hearing loss mice by regulating the inhibitor of kappa B kinase(IKK)/inhibitory subunit of nuclear factor-kappa B alpha(IκBα)/nuclear factor-kappa B(NF-κB)pathway.Methods A total of 48 C57BL/6J mice were randomly divided into age-related hearing loss model group(model group),low-dose Danggui Shaoyao powder group(traditional Chinese medicine-L group,3.2 g/kg crude drug),high-dose Danggui Shaoyao powder group(traditional Chinese medicine-H group,6.4 g/kg crude drug),and high-dose Danggui Shaoyao powder+IKK/IκBα/NF-κB signaling pathway activator resveratrol(RES)group(tradi-tional Chinese medicine-H+RES group,6.4 g/kg crude drug+43.33 mg/kg RES),with 12 mice in each group.Twelve 2-month-old C57BL/6J mice were selected as the control group.Auditory brain stem response(ABR)was used to detect the audi-tory threshold of mice in each group.HE staining was used to observe the pathological changes of spiral ganglions of the mouse cochlea,and the number of spiral ganglion cells in the middle and bottom gyrus of the mouse cochlea was counted.The apoptosis of spiral ganglion cells in mouse cochlea was detected by TUNEL staining.The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in mouse cochlear tissue were detected by ELISA.The mRNA levels of IL-1β,IL-6 and TNF-α in mouse co-chlear tissues were detected by qRT-PCR.Western blot was used to detect the expression of IKK/IκBα/NF-κB pathway and ap-optosis related proteins in mouse cochlear tissue.Results Compared with the control group,the auditory thresholds at 8 kHz,16 kHz,24 kHz,and 32 kHz,the number of TUNEL positive cells in the cochlear spiral ganglion tissue,the level of MDA,and the mRNA level of IL-1β,IL-6 and TNF-α in the cochlear tissue,the expression of p-IκBα,apoptosis protein(Bax,and cleaved-Caspase-3),and the phosphorylation levels of IKK and NF-κB p65 in the model group were significantly increased(all P＜0.05),the number of cochlear spiral ganglion cells,the level of SOD,and the expression of IκBα protein were significantly re-duced(all P＜0.05),the morphology of cochlear spiral ganglion cells was abnormal,with loose and disordered arrangement,re-sulting in vacuolization and pathological damage.The changes in corresponding indicators of mice in the traditional Chinese med-icine-L group and traditional Chinese medicine-H group were opposite to those in the model group(all P＜0.05).RES alleviated the inhibitory effect of Danggui Shaoyao powder on the apoptosis of cochlear spiral ganglion cells in age-related hearing loss mice.Conclusion Danggui Shaoyao powder may inhibit apoptosis of cochlear spiral ganglion cells of age-related hearing loss mice by downregulating the IKK/IκBα/NF-κB pathway.

Objective To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T(UBE2T)on radiosensitivity of hepatocellular carcinoma(HCC).Methods Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector,and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay.The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice,and tumor growth following irradiation were recorded.The xenografts were collected for analyzing infiltration of CD4+T cells and regulatory T cells(Tregs)using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting.The correlations of UBE2T expression with immune cell infiltration,glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database,and the results were verified in a co-culture system of Hepa1-6 cells and Tregs.Results UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models(especially in C57BL/6 mice).CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells,T follicular helper cells,M2 macrophages,monocytes,lymphocytes and Tregs in HCC.The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA,and irradiation increased infiltration of CD4+T cells and Tregs in the tumor microenvironment.Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration.GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC.In the cell co-culture system,UBE2T overexpression significantly enhanced lactate production,proliferation and immunosuppressive functions of Tregs.Conclusion A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.

Background: and Purpose The optimal management of patients with acute basilar artery occlusion (BAO) is uncertain. We aimed to evaluate the safety and efficacy of endovascular thrombectomy (EVT) compared to medical management (MM) for acute BAO through a meta-analysis of randomized controlled trials (RCTs). Methods: We performed a systematic review and meta-analysis of RCTs of patients with acute BAO. We analyzed the pooled effect of EVT compared to MM on the primary outcome (modified Rankin Scale [mRS] of 0–3 at 3 months), secondary outcome (mRS 0–2 at 3 months), symptomatic intracranial hemorrhage (sICH), and 3-month mortality rates. For each study, effect sizes were computed as odds ratios (ORs) with random effects and Mantel-Haenszel weighting. Results: Four RCTs met inclusion criteria including 988 patients. There were higher odds of mRS of 0-3 at 90 days in the EVT versus MM group (45.1% vs. 29.1%, OR 1.99, 95% confidence interval [CI] 1.04–3.80; P=0.04). Patients receiving EVT had a higher sICH compared to MM (5.4% vs. 0.8%, OR 7.89, 95% CI 4.10–15.19; P<0.01). Mortality was lower in the EVT group (35.5% vs. 45.1%, OR 0.64, 95% CI 0.42–0.99; P=0.05). In an analysis of two trials with BAO patients and National Institutes of Health Stroke Scale (NIHSS) <10, there was no difference in 90-day outcomes between EVT versus MM. Conclusion In this systematic review and meta-analysis, EVT was associated with favorable outcome and decreased mortality in patients with BAO up to 24 hours from stroke symptoms compared to MM. The treatment effect in BAO patients with NIHSS <10 was less certain. Further studies are of interest to evaluate the efficacy of EVT in basilar occlusion patients with milder symptoms.

Objective To analyze the infection situation of Helicobacter pylori (Hp) and its correlation with pepsinogen (PG) in the 60~80 year old population in Jianye District, Nanjing City. Methods From December 2018 to December 2020, 758 elderly people aged 60 to 80 in the community in Jianye District Nanjing City. were selected. All subjects were tested for Hp by 13C-UBT method, and clinical signs of Hp positive people aged 60 to 80 years were analyzed. Including gender, age, alcohol consumption, family history of stomach cancer, chronic gastritis, and spicy eating habits; Hp positive group was given amoxicillin capsule 1.0g/ time, twice a day, esomeprazole magnesium enteric-coated tablet 20mg/ time, twice a day, clarithromycin tablet 0.5g/ time, twice a day for 8 weeks, and Hp was detected again after the end of treatment. All levels of PGI, PGII and PGI/PGII were determined by ELISA. The serum PG level of the experimental group and the control group and the serum PG level of the Hp positive population before and after Hp eradication were compared, and the correlation between Hp infection and PG level in the elderly population was analyzed by Pearson correlation. Results A total of 161 cases (21.24%) of 758 patients with chronic gastritis had Hp infection. The proportion of Hp infection in males was significantly higher than that in females (χ²=4.128，P<0.05). The proportion of Hp infection in 70-80 years was higher than that in 60-69 years(χ²=6.771, P<0.05). The proportion of Hp infection in drinking elderly was higher than that in non-drinking elderly (χ² =8.305，P<0.05). The proportion of Hp infection in the elderly with family history of gastric cancer was higher than that in the elderly without family history of gastric cancer (χ²=6.169，P<0.05). The proportion of Hp infection in elderly patients with chronic gastritis was higher than that in patients without chronic gastritis (χ²=5.576 , P<0.05). The proportion of Hp infection in the elderly with spicy diet was higher than that in the non-spicy diet group(χ²=7.936, P<0.05). The levels of PGI and PGI/PGII in the experimental group were significantly higher than those in the control group (P<0.05). The level of PGII in experimental group was significantly lower than that in control group (P<0.05). After treatment, 76 hP-positive patients turned negative, and PGI and PGI/PGII levels after Hp eradication were significantly lower than those before Hp eradication (P<0.05). PGII after Hp eradication was significantly higher than before (P<0.05). According to Pearson correlation analysis, Hp infection in elderly population was positively correlated with PGI and PGI/PGII levels, with correlation coefficients (r1=0.408,r2=0.412,P<0.05), and negatively correlated with PGII, with correlation coefficients (r=-0.469, P<0.05). Conclusions The Hp infection rate in patients with chronic gastritis is high, mainly in elderly men in Jianye District, Nanjing City.The levels of PGI and PGII in HP-positive patients are high, and the levels of PGI/PGII are low. The serum PG level can be used to evaluate the diagnosis and treatment effect of patients with Hp infection.

Objective To evaluate the clinical significance of the level of [gG4 in the bronchoalveolar lavage fluid (BALF) of patients with rheumatic disease related interstitial lung disease (RD-ILD).Methods Eighteen patients with RD-ILD,14 patients with pulmonary infection and 12 patients without ILD or pulmonary infection,were recruited consecutively from the in-patient ward of Peking University People's Hospital.Clinical features and laboratory data were extracted from the medical record database of Peking University People's Hospital.The level of IgG4 was determined by ELISA.The statistical analysis of data using t test,and the correlation between the two variables were analyzed using linear regression analysis.Results The level of IgG4 was significantly higher in BALF of patients with RD-ILD than patients' without ILD or pulmonary infection,whereas there was no difference compared to patients with pulmonary infection.The level of IgG4 in BALF of patients with RD-ILD was positively correlated with the percentage of lymphocytes (r=0.53,P=0.03),and significantly negatively correlated with the percentage of macrophages (r=-0.65,P=0.005).Conclusion The level of IgG4 is significantly elevated in BALF of patients with RD-ILD,which is probably secreted from the lymphocyte of the lung.

OBJECTIVE To understand the antibacterial usage among outpatients in our hospital and provide reference for their rational use in clinic treatment.METHODS Totally 18 232 prescriptions in 2007 were investigated and analyzed.RESULTS The rate of antibacterial usage was 21.9% which took up 6.25% of total cost.As for active treatment single drug consisted of 91.21%,two-drugs 9.09%,and three-drugs of 0.55%.CONCLUSIONS The antibiotic service is basically rational.