Objective To investigate the mechanism by which conbercept reverses transforming growth factor-β2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(HLECs).Methods Cultured HLEC SRA01/04 cells were treated with TGF-β2,conbercept,or both,and the changes in cell proliferation,apoptosis,and migration were observed using MTT assay,flow cytometry,scratch assay,and Transwell assay.Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers(E-Cadherin,α-SMA,and Snail),extracellular matrix components,and genes related to the TGF-β/Smad signaling pathway.Results Conbercept significantly reduced TGF-β2-induced EMT of SRA01/04 cells,decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA,Snail,collagen I,collagen IV,and FN1,and upregulated the protein and mRNA expressions of E-cadherin(P<0.05).Transwell assay showed significantly lower cell migration ability in TGF-β2+conbercept group than in TGF-β2 group(P<0.05).Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-β2-induced EMT(P<0.01).Conclusion Conbercept inhibits TGF-β2 induced EMT by downregulating the expression of pSmad2/3 in TGF-β/Smad signaling pathway,indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.

Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

Objective To investigate the mechanism by which conbercept reverses transforming growth factor-β2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(HLECs).Methods Cultured HLEC SRA01/04 cells were treated with TGF-β2,conbercept,or both,and the changes in cell proliferation,apoptosis,and migration were observed using MTT assay,flow cytometry,scratch assay,and Transwell assay.Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers(E-Cadherin,α-SMA,and Snail),extracellular matrix components,and genes related to the TGF-β/Smad signaling pathway.Results Conbercept significantly reduced TGF-β2-induced EMT of SRA01/04 cells,decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA,Snail,collagen I,collagen IV,and FN1,and upregulated the protein and mRNA expressions of E-cadherin(P<0.05).Transwell assay showed significantly lower cell migration ability in TGF-β2+conbercept group than in TGF-β2 group(P<0.05).Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-β2-induced EMT(P<0.01).Conclusion Conbercept inhibits TGF-β2 induced EMT by downregulating the expression of pSmad2/3 in TGF-β/Smad signaling pathway,indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.

The development of liver inflammatory diseases is associated with autoimmunity and inflammatory response. As a negative feedback regulator of cell signal, suppressor of cytokine signaling 1 (SOCS1) plays a key role in the development and progression of inflammatory diseases. This article mainly introduces the mechanism of action of SOCS1 in autoimmunity and inflammatory response and briefly describes its role in the development and progression of liver inflammatory diseases such as viral hepatitis and nonalcoholic steatohepatitis. The analysis shows that the abnormal expression of SOCS1 in inflammatory response is associated with the regulation of cytokine receptor, Toll-like receptor, and hormone receptor signal, which leads to the development of inflammatory diseases. Therefore, SOCS1 has potential prospects as an auxiliary means for the diagnosis and treatment of liver inflammatory diseases.

Objective:To explore the association between polygenic risk score (PRS) and age at onset and early-onset risk of gastric cancer (GC).Methods:Gastric cancer cases from existing genome-wide association study were included, and 112 single nucleotide polymorphisms associated with GC risk were used to derive individual PRS. Analysis of variance and Pearson correlation test was used to depict the relationship between PRS and GC onset age. Cases diagnosed before 50 years old were defined as early-onset gastric cancer. Cox proportional hazard model was used to test the association between PRS and early-onset GC risk with early-onset age as the timescale and low genetic risk (PRS ≤20%) as the reference group.Results:A total of 8 629 cases, including 6 284 males (72.82%) and 2 345 females (27.18%), were included, and the mean age was (60.61±10.80) years old. The PRS was negatively correlated with age of GC onset ( r=-0.05, P<0.001). The mean age of gastric cancer cases with low, intermediate, and high genetic risk were (61.68±10.33), (60.53±10.79), (59.80±11.20), respectively. PRS was significantly associated with the risk of early-onset GC in a dose-response manner (intermediate genetic risk: HR=1.19, 95% CI: 1.03-1.39, P=0.022; high genetic risk: HR=1.44, 95% CI: 1.20-1.71, P<0.001). Conclusions:PRS may contribute to the risk of both GC and early-onset GC. PRS can be used as a measurable indicator for risk prediction for occurrence and early-onset of GC.

Objective To investigate the possible role of high mobility group box 1 protein (HMGB1) and its advanced gly‐cation end products receptor (RAGE) in the pathogenesis of systemic lupus erythematosus (SLE) .Methods The enzyme‐linked immunosorbent assay (ELISA) was used to determine the level of plasma HMGB1 in 52 cases of SLE (SLE group) and 40 healthy females undergoing physical examination (HC group) ,at the same time real time quantitative polymerase chain reaction (RT‐qPCR) was employed to detect the expression of HMGB1 and RAGE mRNA in peripheral blood mononuclear cells (PBMCs) .The correlation between plasma HMGB1 ,PBMCs HMGB1 and RAGE mRNA levels with clinical indicators was analyzed .Results The levels of plasma HMGB1 ,PBMCs HMGB1 mRNA in the SLE group were significantly higher than those in the HC group ,the differences were statistically significant (P< 0 .05) ,while the level of PBMCs RAGE mRNA had no statistical difference (P>0 .05);the Spearman correlation analysis showed that the level of plasma HMGB1 was positively correlated with antinuclear anti‐bodies titers and SLEDAI score in the SLE patients (P<0 .01) ,while had no obvious correlation with the other clinical and labora‐tory indicators(P>0 .05);the HMGB1 mRNA expression level was positively correlated with the RAGE mRNA expression level and SLEDAI scores(P<0 .01 ,P<0 .05) ,and had no obvious correlation with other clinical and laboratory indicators (P>0 .05) . Conclusion The abnormal expression of plasma HMGB1 and PBMCs HMGB1 mRNA in SLE patients prompts that which might be involved in the occurrence and development of SLE ,might participate in the immune and inflammatory regulation of SLE .

Objective To detect the changes of microbial community functional diversity of corpses with different postmortem interval(PMI)and to evaluate forensic application value for estimating PMI. Methods The cultivation of microbial community from the anal swabs of aSusscrofaand a human corpse placed in field environment from 0 to 240 h after death was performed using the Biolog-Eco Mi-croplate and the variations of the absorbance values were also monitored. Combined with the technology of forensic pathology and flies succession, the metabolic characteristics and changes of microbial commu-nity on the decomposed corpse under natural environment were also observed.Results The diversity of microbial metabolism function was found to be negatively correlated with the number of maggots in the corpses. The freezing processing had the greatest impact on average well color development value at 0 h and the impact almost disappeared after 48 h. The diversity of microbial metabolism of the samples be-came relatively unstable after 192 h. The principal component analysis showed that 31 carbon sources could be consolidated for 5 principal components(accumulative contribution ratio >90%). The carbon source tsquare-analysis showed thatN-acetyl-D-glucosamine andL-serine were the dominant carbon sources for estimating the PMI(0=240 h)of theSusscrofaand human corpse.Conclusion The Biolog-Eco method can be used to reveal the metabolic differences of the carbon resources utilization of the microbial community on the corpses during 0-240 h after death, which could provide a new basis for estimating the PMI.