Objective To explore the role and underlying mechanism of the transcriptional coactivator with PDZ-binding motif(TAZ)and a histone variant of acute histone H2A(H2A.Z)in the repair of hypoxia-induced lung injury.Methods A mouse model of hypoxic lung injury was established by being placed in a hypoxia chamber(simulating an altitude of 5 800 m)for 4 d.HE staining was used to observe the severity of lung injury.A hypoxia model of murine alveolar epithelial cells(murine lung epithelial-12,MLE12)was constructed by treating the cells in a hypoxia workstation(1%O2 concentration)for 24 h.Western blotting was employed to detect TAZ expression.The proliferation of alveolar epithelial cells(AECs)was evaluated by CCK-8 assay.Co-immunoprecipitation(Co-IP)assay was utilized to verify the interaction between TAZ and H2A.Z.CUT&Tag sequencing was performed to determine the effect of TAZ on the chromatin deposition of H2A.Z.Results Hypoxia significantly induced alveolar atrophy and inflammatory infiltration in mouse lung tissues(P＜0.01).Hypoxia significantly up-regulated the protein level of TAZ in MLE12 cells(P＜0.05).CCK-8 assay showed that knockdown of TAZ significantly reduced the proliferative capacity of AECs(P＜0.01).Co-IP assay confirmed the physical interaction between TAZ and H2A.Z.CUT&Tag sequencing revealed that hypoxia promoted the deposition of H2A.Z on chromatin(31 817 peaks under normoxia,44 078 peaks under hypoxia),which was partially reversed by TAZ knockdown(37 840 peaks).Conclusion Hypoxia significantly up-regulates the expression of TAZ,which combines with H2A.Z and promotes the deposition of H2A.Z on chromatin,thus enhancing the proliferation of AECs in response to hypoxic injury.

In recent years,the potential role of mitochondrial dynamics imbalance in the pathogenesis of various psychiatric disorders has attracted growing attention.Mitochondria regulate energy metabolism,oxidative stress,apoptosis,and neuronal function through dynamic processes such as fission and fusion.Disruption of these processes may impair synaptic function and neural network stability.In schizophrenia,depression,bipolar disorder,Alzheimer disease,and autism spectrum disorders,studies have reported dysregulated expression of mitochondrial fission-related proteins DRP1 and FIS1,as well as fusion-related proteins MFN1,MFN2,and OPA1,accompanied by structural and functional mitochondrial impairments,neuronal apoptosis,and synaptic loss.Evidence from clinical studies,animal models,and cell experiments further supports that these mitochondrial dynamics abnormalities are closely associated with cognitive deficits,emotional disturbances,and neurodegenerative changes.Although mitochondrial dynamic dysfunction alone cannot fully explain the onset of psychiatric disorders,it may represent a potential biological mechanism that offers new insights into disease mechanisms and provide a theoretical basis for developing targeted intervention strategies.

Objective To investigate the impact of chronic observational social defeat stress on multidimensional behaviors in female mice,including social interaction,emotion,and cognition,as well as the underlying molecular mechanisms.Methods Adult female C57BL6N mice were divided into a stress group and a control group.Behavioral assessment were conducted through social interaction tests,anxiety-like behavior tests,and cognitive tests(novel object recognition and spatial memory).Synaptic plasticity-related proteins in the hippocampus were detected using Western blot.Results Behavioral tests revealed that the stress group showed reduced social interaction time compared to the control group[(106.2±9.31)s vs.(156.5±14.81)s,P<0.05].In a novel environment,the stress group consumed less food than the control group[(0.10±0.01)g vs.(0.16±0.02)g,P<0.05].Cognitive tests demonstrated that the stress group exhibited impaired novel object recognition[(52.17%%±2.67%)vs.(65.91%±5.23%)]and spatial memory[(61.84%±3.14%)vs.(74.13%±1.94%)]compared to the control group(P<0.05).Western blot analysis showed that the expression of hippocampal synaptic plasticity-related proteins,including the glutamate ionotropic receptor N-methyl-D-aspartate(NMDA)receptor subunit NR2A[(0.66±0.05)vs.(0.89±0.08)]and brain-derived neurotrophic factor(BDNF)[(0.81±0.05)vs.(1.14±0.06)],was significantly decreased in the stress group(P<0.05).Conclusion Chronic observational social defeat stress induces social withdrawal,anxiety-like behaviors,and cognitive deficits in female mice.These effects may be associated with reduced expression of NR2A and BDNF in the hippocampus.

In recent years,the potential role of mitochondrial dynamics imbalance in the pathogenesis of various psychiatric disorders has attracted growing attention.Mitochondria regulate energy metabolism,oxidative stress,apoptosis,and neuronal function through dynamic processes such as fission and fusion.Disruption of these processes may impair synaptic function and neural network stability.In schizophrenia,depression,bipolar disorder,Alzheimer disease,and autism spectrum disorders,studies have reported dysregulated expression of mitochondrial fission-related proteins DRP1 and FIS1,as well as fusion-related proteins MFN1,MFN2,and OPA1,accompanied by structural and functional mitochondrial impairments,neuronal apoptosis,and synaptic loss.Evidence from clinical studies,animal models,and cell experiments further supports that these mitochondrial dynamics abnormalities are closely associated with cognitive deficits,emotional disturbances,and neurodegenerative changes.Although mitochondrial dynamic dysfunction alone cannot fully explain the onset of psychiatric disorders,it may represent a potential biological mechanism that offers new insights into disease mechanisms and provide a theoretical basis for developing targeted intervention strategies.

Objective To screen hub genes and signaling pathways associated with acute ischemic stroke(AIS)using bioinformatics methods,identify potential biomarkers,and provide new evidence for the mechanism research of AIS.Methods The gene expression dataset GSE37587 of AIS patients and healthy controls was obtained from the public database gene expression omnibus(GEO).The differentially expressed genes(DEGs,|log2 FC|≥1.2,FDR＜0.05)were screened using the limma package.The enrichment analysis of GO/KEGG was performed with the DAVID database.The weighted correlation network analysis(WGCNA)was used to construct a gene co-expression network for screening key modules.Then,a protein-protein interaction(PPI)network was constructed based on the STRING database and Cytoscape software to identify hub genes.The dataset GSE16561 was used to validate.Meanwhile,the clinical samples from 30 AIS patients and 30 healthy controls visited Zibo First Hospital from January to May 2025 were validated by the real time fluorescence quantitative PCR(qRT-PCR).The diagnostic efficacy was evaluated using the receiver operating characteristics(ROC)curve.Results A total of 653 DEGs were identified,including 252 up-regulated and 401 down-regulated genes.They were mainly enriched in biological processes such as ribosome biogenesis,endoplasmic reticulum protein processing,and oxidative phospho-rylation,as well as signaling pathways such as viral infection-related pathways and PD-L1/PD-1 checkpoint pathways in cancer.The core genes in the light green module identified by the WGCNA analysis were significantly enriched in the pathways such as mitophagy,ribosome,and endocytosis.The hub genes such as RPL34 and DDIT3 were screened from the PPI network,and their expression levels were significantly correlated with AIS.The analysis of the ROC curve showed that the areas under the ROC curve(AUCROC)of the hub genes for the diagnosis of AIS were 0.78-0.82,which had high clinical application value.Conclusion Ribosomal proteins,endoplas-mic reticulum stress-related genes,and viral infection response pathways are key molecular events in the occurrence of AIS.The genes such as RPL34 and DDIT3 are expected to be potential biomarkers for AIS,providing experimental evidence for the development of di-agnostic markers.

Objective To investigate the impact of chronic observational social defeat stress on multidimensional behaviors in female mice,including social interaction,emotion,and cognition,as well as the underlying molecular mechanisms.Methods Adult female C57BL6N mice were divided into a stress group and a control group.Behavioral assessment were conducted through social interaction tests,anxiety-like behavior tests,and cognitive tests(novel object recognition and spatial memory).Synaptic plasticity-related proteins in the hippocampus were detected using Western blot.Results Behavioral tests revealed that the stress group showed reduced social interaction time compared to the control group[(106.2±9.31)s vs.(156.5±14.81)s,P<0.05].In a novel environment,the stress group consumed less food than the control group[(0.10±0.01)g vs.(0.16±0.02)g,P<0.05].Cognitive tests demonstrated that the stress group exhibited impaired novel object recognition[(52.17%%±2.67%)vs.(65.91%±5.23%)]and spatial memory[(61.84%±3.14%)vs.(74.13%±1.94%)]compared to the control group(P<0.05).Western blot analysis showed that the expression of hippocampal synaptic plasticity-related proteins,including the glutamate ionotropic receptor N-methyl-D-aspartate(NMDA)receptor subunit NR2A[(0.66±0.05)vs.(0.89±0.08)]and brain-derived neurotrophic factor(BDNF)[(0.81±0.05)vs.(1.14±0.06)],was significantly decreased in the stress group(P<0.05).Conclusion Chronic observational social defeat stress induces social withdrawal,anxiety-like behaviors,and cognitive deficits in female mice.These effects may be associated with reduced expression of NR2A and BDNF in the hippocampus.

Objective To screen hub genes and signaling pathways associated with acute ischemic stroke(AIS)using bioinformatics methods,identify potential biomarkers,and provide new evidence for the mechanism research of AIS.Methods The gene expression dataset GSE37587 of AIS patients and healthy controls was obtained from the public database gene expression omnibus(GEO).The differentially expressed genes(DEGs,|log2 FC|≥1.2,FDR＜0.05)were screened using the limma package.The enrichment analysis of GO/KEGG was performed with the DAVID database.The weighted correlation network analysis(WGCNA)was used to construct a gene co-expression network for screening key modules.Then,a protein-protein interaction(PPI)network was constructed based on the STRING database and Cytoscape software to identify hub genes.The dataset GSE16561 was used to validate.Meanwhile,the clinical samples from 30 AIS patients and 30 healthy controls visited Zibo First Hospital from January to May 2025 were validated by the real time fluorescence quantitative PCR(qRT-PCR).The diagnostic efficacy was evaluated using the receiver operating characteristics(ROC)curve.Results A total of 653 DEGs were identified,including 252 up-regulated and 401 down-regulated genes.They were mainly enriched in biological processes such as ribosome biogenesis,endoplasmic reticulum protein processing,and oxidative phospho-rylation,as well as signaling pathways such as viral infection-related pathways and PD-L1/PD-1 checkpoint pathways in cancer.The core genes in the light green module identified by the WGCNA analysis were significantly enriched in the pathways such as mitophagy,ribosome,and endocytosis.The hub genes such as RPL34 and DDIT3 were screened from the PPI network,and their expression levels were significantly correlated with AIS.The analysis of the ROC curve showed that the areas under the ROC curve(AUCROC)of the hub genes for the diagnosis of AIS were 0.78-0.82,which had high clinical application value.Conclusion Ribosomal proteins,endoplas-mic reticulum stress-related genes,and viral infection response pathways are key molecular events in the occurrence of AIS.The genes such as RPL34 and DDIT3 are expected to be potential biomarkers for AIS,providing experimental evidence for the development of di-agnostic markers.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.