OBJECTIVE To investigate the role and mechanism of microRNA-125b (miR-125b) in downregulating ion channel-related protein expression in a cardiac hypertrophy model.METHODS① In vivo:Lentiviral vectors for miR-125b overexpression and knockdown were constructed,and male C57BL/6 mice were divided into the following groups:sham group (thoracotomy without virus injection),LV-miR-125b group (mmu-miR-125b mimic),LV-miR-125b-inhibitor group (mmu-miR-125b-inhibitor),and negative control group (LV-NC).The mice were raised under normal conditions for 4 weeks.The ultrastructural changes in myocardium tissue sections of LV-miR-125b mice were observed using trans-mission electron microscopy.The cardiac hypertrophy model in mice was established using thoracic aortic constriction (TAC).Echocardiography was performed to measure ejection fraction (EF) and frac-tional shortening (FS),and the ratio of heart weight to body weight (HW/BW),ratio of heart weight to tibia length (HW/TL),as well as the expression level of the myocardial hypertrophy marker β-myosin heavy chain (β-MHC) were calculated to evaluate the success of the TAC-induced hypertrophy model.Subse-quently,C57BL/6 mice were divided into four groups:Sham group,TAC model group,LV-miR-125b-inhibitor+TAC group,and LV-NC+TAC group.Protein expression levels of cardiac sodium channel (Nav1.5) and calcium channel (Cav1.2) were detected using Western blotting.RT-qPCR was performed to assess the levels of miR-125b and mRNA expression of myocardial hypertrophy markers,including atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and β-MHC.② In vitro:Primary cultured neonatal Kunming mouse cardiomyocytes were divided into four groups:cell control group (no treatment),miR-125b overexpression group,miR-125b-inhibitor group,and negative control group (NC).RT-qPCR was used to detect the levels of miR-125b,ANP,BNP,and β-MHC.Western blotting and immunofluorescence were performed to assess the expression levels of Nav1.5 and Cav1.2 in the cardiomyocytes.Luciferase reporter gene assay was used to evaluate the direct effect of miR-125b on the target proteins Nav1.5 and Cav1.2.RESULTS ① In vivo:Compared to the Sham group,the TAC model mice showed significantly increased the ratio of heart weight to body weight (HW/BW),the ratio of heart weight to tibia length (HW/TL),and expression levels of the myocardial hypertrophy marker β-MHC (P＜0.05),indicating the successful establishment of the TAC model.Furthermore,miR-125b expression was significantly elevated in the TAC model group (P＜0.01).In the LV-miR-125b group,compared to the LV-NC group,the expression levels of myocardial hypertrophy markers ANP,BNP,and β-MHC were significantly increased (P＜0.01),while the ejection fraction (EF) and fractional short-ening (FS) values of the mice were significantly reduced (P＜0.01).Additionally,Additionally,myocardium ultrastructure of LV-miR-125b group was damaged.Compared to the LV-NC+TAC group,the LV-miR-125b-inhibitor+TAC group showed a significant increase in ejection fraction (EF) and fractional shortening (FS) values (P＜0.05).Additionally,the levels of Nav1.5 and Cav1.2 in myocardium tissue were signifi-cantly elevated in the LV-miR-125b-inhibitor+TAC group compared to the LV-NC+TAC group (P＜0.05).② In vitro:Compared to the NC group,the miR-125b overexpression group showed a significant increase in miR-125b expression (P＜0.01),as well as elevated levels of ANP,BNP,and β-MHC (P＜0.01).However,miR-125b-inhibitor significantly reversed the increases in ANP,BNP,and β-MHC (P＜0.01).Western blotting and immunofluorescence results showed that,compared to the NC group,the miR-125b mimic group exhibited significantly decreased levels of Nav1.5 and Cav1.2 (P＜0.01),while miR-125b-inhibitor led to an increase in the levels of both Nav1.5 and Cav1.2.Luciferase assay results demon-strated that miR-125b directly binds to the ion channel proteins Nav1.5 and Cav1.2,encoded by the SCN5A and CACNA1C genes.CONCLUSION miR-125b promotes the development of cardiac hyper-trophy by inhibiting the voltage-gated ion channel proteins Nav1.5 and Cav1.2 Inhibition of miR-125b expression improves cardiac hypertrophy.

Objective:To investigate whether discontinuation of previous targeted immunotherapy increases the risk of rebleeding in patients with advanced liver cancer complicated with esophageal and gastric variceal bleeding after endoscopic treatment.Methods:A retrospective cohort study was conducted to include advanced liver cancer patients who were diagnosed with esophageal and gastric variceal bleeding through endoscopic examination and treated under endoscopy at Zhongshan Hospital, Fudan University from March 1, 2020 to March 1, 2022, due to upper gastrointestinal bleeding. We collected clinical data from patients and divided them into targeted immunotherapy group and non targeted immunotherapy group based on whether they received targeted immunotherapy before bleeding; Follow up observation was conducted for 6 months to evaluate the patient′s re bleeding and survival status.Results:A total of 55 patients were included, of which 24 had previously received targeted immunotherapy and 31 had not received targeted immunotherapy. There was no significant difference between the two groups in gender distribution, etiology, hypertension and diabetes (all P>0.05). The age of the target immunotherapy group was younger than that of the non target immunotherapy group, and the level of fibrinogen was higher than that of the non target immunotherapy group, with statistical significance ( P=0.002, 0.017). There was no statistically significant difference in the 6-month re bleeding rate (20.83% vs 22.58%, P=0.269) and 6-month mortality rate (45.83% vs 29.03%, P=0.199) between the targeted and non targeted groups of patients. Further Cox regression multivariate analysis revealed that Child-pugh grading was an independent risk factor for 6-month survival in patients with advanced liver cancer with esophageal and gastric varices ( HR=2.64, P=0.009). Conclusions:Targeted immunotherapy does not increase the rate of rebleeding in patients with advanced unresectable liver cancer after endoscopic treatment of esophageal and gastric varices. Child-pugh grading is a factor that affects the 6-month survival of advanced liver cancer patients after bleeding, and the poorer the liver function, the shorter the survival period.

Objective:Artificial intelligence-assisted esophageal cytology was used to develop and validate a risk prediction model for screening esophageal precancerous lesions.Methods:This study was a secondary analysis of data from the esophageal cancer screening trial (EAST). A total of 17 294 subjects were included who underwent upper gastrointestinal endoscopy and artificial intelligence-assisted esophageal cytology screening at 39 tertiary or secondary hospitals and 5 community service centers in areas with high incidence of esophageal squamous cell carcinoma in China from January 1, 2021 to June 30, 2022. Subjects ( n=14 415) screened in the hospital constituted the hospital opportunistic screening cohort, which served as the training set. An artificial intelligence-assisted esophageal cytological risk prediction model (LightGBM model for short) was developed based on light-gradient boosting machine (LightGBM) machine learning algorithm. Subjects undergoing screening at 5 community health service centers ( n=2 879) constituted a community screening cohort, which served as a validation set. The diagnostic efficacy of LightGBM model for esophageal precancerous lesions in the community screening cohort was evaluated by using pathological results of endoscopic biopsy as the golden standard. Results:The LightGBM model, trained in the opportunistic screening cohort, exhibited an area under the receiver operator characteristic (ROC) curve of 0.93 (95% CI: 0.91-0.95) for detecting precancerous lesions. The cutoff value of the ROC curve was determined as 0.08 based on the maximum Youden index. The sensitivity and specificity of LightGBM model were 91.0% (95% CI: 86.9%-95.1%) and 86.2% (95% CI: 85.7%-86.8%), respectively, when the risk prediction score was >0.08 as the screening criterion for precancerous lesions. The sensitivity, specificity, and accuracy of LightGBM model for precancerous lesions in the community screening cohort were 95.2% (20/21), 87.5% (2 502/2 858), and 87.6% (2 522/2 879), respectively. Conclusion:The artificial intelligence-assisted esophageal cytology risk prediction model showcased remarkable sensitivity and specificity in screening for esophageal precancerous lesions, underscoring its potential for widespread adoption and application in esophageal cancer screening.

Objective To establish a machine learning radiomics model that can accurately predict MRI enhancement patterns of glioma based on T2 fluid attenuated inversion recovery(T2-FLAIR)images for optimizing the workflow of magnetic resonance imaging(MRI)examinations of glioma patients.Methods We retrospectively collected preoperative MR T2-FLAIR images from 385 patients with pathologically confirmed glioma,who were divided into enhancing and non-enhancing groups according to the enhancement pattern.Predictive radiomics models were established using Gaussian Process,Linear Regression,Linear Regression-Least absolute shrinkage and selection operator,Support Vector Machine,Linear Discriminant Analysis or Naive Bayes as the classifiers in the training cohort(n=201)and tested both in the internal(n=85)and external validation cohorts(n=99).The receiver-operating characteristic curve was used to assess the predictive performance of the models.Results The predictive model constructed based on 15 radiomics features using Gaussian Process as the classifier had the best predictive performance in both the training cohort and the internal validation cohort,with areas under the curve(AUC)of 0.88(95%CI:0.81-0.94)and 0.80(95%CI:0.71-0.88),respectively.In the external validation cohort,the model showed an AUC of 0.81(95%CI:0.71-0.90)with sensitivity,specificity,positive predictive value and negative predictive value of 0.98,0.61,0.76 and 0.96,respectively.Conclusion The T2-FLAIR-based machine learning radiomics model can accurately predict the enhancement pattern of gliomas on MRI.

Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Objective To establish a machine learning radiomics model that can accurately predict MRI enhancement patterns of glioma based on T2 fluid attenuated inversion recovery(T2-FLAIR)images for optimizing the workflow of magnetic resonance imaging(MRI)examinations of glioma patients.Methods We retrospectively collected preoperative MR T2-FLAIR images from 385 patients with pathologically confirmed glioma,who were divided into enhancing and non-enhancing groups according to the enhancement pattern.Predictive radiomics models were established using Gaussian Process,Linear Regression,Linear Regression-Least absolute shrinkage and selection operator,Support Vector Machine,Linear Discriminant Analysis or Naive Bayes as the classifiers in the training cohort(n=201)and tested both in the internal(n=85)and external validation cohorts(n=99).The receiver-operating characteristic curve was used to assess the predictive performance of the models.Results The predictive model constructed based on 15 radiomics features using Gaussian Process as the classifier had the best predictive performance in both the training cohort and the internal validation cohort,with areas under the curve(AUC)of 0.88(95%CI:0.81-0.94)and 0.80(95%CI:0.71-0.88),respectively.In the external validation cohort,the model showed an AUC of 0.81(95%CI:0.71-0.90)with sensitivity,specificity,positive predictive value and negative predictive value of 0.98,0.61,0.76 and 0.96,respectively.Conclusion The T2-FLAIR-based machine learning radiomics model can accurately predict the enhancement pattern of gliomas on MRI.

Objective To explore the effects of anticoagulation treatment to postoperative bleeding events in liver cirrhosis patients with gastric varices and portal vein thrombosis.Methods Patients diagnosed with portal vein thrombosis and treated with endoscopic cyanoacrylate injection at Zhongshan Hospital,Fudan University due to gastric variceal bleeding from January 2023 to December 2023 were included.Clinical data of patients were collected,and patients were divided into anticoagulant group and non-anticoagulant group based on whether anticoagulant treatment was performed within 48 h after treatment.Re-bleeding in patients was evaluated in 6 weeks of follow-up.Cox regression was used for univariate and multivariate analysis of re-bleeding within 6 weeks after treatment.Results A total of 160 patients were included,of whom 65 patients received anticoagulation treatment within 48 h after endoscopic cyanoacrylate injection.There were no statistically significant differences in gender,etiology of liver cirrhosis,dosage of cyanoacrylate and sclerosing agents,and Child-Pugh grading between the two groups.There was no statistically significant difference in re-bleeding rate within 6 weeks after treatment between the two groups(1.54％vs 1.05％,P=0.795).Multivariate Cox regression analysis showed that the large amount of cyanoacrylate was a risk factor for re-bleeding within 6 weeks after endoscopic treatment(HR=5.862,P=0.015).Conclusions For patients with liver cirrhosis,gastric varices,and portal vein thrombosis,who receive endoscopic cyanoacrylate injection,early anticoagulation does not increase the risk of re-bleeding after treatment,while a large amount of cyanoacrylate injection may be a risk factor for re-bleeding.However,sample should be increased to verify.

Objective To compare the efficacy and safety of endoscopic ligation treatment and endoscopic tissue glue injection for secondary prevention of gastric variceal bleeding.Methods Patients with cirrhosis and esophagogastric variceal bleeding treated with gastric variceal ligation in Zhongshan Hospital,Fudan University,from January 2017 to December 2019 were screened(ligation group).And during the same period,patients underwent endoscopic cyanoacrylate treatment were also screened(tissue glue group).59 patients were included in the two groups after propensity score matching.Univariate and multivariate Cox proportional hazard regression models were used to anslyze risk factors for re-bleeding.Kaplan-Meier curves were plotted to analyze re-bleeding rate and mortality of the two treatment groups.Results There was no statistically significant difference in the eradication rate of esophagogastric varices between the ligation group and the tissue glue group(83.05％vs 79.66％,P=0.778);the ligation group required fewer median endoscopic treatments for variceal eradication(2 vs 3,P=0.017)and a lower average dosage of cyanoacrylate(0.70 mL vs 2.67 mL,P＜0.001).Multivariate Cox regression analysis showed that portal shunt was a risk factor for esophagogastric varices re-bleeding(HR=3.14,95％CI 1.02-9.68,P=0.046),endoscopic variceal ligation was a protective factor against re-bleeding(HR=0.25,95％CI 0.08-0.71,P=0.010).Compared with endoscopic cyanoacrylate injection,endoscopic ligation treatment did not significantly increase the 2-year risk of esophagogastric variceal re-bleeding(18.69％vs 36.29％,P=0.067)or risk of death(1.69％vs 3.39％,P=1.000);patients with GOV1 type had a significantly lower risk of re-bleeding after endoscopic ligation treatment(0 vs 40.27％,P=0.012)and there was a trend towards a lower re-bleeding risk in patients with GOV2 type after endoscopic ligation treatment(13.27％vs 34.16％,P=0.056).Conclusions Endoscopic ligation treatment has higher eradication rate for esophagogastric varices,and does not increase the risk of re-bleeding,death,or other adverse events.Therefore,it can be considered an effective secondary prevention way for patients with gastric varices.

Objective To explore the predictive value of systolic pulmonary artery pressure (SPAP) on autonomic nerve excitation in patients with valvular disease, so as to provide reference for the formulation of clinical intervention plans. Methods The clinical data of patients with valvular disease who received surgical treatment in the General Hospital of Northern Theater Command from August 28, 2020 to February 3, 2021 were prospectively collected. According to the standard deviation of normal-to-normal R-R intervals (SDNN) of the heart rate variability (HRV) of the long-range dynamic electrocardiogram (ECG) 7 days before the operation, the patients were divided into three groups: a sympathetic dominant (SE) group (SDNN≤50 ms), a balance group (50 ms

OBJECTIVE To investigate the role and mechanism of microRNA-125b (miR-125b) in downregulating ion channel-related protein expression in a cardiac hypertrophy model.METHODS① In vivo:Lentiviral vectors for miR-125b overexpression and knockdown were constructed,and male C57BL/6 mice were divided into the following groups:sham group (thoracotomy without virus injection),LV-miR-125b group (mmu-miR-125b mimic),LV-miR-125b-inhibitor group (mmu-miR-125b-inhibitor),and negative control group (LV-NC).The mice were raised under normal conditions for 4 weeks.The ultrastructural changes in myocardium tissue sections of LV-miR-125b mice were observed using trans-mission electron microscopy.The cardiac hypertrophy model in mice was established using thoracic aortic constriction (TAC).Echocardiography was performed to measure ejection fraction (EF) and frac-tional shortening (FS),and the ratio of heart weight to body weight (HW/BW),ratio of heart weight to tibia length (HW/TL),as well as the expression level of the myocardial hypertrophy marker β-myosin heavy chain (β-MHC) were calculated to evaluate the success of the TAC-induced hypertrophy model.Subse-quently,C57BL/6 mice were divided into four groups:Sham group,TAC model group,LV-miR-125b-inhibitor+TAC group,and LV-NC+TAC group.Protein expression levels of cardiac sodium channel (Nav1.5) and calcium channel (Cav1.2) were detected using Western blotting.RT-qPCR was performed to assess the levels of miR-125b and mRNA expression of myocardial hypertrophy markers,including atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and β-MHC.② In vitro:Primary cultured neonatal Kunming mouse cardiomyocytes were divided into four groups:cell control group (no treatment),miR-125b overexpression group,miR-125b-inhibitor group,and negative control group (NC).RT-qPCR was used to detect the levels of miR-125b,ANP,BNP,and β-MHC.Western blotting and immunofluorescence were performed to assess the expression levels of Nav1.5 and Cav1.2 in the cardiomyocytes.Luciferase reporter gene assay was used to evaluate the direct effect of miR-125b on the target proteins Nav1.5 and Cav1.2.RESULTS ① In vivo:Compared to the Sham group,the TAC model mice showed significantly increased the ratio of heart weight to body weight (HW/BW),the ratio of heart weight to tibia length (HW/TL),and expression levels of the myocardial hypertrophy marker β-MHC (P＜0.05),indicating the successful establishment of the TAC model.Furthermore,miR-125b expression was significantly elevated in the TAC model group (P＜0.01).In the LV-miR-125b group,compared to the LV-NC group,the expression levels of myocardial hypertrophy markers ANP,BNP,and β-MHC were significantly increased (P＜0.01),while the ejection fraction (EF) and fractional short-ening (FS) values of the mice were significantly reduced (P＜0.01).Additionally,Additionally,myocardium ultrastructure of LV-miR-125b group was damaged.Compared to the LV-NC+TAC group,the LV-miR-125b-inhibitor+TAC group showed a significant increase in ejection fraction (EF) and fractional shortening (FS) values (P＜0.05).Additionally,the levels of Nav1.5 and Cav1.2 in myocardium tissue were signifi-cantly elevated in the LV-miR-125b-inhibitor+TAC group compared to the LV-NC+TAC group (P＜0.05).② In vitro:Compared to the NC group,the miR-125b overexpression group showed a significant increase in miR-125b expression (P＜0.01),as well as elevated levels of ANP,BNP,and β-MHC (P＜0.01).However,miR-125b-inhibitor significantly reversed the increases in ANP,BNP,and β-MHC (P＜0.01).Western blotting and immunofluorescence results showed that,compared to the NC group,the miR-125b mimic group exhibited significantly decreased levels of Nav1.5 and Cav1.2 (P＜0.01),while miR-125b-inhibitor led to an increase in the levels of both Nav1.5 and Cav1.2.Luciferase assay results demon-strated that miR-125b directly binds to the ion channel proteins Nav1.5 and Cav1.2,encoded by the SCN5A and CACNA1C genes.CONCLUSION miR-125b promotes the development of cardiac hyper-trophy by inhibiting the voltage-gated ion channel proteins Nav1.5 and Cav1.2 Inhibition of miR-125b expression improves cardiac hypertrophy.