1.Changes in renal function in chronic hepatitis B patients treated initially with entecavir versus tenofovir alafenamide fumarate and related influencing factors
Shipeng MA ; Yanqing YU ; Xiaoping WU ; Liang WANG ; Liping LIU ; Yuliang ZHANG ; Xin WAN ; Shanfei GE
Journal of Clinical Hepatology 2025;41(1):44-51
ObjectiveTo investigate the influence of entecavir (ETV) versus tenofovir alafenamide fumarate (TAF) on renal function in previously untreated patients with chronic hepatitis B (CHB). MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023, and according to the antiviral drug used, they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data, propensity score matching (PSM) was used for matching and analysis at a ratio of 2∶1, and the two groups were compared in terms of estimated glomerular filtration rate (eGFR) and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48, the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function, and the receiver operating characteristic (ROC) curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function, and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching, there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group (all P>0.05), with an eGFR level of 112.29±9.92 mL/min/1.73 m2 in the ETV group and 114.72±12.15 mL/min/1.73 m2 in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups, and compared with the TAF group at week 48, the ETV group had a significantly lower eGFR (106.42±14.12 mL/min/1.73 m2 vs 112.25±13.44 mL/min/1.73 m2, t=-2.422, P=0.017) and a significantly higher incidence rate of abnormal renal function (17.00% vs 4.00%, χ2=5.092, P=0.024). After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients, the univariate analysis showed that there were significant differences between the two groups in age (Z=-2.039, P=0.041), treatment drug (ETV/TAF) (χ2=5.092, P=0.024), and baseline eGFR level (t=4.023, P<0.001), and the multivariate Logistic regression analysis showed that baseline eGFR (odds ratio [OR]=0.896, 95% confidence interval [CI]: 0.841 — 0.955, P<0.001) and treatment drug (OR=5.589, 95%CI: 1.136 — 27.492, P=0.034) were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients, with a cut-off value of 105.24 mL/min/1.73 m2, a sensitivity of 73.68%, and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m2 had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m2 (χ2=22.330, P<0.001), and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group (χ2=4.961, P=0.026). With the initiation of antiviral therapy, both the ETV group and the TAF group had a significant reduction in eGFR (F=5.259, P<0.001), but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 (t=-2.422, P=0.017); both the baseline eGFR≤105.24 mL/min/1.73 m2 group and the baseline eGFR>105.24 mL/min/1.73 m2 group had a significant reduction in eGFR (F=5.712, P<0.001), and there was a significant difference in eGFR between the two groups at baseline and weeks 12, 24, 36, and 48 (t=-13.927, -9.780, -8.835, -9.489, and -8.953, all P<0.001). ConclusionFor CHB patients initially treated with ETV or TAF, ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.
2.Preparation of Lonicerae japonicae flavonoids liposome membrane and its antibacterial mechanism against methicillin-resistant Staphylococcus aureus
Rui XIONG ; Shipeng ZHANG ; Hengxu LIU ; Lu WANG ; Xiaodan LAI
China Pharmacy 2024;35(21):2616-2621
OBJECTIVE To prepare Lonicerae japonicae flavonoids liposome membrane (LFLM), and to study the mechanism of its anti-methicillin-resistant Staphylococcus aureus (MRSA). METHODS L. japonicae flavonoids liposome (LFL) were prepared by ethanol injection with phospholipids and cholesterol as carriers. LFLM was prepared by loading LFL in mixed membranes of chitosan and polyvinyl alcohol. The particle size of LFL, polydispersity index (PDI) and release rate of LFLM were measured. A control group, LFLM low-concentration group (2.5 mg/mL), LFLM-medium concentration group (5 mg/mL), LFLM high-concentration group (10 mg/mL), positive group (10 μg/mL vancomycin), and combination therapy group (10 mg/mL LFLM and 10 μg/mL vancomycin) were set up. The effects of LFLM on MRSA colony formation and survival as well as the formation of MRSA biofilm were evaluated. The contents of K+, Mg2+, lactic dehydrogenase (LDH), and alkaline phosphatase (AKP) in the supernatant of MRSA were determined. mRNA expressions of mecA and mecR1 in MRSA were determined. RESULTS The particle size of LFL was (80.91±3.96) nm, and the PDI was 0.26±0.07. The release rate of LFLM was 55% within 12 h and 73% within 36 h. Compared with the control group, the number of MRSA colony formation decreased significantly in LFLM medium-concentration and high-concentration groups, and the positive group (P<0.05). The ratio of dead to live bacteria, biofilm inhibition rate, and the contents of K+, Mg2+, LDH and AKP were increased significantly (P<0.05), while the mRNA expressions of mecA and mecR1 were decreased significantly (P<0.05). The combination of LFLM and vancomycin further enhanced the anti-MRSA effect. CONCLUSIONS LFLM is prepared successfully in the study and has good drug release characteristics. LFLM can exert anti-MRSA activity by promoting cell wall and membrane damage, and suppressing the mRNA expression of mecA and mecR1.
3.Incidence and influencing factors of non-alcoholic fatty liver disease among rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps
Caiyin LI ; Shuxia GUO ; Yu LI ; Heng GUO ; Rulin MA ; Xianghui ZHANG ; Xinping WANG ; Yunhua HU ; Keerman MULATIBIEKE ; Shipeng GAO ; Jia HE
Chinese Journal of Epidemiology 2024;45(8):1149-1157
Objective:To investigate the incidence characteristics and influencing factors of non-alcoholic fatty liver disease (NAFLD) in rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps and to provide scientific evidence for early identification and prevention of NAFLD for residents.Methods:A total of 10 158 participants were included from the Xinjiang Uygur ethnic group population cohort. A prospective cohort study and Cox proportional hazards regression model analysis were used to explore the influencing factors and clustering of NAFLD, and the dose-response relationship between related biochemical indicators and the risk of NAFLD was studied using a restricted cubic spline.Results:The cumulative incidence rate of NAFLD was 6.9%, and the incidence density of NAFLD was 12.06/1 000 person-years. The incidence density of NAFLD in females was higher than in males (14.72/1 000 person-years vs. 9.17/1 000 person-years, P<0.001). The incidence density of NAFLD gradually increased with age in the total population, both men and women (all P<0.001). In the general population, an education level of junior high school or above was a protective factor for NAFLD, while older age, divorce, widowhood, overweight, obesity, hypertension, increased glomerular filtration rate, decreased HDL-C, increased LDL-C, and increased ALT were risk factors for NAFLD. Estimated glomerular filtration rate (eGFR), HDL-C, LDL-C, and ALT were non-linearly correlated with the incidence of NAFLD, and there was a significant dose-response relationship between them. Only 19.1% of residents had no NAFLD risk factors; over 80.9% had ≥1 NAFLD risk factors. The risk of NAFLD increased with the number of risk factors. Conclusions:The incidence of NAFLD in rural Uygur ethnic group residents in Xinjiang Production and Construction Corps was relatively low, but most residents had one or more risk factors for NAFLD. Prevention and control of NAFLD in this population cannot be ignored. In addition, people of older age, divorced or widowed, low education level, overweight or obese, hypertension, and abnormal eGFR, HDL-C, LDL-C, and ALT were the high-risk groups of NAFLD that need to be paid attention to in this population.
4.Establishment and evaluation of a textbook outcome prediction model of laparoscopic radical surgery for patients with pancreatic body and tail tumor
Senmao MU ; Bingyao LI ; Changqian TANG ; Yongnian REN ; Xingbo WEI ; Yuqi GUO ; Shipeng LI ; Yafeng WANG ; Liancai WANG ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2024;30(7):509-515
Objective:To analyze the influencing factors of not achieving textbook outcome (TO) after laparoscopic radical surgery in patients with malignant pancreatic body and tail tumor, and to establish and evaluate a nomogram for predicting the failure to achieve TO.Methods:The clinical data of 111 patients with malignant pancreatic body and tail tumors undergoing laparoscopic radical surgery in the Department of Hepatobiliary and Pancreatic Surgery in Henan Provincial People's Hospital from January 2020 to December 2022 were retrospectively analyzed, including 44 males and 67 females, aged (53.8±14.7) years. All patients were staged TNM I to II, including pancreatic ductal adenocarcinoma ( n=102, 91.9%), pancreatic neuroendocrine tumor ( n=5, 4.5%), and pancreatic intraductal papillary mucinous tumors ( n=4, 3.6%). The patients were randomly divided into a training set ( n=78) and a test set ( n=33) at a ratio of 7∶3. The 78 patients in the training set were further divided into TO group ( n=28) and control group ( n=50, not achieving TO). Based on the univariate and multivariate logistic regression analysis of training set, the influencing factors of failure to achieve TO after laparoscopic radical surgery in patients with pancreatic body and tail tumor were analyzed. A nomogram based on the multi-factors were established to predict the failure to achieve TO. Receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) were utilized to evaluate the nomogram. Results:There were significant differences in tumor diameter, positive lymph nodes, operation time and CT value of pancreas between the TO and control groups (all P<0.05). Multivariate logistic regression analysis showed that tumor diameter >4 cm ( OR=9.673, 95% CI: 2.198-42.579), positive lymph node ( OR=5.385, 95% CI: 1.514-19.154), pancreatic CT value ( OR=0.594, 95% CI: 0.392-0.902) were the influencing factors for patients who did not achieve TO (all P<0.05). Based on the results of multiple factors, a nomogram was established to predict the failure to achieve TO after laparoscopic radical surgery. The area under the ROC curve of the nomogram was 0.849 (95% CI: 0.757-0.940) and 0.873 (95% CI: 0.730-1.000) in the training and test sets, respectively. The calibration curve was close to the ideal curve and the predicted results of the nomogram matched well with the actual results. The DCA showed that the nomogram has obvious positive net benefit. Conclusion:The nomogram constructed with tumor diameter > 4 cm, positive lymph nodes and CT value of pancreas for prediction of the patients with pancreatic body and tail malignant tumor after laparoscopic radical surgery did not achieve TO has good performance.
5.Clinical analysis of laparoscopic versus open hepatectomy for hepatocellular carcinoma in the central region of liver based on three-dimensional image reconstruction
Yuqi GUO ; Yaxin GUO ; Shipeng LI ; Yafeng WANG ; Changqian TANG ; Wensen WANG ; Deyu LI ; Liancai WANG
Chinese Journal of Hepatobiliary Surgery 2024;30(10):733-737
Objective:To compare the therapeutic efficacy of laparoscopic versus open hepatectomy based on three-dimensional image reconstruction in the treatment of hepatocellular carcinoma (HCC) in the central region of liver.Methods:Clinical data of 118 patients with HCC located in the central region of liver undergoing hepatectomy in the People's Hospital of Zhengzhou University from January 2020 to December 2023 were retrospectively analyzed, including 85 males and 33 females, aged (57.5±8.9) years old. According to surgical approach, patients were divided into two groups: the open surgery group ( n=66) and laparoscopic surgery group ( n=52). All patients underwent three-dimensional image reconstruction preoperatively to determine the tumor location and its relationship with the hepatic vessels. The operative duration, intraoperative blood loss, incidence of postoperative complications, postoperative hospital stay, and prognosis were compared between the groups. Results:Compared to open surgery, patients in laparoscopic group were younger [(55±9) years old vs. (59±8) years old], and experienced a longer operative time [212.5 (152.5, 262.3) min vs. 161.5 (135.8, 210.0) min] and a shorter postoperative hospital stay [11.0(9.0, 13.0) d vs. 13.0(11.0, 15.3) d] (all P<0.05). Postoperative pathology indicated that R0 resection was achieved in both groups. The incidence of postoperative complications were comparable between the two groups [34.6% (18/52) vs. 39.4% (26/66), χ2=0.28, P=0.594]. The 1-year and 3-year recurrence-free survivals were 69.7% and 53.0% in laparoscopic group, similar to those in open group (71.2% and 53.8%, respetctively, P=0.953). Conclusion:Laparoscopic hepatectomy based on three-dimensional image reconstruction is safe and feasible for HCC in central region in terms of clinical prognosis. Laparoscopic surgery is also associated with a shorter postoperative hospital stay.
10.Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway
Shan-Shan LI ; Lu PAN ; Zhen-Ye ZHANG ; Meng-Dan ZHOU ; Xu-Fei CHEN ; Ling-Ling QIAN ; Min DAI ; Juan LU ; Zhi-Ming YU ; Shipeng DANG ; Ru-Xing WANG
Diabetes & Metabolism Journal 2024;48(4):716-729
Background:
Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified.
Methods:
In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed.
Results:
In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation.
Conclusion
Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

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