1.Effects of sinomenine hydrochloride on ultrastructure and STING ex-pression in kidney tissues of db/db mice
Tongtong HE ; Xiaofei JIN ; Chunyue ZUO ; Xiaohong ZHOU ; Yu GAO ; Xiangmei CHEN ; Weijuan GAO
Chinese Journal of Pathophysiology 2024;40(11):2074-2080
AIM:This study aimed to investigate the effects of sinomenine hydrochloride(SIN)on the ultra-structure of renal tissue and the expression of interferon gene-stimulating factor in db/db mice.METHODS:Sixteen 12-week-old male db/db mice were randomly divided into two groups:a model group and a sinomenine hydrochloride(SIN)group,each consisting of 8 mice.An additional 8 wild-type(WT)mice served as the normal control group.The sinome-nine hydrochloride group was administered the treatment for 8 weeks,followed by a 20-week observation period,while the normal and model groups received an equal volume of saline via gavage.Weekly measurements were taken for body weight and fasting blood glucose.Serum creatinine(SCr)and blood urea nitrogen(BUN)levels were assessed,and 24-hour uri-nary microalbumin(ALB)levels,as well as serum inflammatory cytokines interleukin-1β(IL-1β),IL-6 and tumor necro-sis factor-α(TNF-α),were determined using ELISA.Pathological changes in renal tissue were evaluated through hema-toxylin-eosin(HE)staining,while ultrastructural alterations were examined using transmission electron microscopy.Im-munohistochemistry and Western blotting were employed to assess STING protein expression in renal tissue,and STING mRNA expression was quantified via RT-qPCR.RESULTS:Compared to the normal group,the model group exhibited significant increases in BUN,ALB,and SCr levels(P<0.01),alongside elevated inflammatory markers IL-1β,IL-6,and TNF-α(P<0.01).Notable pathological changes included leukocyte wall thickening in capillaries,inflammatory cell infiltration,increased mesangial matrix,disorganized and linear alignment of podocytes,and thickening of the basement membrane.Moreover,STING protein and mRNA expression levels were significantly elevated(P<0.01).In contrast,the sinomenine hydrochloride group demonstrated significantly reduced levels of renal function markers(BUN,ALB and SCr)compared to the model group(P<0.01),as well as decreased concentrations of inflammatory factors IL-1β,IL-6,and TNF-α(P<0.01).Improvements in renal histopathology included decreased leukocyte wall thickening,reduced inflam-matory cell presence,diminished mesangial matrix,and a significant reduction in foot process fusion,alongside thinner basement membranes.Both STING protein and mRNA expression levels were also significantly lower(P<0.01).CON-CLUSION:Sinomenine hydrochloride effectively mitigates renal tissue injury,improves ultrastructural alterations,and inhibits inflammatory responses in db/db mice.Its mechanism of action appears closely linked to the downregulation of STING protein and mRNA expression.
2.Association of energy metabolic markers with the short-term risk of spontaneous bacterial peritonitis in patients with decompensated hepatitis B virus-related liver cirrhosis
Xiumin CHEN ; Shenglong LIN ; Xiangmei WANG ; Huaxi MA ; Dongqing ZHANG ; Ziyuan LIAO ; Minghua LIN ; Haibing GAO
Journal of Clinical Hepatology 2022;38(6):1311-1316
Objective To investigate the association of energy metabolic markers with the risk of spontaneous bacterial peritonitis (SBP) in patients with decompensated hepatitis B virus-related liver cirrhosis (HBV-LC). Methods A retrospective analysis was performed for the clinical data of the patients with decompensated HBV-LC who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2019, and baseline clinical parameters and energy metabolic markers were compared between the patients with SBP and those without SBP within 2 weeks after admission. A multivariate logistic regression analysis was performed to investigate the risk factors for SBP. The t -test was used for comparison of normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between two groups; the Fisher's exact test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency of the newly established logistic regression model, and with the corresponding point of Youden index as the cut-off value, the DeLong test was used to compare the area under the ROC curve (AUC). Results A total of 50 patients with decompensated HBV-LC were included, among whom 23 (46%) developed SBP within 2 weeks after admission and 27 (54%) had no SBP during hospitalization. Compared with the non-SBP patients, the SBP patients had significantly lower triglyceride, prealbumin, and prothrombin time activity (PTA) and significantly higher international normalization ratio, C-reactive protein (CRP), and Model for End-Stage Liver Disease score (all P < 0.05). Comparison of baseline energy metabolic markers showed that compared with the non-SBP patients, the SBP patients had significantly lower respiratory quotient (RQ) [0.79(0.76-0.86) vs 0.85(0.79-0.91), P =0.041] and carbohydrate oxidation (CHO) rate [20.50%(15.25%-41.05%) vs 41.6%(22.25%-68.05%), P =0.041]. The multivariate logistic regression analysis showed that PTA was an independent risk factor for SBP in the patients with decompensated HBV-LC during hospitalization (odd ratio=0.004, P =0.008), and the regression model established based on the variables including PTA, CRP, RQ, and CHO had an AUC of 85.0% and a cut-off value of 0.60 at the maximum Youden index, with a specificity of 85.19% and a sensitivity of 73.91%, suggesting that this model had a better discriminatory ability than CRP (AUC=74.5%, P =0.049) and procalcitonin (AUC=56.4%, P < 0.01). Conclusion There are significant reductions in the energy metabolic markers RQ and CHO in the patients with decompensated HBV-LC who develop SBP within a short term, and their combination with PTA, CRP, and CHO/RQ ratio can help clinicians identify the patients at a high risk of SBP in the early stage and enhance nutrition support for such patients.
3.Energy metabolism characteristic with risk of secondary bacterial infection in patients with hepatitis B virus-related chronic liver disease
Shenglong LIN ; Minghua LIN ; Xiangmei WANG ; Xiumin CHEN ; Hanhui YE ; Huaxi MA ; Dongqing ZHANG ; Wenjun WU ; Jiahuang LIN ; Ziyuan LIAO ; Ruidan ZHENG ; Haibing GAO
Chinese Journal of Hepatology 2021;29(6):558-564
Objective:To investigate and analyze the energy metabolism characteristics and the correlation between energy metabolism and the risk of secondary bacterial infection in patients with hepatitis B virus-related chronic liver disease (HBV-CLD).Methods:Data of 183 cases admitted to the Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2020 were retrospectively analyzed. 79 cases of chronic hepatitis B, 51 cases of hepatitis B-related liver cirrhosis, and 53 cases of hepatitis B-related liver failure were collected. Among them patients with liver failure and decompensated liver cirrhosis were defined as severe liver disease group. The Quark RMR indirect calorimetry (COSMED Corporation, Italy) was used to exam the patients' energy metabolism condition, and the incidences of secondary bacterial infection of the patients during hospitalization were recorded. Shapiro-Wilk test and normal QQ plot were used to analyze the normal distribution of continuous variable data, which was consistent with the normal distribution and was described by mean ± standard deviation. In addition, if it did not conform to the normal distribution, the median and interquartile distance were used to describe it. Levene’s test was used to test the homogeneity of variance of the data, which was consistent with the normal distribution. The t-test was used to compare the means of the two groups of samples. One-way analysis of variance was used to compare the mean values of the three groups of samples, and then the Tukey's test was used to compare the two groups. If the variance was uneven or did not conform to the normal distribution, the Wilcoxon rank sum test was used to compare the differences between the two groups. Kruskal-Wallis test (H test) was used to compare the differences between the three groups of samples, and then the Dunnett’s test (Z test) was used for comparison between the two groups. Categorical variable data were analyzed using chi-square test. Logistic regression analysis was used to screen independent risk factors, and the criteria for variable inclusion ( P < 0.05). Results:The respiratory entropy (RQ) and non-protein respiratory entropy (npRQ) of the three groups had statistically significant difference ( P < 0.05). Among them, the RQ and npRQ of the chronic hepatitis B group were higher than hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group. There were statistically significant differences in fat oxidation rate (FAT%) and carbohydrate oxidation rate (CHO%) between the three groups ( P < 0.05). Compared with hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group, chronic hepatitis B group ( P < 0.05) had lower FAT% and higher CHO%. There were no statistically significant differences in the measured and predicted resting energy expenditure and protein oxidation rate (PRO%) between the three groups. The incidence of secondary bacterial infection in patients with severe liver disease was 48.39% (45/93). Compared with the non-infected group, the RQ and npRQ values ??of the infected group were significantly decreased ( P < 0.05), while FAT% was significantly increased ( P < 0.05). Logistic regression analysis showed that glutamyltransferase, cholesterol, and npRQ were independent risk factors for secondary bacterial infections in patients with severe liver disease. Glutamyltransferase elevation, and cholesterol and npRQ depletion had suggested an increased risk of secondary bacterial infection. Subgroup analysis of patients with hepatitis B-related liver failure also showed that compared with non-infected group, RQ value and npRQ value of secondary bacterial infection group were significantly decreased ( P < 0.05), while FAT% was significantly increased ( P < 0.05). Conclusion:Patients with hepatitis B virus-related chronic liver disease generally have abnormal energy metabolism. Low RQ, npRQ, CHO% and high FAT% are related to the severity of the disease; while npRQ reduction is related to the risk of secondary bacterial infection in patients with severe liver disease, and thus can be used as a clinical prognostic indicator.
4.Influencing factors for the 90-day prognosis of patients with HBV-related acute-on-chronic liver failure
Dongqing ZHANG ; Ruidan ZHENG ; Minghua LIN ; Wenjun WU ; Shenglong LIN ; Xiangmei WANG ; Huaxi MA ; Qin LI ; Hanhui YE ; Haibing GAO
Journal of Clinical Hepatology 2021;37(10):2316-2319
Objective To investigate the risk factors for short-term prognosis in patients with HBV-related acute-on-chronic liver failure (ACLF). Methods A retrospective analysis was performed for the clinical data of 119 patients with HBV-related ACLF who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from October 2019 to October 2020, and according to their survival status on day 90, they were divided into death group and survival group. The patients were given antiviral therapy with entecavir or tenofovir. Related clinical data were collected, including alanine aminotransferase (ALT), aspartate aminotransferase, cholinesterase (ChE), albumin (Alb), cholesterol, alpha-fetoprotein, and HBV DNA at baseline, as well as the incidence rate of important complications. Model for End-Stage Liver Disease (MELD) score was also calculated. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-squared test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for the 90-day prognosis of patients with HBV-related ACLF and establish a new predictive model; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the new model in predicting the prognosis of HBV-related ACLF. Results Of all patients, 33 died within 90 days, resulting in a mortality rate of 27.7%. There were significant differences between the survival group and the death group in age, ALT, Alb, ChE, MELD score, and incidence rates of hepatic encephalopathy, primary peritonitis, and hepatorenal syndrome (all P < 0.05). The logistic regression analysis showed that baseline hepatic encephalopathy (odds ratio [ OR ]=10.404, 95% confidence interval [ CI ]: 2.522-42.926, P =0.001), serum Alb at baseline ( OR =0.853, 95% CI : 0.764-0.952, P =0.005), and MELD score at baseline ( OR =1.143, 95% CI : 1.036-1.261, P =0.008) were independent predictive factors for the short-term prognosis of patients with HBV-related ACLF. A new predictive model was established based on the combination of these three indices, and the ROC curve analysis showed that this new model had an area under the curve of 0.833, while MELD score had an area under the ROC curve of 0.672. Conclusion As for the evaluation of the 90-day prognosis of patients with HBV-related ACLF, the new prognostic model established based on hepatic encephalopathy, Alb, and MELD score has a better predictive value than MELD score alone.
5.Potential mechanism of microRNA in hepatitis B virus infection by using genechip and public database data
Shenglong LIN ; Xiangmei WANG ; Huaxi MA ; Dongqing ZHANG ; Wenjun WU ; Jiahuang LIN ; Ziyuan LIAO ; Minghua LIN ; Ruidan ZHENG ; Haibing GAO
Chinese Journal of Infectious Diseases 2020;38(11):717-722
Objective:To investigate the potential mechanism of microRNA (miRNA) in hepatitis B virus (HBV) infection.Methods:The peripheral blood samples were collected from four chronic hepatitis B (CHB) patients who visited Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017, and those were also collected from four healthy controls. Affymetrix GeneChip microRNA 4.0 was applied to detect the expressions of miRNA between CHB patients and healthy controls. The CHB relative differential expressions of miRNA were obtained. The functions of CHB relative miRNA were analyzed by the combination of bioinformatics tools and public database data.Results:A total of seven miRNA were differentially expressed in the peripheral blood of CHB patients. Among them, miRNA-122-5p (log 2 fold change (log 2FC)=7.78, P=0.007 3), let-7c-5p (log 2FC=3.52, P=0.019 6), miRNA-6794-5p (log 2FC=1.15, P=0.033 2), and miRNA-1226-5p (log 2FC=0.68, P=0.034 3) were up-regulated, while miRNA-619-5p (log 2FC=-1.83, P=0.002 6), miRNA-1273g-3p (log 2FC=-2.69, P=0.025 1), and miRNA-4440 (log 2FC=-3.99, P=0.047 8) were down-regulated. Further analysis showed that these miRNA could directly interact with HBV gene sequence and impact the replication of the virus. Among them, miRNA-122-5p, miRNA-6794-5p and miRNA-1226-5p could negatively regulate target genes expression to influence the formation of ficolin-1 rich granule, ficolin-1 rich granule lumen, podosome and membrane ruffle, which participated in the cell membrane movement and cell-matrix adhesion. Conclusion:MiRNA could impact the molecular movement in the cell membrane and facilitate HBV entry to liver cells, playing an important supporting role in HBV infection process.
6.Data analysis of active surveillance of foodborne diseases in the sentinel hospital of Shiyan City, 2013-2018
Yanli LI ; Shixiu CHENG ; Kang YANG ; Jingzhi GAO ; Yufen LI ; Xiangmei ZHENG
Journal of Public Health and Preventive Medicine 2020;31(5):57-60
Objective To investigate the epidemiological and etiological characteristics of foodborne diseases in Shiyan City, and to provide targeted measures for the prevention and control of foodborne diseases. Methods The surveillance data of foodborne diseases reported by Taihe Hospital of Shiyan City from 2013 to 2018 was collected and analyzed. Results A total of 1 742 cases of foodborne diseases were analyzed. The incidence peaked twice during the year, May to August and October to November. The pre-school children (≤6 years old) were at the highest risk of contracting foodborne diseases, and were mainly those in kindergartens, as well as those not in school. Grain and grain products accounted for the highest proportion of the presumably exposed foods. The main location of eating contaminated foods was in households. A total of 1 217 samples were tested, and 92 were positive, of which 71 strains were detected with Salmonella, accounting for the highest proportion. Preschool children and the elderly (≥66 years old) had higher detection rates than others. The food of infants and young children was found to have the highest detection rate. Conclusion According to the epidemiology and etiological characteristics of foodborne diseases in Shiyan City, the publicity and education of food safety should be strengthened and the surveillance network system of foodborne diseases should be further improved.
7. Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia
Guiwen GUAN ; Lin GAO ; Jianwen WANG ; Xiajie WEN ; Tianhao MAO ; Siwen PENG ; Ting ZHANG ; Xiangmei CHEN ; Fengmin LU
Chinese Journal of Hepatology 2020;28(2):E002-E002
Objective:
To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP).
Methods:
The correlation between ALT, AST and other liver enzyme changes condition and NCP patients’ disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy.
8.Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model.
Hanyu ZHU ; Bo FU ; Yong WANG ; Jing GAO ; Qiuxia HAN ; Wenjia GENG ; Xiaoli YANG ; Guangyan CAI ; Xiangmei CHEN ; Dong ZHANG
Frontiers of Medicine 2019;13(5):618-625
This study aimed to compare clinical features between membranous nephropathy (MN) and nonmembranous nephropathy (non-MN), to explore the clinically differential diagnosis of these two types, and to establish a diagnostic model of MN. After renal biopsy was obtained, 798 patients were divided into two groups based on their examination results: primary MN group (n = 248) and non-MN group (n = 550). Their data were statistically analyzed. Logistic regression analysis indicated that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN, and these three parameters were then used to establish the MN diagnostic model. A receiver operating characteristic (ROC) curve confirmed that our diagnostic model could distinguish between patients with and without MN, and their corresponding sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The cutoff value for this combination in MN diagnosis was 0.34. The established diagnostic model that combined multiple factors shows a potential for broad clinical applications in differentiating primary MN from other kidney diseases and provides reliable evidence supporting the feasibility of noninvasive diagnosis of kidney diseases.
9.Analysis of prognostic factors for 24-month survival of hepatitis B virus-associated acute-on-chronic liver failure patients treated with telbivudine
Haibing GAO ; Xiangmei WANG ; Huaxi MA ; Shenglong LIN ; Dongqing ZHANG ; Wenjun WU ; Jiankai FANG ; Minghua LIN ; Ruidan ZHENG
Chinese Journal of Infectious Diseases 2018;36(11):641-647
Objective To investigate the baseline independent prognostic factors for 24 months survival of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) patients treated with telbivudine.Methods The prospective cohort study was conducted in HBV-associated ACLF patients who were hospitalized in Mengchao Hepatobiliary Hospital of Fujian Medical University and volunteered to be treated with telbivudine for more than 24 months.The patients were observed for survival at month 1,3,6,12,and 24 after treatment.The baseline biochemical index,coagulant function,model for end-stage liver disease (MELD) score,HBV DNA level as well as comorbidities were analyzed in this study.The count data were compared with kappa test or Fisher's exact test.For the normal distributed measurement data,the homogeneity test of variances (Levene test) was firstly used for comparison between groups.Further,the group t test was applied for variance homogeneity,while the approximate t test was applied for variance non-homogeneity and the Mann-Whitney U test was applied for the non-distributed measurement data.Results A total of 41 patients were enrolled,including 3 drop-outs and 38 accomplishments.Among these 38 patients,there were 3 females (7.9 %) and 35 males (92.1%),with ages (38.5 ± 11.1) years.There were 32 patients alive and 6 dead during 1 month's follow-up,while baseline MELD score was the independent prognostic factor (RR=1.864,95%CI:1.151-3.019) for survival.There were 31 patients alive and 7 dead during 3 months' follow-up,while baseline MELD score and upper gastrointestinal hemorrhage (UGH) were the independent prognostic factors (RR =2.053,95%CI:1.163-3.625;RR=394.939,95%CI:1.880-82 948.817).There were both 26 patients alive and 12 dead during 6 and 12 months' follow-up,while baseline MELD score was the independent prognostic factor (RR=1.761,95% CI:1.230-2.523).At the end of 24 months' follow-up,there were 15 patients alive and 23 dead.Viral rebounds were observed in 6 patients and 3 of them were dead.Baseline HBV DNA level,MELD score and electrolyte imbalance were the independent prognostic factors (RR-9.722,95% CI:1.607-58.821;RR=l.518,95% CI:1.066-2.162;RR=87.505,95% CI:2.263-3 384.232) for 24 months'survival.Conclusions Although telbivudine is not recommended as the first-line treatment,ACLF patients with low MELD score and low HBV DNA level at baseline,individualized treatment may improve patient's survival rate.UGH and electrolyte imbalance may affect the efficacy of telbivudine and reduce the survival rate of ACLF patient.
10.Analysis of hepatitis B virus infection in patients with non-Hodgkin lymphoma
Kunli GAO ; Hongyun XING ; Tierong BIAN ; Xiangmei XU ; Liying HAN
Journal of Leukemia & Lymphoma 2018;27(2):98-102
Objective To investigate the association between non-Hodgkin lymphoma (NHL) and hepatitis B virus (HBV). Methods The serum HBV markers in 305 NHL patients who were diagnosed in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2016 was detected by automatic chemiluminescence immunoassay. The infection rate of HBV in NHL patients was compared with that in 312 colorectal cancer patients and the national general population (81775 peoples). Results The positive rates of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) in 305 patients of NHL were compared with the general population [19.0 % (58/305) vs. 7.2 % (5888/81775), 44.3 % (135/305) vs. 50.1 % (40969/81775), 45.9 % (140/305) vs. 34.1 %(27885/81775)], and the differences were statistically significant (χ2 values were 63.1, 4.1, 18.8, all P<0.05). The positive rate of HBsAg in NHL patients was compared with colorectal cancer patients and the general population, and the differences were statistically significant (χ2= 65.7, P< 0.01). The positive rate of HBsAg in B-cell NHL was statistically different from T-cell NHL [21.3%(51/239) vs. 10.6%(7/66),χ2=3.869, P<0.05]. But the positive rate of HBcAb and HBsAb in B-cell NHL were compared with T-cell NHL, and there was no statistically significant difference (both P> 0.05). Among 133 NHL patients, the HBV DNA positive rate was 33.1 % (44/133), and 74.1 % (43/58) in 58 cases of HBsAg-positive NHL, while 4.2 % (1/24) in 24 cases of HBsAg-negative but HBcAb-positive NHL. Conclusions The infection rate of HBV in NHL patients is higher than that in colorectal cancer patients and the general population, in which the occult HBV infection is worthy of much attention. The positive rate of HBsAg in T-cell NHL patients is lower than that in B-cell NHL patients. For NHL patients with HBV infection, anti-HBV treatment to prevent reactivation of the virus should be given before the anti-tumor treatment.


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