Objective To investigate the anti-inflammatory effect and mechanism of sappanone A(SA)on lipopolysaccharide(LPS)-induced RAW264.7 cell model based on JAK2-STAT3 signaling pathway.Methods MTT assay was used to detect the effects of sappanone A,LPS and AG490 on RAW264.7 cell viability.The LPS-induced inflammatory model in RAW264.7 cells was established,and the secretion level of interleukin-6(IL-6)in the supernatant was detected by ELISA.mRNA expressions of IL-6,Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)were tested by RT-PCR.The protein expressions of JAK2,phosphorylated JAK2(p-JAK2),STAT3 and phosphorylated STAT3(p-STAT3)were determined by Western Blot.Results Compared with control group,IL-6 secretion level was significantly increased,mRNA expressions of IL-6,JAK2 and STAT3 were up-regulated,and protein expressions of p-JAK2 and p-STAT3 were increased(all P＜0.01)in model group.Compared with model group,high-dosed sappanone A(5 μg·mL-1)was significantly decreased the secretion of IL-6,down-regulated the mRNA expressions of IL-6,JAK2 and STAT3,and inhibited the protein expressions of p-JAK2 and p-STAT3(all P＜0.01).Conclusion Sappanone A may play an anti-inflammatory role by inhibiting the JAK2-STAT3 signaling pathway and hence inhibiting the secretion of IL-6.

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.

Hepatic Encephalopathy/etiology* ; Humans ; Telangiectasia, Hereditary Hemorrhagic/complications* ; Tomography, X-Ray Computed

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.

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.

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.

ABSTRACT OBJECTIVE：To study pharmacokinetic characteristics of single dose and multiple dose administration of Gefitinib emulsion in rats. METHODS：The rats were divided into single administration group and multiple administration group. Single administration group was subdivided into Gefitinib raw medicine group（50 mg/kg，i.g.）and Gefitinib emulsion group（50 mg/kg，i.g.），with 6 rats in each group，gavage once. Multiple administration group were subdivided into Gefitinib raw medicine group （50 mg/kg）and Gefitinib emulsion group（50 mg/kg），with 8 rats in each group；they were given relevant medicine intragastricaly for consecutive 7d，once a day. 0.3 mL blood of rats in Gefitinib raw medicine group was taken before medication and 1，2，2.5， 3，3.5，3.75，4，4.25，4.5，6，8，12 and 24 h after medication；0.3 mL blood of rats in Gefitinib emulsion group was taken before medication and 2，4，6，8，9，10，11，12，13，14，16，24，36 and 48 h after administration（Multiple administration group is after 7 d of administration）. HPLC method was used to determine the plasma concentration of gefitinib in rat，and plasma concentration-time curves were drawn. Pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS：After single administration，compared with the tmax（[ 2.67±0.75）h]，MRT0-24 h （[ 8.68±0.91）h]，MRT0- ∞ （[ 14.20±3.45）h] of Gefitinib raw medicine group，tmax （[ 8.33±4.41）h]，MRT0-48 h （[ 15.00±1.60）h]，MRT0-∞ （[ 17.60±2.66）h] of Gefitinib emulsion group were increased significantly（P＜0.05）. After multiple administration，compared with the tmax （[ 6.79±3.75）h]，AUC0-48 h （[ 41.10±8.92） mg·h/L]，Vz/F [（16.30±5.45）L/kg]，CLz/F [（0.94±0.19） L/（h·kg）]，MRT0-48 h （[ 10.10 ± 0.36） h] of Gefitinib raw medicine group，Vz/F [（44.20±30.3）L/kg]，CLz/F[（1.89± 1.56） L/（h·kg）]，MRT0-48 h （[ 16.20 ± 2.52） h] of Gefitinib emulsion group were increased significantly （P＜0.05） AUC0-48 h （[ 38.70±26.20）mg·h/L] was decreased significantly （P＜0.05），and tmax （[ 10.40±3.25）h] was increased，without statistical significance. CONCLUSIONS： Compared with Gefitinib raw medicine，single and multiple administration of Gefitinib emulsion can effectively prolong the peak time，the results of this study can provide reference for new delivery system study of Gefitinib.

Substantial evidence supports the neurodevelopmental hypothesis of schizophrenia. Meanwhile, progressive neurodegenerative processes have also been reported, leading to the hypothesis that neurodegeneration is a characteristic component in the neuropathology of schizophrenia. However, a major challenge for the neurodegenerative hypothesis is that antipsychotic drugs used by patients have profound impact on brain structures. To clarify this potential confounding factor, we measured the cortical thickness across the whole brain using high-resolution T1-weighted magnetic resonance imaging in 145 first-episode and treatment-naïve patients with schizophrenia and 147 healthy controls. The results showed that, in the patient group, the frontal, temporal, parietal, and cingulate gyri displayed a significant age-related reduction of cortical thickness. In the control group, age-related cortical thickness reduction was mostly located in the frontal, temporal, and cingulate gyri, albeit to a lesser extent. Importantly, relative to healthy controls, patients exhibited a significantly smaller age-related cortical thickness in the anterior cingulate, inferior temporal, and insular gyri in the right hemisphere. These results provide evidence supporting the existence of neurodegenerative processes in schizophrenia and suggest that these processes already occur in the early stage of the illness.

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.