Objective To investigate the application value of tenofovir alafenamide fumarate(TAF)in patients with first-time hepatitis B virus-related decompensated cirrhosis(HBV-DC)and its impact on renal function and lipid metabolism.Methods A total of 57 patients with first-time HBV-DC who were hospitalized and received TAF antiviral therapy in The Affiliated Hospital of Xuzhou Medical University from January 1,2020 to December 31,2022 were enrolled,and all of them received TAF antiviral therapy.Related data were collected at baseline and at weeks 12,24,and 48 of treatment,including virological and serological indicators,liver and renal function,serum phosphorus,and blood lipids.The paired t-test or single group repeated measures ANOVA were used for comparison of normally distributed continuous data,the Friedman test was used for comparison of non-normally distributed continuous data,and the chi-square test or the Fisher's exact test were used for categorical data.Results A total of 52 patients completed the 48 weeks of follow-up.After 12,24,and 48 weeks of treatment,the patients achieving HBV DNA seroconversion accounted for 38.5%,63.5%,and 84.6%,respectively;the alanine aminotransferase normalization rate were 71.2%,82.7%,and 82.7%,respectively;the proportion of the patients with Child-Pugh class A disease increased to 55.8%,73.1%,and 92.3%,respectively.Within the 48 weeks of treatment,there were significant increases in the levels of cystatin C(χ2=35.163,P＜0.001)and serum phosphorus(F=8.600,P＜0.001)and low-density lipoprotein cholesterol(χ2=10.064,P=0.018).The ratio of total cholesterol/high-density lipoprotein cholesterol decreased continuously from 3.61(2.61～5.84)to 3.27(2.70～4.36)(χ2=5.000,P=0.172).Conclusion TAF can rapidly inhibit HBV replication and significantly improve liver function in HBV-DC patients,with no significant impact on renal function.However,blood lipid should be closely monitored.

Objective:To study the clinical features and prognostic impact of transarterial chemoembolization (TACE), immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs) combination therapy regimens in the treatment of patients with hepatitis B virus-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis.Methods:Patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma (HBV) who visited the Affiliated Hospital of Xuzhou Medical University between January 1, 2020, and December 31, 2022, were enrolled. TACE+TKIs +ICIs combination therapy was used to treat all patients. The occurrence and factors influencing cholestasis, as well as the impact on prognosis after combined therapy, were analyzed. The measurement data were compared using a t-test and a non-parametric rank sum test. The count data was compared using the χ2 test. The survival rates were compared using a log-rank test between different groups. Results:A total of 106 cases with HBV-related intermediate-and advanced-stage hepatocellular carcinoma were enrolled. The probabilities of secondary cholestasis within 3 and 6 months, 1, 2, and 3 years after TACE+ICIs+TKIs combination therapy were 9.4%, 12.3%, 14.2%, 24.5%, and 24.5%, respectively. Patients with secondary cholestasis had persistent symptoms and rapid progression. During the treatment course, the median survival time was significantly longer in patients with hepatocellular carcinoma without secondary cholestasis than that of patients with cholestasis (26.9 months vs. 13.7 months, respectively, P < 0.05). Secondary cholestasis, baseline aspartate aminotransferase, and prothrombin activity levels were independent risk factors that affected the survival and prognosis of patients treated with combination therapy. There was no statistically significant difference in the occurrence of other adverse reactions between the two groups with secondary and non-secondary cholestasis during the treatment course (47.5% vs. 43.3%, χ2=0.058, P = 0.810). Conclusion:TACE+ICIs+TKIs therapy combination is relatively common in the treatment of patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis. Moreover, accelerated disease progression is an independent risk factor affecting the survival and prognosis of patients.

ObjectiveTo investigate the influencing factors for persistent low-level viremia (LLV) in chronic hepatitis B(CHB) patients receiving long-term entecavir antiviral therapy. MethodsThe CHB patients who received entecavir antiviral therapy for at least one year in The Affiliated Hospital of Xuzhou Medical University from November 2018 to June 2020 were enrolled as subjects, and according to HBV DNA load at the end of the observation period, the patients were divided into LLV group and sustained virological response (SVR) group. Demographic features and laboratory markers were observed for all patients. 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 was used for comparison of categorical data between two groups. A multivariate logistic regression analysis was used to investigate the influencing factors for LLV in patients receiving long-term entecavir treatment. ResultsA total of 560 CHB patients were enrolled, with 204 in the LLV group and 356 in the SVR group. There were significant differences between the two groups in age (Z=-3.530, P＜0.001), sex (χ2=4.270, P=0.039), presence or absence of liver cirrhosis (χ2=53.879, P＜0.001), medication compliance (χ2=5.326, P=0.021), HBeAg positive rate (χ2=90.681, P＜0.001), baseline HBV DNA load before treatment (Z=-8.337, P＜0.001), baseline HBsAg quantification (Z=-10.472, P＜0.001), and medication type (χ2=7.558, P=0.006). The multivariate logistic regression analysis showed that baseline HBeAg status before treatment (odds ratio ［OR］=3.381, 95% confidence interval ［CI］: 1.985-5.756, P＜0.001), HBV DNA load before treatment (OR=1.223, 95%CI: 1.050-1.424, P=0.010), and HBsAg quantification before treatment (OR=2.448, 95%CI: 1.743-3.438, P＜0.001) were risk factors for LLV in long-term entecavir antiviral therapy. ConclusionIn clinical practice, CHB patients with high HBV DNA load, high HBsAg quantification, and positive HBeAg tend to have a high risk of LLV even after long-term entecavir antiviral therapy. Therefore, such population should be taken seriously with the dynamic monitoring of HBsAg quantification, HBV DNA load, and HBeAg status.

Objective To investigate whether myricetin (Myr) exert protective effects on acute lung injury induced by LPS and to explore its underlying mechanisms. Methods A total of 72 mice were divided into the control group, model group, myricetin group and active group, 18 in each group. Male BALB/c mice of the myricetin were given an intragastric injection of Myr (50 mg/kg), and the active group dexamethasone (Dex, 5 mg/kg) 1 h before intranasal instillation of LPS. While the other groups were given the same volum saline. 24 hours after LPS exposure, mice were sacrificed and various samples were collected for further analysis. Both levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the bronchoalveolar lavage fluid (BALF) were measured by ELISA kits. The numbers of total cells, macrophages, and neutrophils in the BALF were also determined using differential leukocyte cell count method. The phosphorylations of nuclear factor-kappa B (NF-κB) and IκB were further detected by western blot analysis. Results Compared with the model group, the levels of macrophages and neutrophils in BALF in the myricetin and active groups significantly decreased (P<0.01), while the total protein and W/D ratio of the lung tissue significantly decreased (P<0.05). Compared with the model group, the levels of TNF-α (5.47 ± 2.54 pg/ml, 4.19 ± 0.50 pg/ml vs. 15.28 ± 1.27 pg/ml), IL-1β(336.20 ± 41.06 pg/ml, 247.99 ± 25.12 pg/ml vs. 464.88 ± 34.51pg/ml), the MPO (0.74 ± 0.12 U/g, 0.61 ± 0.08 U/g vs. 1.66 ± 0.07U/g) in the myricetin and active groups significantly decreased (P<0.01). Compared with the model group, the expression of p-IκB/IκB (0.61 ± 0.01, 0.59 ± 0.01 vs. 0.95 ± 0.01), p-NF-κB/NF-κB (0.54 ± 0.01, 0.59 ± 0.03 vs. 0.96 ± 0.02) of the lung tissue in the myricetin and active groups significantly decreased (P<0.01). Conclusions Collectively, these findings revealed that Myr may alleviate the LPS-induced acute lung injury via relief of inflammatory reactions associated with blockage of the NF-κB signaling pathway.

Objective: To evaluate the clinical efficacy and side effects of cyberknife therapy in the treatment of retroperitoneal lymph node metastatic tumor. Methods: Among the 81 patients presenting with postoperative retroperitoneal lymph node metastases, 33 cases suffered from abdominal pain or low back pain, 7 had unilateral hydronephrosis and ureteral dilatation, and 8 developed unilateral or bilateral lower limb swelling. Using stereotactic radiotherapy with a cyberknife, DT was delivered at 33-45 Gy/3-6 F. The improvement of symptoms, objective tumor response rate, and irradiation-induced side effects were observed. Results: At 4 weeks after treatment, pain and swelling of the lower extremities were completely mitigated, and hydronephrosis was fully healed in all patients. Enhanced CT or MRI was performed every 2 to 3 months. After 6-month follow-up, the complete response (CR) rate was calculated as 77%(62/81), 21%(17/81) for the partial response (PR) rate, 3%(2/81) for the stable disease (SD) rate and the effective rate (CR+ PR) was 98%.No case progressed. The main side effect was intestinal injury, including grade 1 in 16%(13/81), grade 2 in 9%(7/81). Multivariate analysis demonstrated the CR rate was not correlated with the type of the primary tumor or the size of the tumor (P>0.05), but was significantly associated with the distance of>0.5 cm between the tumor and intestine and the BED (α/β=10)>70 Gy of the tumor irradiation (P<0.01). The incidence of irradiation-related side effects was correlated with the maximum diameter of tumor>5 cm and the distance of<0.5 cm between the tumor and intestine (P<0.01). Conclusion Cyberknife is an efficacious and safe approach in the treatment of retroperitoneal lymph node metastatic tumors.

OBJECTIVETo investigate the correlation of serum osteoprotegerin (OPG) with the progression of nonalcoholic fatty liver disease (NAFLD) and the noninvasive prediction and diagnosis of nonalcoholic steatohepatitis (NASH).

METHODSA total of 136 patients with NAFLD were enrolled, and their tissue samples for liver biopsy and serum samples obtained at 1 week after liver biopsy were collected; 83 healthy subjects without the symptoms of fatty liver disease proved by ultrasound examination were enrolled as controls. The physiological indicators including height, body weight, and waist circumference were measured, and body mass index was calculated. The biochemical parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, alkaline phosphatase, gamma-glutamyl transferase, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. Double-antibody sandwich enzyme-linked immunosorbent assay was used to determine the serum level of OPG. The rank sum test, chi-square test, t-test, one-way analysis of variance, Spearman correlation analysis, least significant difference test, and receiver operating characteristic (ROC) curve were applied for statistical analysis of various data.

RESULTSSerum OPG level was correlated with AST and TG (P < 0.05), and was highly correlated with hepatocyte fatty degeneration, ballooning degeneration, intralobular inflammation, portal inflammation, and fibrosis degree (P < 0.01). With the increasing NAFLD activity score (NAS), serum OPG level decreased, and there was a highly negative correlation between them (r = -0.928, P < 0.01). Serum OPG level was significantly lower in NASH patients than non-NASH patients. The area under the ROC curve of serum OPG level was 0.963, and according to the Youden index, its optimal sensitivity and specificity were 96.1% and 97.4%, respectively, at an optimal cut-off value of 242.96 ng/L, which suggested a high diagnostic power.

CONCLUSIONIn NASH patients, serum OPG level decreases significantly. Serum OPG level can be used as an independent predictive factor to evaluate NASH and its severity, as well as a noninvasive diagnostic index for NASH.

Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Aspartate Aminotransferases ; blood ; Biopsy ; Body Mass Index ; Case-Control Studies ; Cholesterol ; blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Fibrosis ; Humans ; Inflammation ; pathology ; Liver ; pathology ; Non-alcoholic Fatty Liver Disease ; blood ; diagnosis ; Osteoprotegerin ; blood ; ROC Curve ; Triglycerides ; blood ; gamma-Glutamyltransferase ; blood

Objective To investigate the diagnostic value of the acoustic radiation force impulse (ARFI) technology and AST/PLT ratio index (APRI） for the assessment of the liver fibrosis in chronic hepatitis C patients.Methods 107 patients with chronic hepatitis C were included,the subjects were underwent liver biopsy,liver function,blood count,as well as real-time acoustic elastography examination.The APRI was calculated according the following formula,APRI =AST (ULN)/PLT (109/L).ARFI and APRI were compared by correlation with liver fibrosis stage in chronic hepatitis C.Referring to the histologic fibrosis stage on liver biopsy,all the ARFI and the APRI value were assessed by using ROC curve analysis.The corresponding cut-off values,sensitivity and specificity were also calculated and compared.Results The mean values of ARFI and APRI were (1.26 ± 0.27)m/s and 0.30 ± 0.46 for the patients with S1,(1.45 ± 0.51)m/s and 0.29 ± 0.21 for those with S2,(2.03 ± 0.54) m/s and 0.59 ± 0.56 for those with S3,(2.29 ± 0.82) m/s and 0.63 ± 0.35 for those with S4,respectively.ARFI (r =0.61,P ＜0.001) had a better correlation with liver fibrosis stage in chronic hepatitis C than APRI (r =0.49,P ＜0.001).Cut-off points of ARFI and APRI were 1.529 m/s and 0.170 for S≥2,1.780 m/s and 0.277 for S≥3,1.780 m/s and 0.446 for S =4,respectively.Accordingly,the areas under the ROC curves for ARFI and APRI were 0.779 and 0.724 for S≥2,0.866 and 0.786 for S≥3,0.790 and 0.779 for S=4,respectively.Conclusions As a non-invasive technology,ARFI is more accurate when applied to evaluate liver fibrosis in patients with chronic hepatitis C than APRI.ARFI technology has potential value for quantitatme evaluation of the liver fibrosis for chronic hepatitis C.

Objective To study the effect of ginsenoside Rb1(Rb1) and total saponin of dipsacus asper(tSDA) on intracellular free calcium concentration([Ca2+]i) mediated by β-amyloid protein(A β).So as to lay a foundation for developing effective Chinese traditional medicine to treat Alzheimer's disease(AD).Methods The technique of laser scanning confocal microscopy combining primary cultured neurons was adopted to quantitatively analyze the change of [Ca2+]i.Results The [Ca2+]i of primary cultured hippocampal neurons was (185.76±56.22)nmol*L-1 on basal levels.Control group showed obvious change of calcium vibration,[Ca2+]i was elevated to (1383.78±62.83)nmol*L-1.The peak of [Ca2+]i of Rb1 group reached (311.95±32.67)nmol*L-1 and was lower than that of control group (P＜0.01).The tSDA group displayed distinct change of calcium vibration too,and [Ca2+]i reached (358.01±35.42)nmol*L-1.There was a significant difference in [Ca2+]i between control and tSDA group (P＜0.01).Conclusion The research indicated that one of mechanisms by which Rb1 and tSDA protected the neurons was to maintain the balance of [Ca2+]i.

Objective: To determine the content of sanguinarine and chelerythrine in Macleaya microcarpa(Maxim) Fedde. Methods: RP-HPLC was adopted, kromasil C 18 column (150mm?4.6mm.5?m) with a mobile phase acetonitrile-0.1%(V/V) phosphoric acid solution(25∶75) by UV detector at 270nm. Results: The average recoveries of chelerythrine and sanguinarine were 90.2%,92.8%,RSD were 1.5%,2.4% respectively. Conclusion: A simple, rapid and sensitive method with good precision was established.