Hepatitis B virus (HBV) causes liver injury by stimulating host immune response and may lead to liver fibrosis, liver cirrhosis, and liver cancer. Progression of liver fibrosis is a key factor in liver disease-related death. This article summarizes the association of HBV genotype, HBV gene mutation in basic core promoter region/pre-C region, pre-S region, and X region, HBV gene splicing, HBV RNA, HBcAg, and HBsAg with the progression of liver fibrosis. It is pointed out that the above biological characteristics of HBV are closely associated with the progression of liver fibrosis.

This article was aimed to study the analgesic and antipyretic effect of Re-Du-Ning (RDN) Injection. Heating model was building on SD rats after subcutaneous injection of yeast. And then, RDN Injection was intravenous injected at the dose of 10.16 g·kg-1, 5.08 g·kg-1, and 2.54 g·kg-1, respectively. Observation was made on changes of rats' temperature. RDN Injection was intravenous injected into ICR mice at the dose of 20.30 g·kg-1, 10.15 g·kg-1, 5.08 g·kg-1 for 7 consecutive days. The methods of mice twist, hot plate and jaw pain were used in the testing of analgesic action of RDN Injection. The results showed that RDN Injection at high and middle dose can significantly reduce the temperature of heating rats models (P < 0.05 or P < 0.01). It can also significantly reduce the twisting times of mice by acetic acid (P< 0.05 or P< 0.01). It can also significantly increase the pain threshold of mice by hot plate and jaw pain (P< 0.05 or P< 0.01). It was concluded that RDN Injection had a good analgesic and antipyretic effect in mice.

This study was aimed to discuss the antibacterial and immunomodulation effect ofRe-Du-Ning (RDN) injection. Mice were randomly divided into the normal group, model group,Shuang-Huang-Lian (SHL) group (7.8 mL·kg-1), RDN high dose group (20.30 g·kg-1), middle dose group (10.15 g·kg-1), and low dose group (5.08 g·kg-1), in order to observe the death protective effect of mice with bacterial infection on antibacterial experimentin vivo. Mice were randomly divided into the normal group, model group,Xiang-Gu Duo-Tang (XGDT) group (0.19 mg·kg-1), RDN high dose group (20.30 g·kg-1), middle dose group (10.15 g·kg-1), and low dose group (5.08 g·kg-1). The 2, 4-dinitrochlorobenzene was used to induce delayed hypersensitivity. Immunomodulation was observed by the content of serum hemolysin and the carbon particle clearance index. The results showed that the RDN high dose group and middle dose group had antibacterial effect, which reduced the mortality of mice. The RDN high dose, middle dose and low dose group can enhance the phagocytosis of macrophage in immunosuppressive mice, increase the formation of hemolysin, and strengthen delayed hypersensitivity reaction among immunocompromised mice. It was concluded that RDN injection had antibacterial effect. Its immunomodulation effect was through the enhancing of non-specific immunity, humoral immunity and cellular immunity of mice.

OBJECTIVETo investigate pharmacokinetic parameters of peoniflorin, albiflorin and amygdaloside after administration of Guizhi Fuling capsule in beagle dogs.

METHODPlasma was collected from forelimb vein of Beagle dogs after oral administration of Guizhi Fuling capsule. HPLC-MS/MS method was used to determine the concentrations of constituents in plasma. The pharmacokinetic parameters were analyzed by program DAS 2.0.

RESULTThe limit of quantitation of peoniflorin, albiflorin and amygdaloside were 0.25, 2.64, 0.04 microg x L(-1), respectively. After administrated with different doses, half-life of peoniflorin in dogs were 4.33, 3.62 h, albiflorin were 6.16, 5.91 h, amygdaloside were 2.43, 1.32 h. The AUC(0-t) of all components were related to dose.

CONCLUSIONThe pharmacokinetic course of peoniflorin, albiflorin and amygdaloside can be described by two-compartment model, and these components have high expose.

Administration, Oral ; Amygdalin ; blood ; Animals ; Area Under Curve ; Benzoates ; blood ; Bridged-Ring Compounds ; blood ; Capsules ; administration & dosage ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Dogs ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Glucosides ; blood ; Half-Life ; Male ; Monoterpenes ; Tandem Mass Spectrometry ; methods

ObjectiveTo investigate the association of high-density lipoprotein cholesterol (HDL-C) with the prognosis of patients with alcohol-related hepatocellular carcinoma (HCC) after radical treatment. MethodsA retrospective analysis was performed for the clinical data of 43 patients with alcohol-related HCC who were admitted to The Fifth Medical Center of Chinese PLA General Hospital and underwent radical treatment from January 2008 to July 2015, and according to HDL-C level, the patients were divided into normal group with 26 patients and abnormal group with 17 patients. The two groups were compared in terms of basic information, laboratory markers, imaging indices, Barcelona Clinic Liver Cancer tumor stage, and Child-Pugh class of liver function. The t-test test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves and the log-rank test was used for comparison between groups. Univariate and multivariate Cox proportional hazards models were used to analyze independent risk factors for prognosis. ResultsThere was a significant difference in prealbumin between the two groups (162.38±60.86 mg/L vs 120.06±64.08 mg/L, t=2.184, P=0.035). Number of tumors (hazard ratio ［HR］=2.839, 95%confidence interval ［CI］: 1.120~7.200,P=0.028), tumor size (HR=2.634, 95%CI: 1.062~6.529,P=0037), and HDL-C level (HR=2.400, 95%CI: 1.040~5.537,P=0.040) were independent risk factors for the overall survival of patients with alcohol-related HCC. There were significant differences in 1-, 3-, and 5-year cumulative survival rates between the normal group and the abnormal group (88.5%/72.4%/55.7% vs 70.6%/43.7%/17.5%, χ2=5.881, P=0.015). ConclusionThe reduction in HDL-C level might indicate poor prognosis of patients with alcohol-related HCC.

Toxicity of Chinese materia medica (CMM) is an important part of Chinese herbal nature theory. In clinical application, the dosage, time limitation and compatibility of CMM is mainly determined by toxicity. At present, there is no uniform toxicity classification standard for the evaluation of Chinese herbal toxicity. Therefore, it is significant to research toxicity classification of CMM. The current situation of toxicity classification of CMM is reviewed in this paper, and proposed research thoughts are as follows: the measurement of toxicity parameters, the confirmation of poisoning target organs, the investigation on toxic mechanism by serum pharmacology and toxicokinetics, the comprehensive evaluation on toxicity based on quantitative theory.
Animals ; Biomedical Research ; China ; Drugs, Chinese Herbal ; analysis ; classification ; history ; toxicity ; History, Ancient ; Humans ; Materia Medica ; analysis ; classification ; history ; toxicity ; Medicine, Chinese Traditional ; adverse effects ; Mice ; Rats

When performing eye movement pattern classification for different tasks, support vector machines are greatly affected by parameters. To address this problem, we propose an algorithm based on the improved whale algorithm to optimize support vector machines to enhance the performance of eye movement data classification. According to the characteristics of eye movement data, this study first extracts 57 features related to fixation and saccade, then uses the ReliefF algorithm for feature selection. To address the problems of low convergence accuracy and easy falling into local minima of the whale algorithm, we introduce inertia weights to balance local search and global search to accelerate the convergence speed of the algorithm and also use the differential variation strategy to increase individual diversity to jump out of local optimum. In this paper, experiments are conducted on eight test functions, and the results show that the improved whale algorithm has the best convergence accuracy and convergence speed. Finally, this paper applies the optimized support vector machine model of the improved whale algorithm to the task of classifying eye movement data in autism, and the experimental results on the public dataset show that the accuracy of the eye movement data classification of this paper is greatly improved compared with that of the traditional support vector machine method. Compared with the standard whale algorithm and other optimization algorithms, the optimized model proposed in this paper has higher recognition accuracy and provides a new idea and method for eye movement pattern recognition. In the future, eye movement data can be obtained by combining it with eye trackers to assist in medical diagnosis.
Animals ; Support Vector Machine ; Whales ; Eye Movements ; Algorithms

Objective:To investigate the use of discriminant analysis to predict the risk of nosocomial mortality in patients with traumatic hemorrhagic shock.Methods:The clinical data of 238 patients with traumatic hemorrhagic shock admitted to Peking University People's Hospital from Sep 2013 to Aug 2020 were retrospectively analyzed. Patients were divided into survival group (214 cases) and death group (24 cases). Stepwise discriminant analysis was used to establish a discriminant model.Results:The difference of history of stroke (9.8% vs. 25.0%), main site of bleeding (extremities)(58.9% vs. 29.2%), APACHEⅡ score (16.4±5.1 vs. 23.2±6.1), blood lactic acid [2.1(1.1-3.5) mmol/L vs. 4.9(2.0-13.4) mmol/L] and surgery (92.5% vs. 58.3%) between the two groups was all statistically significant (all P<0.05). Finally, There are five indicators that entered the discriminant model: history of stroke, main site of bleeding (extremities), blood lactic acid, APACHE Ⅱ score and surgery. The area under the ROC curve for predicting the risk of mortality in patients with traumatic hemorrhagic shock was 0.857, 95% CI 0.754-0.959. Conclusions:The established discriminant model has a high accuracy in predicting the risk of in-hospital mortality in patients with traumatic hemorrhagic shock.

ObjectiveTo investigate the expression of disulfidptosis-related genes in hepatocellular carcinoma （HCC） and the prognostic value of disulfidptosis in HCC， to construct a prognostic model， and to analyze its impact on the biological processes of HCC and sorafenib resistance. MethodsThe TCGA-LIHC database was used to collect the mRNA expression profiles and corresponding clinical data of HCC patients， and the LASSO-Cox regression algorithm was used to construct a four-gene predictive model for prognosis in the TCGA cohort. The external datasets ICGC and GSE14520 were used to validate the prognostic efficacy of the model， and the Cancer Drug Sensitivity Genomics （GDSC） data were used to investigate the value of the disulfidptosis model in predicting sorafenib treatment response， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used to investigate the biological functions of disulfidptosis-related genes. The independent-samples t 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. The Kaplan-Meier curve and the log-rank test were used to evaluate the difference in prognosis， and univariate and multivariate Cox regression analyses were used to investigate whether risk score was an independent influencing factor for patient prognosis. ResultsThe univariate Cox regression analysis in the TCGA cohort showed that seven known disulfidptosis-related genes were significantly associated with overall survival （OS） in HCC （all P<0.05）. The LASSO-Cox regression analysis was used to construct a prognostic model based on disulfidptosis-related genes （DRG）， and the risk score RS-DRG was calculated as RS-DRG=（0.061 6）×GYS1 expression level+（0.152 8）×LRPPRC expression level+（0.268 3）×RPN1 expression level+（0.183 5）×SLC7A11 expression level. The log-rank test showed that the patients with a high risk score based on the disulfidptosis model had a significantly lower OS than those with a low risk score （P<0.001）. Based on the results of the multivariate Cox regression analysis， risk score was an independent predictive factor for OS in both TCGA and ICGC cohorts （TCGA： hazard ratio ［HR］=1.869， P=0.002； ICGC： HR=3.469， P=0.004）. The Spearman correlation analysis showed that RS-DRG was significantly positively correlated with the infiltration level of various immune cells （including B lymphocytes， CD4⁺ T lymphocytes， neutrophils， macrophages， and dendritic cells） in tumor microenvironment （all P<0.05）. The patients in the high-risk score group had a significantly lower IC50 value of sorafenib and were more sensitive to sorafenib （P<0.001）. The KEGG/GO enrichment analysis showed that the differentially expressed disulfidptosis-related genes were significantly enriched in various mitosis-related molecular functions. ConclusionThis study constructed a novel prognostic model based on disulfidptosis-related genes， which has a potential clinical value in predicting the prognosis of HCC， and targeting disulfidptosis-related genes may provide a promising approach for HCC treatment.

ObjectiveTo investigate whether anti-PD-1 monoclonal antibody can improve the efficacy and safety of cryoablation combined with lenvatinib in the treatment of unresectable hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for 232 patients with unresectable HCC who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2022， among whom 128 received cryoablation combined with lenvatinib （double combination） and 104 received cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody （triple combination）. Propensity score matching was performed at a ratio of 1∶1， and finally there were 86 patients in each group. The two groups were evaluated in terms of objective response rate （ORR）， disease control rate （DCR）， overall survival （OS）， progression-free survival （PFS）， and adverse events （AEs）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and 95% confidence interval （CI） and perform the univariate and multivariate analyses of influencing factors for prognosis. ResultsThe median follow-up time was 28 months， and there were 33 deaths （38.0%） in the triple combination group and 40 deaths （46.0%） in the double combination group. Compared with the double combination group， the triple combination group had significantly higher ORR （35.6% vs 14.5%， P=0.008） and DCR （86.1% vs 64.1%， P=0.003）. OS and PFS in the triple combination group were significantly higher than those in the double combination group （P=0.045 and 0.026）. The univariate and multivariate Cox proportional-hazards regression model analyses showed that treatment regimen （HR=0.60， P=0.038） and alpha-fetoprotein level （HR=2.37， P=0.001） were independent risk factors for OS， and treatment regimen （HR=0.65， P=0.025）， diabetes mellitus （HR=1.94， P=0.005）， whether or not to have received local treatment （HR=0.63， P=0.014）， and distant metastasis （HR=0.58， P=0.009） were independent risk factors for PFS. There was no significant difference in the incidence rate of AEs between the two groups （P>0.05）. ConclusionFor patients with unresectable HCC， the triple combination of cryoablation， lenvatinib， and anti-PD-1 monoclonal antibody significantly improves the treatment outcome and survival of patients compared with the double combination of cryoablation and lenvatinib， without increasing AEs， which provides a clinical basis for optimizing the treatment regimen for unresectable HCC.