Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function， inflammation， and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups （39 cases）. Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition， the observation group received Bushen Huoxue prescription. The cardiac function indicators， total response rate regarding symptom alleviation， exercise endurance， urine volume， body mass， quality of life， and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment， the two groups of patients showed no significant differences in terms of 24 h urine volume， body mass， 6 minute walk test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP） level， left ventricular ejection fraction （LVEF）， stroke volume （SV）， and serum levels of interleukin-6 （IL-6）， interleukin-4 （IL-4）， and tumor necrosis factor-alpha （TNF-α）. After treatment， the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association （NYHA） grading of cardiac function （P<0.05）. After treatment， the body mass， MLHFQ score， and IL-6， TNF-α， and NT-proBNP levels decreased in both groups （P<0.05， P<0.01）， and the observation group showed more significant decreases than the control group （P<0.05， P<0.01）. Both groups showed increases in 24-h urine volume， 6MWT， LVEF， SV， and IL-4 after treatment （P<0.05， P<0.01）， and the observation group showed more significant increases than the control group （P<0.05， P<0.01）. ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover， it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.

ObjectiveTo explore the clinical efficacy of Huangjin Shuangshen Jiawei （HJSSJW） granules in treating postoperative anxiety and depression after percutaneous coronary intervention （PCI） for coronary heart disease and the effects of this medicine on inflammatory cytokines. MethodNinety-four patients diagnosed with anxiety and depression after PCI were randomized into observation and control groups （47 cases） by the double-blind method. On the basis of conventional Western medical treatment， the observation group was treated with HJSSJW granules for 12 weeks， and the control group with the simulant of HJSSJW granules for 12 weeks. The two groups were compared in terms of Hamilton Anxiety and Depression Scales （HAMA-14， HAMD-24）， Pittsburgh Sleep Quality Inventory （PSQI）， Seattle Angina Score （SAQ）， TCM symptom scores， traditional Chinese medicine （TCM） symptom score and response rate， serum levels of hypersensitive-C reactive protein （hs-CPR）， tumor necrosis factor （TNF）-α， and interleukin （IL-6）， and incidence of major adverse cardiovascular events （MACEs） and adverse reactions. ResultAfter treatment， both groups showed declined scores of HAMA-14， HAMD-24， and PSQI （P<0.05， P<0.01） and the observation group had lower scores of HAMA-14， HAMD-24， and PSQI than the control group （P<0.01）. The scores of SAQ in both groups increased after treatment （P<0.01）， and the observation group had higher score of each dimension than the control group （P<0.05）. The TCM symptom scores decreased in both groups after treatment （P<0.01）， and they were lower in the observation group than in the control group （P<0.05）. The total response rate regarding TCM symptoms in the observation group was higher than that in the control group （χ²=9.225， P<0.01）. After treatment， the levels of hs-CPR， IL-6， and TNF-α became lowered in both groups （P<0.01）， and the observation group had lower levels of hs-CPR， IL-6， and TNF-α than the control group （P<0.05）. The incidence of MACEs in the observation group was lower than that in the control group during the 90 d of the follow-up period （χ²=4.242， P<0.05）. No adverse reactions associated with the use of HJSSJW granules were observed during the trial period. ConclusionHJSSJW granules can alleviate the bad mood， improve sleep， mitigate somatic symptoms， improve the quality of life， reduce inflammatory damage， and improve prognosis， being safe for clinical use in patients with postoperative anxiety and depression after PCI for coronary heart disease.

OBJECTIVE To construct physiologically based pharmacokinetic model(PBPK) model of rosuvastatin in fasting state to predict its absorption in postprandial state and explore its possible food effect mechanism. At the same time, reasonable dietary suggestions were put forward for hyperlipidemia patients taking statins to improve the absorption of BCS Ⅲ statins. METHODS According to the literature and existing research, the physicochemical parameters, biopharmaceutical parameters and pharmacokinetic parameters of rosuvastatin modeling were obtained. The PBPK prediction model of rosuvastatin postprandial administration was established by GastroPlusTM software, and the model was verified by the measured blood concentration data to determine whether the drug absorption results of rosuvastatin postprandial can be accurately predicted, and the parameter sensitivity analysis was carried out. RESULTS The PBPK model of rosuvastatin was constructed to predict its postprandial absorption. The average folding error and absolute average folding error of the model prediction data and the measured data were calculated to be less than 2, and the fitting correlation coefficient combined with model verification showed that the fitting was good. At the same time, parameter sensitivity analysis showed that high-calorie diet, drug LogD and permeability had a greater impact on the absorption of rosuvastatin. CONCLUSION The established model can better predict the absorption of rosuvastatin after meals. Based on the results of parameter sensitivity analysis, reasonable dietary recommendations are proposed for hyperlipidemia patients taking BCSⅢ statins, including appropriately increasing the proportion of protein in the diet, reducing the proportion of fat and water-soluble dietary fiber, etc., to improve the intestinal absorption of BCSⅢ statins.

Objective:To explore the the evaluation value of stress hyperglycemia ratio (SHR), C-reactive protein (CRP), and serum procalcitonin (PCT) for postoperative infection in patients with open tibiofibular fractures.Methods:This study was a prospective analysis. Patients with open tibiofibular fractures hospitalized in the Department of Orthopaedic Surgery of The Second Hospital of Tangshan and North China University of Science and Technology Affiliated Hospital from January 2018 to January 2023 were collected as the research objects, and a total of 839 cases were assessed for outcome, which were divided into infection group (103 cases) and non-infection group (736 cases) according to whether the selected subjects had postoperative infection. The clinical data of the two groups were analyzed by univariate analysis, and the risk factors of postoperative infection of open fracture of tibia and fibula were analyzed by multivariate Logistic regression, and the receiver operating characteristic (ROC) curve was drawn to analyze the predictive efficacy of SHR, CRP, PCT, and their combined models on adverse outcomes.Results:Univariate analysis showed that the infection group had SHR (1.82±0.31), CRP (92.28±36.07) mg/L, PCT (6.35±1.79) μg/L, the non infection group had (1.05±0.12), (56.35±10.21) mg/L and (2.17±0.41) μg/L, respectively, and there were significant differences between the two groups ( t values were 46.90, 21.60, and 54.17, respectively; all P<0.001). The proportion of albumin (<30 g/L) in the infection group was higher than that in the non-infection group (63.11%(65/103), 37.64%(277/736) (χ 2=24.28, P<0.001), and the two groups had significant differences in the rate of time from injury to operation (the infection group ≥6 h was 71.84%(74/103), <6 h was 28.16%(29/103); the non-infection group ≥6 h was 43.07%(317/736), <6 h was 56.93%(419/736); χ 2=35.37, P<0.001), the rate of Gustilo-Anderson classification (the infection group Ⅰ、Ⅱ was 44.46%(46/103), ⅢA was 33.98%(35/103), ⅢB was 12.62%(13/103), ⅢC was 8.47%(9/103);the non-infection groupⅠ、Ⅱ was 59.10%(435/736), ⅢA was 32.47%(239/736), ⅢB was 5.98%(44/736), ⅢC was 2.45%(18/736); χ 2=20.34, P<0.001) and the rate of postoperative drainage volume (the infection group was 40.60%(48/103),the non-infection group was 58.02%(427/736); χ 2=4.79, P=0.029). Multivariate Logistic regression analysis showed that SHR ( OR=1.871,95% CI 1.621-2.160, P<0.001), CRP ( OR=1.060, 95% CI 1.015-1.107, P=0.009), PCT ( OR=1.497, 95% CI 1.420-1.577, P<0.001) were independent risk factors for postoperative infection in open tibiofibular fractures. Among them, SHR had the highest OR value, which was the strongest factor affecting the outcome of the study. Other independent factors were age ( OR=1.052, 95% CI 1.038-1.066, P<0.001) and Gustilo-Anderson type-ⅢC ( OR=1.875, 95% CI 1.038-2.015, P<0.001). By drawing the ROC curve of SHR, CRP, PCT and their combined model to predict the incidence of postoperative infection in open tibiofibular fractures, the results showed that the combined model had higher diagnostic predictive value than the single application, and its sensitivity and specificity were 86.4% and 70.4%, respectively, which were higher than the sensitivity (78.6%, 77.7%, 75.7%) and specificity (69.2%, 69.3%, 69.6%) of the single assessment. Conclusion:The combined model of SHR, CRP and PCT has a higher predictive value than the single detection, which can provide a better clinical basis for the early diagnosis of postoperative infection in patients with open tibiofibular fractures.

Objective: To understand family food environment and its associated factors of primary and secondary school students in Tongzhou District, so as to provide reference for the improvement of family food environment of primary and secondary school students in Tongzhou District. Methods: From 2021 to 2023, a stratified cluster sampling method was used to conduct a questionnaire survey on 1 485 families of students from 11 schools in Tongzhou District. Single Factor Analysis of Variance (ANOVA) was used to compare the differences in family food environment across different demographic background, and the associated factors were analyzed by the multiple binary Logistic regression model. Results: The average score of family food environment of primary and secondary school students in Tongzhou District was 64.32(12.28) points, and the total compliance rate (≥60 points) was 67.41%. The score of family feeding pattern [58.33 (11.11) points] and the compliance rate (42.76%) ranked the bottom among the five dimensions of family food environment. Rural families (OR=1.78, 95%CI=1.41-2.25), junior high schools (OR=1.42, 95%CI=1.07-1.87), senior high schools (OR=2.28, 95%CI=1.73-3.00), singleparent families (OR=1.89, 95%CI=1.15-3.10) and obese parents (OR=1.81, 95%CI=1.23-2.65) had a higher risk of substandard family food environment (P<0.05). Conclusions Family food environment of primary and secondary school students in Tongzhou District is not optimistic, family feeding mode needs to be improved. Attention should be paid to the family food environment, so as to effectively promote healthy growth of children and adolescents.

Objective To establish a mice model of atopic dermatitis with acute itching and investigate the antipruritic effect and its mechanism of Xiaofeng Zhiyang granules(XFZYG).Methods A mice model of atopic dermatitis was prepared by induction method.Mice were sensitized by calcipotriol and ovalbumin(OVA)applying to the right ear daily for 10 days,and then stimulated by OVA injected intradermally into the right cheek to resulting in acute itching.These mice were divided into 5 groups:blank control group,model group,low dose(7.2 g/kg)and high dose(14.4 g/kg)of XFZYG,and positive control group(montelukast 5 mg/kg).Drugs were administered by gavage at 12 h and 30 min before stimulation.The leukotriene levels in the serum of the mice were measured by Elisa and the basophil ratio and activation status in the blood were measured by flow cytometry.Results The mean number of scratches in the model group was 56 between 30 min and 60 min after stimulation,while the mean number of scratches in the low and high dose of XFZYG groups were 42 and 23 respectively,which were significantly lower than those in the model group(P<0.05).The serum leukotriene levels and the proportion of basophils in the low and high dose of XFZYG groups were significantly lower than those in the model group(P<0.05).Conclusion XFZYG had certain therapeutic effect on acute itching of atopic dermatitis in mice,and the mechanism of its action was related to the reduction of leukotriene level and basophil ratio in serum of mice with atopic dermatitis.

Objective:To improve the teaching quality of Medical Microbiology by optimizing the teaching method,adjusting the teaching content and reforming the assessment model.Methods:The students of grade 2020 and 2021 of the same major were divided into the control group and the reform group.The control group received the traditional teaching method.The reform group received the"online + offline"blended teaching method,which integrates online learning resources and ideological and political education into the theoretical content of the curriculum.And the whole process assessment system was applied to the teaching method.The teaching quality was evaluated by the whole process examination results and questionnaire survey.Results:Compared with the control group,the score in the reform group was significantly improved(P＜0.01).Results of the questionnaire survey showed that students'satisfaction with the mixed teaching method reached 97.5% .The integration of hot issues of microbiology and curriculum ideological and political education significantly improved students'learning interest,and more students wanted to engage in the work of microbiology related fields in the future.Conclusion:The practice results show that optimizing the teaching method,adjusting the teaching content and reforming the assessment mode can stimulate the students'learning interest,improve the students'independent learning ability and improve the teaching quality.

A 50-year-old male patient diagnosed with extensive stage small cell lung cancer was treated with pamiparib in combination with temozolomide.Five days later,the patient developed fever with fatigue.After 10 days,the patient stopped taking the drug due to worsening symptoms and was diagnosed with chemotherapy-induced myelosuppression(grade 4).The clinicist evaluated the patient's condition and assessed the association of adverse reactions using the Naranjo's evaluation scale,and concluded that myelosuppression may be induced by the combination of pamiparib and temozolomide.After symptomatic treatment,the patient's myelosuppression recovered completely.This article discusses the correlation between myelosuppression and the combination of the two drugs,provides treatment measures for this situation,briefly describes the risk factors of myelosuppression,treatment and prevention,and guides medical personnel to adjust the treatment plan in time according to different individuals in the process of using similar programs,and strengthens the monitoring and education of adverse drug reactions,so as to provide references for safe drug use.