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

Objective:To investigate the protective effect of a composite hydrogel against hydrogen peroxide(H2O2)-induced oxidative stress injury in the cardiomyocytes,and to clarify its possible mechanism.Methods:The mice were subcutaneously injected with 100 μL of hydrogel.After normal feeding for 1,14,and 28 d,the mice were sacrificed.Tissue samples were collected and subjected to HE staining to observe the histocompatibity of the hydrogel.The primary cardiomyocytes isolated from 1-day-old SD rats were used to establish an oxidative stress injury model.The primary cardiomyocyties were divided into control,H2O2 and H2O2+Hydrogel groups.The primary cardiomyocytes in control group were cultured normally,the primary cardiomyocytes in H2O2 group were treated with 200 μmol·L-1 H2O2 for 24 h,and the primary cardiomyocytes in H2O2+Hydrogel group were incubated with 1 g·L-1 composite hydrogel and 200 μmol·L-1 H2O2 for 24 h.The viabilities of cardiomyocytes in various groups were assessed by cell counting kit-8(CCK-8)method.Dihydroethidium(DHE)and 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)staining were used to assess the reactive oxygen species(ROS)levels in the cells.The expressions of filamentous actin(F-actin)in the cells in various groups were detected by phalloidin fluorescence staining;the expressions of connexin 43(Cx43)and cardiac troponin T(cTnT)proteins in the cardiomyocytes in various groups were detected by immunofluorescence method.The apoptotic rates of cardiomyocytes in various groups were assessed with TUNEL staining method.The expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)in the cardiomyocytes in various groups were assessed by Western blotting method.Results:The HE staining results showed that the inflammatory cells around the implanted hydrogel were less infiltrated,and the inflammatory reaction of subcutaneous implantation was less.Compared with control group,the viability of cardiomyocytes in H2O2 group was significantly decreased(P＜0.05),the level of ROS in the cells was increased(P＜0.05),the expression levels of Cx43,cTnT and F-actin proteins in the cells were decreased(P＜0.001),the apoptosis rate of cardiomyocytes were decreased(P＜0.01),the expression level of Bcl-2 protein in the cells was increased(P＜0.001),and the expression level of Bax protein was decreased(P＜0.01).Compared with H2O2 group,the viability of cardiomyocytes was significantly increased(P＜0.05),the level of ROS in the cells was decreased(P＜0.01),the expression levels of cTnT,Cx43 and F-actin proteins were increased(P＜0.01),the apoptotic rate of cardiomyocytes were significantly decreased(P＜0.001),the expression level of Bcl-2 protein in the cells were decreased(P＜0.01),and the expression level of Bax protein was increased(P＜0.01).Conclusion:Hydrogel may promote the expression of cardiomyocyte-related proteins by scavenging ROS in the environment and inhibit the cardiomyocyte apoptosis to achieve the protective effect on the cardiomyocytes under oxidative stress.

Middle compartment defects,a common subtype of pelvic floor dysfunction(PFD),are primarily characterized by the prolapse of the uterus or vaginal vault.Magnetic resonance imaging(MRI)has emerged as a valuable diagnostic tool for PFD,offering superior soft tissue resolution while eliminating exposure to ionizing radiation.This review comprehensive summarizes current applications of MRI in the diagnosis and treatment of PFD,covering measurement methods,manifestations of three-level structural defects,postoperative efficacy evaluation,vaginal axial assessment,and evaluation of the mesh status.The authors suggest that MRI enables precise preoperative evaluation of three-level defects,thereby facilitating the development of personalized treatment plans.Additionally,MRI provides an accurate postoperative assessment of surgical outcomes and mesh status,offering a new basis for postoperative assessment.MRI demonstrates unique value in the diagnosis and treatment of middle compartment defects.

Objective To evaluate the perioperative safety and mid-term outcomes of laparoscopic sacrocolpopexy(LSC)and laparoscopic pectopexy(LP)for pelvic organ prolapse(POP).Methods A retrospective analysis was conducted on 274 POP patients,including 178 who underwent LSC and 96 who underwent LP,between August 2017 and January 2023.The extent of prolapse and anatomical restoration were assessed preoperatively and postoperatively using the Pelvic Organ Prolapse Quantification(POP-Q)system.Quality of life outcomes were evaluated with validated questionnaires,including Pelvic Floor Distress Inventory-short form 20(PFDI-20),Pelvic Floor Impact Questionnaire-short form 7(PFIQ-7),and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12(PISQ-12).Postoperative patient satisfaction was assessed during follow-ups.Postoperative anatomical restoration,perioperative status,and postoperative complications,recurrence,and quality of life were compared between the two groups.Multivariate logistic regression was performed to identify postoperative risk factors for recurrence.Results The operative time in the LSC group was significantly shorter than that in the LP group(P<0.05).Intraoperative blood loss was higher in the LSC group compared to that in the LP group(P<0.05).The LSC group also exhibited higher rates of de novo stress urinary incontinence and constipation(P<0.05).The mean follow-up duration was(35.91±16.90)months.The positions of the indicator points(Aa,Ba,C,Ap,and Bp)in the POP-Q classification after the operation were all better than those before the operation.The PFDI-20 score,PFIQ-7 score,and PISQ-12 score all improved compared to those before the operation(P<0.05).Comparison of preoperative and postoperative PFDI-20,PFIQ-7,and PISQ-12 scores showed no intergroup differences.Compared with the LP group,the LSC group had the lower preoperative POP-Q measurements at points Aa and Ba(P<0.05),but superior postoperative measurements for all the indicator points(Aa,Ba,C,Ap,and Bp)(P<0.05).Recurrence occurred in 28 cases in the LP group and 4 cases in the LSC group,with the LP group presenting a significantly higher anatomical recurrence rate than the LSC group did(31.46%[28/89]vs.2.41%[4/166],P<0.05).The subjective cure rate(100%)and objective cure rate(97.59%)in the LSC group were superior to those in the LP group(88.76%and 68.54%,respectively;P<0.05).The results of the multivariate logistic regression analysis showed that,after adjusting for the confounding factors,including age,gravidity,parity,body mass index,and duration of POP,the risk of recurrence after LSC surgery was 0.044 times that after LP(odds ratio[OR],0.044;95%CI,0.015-0.133;P<0.001).Conclusion Mid-term outcomes of LP with partial cervical preservation appear inferior to those of LSC,with LSC demonstrating superior anatomical restoration and lower rates of anatomical recurrence.However,improvements in sexual function and quality of life are comparable between the two procedures.Further evaluation with larger sample sizes and longer follow-up is warranted to better characterize long-term outcomes.

Objective To compare paired boxed gene 1(PAX1)methylation and p16/Ki-67 double staining alone and in combination in thinprep cytologic test(TCT)for distinguishing atypical squamous cells of undetermined significance(ASC-US)and low-grade squamous intraepithelial lesion(LSIL)population.Methods A total of 247 patients with TCT results of ASC-US and LSIL admitted in our hospital from January 2021 to December 2022 were enrolled in this study.Detection efficacy of PAX1 methylation and p16/Ki-67 double staining alone and in combination was evaluated with colposcopic pathologic results as the gold standard and the sensitivity,specificity,accuracy and area under the curve(AUC)as evaluation indexes.Results The positive rates of PAX1 methylation and p16/Ki-67 double staining were increased with the severity of pathological findings.Combined detection of PAX1 methylation and p16/Ki-67 assay had a sensitivity of 91.25％,specificity of 97.72％and accuracy of 95.51％in the women with TCT of ASC-US,and these values were statistically better than those of PAX1 methylation and p16/Ki-67 double staining alone(P＜0.01).Conclusion The combination of PAX1 methylation and p16/Ki-67 double-staining assay can further improve the diagnostic efficacy in patients with ASC-US on TCT results.

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.

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 investigate the effect of temperature on cell proliferation and osteogenic differentiation inhibition of preosteoblast induced by hydrogen peroxide(H2 O2).Methods The MC3T3-E1 cells in the logarithmic phase were randomly divided into 0,450,500,550,600,650 μmol·L-1 H2O2 intervention groups and incubated with 0,450,500,550,600,650 μmol·L-1 H2O2 for 2 h,respectively.Other MC3T3-E1 cells in the logarithmic phase were selected and randomly divided into the control group,model group,low-temperature group,and high-temperature group.Cells in the control group were cul-tured in an incubator with 5％CO2 for 24 h at 37 ℃;cells in the model group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 37 ℃;cells in the low-temperature group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 32 ℃;cells in the high-temperature group were incubated with H2O2 for 2 h and cultured in an incubator with 5％CO2 for 24 h at 40 ℃.The cell proliferation in all groups was detected by cell counting kit-8.The expression levels of Runt-related transcription factor 2(RUNX2),osteopontin(OPN)and osteocalcin(OC)mRNA were detected by real-time fluorescence quantitave polymerase chain reaction;and the expression levels of RUNX2,OPN and OC protein were detected by Western blot.Results There was no statistically significant difference in cell proliferation among the 0,450 and 500 μmol·L-1 H2O2 intervention groups(P＞0.05);the cell proliferation rate in the 550,600 and 650 μmol·L-1 H2O2 intervention groups was significantly lower than that in the 0,450 and 500 μmol·L-1 H2O2 intervention groups,showing a significant decrease in cell proliferation with the increase of H2O2 concentrations(P＜0.05).In order to ensure that there were enough cells to perform the following experiments,550 μmol·L-1 H2 O2 was chosen.The cell proliferation rate in the model group and the low-temperature group was significantly lower than that in the control group and high-temperature group(P＜0.05);there was no significant difference in the cell proliferation rate between the control group and high-temperature group(P＞0.05).The relative expression of RUNX2 mRNA in the model group and high-temperature group were significantly higher than that in the control group and low-temperature group(P＜0.05);the relative expression of RUNX2 mRNA in the low-temperature group was significantly lower than that in the control group(P＜0.05);there was no significant difference in the relative expression of RUNX2 mRNA between the model group and high-temperature group(P＞0.05).The relative expression of OPN mRNA in the model group,low-temperature group and high-temperature group was significantly higher than that in the control group(P＜0.05);the relative expression of OPN mRNA in the low-temperature group and high-temperature group was significantly higher than that in the model group(P＜0.05);the relative expression of OPN mRNA in the low-tem-perature group was significantly higher than that in the high-temperature group(P＜0.05).The relative expression of OC mRNA in the model group,low-temperature group and high-temperature group was significantly than that in the control group(P＜0.05);the relative expression of OC mRNA in the low-temperature group and high-temperature group was significantly higher than that in the model group(P＜0.05);there was no significant difference in the relative expression of OC mRNA between the low-temperature group and high-temperature group(P＞0.05).The relative expressions of RUNX2,OPN and OC protein the model group,low-temperature group and high-temperature group were significantly lower than those in the control group(P＜0.05);the relative expressions of RUNX2 and OPN protein in the low-temperature group were significantly lower than those in the model group and high-temperature group(P＜0.05);the relative expression of OC protein was significantly lower than that in the high-temperature group(P＜0.05);and there was no siqnificantly difference in the relatiwe experesson of OC protein between the low-temperature group and model group(P＞0.05);the relative expressions of RUNX2,OPN and OC protein in the high-temperature group were significantly higher than those in the model group(P＜0.05).Conclusion The inhibitory effects of H2O2 on cell proliferation and osteogenic differentiation are observed in MC3T3-E1 cells;low-tempera-ture incubation can enhance the inhibition of H2O2 on cell proliferation and osteogenic differentiation in MC3T3-E1 cells,while high-temperature incubation can relieve its inhibitory effect on cell proliferation and osteogenic differentiation.RUNX2,OPN and OC protein might play an important role in cell proliferation and osteogenic differentiation mediated by temperature.

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.