Hepatitis B virus （HBV） is a unique hepatotropic DNA virus that forms covalently closed circular DNA within the nucleus of hepatocytes and can partially integrate into the host genome， establishing the molecular basis for persistent viral infection. HBV infection and replication depends on multiple hepatocyte-enriched host factors and is modulated by the hepatic microenvironment. The host achieves natural control and clearance of HBV through various mechanisms， including cytolytic elimination mediated by cellular immunity such as cytotoxic T lymphocytes and natural killer cells， innate immunity and noncytolytic clearance driven by interferons and various cytokines， and antibody-mediated protection and clearance as part of humoral immune response. In addition， intracellular restriction factors and pathways， hepatocyte turnover through division and replacement， and changes in the hepatic microenvironment （such as the increase in matrix stiffness） collectively influence the efficiency and outcome of viral control and clearance. This article clarifies and elaborates on related mechanisms， so as to deepen the understanding of HBV chronicity， spontaneous resolution， and cure and provide a theoretical basis for optimizing clinical management and developing novel therapeutic strategies.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

Objective:To investigate the clinicopathological characteristics of patients with early gastric carcinoma with lymphoid stroma(EGCLS).Methods:A retrospective analysis was conducted on 27 consecutive patients with EGCLS who underwent radical surgery at The Second People's Hospital of Changzhou between January 2007 and December 2023.Sixty-nine cases of conventional early gastric carcinoma with matched T stages were randomly selected as controls.Immunohistochemical staining was performed to detect the expression of P53,mismatch repair(MMR)proteins,programmed death-ligand 1(PD-L1),E-cadherin,and human epidermal growth factor receptor 2(HER2)in the study cohort.FISH analysis was conducted on HER2 2+cases,and in situ hybridization was used to detect Epstein-Barr virus(EBV).Res-ults:No significant differences were observed between the two groups in terms of patient sex,age,tumor location,size,ulceration,lymph-ovascular or perineural invasion,tumor budding grade,P53 expression,or MMR protein deficiency.The EGCLS group showed significantly higher proportions of SM2 invasion(88.9%),poor tumor differentiation(70.4%),pushing tumor border(48.1%),PD-L1 positivity(59.3%),Epstein-Barr virus-encoded small RNA(EBER)positivity(55.6%),and abnormal E-cadherin expression(48.1%)compared to the control group(59.4%,46.4%,18.8%,24.6%,1.4%,and 23.2%,respectively;P<0.05).The frequency of lymph node metastasis(7.4%)and the pro-portion of elevated macroscopic type(14.8%)in the EGCLS group were significantly lower than in the control group(30.4%and 40.6%,re-spectively;P<0.05).Lymphovascular invasion,tumor budding grade,and non-EGCLS status were identified as risk factors for lymph node metastasis,with lymphovascular invasion being the only independent risk factor.Conclusions:EGCLS is a rare subtype of early gastric car-cinoma characterized by a low frequency of lymph node metastasis and a high proportion of EBER positivity or MMR protein deficiency.En-doscopic resection or immunotherapy may be preferred treatment options for patients who are not suitable candidates for surgery.

Objective:To investigate the clinicopathological characteristics of patients with early gastric carcinoma with lymphoid stroma(EGCLS).Methods:A retrospective analysis was conducted on 27 consecutive patients with EGCLS who underwent radical surgery at The Second People's Hospital of Changzhou between January 2007 and December 2023.Sixty-nine cases of conventional early gastric carcinoma with matched T stages were randomly selected as controls.Immunohistochemical staining was performed to detect the expression of P53,mismatch repair(MMR)proteins,programmed death-ligand 1(PD-L1),E-cadherin,and human epidermal growth factor receptor 2(HER2)in the study cohort.FISH analysis was conducted on HER2 2+cases,and in situ hybridization was used to detect Epstein-Barr virus(EBV).Res-ults:No significant differences were observed between the two groups in terms of patient sex,age,tumor location,size,ulceration,lymph-ovascular or perineural invasion,tumor budding grade,P53 expression,or MMR protein deficiency.The EGCLS group showed significantly higher proportions of SM2 invasion(88.9%),poor tumor differentiation(70.4%),pushing tumor border(48.1%),PD-L1 positivity(59.3%),Epstein-Barr virus-encoded small RNA(EBER)positivity(55.6%),and abnormal E-cadherin expression(48.1%)compared to the control group(59.4%,46.4%,18.8%,24.6%,1.4%,and 23.2%,respectively;P<0.05).The frequency of lymph node metastasis(7.4%)and the pro-portion of elevated macroscopic type(14.8%)in the EGCLS group were significantly lower than in the control group(30.4%and 40.6%,re-spectively;P<0.05).Lymphovascular invasion,tumor budding grade,and non-EGCLS status were identified as risk factors for lymph node metastasis,with lymphovascular invasion being the only independent risk factor.Conclusions:EGCLS is a rare subtype of early gastric car-cinoma characterized by a low frequency of lymph node metastasis and a high proportion of EBER positivity or MMR protein deficiency.En-doscopic resection or immunotherapy may be preferred treatment options for patients who are not suitable candidates for surgery.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective:To exploring the effect of selenium on tumor necrosis factor-α (TNF-α) induced inflammatory injury of AC16 cardiomyocytes.Methods:AC16 cardiomyocytes cultured in vitro were divided into control group, selenium pretreatment group (100 μg/L sodium selenite pretreatment for 4 h), 50 μg/L TNF-α group, selenium pretreatment + 50 μg/L TNF-α group, 100 μg/L TNF-α group, and selenium pretreatment + 100 μg/L TNF-α group. After 24 h of culture, the cell culture medium or cells were collected for detection. Griess method was used to detect nitric oxide (NO) level in cell culture medium. Hoechst 33342 nuclear staining was detected by fluorescence inverted microscope and karyopyknosis ratio was analyzed. The mRNA expression levels of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-2 associated X protein (Bax) and inducible nitric oxide synthase (iNOS) were detected by real-time fluorescence quantitative PCR. The protein expression levels of nuclear factor-kappa B (NF-κB) p65 and inhibitory κB-α (IκB-α) were detected by Western blotting. Results:The levels of NO in the control group, selenium pretreatment group, 50 μg/L TNF-α group, selenium pretreatment + 50 μg/L TNF-α group, 100 μg/L TNF-α group and selenium pretreatment + 100 μg/L TNF-α group were (10.58 ± 2.32), (9.07 ± 0.73), (15.53 ± 3.97), (12.05 ± 1.11), (30.65 ± 4.16) and (19.02 ± 3.72) μmol/L, respectively. Selenium and TNF-α had main effects on NO level ( F = 37.71, 99.07, P < 0.001) and interaction effect ( F = 11.80, P < 0.001). Selenium and TNF-α had main effects on karyopyknosis ratio and Bcl-2 and Bax mRNA expression levels ( F = 56.37, 462.81, 18.04, 32.85, 18.38, 170.77, P < 0.05). Selenium and TNF-α had an interactive effect on both karyopyknosis ratio and Bax mRNA expression level ( F = 21.48, 19.96, P < 0.001). Selenium and TNF-α had main effects on iNOS mRNA expression level ( F = 129.98, 1 051.76, P < 0.001) and interaction effect ( F = 53.28, P < 0.001). Selenium and TNF-α had main effects on the protein expression levels of NF-κB p65 and IκB-α ( F = 73.65, 145.49, 710.20, 105.66, P < 0.001) and interaction effects ( F = 26.73, 197.59, P < 0.001). Conclusion:Selenium may inhibits iNOS expression through NF-κB signal system and protects cardiomyocytes from TNF-α induced inflammatory injury.

N-glycosides comprise a broad range of compounds, some of which have demonstrated a variety of bioactivities, such as antiviral, antitumor, and antibacterial activities. Serving as essential building blocks for DNA and RNA, nucleosides are a particularly important subclass of N-glycosides. Accordingly, natural N-glycosides and their analogs have garnered great interests of both organic and pharmaceutical chemists, who have developed numerous synthetic methods for the preparation of N-glycosides. By reviewing the natural N-glycosides published between 1980 and 2023, this article summarizes current strategies for synthesizing N-glycosides, aiming to provide support for the development and research of N-glycosides.

OBJECTIVE: To explore the genetic basis for a child featuring global developmental disorder with epilepsy. METHODS: A child who had presented at Guangzhou Women and Children's Medical Center in July 2022 was selected as the study subject. Clinical data was collected. Potential variant was detected by whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a three-year-old ethnic Zhuang Chinese girl, had presented with global developmental disorder and epilepsy, for which rehabilitation therapy was ineffective. Genetic testing revealed that she has harbored a homozygous c.821T>C (p.Leu274Pro) missense variant of the PIGW gene, for which both of her parents and sister were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of uncertain significance. CONCLUSION The homozygous c.821T>C (p.Leu274Pro) variant of the PIGW gene probably underlay the onset of disease in this child. Above finding has enriched the mutational spectrum of the PIGW gene.
Child, Preschool ; Female ; Humans ; Computational Biology ; Developmental Disabilities ; Epilepsy/genetics* ; Genetic Testing ; Homozygote

Objective:To investigate the relationship between single nucleotide polymorphisms of transforming growth factor-β2 (TGFβ2) gene and Keshan disease (KD) in Han population of Shaanxi Province.Methods:KD region in Huangling County, Yan'an City, Shaanxi Province was selected as the investigation site in this study. Using the method of cluster random sampling, 52 families with KD in 6 administrative villages in Huangling County (Duanjiawan Village, Taoqu Village, Yaoping Village, Jianzhuang Village, Anjiao Village in Yaoping Town, and Houziping Village in Diantou Town) were selected for epidemiological investigation. According to the "Diagnosis of Keshan Disease" (WS/T 210-2011), 285 subjects were identified, including 79 patients with KD (case group) and 206 healthy controls (control group). Genomic DNA was extracted from the peripheral venous blood. The polymorphism of genetic variation of TGFβ2 gene rs6658835 was genotyped by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). Chi-square (χ 2) test and t-test were used to analyze the baseline data, and binary logistic regression model was used to analyze the influencing factors of KD, all samples were tested for Hardy-Weinberg equilibrium using goodness-of-fit χ 2 test, differences in genotype and allele frequencies between case and control groups were compared by χ 2 test, and logistic regression analysis was used to compare the genotype frequencies between two groups after adjusting for confounding factors. Results:Epidemiological investigation showed that there were significant differences in age and heart murmur between case group and control group ( t = 7.03, χ 2 = 9.66, P < 0.05). The analysis of binary logistic regression model showed that the influence of age on KD was statistically significant (χ 2 = 20.72, P < 0.001). The gene frequency distribution of TGFβ2 gene rs6658835 in case group and control group conformed to the Hardy-Weinberg equilibrium (χ 2 = 0.02, P = 0.900). Correlation analysis results: the difference of genotype frequency of TGFβ2 gene rs6658835 in case group (GG, GA, AA: 6.3%, 38.0%, 55.7%) and control group (GG, GA, AA: 10.7%, 43.7%, 45.6%) was not statistically significant (χ 2 = 2.78, P = 0.249). After adjustment by age, the difference of genotype frequency and dominant model of TGFβ2 gene rs6658835 in case group and control group was statistically significant (χ 2adj = 5.43, 4.86, P < 0.05), the difference of recessive model of TGFβ2 gene rs6658835 in case group and control group was not statistically significant (χ 2adj = 2.12, P = 0.145). Conclusion:TGFβ2 gene rs6658835 is associated with KD in Han population of Shaanxi Province.