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.

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.

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 The researchers systematically retrieved,evaluated,and summarized the best evidence for the care of nebulized inhalation in adult patients on mechanical ventilation,to provide a basis for standardizing the care of nebulized inhalation in patients on mechanical ventilation.Methods We systematically searched the domestic and foreign databases to collect the evidence on the literature related to nebulization therapy for mechanical ventilation in adults.The time for the retrieval is from the inception of databases until February 2023.There were 3 researchers who evaluated the quality of the literature,and extracted and summarized the evidence based on this subject.Results A total of 19 articles were obtained in database.42 pieces of evidence were summarized,covering pre-assessment of nebulized inhalation,preparation before nebulized inhalation,medication management,selection and standardized use of nebulization devices,respiratory machine mode and parameter settings,equipment management during nebulized inhalation,evaluation of effect,management of adverse reactions,disposal of materials and environment after nebulized inhalation and management of nebulized inhalation for respiratory infectious diseases.Conclusion This study summarized the best evidence for nebulized inhalation nursing in adult patients with mechanical ventilation,so as to provide a reference of standardized nebulized inhalation therapy for such patients,which is conducive to ensuring the safety of patients.

Objective:To investigate the expression of heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) in human esophageal cancer tissues and its clinical significance.Methods:Single-cell data for esophageal cancer were downloaded from the Gene Expression Omnibus (GEO) database (GSE160269 dataset, last updated on November 29, 2020) to analyze the expression of HNRNPA2B1. Transcriptional sequencing data for esophageal cancer from The Cancer Genome Atlas (TCGA) database, including the fragments per kilobase of transcript per million mapped reads (FPKM) quantitative data (173 samples, consisting of 162 esophageal cancer tissues and 11 adjacent normal tissues), and survival data in the phenotype category were downloaded. Analysis of FPKM quantitative data from the TCGA database for esophageal cancer was performed. The top 250 genes most correlated with HNRNPA2B1 were selected and the R4.3.0 clusterProfiler package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the selected gene set. FPKM quantitative data from the TCGA database for esophageal cancer were imported into the CIBERSORTx website to obtain immune cell abundance scores, and the correlation between HNRNPA2B1 and the degree of immune cell infiltration was analyzed. The clinicopathological data of patients from esophageal cancer tissue microarrays including 114 cases of esophageal squamous cell carcinoma tissues and 66 cases of adjacent normal tissues were collected. The patients underwent surgery from January 2006 to December 2008, and the follow-up period extended until July 2015. Cytokeratin (CK) and HNRNPA2B1 expression in esophageal cancer tissue microarrays were detected by using multi-color immunohistochemical (mIHC) staining, and multispectral tissue imaging was conducted. The R4.3.0 survival package and survminer package in TCGA database were used to calculate the optimal cut-off value of HNRNPA2B1 expression and the proportion of CK + HNRNPA2B1 + cells in tissue microarrays was used to calculate the cut-off value of HNRNPA2B1 expression based on which patients were categorized into high and low expression groups. The overall survival (OS) of both groups was compared and the factors influencing OS were analyzed by using the Cox proportional hazards model. Results:In the GSE160269 dataset of single-cell data for esophageal cancer, the expression level of HNRNPA2B1 in tumor epithelial cells was higher than that in normal epithelial cells, and HNRNPA2B1 was highly expressed in various immune cell subtypes. The high expression level of HNRNPA2B1 was positively correlated with regulatory T cells, naive B cells and memory CD4 + T cells. GO enrichment analysis revealed that HNRNPA2B1 was primarily involved in the biological process of nuclear division, cellular components were mainly enriched in chromosomal regions, and molecular functions were mainly enriched in ATP hydrolysis activity. KEGG enrichment analysis indicated that HNRNPA2B1 was primarily involved in biological processes such as the cell cycle, spliceosome, and DNA replication. Results from mIHC and multispectral tissue imaging demonstrated that CK was predominantly expressed in the cell membranes of tumor cells and normal esophageal epithelial cells, while HNRNPA2B1 was primarily expressed in the nuclei of tumor cells and normal esophageal cells. The expression level of HNRNPA2B1 in esophageal cancer tissues was higher than that in the normal paracancerous tissues ( U = 2 984.00, P < 0.05). Results of tissue microarrays and the survival analysis on the data in the TCGA database indicated that esophageal cancer patients with low HNRNPA2B1 expression had a better OS compared to those with high expression (both P < 0.05). Cox multivariate regression analysis revealed that age ( HR = 1.919, 95% CI: 1.158-3.182, P = 0.011), TNM stage ( HR = 2.404, 95% CI: 1.374-4.207, P = 0.002), T stage ( HR = 2.349, 95% CI: 1.150-4.789, P = 0.019), and the expression of HNRNPA2B1 in tumor epithelial cells ( HR = 2.160, 95% CI: 1.280-3.647, P = 0.004) were independent factors influencing OS in esophageal cancer patients. Conclusions:The high expression of HNRNPA2B1 protein in esophageal cancer tissues may play a role in the developement and progression of esophageal cancer, serving as a crucial biological indicator for prognostic assessment of esophageal cancer.

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 explore the distribution features of resident CD8 + T cells infiltration in human esophageal cancer tissues and its clinical significance. Methods:Data from the Cancer Genome Atlas database were retrieved, the correlation between CD103 + CD8 + T cells and infiltration degree of conventional type 1 dendritic cell (cDC1), conventional type 2 dendritic cell (cDC2), type 3 dendritic cell(DC3) was investigated. From January 2006 to December 2008, 78 esophageal cancer tissues and 75 adjacent normal tissues from 78 esophageal cancer patients were collected by Shanghai Outdo Biotechnology Co., Ltd, the clinical data of patients was followed up by telephone until July 2015. The distribution of CD8 + T cells and CD103 + CD8 + T cells in cancer tissues and adjacent normal tissues was detected by multi-color labeling techniques and multispectral tissue imaging. The differences of the number and the ratio of CD8 + T cells and CD103 + CD8 + T cells in cancer tissues and adjacent normal tissues were compared. The Kaplan-Meier survival curves of patients with tissue infiltration of CD8 + T cells and CD103 + CD8 + T cells at different levels were drawn through the R language " survminer" package, and the best cut-off value was obtained. TNM stage, pathological stage and other clinical parameters of patients with high and low infiltration of CD8 + T cells, CD103 + CD8 + T cells were compared. Wilcoxon rank sum test, chi-square test, log-rank test and Cox proportional risk regression model statistical analysis were used to evaluate the prognostic value of the above indicators. Spearman correlation analysis was used for correlation analysis. Results:In the cancer tissues of patients with esophageal cancer, the infiltration degree of CD103 + CD8 + T cells was positively correlated with the infiltration degree of cDC1 cells, cDC2 cells and DC3 cells ( r=0.67, 0.53 and 0.47, all P<0.001). The percentage of CD8 + T cells in all cells in the whole tissue core of tumor tissues (63.09% (42.14%, 76.21%)) was higher than that of adjacent normal tissues (2.56% (1.68%, 5.38%)), and the difference was statistically significant ( U=41.00, P<0.001). The proportion of CD103 + CD8 + T cells in all cells in the whole tissue core of tumor tissues (7.92% (1.60%, 20.61%)) was higher than that of adjacent normal tissues (0.04% (0.01%, 0.10%)), and the difference was statistically significant ( U=857.50, P<0.001). The percentage of high CD8 + T cells infiltration in esophageal cancer tissues of patients with pathological stage Ⅰ+ Ⅱ was lower than that of patients with stage Ⅲ+ Ⅳ (57.9%, 33/57 vs. 85.7%, 18/21); the percentage of high CD103 + CD8 + T cells in CD8 + T cells in esophageal cancer tissues of patients with TNM stage Ⅰ+ Ⅱ was lower than that of patients with stage Ⅲ+ Ⅳ (21.6%, 8/37 vs. 48.8%, 20/41), and the differences were both statistically significant ( χ2=5.25 and 6.23, P=0.022 and 0.013). The results of Kaplan-Meier survival analysis and univariate Cox proportional risk regression model showed that the overall survival (OS) of patients with high CD8 + T cell infiltration was longer than that of patients with low CD8 + T cell infiltration ( HR=0.57, 95% confidence interval (95% CI) 0.34 to 0.96, P=0.034). There was no significant difference in OS between patients with high CD103 + CD8 + T cell infiltration and patients with low CD103 + CD8 + T cell infiltration ( HR=0.66, 95% CI 0.40 to 1.08, P>0.05). Conclusion:The high infiltration of CD103 + CD8 + T cells in esophageal cancer tissues are expected to be used as a prognostic predictor for patients with esophageal cancer, which is an important component of anti-tumor immune response in tumor microenvironment of esophageal cancer.

Background: and Purpose Previous studies suggested increased visit-to-visit variability of total cholesterol (TC) is associated with stroke. This study aimed to investigate the associations of various lipids measurements variability and the risk of stroke and stroke type (ischemic and hemorrhagic stroke). Methods: Fifty-one thousand six hundred twenty participants in the Kailuan Study without history of myocardial infarction, stroke, and cancer who underwent three health examinations during 2006 to 2010 were followed for incident stroke. Variability in TC, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) measurements were measured using the coefficient of variation (CV), standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Results: During a median of 6.04 years of follow-up, 1,189 incident stroke (1,036 ischemic and 160 hemorrhagic stroke) occurred. In the multivariable-adjusted model, the hazard ratio (HR) comparing participants in the highest versus lowest quartile of CV of HDL-C were 1.21 (95% confidence interval [CI], 1.02 to 1.45; P for trend=0.013) for ischemic stroke. The highest quartile of CV of LDL-C was associated with 2.17-fold risk of hemorrhagic stroke (HR, 2.17; 95% CI, 1.25 to 3.75; P for trend=0.002) compared with the lowest quartile. We did not observe any significant association between TC and triglycerides variability with any of stroke. Consistent results were obtained when calculating variability index using SD, VIM, or ARV. Conclusions These findings suggest the high visit-to-visit HDL-C and LDL-C variability were associated with an increased incidence of ischemic and hemorrhagic stroke, respectively.

Objective To compare the positioning accuracy between personalized polyurethane foam with wing boards and negative pressure vacuum bag in radiotherapy for lung cancer using kilovoltage cone beam computed tomography(CBCT). Methods Thirty-nine patients with lung cancer who received chest radiotherapy in our hospital from 2015 to 2016 were enrolled as subjects. In those patients, 20 were immobilized by negative pressure vacuum bags(VB group)and the others by personalized polyurethane foam with wing boards(PF group).CBCT images were acquired weekly and registered with planning CT images. Setup errors in the left-right, superior-inferior, and anterior-posterior directions, three-dimensional(3D) displacement vector,and setup time were recorded. The margin of the planning target volume(PTV)was calculated using the Van Herk formula(2.5∑+0.7σ). Between-group comparison was made by paired t test. Results The PF group had a significant smaller setup error in the y-direction than the VB group (2.54±1.79 vs.3.19±2.14 mm,P=0.03),while there were no significant differences in setup errors in the x-or z-direction between the two groups(1.80± 1.48 vs. 1.90± 1.41 mm, P=0.46;2.14± 1.75 vs. 2.25± 1.75 mm,P=0.35). There were no significant differences in rotational setup errors in the Rx-,Ry-,or Rz-direction between the two groups(1.15°±0.76°vs. 1.15°±0.85°, P=0.50;0.71°±0.60°vs. 0.72°±0.43°, P=0.45;0.62°±0.54° vs. 0.46°±0.30°,P=0.06). The PTV margins in the x?,y?,and z?directions were expanded by 5.56, 8.57, and 7.02 mm, respectively, in the PF group, and by 5.62, 9.27, and 7.23 mm,respectively,in the VB group. The proportion of patients with 3D displacement vectors larger than 5 mm was 40% in the PF group and 45% in the VB group.Conclusions For patients undergoing radiotherapy for lung cancer,personalized polyurethane foam with wing boards can,to a certain extent,reduce the setup error in the superior-inferior direction and PTV margin expansion.[Key words] Lung neoplasms/radiotherapy; Polyurethane foam; Vacuum bag; Setup errors;Margin