ObjectiveTo investigate the change in the activity of hepatitis B virus （HBV）-specific CD8⁺ T cells after pegylated interferon-α-2b （PEG-IFN-α-2b） therapy in HBeAg-negative patients with chronic HBV infection. MethodsA total of 53 HBeAg-negative patients with chronic HBV infection who attended The First Affiliated Hospital of Xinxiang Medical University and Tangdu Hospital of Air Force Mdical University from April 2020 to June 2022 were enrolled and treated with PEG-IFN-α-2b （180 μg/week， subcutaneous injection） antiviral therapy. The study endpoint was HBsAg clearance （course of treatment<48 weeks） or 48 weeks （course of treatment≥48 weeks）. Peripheral blood mononuclear cells were isolated at baseline and study endpoint， and peripheral blood T cell counts were measured. Enzyme-linked immunospot assay was used to measure the frequency of HBV-specific CD8⁺ T cells secreting perforin， granzyme B， and interferon-γ. A total of 17 HLA-A^*02-restricted patients were selected， and CD8⁺ T cells were purified to establish direct- and indirect-contact co-culture systems for HBV-specific CD8⁺ T cells and HepG2.2.15 cells. The level of lactate dehydrogenase in supernatant was measured to calculate the mortality rate of HepG2.2.15 cells， and the levels of HBV DNA， cytotoxic molecules， and cytokines in supernatant were also measured. Flow cytometry was used to measure the expression of apoptosis ligands， and the cytotoxicity of HBV-specific CD8⁺ T cells was evaluated. The independent samples t-test or the paired t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test or the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsThe HBsAg clearance rate at study endpoint was 30.19% （16/53）. There were no significant differences in peripheral blood T cell counts （CD3⁺， CD4⁺， and CD8⁺ T cells） between baseline and study endpoint （P>0.05）. At study endpoint， there was a significant increase in the frequency of HBV-specific CD8⁺ T cells secreting perforin， granzyme B， and interferon-γ （U=177.50， t=11.90， U=186.50， all P<0.001）， and the patients with HBsAg clearance had a significantly higher frequency of such HBV-specific CD8⁺ T cells than those without HBsAg clearance （U=120.50， t=2.73， U=121.50， all P<0.01）. In the direct- and indirect-contact co-culture systems at study endpoint， HBV-specific CD8⁺ T cells induced a significant reduction in HBV DNA in the supernatant of HepG2.2.15 cells （all P<0.001） and significant increases in the secretion of interferon-γ and tumor necrosis factor-α （all P<0.05）； in the direct-contact co-culture system， HBV-specific CD8⁺ T cells induced significant increases in the mortality rate of HepG2.2.15 cells （13.62%±3.27% vs 11.39%±2.40%， t=2.27， P=0.030） and the secretion of perforin and granzyme B （t=72.50， U=52.50， both P<0.05）. In the direct- and indirect-contact co-culture systems， compared with HBV-specific CD8⁺ T cells from the patients without HBsAg clearance， the HBV-specific CD8⁺ T cells from patients with HBsAg clearance had a significantly greater reduction in HBV DNA （P<0.05） and significant increases in the secretion of interferon-γ and tumor necrosis factor-α （P<0.05）. ConclusionPEG-IFN-‍α‍-2b therapy can help to achieve a relatively high HBsAg clearance rate in HBeAg-negative patients with chronic HBV infection， and the activity of HBV-specific CD8⁺ T cells is significantly enhanced， which is closely associated with HBsAg clearance.

Objective To analyze the structural and phylogenetic characteristics of the mitochondrial genome from Bulinus globosus, so as to provide a theoretical basis for classification and identification of species within the Bulinus genus, and to provide insights into understanding of Bulinus-schistosomes interactions and the mechanisms of parasite transmission. Methods B. globosus samples were collected from the Ruya River basin in Zimbabwe. Mitochondrial DNA was extracted from B. globosus samples and the corresponding libraries were constructed for high-throughput sequencing on the Illumina NovaSeq 6000 platform. After raw sequencing data were subjected to quality control using the fastp software, genome assembly was performed using the A5-miseq and SPAdes tools, and genome annotation was conducted using the MITOS online server. Circular maps and sequence plots of the mitochondrial genome were generated using the CGView and OGDRAW software, and the protein conservation motifs and structures were analyzed using the TBtools software. Base composition and codon usage bias were analyzed and visualized using the software MEGA X and the ggplot2 package in the R software. In addition, a phylogenetic tree was created in the software MEGA X after sequence alignment with the software MAFFT 7, and visualized using the software iTOL. Results The mitochondrial genome of B. globosus was a 13 730 bp double-stranded circular molecule, containing 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes, with a marked AT preference. The mitochondrial genome composition of B. globosus was similar to that of other species within the Bulinus genus. Phylogenetic analysis revealed that the complete mitochondrial genome sequence of B. globosus was clustered with B. truncatus, B. nasutus, and B. ugandae into the same evolutionary clade, and gene superfamily analysis showed that the metabolism-related proteins of B. globosus were highly conserved, notably the cytochrome c oxidase family, which showed a significant consistency. Conclusions This is the first whole mitochondrial genome sequencing to decode the compositional features of the mitochondrial genome of B. globosus from Zimbabwe and its evolutionary relationship within the Bulinus genus, which provides important insights for further understanding of the phylogeny and mitochondrial genome characteristics of the Bulinus genus.

This article reports a diagnostically and therapeutically challenging case of small intestinal marginal zone lymphoma. The patient presented with recurrent abdominal pain as the chief complaint, and imaging revealed multifocal small bowel wall thickening with high uptake, multisegmental luminal stenosis, and proximal dilation. Initial diagnostic workup, including gastroscopy, colonoscopy, and enteroscopy with biopsy, failed to establish a definitive diagnosis. Empirical anti-tuberculosis therapy was ineffective. A repeat enteroscopic biopsy performed over eight months after symptom onset eventually confirmed the diagnosis of mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma. Despite three different chemotherapy regimens, the patient's intestinal obstruction symptoms persisted, with imaging still showing multifocal bowel wall thickening and hypermetabolic activity. A critical diagnostic dilemma arose regarding whether the PET/CT-positive lesions represented residual lymphoma or fibrotic scarring, whether further chemotherapy adjustments were warranted, and whether surgical resection was necessary. Multidisciplinary discussion concluded that imaging had limited discriminatory value in this scenario and that surgical intervention should be pursued if feasible. The patient successfully underwent partial small bowel resection, with postoperative pathology confirming no residual lymphoma but significant fibrotic changes. The patient has since resumed a normal diet, with body weight nearly restored to pre-illness levels. This case highlights that fibrotic transformation is a common sequela of treated marginal zone lymphoma and that PET/CT may misleadingly suggest residual disease, potentially leading to unnecessary chemotherapy. Timely surgical intervention is crucial in such scenarios.

BACKGROUND:The light curing and fluoride light curing enamel adhesives have a certain sealing effect on the etched enamel surface.The fluoride light curing enamel adhesives can also achieve the anti-caries function by releasing fluoride ions.However,the existing researches lack the long-term tracing of fluoride release effect,especially the amount of local pathogenic bacteria after 1-3 months of local fluoride application. OBJECTIVE:To analyze the changes in the expression of Porphyromonas gingivalis and Streptococcus mutans in subgingival plaque of the upper anterior teeth adhered by different components of enamel adhesives in adolescent patients with fixed appliance. METHODS:Ninety adolescent patients who received orthodontic treatment in Shanghai Stomatological Hospital from January to December 2016 were enrolled,including 43 males and 47 females,with a mean age of(13.27±1.12)years.These patients were randomly divided into three groups(n=30 per group).In the chemical curing group,Unite? bonding resin was used to bond fixed appliances.In the light curing group,Transbond XT light curing resin was used to bond the fixed appliance.In the fluoride light curing group,GC light curing orthodontic adhesive was used to bond the fixed appliance with cement.The subgingival plaque was collected on the day of bonding,1st,2nd,and 3rd month follow-up reviews.The expressions of Porphyromonas gingivalis and Streptococcus mutans in subgingival plaque were detected by PCR. RESULTS AND CONCLUSION:(1)Intragroup comparison:With the increase of bonding time,Porphyromonas gingivalis expression increased significantly in the 3rd month in the chemical curing group(P<0.05).In the light curing group,Porphyromonas gingivalis showed a significant decrease in the 1st month(P<0.05).Porphyromonas gingivalis expression decreased significantly in the 1st and 2nd months compared with initial data in the fluoride light curing group(P<0.05).The expression of Streptococcus mutans was higher in the chemical curing group in the 1st,2nd,and 3rd months compared with the initial data(P<0.05).In the fluoride light curing group,the expression of Streptococcus mutans was lower in the 1st,2nd,and 3rd months compared with the initial data(P<0.05).There was no significant difference in the proliferation and expression of Streptococcus mutans during follow-up in the light curing group compared to the initial adhesion(P>0.05).(2)Intergroup comparison:In the 1st month,the expression of Porphyromonas gingivalis was lower in the light curing group and fluoride light curing group than that in the chemical curing group(P<0.05).In the 2nd and 3rd months,the expression of Porphyromonas gingivalis was lower in the fluoride light curing group than that in the light curing group and chemical curing group(P<0.05).In the 1st,2nd,and 3rd months,the expression of Streptococcus mutans was lower in the light curing group and fluoride light curing group than that in the chemical curing group(P<0.05).The expression of Streptococcus mutans was lower in the fluoride light curing group than that in the light curing group(P<0.05).(3)The results show that in the fixed orthodontic process,the use of different components of enamel adhesives has different effects on the proliferation and expression of oral Porphyromonas gingivalis and Streptococcus mutans in the short term.Fluoride light curing enamel adhesives at the initial stage can reduce the occurrence of enamel demineralization,caries,and periodontal inflammation.

Objective To analyze the main factors influencing the management effect of rural epilepsy prevention and control projects in Hubei Province, and to provide reference for further improving the management effect. Methods According to the phenobarbital treatment and management plan of the rural epilepsy project, the target population was screened and reviewed, and patients who met the inclusion criteria were enrolled into the project management. Regular follow-up visits, free drug treatment, health education and other measures were carried out, and all relevant information was collected and integrated into the survey data. After the data was reviewed level by level, SPSS20.0 software was used for statistical analysis. Results From January 1, 2015 to December 31, 2020, among patients treated and managed with phenobarbital in 6 project counties, 1430 patients were treated and managed for more than 1 year, of whom 1119 (78.25%) had no seizures or had more than 75% reduction in the number of seizures during the observation period. Compared with other age groups, the age group of 65 years and above had the highest markedly effective/effective ratio (95.77%). From the point of follow-up, the markedly effective/effective ratio of 5 years and above was the highest (91.51%). Compared with those who received no treatment prior to enrollment and those who received regular treatment, the patients receiving informal treatment had the lowest markedly effective/effective ratio (82.43%). 1213 cases (84.83%) had good compliance during the observation period, of whom 1062 cases (87.55%) had a reduction in the number of seizures by more than 50% compared with that before treatment. Univariate analysis showed that the age of patients, the length of follow-up, the treatment status before enrollment, the average daily dose of phenobarbital and the compliance of patients all had an impact on the management effect, and the difference was statistically significant (P<0.05). Multivariate analysis showed that the markedly effective/effective rate of patients in the age group of 65 years and above was 6.749 times that of the younger age group. Receiving informal treatment prior to enrollment was a risk factor for difficult-to-control epilepsy. The markedly effective/effective rate of patients receiving informal treatment was 0.29 times that of patients never receiving treatment. Good compliance was a protective factor for epilepsy control, and the markedly effective/effective rate of patients with good compliance was 2.058 times that of patients with poor compliance. Conclusion The epilepsy prevention and management project in rural areas has a significant effect on seizure control. Early treatment, standardized treatment, and improvement of treatment compliance are effective ways to improve the management effect of epilepsy patients.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Background and objective Transcription factor(TF)can bind specific sequences that either promotes or represses the transcription of target genes,and exerts important effects on tumorigenesis,migration,invasion.Staphylococcal nuclease-containing structural domain 1(SND1),which is a transcriptional co-activator,is considered as a promising target for tumor therapy.However,its role in lung adenocarcinoma(LUAD)remains unclear.This study aims to explore the role of SND1 in LUAD.Methods Data from The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),Clinical Pro-teomic Tumor Analysis Consortium(CPTAC),and Human Protein Atlas(HPA)database was obtained to explore the associa-tion between SND1 and the prognosis,as well as the immune cell infiltration,and subcellular localization in LUAD tissues.Furthermore,the functional role of SND1 in LUAD was verified in vitro.EdU assay,CCK-8 assay,flow cytometry,scratch assay,Transwell assay and Western blot were performed.Results SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients.In addition,SND1 was predominantly present in the cytoplasm of LUAD cells.Enrichment analysis showed that SND1 was closely associated with the cell cycle,as well as DNA replication,and chro-mosome segregation.Immune infiltration analysis showed that SND1 was closely associated with various immune cell popula-tions,including T cells,B cells,cytotoxic cells and dendritic cells.In vitro studies demonstrated that silencing of SND1 inhib-ited cell proliferation,invasion and migration of LUAD cells.Besides,cell cycle was blocked at G,phase by down-regulating SND1.Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

Infectious disease is a major public health problem threatening human health and social development, and infectious disease teaching is an important part of public health education. However, traditional infectious disease teaching faces challenges such as overly theoretical and fragmented content, overly traditional and monotonous methods, and a narrow and isolated vision, which makes it difficult to adapt to the current complex and changing situation of infectious disease prevention and control. The “One Health” concept emphasizes interdisciplinary, cross-sectoral, and cross-regional communication and cooperation to achieve the harmonious unity of health for humans, animals, and the environment, which is significant in preventing and controlling infectious diseases. This paper proposes some ideas for reforming infectious disease teaching based on the One Health concept, which aims to improve the quality and effectiveness of infectious disease teaching by recognizing the close connection between human health, animal health, and environmental health. Specifically, it is suggested to reform the teaching in four aspects: introducing the basic concepts, principles, and practices of One Health, increasing the content of infectious diseases related to One Health, adopting diversified and interactive teaching methods, and establishing cross-disciplinary teaching cooperation. Concrete recommendations are provided for each aspect. This paper argues that reforming infectious disease teaching based on the One Health concept is conducive to cultivating public health talents with global vision, systems thinking, and cross-disciplinary collaboration capabilities, providing robust talent support for coping with emerging, re-emerging, and endemic infectious disease threats.

The study was designed to investigate the peripheral anti-inflammatory effect of nicotinamide riboside(NR)in experimental autoimmune encephalomyelitis(EAE)mice and its mechanisms.Female C57BL/6 mice were induced by MOG35-55 to prepare EAE model,which then randomly divided into EAE model group and NR treatment group.Mice in EAE model group were given normal saline at a dose of 200 μl/d and mice in NR treatment group were given NR at a dose of 500 mg/kg(200 μl/d)by intragastric administration.Clinical score and body weight of mice in each group were observed and recorded.After mice were sacrificed on the 28th day after immunization,frozen sections of spleen and spinal cord were prepared and proteins of spinal cord were extracted.HE staining was used to detect peripheral inflammatory cells infiltrating spinal cord;immunofluorescence staining was used to detect the number of CD4+T cells and CD68+macrophages in spinal cord of mice;Western blot was used to detect the expression of IFN-γ and IL-1β in spinal cord of mice;immunofluorescence staining was used to detect the number of ROCK-Ⅰ+cells,TLR4+cells,p-NF-κB+cells,TNF-α+cells,IL-1β+cells,IFN-γ+cells,IL-6+cells,IL-10+cells,IL-17+cells,iNOS+cells and Arg-1+cells in spleen of mice.Data showed that compared with EAE model group,NR significantly delayed the onset time of EAE mice(P<0.05),decreased clinical score(P<0.05 or P<0.01),alleviated weight loss,prevented peripheral inflammatory cells from infiltrating spinal cord,decreased the number of CD4+T cells and CD68+macrophages in spinal cord(P<0.01),down-regulated the expression of IFN-γ and IL-1β of spinal cord(P<0.05),inhibited the expression of ROCK-Ⅰ,TLR4 and p-NF-κB in spleen of mice(P<0.01),reduced the secretion of IFN-γ,iNOS,IL-6 and other pro-inflammatory factors in spleen(P<0.05 or P<0.01),and increased the secretion of anti-inflammatory factors Arg-1 and IL-10 in spleen(P<0.05 or P<0.01).In conclusion,NR can effectively alleviate the clinical symptoms of EAE mice and significantly reduce inflammatory response of peripheral and central nervous system,and its mechanism may be related to the inhibition of Rho/ROCK signaling pathway and TLR4/NF-κB signaling pathway in spleen of EAE mice.