Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Objective To investigate the diagnostic potential of combining 3.0T magnetic resonance imag-ing(MRI)T2 mapping sequences with serum nesfatin-1 levels for detecting early osteoarthritis(OA)in elderly knees.Methods 97 elderly patients with knee osteoarthritis(OA group)and 52 elderly individuals undergoing physical examinations(control group)were recruited from a hospital between May 2023 and May 2024.Based on X-ray findings,the OA group was further divided into an early-stage subgroup and a non-early-stage subgroup.All participants underwent 3.0T MRI T2 mapping sequence scans to measure the T2 values in the knee cartilage region,and serum nesfatin-1 levels were assessed.Differences in these indicators were compared between groups.Additionally,a receiver operating characteristic(ROC)curve was constructed to evaluate the diagnostic value of these parameters for early-stage knee OA in elderly individuals.Results Among 97 elderly patients with knee OA,35 cases were classified into the early-stage group,and 62 cases were categorized into the non-early-stage group.The T2 values in five cartilage regions of the knee and serum nesfatin-1 levels were significantly higher in the OA group compared to the control group(P<0.05).Moreover,these values were significantly lower in the early-stage group than in the non-early-stage group(P<0.05).The areas under the curve(AUC)for diagnosing early-stage OA using T2 values in knee cartilage regions and serum nesfatin-1 levels ranged from 0.774 to 0.871.Notably,the AUC for combined diagnosis reached 0.939(P<0.05).Conclusion 3.0T MRI using the T2 mapping sequence in combination with serum nesfatin-1 level detection demonstrates high diagnostic value for early OA in elderly patients with knee involvement.

Objective To identify novel biomarkers for predicting the risk of latent tuberculosis infection(LTBI)activation using bio-informatics and machine-learning algorithms and to establish a risk model.Methods The GSE112104 and GSE193777 datasets were obtained from the Gene Expression Omnibus.Differential gene expression and weighted gene co-expression network analyses were per-formed to identify ferroptosis-related differentially expressed genes(FRG-DEGs)associated with LTBI activation.Three machine-learning algorithms,least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest,were used to identify ferroptosis-related hub genes(FRG-hubs).The reliability of these genes was validated using independent validation datasets and reverse transcription polymerase chain reaction(PCR).A risk model was established using R software.Results In the GSE 112104 dataset,296 genes were upregulated and 1 569 genes were downregulated in active tuberculosis compared to those in LTBI.Among the LTBI progressors,506 genes were upregulated and 1 132 genes were downregulated.Weighted correlation network analysis identified five gene modules,with the blue module showing the strongest correlation with LTBI activation(cor=0.62,P=0.000 04),con-taining 1 340 genes.Intersections with 728 ferroptosis-related genes resulted in eight FRG-DEGs.The machine-learning algorithms iden-tified four FRG-hubs:PLA2G6,GLS2,JUN,and AMN,whose expression decreased with LTBI activation.Reverse transcription PCR con-firmed this trend.A risk model based on these genes yielded an area under the curve of 0.98 to 1.00.Conclusion This study successfully identified novel biomarkers for predicting the risk of LTBI activation and developed an accurate predictive risk model.

To address the issue of reduced signal quality of photoplethysmography caused by local fluctuation,an approach called locally orthogonal weighted polynomial fitting(LOWPF)is proposed for signal smoothing.After determining the positions of the fluctuation sequences using the forward-backward difference XOR method,weighted polynomial fitting is applied to these sequences,and the fitted values are used to replace the fluctuation sequences to achieve signal smoothing.By constructing orthogonal basis functions,the condition number of the coefficient matrix is reduced,and the stability of the equation system solution for higher-order fitting is improved.Simulation results demonstrate that the smoothed signal's XOR smoothness of the proposed method surpasses that of the moving average algorithm and the empirical mode decomposition reconstruction algorithm.The smoothing results on 241 sets of measured PPG signals show that LOWPF achieves an efficiency of smoothness of 89.10%,significantly higher than the 78.05%of empirical mode decomposition and the 59.13%of the 5-point moving average algorithm.LOWPF has promising application prospects for smoothing signals with significant local fluctuations.

Objective To investigate the value of prone-position MRI of lumbar spine for diagnosing pediatric occult tethered cord syndrome(OTCS).Methods A total of 67 children with suspected tethered cord syndrome(TCS)and confirmed OTCS by surgery were prospectively enrolled as OTCS group,while 73 healthy subjects were recruited as control group.Supine-and prone-position lumbar MR examinations were performed in both groups.The position of filum terminale on prone axial T2WI and the presence or absence of"sunset sign"(i.e.filum terminale located within the dorsal 1/2 of spinal canal on prone axial T2WI)were observed,spinal cord conus mobility was calculated.The efficacy of"sunset sign"for diagnosing OTCS in children was calculated through comparison between groups.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of spinal cord conus mobility.Results On prone-position axial T2WI,"sunset sign"was found in 58 cases(58/67,86.57％)but not in 9 cases(9/67,13.43％)in OTCS group,which was not even observed in control group.The sensitivity of"sunset sign"for diagnosing pediatric OTCS was 86.57％(58/67),with specificity of 100％(73/73),positive predictive value of 100％(58/58)and negative predictive value of 89.02％(73/82).The spinal cord conus mobility was(19.30±5.89)％in OTCS group and(31.71±6.58)％in control group,being statistically different between groups(t=-11.722,P＜0.001).The sensitivity,specificity and AUC of spinal cord conus mobility for diagnosing pediatric OTCS was 80.60％,90.41％and 0.920,respectively.Conclusion Prone-position MRI of lumbar spine could be used in diagnosing pediatric OTCS.

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

[Purpose]To analyze the changes in the incidence trend of thyroid cancer from 1990 to 2021,and to predict the future incidence from 2022 to 2030.[Methods]We collected data related to the incidence of thyroid cancer among Chinese residents from 1990 to 2021 in the Global Bur-den of Disease 2021(GBD 2021)study,analyzed the trend of thyroid cancer incidence using the Joinpoint regression model,and constructed a Bayesian age-period-cohort(BAPC)model to pre-dict the future incidence of thyroid cancer during the years of 2022-2030,based on the inci-dence data during the years of 1990-2021.[Results]From 1990 to 2021,the age-standardized incidence rate(ASIR)of thyroid cancer in China showed a fluctuating upward trend,and the ASIR of thyroid cancer in China in 2021 was 2.47/105,slightly lower than the global average(2.91/105)in the same year.In 2021,there were significant differences in new cases and incidence rate of thyroid cancer between men and women,with the incidence rate of women being higher than that of men.Among them,the number of new cases in women was 27 915,the crude incidence rate was 4.02/105,and the ASIR was 2.87/105;in men,the number of new cases was 20 189,the crude incidence rate was 2.77/105,and the ASIR was 2.11/105.Between 1990 and 2021,the increase in the number of new cases,the crude incidence rate,and the ASIR of men in China was much larger than that of women.The ASIR of thyroid cancer in both male and female showed an in-creasing trend,while the average annual percentage change(AAPC)in female was lower than that in male.There were significant gender differences in the age-specific incidence rates of thyroid cancer.In 2021,the incidence rate of women was higher than that of men in the Chinese population＜75 years old,whereas the incidence rate of men was higher than that of women in the population≥75 years old.From 1990 to 2021,the incidence rates of the Chinese male population aged 45～59 years old and ≥75 years old increased significantly;and the incidence rate of the Chinese fe-male popu-lation aged 50～74 years old increased significantly.Projections showed that the ASIR of overall,male and female standardized incidence rates in 2030 increased to 2.90/105,2.44/105 and 3.26/105 respectively.[Conclusion]The incidence rate of thyroid cancer in China is on the rise,with the incidence rate of women being higher than that of men,but the incidence rate of men has increased more than that of women,and the gap between the incidence rates is narrow-ing,and the peak age of incidence of men is mostly in the senior age group.

Background and Aims:Portal hypertensive colopathy(PHC)is a common complication of portal hypertension in patients with liver cirrhosis.It may lead to gastrointestinal bleeding,yet its underlying pathogenesis remains unclear,and systematic research in China is limited.This study aimed to analyze the colonoscopic features in cirrhotic patients and to explore their associations with relevant clinical factors.Methods:A retrospective analysis was conducted on 99 cirrhotic patients who underwent colonoscopy at Xingtai People's Hospital between July 2020 and December 2024.Colonoscopy,gastroscopy,and clinical data were reviewed.Differences between patients with PHC and those without were compared in terms of sex,Child-Pugh classification,platelet count,presence of ascites,and hepatic encephalopathy.Multivariate logistic regression was used to identify independent risk factors for PHC.Additionally,colorectal lesion detection rates were compared with those of a contemporaneous cohort of 444 participants undergoing national colorectal cancer(CRC)screening at the same center.Results:Among the 105 patients with cirrhosis,the detection rates of PHC,adenomatous polyps,and CRC were 32.32%,28.28%,and 3.03%,respectively,while only 37.37%had no abnormal findings.No serious colonoscopy-related complications were observed.The proportion of males in the PHC group was significantly higher than in the non-PHC group(78.13%vs.50.75%,P=0.009).The PHC group also showed significantly higher rates of Child-Pugh class B/C,and lower platelet count(all P<0.05).There was no statistically significant difference in the incidence of ascites and hepatic encephalopathy between the two groups(P>0.05).Multivariate analysis identified that male gender(OR=3.307,95%CI=1.219-8.971)and Child-Pugh class B/C(OR=2.867,95%CI=1.046-7.861)were independent risk factors for PHC.Compared to the CRC screening cohort,cirrhotic patients had a similar adenoma detection rate(28.28%vs.25.00%,P=0.499),and a slightly higher colorectal cancer detection rate that did not reach statistical significance(3.03%vs.0.68%,P=0.135).Conclusion:Colonoscopy revealed a high rate of abnormalities in cirrhotic patients,with PHC and adenomatous polyps being the most common findings.Routine colonoscopy is recommended for cirrhotic patients without contraindications,especially males,and patients with Child-Pugh class B/C,to facilitate early detection of PHC and precancerous lesions,thereby reducing the risk of lower gastrointestinal bleeding and missed diagnoses of malignancy.

Objective:To explore the molecular mechanism by which the methionine adenosyltransferase 2A (MAT2A)/β-catenin/zinc finger E-box binding homeobox 1 (ZEB1)/epithelial-mesenchymal transition (EMT) pathway regulates neural tube defect (NTD) through intracellular S-adenosylmethionine (SAM).Methods:A mouse NTD model was induced using the SAM metabolic disorder inhibitor ethionine. Eighty specific pathogen-free C57BL/6 mice were divided into three groups: a normal group (36 mice), an ethionine group (46 mice), and an ethionine+SAM group (44 mice). Phosphate-buffered saline (PBS), ethionine, and ethionine+SAM were respectively injected intraperitoneally on embryonic day 7.5 (E7.5), and the mice were sacrificed on E10.5. Embryonic tissues were collected, and the morphology of embryos in each group was observed under a stereomicroscope. The interaction between ethionine and MAT2A was analyzed using Autodock software. The expression levels of MAT2A, β-catenin, ZEB1, and EMT-related proteins in the brain tissues of embryos from the three groups were measured using immunofluorescence, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (RT-qPCR). Variance analysis was used for intergroup comparisons.Results:(1) Autodock analysis results showed that MAT2A binds to ethionine through covalent bonds, exhibiting a complementary effect, thereby accelerating the expression of MAT2A. (2) After successful construction of the NTD model, normal embryos were plump with well-developed brains. NTD embryos showed delayed development, obvious anencephaly, unclosed neural tubes, and asymmetry. (3) The levels of SAM and SAH in the embryonic tissues of the ethionine group were significantly lower than those in the normal group (1 737.56±95.64 vs. 872.33±205.11, and 89.17±9.50 vs. 51.25±9.48, respectively). The SAM and SAH levels in the ethionine+SAM group was 1 197.00±222.27 and 66.61±12.25, significantly higher than those in the ethionine group ( P<0.017). Compared with the normal group and the ethionine+SAM group, the expression of MAT2A mRNA in the embryonic brain tissue of the ethionine group was significantly upregulated (1.00±0.00, 1.59±0.52, and 2.42±0.53, respectively, F=49.64, P<0.001; pairwise comparisons between groups P<0.017). (4) Compared with the normal group, the expression of Ctnnb1 in the ethionine group was reduced, and the expression of Ctnnb1 in the ethionine+SAM group was higher than that in the ethionine group (1.00±0.00, 0.38±0.16, and 0.76±0.10, respectively, F=149.03, P<0.001; pairwise comparisons between groups P<0.017). (5) The expression of ZEB1 in the ethionine group was higher than that in the normal group and the ethionine+SAM group (2.91±0.55, 1.00±0.00, and 1.61±0.20, respectively, F=150.01, P<0.001; pairwise comparisons between groups P<0.017). (6) The expression levels of E-cadherin and Vimentin in the ethionine group were lower than those in the normal group. In contrast, the expression of N-cadherin was higher than that in the normal group. After SAM supplementation, the expression levels of E-cadherin and Vimentin were upregulated, and the expression level of N-cadherin was downregulated (0.54±0.12, 1.00±0.00, and 0.72±0.14, respectively, F=87.44; 0.53±0.17, 1.00±0.00, and 0.76±0.09, F=87.44; 3.11±0.53, 1.00±0.00, and 2.13±0.56, F=95.54; all P<0.001; pairwise comparisons within the same index group P<0.017]). Conclusions:Ethionine promotes the expression of MAT2A, leading to reduced SAM production. Ethionine regulates the level of ZEB1 by increasing MAT2A and inhibits the EMT process to interfere with methionine cycle metabolism, ultimately resulting in NTD.

Objective To explore the function of electroacupuncture(EA)on body mass,fasting blood glucose,heat pain threshold,and transient receptor potential vanilloid 4(TRPV4)in the dorsal root ganglia(DRG)of rats with diabetic neuropathic pain(DNP).Methods A DNP rat model was formed by intraperitoneally injecting the animals with STZ.From days 15 to 21,bilateral Zusanli and Kunlun points of the DNP rat model were treated with electroacupuncture once daily for 30 min.We then measured their body mass,fasting blood glucose,and heat pain threshold.The co-expression of TRPV4 and NeuN in the rat L4～L6 DRG was detected by immunofluorescence.The effects of the TRPV4 agonist GSK1016790A on body mass,fasting blood glucose,and the heat pain threshold of DNP rats treated with electroacupuncture were detected.Results After the 7th day,body mass was significantly decreased(P<0.01)and fasting glucose was significantly increased(P<0.01)in the model group compared with the normal group.After the 21st day,compared with the model group,heat pain threshold of the model+electroacupuncture group was significantly higher(P<0.01);the results of co-expression of TRPV4 and NeuN immunofluorescence on rat L4～L6 DRG showed that:the expression of positive cells in the model group was significantly higher(P<0.01)than that in the normal group,the co-expression of TRPV4 and NeuN positive cells in L4～L6 DRG of rats in the model+electroacupuncture group was significantly lower(P<0.01)than that in the model group.The TRPV4 agonist GSK1016790A can reverse the downregulation of thermal pain threshold induced by electroacupuncture in DNP rats(P<0.01).Conclusion Electroacupuncture alleviated the DNP induced by STZ,and its mechanism may involve the inhibition of TRPV4 protein expression in the DRG.