Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

AIM:To evaluate the immediate effect of vocal training on tear film stability in patients with dry eye disease.METHODS:A prospective crossover controlled study. From April 1 to April 20, 2026, volunteers with mild-to-moderate dry eye [Ocular Surface Disease Index-6(OSDI-6)score: 4-8] were enrolled. Participants were randomly allocated into two groups to receive two interventions in different sequences. Group A underwent a 50-min standardized vocal training session during the first intervention, while Group B served as a blank control; The two groups crossed over to the alternative intervention for the second session, with a 1-week washout period between the two interventions. The immediate post-intervention changes in Dry Eye Symptoms Questionnaire(CDES-Q)score, pre-and post-intervention non-invasive tear film breakup time(NIBUT), including first NIBUT and average NIBUT, as well as tear meniscus height(TMH), were recorded for each session.RESULTS:A total of 32 eligible participants(64 eyes)were enrolled and completed the study per protocol. The participants were randomly assigned to two groups with different intervention sequences. Group A(16 participants, 32 eyes)comprised 3 males and 13 females, with a mean age of 61.69±4.56 y and a mean OSDI-6 score of 5.750±1.183. Group B(16 participants, 32 eyes)comprised 3 males and 13 females, with a mean age of 63.19±1.56 y and a mean OSDI-6 score of 5.250±1.438.There were no significant differences in baseline characteristics between the two groups(P>0.05). After vocal training intervention, the net effect size for first NIBUT was 1.883 s(P=0.042), and for average NIBUT was 2.076 s(P=0.019). No significant change was observed in TMH(P=0.652). The CDES-Q score difference was -47.188(P<0.001). Further individual data analysis revealed that 59% of participants exhibited prolonged first NIBUT and 50% exhibited prolonged average NIBUT after vocal training.CONCLUSION: Vocal training can immediately improve tear film stability. This therapeutic approach shows promise for dry eye management and provides a reference for future large scale and long-term investigations.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

OBJECTIVES: Stigma is common among community-dwelling patients with schizophrenia and has a profound negative impact on both psychiatric symptoms and quality of life. This study aims to explore the association between stigma and quality of life in this population and to examine the multiple mediating roles of anxiety and depression symptoms. METHODS: The multi-stage stratified cluster random sampling method was used to select the community-dwelling patients with schizophrenics in Chengdu, Sichuan Province, China. The questionnaire included general demographic characteristics, stigma question, the Generalized Anxiety Disorder-7 (GAD-7) scale, the Patient Health Questionnaire-9 (PHQ-9), and the 12-item Short Form Health Survey (SF-12). The SF-12 was used to measure quality of life, including physical health and mental health dimensions. A multiple mediation model was used to analyse the mediating effects of anxiety and depression symptoms together between stigma and quality of life. RESULTS: A total of 1 087 community patients with schizophrenia were included with a mean age of 50.68±12.73 years; 525 (48.30%) were male. Stigma was reported by 543 patients (49.95%). Anxiety symptoms were present in 292 patients (26.86%), and depression symptoms in 407 patients (37.44%). The physical health quality of life score was 72.01 ± 20.99, and the mental health quality of life score was 71.68 ± 19.38. Multiple mediation analysis showed that stigma directly affected quality of life, and also indirectly affected quality of life through anxiety and depression symptoms. Anxiety and depression jointly mediated 42.26% of the total effect of stigma on physical health quality of life and 47.51% on mental health quality of life. CONCLUSIONS Reducing stigma and preventing anxiety and depression symptoms in community-dwelling patients with schizophrenia can effectively improve their quality of life and support reintegration into society.
Humans ; Quality of Life ; Male ; Depression/psychology* ; Middle Aged ; Social Stigma ; Schizophrenia ; Female ; Anxiety/psychology* ; China ; Surveys and Questionnaires ; Adult ; Schizophrenic Psychology ; Independent Living ; Aged

Objective:To analyze the attributable burden of active smoking on the deaths of cancer in inhabitants aged 30 years and above in Zhejiang Province.Methods:Comparative risk assessment approach in the Global Burden of Disease Study was used with the data from Zhejiang Adult Tobacco Surveillance System and Death Monitoring Surveillance System in 2020, and population attributable fraction (PAF), years of life lost (YLL), work of potential years of life lost (WPYLL) attributed to smoking on the deaths of cancer in inhabitants aged 30 years and above in Zhejiang Province were calculated with a linear regression model.Results:In 2020, there were 81 536 cancer deaths aged 30 years and above in the surveillance areas of Zhejiang Province, of which 24 518 were attributed to active smoking (PAF: 30.07%, attributable mortality rate: 55.04/100 000). The YLL was 553 078 person-years, with a standardized YLL rate of 12.40‰, and the WPYLL was 56 606 person-years. Among various cancer types, laryngeal cancer had the highest smoking-attributable PAF (44.75%), while lung cancer accounted for the most significant number of attributable deaths and life loss, with an age-standardized YLL rate of 4.65‰.Conclusions:Active smoking is a significant risk factor for cancer mortality in Zhejiang Province, with lung cancer posing the most significant disease burden. It is urgent to advance tobacco control legislation, strengthen targeted interventions, and promote early cancer screening to reduce the disease burden associated with smoking-related cancers effectively.

ObjectiveTo explore the effectiveness of health information dissemination and its influencing factors using the "Shanghai CDC" WeChat public account as a case study, providing references for public health institutions to optimize the use of official new media platforms for effective publicity. MethodsA total of 1 030 headline articles published on the "Shanghai CDC" WeChat public account between 2016 and 2019 were analyzed using content analysis and non-parametric tests to examine the impact of factors such as titles and content categories. ResultsFrom 2016 to 2019, the number of WeChat public account followers increased by 280 000, with the articles accumulating over 8.8 million views. The median (P₂₅, P₇₅) open rate of articles was 5.90% (3.69%, 10.31%), and the median (P₂₅, P₇₅) sharing and forwarding rate was 6.60% (4.25%, 9.17%). Factors such as the use of first- and second-person pronouns, degree adverbs, negative adverbs, explicit viewpoints, and title length all significantly affected the open rate of articles, with OR (95%CI) values of 0.175 (0.041‒0.756), 32.606 (2.350‒452.432), 4.079 (1.093‒15.230), 0.106 (0.028‒0.409), and 1.184 (1.063‒1.319),respectively (all P<0.05). In terms of content, statistical significant differences in dissemination effectiveness were observed across article categories and themes (P<0.05). In terms of article categories, articles related to news hotspots and service information had higher open rates of 9.58% and 14.00%, respectively. These two types of articles also obtained higher sharing and forwarding rates of 7.65% and 9.16%, respectively. In terms of article topics, compared with healthy life and health products, among the top four topics in terms of publication volume, the open rates of articles about infectious diseases and disease-causing biology and immunization programs were higher, accounting for 7.88% and 6.88%, respectively, with no significant difference in sharing and forwarding rates. ConclusionThe "Shanghai CDC" WeChat public account demonstrated good dissemination effectiveness. Enhancing article titles by increasing informational content and degree adverbs (e.g., "highly," "most," and "extremely") and negative adverbs (e.g., "no") can improve dissemination reach. Public health WeChat accounts should incorporate news hotspots or service information in their articles. While maintaining their strengths in disseminating knowledge on infectious diseases and immunization programs, they should also enhance public education in other professional fields within their scope of responsibility to improve the overall dissemination impact of health information.

Objective To explore and address the issue of insufficient segmentation accuracy in liver tumor segmentation using the traditional U-Net algorithm,which is caused by the lack of contextual information for both the liver and tumor,as well as the large morphological variability of tumors.Methods A cascaded liver tumor segmentation algorithm,DDR-UNet++,which integrated dilated convolutions and residual modules was proposed.Firstly,CT images from the LiTS-2017 dataset were preprocessed through window width/level adjustment,histogram equalization and Gaussian filtering to reduce noise and smooth edges.Then,a cascaded liver segmentation model was employed to enhance the liver region proportion,mitigate interference from surrounding tissues and address data imbalance issue.For liver tumor segmentation,deformable dilated convolutions and residual networks were introduced to expand the receptive field and improve feature extraction capability.Results DDR-UNet++outperformed the traditional U-Net on the LiTS-2017 dataset,achieving improvements of 4.7%,1.7%,and 8.5%in Dice similarity coefficient,relative volume difference,and Jaccard index,respectively.These enhancements contribute to overcoming the inefficiency and low accuracy issues in conventional tumor segmentation,thereby improving early tumor detection rates,enhancing patient survival outcomes,and alleviating the diagnostic burden on clinicians.Conclusion The proposed method improves the feature extraction capability to some extent by enhancing the model structure and segmentation strategy,effectively increases the accuracy and robustness of liver tumor segmentation,and provides a reliable technical reference for clinical auxiliary diagnosis.

Objective:To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG).Methods:Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People′s Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes ( MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People′s Hospital Affiliated to Jiangsu University (Ethics No. 20150083). Results:① m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. ② mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. ③ Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. ④ MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P<0.05). ⑤ RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P<0.000 5). Conclusion:These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.

Objective: To construct a Family with sequence similarity 50 member A(FAM50A) gene knockout mouse insulinoma pancreatic β-cell line Beta-TC-6 using CRISPR/Cas9 gene editing technology and to prepare polyclonal antibodies specifically recognizing FAM50A. Methods: Two guide RNAs(sgRNAs) targeting the FAM50A gene were designed,and a recombinant plasmid expressing blue fluorescent protein(BFP) was constructed for gene knockout.The successfully constructed plasmid was transfected into Beta-TC-6 cells,and BFP-positive single cells were isolated for clonal expansion.The expanded monoclonal cell lines were genotyped by Sanger sequencing,and FAM50A protein expression was assessed by Western blot.Purified human recombinant FAM50A protein was used to immunize New Zealand rabbits for the preparation of a polyclonal antibody.The specificity of the prepared antibody was then validated using the successfully established FAM50A knockout cell line. Results: A monoclonal cell line with a successful knockout of the FAM50A gene was identified.Sanger sequencing confirmed base deletions at the target site.Western blot analysis showed a complete absence of FAM50A protein expression in this cell line.The prepared polyclonal antibody successfully recognized endogenous murine FAM50A protein in wild-type Beta-TC-6 cells and in hTERT-RPE1 cells overexpressing human FAM50A-GFP fusion protein,while no signal was detected in the FAM50A knockout cells. Conclusion This study successfully established a FAM50A gene knockout Beta-TC-6 cell model and generated a FAM50A polyclonal antibody,providing powerful tools for future research.