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.

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 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.

Objective:To construct a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia based on advanced intelligent analysis technology and to evaluate its application effectiveness in the management of orthopedic thrombophilia.Methods:Established a clinical multidisciplinary medical team guided by early warning management and human-computer interaction theory, and builded a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia based on intelligent analysis technology.Adopting a prospective pre-and post control study method, 674 orthopedic inpatients at the Second Affiliated Hospital of Nanchang University from February 2021 to October 2022 were selected as study participants by convenient sampling method and divided into a control group (308 cases) and an observation group (366 cases) according to their admission periods. The control group underwent conventional management methods for thrombophilia. In contrast, the observation group utilized a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia for intelligent management methods. The two groups were compared regarding risk assessment rates, assessment accuracy, assessment efficiency, dynamic assessment completion rate, knowledge awareness rates, implementation rates of multidisciplinary collaborative preventive measures, and thrombophilia incidence rates.Results:The multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia mainly included four personnel ports (doctor end, nurse end, patient or caregiver end, medical quality control end) and eight modules (patient intelligent scoring, risk grading warning, dynamic evaluation of prevention contraindications, prevention measure decision-making, health education, inpatient data monitoring, department indicator statistics, medical management). Both groups of patients completed the study. There were 238 males and 70 females in the control group, aged (42.83 ± 8.69) years old. There were 278 males and 88 females in the observation group, aged (42.35 ± 8.13) years old. The risk assessment rate, assessment accuracy rate, and dynamic assessment completion rate of the observation group for thrombophilia were 100.00% (366/366), 98.90% (362/366), and 100.00% (366/366), respectively, all higher than the control group's 94.15% (290/308), 90.58% (279/308), and 91.55% (282/308), and the differences were statistically significant ( χ2=21.99, 24.88, 32.16, all P<0.01). The knowledge awareness rate of preventing thrombophilia among high-risk patients in the observation group was 95.90% (211/220), the implementation rates of basic prevention, physical prevention, drug prevention, and combined prevention in the multidisciplinary collaborative prevention measures were 87.37% (173/198), 97.72% (215/220), 39.09% (86/220), 46.37% (102/220), and 27.73% (61/220), respectively, all higher than the control group's 85.86% (170/198), 24.74% (49/198), 30.81% (61/198), and 12.12% (24/198), and the differences were statistically significant ( χ2 values were 9.81-20.19, all P<0.05). The risk assessment time for the observation group was (3.95 ± 1.03) minutes, and the incidence of thrombophilia was 1.91% (7/366), both lower than the control group's (9.56 ± 1.65) minutes and 7.47% (23/308), with statistically significant differences ( t=53.78, χ2=6.33, both P<0.05). Conclusions:The application of the multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia has improved the implementation rate of prevention and treatment interventions by medical staff, increased job satisfaction, and also enhanced the awareness rate of prevention knowledge among patients, thereby improving the management status of thrombophilia in orthopedic inpatients.

The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

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

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

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.

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.