Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

In 2025， European Association for the Study of the Liver published the clinical practice guidelines on vascular diseases of the liver. The guidelines comprehensively elaborate on the vascular diseases of the liver from the aspects of risk factors， diagnosis， and treatment strategies， in order to provide guidance for the management of patients with these conditions based on the best evidence available. This article gives an excerpt of the recommendations and guidance statements in the clinical practice guidelines.

Objective: To explore a simple, effective, and safe method for excluding false positives and identifying infections by comprehensively evaluating blood donors with reactive HIV screening results, thereby providing a basis for developing management strategies for such donors. Methods: HIV testing data of blood donors from our laboratory from January 2022 to December 2024 were collected. The results of ELISA and nucleic acid testing (NAT) were combined with confirmatory results from the CDC and analyzed. Results: A total of 605 929 samples were tested for HIV over the three-year period, with 682 reactive samples (reactive rate: 11.25 per 10 000). All were sent to the CDC for Western blot (WB) confirmation, resulting in 53 confirmed positives ((confirmed positive rate: 7.77%). Among these, 619 samples showed isolated HIV Ag&Ab reactivity with non-reactive NAT (HIV Ag&Ab+-&HIV RNA or NAT NR), with a confirmed infection rate of 0%; 9 samples showed dual HIV Ag&Ab reactivity with non-reactive NAT (HIV Ag&Ab++&HIV RNA NR or NAT NR), also with 0% confirmed infection; 52 samples showed dual HIV Ag&Ab reactivity and reactive NAT (HIV Ag&Ab++&HIV RNA R or NAT R), all confirmed as positive (100% infection rate); and 2 HIV Ag&Ab dual-reactive samples without NAT detection were also confirmed infected (100%). For all four HIV Ag&Ab assays, the S/CO values in the true positive group with dual reactivity were significantly higher than those in the false-positive groups (P<0.05). The S/CO distributions for both single-reactive false positives and dual-reactive false positives were narrow, with the upper box (Q3, 75th percentile) below optimal cutoff values in all cases (The optimal cutoff values for the four reagents were 5.00, 11.67, 8.50, and 20.90, respectively). Conclusion: Blood donors with positive NAT results in HIV blood screening are permanently deferred. Donors with dual positive HIV Ag&Ab but negative NAT results are classified and managed based on the S/CO values of HIV Ag&Ab and the optimal screening thresholds. Donors with single positive HIV Ag&Ab but negative NAT results are placed under evaluation status and retain their eligibility to donate blood. Optimizing the management measures for blood donors and establishing a scientific stratified management and assessment mechanism can effectively maintain the stability of the blood donor team.

Bacterial reinfection in the lungs of patients with influenza virus(IV)is a key factor leading to serious illness and death.The adverse consequences caused by co-infection with IV and Streptococcus pneumoniae(SPN)impose a serious burden on patients.However,the specific pathogenesis is complex,how to make better use of the mouse animal model of IV/SPN co-infection for subsequent basic research is of great significance.This article reviews the selection of animals,the selection of pathogen types,the selection of different modeling times,the identification of the co-infection model,and its applications in the IV/SPN co-infection model,so as to provide a reference for the selection of animal models of IV/SPN co-infection in the future.

Objective:To explore the effects of the "group+individual" combined internet occupational health management model on the physiological indicators, pulmonary imaging changes and self-management ability of people with pneumoconiosis.Methods:In November 2022, patients diagnosed with pneumoconiosis in Baotou city from January 2012 to January 2022 were selected. Eighty cases exhibiting a decline in forcect expiratory volume in one second (FEV 1) and pulmonary imaging changes (primarily ground-glass opacity variations) were chosen as study subjects. These patients were randomly divided into a control group and an experimental group using the sealed envelope method, with 40 patients in each group. The control group received conventional outpatient follow-up and occupational health surveillance management, while the experimental group underwent a remote occupational health management model combining "group+individual" approaches over 12 months, with interventions administered once every 3 months. Comparative analysis was conducted on pre-and pos-management indicators between the two groups, including pulmonary function, pulmonary imaging changes, and self-management ability scores. Results:After occupational health management, the experimental group showed superior improvement in observed indicators (including pulmonary function and pulmonary imaging indicators) compared to the control group ( P<0.05). The self-management ability scores of the experimental group after occupational health management were also better than those of the control group (all P<0.05) . Conclusion:The remote occupational health management model combining group management and individualized guidance, when applied to patients with pneumoconiosis, is beneficial for improving their physiological indicators, pulmonary imaging indicators, and enhancing self-management abilities.

The novel coronavirus(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2),classified as a single-stranded RNA virus,replicates and transcribes its genome through the action of an RNA-dependent RNA polymerase,which is itself comprised of numerous non-structural pro-teins(non-structural proteins,Nsps).The present study delineates the development of a detection system founded on a bicistronic reporter plasmid in conjunction with an array of Nsp plasmids,ai-ming to investigate the influence of SARS-CoV-2 Nsps on the virus's replication and expression profiles.Specifically,a bicistronic reporter gene plasmid along with twelve distinct Nsp plasmids(encompassing Nsp3C-Flag,Nsp4,Nsp6-Nsp10,Nsp12-Nsp16)were meticulously constructed via molecular cloning techniques.The successful expression of these Nsps was subsequently confirmed through Western blot analysis.Initially,the activity of the RNA-dependent RNA polymerase was assessed by co-transfection of the reporter plasmid with Nsp12,in the presence of its auxiliary fac-tors Nsp7 and Nsp8,with careful regulation of the co-transfection ratio,culturing temperature,and the timing of activity determination for the triad of Nsp plasmids.The normalized NLuc fluorescein value,in reference to the FLuc fluorescein value of the housekeeping gene,served as a metric for determining the polymerase activity.Building upon this foundation,the co-transfection concentra-tions of Nsp9-16 were fine-tuned,followed by the incremental addition of varying doses of Nsp3C,Nsp4,and Nsp6,to further elucidate the activity of RNA-dependent RNA polymerase(RdRp).The findings indicated that upon transfection with varying ratios of Nsp7,Nsp8,and Nsp12 at a propor-tion of 1∶8∶24,the polymerase activity was markedly elevated compared to the control group,with a statistical significance level(P＜0.001).Furthermore,in the absence of Nsp3,Nsp4,and Nsp6,the inclusion of Nsp10-16 substantially augmented the activity of the RdRp,particularly in scenarios where Nsp9 was not introduced,achieving statistical significance(P＜0.001).In the pres-ence of Nsp3 and Nsp4,the RdRp activity was augmented further upon the addition of Nsp9,reac-hing a level of significance(P＜0.05).The data imply that Nsp9 is capable of enhancing the RdRp activity of SARS-CoV-2 exclusively in the context of Nsp3 and Nsp4 coexistence,suggesting that the stimulatory influence of Nsp9 on viral replication may be contingent upon the formation of double-membrane vesicles.

Magnetic resonance angiography(MRA)is a non-invasive imaging technique used to observe blood vessels.Quantitative analysis of MRA images enables visualization of vascular pathways,condition,and blood flow dynamics,which is essential for diagnosing vascular diseases such as vascular lesions,stenosis,and occlusions.Vessel segmentation serves as the fundamental basis for quantitative vascular analysis.However,the complex morphology of vessels,difficulties in labeling,and scarcity of accurate 3D vascular annotations pose significant challenges for MRA-based vessel segmentation.A strategy of selectively occluding vessels during model training is proposed to enhance the algorithm's capacity to capture the topological structure of blood vessels,thereby improving the continuity of vessel segmentation results.Additionally,a Refine network is incorporated to refine the binary segmentation results of the segmentation network,thereby further improving segmentation accuracy.Model training and testing are carried out using 42 cases of 3D MRA data from the public MIDAS dataset.For the test set,the 3D U-Net baseline model with vessel occlusion strategy shows a β0 Error of 1.2742±0.2103 and a β1 Error of 0.3393±0.0818,respectively,which are 0.1136 and 0.0280 lower than the baseline.The model integrating vessel occlusion strategy and Refine network achieves an average Dice score of 0.7105±0.0125,which is 0.0028 higher than the baseline.These results demonstrate that the proposed method effectively improves both vascular connectivity and segmentation accuracy.

Crohn 's disease (CD) is an intestinal inflammatory disease of unknown etiology, the pathophysiological mechanism is still unclear. The enteric nervous system (ENS) is responsible for the autonomous regulation of intestinal function. Therefore, ENS dysfunction may be the core of the pathophysiological mechanism of CD. Here, we review the pathophysiological mechanism by which ENS contributes to the development of CD, with a focus on the role of aberrant histological manifestations of ENS and plexitis in predicting the recurrence of CD following surgery.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To analyze and predict the biological properties and function of Treponema pallidum OmpH protein by bioinformatics methods, purify the target protein, and prepare polyclonal antibodies. Methods:From January 2024 to February 2025, the research team from the Department of Clinical Laboratory at The First Affiliated Hospital of Hunan Traditional Chinese Medical College (Hunan Province Directly Affiliated Traditional Chinese Medical Hospital) conducted a study employing integrative approaches combining bioinformatics analysis with animal experimentation. During this investigation, the coding sequence of the T. pallidum outer membrane protein H (TpOmpH) was systematically retrieved from the National Center for Biotechnology Information (NCBI) database. And the bioinformatics tools, such as Protparam, Protscale,SignalP 6.0,NetNGlyc-1.0,TMHMM2.0,NetPhos-3.1,SOPMA,AlphaFold3,IEDB,STRING,C-immsim were used to analyze and predict the biological and immunological characteristics of TpOmpH protein. The full length of TpOmpH gene was synthesized and was cloned into the pET28a to construct the recombinant plasmid pET28a-TpOmpH. The the expression of target protein was induced by IPTG and was purified using affinity chromatography. The TpOmpH protein was used to immunize mice and the anti-serum was harvested, then the titer of antibody was detected. Results:TpOmpH is a hydrophobic outer membrane protein with a molecular weight of 19.7 kDa and strong stability. The TpOmpH protein is located outside the cell membrane and contains 11 serine, 4 threonine, and 1 tyrosine phosphorylation site, but no glycosylation sites. The 77.91% of the amino acids in TpOmpH protein are alpha helix, 8.72% are extended strand, 10.47% are random coils, and 2.91% are beta turns. The tertiary structure predicted by AlphaFold3 is in its optimal state. The TpOmpH protein has 4 CTL epitopes, 4 linear epitopes, and 5 spatial epitopes. The TpOmpH protein can interact with Tp92,MutS,SurA,TPANIC_0600 and other proteins which may be involved in Tp invasion. TpOmpH protein can induce an increase in B cell count, antibody content, Th cell count, NK cell count, as well as the expression of various cytokines. High purity TpOmpH protein was obtained through Ni 2+ affinity chromatography, which is consistent with the theoretical molecular weight. TpOmpH protein can induce mice to secrete polyclonal antibodies with antibody titers higher than 1∶10 000. Conclusion:TpOmpH protein is a hydrophobic protein located on the outer membrane of Tp, can induce mice to secrete high titer antibodies, which providing experimental basis for the pathogenesis of Tp and vaccine development.