Cerebral small vessel disease (CSVD) is an important cause of stroke and cognitive impairment, with complex pathogenesis and limited therapeutic options. Although monogenic hereditary CSVD has a low incidence, its well-defined causative genes provide a unique " natural model" for revealing the core molecular pathways of CSVD. Based on previous studys, this article systematically sorts out the newly identified pathogenic genes of monogenic CSVD, such as NIT1, MAP3K6 and ARHGEF15, and precisely identifies core pathophysiological processes including vascular smooth muscle cell dysfunction and extracellular matrix homeostasis imbalance. Furthermore, it reviews the latest advances in genome-wide association studies (GWAS) on sporadic CSVD and its imaging markers, and confirms an overlap in their genetic architectures. Finally, this article discusses the research strategy of integrating multi-omics data such as transcriptomics and proteomics to deeply analyze the biological mechanisms of risk variants, and summarizes the clinical translational value of genetic research in the precision diagnosis, risk stratification, drug target mining and drug repositioning of CSVD.

ObjectiveTo systematically review the effect of dual-task training (DTT) on mobility and balance in stroke patients. MethodsCNKI, Wanfang Data, VIP, PubMed, Web of Science, Embase and Cochrane Library were searched for randomized controlled trials (RCT) on DTT in stroke rehabilitation from inception to June, 2025. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool and the PEDro scale. Meta-analysis was performed using RevMan 5.4. ResultsA total of eleven RCT involving 517 stroke patients were included, and the scores of PEDro scale were four to eight. DTT was more effective on the score of Fugl-Meyer Assessment-Lower Extremity (MD = 3.70, 95%CI 1.88 to 5.53, P < 0.001) and Berg Balance Scale (BBS) (MD = 3.04, 95%CI 1.58 to 4.49, P < 0.001), fall incidence (OR = 0.32, 95%CI 0.11 to 0.87, P = 0.025), gait speed under a single-task condition (MD = 0.08, 95%CI 0.03 to 0.12, P = 0.002), gait speed under a dual-task condition (MD = 0.13, 95%CI 0.10 to 0.16, P < 0.001), Timed Up and Go Test time (MD = -2.78, 95%CI -3.85 to -1.72, P < 0.001), and score of modified Barthel Index (MD = 4.77, 95%CI 1.88 to 7.66, P = 0.001). Subgroup analysis indicated that motor-motor DTT was more effective than cognitive-motor DTT on BBS scores and single-task gait speed. ConclusionsDTT can improve mobility and balance in stroke patients, especially with motor-motor tasks.

OBJECTIVE To develop and validate interpretable machine learning models for predicting the risk of medication-related osteonecrosis of the jaw （MRONJ） and surgical outcomes， thereby providing quantitative support for MRONJ risk assessment and treatment decision-making.METHODS Two study cohorts were established. Cohort A adopted a nested case-control study design to develop a predictive model for the risk of MRONJ onset. Cohort B comprised patients with MRONJ from Cohort A who underwent surgical treatment and met the follow-up eligibility criteria， and employed a prospective follow-up cohort study design to develop a predictive model for the efficacy of MRONJ surgery. After missing-data processing， variable standardization， and encoding， predictive features were selected using the least absolute shrinkage and selection operator （LASSO） regression， and collinearity was assessed using the variance inflation factor （VIF）. Random Forest （RF）， eXtreme Gradient Boosting （XGB）， Multi-layer Perceptron （MLP）， Support Vector Machine （SVM）， and Gaussian Naive Bayes （NB） models were subsequently developed using the selected features. Hyperparameter optimization and internal performance evaluation were performed using two-level nested cross-validation repeated 20 times. In Cohort B， the synthetic minority over-sampling technique （SMOTE） was applied within the inner training folds to address class imbalance. Model performance was comprehensively evaluated using the receiver operating characteristic （ROC） curve， the precision-recall （PR） curve， calibration curve， and decision curve analysis （DCA）. Shapley additive explanations （SHAP） were used to quantify the relative contributions of individual clinical features to model predictions.RESULTS Seven clinical features， including alkaline phosphatase and tooth extraction， were retained for Cohort A； whereas eight clinical features， including age and duration of medication use， were retained for Cohort B. In Cohort A， the area under the ROC curve， the area under the PR curve， Brier score， sensitivity， and specificity of the RF model were 0.94， 0.92， 0.09， 0.92， and 0.85， respectively； the corresponding values in Cohort B were 0.93， 0.93， 0.12， 0.83， and 0.93， respectively. The results of calibration curves and DCA indicated that the RF models achieved favorable calibration and clinical net benefit， with VIF values for all variables below 5. SHAP visualization results showed that alkaline phosphatase， tooth extraction， and cumulative drug dose made substantial contributions to MRONJ risk prediction in Cohort A， whereas age， duration of medication use， and MRONJ stage contributed substantially to surgical outcome prediction in Cohort B.CONCLUSIONS The RF-based models for predicting MRONJ risk and surgical outcomes demonstrated good discrimination， accuracy of probabilistic predictions， and potential clinical utility during internal validation. These models may provide decision support for comprehensive MRONJ risk management and individualized clinical decision-making. However， external validation in independent， multicenter， and geographically diverse cohorts is still required.

Foodborne illnesses caused by Salmonella pose significant threats to worldwide public health safety.In this study,a rapid method for screening viable Salmonella in oyster sauce and milk was developed by utilizing an electronic microbial growth analyzer(EMGA).Target food samples were diluted 10-fold with RVS broth and loaded into test tubes.Test tubes were positioned in the EMGA to determine the bacterial growth curves and the time required to reach the maximum growth rate(Tmgr).Using Salmonella typhimurium(S.typhimurium)asan model species,there was linear relationship between the logarithmic value of viable bacterial concentration(lgC)and Tmgr over the range of 5×101-5×106 CFU/mL,with a detection limit of 10 CFU/mL.For oyster sauce,the regression equation was Tmgr(min)=-80.775lg[C/(CFU/mL)]+754.96(R2=0.9907),and the recovery rates of S.typhimurium ranged from 95.2%to 119.8%,with relative standard deviations(RSD)ranging from 3.5%to 16.3%.For milk,the regression equation was Tmgr(min)=-71.922 lg[C/(CFU/mL)]+618.65(R2=0.9985),with recovery rates ranging from 98.4%to 110.6%and RSD ranging from 6.4%to 12.8%.The EMGA method required only one portable instrument,and involving only three manual steps,i.e.,dilution,transfer,and insertion.When S.typhimurium contamination reached 106 CFU/mL,the total time consumption,from the unwrapping of samples to the readout of bacterial concentration,was no more than 7 h.When applied to detection of actual oyster sauce and milk samples,the new method demonstrated strong consistency with plate counting results in positive detection rates.This method was superior to the plate counting method,which was generally considered as a gold standard,in terms of accuracy,precision,simplicity and efficiency,representing a promising alternative for the on-site screening and quantification of viable Salmonella in oyster sauce and milk products.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

Objective:To explore the perioperative precautions, rehabilitation effect, and affecting factors in cochlear implantation (CI) among patients with hereditary syndromic hearing loss.Methods:This was a retrospective cohort study. 47 patients diagnosed as hereditary syndromic deafness were treated in the Department of Otolaryngology-Head and Neck Surgery of the Chinese PLA General Hospital from 2010 to 2021, including 26 males and 21 females, aged 0.9-25 years. All patients received unilateral or bilateral CI. Clinical manifestation combined with genetic testing was used to diagnose syndromic hearing loss. The risks and precautions of CI in these patients were summarized from preoperative imaging, intraoperative observations, and postoperative complications. Single factor linear regression and multiple linear regression models in SPSS 26.0 software were used to evaluate the effects of various factors on auditory and speech rehabilitation after CI for syndromic hearing loss. The postoperative outcomes were analyzed through aided hearing thresholds, categories of auditory performance (CAP) scale, and speech intelligibility rate (SIR) scale.Results:Thirteen kinds of syndromes, totally 47 cases, including CHARGE (20 cases), Waardenburg (9 cases), Autosomal dominant deafness-onychodystrophy (DDOD, 4 cases), Pendred (3 cases), Noonan Syndrome with Multiple Lentigines (NSML, 2 cases), Branchio-Oto-Renal (BOR, 2 cases), Bart-Pumphery (1 case), Perrault (1 case), Kabuki (1 case), Frontometaphyseal dysplasia type 2 (FMD 2, 1 case), Mandibulofacial dysostosis Guion-Almeida type (MFDGA, 1 case), Coffin-Siris (1 case), and 10q26.12-q26.3 del (1 case), were enrolled. The perioperative special management included the following measures. For patients with cardiac and/or cartilage development issues, preoperative assessments of cardiac function and/or laryngeal cartilage development were performed to minimize anesthetic risks. For patients with mild intellectual disability and/or an auditory neuropathy phenotype, preoperative communication with the patients′ families was conducted to explain the limitations of CI and assist in setting reasonable expectations. For syndromic hearing loss patients who commonly present with inner ear malformations, facial nerve anomalies, and/or intraoperative cerebrospinal fluid leakage, appropriate electrodes were selected prior to surgery, intraoperative facial nerve monitoring and careful cerebrospinal fluid leak repair were conducted, respectively. For patients with NSML accompanied by coagulation issues, the postoperative compression bandaging duration was extended to reduce the risk of hematoma formation. The daily duration of cochlear implant use, the presence of cochlear malformation, and developmental delay were independent factors influencing postoperative CAP scores. The daily duration of cochlear implant use, developmental delay, and unilateral or bilateral CI were independent factors influencing postoperative SIR scores.Conclusions:Hereditary syndrome deafness is a rare disease that affects multiple organs and causes extensive functional impairment. Before CI, a comprehensive evaluation of major affected organ functions is required to assess anesthetic and surgical risks. Genetic diagnosis not only identifies the molecular etiology of patients with syndromic hearing loss and reveals rare phenotypes, but also aids in prognostic evaluation. The main factors affecting CI outcomes in patients with syndromic hearing loss include the presence of cochlear malformations, developmental delays, daily duration of cochlear implant use, and bilateral implantation status.

Objective To explore the resistance mechanism of tigecycline insensitivity of multidrug-resistant Acine-tobacter baumannii,and provide reference for clinical rational antimicrobial use as well as prevention and control of healthcare-associated infection.Methods 22 strains of tigecycline insensitive multidrug-resistant Acinetobacter bau-mannii(TIS-MDR-AB)and 22 strains of tigecycline sensitive multidrug-resistant Acinetobacter baumannii(TS-MDR-AB)isolated clinically from the First Affiliated Hospital of Guangzhou Medical University from April 2022 to May 2023 were collected.Efflux pump phenotype inhibition assay was performed using efflux pump inhibitor car-bonyl cyanide m-chlorophenylhydrazone(CCCP).The main efflux pump genes(adeB,adeG,adeJ),as well as tigecycline-resistant gene tet(X),were screened by polymerase chain reaction(PCR)technique,and their mRNA expression levels were detected by real-time fluorescence quantitative PCR.Mutations in the efflux pump regulatory gene adeRS were analyzed by Sanger sequencing analysis.Results The detection rates of efflux pump genes adeB,adeG and adeJ were all above 95％in two MDR-AB groups,and tet(X)gene was not detected.Efflux pump inhibi-tor assay showed that the minimum inhibitory concentration(MIC)of TIS-MDR-AB strains decreased after adding CCCP,3 strains showed positive efflux pump phenotype.The mRNA expression level of MDR-AB adeB in the TIS-MDR-AB group was higher than that in the TS-MDR-AB group(P＜0.01),while the expression of adeG and adeJ genes was no statistically different.Multiple mutations were found in the adeR and adeS genes,the adeS of 2 strains was inserted ISAba1,and 3 strains were inserted ISAba13.Conclusion The overexpression of adeABC in the efflux pump system may play an important role in the mechanism of reduced sensitivity of MDR-AB to tigecycline,and its overexpression may be related to the insertion sequence or mutation in the efflux pump regulatory gene adeRS.

mRNA therapy is an emerging treatment that has become a frontier and hot topic in the field of biomedicine.To explore the trend in the development of mRNA therapy,this paper conducts an analysis from the perspectives of papers and patents,examining multiple dimensions including development trend,research areas,and high-value research.The study reveals the following findings:Global research in mRNA therapy is growing rapidly.Basic research mainly focuses on oncology,chemistry-multidisciplinary,biochemistry and molecular biology,while applied research centers on mRNA concerning genetic engineering,isolation,synthesis,purification,and the development of medicines.High-value research mainly centers on topics such as mRNA delivery,composition,manufacture,modification,and the development of various mRNA-based therapies.