Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

Esophageal squamous cell carcinoma is the main histological type of esophageal cancer in China, which seriously threatens the health of people. The application of immunotherapy, mainly immune checkpoint inhibitors, has greatly improved the prognosis of patients with esophageal squamous cell carcinoma, but the efficacy of treatment is still limited. Tertiary lymphoid structure (TLS) is an ectopic organized lymphoid structure that accumulates in non-lymphoid organs. Previous studies have found that TLS in esophageal squamous cell carcinoma is associated with better patient outcomes and enhanced immunotherapy efficacy. Based on current researches about TLS in esophageal squamous cell carcinoma, this paper reviews the relationship between TLS and the prognosis and immunotherapy of patients. We hope to provide reference for the precise immunotherapy of esophageal squamous cell carcinoma.

Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

ObjectiveTo construct a prediction model for high responsiveness to short-term aerobic training in patients with Parkinson's disease (PD) based on dual-task gait assessment, and to provide evidence for identifying individuals who are most likely to benefit from such interventions. MethodsA total of 42 patients with PD who visited the outpatient clinic of Tianjin Huanhu Hospital between August 29, 2023 and December 19, 2024 were enrolled. All participants completed a 4-week home-based aerobic cycling training program and underwent dual-task gait assessments pre- and post-training. Patients were classified into high-response group (n = 12) and low-response group (n = 30) according to whether the improvement in gait speed reached the minimal clinically important difference of 0.1 m/s. The clinical validity of this grouping was verified by comparing differences in cardiopulmonary exercise testing parameters and dual-task gait indicators between the two groups pre- and post-training. Based on baseline characteristics, Firth's penalized maximum likelihood logistic regression was applied to construct a predictive model for high responsiveness, and the discriminative performance of the model was assessed preliminarily. ResultsThe high-response group showed significantly greater improvement in gait speed, step length, cadence and the anaerobic threshold to maximal oxygen uptake ratio after training compared with the low-response group (P < 0.05), confirming the clinical validity of the grouping. The baseline anaerobic threshold to maximal oxygen uptake ratio (OR = 3.348), body mass index (OR = 2.229) and age (OR = 0.428) demonstrated certain discriminative ability in the present sample. The area under the receiver operating characteristic curve was 0.831, with an overall prediction accuracy of 81.0%, specificity of 83.3% and sensitivity of 75.0%. Robustness of the model was confirmed via internal validation using the Bootstrap method, which suggested that the results were informative, but further validation was still required. ConclusionThe anaerobic threshold/maximal oxygen uptake ratio, body mass index and age may predict the response to short-term aerobic training in patients with PD.

Abstract Adolescents are a high risk group for non suicidal self injury (NSSI), and the severity of the issue has been increasing. However, stigma originating from self perceptions, the public, and healthcare professionals poses significant barriers to help seeking and recovery among adolescents with NSSI. The paper systematically reviews the main intervention strategies targeting NSSI related stigma in adolescents, along with their effectiveness, from three perspectives: educational approaches, contact based interventions, and public advocacy against stigma, aiming to inform the development of a scientific, effective, and multi stakeholder collaborative integrated intervention framework to provide a basis for reducing and ultimately eliminating stigma associated with adolescent NSSI.

The surgical management of empyema (excluding those caused by mycobacterium tuberculosis and non-tuberculous mycobacteria) is rapidly evolving towards minimally invasive, precise, and stepwise approaches. The traditional three-stage classification (exudative, fibrinopurulent, and organizing) has limitations in guiding dynamic clinical decision-making. For the first time, this consensus explicitly identifies two critical junctures in the pathological progression of empyema: "early transformation" (stage Ⅰ to Ⅱ) and "late transformation" (stage Ⅱ to Ⅲ), and thereby constructs a corresponding "identification-early warning-intervention" stepwise therapeutic framework. The consensus emphasizes that proactive debridement via video-assisted thoracoscopic surgery should be performed during the early transformation phase to halt disease progression. Conversely, during the late transformation phase, therapeutic goals should be rationally adjusted to prioritize adequate drainage, avoiding futile pleural decortication. Moreover, the consensus underscores the pivotal role of precise perioperative etiological diagnosis (e.g. metagenomic nest-generation sequencing) and standardized anti-infective therapy. Integrating practical experiences from multiple thoracic surgery centers in China and relevant evidence-based literature, this consensus formulates recommendations on the precise definitions of staging, surgical indications for each phase, key technical points, perioperative management, and training systems. It aims to promote the standardized and individualized surgical management of empyema, ultimately optimizing patient prognosis.

Objective To investigate the efficacy of subcutaneous flap and/or pedicled penile skin flap combined with advancement flap coverage technique in the treatment of urethrocutaneous fistula(UCF)secondary to failed repair and to improve the success rate. Methods The clinical data of 36 UCF patients after urethral repair admitted to our hospital during Jan. 2020 and Jan. 2024 were retrospectively analyzed. According to the location and surrounding condition of the fistula, the fistula was closed without tension, the subcutaneous flap and/or pedicled penile skin flap was combined with advancement flap coverage technique. The effects of the treatment were followed up. Successful repair was defined as unobstructed urination, no recurrence of fistula and no urethral stricture. Results The patients' age was(25.7±11.6)years, and the diameter of fistula was(8.1±2.2)mm. UCF occurred in 24 cases after hypospadias repair, and in 12 cases after the repair of other urethral injuries, including 2 cases of urethral compression injury after improper indwelling catheterization, 2 cases of urethral stone removal, 2 cases of urethral diverticulum repair, 2 cases of circumcision repair, 1 case of congenital anal atresia repair, and 3 cases of other urethral repair. The primary repair success rate was 83.3%(30/36). Among the 6 patients with unsuccessful primary repair, 3 were cured with a secondary repair, 1 was cured after wound dressing, and 2 were lost to follow-up. The primary repair success rates of penile shape, penile scrotal junction, and perineal urethral skin fistulas were 82.1%(23/28), 83.3%(5/6), and 100%(2/2), respectively. The primary repair success rates for fistulas with diameter ≤1.0 cm and＞1.0 cm were 85.2%(23/27)and 77.8%(7/9), respectively; for single and two urethrocutaneous fistulas, the success rates were 84.8%(28/33)and 66.7%(2/3); for patients with 1 and ≥2 previous repair attempts, the success rates were 87.5%(14/16)and 80.0%(16/20). During the follow-up of(15.1±3.5)months, no recurrence of fistula occurred, and all patients experienced unobstructed urination with a maximum urinary flow rate of(19.5±4.2)mL/s. Conclusion The failure rate of UCF repair is still high. Based on the location of the fistulas and the condition of the surrounding tissue, the surgical success rate can be improved by utilizing subcutaneous flap and/or pedicled penile skin flap combined with advancement flap coverage technique. This approach allows for tension-free suturing and multi-layer closure of the fistula.

This study was aimed at investigating the immunoregulatory function of Mycobacterium tuberculosis Rv3641c gene in modulating host type Ⅰ interferon responses.The shuttle plasmid pMV261 was used to construct Rv3641c overexpression recombinant Mycobacterium smegmatis,and the biological characteristics of the recombinant bacteria were analyzed to explore the effect of Rv3641c on the growth curve,colony morphology and stress resistance of Mycobacterium.Subsequently,RAW264.7 cells were infected with Rv3641c overexpressing Mycobacterium smegmatis,and the transcriptional expression of genes related to the inhibition of type I inter-feron pathway was determined by RT-PCR.The expression level of IFN-βprotein was determined by ELISA,and the intracellular sur-vival level was determined.As a result,the recombinant rMS::pMV261-Rv3641c was successfully constructed.The results of biologi-cal characteristics analysis showed that Rv3641c did not affect the growth of mycobacteria,but significantly changed the colony mor-phology of mycobacteria and improved its resistance to H2O2.The results of recombinant bacteria infection experiments showed that Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1β in host cells,and Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1βin host cells.The results of intracellular colonization experiments showed that the intracellular mycobacte-ria in the overexpression recombinant bacteria infection group were significantly higher than those in the empty vector group,indicat-ing that Rv3641c could promote the intracellular surviv al of mycobacteria.In summary,the Rv3641c gene of M.tuberculosis can inhibit the host type I interferon response and promote the intracellular survival of M.tuberculosis,which provides a new idea for further explor-ing the immune escape function of M.tuberculosis and the discovery of new targets for anti-tuberculosis drugs.

Objective To observe the clinical efficacy of Qishao Huoxue Prescription in treating low back pain caused by lumbar disc herniation with qi stagnation and blood stasis syndrome.Methods Totally 80 patients of lumbar disc herniation with qi stagnation and blood stasis syndrome were divided into observation group and control group according to random number table method,with 40 cases in each group.The observation group received oral administration of Qishao Huoxue Prescription,while the control group received oral celecoxib capsules for 3 weeks.Follow-ups were conducted after 1 month and 3 month of treatment,and the clinical efficacy of two groups after 3 months of treatment was evaluated.The Visual Analog Scale(VAS)scores,Japanese Orthopaedic Association Assessment of Treatment Score(JOA),Oswestry Disability Index(ODI)and Quality of Life(SF-36)scores for pain before treatment,1 and 3 weeks after treatment,and 1 and 3 months after treatment in two groups were observed;the blood flow changes of two groups before and after 3 weeks of treatment were observed,including whole blood high shear,medium shear,and low shear viscosity,plasma viscosity,and fibrinogen(FIB);adverse reactions in both group were recorded.Results The total effective rate in the observation group was 97.5%(39/40),significantly higher than 87.5%(35/40)in the control group(P<0.05).At 1 and 3 weeks of treatment and 1 and 3 months after treatment,VAS scores and ODI scores significantly decreased compared to before treatment,while JOA scores and SF-36 scores significantly increased in both groups.The improvement in scores in the observation group was better than that in the control group(P<0.01).The observation group showed a significant decrease in blood high,medium,and low shear viscosity,PV and FIB levels after 3 weeks of treatment compared to before treatment(P<0.05),and all levels were lower than those in the control group(P<0.05).No significant adverse reactions were observed in both groups.Conclusion Qishao Huoxue Prescription can significantly improve the clinical symptoms,hemorheological indicators,and quality of life of low back pain caused by lumbar disc herniation with qi stagnation and blood stasis syndrome,with good safety.

BACKGROUND:Bone marrow mesenchymal stem cells are one of the sources of adipocytes and express all renin-angiotensin system components,but the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue is not clear.OBJECTIVE:To observe the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue and investigate the role of angiotensin 1a receptor knockout in effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipocytes and its potential mechanisms.METHODS:After isolation and culture of bone marrow mesenchymal stem cells in wild-type and angiotensin 1a receptor knockout SD rats,the cells were cultured to the third generation and randomly divided into four groups:wild type group,knockout group,wild type+angiotensin Ⅱ group,and knockout+angiotensin Ⅱ group.The differentiation was induced in the brown fat induced differentiation medium for 14 days.Angiotensin Ⅱ(100 nmol/L)was added for intervention when the differentiation medium was changed each time in the latter two groups.Western blot assay,qRT-PCR,immunofluorescence,and other methods were used to detect the expression of induced differentiation,lipolysis,β oxidation,and mitochondrial biogenesis in brown fat.RESULTS AND CONCLUSION:Angiotensin Ⅱ could inhibit the browning of rat bone marrow mesenchymal stem cells.Knockout of angiotensin 1a receptor could improve the inhibitory effect of angiotensin Ⅱ on brown lipid formation of rat bone marrow mesenchymal stem cells by promoting lipolysis,enhancing fatty acid β oxidation,promoting mitochondrial biogenesis,and enhancing mitochondrial function.These findings provide new research directions and potential therapeutic targets for obesity treatment,revealing the important role of renin angiotensin systems in fat metabolism and its potential as a therapeutic target.