Acquired paralytic strabismus is a common neuromuscular disorder in adults,characterized by diplopia, visual confusion, impaired ocular motility, and ocular deviation, which severely affects the patient's quality of life and overall health. The disease has a complex etiology, encompassing multiple pathological mechanisms such as vascular pathologies, trauma, inflammation, neoplasms, and immune-related disorders. Treatment primarily focuses on addressing the underlying cause. While conventional Western approaches, such as medication and surgery, can alleviate symptoms, some carry the risk of adverse effects, and their long-term recurrence rates warrant careful consideration. Traditional Chinese medicine utilizes distinctive therapies such as herbal medicine, acupuncture, and other adjunctive therapies, which have shown promising therapeutic effects but are constrained by a lack of high-quality evidence from large-scale randomized controlled trials. This review systematically summarizes recent advances in the etiological classification and traditional Chinese and Western medical treatments of acquired paralytic strabismus. It innovatively summarizes the clinical features associated with different causes, analyzes current therapeutic strategies and research landscape, aiming to inform clinical practice and suggest future research directions.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective To evaluate the impact of incorporating two doses of varicella vaccine into the immunization program in Shanghai on the incidence of varicella, age-specific incidence, and varicella outbreaks in kindergartens and schools in Jinshan District, and to assess its prevention and control effects. Methods Descriptive epidemiological methods were used to analyze and compare the population distribution characteristics and the occurrence of varicella outbreaks before (2013-2017) and after (2018-2024) the implementation of the strategy. Interrupted time series (ITS) design and its segmented regression model were used to analyze the changes in the incidence of varicella in the two stages before and after the implementation of the vaccination of two doses of varicella vaccine, and to evaluate the short-term and long-term preventive and control effects of the strategy. Results After the incorporation of two doses of varicella vaccine into the immunization program, the average annual incidence of varicella in Jinshan District decreased from 82.19/100 000 (2013-2017) to 53.51/100 000 (2018-2024). The interrupted time series analysis showed that after the implementation of the strategy, the slope change in the incidence of varicella was -10.20/100 000 (t=-2.38, P=0.04), and the overall trend was downward (slope β₁+β₃= -8.34/100 000). Except for the 30-49 years old group, the incidence rates in all other age groups decreased to varying degrees. Among them, the 5-9 years old group had a better vaccine efficacy (VE) of 52.23% (95% CI: 49.07-60.65), followed by the 10-14 years old group. The number of potential varicella outbreaks and cluster outbreaks in nurseries, kindergartens, and schools across the district dropped significantly. Conclusion Incorporating two doses of varicella vaccine into the immunization program can effectively reduce the incidence of varicella and the number of varicella outbreaks in kindergartens and schools, which is of great significance for the prevention and control of varicella.

Objective:To investigate the expression of Neurexophilin 4(NXPH4)in hepatocellular carcinoma(HCC)and its clinical significance and function.Methods:Retrieved LIHC project data(mRNA expression profiles and clinical records)from TCGA,analyzed differential NXPH4 expression in HCC versus adjacent non-tumor tissues,and investi-gated correlations between NXPH4 expression and clinicopathological characteristics/prognostic outcomes in HCC.Using GOEA and GSEA to investigate potential biological functions of NXPH4 in hepatocellular carcinoma.Results:NXPH4 exhibited significant upregulation in 23 cancer types(P<0.05),with significant associations to advanced HCC progression markers including TNM stage(P<0.05),histologic grade(P<0.05),and vascular invasion(P<0.05).Clinically,elevated NXPH4 expression correlated with reduced OS(HR=1.64,95%CI:1.15-2.33,P=0.006)and DSS(HR=1.88,95%CI:1.19-2.96,P=0.007).The immune infiltration results showed that NXPH4 expression was significantly correlated with Th2 cells and Th17 cells(all P values<0.05).Furthermore,NXPH4 expression was positively correlated with the levels of several immune checkpoint markers:TIGIT(r=0.265),PD-1(r=0.297),CTLA-4(r=0.302),and LAG-3(r=0.179,all P<0.001).Gene enrichment analysis revealed NXPH4 was significantly enriched in:pattern specification process(P<0.001);receptor ligand activity(P<0.001);collagen formation(P=0.009);activation of matrix metalloproteinases(P<0.001);neuro-active ligand receptor interactions(P<0.001);and ALK2 signaling(P=0.039).Conclusion:NXPH4 is associated with clinical pathological staging and poor prognosis in HCC patients;NXPH4 is associated with oncogenic pathways and im-mune infiltration,and has high value in predicting patient prognosis and immunotherapy.

Objective:To explore the mediating effect of psychological resilience between family function and post-traumatic growth in young and middle-aged stroke patients,and to provide a theoretical basis for formulating targeted intervention strategies.Methods:This study was a prospective study,a total of 80 young and middle-aged stroke patients admitted in our hospital from February 2023 to August 2024 were selected by the convenient sampling method.The general information of the patients was collected by using a self-made questionnaire,the Connor-Davidson resilience scale(CD-RISC),family care index questionnaire(APGAR)and post-traumatic growth inventory(PTGI)were used to measure psychological resilience,family function and post-traumatic growth levels respectively.The correlations among family function,post-traumatic growth and psychological resilience were analyzed through Person correlation analysis.Construct models of family function and post-traumatic growth to exam ine the mediating effect of psychological resilience,and the scatter plots of correlations and the mediating effect model diagrams were drawn.Results:There were significant differences in the scores of family function,psychological resilience and post-traumatic growth among patients with different characteristics(P＜0.05).The scores of family function,psychological resilience and post-traumatic growth of patients with characteristics such as being married,having a higher educational level,being slightly dependent on daily living skills and having their spouses as the main caregivers were significantly higher(P＜0.05).Pearson correlation analysis showed that family function was significantly positively correlated with psychological resilience(r=0.951,P＜0.05),family function was significantly positively correlated with post-traumatic growth(r=0.939,P＜0.05)and post-traumatic growth was significantly positively correlated with post-traumatic growth(r=0.959,P＜0.05).The structural equation model indicates that psychological resilience plays a partial mediating role between family function and post-traumatic growth,with the mediating effect accounting for 28.42％(95％CI:0.12-0.30)of the total effect.Conclusion:Family function can play an indirect role through psychological resilience to promote post-traumatic growth in young and middle-aged stroke patients,clinically,the collaborative intervention of family function and psychological resilience should be emphasized.

Objective:This paper investigates residents'awareness and preference for Traditional Chinese Medicine intelligent diagnostic device(hereinafter referred to as the device),and provides basis and suggestions for further promoting the integrated development of artificial intelligence and traditional Chinese medicine clinical diagnosis.Method:A random sampling survey was conducted,and a Discrete Choice Experiment was designed to conduct an offline survey in Beijing.Use chi square test,count analysis,and conditional Logit model for data analysis.Result:A total of 480 valid questionnaires were collected and surveyed.Most respondents have heard of it(58.96%),a few have used it(31.67%),and most would recommend the device(71.25%).Knowing and using experience will increase the probability of recommendation.Residents attach the highest importance to annual average expenses;More inclined to use devices in the community that can see family data,connect data and hospitals,monitor electrocardiogram,provide comprehensive health reports,and have low annual costs;Willing to pay an additional 572 yuan per year for the comprehensive health report device.Conclusion:There should be more collaboration with hospitals in usage scenarios and cloud data.In addition,manufacturers should enrich output information and service methods of the e.

Aim To perform high-throughput screen-ing of immunomodulatory traditional Chinese medicine(TCMs)based on an in vitro B cell differentiation-antibody secretion model,identifying active herbal candidates with immune-enhancing properties to pro-vide novel therapeutic options and theoretical support for influenza virus treatment in immunocompromised in-dividuals.Methods B cells were stimulated with dif-ferent concentrations of cytosine-phosphate-guanine oli-godeoxynucleotide 2006(CpG)and nterleukin-2(IL-2)to promote proliferation,differentiation,and anti-body secretion,and the effects of varying concentra-tions of the solvent DMSO were also evaluated.The op-timal conditions for the B cell differentiation-anti-body secretion model were determined based on the se-cretion levels of three antibody isotypes.The feasibility of the model was further validated using rapamycin,a known B cell function inhibitor.On this basis,a high-throughput screening platform for immunomodulatory a-gents was optimized and established.Subsequently,the immune-enhancing activity of 465 polarity extract from TCMs was evaluated.Results The optimal con-ditions for the model were determined as 2 mg·L-1 CpG,1.67 × 106 nkat·L-1 IL-2,and DMSO with a volume fraction of 0.1％.Rapamycin effectively inhib-ited B cell differentiation into plasmablast and signifi-cantly reduced antibody production,indicating the reli-ability of the model.Multiple rounds of screening re-vealed that the dichloromethane extract of licorice,the dichloromethane extract of Vinegar-processed Curcumae Rhizoma,the cyclohexane extract of Honey-prepared Radix Asteris,and the aqueous extract of Siphonostegia chinensis Benth were identified to significantly promote both B cell proliferation and differentiation and anti-body secretion at a concentration of 600 μg·L-1.Conclusion This study successfully optimizes an in vitro B cell differentiation-antibody secretion model and identifies several TCM extracts,including licorice,with potential immune-enhancing activity.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.

This study explored the effects and underlying mechanism of Raf kinase inhibitory protein(RKIP)on apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid.Bone marrow-derived mast cells(BMMCs)were isolated and cultured from RKIP knockout(KO)and wild-type(WT)C57BL/6 mice.Cells were divided into control and sensitized groups.The sensitized group was incubated for 24 h in RPMI1640 medium containing 10%serum from mice infected with E.granulosus,then activated for 3 h or 6 h with E.granulosus cyst fluid.The control group was incubated for 24 h in RPMI1640 medium,and then received an equal vol-ume of PBS.Cells and supernatants were collected for analysis.Flow cytometry was used to detect the expression of CD117 and FcεRⅠα on BMMCs.The levels of β-hexosaminidase,IL-4,and TNF-α in the supernatant were quantified with ELISA.Western blot analy-sis was used to assess expression changes in RKIP,apoptosis-related proteins,and pathway proteins in BMMC before and after sensi-tization.Flow cytometry analysis revealed that after 4 weeks of induction,the CD117 and FcεRⅠα double-positivity rates on both WT and KO BMMC exceeded 90%.ELISA indicated that the E.granulosus cyst fluid resulted in significantly greater β-hexosaminidase re-lease(F=16.88,P<0.05),and levels of IL-4(F=16.51,P<0.05)and TNF-α(F=9.78,P<0.05)in the KO sensitized group than the WT sensitized group.With respect to the WT control group,the WT sensitized group showed significantly down-regulated pro-tein expression levels of RKIP(F=8.20,P<0.05)and Bcl-2(F=101.40,P<0.01)after 3 h,but significantly up-regulated levels of p-PI3K(F=8.04,P<0.05),p-Akt(F=32.52,P<0.01),p-P65(F=13.29,P<0.05),and cleaved-caspase-3(F=46.34,P<0.01).With respect to the WT sensitized group,the KO sensitized group showed significantly up-regulated protein expression of p-PI3K(F=8.45,P<0.05),p-Akt(F=8.58,P<0.05),p-P65(F=11.02,P<0.05),and Bcl-2(F=84.50,P<0.001)after 3 h,but significantly down-regulated expression of cleaved-caspase-3(F=15.66,P<0.05).In conclusion,RKIP may inhibit the PI3K/Akt/NF-κB pathway,thereby inducing apoptosis in mast cells sensitized by E.granulosus cyst fluid.This process may help ease aller-gic reactions caused by mast cells in echinococcosis,thus offering a promising new approach for preventing and treating such reactions.