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.

Objective To explore the effect of miR-125a-5p on thymic regulatory T cell(Treg)in mice with experimental auto-immune myasthenia gravis(EAMG).Methods The EAMG model was established by immunoinduction with murine-derived acetylcho-line receptor α subunit 97-116 peptide and randomly divided into control group and EAMG group,and the mice were subjected to Len-non scoring and low-frequency repetitive electrical stimulation experiments to evaluate the model.To further explore the effect of miR-125a-5p on Treg cells,EAMG mice were injected with negative control adenovirus and miR-125a-5p-inhibited adenovirus by tail vein injection respectively,and the experimental groups were the negative control group and miR-125a-5p inhibiting group.The mRNA expression levels of miR-125a-5p and forkhead box protein P3(Foxp3)were detected by real-time fluorescence quantitative polymer-ase chain reaction(RT-qPCR),while the protein expression level of Foxp3 was detected by Western blot.The percentage of the number of Treg cells was detected by flow cytometry,and serum concentrations of interleukin-10(IL-10)and transforming growth factor-β1(TGF-β1)were assessed using enzyme-linked immunosorbent assay(ELISA).Results The EAMG mouse model was successfully established.Compared to the control group,the EAMG group exhibited a significantly higher Lennon score,positive responses to low-frequency repetitive electrical stimulation at 5Hz,and an upregulated expression of miR-125a-5p,downregulated of Foxp3mRNA and protein,reduced percentage number of Treg cells,and decreased expression of IL-10 and TGF-β1.Upon inhibition of miR-125a-5p expression in EAMG mice,compared with the negative control group,the expression of miR-125a-5p in the miR-125a-5p inhibiting group was decreased,and the Lennon score was decreased,Foxp3mRNA and protein expression were increased,with a significant in-crease in the percentage of Treg cells and enhanced expression of IL-10 and TGF-β1,and the differences were all statistically signifi-cance(P＜0.05).Conclusion The expression of miR-125a-5p was upregulated in EAMG.Inhibition of miR-125a-5p expression led to upregulation of Foxp3,an increase in the number of Treg cells,elevated levels of IL-10 and TGF-β1,and attenuation of myas-thenia gravis symptoms in EAMG mice.These results suggest that miR-125a-5p may be involved in developing myasthenia gravis dis-ease by affecting Foxp3,leading to decreased Treg cell numbers and abnormal function.

Objective To explore the latent profile of health-promoting lifestyle in patients with lumbar disc herniation treated conservatively and analyze its influencing factors,so as to provide reference for the develop-ment of targeted interventions.Methods Patients with conservative treatment of Lumbar Disc Herniation at the orthopedic outpatient clinic of a tertiary hospital in Guangzhou from March to December 2024 were selected as study subjects.General Information Questionnaire,Health-Promoting Lifestyle Profile Revised-Ⅱ,Visual Analogue Scale,Oswestry Disability Index and Social Support Rating Scale were used for the investigation.Latent profile analysis was used to explore the potential categories of health-promoting lifestyle in patients with lumbar disc her-niation and the influencing factors were identified by univariate analysis and disordered multiple logistic regression analysis.Results A total of 422 lumbar disc herniation patients treated conservatively were included and the score of Health-Promoting Lifestyle Profile Revised-Ⅱ Scale was(102.44±13.19)points.The health-promoting lifestyle of patients with lumbar disc herniation can be divided into three potential profile:low health promotion group-low responsibility and less exercise type(18.7%),balanced health promotion group(51.7%)and high health promotion group-spiritual social leading type(29.6%).The results of logistic regression analysis showed that course of disease,oswestry disability index,social support level and take regular physical exercise are the influenc-ing factors of health-promoting lifestyle in patients with conservative treatment of lumbar disc herniation(P<0.05).Conclusions There is heterogeneity in the health-promoting lifestyle in patients with conservative treat-ment of lumbar disc herniation.Nursing staff can carry out targeted interventions according to the latent profile type of health-promoting lifestyle in lumbar disc herniation patients treated conservatively to improve their health-promoting lifestyle.

Objective Genome structural equation modeling(GSEM)was used to study the shared genetic structure between Alzheimer's disease(AD)and eight cardiovascular diseases(CVD).Methods In this study,based on AD and CVD data from large consortia and genome-wide association studies,we used chained unbalanced score regression to assess the genetic correlation between the diseases;GSEM was introduced to cross-validate with exploratory factor analysis at odd chromosomes and validation factor analysis at even chromosomes,and pathway analysis was combined to establish three-factor,cofactor,and bifactorial models,so as to reveal the complex genetic relationships between the diseases.Additionally,a cross-validation was performed by swapping the positions of odd and even chromosomes.Results The nine selected diseases can be explained by a three-factor model consisting of three independent factors;a cofactor model explains the relationship between a cofactor and each disease;and an extended two-factor model(a combination of the three-factor model and the cofactor model)performs best in fitting the study data.Conclusion GSEM can be used to explore the shared genetic structure between AD and CVD to discover their interactions,laying a methodological foundation for understanding the genetic relationship between complex diseases.

Objective The Bayesian joint model was applied to predict conversion from mild cognitive impairment(MCI)to Alzheimer's disease(AD),and to compare time effect in longitudinal outcomes,and functional forms for the longitudinal outcomes that are included in the survival model.Methods The longitudinal sub-model used generalized linear mixed models to model the trajectory of longitudinal neuropsychological tests changes pattern,and the survival sub-model adopted a Cox proportional risk model.The longitudinal sub-model utilized two forms of effects,t and t2,and the link structures of longitudinal sub-model and survival sub-model adopted three functional forms(updated value,slope,and area).The data were divided into training and validation sets according to 7∶3,the model parameters were estimated based on Bayesian algorithm,and the dynamic AUC was used to evaluate model prediction performance.Results There were 374(54.20％)of 690 patients with MCI progressed to AD during the follow-up period.In training set,the results of Bayesian joint model with a time effect of t and area effect of three longitudinal neuropsychological tests were optimal,with a mean dynamic AUC of 0.8336.The APOEε4 gene and a low functional activities questionary were risk factors for MCI conversion to AD.The dynamic AUCs of the joint model with the t time effects and area effect for longitudinal data were above 0.75 in the validation sets.Conclusion The application of multivariate Bayesian joint model to MCI risk prediction may provide a theoretical basis for individualized interventions for cognitive impairment and inform statistical methods for survival modeling of chronic diseases.

Objectives:This study aims to investigate the relationship between neutrophil to high-density lipoprotein cholesterol ratio(NHR)and incidence of cardiovascular disease(CVD)among individuals with metabolic associated fatty liver disease(MAFLD).Methods:We conducted a prospective cohort study utilizing health check-up data from 2006 to 2007 at Kailuan General Hospital and its 10 affiliated hospitals.The study population consisted of employees and retirees diagnosed with MAFLD,excluding those with incomplete neutrophil and high-density lipoprotein cholesterol data or a history of heart failure,myocardial infarction,cerebral hemorrhage,or cerebral infarction.CVD was defined as the presence of heart failure,myocardial infarction,cerebral hemorrhage,or cerebral infarction.Annual follow-ups were conducted from 2006,new-onset CVD cases identified through discharge records from the 11 Kailuan Group hospitals and records from municipal social insurance agencies,the final follow up date was December 31,2022.NHR was calculated as the ratio of neutrophil to high-density lipoprotein cholesterol,and the MAFLD cohort(n=28 952)was stratified into four groups by NHR quartiles:Q1 group(NHR<1.97,n=7 241),Q2 group(1.97≤NHR<2.57,n=7 235),Q3 group(2.57≤NHR<3.36,n=7 240),and Q4 group(NHR≥3.36,n=7 236).The Kaplan-Meier method was employed to plot survival curves for new-onset CVD,and the cumulative incidences of CVD across different NHR quartiles groups were determined.Intergroup comparisons were made using the log-rank test,and a multifactorial Cox proportional hazards regression model was used to assess the association between NHR quartiles and the risk of new-onset CVD in the MAFLD population.Results:The average follow-up duration was(14.03±3.99)years,during which 4 666 new CVD cases were recorded among the study population.The number of CVD cases across Q1 group to Q4 group were 1 061,1 167,1 186 and 1 252,respectively,with an overall incidence density of 11.5 cases per 1 000 person-years.The incidence densities for Q1 group to Q4 group were 10.4,11.4,11.7 and 12.5 cases per 1 000 person-years,respectively.The multifactorial Cox proportional hazards regression analysis revealed that higher NHR quartiles were associated with an increased relative risk of new-onset CVD(Q2 group:HR=1.13,95%CI:1.04-1.23;Q3 group:HR=1.15,95%CI:1.05-1.25;Q4 group:HR=1.22,95%CI:1.12-1.33).Conclusions:The risk of new-onset cardiovascular disease in individuals with MAFLD escalates with increasing NHR.

Objective To explore the immediate,long-term,and delayed effects of spiral stabilizing muscle chain technique compared to static distraction and Proprioceptive Neuromuscular Facilitation(PNF)stretching techniques on the flexibility of hip flexors.Methods Ninety subjects were randomly divided intothree groups of 30 each.Group 1 underwent the static stretching of the hip joint.Group 2 received PNF stretching,and Group 3 participated in SPS training.All participants were measured for hip extension angle to assess hip flexor flexibility before training,immediately after the first training session,at the end of 4 weeks of training,and 2 weeks after training cessation.Results Within-group comparisons showed significant increases in hip extension angles after one training session,after 4 weeks of training,and after 2 weeks of cessation compared to pre-training(P＜0.05).Between-group comparisons indicated no statistically significant differences in hip extension angle improvements among the three groups after one training session,after 4 weeks of training,and after 2 weeks of cessation(P＞0.05).Conclusion SPS training,static stretching,and PNF stretching all demonstrate good immediate,long-term,and delayed effects on improving hip extension angles,with consistent stretching outcomes.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease