ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

BackgroundWith the acceleration of population aging in China， studies have documented an increased prevalence of dementia in the elderly. Behavioral and psychological symptoms and impaired cognitive function are important problems affecting the quality of life in the elderly with dementia. It has been noted that there are certain limitations on the management of problems mentioned above by drug treatment alone， while its combination with music intervention is emerging as an effective approach. However， the application of this approach in the elderly with moderate to severe dementia is still in its relative infancy. ObjectiveTo investigate the effect of music assisted drug treatment on behavioral and psychological symptoms and cognitive function in the elderly with moderate to severe dementia， so as to provide insights for the development of effective intervention. MethodsA randomized controlled study was utilized to enroll a coherent of 43 elderly patients with moderate to severe dementia who were hospitalized in Geriatric Psychiatry of Deyang Mental Health Center from January to July 2023 and met the International Classification of Diseases， tenth edition （ICD-10） diagnostic criteria for dementia. Eligible subjects were divided into study group （n=22） and control group （n=21） based on random allocation using SPSS 26.0. Both groups received routine drug treatment and nursing care， while the study group added music intervention， which consisted of two 30-minute sessions per week for 8 weeks. Neuro Psychiatric Inventory （NPI） and Mini-Mental State Examination （MMSE） were administered to all patients before and after intervention. ResultsA total of 36 patients completed the study， including 20 case in study group and 16 case in control group. No statistical difference was noted in baseline NPI score and MMSE score between two groups （P>0.05）. After intervention， study group reported a statistical reduction in NPI total score ［58.00 （49.00， 79.25） vs. 78.50 （55.00， 95.50）， Z=-3.902， P<0.01）］ along with a clinically unremarkable increase in MMSE score （P>0.05） compared with baseline data. After intervention， NPI total score and scores on sub-domains including agitation/aggression， depression/dysphoria， anxiety and aberrant motor behavior were all significantly lower in study group than those in control group （Z=-2.183， -2.438， -2.691， -3.716， -2.250， P<0.05 or 0.01）， while there was no significant difference in MMSE score between two groups （P>0.05）. ConclusionMusic assisted drugintervention may ameliorate behavioral and psychological symptoms in the elderly with moderate to severe dementia， while no significant improvement is documented on cognitive function. ［Fund by the "14^th Five Year Plan" for Philosophy and Social Sciences Research in Deyang （number， DY232C002）］

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Objective To explore the effects of home-based exercise rehabilitation on cardiac structure, valvular function, and exercise capacity in patients with severe aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR). Methods 49 patients with severe AS who underwent TAVR at Zhongshan Hospital, Fudan University, from January 2024 to February 2025 were enrolled. They were divided into an exercise group (n＝25) or a non-exercise group (n＝24) based on participating or not in home-based rehabilitation after TAVR. The exercise group received 12 weeks of home-based exercise training (aerobic exercise plus resistance training every week); the non-exercise group received routine care. Transthoracic echocardiography (TTE) was used to assess cardiac structural parameters before discharge (T0) and after 12 weeks of exercise (T1). Functional outcomes including the 6-minute walk test (6MWT), Duke Activity Status Index (DASI), and Short Physical Performance Battery (SPPB) were compared between the two groups. A linear mixed-effects model was used to analyze the effect of home-based rehabilitation on echocardiographic parameters. Patients were stratified by baseline 6MWT (＜240 m as low-function subgroup, ≥240 m as high-function subgroup) to compare exercise-related outcomes between subgroups. Results At T1, the exercise group had a longer 6MWT distance than the non-exercise group (P＝0.012). The linear mixed-effects model showed that after 12 weeks of exercise, the left ventricular end-diastolic diameter (LVEDD) decreased in the exercise group but slightly increased in the non-exercise group, with a significant difference in changes over time between the two groups (P_interaction＝0.030). The exercise group also showed greater improvement in effective orifice area index (P_interaction＝0.028) and effective orifice area (P_interaction＝0.042) than the non-exercise group. Subgroup analysis revealed that in the low-function subgroup, the exercise group showed greater improvement in the 6MWT (P_interaction＝0.035) and the effective orifice area index (P_interaction＝0.046) compared to the non-exercise group; in the high-function subgroup, the exercise group showed greater improvement only in LVEDD compared to the non-exercise group (P_interaction＝0.046). Conclusions Home-based exercise rehabilitation improves exercise capacity, optimizes left ventricular remodeling, and enhances valvular function in patients with severe AS after TAVR, with greater benefits observed in patients with lower baseline 6MWT.

A qualitative analysis by high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-QTOF-MS/MS) was performed for the identification of main constituents in Gentiana veitchiorum. High-performance liquid chromatography (HPLC) was developed for the quantification of seven major components, including loganic acid (1), swertiamarin (2), gentiopicroside (3), sweroside (4), isoorientin (5), isoscoparin (6), and gentiournoside A (7). A total of 42 compounds, including 31 flavonoids, and 11 Iridoids, were identified based on their retention behaviors, and MS fragment information. Furthermore, regression equations for these seven chemical components were established, with good linear relationships (r2 > 0.9999), and the sample recovery rate was 97.02%-103.08%. This method was successfully applied for simultaneous determination of seven components in 7 batches of G. veitchiorum samples by HPLC-UV method. The method established in this study is simple and reliable, capable of qualitatively and quantitatively analyzing the main chemical components of G. veitchiorum, and is applicable to its quality evaluation.

Objective To analyze the composition and function of residual cells in pre-transplantation human thymic slices by single-cell transcriptomics sequencing(scRNA-seq),and established a quality assessment method for thymic slices based on the expression levels of molecular markers in the culture supernatant.Methods The discarded thymus from 18 patients with congenital heart disease undergoing surgical treatment in Department of Cardiothoracic Surgery of Children's Hospital Affiliated to Chongqing Medical University from May 2023 to January 2024 were collected and prepared into thymic slices.After the slices were cultured in vitro for 14 d,scRNA-seq was employed to identify the residual cell types,and gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis was performed to analyze the biological function of the residual cells.Then based on the literature concerning thymic slice culture,the molecular markers indicating thymocyte function were screened out.ELISA was applied to detect the changes in protein levels of molecular markers in the supernatant.Receiver operating characteristic(ROC)curve was plotted and assess the value of the molecular markers in the supernatant in evaluating the quality of thymic slices with area under the curve(AUC).Then,the qualified and unqualified thymic slices determined by our obtained molecular markers were transplanted subcutaneously into male nude mice(6～8 weeks old,weighing 14～17 g),respectively,and the male nude mice without transplantation of the thymic slices served as control group.Flow cytometry and histologic analysis were utilized to observe the immune reconstitution after transplantation.Results ① scRNA-seq identified 11 cell types in thymic slices,dominated with epithelial cells,fibroblasts,and T cells.GO and KEGG enrichment analysis showed that epithelial cells were involved in enrichment entries related to chemotaxis,epithelial cell development,cell matrix adhesion and tight junction;fibroblasts were involved in enrichment entries related to extracellular matrix,epithelial cell proliferation,negative regulation of cell migration,and regulation of actin cytoskeleton;T cells were mainly related to T cell differentiation,regulation of T cell activation,T cell apoptosis,and T cell receptor signaling.② Molecular markers,CCL19,CCL21,CXCL12,CXCL16,IL16 and SELL were identified to indicate thymocyte function.Compared with the levels of the first day,the protein secretions of CCL19,CCL21,CXCL12 and CXCL16 were significantly increased during in vitro culture(P<0.05),while the protein secretions of IL16 and L-selectin(protein form of SELL)were significantly decreased(P<0.05).The combined predictor Pre1 from subset of cytokines(IL16 and L-selectin)had the highest value in the quality assessment of thymic slices after 1 d of culture(AUC=0.883),and the combined predictor Pre2 from subset of cytokines(CCL19,CCL21,CXCL12 and CXCL16)had the highest value in the quality assessment after 14 d of culture(AUC=0.948).③ Transplantation in nude mice indicated that the qualified thymic slices could develop to thymus structure in vivo,and effectively increase the proportion of T cells in peripheral blood(P<0.01),while the unqualified thymic slices could not obtain the reconstitution of T cell development.Conclusion The main residual component cells in thymic slices are epithelial cells,fibroblasts and T cells.IL16 and L-selectin can be used as potential indicators to determine the quality of donor thymic samples.CCL19,CCL21,CXCL12 and CXCL16 can effectively evaluate the quality of thymic slices before transplantation.

Objective To investigate the alterations in skeletal muscle function and mass in an experimental mouse model of high-intensity exercise in a hot and humid environment.Methods Twenty-four male C57BL/6J mice(7～8 weeks old,weighing 21.30±0.67 g)were randomly assigned to a control group(CON group),a normal temperature and humidity exercise group(NE group),and a high temperature and humidity exercise group(HE group),with 8 mice in each group.The HE group was subjected to a high-temperature simulation chamber,maintaining a temperature of 37～39℃and humidity of 70%～80%,for a 60-minute exercise intervention at a 10° incline and 80%of maximum velocity(12 min of exercise followed by 8 min of rest,for 3 cycles).The CON group did not exercise,while the NE group exercised in the same manner in a normal temperature and humidity environment.The overall condition of the mice was evaluated by monitoring their body weight and analyzing their body composition.Their serum creatinine and urea levels were detected using an automated biochemical analyzer.After exercise,skeletal muscle function in the mice of each group was assessed by measuring their grip strength and exhaustion time.The skeletal muscle contractility and resistance to fatigue were evaluated using an in situ/in vivo/ex vivo muscle testing system.HE staining was employed to observe the morphological and structural changes in the skeletal muscles,and the average cross-sectional area and diameter of the muscle fibers were analyzed.Genes related to protein synthesis(Eif4ebp1,p70S6k)and breakdown(Foxo3,Fbxo32,Trim63)and heat stress-related genes(Hsf-1,Hspa1a,Hsp90aa)were quantified using RT-qPCR.Results ① Compared with the CON and NE groups,the HE group exhibited significant decreases in body weight(P<0.01)and lean body mass(P<0.05),an upward trend of creatinine level(P<0.05),and increases in the urea content(P<0.01).② The mice in the HE group had notably reduced grip strength(P<0.001),diminished skeletal muscle contraction,and weakened resistance to fatigue(P<0.05)than the CON and NE groups.③ The HE group demonstrated a reduction in the average cross-sectional area of muscle fibers(P<0.05)and a decrease in average fiber diameter(P<0.05),with particular up-regulation of Fbxo32,Trim63 and Eif4ebp1(P<0.01)and down-regulation of p70S6k(P<0.05)in comparison to the NE and CON groups.④ The expression levels of heat stress-related genes were higher in the HE group than the CON and NE groups(P<0.05).Conclusion High-intensity exercise in a hot and humid environment can lead to a decline in skeletal muscle function and mass in mice,potentially due to the disturbance of skeletal muscle protein synthesis and degradation triggered by excessive heat stress.

Objective To investigate the analgesic effect of combined spinal-epidural analgesia and its impact on stress levels in multiparous women during labor in a high-altitude region.Methods A total of 86 multiparous women were enrolled as study subjects.They were divided into observation group(43 cases)and control group(43 cases)based on whether they received labor analgesia.The obser-vation group received combined spinal-epidural analgesia during the first stage of labor.Pain levels[Visual Analogue Scale(VAS)],labor psychological experience[Chinese version of the Childbirth Self-Efficacy Inventory(CBSEI-C32)and Coping with Childbirth(CCB)],stress levels[serum cor-tisol(Cor),norepinephrine(NE)and adiponectin(APN)]as well as maternal and neonatal out-comes were compared between the two groups.Results The VAS scores during the first,second and third stages of labor were significantly lower in the observation group than those in the control group(P＜0.05).The CBSEI-C32 and CCB scores at 24 hours postpartum in the observation group were significantly higher than those in the control group(P＜0.05).The serum levels of Cor,NE and APN at 12 hours postpartum in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of adverse maternal and neonatal outcomes in the observation group was 0％,which was significantly lower than 9.30％in the control group(P＜0.05).Con-clusion In high-altitude regions,combined spinal-epidural analgesia is effective in reducing labor pain,improving labor psychological experience,lowering stress levels,and reducing adverse maternal and neonatal outcomes in multiparous women.

Objective: To evaluate the effect of Tai Chi and Qigong on patients with lumbar disc herniation (LDH). Methods: Relevant data were retrieved from nine English and Chinese databases, including Cochrane Library, PubMed, and Wanfang Data, etc. from inception to June 2024. All published randomized controlled trials assessing the effect of Tai Chi and Qigong on visual analog scale (VAS), Japanese Orthopedic Association (JOA) score, and other health indicators in participants with LDH compared to usual medical care or other treatments were included. Grey literature, trials involving the pushing of hands (Tui Shou) or Tai Chi with weapons, and trials with co-interventions (Tai Chi/Qigong plus another treatment) were excluded. Methodological quality was analyzed using the Cochrane risk of bias tool, and evidence quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Results: Fourteen trials (954 patients) were included in this study. Tai Chi and Qigong were associated with lower VAS pain scores (standardized mean difference −0.55, 95% confidence interval [CI] −0.95 to −0.15, P = .01), higher JOA scores (mean difference [MD] 4.40, 95% CI 2.62 to 6.18, P < .001) and straight leg raise test results (MD 9.40°, 95% CI 7.64 to 11.15, P < .001) in patients with LDH. Furthermore, compared with usual care, Tai Chi and Qigong showed enhanced effects on pain and JOA scores. When compared to other exercises or massage, the effect on pain scores was similar but that on JOA scores was significant. Conclusions Tai Chi and Qigong may have favorable effects on VAS pain and JOA scores compared with usual care, and on JOA scores compared with other exercises or massage in patients with LDH. Given the overall poor quality of the evidence, the results of current study should be interpreted cautiously.