ObjectiveTo explore the effect of the medical-community linkage model on activities of daily living, psychological status and motor function of stroke patients in the community. MethodsA total of 60 stroke patients admitted to two community health service centers and their affiliated stations in Fengtai District, Beijing, from January, 2024 to August, 2025 were enrolled and randomly divided into control group (n = 30) and intervention group (n = 30). The control group received routine medicine, dietary care and rehabilitation management, while the intervention group underwent rehabilitation with the medical-community linkage model, for twelve weeks. They were assessed with modified Barthel Index (MBI), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and Fugl-Meyer Assessment (FMA) before and after intervention. ResultsAfter intervention, the MBI, HAMA, HAMD and FMA scores of patients improved in both groups (|t| > 5.599, P < 0.001), and improved more in the intervention group than in the control group (P < 0.05), except MBI. The HAMA and HAMD scores of family members decreased in both groups (|t| > 10.333, P < 0.001), and decreased more in the intervention group than in the control group (t > 5.681, P < 0.001). ConclusionThe medical-community linkage model can further improve the motor function of stroke patients in community, as well as the psychological status of both patients and their family members.

BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

Objective To explore the therapeutic effect of LuoFuShan Rheumatism Plaster(LFS)on neuropathic pain(NP)and its molecular mechanism.Methods Mouse models of sciatic nerve chronic constriction injury(CCI)were treated with low,medium,and high doses(2.2,4.4,and 8.8 cm2,respectively)of LFS by topical application for 14 consecutive days.The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold(MWT),paw withdrawal latency(PWL),plasma IL-6 and TNF-α levels,and histopathology of the sciatic nerve.Network pharmacology and molecular docking were used to identify the key targets and signaling pathways.The key targets were verified by RT-qPCR and immunohistochemistry.The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart,liver,and kidneys.Results Compared with the CCI group,LFS dose-dependently increased MWT and PWL,reduced plasma IL-6 and TNF-α levels,and alleviated sciatic nerve inflammation in the mouse models.Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling.Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF-α.In the mouse models of sciatic nerve CCI,LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve.LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart,liver and kidneys as compared with those in the CCI model group and sham-operated group.Conclusion LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.

Objective:To investigate the efficacy and safety of transurethral incision for the treatment of ureterocele in infants.Methods:A retrospective analysis of 28 cases of ureterocele admitted from March 2012 to May 2023 were reviewed, all of which were less than 1 year old, 16 male and 12 female, with an average age of(5.7±3.5)months. The ureterocele was located on the left side in 8 cases, on the right side in 15 cases, and bilaterally in 5 cases. There were 12 cases of single system ureterocele, of which 7 cases were unilateral and 5 cases were bilateral. Duplex system ureterocele was observed in 16 cases, all of which were unilateral. Clinical manifestations: urinary tract infection in 13 cases, 11 cases of ureterocele or hydronephrosis and ureteral dilation were found during antenatal examination, and 4 cases of ureterocele were found after birth. Urological ultrasound, intravenous pyelography(IVP) and voiding cystourethrography(VCUG) were performed in all children, and 17 cases underwent magnetic resonance urolography (MRU), and confirm the diagnosis of ureterocele preoperatively. All of the cases were performed the transurethral incision.The ureterocele was punctured and incised 1-2 mm at the base of the bulge, and 2-4 points were punctured according to the bulge atrophy. Bilateral ureteroceles were punctured and incised simultaneously. Postoperative urine routine test, urinary tract color ultrasound and VCUG were performed to determine if there is urinary tract infection, hydronephrosis, ureteral dilation and bulging, and whether a second surgery is needed.Results:All operations were conducted successfully. The intraoperative bleeding was less than 3 ml and no intraoperative complications. The operative time was (28.4±10.3) min. The median postoperative follow-up was 34 (32, 36) months. Six cases underwent postoperative VCUG examination. Eleven children were recovered well with single systemic ureterocele. One child developed grade Ⅳ vesicoureteral reflux(VUR)and combined with bladder diverticulum, and ureterocele underwent open diverticulotomy and ureteral reimplantation six months after surgery. Nine children were recovered well with duplex systemic ureterocele. Six cases of children developed infection, of which 2 cases had an infection once within one month after TUI, and the other four cases still had intermittent infections after six months and VCUG was performed, and one case showed grade Ⅲ VUR of the lower ureter, which was observed conservatively, while the other three cases had enlarged cysts but no VUR, and upper heminephrectomy was performed, and the patients recovered well after surgery. Except for these 6 exceptions, in another case, after ten years of follow-up, the ureterocele became larger but no VUR, and the results were good after a second transurethral incision. There was no significant difference in the postoperative infections, new VUR cases, and secondary surgeries between the two groups.Conclusions:Transurethral incision has good surgical effect on children with single system ureterocele and duplex system ureterocele, and has advantages of easy operation, less trauma, safety and effectiveness, and few complications. It deserves to be recommended as the treatment of choice, especially for infants and young children.

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

Objective: To explore differences in the factors influencing parents and teachers assessments of preschool children s mental health using the Strengths and Difficulties Questionnaire (SDQ), so as to provide reference for promoting children s mental health. Methods: A retrospective analysis was conducted on the SDQ survey data of 14 763 middle and senior kindergarten children in Nanshan District, Shenzhen, from March to June 2023. Chi square χ 2 tests were used to analyze differences in mental health assessments between parents and teachers. Multivariate Logistic regression was employed to examine the factors influencing parental assessments, and Kappa coefficients were used to evaluate the consistency between parent and teacher evaluations. Results: The positive rate of mental health problems reported by parents (7.2%) was significantly higher than that reported by teachers (6.2%) ( χ 2=254.27, P <0.01). Gender differences revealed that parents reported a lower positive rate for boys (7.9%) compared to teachers (8.5%), whereas for girls, the parental positive rate (6.4%) was higher than that reported by teachers (3.8%) ( χ 2=163.59, 81.26, all P <0.01). Age related differences showed that parental positive rates for 4, 5, and 6 year olds (8.5%, 7.4%, 5.8%) were consistently higher than teachers assessments (6.3%, 6.7%, 5.4%) ( χ 2=41.23, 157.53, 63.67, all P <0.05). Univariate analysis of parental assessments indicated higher positive rates among boys (7.9%), 4 year olds (8.5%), mothers aged 20-35 ( 6.6 %), mothers with high school education or below (9.8%), fathers aged 23-40 (6.4%), fathers with high school education or below (10.3%), and children exposed to secondhand smoke (7.9%) ( χ 2=23.56-235.24, all P <0.01). Multivariate Logistic regression identified lower parental education levels and exposure to secondhand smoke as significant risk factors for abnormal SDQ assessments by parents ( χ 2=2.05, 1.62, 3.15, all P <0.05). The Kappa coefficients for parent-teacher agreement across SDQ subscales and total difficulties ranged from 0.04 to 0.12 (all P <0.01). Conclusions Parental education level and exposure to secondhand smoke are significant factors influencing preschool children s mental health. Differences exist between parental and teacher assessments of children s mental health, and incorporating teacher evaluations can provide a more comprehensive understanding of preschoolers psychological well being.

OBJECTIVES: To explore the therapeutic effect of LuoFuShan Rheumatism Plaster (LFS) on neuropathic pain (NP) and its molecular mechanism. METHODS: Mouse models of sciatic nerve chronic constriction injury (CCI) were treated with low, medium, and high doses (2.2, 4.4, and 8.8 cm², respectively) of LFS by topical application for 14 consecutive days. The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), plasma IL-6 and TNF-α levels, and histopathology of the sciatic nerve. Network pharmacology and molecular docking were used to identify the key targets and signaling pathways. The key targets were verified by RT-qPCR and immunohistochemistry. The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart, liver, and kidneys. RESULTS: Compared with the CCI group, LFS dose-dependently increased MWT and PWL, reduced plasma IL-6 and TNF-α levels, and alleviated sciatic nerve inflammation in the mouse models. Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling. Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF‑α. In the mouse models of sciatic nerve CCI, LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve. LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart, liver and kidneys as compared with those in the CCI model group and sham-operated group. CONCLUSIONS LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.
Animals ; Toll-Like Receptor 4/metabolism* ; Neuralgia/metabolism* ; Mice ; Signal Transduction/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sciatic Nerve/injuries* ; Male ; Molecular Docking Simulation ; Disease Models, Animal ; Interleukin-6

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigate the protective effect and regulatory mechanism of ciprofol on Parkinson's disease(PD)rats based on the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α)signaling pathway.Methods Wistar rats were divided into blank control group,model group,ciprofol group,and ciprofol+AMPK inhibitor dorsomorphin group(ciprofol+Dor group),with 10 rats in each group.Except for the blank control group,PD models were estab-lished in the other three groups.Behavioral experiments were used to assess the motor and cognitive functions of rats in each group.Enzyme-linked immunosorbent assay(ELISA)was employed to de-tect the levels of dopamine(DA)and 5-hydroxytryptamine(5-HT)in the rat brain striatum.Immu-nofluorescence staining was conducted to measure the level of tyrosine hydroxylase(TH)in the rat brain substantia nigra.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was applied to detect the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,and Bax in the rat brain striatum.Western blot was used to determine the relative protein expression levels of ULK1,beclin1,Bcl-2,Bax,phosphorylated(p)-AMPK,SIRT1,PGC1α,and the ratio of LC3 Ⅱ to LC3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ)in the rat brain striatum.Results Compared with the blank control group,the motor and cognitive functions of rats in the model group were reduced,the levels of DA and 5-HT in the brain striatum decreased,the fluorescence intensity of TH in the brain substantia nigra weakened,and the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were reduced.In contrast,the relative mRNA expression level of Bax and the relative protein expression level of Bax increased,with statistically significant differ-ences(P＜0.05).Compared with the model group,the motor and cognitive functions of rats in the ciprofol group were improved,the levels of DA and 5-HT in the brain striatum increased,the fluo-rescence intensity of TH in the brain substantia nigra strengthened,and the relative mRNA expres-sion levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were elevated.Meanwhile,the relative mRNA expression level of Bax and the relative protein expression level of Bax decreased,with statistically significant differences(P＜0.05).The comparison between the ciprofol+Dor group and the ciprofol group revealed that the AMPK inhibitor dorsomorphin could re-verse the effects of ciprofol(P＜0.05).Conclusion Ciprofol may exert neuroprotective effects for PD rats by promoting autophagy through activating the AMPK/SIRT1/PGC1α signaling pathway.

Objective To investigate the effects and related molecular mechanisms of esket-amine on the proliferation,epithelial-mesenchymal transition(EMT),and stem cell properties of colorectal cancer(CRC)cells.Methods CRC cell line SW480 was cultured with varying concentra-tions of esketamine,and the cells were divided into blank group(0 μmol/L),low-concentration group(1 μmol/L),medium-concentration group(5 μmol/L)and high-concentration group(10 μmol/L).Cell proliferation activity was assessed using the EdU proliferation assay,cell spheroid-forming ability was evaluated via the spheroid formation assay,cell migration capacity was measured using the scratch assay,cell invasion ability was determined through the transwell assay,and the expression levels of tumor stem cell property markers[NANOG homeobox(NANOG),SRY-box transcription fac-tor(SOX)2,SOX4],the neurogenic locus Notch homolog protein 1(Notch1)receptor and the Notch1 intracellular domain(Notch1 ICD)were detected by western blot.A recovery test was con-ducted by adding the Notch1 receptor agonist Jagged1 to the culture groups with different concentra-tions of esketamine.Results Compared with the blank group,esketamine significantly inhibited the proliferation activity,spheroid-forming ability,migration ability,and invasion ability of CRC cells in a concentration-dependent manner.The intracellular expression levels of SOX2,SOX4,NANOG,and Notch1 ICD proteins were significantly decreased,while the expression level of the Notch1 recep-tor was significantly increased in the esketamine groups(P＜0.05).After the addition of Jagged1,the inhibitory effects of esketamine on the proliferation activity,metastatic ability,and stem cell properties of CRC cells were alleviated.Conclusion Esketamine inhibits CRC cell proliferation,metastasis,EMT,and stem cell properties by reducing the activation level of the Notch1 receptor,demonstrating a potential for clinical anti-tumor applications.