ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.

Objective To study the dynamic regulatory role of early growth response 4(EGR4)in mouse neurodevelopment.Methods Data on single-cell chromatin accessibility(single-cell assay for transposase-accessible chromatin by sequencing,scATAC-seq)and transcriptome(single-cell RNA sequencing,scRNA-seq)from seven key stages spanning from the embryonic period to adulthood was collected and analyzed.The transcription factor binding site network was inferred,a quantitative analysis from a temporal perspective was conducted,its functional modules were parsed,and the results were visualized.Results egr4 was significantly highly expressed from the late embryonic stage to adulthood,and specifically activated during the maturation of inhibitory neurons[parvalbumin(PV)and somatostatin(SST)subtypes].Moreover,its transcription was not directly regulated by changes in chromatin accessibility.Temporal network analysis indicated that EGR4 became a regulatory hub in the late embryonic stage and drove neuron differentiation and subtype specification.Functional enrichment analysis showed that EGR4 regulated the"cell differentiation"pathway through dynamic interacting factors,and there were subtype-specific interaction modules in PV/SST neurons respectively.Conclusion EGR4 can participate in the late-stage maturation of cortical neurons through a stage-specific regulatory network.This study provides a new perspective on mechanisms underlying the temporal logic of neural development.

Objective To establish a prognostic model that predicts the survival and prognosis of gastric adenocarcinoma patients by studying the LncRNAs related to iron death in gastric cancer cells,thereby providing a theoretical basis for the development of their biomarkers and therapeutic targets.Methods The transcript sequencing data of gastric adenocarcinoma patients in the TCGA database were analyzed and intersected with iron death-related genes,which were screened for iron death-related LncRNAs by co-expression and differential analysis methods.One-way and multifactorial Cox regression analyses were used to screen out the prognostic-related LncRNAs in gastric adenocarcinoma patients,so as to establish the prognostic scoring models.On this basis,risk values were calculated for each sample,and the reliability of the model was fully verified.According to the model results,differences in the immune infiltration and immune response between the high-and low-risk groups were analyzed.Results Tumor tissues were screened for 503 LncRNAs(431 up-regulated and 72 down-regulated)associated with iron death compared to the normal tissues;univariate Cox regression analysis yielded 33 LncRNAs that could be used as the independent risk factors,whereas multivariate Cox regression analysis constructed a predictive model consisting of 17 LncRNAs.Survival curves indicated that patients with the high risk had the significantly lower survival rates than those with the low risk(P<0.001).Unifactorial and multifactorial independent prognostic analyses showed that age,stage,and risk value were independent risk factors for patients;Time-dependent ROC curves suggested that the predicted AUC values of the model's 1-,2-,and 3-year survival rates were 0.751,0.799,and 0.779 respectively,proving that the model was reliable and stable.There were significant differences in multiple immune activation responses,the degree of immune cell infiltration,and the expression levels of immune check points between the high-and low-risk groups.Conclusion The established prognostic prediction model based on iron death-related lncRNAs for gastric adenocarcinoma patients can better assess the prognosis of patients,and the lncRNAs included in the model have the feasibility of being developed into biomarkers and therapeutic targets.

Objective: To investigate the molecular mechanism of NOD-like receptor(NLR) signaling pathway induced cellular focal death in mouse kidney tissues under plateau hypoxia based on transcriptomic sequencing technology. Methods: Animal models were constructed in high-altitude kidney test group(HKT group) and plain kidney control group(PKC group),and C57/BL6 mice were bred at an altitude of 4 200 m and 400 m,respectively.Kidney tissues were aseptically taken out after 30 d and used for observation of renal histopathological changes and transcriptomics sequencing,respectively,and then differentially expressed genes(DEGs) were enriched by KEGG and GO analysis.Key gene and protein expression levels were verified by reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot analysis. Results: Hematoxylin-eosin(HE) staining showed that the renal tubules of HKT mice were disorganized,and the tubular epithelial cells were edematous with inflammatory cell aggregation.Transcriptomics sequencing analysis revealed that a total of 3 007 DEGs were identified in the HKT group,and KEGG analysis showed that DEGs were significantly enriched in the NLR signaling pathway.The mRNA expression of the key differentially expressed genes,CASP1,CASP11,GSDMD,IFI16,NAIP5,IRF9,and the downstream inflammatory factors,IL-1β and IL-18,was upregulated,and protein expression of CASP1,CASP11,and GSDMD was up-regulated. Conclusion The plateau hypoxic environment induces cellular pyroptosis by regulating the expression of NLR signaling pathway and releases downstream inflammatory factors to cause inflammatory responses.

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

ObjectiveTo investigate the possible mechanism of action of Xibining Formula （膝痹宁） for cartilage damage in knee osteoarthritis （KOA） through the cyclic guanosine-adenosine monophosphate synthase （cGAS）- stimulator of interferon genes （STING） signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups （10 per group）， sham operation group， KOA model group， low-dose Xibining Formula group， high-dose Xibining Formula group， and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus （DMM） method in all groups but the sham surgery group. Two weeks after surgery， the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/（kg·d） and 14.32 g/（kg·d） respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/（kg·d） of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan （DMXAA） at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/（kg·d） via gavage， once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were measured by ELISA； pathological changes in cartilage tissue were observed using hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system； the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 （MMP3）， matrix metalloproteinase 13 （MMP13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS）， type-Ⅱ collagen （CⅡ） and aggregated proteoglycan （Aggrecan）， and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group， the KOA model group showed severe cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with the control group， serum level of IL-6， IL-1β， TNF-α in all the intervented groups decreased （P＜0.01）， while compared with high-dose Xibining Formula group， level of IL-6， IL-1β， and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased （P＜0.01）. Compared with the KOA model group， all the intervention groups exhibited alleviated cartilage pathological changes， signi-ficantly reduced Mankin scores， significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly decreased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with high-dose Xibining Formula group， high-dose Xibining Formula + agonist group showed cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway， decreasing matrix degradation-related proteins， and elevating matrix composition-related proteins.

Objective To investigate the relationship between serum forkhead box F1(FOXF1)and Ape-lin-13 levels and carotid atherosclerosis(CAS)in elderly patients with type 2 diabetes mellitus(T2DM).Methods From January 2022 to March 2024,207 elderly T2DM patients admitted to the hospital(T2DM group)and 52 healthy elderly patients underwent physical examination(control group)were selected as the study objects.The elderly T2DM patients were divided into CAS group(128 cases)and non-CAS group(79 cases)according to the occurrence of CAS.Serum FOXF1 and Apelin-13 levels were detected by real-time flu-orescent quantitative PCR and enzyme-linked immunoadsorption assay.The influencing factors of CAS in eld-erly T2DM patients were determined by multivariate unconditional Logistic regression,and the predictive effi-cacy of serum FOXF1 and Apelin-13 levels was analyzed by receiver operating characteristic curve.Results The levels of FOXF1 and Apelin-13 in T2DM group were lower than those in control group(P＜0.05).The inci-dence of CAS in 207 elderly T2DM patients was 61.84％(128/207).The levels of serum FOXF1 and Apelin-13 in CAS group were lower than those in non-CAS group(P＜0.05).The independent risk factors of CAS in elderly T2DM patients were the duration of T2DM,glycosylated hemoglobin and low density lipoprotein cho-lesterol(P＜0.05),and the independent protective factors were FOXF1 and Apelin-13(P＜0.05).The com-bined prediction of serum FOXF1 and Apelin-13 levels for CAS in elderly T2DM patients was 0.882,which was larger than 0.782 and 0.791 predicted by serum FOXF1 and Apelin-13 levels alone(P＜0.05).Conclu-sion The decrease of serum FOXF1 and Apelin-13 levels in elderly T2DM patients is closely related to CAS,and the combined detection of serum FOXF1 and Apelin-13 levels has a high predictive effect on CAS in elder-ly T2DM patients.

Objective:To investigate the efficacy and safety of endovascular therapy (EVT) for early neurological deterioration (END) in patients with minor stroke due to acute anterior circulation large vessel occlusion.Methods:Consecutive patients with mild stroke due to acute anterior circulation large vessel occlusion admitted to Mianyang Central Hospital from October 2015 to October 2023 were included retrospectively. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score <6. END was defined as an increase of ≥4 in NIHSS score compared to baseline within 12 hours of onset. According to whether EVT was performed or not, they were divided into EVT group and standard medical treatment (SMT) group. At 90 days after onset, the modified Rankin Scale was used to evaluate the outcome. 0-1 was defined as excellent outcome (primary outcome measure) and 0-2 was defined as good outcome (secondary outcome measure). The safety endpoints included symptomatic intracranial hemorrhage (sICH) within 72 hours after EVT and all-cause mortality within 90 days. Multivariate logistic regression analysis was used to determine the correlation between EVT and clinical outcome. Results:A total of 164 patients with minor stroke due to acute anterior circulation large vessel occlusion were included. Eighty-four patients (51.2%) developed END, of which 52 (61.9%) underwent EVT and 32 (38.1%) received SMT; 60 patients (71.4%) had excellent outcome, and 64 (76.2%) had good outcome. There was no significant difference in demographic and baseline clinical data between the EVT group and the SMT group. The excellent outcome rate of the EVT group at 90 days after onset showed a trend higher than that of SMT group (78.8% vs. 59.4%; χ2=3.680, P=0.055), but there was no significant difference in the good outcome rate and safety endpoints between the two groups. Multivariate logistic regression analysis showed that after adjusting for confounding factors, EVT was significantly and independently associated with excellent outcome at 90 days (odds ratio 4.955, 95% confidence interval 1.331-22.284; P=0.024). Conclusion:For patients with minor stroke due to anterior circulation large vessel occlusion who experience END, EVT may improve their functional outcome without increasing the risk of sICH and mortality.

[Objective]To explore the patterns of diagnosis and prescription in traditional Chinese medicine(TCM),specifically using Polygala tenuifolia Willd formulas,for the treatment of Alzheimer's disease(AD),grounded in the fundamental theories of TCM.[Methods]The medical case documents containing"Poly gala tenuifolia Willd formula for dementia"were included in China National Knowledge Infrastructure(CNKI),VIP,Wanfang and Gujin Medical Case Cloud Platform databases.Furthermore,an Excel 2019 database was created and subsequently standardized.The database was then mined for patterns related to the administration and utilization of medications,by utilizing the Gujin Medical Case Cloud Platform and the Python programming language.Following standardization,the drug application rules were explored by using the Ancient and Modern Medical Case Cloud Platform and Python.[Results]It employed the Ancient and Modern Medical Case Cloud Platform and Python following standardization.A total of 211 kinds of drugs were recorded in 165 medical records,with warm being the most prevalent,followed by neutral.These drugs were mainly sweet,pungent and bitter in taste,and the main effects of the drugs were attributed to the liver,heart,kidney,spleen and lung meridians,and most of the drugs that were paired with Poly gala tenuifolia Willd had functions of opening the orifices,inducing drainage and seepage of dampness,invigorating blood circulation,removing blood stasis and tonifying the deficiency.Acorus calamus and Poly gala tenuifolia Willd were the core pair of drugs with the common dosage of 10 g and 15 g respectively,and the proportion of the two was mostly 1︰1,2︰3.Acorus calamus-Poly gala tenuifolia Willd was often paired with Poria,commonly used pairs were Radix Rehmanniae Preparata-Cornu Cervi,Ligusticum Chuanxiong-Salviae Miltiorrhizae,the complex network analysis showed that the core composition of treating AD was the prescription of Kaixin Powder which removed ginseng but added with the participation of the Radix Rehmanniae Preparata,Salviae Miltiorrhizae,Ligusticum Chuanxiong and Glycyrrhiza glabra.[Conclusion]In this study,among the formulas containing Polygala tenuifolia Willd for AD,the highest correlation was found between Polygala tenuifolia Willd and Acorus calamus,which was mainly used to replenish deficiency and for diarrhea,and focused on strengthening the spleen,resolving dampness and expelling phlegm,regulating the liver and activating the blood,and benefiting the kidneys and filling in the marrow on the basis of tranquilizing the spirit and opening up the aperture to awaken the mind.The preliminary clarification of the medication law of the formulas containing Polygala tenuifolia Willd for the treatment of AD can provide a basis for the clinical use of medication and the development of new prescriptions.

Objective:To construct a VP8-mRNA vaccine using human rotavirus spike protein VP8 domain as the immunogen and analyze its immunogenicity in mice.Methods:The VP8-mRNA sequence was designed, optimized, and synthesized. The VP8 gene of rotavirus G1P[8] type was used to construct the plasmid pUC57-VP8-Kan-SapⅠ, which was then sequenced. The plasmid confirmed by sequencing was subjected to large-scale amplification and extraction, followed by linearization, in vitro transcription, and capping. The purified capped products were encapsulated with lipid nanoparticles using a microfluidic control apparatus. The encapsulated VP8-mRNA vaccine was administered intramuscularly to mice at 10, 15, and 20 μg. Serum samples were collected for antibody detection by ELISA. Cellular immune responses were detected by flow cytometry and ELISPOT. Statistical analysis was performed using one-way or two-way analysis of variance and Tukey-Kramer test. Results:The encapsulated VP8-mRNA vaccine was rounded and spherical, with a particle size of about 100 nm, a polymer dispersion index of 0.088, and an encapsulation rate of 92.3%. Two doses of VP8-mRNA vaccine immunization could induce a good immune response in mice. The level of IgG antibody induced after immunization in the 15 μg group was comparable to that of the 20 μg group, and there was no statistical difference ( P>0.05), but the antibody levels in the two groups were significantly higher than that in the 10 μg group ( P<0.000 1). VP8-mRNA vaccine could induce neutralizing antibodies against rotavirus G1 and G9 types. The highest level of neutralizing antibodies against rotavirus type G1 was observed in the 15 μg group, which was significantly higher than that in the 10 μg group ( P<0.05). All immunization groups exhibited good neutralizing ability against rotavirus G9 type. The results of ELISPOT showed that lymphocytes from mice in each vaccine group were able to secrete IFN-γ when stimulated with VP8 peptide. Flow cytometry showed that the proportions of CD8 + T cell subsets in the vaccine groups were higher than that in the control group. Conclusion:The VP8-mRNA vaccine has good immunogenicity in mice and can induce good humoral and T-cell immune responses.