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.

ObjectiveTo establish the fingerprints of 15 batches of Hengzhi Kechuan capsules， to quantitatively analyze 10 index components， and to evaluate the quality uniformity of samples from different batches. MethodsThe fingerprints and quantitative analysis of Hengzhi Kechuan capsules were established by a combination method of high performance liquid chromatography coupled with diode array detector and charged aerosol detector（HPLC-DAD-CAD）， adenosine， guanosine， vanillic acid， safflomin A， agarotetrol， naringin， hesperidin， militarine， ginsenoside Rb₁， and glycyrrhizic acid were selected as quality attribute indexes. A total of 15 batches of Hengzhi Kechuan capsules from 2022 to 2024（3 boxes per batch） were qualitatively and quantitatively analyzed， and the quality uniformity level of the manufacturers was characterized by parameters of intra-batch consistency（P_A） and inter-batch consistency（P_B）. The homogeneity and difference of quality attribute indexes of samples from different years were analyzed by heatmap clustering analysis. ResultsHPLC fingerprints and quantitative method of Hengzhi Kechuan capsules were established， and the methods could be used for qualitative and quantitative analysis of this preparation， which was found to be stable and reliable by method validation. The similarity of fingerprints of 15 batches of samples was 0.887-0.975， a total of 13 common peaks were calibrated， and 10 common peaks were designated， all of which were quality attribute index components. The results of quantitative analysis showed that the contents of the above 10 ingredients in the samples were 0.038-0.078， 0.115-0.251， 0.007-0.018， 0.291-0.673， 0.122-0.257， 0.887-1.905， 1.841-3.364， 1.412-2.450， 2.207-3.112， 0.650-1.161， respectively. And the contents of ginsenoside Rb₁ and glycyrrhizic acid met the limit requirements in the 2020 edition of Chinese Pharmacopoeia. For the samples from 15 batches， the P_A values of the 10 index components were all <10%， indicating good intra-batch homogeneity， and the P_B values ranged from 33.86% to 92.97%， suggesting that the inter-batch homogeneity was poor. Heatmap clustering analysis showed that the samples from different years were clustered into separate categories， and adenosine， guanosine， safflomin A， naringin， hesperidin and agarotetrol were the main differential components. ConclusionThe intra-annual quality uniformity of Hengzhi Kechuan capsules is good and the inter-annual quality uniformity is insufficient， which may be related to the quality difference of Pinellinae Rhizoma Praeparatum， Carthami Flos， Citri Sarcodactylis Fructus， Citri Reticulatae Pericarpium， Aquilariae Lignum Resinatum， Citri Fructus， etc. In this study， the fingerprint and multi-indicator determination method of Hengzhi Kechuan capsules was established， which can be used for more accurate and efficient quality control and standardization enhancement.

BACKGROUND:Traditional methods of urinary tract reconstruction are limited by donor scarcity,high complication rates,and suboptimal functional recovery.Tissue engineering strategies offer new directions in this field.Since the urinary tract is mainly composed of muscle tissue,the key is to find suitable seed cells and efficiently induce them to differentiate into smooth muscle cells.Comparative studies on the efficacy of different smooth muscle cell induction regimens are still lacking. OBJECTIVE:To isolate,culture,and identify human urine-derived stem cells,and to compare the effects of two different induction protocols. METHODS:Human urine-derived stem cells were isolated from urine samples of 11 healthy adult volunteers by multiple centrifugations.Surface markers were identified by flow cytometry.The multi-directional differentiation potential of human urine-derived stem cells was verified through osteogenic and adipogenic differentiation.Differentiation was induced by transforming growth factor-β1 or transforming growth factor-β1 combined with platelet derived growth factor for 14 days.Immunofluorescence staining and western blot assay were employed to compare the expression differences of smooth muscle-specific proteins(α-SMA and SM22). RESULTS AND CONCLUSION:(1)Urine-derived stem cells were successfully isolated from the eight urine samples of healthy people.These cells exhibit a"rice grain"-like morphology and possess a robust proliferative capacity.(2)Urine-derived stem cells exhibited high expression of mesenchymal stem cell surface markers(CD73,CD90,and CD44)and extremely low expression of hematopoietic stem cell surface markers(CD34 and CD45).These cells did not express CD19,CD105,and HLA-DR.(3)After osteogenic and adipogenic differentiation,the formation of calcium nodules and lipid droplets was observed,with positive staining results from Alizarin Red S and Oil Red O staining.(4)After 14 days of smooth muscle induction culture,immunofluorescence staining revealed that the smooth muscle differentiation rate of urine-derived stem cells treated with a combination of transforming growth factor-β1 and platelet derived growth factor was significantly higher compared to those treated with transforming growth factor-β1 alone(P<0.005).(5)After 14 days of smooth muscle induction culture,western blot assay further demonstrated that the expression levels of α-SMA and SM22 in the transforming growth factor-β1/platelet derived growth factor group were significantly elevated compared to those in the transforming growth factor-β1 only group(P<0.005).These findings confirm that urine-derived stem cells can be non-invasively isolated using multiple rounds of centrifugation.Compared with transforming growth factor-β1 alone,the combination of transforming growth factor-β1 and platelet derived growth factor can improve the efficiency of inducing urine-derived stem cells to differentiate into smooth muscle cells.

OBJECTIVE To evaluate the quality of evidence in the systematic evaluation/meta-analysis of traditional Chinese medicine （TCM） for diabetes retinopathy （DR） based on the GRADE system. METHODS Chinese and English databases were searched to obtain the relevant studies of systematic evaluation/meta-analysis of traditional Chinese medicine in the treatment of DR. The search time was from the establishment of each database to January 13th， 2024. According to the inclusion and exclusion criteria， literature screening was conducted. After extracting relevant information from the included literature， the GRADE system was used to evaluate the quality level of the evidence body in the included studies， and the evidence of the outcome indicators was integrated and summarized. RESULTS A total of 51 studies were ultimately included， encompassing 135 outcome indexes. Among these， 19 indicators （14.1%） were of high quality， 87 （64.4%） were of medium quality， 26 （19.3%） were of low quality， and 3 （2.2%） were of very low quality. Overall， the evidence quality of the outcome indicators in the included studies was medium to low quality. The integrated results of evidence on the efficacy of outcome indexes showed that compared with conventional Western medicine， calcium dobesilate or placebo， TCM had significant advantages in improving overall efficacy， reducing bleeding spot area， reducing macular foveal thickness， and increasing visual improvement rate. In addition，the combination of TCM and conventional Western medicine or calcium dobesilate was significantly more effective than using conventional Western medicine or calcium dobesilate alone. CONCLUSIONS The overall quality of the evidence in the systematic evaluation/meta-analysis study on the treatment of DR with TCM is medium to low quality. Based on existing research findings， TCM demonstrates good clinical efficacy in the treatment of DR.

The innate immune system detects cellular stressors and microbial infections, activating programmed cell death (PCD) pathways to eliminate intracellular pathogens and maintain homeostasis. Among these pathways, pyroptosis, apoptosis, and necroptosis represent the most characteristic forms of PCD. Although initially regarded as mechanistically distinct, emerging research has revealed significant crosstalk among their signaling cascades. Consequently, the concept of PANoptosis has been proposed—an inflammatory cell death pathway driven by caspases and receptor-interacting protein kinases (RIPKs), and regulated by the PANoptosome, which integrates key features of pyroptosis, apoptosis, and necroptosis. The core mechanism of PANoptosis involves the assembly and activation of the PANoptosome, a macromolecular complex composed of three structural components: sensor proteins, adaptor proteins, and effector proteins. Sensors detect upstream stimuli and transmit signals downstream, recruiting critical molecules via adaptors to form a molecular scaffold. This scaffold activates effectors, triggering intracellular signaling cascades that culminate in PANoptosis. The PANoptosome is regulated by upstream molecules such as interferon regulatory factor 1 (IRF1), transforming growth factor beta-activated kinase 1 (TAK1), and adenosine deaminase acting on RNA 1 (ADAR1), which function as molecular switches to control PANoptosis. Targeting these switches represents a promising therapeutic strategy. Furthermore, PANoptosis is influenced by organelle functions, including those of the mitochondria, endoplasmic reticulum, and lysosomes, highlighting organelle-targeted interventions as effective regulatory approaches. Cardiovascular diseases (CVDs), the leading global cause of morbidity and mortality, are profoundly impacted by PCD. Extensive crosstalk among multiple cell death pathways in CVDs suggests a complex regulatory network. As a novel cell death modality bridging pyroptosis, apoptosis, and necroptosis, PANoptosis offers fresh insights into the complexity of cell death and provides innovative strategies for CVD treatment. This review summarizes current evidence linking PANoptosis to various CVDs, including myocardial ischemia/reperfusion injury, myocardial infarction, heart failure, arrhythmogenic cardiomyopathy, sepsis-induced cardiomyopathy, cardiotoxic injury, atherosclerosis, abdominal aortic aneurysm, thoracic aortic aneurysm and dissection, and vascular toxic injury, thereby providing critical clinical insights into CVD pathophysiology. However, the current understanding of PANoptosis in CVDs remains incomplete. First, while PANoptosis in cardiomyocytes and vascular smooth muscle cells has been implicated in CVD pathogenesis, its role in other cell types—such as vascular endothelial cells and immune cells (e.g., macrophages)—warrants further investigation. Second, although pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are known to activate the PANoptosome in infectious diseases, the stimuli driving PANoptosis in CVDs remain poorly defined. Additionally, methodological challenges persist in identifying PANoptosome assembly in CVDs and in establishing reliable PANoptosis models. Beyond the diseases discussed, PANoptosis may also play a role in viral myocarditis and diabetic cardiomyopathy, necessitating further exploration. In conclusion, elucidating the role of PANoptosis in CVDs opens new avenues for drug development. Targeting this pathway could yield transformative therapies, addressing unmet clinical needs in cardiovascular medicine.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.

BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome