BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

Objective To analyze the problems in the operation and management of drug clinical trials and put forward targeted suggestion. Methods An electronic questionnaire survey was conducted among medical staff in about 80 hospitals in the yangtze river delta region. Results 606 valid questionnaires were received. 71% of the respondents expressed their willingness to study and participate in drug clinical trials. There were significant differences in the cognitive demands, willingness and motivation of the respondents with different occupations and educational backgrounds about the drug clinical trial work （P<0.05）. During the operation of drug clinical trials, respondents reported the main factors affecting the quality of clinical trials which including good clinical practice (GCP) awareness and subjective enthusiasm of investigators （response rate 27%）, job stability of supervisors and research coordinators （27%）, compliance of subjects （45%）, quality control of the whole process of the circulation of test drugs, medical devices and biological samples （52%）, and the informatization level of clinical trial institutions （30%）. Conclusion Hospitals, institutions and project teams could take measures to cultivate and stabilize the drug clinical trial talent team, improve the quality management system of drug clinical trials, improve work efficiency, and promote the high-quality development of drug clinical trials in medical institutions.

BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

Objective To investigate the association between physical activity levels and blood lipids among college freshmen, and to provide scientific evidence for the health management of college freshmen. Methods An electronic questionnaire survey on physical activity was conducted on freshmen of a university, and fasting blood biochemical indicators were detected. The International Physical Activity Questionnaire (IPAQ) short form was used to evaluate the physical activity levels of the participants. Dyslipidemia was defined as an abnormality in any one of the following serum lipid parameters: total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or non-high-density lipoprotein cholesterol. Binary logistic regression and stratified analyses were employed to explore the relationship between physical activity and blood lipids. Results A total of 3 401 participants were included, with an average age of 18.45 ± 0.92 years, and 60.5% were female. The prevalence of dyslipidemia was 17.7%, with a higher rate among males (22.1%) than females (14.8%). After adjusting for confounding factors related to blood lipids, high-intensity physical activity was negatively associated with the risk of elevated LDL-C among males (OR = 0.36, 95% CI: 0.13–0.99, P = 0.049). Conclusion Among freshmen at a medical college in Hubei Province, high-intensity physical activity is negatively associated with the risk of elevated LDL-C in males, but this association needs to be further confirmed by larger prospective cohort studies.

ObjectiveTo evaluate the clinical efficacy and economic value of the Jiangsu Traditional Chinese Medicine （TCM） Diagnosis and Treatment Protocol for Dominant Diseases （abbreviated as the Diagnosis and Treatment Protocol） in adult patients with non-severe community-acquired pneumonia （CAP） based on real-world clinical data. MethodsA retrospective real-world cohort study was conducted using electronic medical records of adult patients hospitalized for non-severe CAP from September 1st， 2023 to December 31st， 2024 across 10 TCM hospitals in Jiangsu province. Patients were classified into an exposure group and a non-exposure group based on whether they received Chinese herbal medicine （CHM） according to the Diagnosis and Treatment Protocol. The non-exposure group received only conventional western medicine， while the exposure group additionally received differentiated CHM for at least five consecutive days. Outcomes were compared between two patient groups， including cough resolution rate， sputum resolution rate （assessed by volume， color， and consistency）， incidence of abnormal C-reactive protein （CRP）， incidence of abnormal white blood cell （WBC） count， and radiographic resolution rate of pulmonary infiltrates on chest imaging. Multivariable logistic regression was performed to identify factors influencing clinical efficacy. Subgroup analyses were conducted according to age， gender， smoking status， history of hypertension， and pneumonia severity score （CURB-65）， and the efficacy of treatment for cough and sputum was analyzed within each subgroup. Cost-effectiveness analysis was conducted using cough resolution rate as the outcome measure， evaluating the pharmacoeconomics of the two groups. ResultsA total of 1688 patients were included with 1293 in the exposure group and 395 in the non-exposure group. Compared to the non-exposure group， the exposure group demonstrated significantly higher resolution rates of cough， sputum volume， color， and consistency， as well as a significantly lower incidence of abnormal CRP （P＜0.05）. No statistically significant difference was observed between the groups in terms of abnormal WBC count and radiographic resolution rate of pulmonary infiltrates （P＞0.05）. Logistic regression analysis showed that the cough resolution rate in the exposure group was 1.83 times that of the non-exposure group， while the probabilities of resolution in sputum volume， color， and consistency were 1.37， 2.09， and 1.56 times those of the non-exposure group， respectively （P＜0.05）. Subgroup analyses showed that the exposure group achieved significantly higher cough resolution rates across most subgroups except for populations with a CURB-65 score ≥2 or those with a history of hypertension （P＜0.05）. Specifically， among females， patients aged ≥18 and ＜65 years， non-smokers， those without hypertension， and those with a CURB-65 score of 0， the exposure group showed a higher cough resolution rate than the non-exposure group （P＜0.05）. From an economic perspective， total hospitalization cost， length of stay， antibiotic cost， and CHM cost all differed significantly between groups （P＜0.05）. The cost-effectiveness ratio （CER） was 10,788.80 CNY/case in the exposure group， while 22,513.80 CNY/case in the non-exposure group. This implies that， compared with the exposure group， the non-exposure group incurred an additional 17,302.27 CNY to achieve one case of cough resolution. When the willingness-to-pay threshold ranged from 0 to 50,000 CNY， the probability of economic advantage was consistently higher in the exposure group than in the non-exposure group. ConclusionOn the basis of conventional western medicine， the addition of CHM in accordance with the Diagnosis and Treatment Protocol can effectively improve clinical symptoms， reduce inflammatory markers， promote clinical recovery， and is more cost-effective in treating adults with non-severe CAP.

ObjectiveTo observe the real‑world effectiveness and economic outcomes of Weishi Qingjin Formula （苇石清金方， WQF） in the treatment of adult community‑acquired pneumonia （CAP） with phlegm‑heat obstructing the lung syndrome. MethodsBased on a multicenter， real-world retrospective cohort study， clinical data were collected from hospitalized adult patients diagnosed with non‑severe CAP and phlegm‑heat obstructing the lung syndrome in 10 traditional Chinese medicine （TCM） hospitals in Jiangsu province. Patients were divided into an exposure group （those who received oral WQF） and a non‑exposure group （those who did not）. The following outcomes were compared between the two groups before and after treatment， which were remission rates of clinical symptoms including cough， expectoration （sputum volume， color， consistency）， and chest pain， levels of inflammatory markers including C‑reactive protein （CRP） and white blood cell count （WBC）， and the rate of pulmonary inflammatory absorption on chest CT. Subgroup analyses were performed based on age， gender， smoking status， presence of hypertension， and the severity of community-acquired pneumonia （CURB‑65） score， comparing the two groups in terms of cough remission rate， chest pain remission rate， and chest CT absorption rate. For health economic evaluation， cost‑effectiveness analysis was used to calculate the cost‑effectiveness ratio （CER） and incremental cost‑effectiveness ratio （ICER）. Univariate sensitivity analysis and probabilistic sensitivity analysis were performed to test the robustness of the results. ResultsA total of 647 patients in the exposure group and 1491 patients in the non-exposure group were included in the final statistical analysis. There was no statistically significant difference in length of hospital stay， gender， marital status， smoking history， bronchoscopy history， and comorbidities between the groups （P＞0.05）， but age， CURB-65 score， and antibiotic use. The exposure group had significantly higher remission rates of cough and sputum consistency than the non-exposure group （P＜0.05）. After adjusting for confounders using propensity score matching and logistic regression， the cough remission rate in the exposure group was 1.49 times that of the non-exposure group （P＜0.01）. No significant difference was observed between groups in the reduction rates of CRP and WBC， and in the rate of pulmonary inflammatory absorption on chest CT （P＞0.05）. Subgroup analyses revealed that the cough remission rate in the exposure group was significantly better than that in the non-exposure group except for patients aged ≥65 years， smokers， hypertensive patients， those using other type antibiotics or not using antibiotics， and those with a CURB-65 score ≥1 （P＜0.05）. Among smokers， the chest pain remission rate in the exposure group was 4.38 times that of the non-exposure group （P＜0.01）. No significant difference in chest CT absorption rate was found between groups across subgroups of gender， age， hypertension status， or antibiotic type （P＞0.05）. In terms of economic evaluation， CER was 10,877.60 CNY/case in the exposure group and 16,773.10 CNY/case in the non-exposure group. Compared to the exposure group， the non-exposure group incurred an additional 15,034.26 CNY to achieve one case of cough resolution， indicating a more favorable cost-effectiveness profile. Probabilistic sensitivity analysis yielded results consistent with the cost-effectiveness analysis， confirming the robustness of the findings. ConclusionWQF demonstrates significant efficacy in improving cough symptoms in the treatment of adult CAP with phlegm-heat obstructing the lung syndrome， and also exhibits favorable economic benefits.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo evaluate the clinical efficacy and economic value of the Jiangsu Traditional Chinese Medicine （TCM） Diagnosis and Treatment Protocol for Dominant Diseases （abbreviated as the Diagnosis and Treatment Protocol） in adult patients with non-severe community-acquired pneumonia （CAP） based on real-world clinical data. MethodsA retrospective real-world cohort study was conducted using electronic medical records of adult patients hospitalized for non-severe CAP from September 1st， 2023 to December 31st， 2024 across 10 TCM hospitals in Jiangsu province. Patients were classified into an exposure group and a non-exposure group based on whether they received Chinese herbal medicine （CHM） according to the Diagnosis and Treatment Protocol. The non-exposure group received only conventional western medicine， while the exposure group additionally received differentiated CHM for at least five consecutive days. Outcomes were compared between two patient groups， including cough resolution rate， sputum resolution rate （assessed by volume， color， and consistency）， incidence of abnormal C-reactive protein （CRP）， incidence of abnormal white blood cell （WBC） count， and radiographic resolution rate of pulmonary infiltrates on chest imaging. Multivariable logistic regression was performed to identify factors influencing clinical efficacy. Subgroup analyses were conducted according to age， gender， smoking status， history of hypertension， and pneumonia severity score （CURB-65）， and the efficacy of treatment for cough and sputum was analyzed within each subgroup. Cost-effectiveness analysis was conducted using cough resolution rate as the outcome measure， evaluating the pharmacoeconomics of the two groups. ResultsA total of 1688 patients were included with 1293 in the exposure group and 395 in the non-exposure group. Compared to the non-exposure group， the exposure group demonstrated significantly higher resolution rates of cough， sputum volume， color， and consistency， as well as a significantly lower incidence of abnormal CRP （P＜0.05）. No statistically significant difference was observed between the groups in terms of abnormal WBC count and radiographic resolution rate of pulmonary infiltrates （P＞0.05）. Logistic regression analysis showed that the cough resolution rate in the exposure group was 1.83 times that of the non-exposure group， while the probabilities of resolution in sputum volume， color， and consistency were 1.37， 2.09， and 1.56 times those of the non-exposure group， respectively （P＜0.05）. Subgroup analyses showed that the exposure group achieved significantly higher cough resolution rates across most subgroups except for populations with a CURB-65 score ≥2 or those with a history of hypertension （P＜0.05）. Specifically， among females， patients aged ≥18 and ＜65 years， non-smokers， those without hypertension， and those with a CURB-65 score of 0， the exposure group showed a higher cough resolution rate than the non-exposure group （P＜0.05）. From an economic perspective， total hospitalization cost， length of stay， antibiotic cost， and CHM cost all differed significantly between groups （P＜0.05）. The cost-effectiveness ratio （CER） was 10,788.80 CNY/case in the exposure group， while 22,513.80 CNY/case in the non-exposure group. This implies that， compared with the exposure group， the non-exposure group incurred an additional 17,302.27 CNY to achieve one case of cough resolution. When the willingness-to-pay threshold ranged from 0 to 50,000 CNY， the probability of economic advantage was consistently higher in the exposure group than in the non-exposure group. ConclusionOn the basis of conventional western medicine， the addition of CHM in accordance with the Diagnosis and Treatment Protocol can effectively improve clinical symptoms， reduce inflammatory markers， promote clinical recovery， and is more cost-effective in treating adults with non-severe CAP.