Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

BACKGROUND:The number of patients receiving total knee arthroplasty has been increasing globally each year.Pain management is a crucial aspect following total knee arthroplasty,as effective pain control can facilitate early mobilization,reduce complications,enhance patient satisfaction,and accelerate the rehabilitation process.OBJECTIVE:To construct a visual map of post-total knee arthroplasty pain,understand the international research status and trends in this field,and provide a reference for future studies.METHODS:Relevant research articles on post-total knee arthroplasty pain were retrieved from the CNKI,WanFang Data,and Web of Science core databases,covering the period from January 2000 to December 2023.The CiteSpace software(version 6.2.3)was used to analyze the annual publication output,authors,institutions,countries,keywords,and references.Utilizing R programming language(version 4.4.1),a database was established to create line charts and bar graphs.RESULTS AND CONCLUSION:(1)Our analysis included 3 796 publications,predominantly in Chinese(3 509 articles)with the remainder in English(287 articles).(2)The United States was the most productive country in English literature,with Harvard University leading institutional output.Guangzhou University of Chinese Medicine was the top publishing institution in Chinese literature.(3)Keyword clustering identified"quality of life,""phobia,"and"acupuncture"as emerging focal points in Chinese literature,while"satisfaction"and"psychological factors"were prominent in English literature over the past five years.Co-occurrence and clustering analysis revealed dense internal connections among institutions,authors,and publications,but sparse external collaborations.(4)The study's bias on visualization analysis may have introduced bias by excluding less influential papers.(5)Regarding research hotspots,domestic research emphasized the efficacy and exploration of analgesic methods,in contrast to international research that focused on pain mechanism subtyping and analgesic drug innovation.Future research is expected to trend towards traditional Chinese medicine for postoperative pain,multimodal analgesia,and the investigation and prevention of pain typing mechanisms.

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 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.

BACKGROUND:The number of patients receiving total knee arthroplasty has been increasing globally each year.Pain management is a crucial aspect following total knee arthroplasty,as effective pain control can facilitate early mobilization,reduce complications,enhance patient satisfaction,and accelerate the rehabilitation process.OBJECTIVE:To construct a visual map of post-total knee arthroplasty pain,understand the international research status and trends in this field,and provide a reference for future studies.METHODS:Relevant research articles on post-total knee arthroplasty pain were retrieved from the CNKI,WanFang Data,and Web of Science core databases,covering the period from January 2000 to December 2023.The CiteSpace software(version 6.2.3)was used to analyze the annual publication output,authors,institutions,countries,keywords,and references.Utilizing R programming language(version 4.4.1),a database was established to create line charts and bar graphs.RESULTS AND CONCLUSION:(1)Our analysis included 3 796 publications,predominantly in Chinese(3 509 articles)with the remainder in English(287 articles).(2)The United States was the most productive country in English literature,with Harvard University leading institutional output.Guangzhou University of Chinese Medicine was the top publishing institution in Chinese literature.(3)Keyword clustering identified"quality of life,""phobia,"and"acupuncture"as emerging focal points in Chinese literature,while"satisfaction"and"psychological factors"were prominent in English literature over the past five years.Co-occurrence and clustering analysis revealed dense internal connections among institutions,authors,and publications,but sparse external collaborations.(4)The study's bias on visualization analysis may have introduced bias by excluding less influential papers.(5)Regarding research hotspots,domestic research emphasized the efficacy and exploration of analgesic methods,in contrast to international research that focused on pain mechanism subtyping and analgesic drug innovation.Future research is expected to trend towards traditional Chinese medicine for postoperative pain,multimodal analgesia,and the investigation and prevention of pain typing mechanisms.

Jansen-de Vries syndrome, also known as intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, is a rare autosomal dominant disorder characterized by multisystem involvement. This article reports the case of a young child who presented with global developmental delay, gastrointestinal dysfunction, intellectual disability, and short stature. Distinct facial features included a broad forehead, low nasal bridge, thin upper lip, and widely spaced and misaligned teeth. Additional phenotypic findings involved small hands and feet, as well as digital anomalies. Through whole-exome sequencing (WES) and copy number variation (CNV) analysis, a pathogenic variant was identified in the PPM1D gene: c.1281G > A (p.Trp427Ter). This report also reviews the current literature on the clinical characteristics, diagnostic approaches, and therapeutic advances related to this condition, aiming to provide valuable insights for its clinical diagnosis and management.

Objective:To discuss the role of angiopoietin-like protein 6(ANGPTL6)in liver fibrosis,and to analyze the improving effect of engineered exosome(Exo)-delivered ANGPTL6 mRNA on liver fibrosis.Methods:A total of 12 C57BL/6 mice were randomly divided into olive oil group(OIL group)(intraperitoneally injected with olive oil)and carbon tetrachloride(CCl4)group(intraperitoneally injected with a mixture of olive oil and CCl?),with 6 mice in each group;another 12 C57BL/6 mice were randomly divided into control group(fed a with methionine-choline sufficient diet)and methionine-choline deficient(MCD)group(fed a with MCD diet),and two kinds of mouse liver fibrosis models were established.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the ANGPTL6 mRNA and protein expression levels in liver tissue of the mice in various groups.A total of 30 mice were randomly divided into olive oil+phosphate buffered saline(PBS)group(OIL+PBS group)(intraperitoneally injected with olive oil twice a week for 8 weeks,then injected with PBS buffer by tail vein twice a week for 6 weeks),CCl4+Exo-green fluorescent protein(GFP)mRNA group(established liver fibrosis model by intraperitoneal injection of CCl4 mixture and were injected by tail vein with engineered Exo loaded with GFP mRNA for 6 weeks),and CCl?+Exo-ANGPTL6 mRNA group(established liver fibrosis model by intraperitoneal injection of CCl4 mixture and were injected by tail vein with engineered Exo loaded with ANGPTL6 mRNA for 6 weeks),with 10 mice in each group.The mice in CCl4+Exo-GFP mRNA group and CCl4+Exo-ANGPTL6 mRNA group were injected with engineered Exo twice a week,20 μg per mouse each time(volume 100 μL).ELISA method was used to detect the serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities in the mice in various groups;Masson staining and Sirius red staining were used to observe the collagen deposition in liver tissue of the mice in various groups;immunohistochemistry method was used to detect the α-smooth muscle actin(α-SMA)expression levels in liver tissue of the mice in various groups;RT-qPCR method was used to detect the expression levels of α-SMA,collagen type Ⅰ alpha 1 chain(Col1a1),transforming growth factor β1(TGF-β1),and tissue inhibitor of metalloproteinase 1(TIMP-1)mRNA in liver tissue of the mice in various groups.Results:The bioinformatics analysis results showed that ANGPTL6 expression was significantly down-regulated in activated hepatic stellate cell(aHSC).The ultrasound examination results showed that the liver surface of the mice in OIL group was fine and smooth;compared with OIL group,the liver section of the mice in CCl? group was rough and uneven.The RT-qPCR and Western blotting results showed that compared with OIL group,the ANGPTL6 mRNA and protein expression levels in liver tissue of the mice in CCl? group were significantly decreased(P<0.05).The engineered Exo extracted from the supernatant of HEK293T cells had intact structure and could be largely enriched in the fibrotic liver after tail vein injection,with GFP protein being largely expressed in the liver.The ELISA assay results showed that compared with OIL+PBS group,the ALT and AST activities in CCl4+Exo-GFP mRNA group were significantly increased(P<0.05);compared with CCl4+Exo-ANGPTL6 mRNA group,the serum ALT and AST activities in CCl4+Exo-GFP mRNA group were significantly decreased(P<0.05).The Masson staining and Sirius red staining results showed that compared with OIL+PBS group,the collagen deposition in liver tissue of the mice in CCl?+Exo-GFP mRNA group was significantly increased,and the relative collagen area was increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the collagen deposition in tissue liver of the mice in CCl?+Exo-ANGPTL6 mRNA group was significantly decreased,and the relative collagen area was decreased(P<0.05).The immunohistochemistry results showed that compared with OIL+PBS group,the α-SMA protein expression level in liver tissue of the mice in CCl?+Exo-GFP mRNA group was significantly increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the α-SMA protein expression level in liver tissue of the mice in CCl?+Exo-ANGPTL6 mRNA group was significantly decreased(P<0.05).The RT-qPCR results showed that compared with OIL+PBS group,the expression levels of Col1a1,α-SMA,TGF-β1,and TIMP-1 mRNA in liver tissue of the mice in CCl?+Exo-GFP mRNA group were significantly increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the expression levels of Col1a1,α-SMA,TGF-β1,and TIMP-1 mRNA in liver tissue of the mice in CCl?+Exo-ANGPTL6 mRNA group were significantly decreased(P<0.05).Conclusion:Engineered Exo-delivered ANGPTL6 mRNA injected via the tail vein in the mice is mainly enriched in the liver,and engineered Exo delivery of ANGPTL6 mRNA has an improving effect on liver fibrosis in the mice.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.