Objective To analyze the clinical efficacy of real-world bulleyaconitine A tablets combined with salt and pepper seven-seed hot package in the treatment of knee osteoarthritis(KOA).Methods 110 outpatient patients from the Department of Orthopedics,Shenzhen Traditional Chinese Medicine Hospital from December 2023 to August 2024 were selected,they were randomly divided into control group of 53 cases and treatment group of 57 cases.The patients in control group were treated with flurbiprofen gel paste,the patients in treatment group received oral administration of bulleyaconitine A tablets and external application of Jiaoyan Qizi hot package,the treatment course were all 4 weeks.All patients were followed up for 2 weeks after the end of treatment.Western Ontario and McMaster University osteoarthritis index(WOMAC)score,Lequesne score,12-item short form health survey(SF-12)score and clinical efficacy were compared between two groups,and adverse events were recorded.Results The total effective rate of treatment group was 87.7％,which was significantly higher than 71.7％of control group(P＜0.05);After treatment,WOMAC score,Lequesne score and SF-12 score in two groups were better than before treatment(P＜0.05).The improvement of WOMAC score,Lequesne score and SF-12 score in treatment group were more obvious(P＜0.05).Conclusion For KOA patients with cold and damp obstruction syndrome,the use of bulleyaconitine A tablets combined with Jiaoyan Qizi hot package can alleviate knee joint pain,improve knee joint mobility,and enhance patients'quality of life.

Objective To analyze the clinical efficacy of real-world bulleyaconitine A tablets combined with salt and pepper seven-seed hot package in the treatment of knee osteoarthritis(KOA).Methods 110 outpatient patients from the Department of Orthopedics,Shenzhen Traditional Chinese Medicine Hospital from December 2023 to August 2024 were selected,they were randomly divided into control group of 53 cases and treatment group of 57 cases.The patients in control group were treated with flurbiprofen gel paste,the patients in treatment group received oral administration of bulleyaconitine A tablets and external application of Jiaoyan Qizi hot package,the treatment course were all 4 weeks.All patients were followed up for 2 weeks after the end of treatment.Western Ontario and McMaster University osteoarthritis index(WOMAC)score,Lequesne score,12-item short form health survey(SF-12)score and clinical efficacy were compared between two groups,and adverse events were recorded.Results The total effective rate of treatment group was 87.7％,which was significantly higher than 71.7％of control group(P＜0.05);After treatment,WOMAC score,Lequesne score and SF-12 score in two groups were better than before treatment(P＜0.05).The improvement of WOMAC score,Lequesne score and SF-12 score in treatment group were more obvious(P＜0.05).Conclusion For KOA patients with cold and damp obstruction syndrome,the use of bulleyaconitine A tablets combined with Jiaoyan Qizi hot package can alleviate knee joint pain,improve knee joint mobility,and enhance patients'quality of life.

Objective To investigate the mechanism by which Huangqi Guizhi Wuwu decoction(HQGZWWD)regulates nerve injury(NI)through vascular endothelial growth factor(VEGF)pathway based on a combination of network pharmacology and molecular docking techniques.Methods Active ingredients and targets of HQGZWWD were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.A drug-ingredient-target network was constructed by integrated with data from OMIM,GeneCards,and CTD databases to identify VEGF/NI-related targets.Protein-protein interaction analyses were conducted by using STRING network platform,which were further analyzed by using the DAVID database for Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.A"compound-target-pathway"network was constructed by using Cytoscape.Molecular docking was performed to validate the binding ability of core components with the targets.Results The primary constituents(quercetin,kaempferol)and principal targets[signal transducer and activator of transcription 3(STAT3),caspase 3,epidermal growth factor receptor(EGFR),etc.]of HQGZWWD were identified.KEGG analysis revealed that the targets were enriched cancer,EGFR inhibitor resistance,and advanced glycation end-products-receptor for advanced glycation end-products etc.signaling pathways.Molecular docking demonstrated binding energy between core components and STAT3,caspace 3,EGFR,etc.,specifically,the core components exhibited strong binding energy such as STAT3(≤-7.37kcal/mol).Conclusion HQGZWWD shows potency in suppressing inflammation,oxidative stress,and apoptosis,while promoting neural repair through VEGF regulation.The integration of network pharmacology and molecular docking offers a foundational framework for mechanistic investigations.

OBJECTIVE:Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease,which seriously affects patients'quality of life.Non-invasive brain stimulation,as a common non-pharmacological treatment,has good efficacy in improving cognitive impairment after Parkinson's disease,but how to choose the optimal stimulation modality of non-invasive brain stimulation in clinical practice is still unclear.This study assessed the effects of different stimulation modalities of non-invasive brain stimulation on cognitive function in patients with Parkinson's disease by means of the network Meta-analysis,which provides an evidence-based basis for the selection of non-invasive brain stimulation modalities in the clinic.METHODS:PubMed,EMbase,Web of Science,Cochrane Library,CNKI,CBM,and WanFang databases were searched for randomized controlled trials on the effects of non-invasive brain stimulation interventions on cognitive function in patients with Parkinson's disease from the inception to August 2024.The control group was treated with conventional therapy(rehabilitation training and conventional medication)or sham stimulation,and the experimental group was treated with non-invasive brain stimulation based on the treatment in the control group.The Cochrane Risk of Bias Assessment Tool for Randomized Controlled Trials RoB 2 was used to evaluate the quality of the included studies.Literature screening and data extraction were performed independently by two researchers and the risk of bias for the included studies was evaluated.Traditional Meta-analysis and network Meta-analysis of short-term cognitive functioning scale scores and long-term cognitive functioning scale scores were performed using RevMan 5.4 and Stata 16.0 software to draw network relationship,diagrams league table and cumulative probability ranking tables.GRADE was used to rate the level of evidence for the outcome indicators.RESULTS:(1)A total of 31 randomized controlled trials were included,of which 8 studies were rated as low-risk,23 studies were rated as medium-risk,and there were no high-risk studies,comprising 1 670 subjects and involving different stimulation modalities for 14 types of non-invasive brain stimulation.(2)Network Meta-analysis showed that compared with conventional treatment,high-frequency repetitive transcranial magnetic stimulation of the first motor cortex(standardized mean difference[SMD]=0.73,95％confidence interval[CI]=0.14-1.32,P＜0.05,the surface under the cumulative ranking curve[SUCRA]=66.2％)was the most effective in improving short-term cognitive functioning in Parkinson's patients,followed by transcranial direct current stimulation of the dorsolateral prefrontal cortex(SMD=0.56,95％CI=0.14-0.98,P＜0.05,SUCRA=54.4％)and high-frequency repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex(SMD=0.52,95％CI=0.11-0.93,P＜0.05,SUCRA=51.4％);and in terms of improvement of long-term cognitive functioning in patients with Parkinson's disease,high-frequency repetitive transcranial magnetic stimulation of the first motor cortex(SMD=1.17,95％CI=0.48-1.85,P＜0.05,SUCRA=91.2％)was the most effective.CONCLUSION:Low-level intensity clinical evidence suggests that high-frequency repetitive transcranial magnetic stimulation of the first motor cortex is the most effective in improving short-term cognitive function in patients with Parkinson's disease,followed by transcranial direct current stimulation of the dorsolateral prefrontal cortex and high-frequency repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex.Also high-frequency repetitive transcranial magnetic stimulation of the first motor cortex is the best stimulation modality in improving long-term cognitive function in patients with Parkinson's disease.

Objective To investigate the mechanism by which Huangqi Guizhi Wuwu decoction(HQGZWWD)regulates nerve injury(NI)through vascular endothelial growth factor(VEGF)pathway based on a combination of network pharmacology and molecular docking techniques.Methods Active ingredients and targets of HQGZWWD were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.A drug-ingredient-target network was constructed by integrated with data from OMIM,GeneCards,and CTD databases to identify VEGF/NI-related targets.Protein-protein interaction analyses were conducted by using STRING network platform,which were further analyzed by using the DAVID database for Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.A"compound-target-pathway"network was constructed by using Cytoscape.Molecular docking was performed to validate the binding ability of core components with the targets.Results The primary constituents(quercetin,kaempferol)and principal targets[signal transducer and activator of transcription 3(STAT3),caspase 3,epidermal growth factor receptor(EGFR),etc.]of HQGZWWD were identified.KEGG analysis revealed that the targets were enriched cancer,EGFR inhibitor resistance,and advanced glycation end-products-receptor for advanced glycation end-products etc.signaling pathways.Molecular docking demonstrated binding energy between core components and STAT3,caspace 3,EGFR,etc.,specifically,the core components exhibited strong binding energy such as STAT3(≤-7.37kcal/mol).Conclusion HQGZWWD shows potency in suppressing inflammation,oxidative stress,and apoptosis,while promoting neural repair through VEGF regulation.The integration of network pharmacology and molecular docking offers a foundational framework for mechanistic investigations.

OBJECTIVE:Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease,which seriously affects patients'quality of life.Non-invasive brain stimulation,as a common non-pharmacological treatment,has good efficacy in improving cognitive impairment after Parkinson's disease,but how to choose the optimal stimulation modality of non-invasive brain stimulation in clinical practice is still unclear.This study assessed the effects of different stimulation modalities of non-invasive brain stimulation on cognitive function in patients with Parkinson's disease by means of the network Meta-analysis,which provides an evidence-based basis for the selection of non-invasive brain stimulation modalities in the clinic.METHODS:PubMed,EMbase,Web of Science,Cochrane Library,CNKI,CBM,and WanFang databases were searched for randomized controlled trials on the effects of non-invasive brain stimulation interventions on cognitive function in patients with Parkinson's disease from the inception to August 2024.The control group was treated with conventional therapy(rehabilitation training and conventional medication)or sham stimulation,and the experimental group was treated with non-invasive brain stimulation based on the treatment in the control group.The Cochrane Risk of Bias Assessment Tool for Randomized Controlled Trials RoB 2 was used to evaluate the quality of the included studies.Literature screening and data extraction were performed independently by two researchers and the risk of bias for the included studies was evaluated.Traditional Meta-analysis and network Meta-analysis of short-term cognitive functioning scale scores and long-term cognitive functioning scale scores were performed using RevMan 5.4 and Stata 16.0 software to draw network relationship,diagrams league table and cumulative probability ranking tables.GRADE was used to rate the level of evidence for the outcome indicators.RESULTS:(1)A total of 31 randomized controlled trials were included,of which 8 studies were rated as low-risk,23 studies were rated as medium-risk,and there were no high-risk studies,comprising 1 670 subjects and involving different stimulation modalities for 14 types of non-invasive brain stimulation.(2)Network Meta-analysis showed that compared with conventional treatment,high-frequency repetitive transcranial magnetic stimulation of the first motor cortex(standardized mean difference[SMD]=0.73,95％confidence interval[CI]=0.14-1.32,P＜0.05,the surface under the cumulative ranking curve[SUCRA]=66.2％)was the most effective in improving short-term cognitive functioning in Parkinson's patients,followed by transcranial direct current stimulation of the dorsolateral prefrontal cortex(SMD=0.56,95％CI=0.14-0.98,P＜0.05,SUCRA=54.4％)and high-frequency repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex(SMD=0.52,95％CI=0.11-0.93,P＜0.05,SUCRA=51.4％);and in terms of improvement of long-term cognitive functioning in patients with Parkinson's disease,high-frequency repetitive transcranial magnetic stimulation of the first motor cortex(SMD=1.17,95％CI=0.48-1.85,P＜0.05,SUCRA=91.2％)was the most effective.CONCLUSION:Low-level intensity clinical evidence suggests that high-frequency repetitive transcranial magnetic stimulation of the first motor cortex is the most effective in improving short-term cognitive function in patients with Parkinson's disease,followed by transcranial direct current stimulation of the dorsolateral prefrontal cortex and high-frequency repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex.Also high-frequency repetitive transcranial magnetic stimulation of the first motor cortex is the best stimulation modality in improving long-term cognitive function in patients with Parkinson's disease.

BACKGROUND:Medical hydrogels are new functional polymer materials with three-dimensional structural networks and excellent biocompatibility,which have been widely studied in the field of tissue engineering and drug carriers,but the research on the combination of medical hydrogels and Chinese medicine for the treatment of diseases based on tissue engineering is still in the early exploration stage.Therefore,through the analysis of the mechanism of the role of medical hydrogels,the integration of medical hydrogels and Chinese medicine in the research of the joint application of the article,can better provide ideas for scientific researchers,and the joint application of Chinese medicine and medical hydrogels is of great significance. OBJECTIVE:To explore the strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment based on tissue engineering research. METHODS:PubMed and CNKI were used to retrieve articles about the application of Chinese medicine combined with medical hydrogel in tissue engineering from January 2010 to November 2022,with the Chinese and English search terms"hydrogel,traditional Chinese medicine,drug carrier,tissue engineering".After the initial screening of all articles according to the inclusion and exclusion criteria,the 61 articles with high relevance were retained for review. RESULTS AND CONCLUSION:(1)Although the application of Chinese medicine combined with medical hydrogel is involved in intra-articular,intra-tissue organ,soft tissue wounds,tissue engineering,etc.,except for the clinical application of Chinese medicine combined with hydrogel dressing for soft tissue injury,other aspects are still in the experimental stage.(2)The development of Chinese medicine combined with medical hydrogel has great potential and development prospects,but there is a certain difficulty in the manufacture of the gel with high-performance requirements,and it is difficult to master the physical and chemical properties precisely.(3)At present,the comprehensive view of injectable hydrogel with the characteristics of easy to use,its joint use of Chinese medicine can be extended to a wider range,can be used for joint,organ,tissue engineering-related disease treatment.Smart hydrogel has high sensitivity and reversible transformation can also meet the use of the special environment.During the combined use of Chinese medicine,it also needs to understand the mechanism of action of Chinese medicine components.(4)The strategy of combining Chinese medicine with medical hydrogels for disease treatment should start with matching the therapeutic effects of Chinese medicine on organs,tissues and cells combined with appropriate types of medical hydrogels to make up for the shortcomings of traditional Chinese medicine delivery methods and frequent drug delivery.In tissue engineering,hydrogels can be loaded with stem cells after Chinese medicine intervention,or with both Chinese medicine and stem cells for disease treatment.(5)In future research of combined Chinese medicine and medical hydrogel application,we also need to consider:we should ensure that the biological properties of medical hydrogel can be quantified,and grasp the characteristics of hydrogel with different manufacturing processes of different materials to produce the required medical hydrogel that meets the application conditions.In Chinese medicine,we need to comprehensively understand and analyze the therapeutic effects and application mechanisms of known Chinese medicine monomer and Chinese medicine compound extracts,so as to achieve a more perfect combination between Chinese medicine and medical hydrogel under a more clear mechanism.With the continuous improvement of medical science and technology innovation,the medical hydrogel can be innovatively combined with other traditional treatment methods of Chinese medicine,such as acupuncture,massage,cupping and so on,to be used from multiple angles.

Objective To explore the causal relationship between sarcopenia and cognitive impairment by using a two-sample Mendelian randomization(MR)study design.Methods Hand grip strength,usual walking pace,and appendicular lean mass(ALM)were identified as the primary exposure factors for sarcopenia,while cognitive function and cognitive performance associated with cognitive impairment were considered as the outcome.The MR statistical method was applied to examine the causal associations between both variables.Results The analysis revealed a positive correlation between sarcopenia,as indicated by hand grip strength,usual walking pace and ALM,and cognitive performance.Usual walking pace and ALM were positively associated with cognitive function.No significant causal relationship was detected between hand grip strength and cognitive function.In the reverse MR analysis,cognitive performance showed a positive correlation with usual walking pace and ALM,but no significant causal link was found with hand grip strength.Cognitive function was positively related to usual walking pace,but no significant associations were observed with hand grip strength and ALM.Conclusion Sarcopenia is associated with an increased risk of cognitive impairment,and a bidirectional causal relationship appears to exist between ALM and cognitive performance.

Objective To explore the causal relationship between sarcopenia and cognitive impairment by using a two-sample Mendelian randomization(MR)study design.Methods Hand grip strength,usual walking pace,and appendicular lean mass(ALM)were identified as the primary exposure factors for sarcopenia,while cognitive function and cognitive performance associated with cognitive impairment were considered as the outcome.The MR statistical method was applied to examine the causal associations between both variables.Results The analysis revealed a positive correlation between sarcopenia,as indicated by hand grip strength,usual walking pace and ALM,and cognitive performance.Usual walking pace and ALM were positively associated with cognitive function.No significant causal relationship was detected between hand grip strength and cognitive function.In the reverse MR analysis,cognitive performance showed a positive correlation with usual walking pace and ALM,but no significant causal link was found with hand grip strength.Cognitive function was positively related to usual walking pace,but no significant associations were observed with hand grip strength and ALM.Conclusion Sarcopenia is associated with an increased risk of cognitive impairment,and a bidirectional causal relationship appears to exist between ALM and cognitive performance.

CLDN6 is a member of the CLDNs family that is specifically and highly expressed in cancers such as ovarian, testicular, endocervical, liver and lung adenocarcinoma, but hardly expressed in adult normal tissues. CLDN6 is able to activate multiple signaling pathways, which take part in the development and progression of cancer, including promoting tumor growth, migration and invasion, and promoting chemoresistance in cancer. In recent years, CLDN6 has received much attention as a novel target for cancer therapeutics. Many types of anticancer drugs targeting CLDN6 have been developed, including antibody-conjugated drugs (ADC), monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T-cell immunotherapy (CAR-T). This paper briefly summarizes the structure, expression and function of CLDN6 in tumors, and reviews the current status and ideas of developing targeted CLDN6 anticancer drugs.
Signal Transduction ; Immunotherapy ; Antibodies, Monoclonal ; Neoplasms/drug therapy*