BACKGROUND: Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted. OBJECTIVE: To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT). SEARCH STRATEGY: World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023. INCLUSION CRITERIA: Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment. DATA EXTRACTION AND ANALYSIS: Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I². RESULTS: Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I² = 68%) and low certainty. CONCLUSION CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; 23(2): 126-137.
Humans ; Dyspnea/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; COVID-19/complications* ; Fatigue/drug therapy* ; SARS-CoV-2 ; Anxiety/drug therapy* ; Depression/drug therapy* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Betacoronavirus

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective To investigate the changing trend and epidemiological characteristics of the incidence and mortality of chronic kidney disease (CKD) with age, period and birth cohort in Chinese population. Methods Based on the data of incidence and mortality of CKD in Chinese population aged 20-80 years from 1990 to 2019 in GHDx database, joinpoint regression model was used to analyze the incidence and mortality trend of CKD. An age-period-cohort model was constructed to analyze the effects of age, period, and birth cohort on the trend of CKD incidence and mortality. Results Joinpoint regression analysis showed that the standardized incidence rate of chronic kidney disease in Chinese population increased from 146.37/100 000 in 1990 to 161.52/100 000 in 2019, while the standardized mortality rate decreased from 12.98/100 000 in 1990 to 11.23/100 000 in 2019. The APC model analysis showed that the risk of CKD incidence and death in the Chinese population increased with age, while the risk of CKD incidence increased with the increase of period. The risk of death did not change significantly with the increase of period. The cohort born later had a lower risk of CKD incidence and death compared to the cohort born earlier. Conclusion At present, the age effect and period effect of the incidence and death risk of chronic kidney disease in China are dominant. It is important to take effective measures and intervene in a timely manner, especially to strengthen the protection of older high-risk groups born earlier.

Objective To investigate the effect of Euphorbia helioscopia on biological behaviors of non-small cell lung cancer(NSCLC)cells.Methods NSCLC cell lines PC-9 and A549 treated with different concentrations of Euphorbia helioscopia preparations were examined for changes in proliferation,apoptosis,invasion and migration using CCK-8 assay,colony formation assay,flow cytometry,wound healing assay and Transwell assay.Western blotting was performed to detect the changes in protein expressions of Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9 in the treated cells.PC-9 cells were injected subcutaneously into BALB/C nude mice to establish a nude mouse subcutaneous tumor model.According to the growth of subcutaneous tumors,mice were randomly divided into control group:gavaged daily with saline;Euphorbia helioscopia-treated group:gavaged daily with Euphorbia helioscopia 65 mg/mL,and Euphorbia helioscopia granules were dissolved in saline;cisplatin-treated group:injected intraperitoneally with cisplatin 4 mg/kg every 5 days,6 mice per group.The subcutaneous tumor volume and mass changes of mice were measured,and the toxic effects of Euphorbia helioscopia on heart,liver,spleen,lung and kidney as well as the therapeutic effects of Euphorbia helioscopia were observed in the mice bearing tumor.Results Euphorbia helioscopia granules concentration-dependently inhibited the proliferation and survival of PC-9 and A549 cells,significantly promoted cell apoptosis,suppressed invasion and migration abilities of the cells,up-regulated the expression levels of E-cadherin and Bax,and down-regulated the expressions of Bcl-2,vimentin,MMP2,and MMP9.In the tumor-bearing mice,treatment with Euphorbia helioscopia significantly inhibited tumor growth without producing obvious toxicity in the vital organs.Conclusion Euphorbia helioscopia can inhibit proliferation,invasion,and migration and induces apoptosis of NSCLC cells in vitro.

Chinese medicine has been used for centuries to treat a range of health conditions.This history has produced a wealth of classical literature,case studies and clinical research data detailing its use and effectiveness.However,high-quality and conclusive evidence that meets modern requirements for clinical decision support is lacking.This evidence gap limits the integration of Chinese medicine with contemporary medicine,which in turn limits global access and acceptance of Chinese medicine as a form of safe and effective health care.Over the past 20 years,researchers and organisations around the world,including the World Health Organization(WHO)and United Nations,have worked to support the integration of traditional medicines,such as Chinese medicine,with conventional medicines to improve global health care.This paper provides an overview of Chinese medicine studies published in the top four general medical journals(BMJ,JAMA,Lancet and New England Journal of Medicine)from February 2005 to February 2024 in the past 20 years to highlight the progress in the development of this evidence base.It also highlights key actions taken to promote evidence-based clinical Chinese medicine,including product and practitioner regulation,formalising education standards,and international collaborations.Research conducted at the China-Australia International Research Centre for Chinese Medicine demonstrates the benefits of such a collaboration.Through development of its unique and inclusive'whole-evidence'approach,plus clinical studies and systematic reviews,the Centre has significantly contributed to the evidence base for clinical Chinese medicine.In addition,its high-impact papers and groundbreaking monographs have been cited in international conventional medicine guidelines.While progress has certainly been made during the past 20 years to build a stronger evidence base for clinical Chinese medicine,there is still a considerable gap that limits its integration with conventional medicine.Future funding and research are needed to continue this work and achieve to safe,effective and accessible traditional medicine as part of the WHO's Universal Health Coverage strategy.

Objective:To investigate the metabolism-related proteins and their presence in the plasma of female androgenetic alopecia (FAGA) patients.Methods:From March 2021 to March 2023, FAGA patients aged 18-50 (FAGA group) and healthy women (HC group) were recruited from the Dermatology Outpatient Department of Huashan Hospital. 3 ml of peripheral venous blood was collected from each participant and centrifuged to obtain plasma. Olink proteomics analysis was performed on the collected plasma, differentially expressed proteins were screened with R language, the diagnostic accuracy of the differentially expressed proteins was assessed using receiver operating characteristic (ROC) curve. Gene ontology (GO) analysis was performed on differentially expressed proteins. Immunofluorescence analysis on hair follicles in the parietal region of the FAGA group and the occipital region of the HC group was performed to validate the differentially expressed proteins identified. SPSS 25.0 software was used to analyze the data, with normal distribution metric data represented by Mean±SD. Student’s t-test was used to compare the basic information of two groups of subjects and the relative fluorescence intensity of differentially expressed proteins in hair follicles. Pearson correlation analysis was performed on plasma metabolism-related proteins and the basic information of subjects. P<0.05 indicates a statistically significant difference. Results:Sixty-one cases were included in the FAGA group, with an average age of (33.8±7.4) years and an onset age of (29.5±7.8) years. Among them, 38 cases were mild FAGA, 14 cases were moderate, and 9 cases were severe. Twenty-seven cases were included in the HC group, with an average age of (32.0±7.7) years. There was no statistically significant difference in the basic information (age, body mass index, testosterone, 25-hydroxyvitamin D, uric acid, and ferritin levels) between the two groups of subjects ( P>0.05). Compared to the HC group, the plasma of the FAGA group showed 26 significantly upregulated differentially expressed proteins ( P<0.05), with AHCY and NECTIN2 exhibiting the most significant differences (all P=0.003). The ROC curve evaluation revealed that the area under the curve for AHCY and NECTIN2 was greater than 0.7, indicating good diagnostic accuracy. The GO analysis revealed that the differentially expressed proteins were primarily enriched in the BAT3 complex (cellular component), ubiquitin-dependent ERAD pathway, natural killer cell activation (biological process), as well as ubiquitin protein ligase binding and ubiquitin-specific protease binding (molecular function). Pearson correlation analysis revealed that AHCY ( r=-0.23, P=0.010) and NECTIN2 ( r=-0.31, P=0.033) were negatively correlated with the severity of hair loss in FAGA patients. The results of hair follicle immunofluorescence analysis showed that the relative fluorescence intensity of AHCY and NECTIN2 in the FAGA group was higher than that in the HC group ( P<0.05). In other words, both AHCY and NECTIN2 were upregulated in the FAGA group. Conclusion:Metabolism-related proteins play an important role in FAGA. AHCY and NECTIN2 may serve as early diagnostic biomarkers for FAGA.

Objective:To investigate the metabolism-related proteins and their presence in the plasma of female androgenetic alopecia (FAGA) patients.Methods:From March 2021 to March 2023, FAGA patients aged 18-50 (FAGA group) and healthy women (HC group) were recruited from the Dermatology Outpatient Department of Huashan Hospital. 3 ml of peripheral venous blood was collected from each participant and centrifuged to obtain plasma. Olink proteomics analysis was performed on the collected plasma, differentially expressed proteins were screened with R language, the diagnostic accuracy of the differentially expressed proteins was assessed using receiver operating characteristic (ROC) curve. Gene ontology (GO) analysis was performed on differentially expressed proteins. Immunofluorescence analysis on hair follicles in the parietal region of the FAGA group and the occipital region of the HC group was performed to validate the differentially expressed proteins identified. SPSS 25.0 software was used to analyze the data, with normal distribution metric data represented by Mean±SD. Student’s t-test was used to compare the basic information of two groups of subjects and the relative fluorescence intensity of differentially expressed proteins in hair follicles. Pearson correlation analysis was performed on plasma metabolism-related proteins and the basic information of subjects. P<0.05 indicates a statistically significant difference. Results:Sixty-one cases were included in the FAGA group, with an average age of (33.8±7.4) years and an onset age of (29.5±7.8) years. Among them, 38 cases were mild FAGA, 14 cases were moderate, and 9 cases were severe. Twenty-seven cases were included in the HC group, with an average age of (32.0±7.7) years. There was no statistically significant difference in the basic information (age, body mass index, testosterone, 25-hydroxyvitamin D, uric acid, and ferritin levels) between the two groups of subjects ( P>0.05). Compared to the HC group, the plasma of the FAGA group showed 26 significantly upregulated differentially expressed proteins ( P<0.05), with AHCY and NECTIN2 exhibiting the most significant differences (all P=0.003). The ROC curve evaluation revealed that the area under the curve for AHCY and NECTIN2 was greater than 0.7, indicating good diagnostic accuracy. The GO analysis revealed that the differentially expressed proteins were primarily enriched in the BAT3 complex (cellular component), ubiquitin-dependent ERAD pathway, natural killer cell activation (biological process), as well as ubiquitin protein ligase binding and ubiquitin-specific protease binding (molecular function). Pearson correlation analysis revealed that AHCY ( r=-0.23, P=0.010) and NECTIN2 ( r=-0.31, P=0.033) were negatively correlated with the severity of hair loss in FAGA patients. The results of hair follicle immunofluorescence analysis showed that the relative fluorescence intensity of AHCY and NECTIN2 in the FAGA group was higher than that in the HC group ( P<0.05). In other words, both AHCY and NECTIN2 were upregulated in the FAGA group. Conclusion:Metabolism-related proteins play an important role in FAGA. AHCY and NECTIN2 may serve as early diagnostic biomarkers for FAGA.

Objective To investigate the effect of Euphorbia helioscopia on biological behaviors of non-small cell lung cancer(NSCLC)cells.Methods NSCLC cell lines PC-9 and A549 treated with different concentrations of Euphorbia helioscopia preparations were examined for changes in proliferation,apoptosis,invasion and migration using CCK-8 assay,colony formation assay,flow cytometry,wound healing assay and Transwell assay.Western blotting was performed to detect the changes in protein expressions of Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9 in the treated cells.PC-9 cells were injected subcutaneously into BALB/C nude mice to establish a nude mouse subcutaneous tumor model.According to the growth of subcutaneous tumors,mice were randomly divided into control group:gavaged daily with saline;Euphorbia helioscopia-treated group:gavaged daily with Euphorbia helioscopia 65 mg/mL,and Euphorbia helioscopia granules were dissolved in saline;cisplatin-treated group:injected intraperitoneally with cisplatin 4 mg/kg every 5 days,6 mice per group.The subcutaneous tumor volume and mass changes of mice were measured,and the toxic effects of Euphorbia helioscopia on heart,liver,spleen,lung and kidney as well as the therapeutic effects of Euphorbia helioscopia were observed in the mice bearing tumor.Results Euphorbia helioscopia granules concentration-dependently inhibited the proliferation and survival of PC-9 and A549 cells,significantly promoted cell apoptosis,suppressed invasion and migration abilities of the cells,up-regulated the expression levels of E-cadherin and Bax,and down-regulated the expressions of Bcl-2,vimentin,MMP2,and MMP9.In the tumor-bearing mice,treatment with Euphorbia helioscopia significantly inhibited tumor growth without producing obvious toxicity in the vital organs.Conclusion Euphorbia helioscopia can inhibit proliferation,invasion,and migration and induces apoptosis of NSCLC cells in vitro.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

Skin microbiota is associated with various skin diseases. Scalp hair follicles penetrate deeply into the skin, and carry complex microbial communities distinct from those on the skin surface. Local imbalance of microbial communities may impair the skin barrier function, leading to a variety of hair and scalp diseases. This review discusses changes in microbial diversity and colonization by specific microorganisms in various hair diseases, including dandruff, folliculitis decalvans, etc., and provides new ideas for exploring the pathogenesis of and therapeutic strategies for various hair and scalp diseases.