Research progress on the mechanism of astragaloside IV in the treatment of asthma.

Asthma is a common chronic respiratory disease, and its treatment is a core problem and challenge in clinical practice. Glucocorticoids (GCs) are the first-line therapy for the treatment of asthma. Local and systemic adverse reactions caused by GCs create obstacles to the treatment of asthma. Therefore, the research target is to find a new, safe, and effective therapeutic medicine at present. Natural products are an important source for treating asthma with low cost and low toxicity. Astragaloside IV (AS-IV) is an active ingredient of traditional Chinese medicine Astragalus mongholicus Bunge. Previous studies have indicated that AS-IV plays a therapeutic role in the treatment of asthma by inhibiting airway inflammation and remodeling the airway, and by regulating immunity and neuroendocrine function (Fig. 1) . It has a variety of biological characteristics such as multi-target intervention, high safety, and good curative effect. This article reviews the specific mechanism of AS-IV for the treatment of asthma to provide references for subsequent research.

Prognostic Significance of ANGPTL4 in Lung Adenocarcinoma: A Meta-Analysis Based on Integrated TCGA and GEO Databases.

Lung adenocarcinoma (LUAD) is a common malignant tumor with a poor prognosis. Recent studies have found that angiopoietin-like 4 (ANGPTL4) is abnormally expressed in many tumors, so it can serve as a potential prognostic marker and therapeutic target. However, its prognostic value in LUAD remains unclear. We downloaded RNA sequence data for LUAD from The Cancer Genome Atlas (TCGA) database, methylation data from the University of California Santa Cruz genome database, and clinical information. R software (version 4.1.1) was applied to analyze the ANGPTL4 expression in LUAD and nontumor samples, and the correlation with clinical characteristics to assess its prognostic and diagnostic value. In addition, we analyzed the relationship between the ANGPTL4 expression and methylation levels. Tumor IMmune Estimation Resource (TIMER) tool was taken for immune infiltration analysis, and two Gene Expression Omnibus (GEO) datasets were combined for meta-analysis. Finally, differentially expressed genes (DEGs) related to ANGPTL4 were analyzed to clarify its function. As shown in our results, ANGPTL4 was upregulated in LUAD and was an independent risk factor for the diagnosis and prognosis of LUAD. The general methylation level and eight ANGPTL4 methylation sites were significantly negatively correlated with the ANGPTL4 expression. Furthermore, we found that B cell infiltration was negatively correlated with ANGPTL4 expression and was an independent risk factor. Meta-analysis showed that the high expression of ANGPTL4 was closely associated with a poor prognosis. 153 DEGs, including the matrix metalloproteinase family, the chemokines subfamily, and the collagen family, were correlated with ANGPTL4. In this study, we found that ANGPTL4 was significantly elevated in LUAD and was closely associated with the development and poor prognosis of LUAD, suggesting that ANGPTL4 may be a prognostic biomarker and a potential therapeutic target for LUAD.

Methyl Gallate Suppresses the Migration, Invasion, and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells via the AMPK/NF-κB Signaling Pathway in vitro and in vivo.

Methyl gallate (MG), a polyphenolic compound found in plants, is widely used in traditional Chinese medicine. MG is known to alleviate several cancer symptoms. However, most studies that have reported the antitumor effects of MG have done so at the cellular level, and the inhibitory effect and therapeutic mechanism of MG in hepatocellular carcinoma (HCC) have not been extensively explored in vivo. We aimed to understand the therapeutic mechanism of MG in HCC in vitro and in vivo. MTT and colony formation assays were used to determine the impact of MG on the proliferation of a human HCC cell line, BEL-7402; wound healing and transwell assays were used to quantify the migration and invasion of HCC cells. Western blotting was used to quantify the expression of the AMPK/NF-κB signaling pathway proteins. In vivo tumor growth was measured in a xenograft tumor nude mouse model treated with MG, and hematoxylin-eosin staining and immunohistochemistry (IHC) were used to visualize the histological changes in the tumor tissue. We found that MG showed anti-proliferative effects both in vitro and in vivo. MG downregulated the protein expression of AMPK, NF-κB, p-NF-κB, and vimentin and upregulated the expression of E-cadherin in a dose-dependent manner. Additionally, MG inhibited the migration and invasion of HCC cells by decreasing MMP9 and MMP2 expression and increasing TIMP-2 expression. These were consistent with the results of IHC in vivo. MG inhibited the proliferation, migration, and invasion of HCC cells. This effect potentially involves the regulation of the AMPK/NF-κB pathway, which in turn impacts epithelial-mesenchymal transition and MMP expression.

The Efficacy and Safety of Acupuncture for Treating Osteoporotic Vertebral Compression Fracture- (OVCF-) Induced Pain: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) are common health issues in the elderly that cause chronic pain in over one-third of patients. This study was sought to evaluate the efficacy and safety of acupuncture for alleviating pain caused by OVCFs. METHODS: We performed a search of 8 electronic databases for publications from the inception to 30th March 2021. Eligible studies were randomized clinical trials (RCTs) that evaluated the effect of acupuncture for the treatment of OVCFs. Two investigators evaluated literature quality and extracted data independently. RevMan V.5.4.1 was used for data analyses, with pooled risk estimates presented as mean difference (MD) or relative risk (RR) along with corresponding 95% confidence intervals (CIs), as appropriate. RESULTS: Fourteen RCTs involving 1,130 patients were included in this meta-analysis. Compared with the control group, acupuncture showed a greater benefit on pain reduction caused by OVCFs (1 week: MD = -1.26, 95% CI: (-1.82,-0.70); 1 month: MD = -1.63, 95% CI: (-1.82,-1.43); 6 months: MD = -1.13, 95% CI: (-1.55, -0.70)). Acupuncture treatment was also associated with fewer adverse events, lower ODI index, and higher bone density than the control group (safety: (RR: 0.30, 95% CI: 0.12-0.75); ODI: MD = -3.19, 95% CI: (-5.20, -1.19); bone density: MD = 0.15, 95% CI: (0.05, 0.26)). The GRADE quality of these results was assessed as low or very low. CONCLUSIONS: Compared with the control treatment, acupuncture was more effective and safer in relieving the pain caused by OVCF and made a greater improvement on patient's ODI score and bone density. Given the low level of our study evidence, future high-quality studies are needed to verify our study findings.

Acupuncture for chronic persistent asthma based on the theory of Meridian-viscera Association: study protocol for a multi-center randomized controlled trial in China.

BACKGROUND: Acupuncture is effective in symptom and quality of life improvement of chronic asthma, but the efficacy differences between different acupoints are uncertain. In terms of the theory of Meridian-viscera Association, the study aims to investigate the different effectiveness between acupoints in Lung meridian and the acupoints in Heart meridian, so as to provide the evidence to develop a better prescription of the acupuncture treatment of chronic persistent asthma. METHODS: This study is a multicentral randomized controlled trial. A total of 68 chronic persistent asthma patients will be randomly allocated into two groups: the Lung meridian group and the Heart meridian group. This trial will include a 2-week baseline period, a 4-week treatment period with 12 sessions' acupuncture, and an 8-week follow-up period. The primary outcome is the Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes are the Asthma Control Test (ACT), Peak Expiratory Flow (PEF), and Forced Expiratory Volume in 1 s (FEV1). The AQLQ and ACT will be collected at baseline, week 4, week 8, and week 12 after randomization. PEF, FEV1, the Self-rating Anxiety Scale (SAS), and the Self-rating Depression Scale (SDS) will be assessed at baseline and week 4. DISCUSSION: The results will provide evidence for acupuncture prescription selection and the clinical efficacy improvement. The results of this trial will also be used to determine whether or not a full definitive trial will go ahead, which will further confirm the theory of Meridian-viscera Association. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/showproj.aspx?proj=43803 ) ChiCTR1900027284. Registered on 7 November 2019.

The efficacy and safety of health qigong for anti-aging: Protocol for a systematic review and meta-analysis.

BACKGROUND: Aging is a phenomenon that human's physiology and psychology is progressive decline for natural environment. Health Qigong, as a convenient and effective exercise therapy,is widely used for anti-aging. However, there are no systematic reviews or meta-analysises to evaluate the efficacy and safety of Health Qigong on anti-aging. METHODS: We will systematically search for 7 English databases(PubMed, Excerpta Medica Database, MEDLINE, Web of Science, Cochrane Library, SpringerLink, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases(namely the China National Knowledge Infrastructure Database, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical Literature Database) from their inceptions to August 2020. Randomized controlled trials (RCTs) using Health Qigong to anti-aging will be included. After the selection and extraction of eligible studies, a meta-analysis will be undertaken to assess the efficacy and safety of Health Qigong on anti-aging. Moreover, study selection, data extraction, and the evaluation of the methodological quality of trials will each be independently completed by at least 2 researchers. The Review Manager Software V.5.3 will be employed for meta-analysis to assess the risk of bias, data synthesis, and subgroup analysis. RESULTS: This review will provide the latest knowledge and evidence on the efficacy and safety of Health Qigong for anti-aging through the analysis of various evaluation scales. CONCLUSION: The conclusion of this review will help clinicians provide effective exercise therapy for anti-aging. REGISTRATION NUMBER: INPLASY202090017.

Analysis of Traditional Chinese Medicine Diagnosis and Treatment Strategies for COVID-19 Based on "The Diagnosis and Treatment Program for Coronavirus Disease-2019" from Chinese Authority.

In December 2019, coronavirus disease-2019 (COVID-19) broke out in Wuhan and other places. Seven versions of the Diagnosis and Treatment Program for Coronavirus Disease-2019 successively issued by the Chinese government have designated traditional Chinese medicine (TCM) as a necessary medical strategy. Based on the changes in TCM diagnosis and treatment strategies in these seven versions of Diagnosis and Treatment Program for Coronavirus Disease-2019, this paper collected data reported by the Chinese government media; analyzed the understanding of the etiology, pathogenesis, syndrome differentiation, treatment methods, and prescriptions of COVID-19 by TCM and evaluated the clinical efficacy of TCM strategies. COVID-19 is associated with TCM disease of pestilence, and its pathogenesis can be summarized as an "epidemic pathogen invading the body, followed by entering the internal organs and transforming into heat, resulting in pathogen trapping in the interior and healthy qi collapsing, and deficiency of qi and yin". Pathological processes should be emphasized in syndrome differentiation. The manifestations of qi deficiency and yin deficiency are exhibited during the recovery period. TCM strategies represented by Qing Fei Pai Du Tang have shown apparent advantages in improving symptoms, promoting virus clearance, and shortening hospitalization, as well as surprising efficacy of zero patient progressing from mild to severe cases in a TCM cabin hospital. Clinical data illustrate the effectiveness of TCM strategies proposed by the Chinese government. This major epidemic may bring new opportunities for TCM development.

Xiaoqinglong Decoction Protects the Lungs of AECOPD Mice through the AMPK/mTOR Signaling Pathway.

METHOD: Male C57BL/6J mice were used to establish AECOPD model by cigarette smoke and bacterial exposure. Mice were randomly divided into normal control (NC), AECOPD, XQLD, Compound C (Com C), Com C + XQLD, and Clarithromycin (CLA) groups. After treatment, the pulmonary function was evaluated by whole-body plethysmograph. The lung histopathology was observed by HE staining. The serum levels of IL-6, TNF-α, and COX-2 were detected by ELISA assay. The apoptotic index was measured by TUNEL assay, and the protein expressions of Bax, Bcl-2, Caspase-3, GRP78, and CHOP in the lung tissues were measured by western blot assay. RESULTS: XQLD treatment can improve pulmonary function (PF), ameliorate lung injury, and suppress inflammation and apoptosis of lung tissues. In addition, XQLD also markedly attenuated endoplasmic reticulum stress (ERS) and activated AMPK/mTOR pathway in the lung tissues of mice with AECOPD. However, the AMPK inhibitor Compound C decreased the protective effect of XQLD in AECOPD mice. CONCLUSION: These findings suggested that XQLD has protective effect against inflammation and apoptosis in AECOPD mice by attenuating ER stress via AMPK/mTOR pathway.

Traditional Chinese medicine may reduce the dosage of systemic glucocorticoids in required patients with acute exacerbation of chronic obstructive pulmonary disease: Study protocol for a randomized placebo-controlled trial.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) involves a severe inflammatory response. Systemic glucocorticoids are very important for the treatment of the acute exacerbation period; however, their use causes serious adverse effects. There is still no evidence on whether traditional Chinese medicine (TCM) can be used to reduce the dosage of systemic glucocorticoids in the treatment of patients with AECOPD. METHODS: In this trial, we plan to enroll 204 eligible patients with AECOPD who will be randomly assigned to receive TCM or a placebo. The effect of TCM in the treatment of patients with AECOPD will be measured by the dosage of systemic glucocorticoids (at which COPD assessment test [CAT] scores improve by 50%). Safety will also be assessed. TRIAL REGISTRATION: ChiCTR2000029568.

A randomized controlled trial for prevention of acute exacerbation of stable chronic obstructive pulmonary disease with acupoint application of traditional Chinese medicine: Study protocol clinical trial (SPIRIT Compliant).

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major public health problem that severely affects the quality of life of patients and may even endanger their lives. Although modern medicine has achieved significant results in relieving the clinical manifestations of COPD, it is difficult to prevent its progression and acute exacerbation entirely. As one of the classic aspects of acupuncture and moxibustion therapy, acupoint application of traditional Chinese medicine (TCM) can improve the clinical efficacy of western medicine in treating COPD. To date, however,there is no high-quality clinical trial to assess the effectiveness of TCM acupoint application directly in preventing acute exacerbation of stable COPD. METHODS: The study is a randomized, double-blind, placebo-controlled trial, in which 200 stable COPD patients will be randomly and equally divided into the experimental group or control group. Both groups will undergo standard Western medicine treatment; however, the patients in the experimental group will be also treated with TCM acupoint application, while the control group will be given placebo acupoint application. The duration of the treatment will be 1 month and a follow-up for 11 months. The primary outcome will be the number of acute exacerbation episodes of COPD, and the secondary outcomes will include the lung function, St George's Respiratory Questionnaire, COPD Assessment Test, and 6-Minute Walk Test. A safety assessment will also be performed during the trial. DISCUSSION: The aim of this study is to evaluate the efficacy and safety of TCM acupoint application in preventing acute exacerbation of stable COPD. Our study will provide sound evidence to support the evidence-based medicine of TCM acupoint application as an additional measure in the prevention of acute exacerbation of stable COPD. TRIAL REGISTRATION: ChiCTR1900026564, Registered 14 October, 2019.

A randomized controlled trial study protocol for Xiao-Qing-Long decoction in the treatment of refractory asthma: Study protocol clinical trial (spirit compliant).

INTRODUCTION: People with refractory asthma (RA) often seek help from Chinese medicine due to dissatisfaction with conventional treatments. External cold and internal fluid syndrome is the most common type of asthma and the Chinese herbal medicine formula Xiao-Qing-Long (XQL) decoction is commonly prescribed for patients with asthma with this syndrome. However, there is no direct evidence to support the efficacy and safety of XQL decoction for RA treatment and its potential mechanism is still unclear. METHODS: We propose a double-blind, placebo-controlled, randomized superiority trial. After a 2-week run-in period, 112 eligible participants will be recruited and randomly allocated to an experimental group or control group in a 1:1 ratio. Patients in the experimental group will take XQL decoction, while patients in the control group will receive a matched placebo. Symbicort Turbuhaler and Montelukast sodium tablets will be provided as the basic treatment for the 2 groups. All participants will receive 4 weeks of treatment and 12 weeks of follow-up. The primary outcome is the mean change in the asthma control test score from the baseline to 4 weeks posttreatment. The secondary outcomes include quality of life, lung function, curative effect of traditional Chinese medicine, and rescue medication used. This trial will also include analyses of the associations between intestinal microbiota and RA treatment. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide consolidated evidence of the effect of XQL decoction for RA and the potential mechanism by which XQL decoction acts, which will inform treatment options for patients with RA.

Meditative Movements for Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVE: Physical activity plays a specific role in the fundamental aspect of diabetes care. It is necessary to develop exercise programs for these patients. The aim of this systematic review is to summarize current evidence regarding the effectiveness of meditative movement in patients with type 2 diabetes. METHODS: The following databases were searched: PubMed, CENTRAL, Web of Science, Ovid LWW, and EMBASE. Two independent investigators searched and screened the studies by finding duplications, excluding irrelevant titles and abstracts, and then selecting eligible studies by reviewing full texts. 21 studies fulfilled the inclusion criteria. Meta-analyses were performed on glycated hemoglobin (HbA1c), fasting blood glucose (FBG) and postprandial blood glucose (PPBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and body mass index (BMI). RESULTS: Meta-analyses showed that meditative movements significantly improved FBG, HbA1c, PPBG, TC, LDL-C, and HDL-C. No improvement was found in BMI. CONCLUSIONS: The results demonstrated a favorable effect or tendency of meditative movements to improve blood glucose and blood lipid levels in patients with type 2 diabetes mellitus. The special effects of meditative movements in type 2 diabetes mellitus patients need further research.

Identification and functional characterization of NEMO in Crassostrea gigas reveals its crucial role in the NF-κB activation.

NEMO (NF-κB essential modulator) is one of the important regulatory subunits of the IκB kinase (IκK) complex that controls the activation of the NF-κB signaling pathway. Here, we have identified the homolog of NEMO from the pacific oyster Crassostrea gigas. CgNEMO harbors the conserved the IκK binding region, NEMO ubiquitin binding domain and Zinc finger domain. In terms of tissue distribution, CgNEMO is expressed in various tissues with an observed highest expression in the hemocytes. Furthermore, infection by two related Vibrio strains significantly increased CgNEMO expression in the hemocytes. Cell culture based luciferase reporter assays showed that CgNEMO activates the NF-κB reporter in a dose-pendent manner. Moreover, CgNEMO was also found to counter the IkB-dependent inhibitory effect on NF-κB activation, providing a plausible mechanism of NF-κB activation by CgNEMO. Meanwhile, site-directed mutagenesis demonstrated that the putative ubiquitination site K535 is required for the activation of NF-κB, implying that ubiquitination of NEMO may be involved in regulating its activity. Finally, RNAi mediated knockdown of CgNEMO in vivo significantly compromised the bacterial induction of key cytokines TNF-α and IL-17, strongly suggesting a role for CgNEMO in acute immune defense in oyster. In conclusion, this study provides new insights into our understanding about the evolution of NEMO mediated NF-κB activation and the induction of cytokine. Our findings may provide valuable information about diseases control and management in oyster aquaculture.

Cupping therapy for treating knee osteoarthritis: The evidence from systematic review and meta-analysis.

OBJECTIVE: Cupping therapy is widely used in East Asia, the Middle East, or Central and North Europe to manage the symptom of knee osteoarthritis (KOA). The purpose of this systematic review was to evaluate the available evidence from randomized controlled trials (RCTs) of cupping therapy for treating patients with KOA. METHODS: The following databases were searched from their inception until January 2017: PubMed, Embase, the Cochrane Central Register of Controlled Trials and four Chinese databases [WanFang Med Database, Chinese BioMedical Database, Chinese WeiPu Database, and China National Knowledge Infrastructure (CNKI)]. Only the RCTs related to the effects of cupping therapy on KOA were included in this systematic review. A quantitative synthesis of RCTs will be conducted using RevMan 5.3 software. Study selection, data extraction, and validation was performed independently by two reviewers. Cochrane criteria for risk-of-bias were used to assess the methodological quality of the trials. RESULTS: Seven RCTs met the inclusion criteria, and most were of low methodological quality. Study participants in the dry cupping therapy plus the Western medicine therapy group showed significantly greater improvements in the pain [MD = -1.01, 95%CI (-1.61, -0.41), p < 0.01], stiffness [MD = -0.81, 95%CI (-1.14, -0.48), p < 0.01] and physical function [MD = -5.53, 95%CI (-8.58, -2.47), p < 0.01] domains of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to participants in the Western medicine therapy group, with low heterogeneity (Chi2 = 0.00 p = 1.00, I2 = 0% in pain; Chi2 = 0.45 p = 0.50, I2 = 0% in stiffness; Chi2 = 1.09 p = 0.30, I2 = 9% in physical function). However, it failed to do so on a Visual Analog Scale (VAS) [MD = -0.32, 95%CI (-0.70, 0.05), p = 0.09]. In addition, when compared with Western medicine therapy alone, meta-analysis of four RCTs suggested favorable statistically significant effects of wet cupping therapy plus western medicine on response rate [MD = 1.06, 95%CI (1.01, 1.12), p = 0.03; heterogeneity: Chi2 = 1.13, p = 0.77, I2 = 0%] and Lequesne Algofunctional Index (LAI) [MD = -2.74, 95%CI (-3.41, -2.07), p < 0.01; heterogeneity: Chi2 = 2.03, p = 0.57, I2 = 0% ]. CONCLUSION: Only weak evidence can support the hypothesis that cupping therapy can effectively improve the treatment efficacy and physical function in patients with KOA.

[Determination of oleanolic acid and ursolic acid in Damnacanthus indicus from different places by RP-hPLC].

OBJECTIVE: To establish A RP-HPLC method for determination of oleanolic acid and ursolic acid in Damnacanthus indicus from different places. METHODS: After ultrasonic extraction with 95% ethanol,the separation was achieved on a Kromasil C18 column at 25 degrees C using methanol-2.0% phosphoric acid solution (90:10, v/v) as the mobile phase at a flow rate of 0.8 mL/min. The detection wavelength was 210 nm. RESULTS: Oleanolic acid showed good linear at the range of 0.124-1.24 microg (r = 0.9997). The recovery was 97.6% and RSD was 2.2%. Ursolic acid showed good linear at the range of 0.192-1.92 microg (r = 0.9999). The recovery was 102.4% and RSD was 1.9%. CONCLUSION: The proposed method is simple and accurate. It can provide reliable evidence for quality control, development and utilization of Damnacanthus indicus.