Armeniacae semen amarum: a review on its botany, phytochemistry, pharmacology, clinical application, toxicology and pharmacokinetics.

Armeniacae semen amarum-seeds of Prunus armeniaca L. (Rosaceae) (ASA), also known as Kuxingren in Chinese, is a traditional Chinese herbal drug commonly used for lung disease and intestinal disorders. It has long been used to treat coughs and asthma, as well as to lubricate the colon and reduce constipation. ASA refers to the dried ripe seed of diverse species of Rosaceae and contains a variety of phytochemical components, including glycosides, organic acids, amino acids, flavonoids, terpenes, phytosterols, phenylpropanoids, and other components. Extensive data shows that ASA exhibits various pharmacological activities, such as anticancer activity, anti-oxidation, antimicrobial activity, anti-inflammation, protection of cardiovascular, neural, respiratory and digestive systems, antidiabetic effects, and protection of the liver and kidney, and other activities. In clinical practice, ASA can be used as a single drug or in combination with other traditional Chinese medicines, forming ASA-containing formulas, to treat various afflictions. However, it is important to consider the potential adverse reactions and pharmacokinetic properties of ASA during its clinical use. Overall, with various bioactive components, diversified pharmacological actions and potent efficacies, ASA is a promising drug that merits in-depth study on its functional mechanisms to facilitate its clinical application.

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.

Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-κB signaling cascade and inhibiting NLRP3 inflammasome activation.

Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-κB signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.

Auricular Acupuncture as a Traditional Chinese Medicine Therapy for Chronic Obstructive Pulmonary Disease Combined with Sleep Disorders.

Chronic obstructive pulmonary disease (COPD) is a clinical syndrome characterized by persistent and irreversible airflow limitation and chronic respiratory symptoms. It has a wide spectrum of complications, and sleep disorders, as part of it, are common in severe cases, especially in elderly patients. Long-term lack of sleep may lead to the aggravation of the original disease, reducing patients' quality of life. Benzodiazepines are mainly used for symptomatic treatment of COPD combined with sleep disorders. However, such drugs have the side effect of respiratory central inhibition and could probably aggravate hypoxia symptoms. Auricular acupuncture is a special method of treating physical and psychosomatic dysfunctions by stimulating specific points in the ear. This article explains the specific methods of clinical operation of auricular acupuncture in detail, including assessment of patient eligibility, medical devices used, acupuncture points, course of treatment, post-treatment care, responses to emergencies, etc. The Pittsburgh sleep quality index (PSQI) and chronic obstructive pulmonary disease assessment scale (CAT) were used as the observational index of this method. So far, clinical reports have proved that auricular acupuncture has a definite curative effect in the treatment of COPD combined with sleep disorders, and its advantages of simple operation, few adverse reactions are worthy of further study and promotion, which provide a reference for the clinical treatment of such diseases.

Acupoint Application Combined with Acupoint Massage for Treating Constipation in a Patient with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a common and frequent disease in elderly patients, with a tendency for progressive exacerbation. Constipation that reduces the quality of life and triggers the risk of diseases is a common concomitant symptom in patients with COPD. Currently, western medical treatment does not achieve the desired results for patients. A high recurrence rate accompanies it, whereas traditional Chinese medicine (TCM) has a long history and rich experience in treating chronic diseases. Both acupoint application and acupoint massage are characteristic therapies of TCM, with minor side effects, high safety, simple operation, and outstanding advantages. They are effective in treating constipation for patients with COPD and are considered an ideal alternative therapy for patients with chronic constipation. The purpose of this article is to introduce the method of acupoint application combined with acupoint massage for the treatment of constipation in patients with COPD, including the selection of points, items, treatment time, and operation procedure.

Traditional Chinese medicine monomers: Targeting pulmonary artery smooth muscle cells proliferation to treat pulmonary hypertension.

Pulmonary hypertension (PH) is a complex multifactorial disease characterized by increased pulmonary vascular resistance and pulmonary vascular remodeling (PVR), with high morbidity, disability, and mortality. The abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main pathological change causing PVR. At present, clinical treatment drugs for PH are limited, which can only improve symptoms and reduce hospitalization but cannot delay disease progression and reduce survival rate. In recent years, numerous studies have shown that traditional Chinese medicine monomers (TCMs) inhibit excessive proliferation of PASMCs resulting in alleviating PVR through multiple channels and multiple targets, which has attracted more and more attention in the treatment of PH. In this paper, the experimental evidence of inhibiting PASMCs proliferation by TCMs was summarized to provide some directions for the future development of these mentioned TCMs as anti-PH drugs in clinical.

Radical oxygen species: an important breakthrough point for botanical drugs to regulate oxidative stress and treat the disorder of glycolipid metabolism.

Background: The incidence of glycolipid metabolic diseases is extremely high worldwide, which greatly hinders people's life expectancy and patients' quality of life. Oxidative stress (OS) aggravates the development of diseases in glycolipid metabolism. Radical oxygen species (ROS) is a key factor in the signal transduction of OS, which can regulate cell apoptosis and contribute to inflammation. Currently, chemotherapies are the main method to treat disorders of glycolipid metabolism, but this can lead to drug resistance and damage to normal organs. Botanical drugs are an important source of new drugs. They are widely found in nature with availability, high practicality, and low cost. There is increasing evidence that herbal medicine has definite therapeutic effects on glycolipid metabolic diseases. Objective: This study aims to provide a valuable method for the treatment of glycolipid metabolic diseases with botanical drugs from the perspective of ROS regulation by botanical drugs and to further promote the development of effective drugs for the clinical treatment of glycolipid metabolic diseases. Methods: Using herb*, plant medicine, Chinese herbal medicine, phytochemicals, natural medicine, phytomedicine, plant extract, botanical drug, ROS, oxygen free radicals, oxygen radical, oxidizing agent, glucose and lipid metabolism, saccharometabolism, glycometabolism, lipid metabolism, blood glucose, lipoprotein, triglyceride, fatty liver, atherosclerosis, obesity, diabetes, dysglycemia, NAFLD, and DM as keywords or subject terms, relevant literature was retrieved from Web of Science and PubMed databases from 2013 to 2022 and was summarized. Results: Botanical drugs can regulate ROS by regulating mitochondrial function, endoplasmic reticulum, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), erythroid 2-related factor 2 (Nrf-2), nuclear factor κB (NF-κB), and other signaling pathways to improve OS and treat glucolipid metabolic diseases. Conclusion: The regulation of ROS by botanical drugs is multi-mechanism and multifaceted. Both cell studies and animal experiments have demonstrated the effectiveness of botanical drugs in the treatment of glycolipid metabolic diseases by regulating ROS. However, studies on safety need to be further improved, and more studies are needed to support the clinical application of botanical drugs.

Spherical pneumonia caused by Ralstonia mannitolilytica: a case report and literature review.

BACKGROUND: Spherical pneumonia is an extremely rare condition that is difficult to diagnose. It is a specific type of lung infection that often manifests as a round or round-like mass on chest imaging. Spherical pneumonia is easily misdiagnosed as a pulmonary tumor; therefore, awareness of this disease must be strengthened. CASE PRESENTATION: The patient was a 29-year-old female who had persistent cough and sputum for approximately 1 month and fever for 5 days. Chest computed tomography (CT) at our hospital revealed a mass in the lower lobe of the right lung near the hilar region, with obstructive pulmonary atelectasis and obstructive pneumonia. Although lung cancer was suspected, Ralstonia mannitolilytica was detected by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid, and no cancer cells or Mycobacterium tuberculosis were detected. Finally, the patient was diagnosed with spherical pneumonia caused by R. mannitolilytica. Anti-infective treatment, symptomatic treatment, and administration of a traditional Chinese medicine decoction were performed based on the syndrome differentiation. After 10 days of treatment, chest CT revealed few lesions in the lower lobe of the right lung, which were significantly reduced compared with those in the past. CONCLUSIONS: Spherical pneumonia caused by R. mannitolilytica has not yet been reported and differential diagnosis is key in clinical diagnosis. When spherical pneumonia is difficult to diagnose, mNGS may be a better alternative.

Astragalus and its formulas as a therapeutic option for fibrotic diseases: Pharmacology and mechanisms.

Fibrosis is the abnormal deposition of extracellular matrix, characterized by accumulation of collagen and other extracellular matrix components, which causes organ dysfunction and even death. Despite advances in understanding fibrosis pathology and clinical management, there is no treatment for fibrosis that can prevent or reverse it, existing treatment options may lead to diarrhea, nausea, bleeding, anorexia, and liver toxicity. Thus, effective drugs are needed for fibrotic diseases. Traditional Chinese medicine has played a vital role in fibrotic diseases, accumulating evidence has demonstrated that Astragalus (Astragalus mongholicus Bunge) can attenuate multiple fibrotic diseases, which include liver fibrosis, pulmonary fibrosis, peritoneal fibrosis, renal fibrosis, cardiac fibrosis, and so on, mechanisms may be related to inhibition of epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS), transforming growth factor beta 1 (TGF-ß1)/Smads, apoptosis, inflammation pathways. The purpose of this review was to summarize the pharmacology and mechanisms of Astragalus in treating fibrotic diseases, the data reviewed demonstrates that Astragalus is a promising anti-fibrotic drug, its main anti-fibrotic components are Calycosin, Astragaloside IV, Astragalus polysaccharides and formononetin. We also review formulas that contain Astragalus with anti-fibrotic effects, in which Astragalus and Salvia miltiorrhiza Bunge, Astragalus and Angelica sinensis (Oliv.) Diels are the most commonly used combinations. We propose that combining active components into new formulations may be a promising way to develop new drugs for fibrosis. Besides, we expect Astragalus to be accepted as a clinically effective method of treating fibrosis.

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.

Potential Natural Small Molecular Compounds for the Treatment of Chronic Obstructive Pulmonary Disease: An Overview.

Chronic obstructive pulmonary disease (COPD) is one of the major diseases threatening human life and health. According to the report released by the World Health Organization (WHO) in 2020, COPD has become the third leading cause of death in the world, featuring a sustainable growth of incidence rate as well as population age. The purpose of this review focuses on the advancement of bioactive natural compounds, such as baicalin, quercetin, resveratrol, and curcumin, which demonstrate promising therapeutic/interventional effects on CODP in vitro and in vivo. Information emphasizing on COPD was systematically collected from several authoritative internet databases including Web of Science, PubMed, Elsevier, Wiley Online Library, and Europe PMC, with a combination of keywords containing "COPD" and "natural small molecular compounds". The new evidence indicated that these valuable molecules featured unique functions in the treatment of COPD through various biological processes such as anti-inflammatory, anti-oxidant, anti-apoptosis, and anti-airway fibrosis. Moreover, we found that the promising effects of these natural compounds on COPD were mainly achieved through JAK3/STAT3/NF-κB and MAPK inflammatory signaling pathways, Nrf2 oxidative stress signaling pathway, and TGF-ß1/Smad 2/3 fibrosis signaling pathway, which referenced to multiple targets like TNF-α, IL-6, IL-8, TIMP-1, MMP, AKT, JAK3, IKK, PI3K, HO-1, MAPK, P38, ERK, etc. Current challenges and future directions in this promising field are also discussed at the end of this review. For the convenience of the readers, this review is divided into ten parts according to the structures of potential natural small molecular compounds. We hope that this review brings a quick look and provides some inspiration for the research of COPD.

Tiao-bu-fei-shen formula promotes downregulation of the caveolin 1-p38 mapk signaling pathway in COPD - Associated tracheobronchomalacia cell model.

ETHNOPHARMACOLOGICAL RELEVANCE: The Tiao-bu-fei-shen (TBFS) formula, extensively used in Traditional Chinese Medicine (TCM), can enhance therapeutic efficacy and reduce the frequency of acute exacerbations of lung-kidney Qi deficiency in patients with chronic obstructive pulmonary disease (COPD). According to both TCM theory and long-term observation of practice, TBFS has become an effective treatment for COPD-associated tracheobronchomalacia (TBM). AIM OF THE STUDY: To investigate the mechanism of the TBFS formula in treating COPD-associated TBM based on caveolin 1-p38 MAPK signaling and apoptosis. MATERIALS AND METHODS: A rat COPD model was prepared by exposure to smoking combined with tracheal lipopolysaccharide injection. The trachea or bronchus chondrocytes from COPD rats were isolated, cultured, and treated with 10 ng/mL IL-1ß for 24 h to develop a model of COPD-associated TBM. Normal rats were administered TBFS to prepare drug-containing serum, and CCK8 assays were used to screen the optimal drug-containing serum concentration and SB203580 dose. TBFS drug-containing serum and SB203580 were processed separately for the control, model, drug-containing serum, blocker, and drug-containing serum combined with blocker groups. Flow cytometry and CCK8 assays were used to detect apoptosis and proliferative activity. Toluidine blue staining and immunohistochemistry were used to analyze the chondrocyte proteoglycan and type II collagen content. Western blotting was used to detect the expression of caveolin 1, p-p38 MAPK, TNF-α, IL-1ß, MMP-13, Bax, and Bcl-2 proteins. Quantitative PCR was used to detect the expression of caveolin 1, p38 MAPK, IL-1ß, MMP-13, Bax, Bcl-2, and miR-140-5p. RESULTS: The isolation and identification of bronchial chondrocytes from COPD rats revealed that 10 ng/mL IL-1ß can produce a stable COPD-associated TBM model. Screened via the CCK8 method, fourth-generation bronchial chondrocytes were determined as the optimal cells, and 5 µM SB203580 and 5% low-dose drug-containing serum were the optimal intervention doses. The experimental chondrocytes of each group were treated separately for 48 h. Toluidine blue staining and immunohistochemical analysis revealed that TBFS drug-containing serum, SB203580, and TBFS drug-containing serum combined with SB203580 can effectively increase the proteoglycan and type II collagen content after chondrocyte degradation. Flow cytometry of cells treated with SB203580 and TBFS drug-containing serum combined with SB203580 revealed significantly reduced cell apoptosis and enhanced cell proliferation activity. Western blot and qPCR analyses revealed that the TBFS drug-containing serum, SB203580, and TBFS drug-containing serum combined with SB203580 effectively inhibit the expression of caveolin 1, p-p38 MAPK, MMP-13, IL-1ß, TNF-α, and Bax proteins while promoting Bcl -2 protein expression. Treatment with TBFS drug-containing serum and SB203580 effectively inhibited the expression of MMP-13, p38 MAPK, caveolin 1, and Bax genes, and promoted the expression of Bcl-2 and miR-140-5p genes. CONCLUSIONS: A concentration of 10 ng/mL of IL-1ß can generate a stable COPD-associated TBM cell model. TBFS can improve the proteoglycan and type II collagen content, increase cell activity, and reduce the amount of chondrocyte apoptosis. The role of TBFS may be related to mechanisms of inhibiting the expression of the key signaling molecules caveolin 1 and p-p38 MAPK in the caveolin 1-p38 MAPK signaling pathway, thereby reducing the expression of the downstream effector products MMP-13, IL-1ß, and TNF-α, while inhibiting the expression of the apoptotic gene Bax and improving the expression of Bcl-2 and miR-140-5p genes.

Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/ß-NF-κB and Keap1-Nrf2 Signalling Pathways.

Dehydrocostus lactone (DCL) is a major sesquiterpene lactone isolated from Aucklandia lappa Decne, a traditional Chinese herbal medicine that used to treat gastrointestinal diseases. This study aimed to examine the therapeutic effects of DCL on dextran sulfate sodium (DSS)-induced colitis with a focus on identifying the molecular mechanisms involved in DCL-mediated anti-inflammatory activity in macrophages. First, oral administration of DCL (5-15 mg/kg) not only ameliorated symptoms of colitis and colonic barrier injury, but also inhibited the expression of proinflammatory cytokines and myeloperoxidase in colon tissues in DSS-challenged mice. Furthermore, DCL also exhibited significant anti-inflammatory activity in LPS/IFNγ-stimulated RAW264.7 macrophages. Importantly, DCL significantly suppressed the phosphorylation and degradation of IκBα and subsequent NF-κB nuclear translocation, and enhanced the nuclear accumulation of Nrf2 in LPS/IFNγ-treated RAW264.7 cells. Mechanistically, DCL could directly interact with IKKα/ß and Keap1, thereby leading to the inhibition of NF-κB signalling and the activation of Nrf2 pathway. Furthermore, DCL-mediated actions were abolished by dithiothreitol, suggesting a thiol-mediated covalent linkage between DCL and IKKα/ß or Keap1. These findings demonstrated that DCL ameliorates colitis by targeting NF-κB and Nrf2 signalling, suggesting that DCL may be a promising candidate in the clinical treatment of colitis.

Effect of Gut Microbiota on the Metabolism of Chemical Constituents of Berberis kansuensis Extract Based on UHPLC-Orbitrap-MS Technique.

The dried stem bark of Berberis kansuensis is a commonly used Tibetan herbal medicine for the treatment of diabetes. Its main chemical components are alkaloids, such as berberine, magnoflorine and jatrorrhizine. However, the role of gut microbiota in the in vivo metabolism of these chemical components has not been fully elucidated. In this study, an ultra-high performance liquid chromatography method coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap-MS) technology was applied to detect and identify prototype components and metabolites in rat intestinal contents and serum samples after oral administration of a B. kansuensis extract. A total of 16 prototype components and 40 metabolites were identified. The primary metabolic pathways of the chemical components from B. kansuensis extract were demethylation, desaturation, deglycosylation, reduction, hydroxylation, and other conjugation reactions including sulfation, glucuronidation, glycosidation, and methylation. By comparing the differences of metabolites between diabetic and pseudo-germ-free diabetic rats, we found that the metabolic transformation of some chemical components in B. kansuensis extract such as bufotenin, ferulic acid 4-O-ß-D-glucopyranoside, magnoflorine, and 8-oxyberberine, was affected by the gut microbiota. The results revealed that the gut microbiota can affect the metabolic transformation of chemical constituents in B. kansuensis extract. These findings can enhance our understanding of the active ingredients of B. kansuensis extract and the key role of the gut microbiota on them.

Oridonin: A Review of Its Pharmacology, Pharmacokinetics and Toxicity.

Oridonin, as a natural terpenoids found in traditional Chinese herbal medicine Isodon rubescens (Hemsl.) H.Hara, is widely present in numerous Chinese medicine preparations. The purpose of this review focuses on providing the latest and comprehensive information on the pharmacology, pharmacokinetics and toxicity of oridonin, to excavate the therapeutic potential and explore promising ways to balance toxicity and efficacy of this natural compound. Information concerning oridonin was systematically collected from the authoritative internet database of PubMed, Elsevier, Web of Science, Wiley Online Library and Europe PMC applying a combination of keywords involving "pharmacology," "pharmacokinetics," and "toxicology". New evidence shows that oridonin possesses a wide range of pharmacological properties, including anticancer, anti-inflammatory, hepatorenal activities as well as cardioprotective protective activities and so on. Although significant advancement has been witnessed in this field, some basic and intricate issues still exist such as the specific mechanism of oridonin against related diseases not being clear. Moreover, several lines of evidence indicated that oridonin may exhibit adverse effects, even toxicity under specific circumstances, which sparked intense debate and concern about security of oridonin. Based on the current progress, future research directions should emphasize on 1) investigating the interrelationship between concentration and pharmacological effects as well as toxicity, 2) reducing pharmacological toxicity, and 3) modifying the structure of oridonin-one of the pivotal approaches to strengthen pharmacological activity and bioavailability. We hope that this review can provide some inspiration for the research of oridonin in the future.

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.

Modified Maimendong decoction in the treatment of patients with idiopathic pulmonary fibrosis: Study protocol for a randomized controlled trial.

INTRODUCTION: With dissatisfaction of western medicine, traditional Chinese medicine becomes alternative treatment for idiopathic pulmonary fibrosis patients. The common syndrome of idiopathic pulmonary fibrosis (IPF) is qi and yin deficiency syndrome. The prescription, Modified Maimendong Decoction (MMD), is usually used for IPF patients with qi and yin deficiency syndrome. However, there is no convinced evidence for the efficacy and safety of MMD to treat IPF. METHODS: A double-blind, placebo-controlled, randomized clinical trial was put forward by us. After a 1-day run-in period, 60 eligible patients will be included in the study. These subjects will be allocated to the experiment group or control group in a 1:1 ratio. Patients in the experiment group will take MMD plus Pirfenidone capsule. At the same time, patients in the control group will receive a matched placebo plus Pirfenidone capsule. All subjects will receive 24 weeks of treatment and follow-up period. The primary outcomes are the mean change from the baseline in forced vital capacity and times of acute exacerbations at week 4, 12, 24. Secondary outcomes are the mean change from baseline in the St. George's respiratory questionnaire total score, forced expiratory volume in 1 second percentage/forced vital capacity, diffusing capacity of Carbon monoxide, brain natriuretic peptide, and curative effect of traditional Chinese medicine syndrome at week 4, 12, and 24. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide the evidence for the effect of MMD in patients with idiopathic pulmonary fibrosis.

A randomized controlled clinical trial study protocol of Liuwei Dihuang pills in the adjuvant treatment of diabetic kidney disease.

INTRODUCTION: A large number of patients with diabetic kidney disease (DKD) approach traditional Chinese medicine (TCM) owing to discontent with standard treatments. Based on TCM theory and clinical experience, the syndrome of kidney yin deficiency is a common type of DKD. Liuwei Dihuang pills (LDPs) is a common prescription of a Chinese herbal formula for patients presenting this syndrome of DKD. However, well-established data supporting the efficacy and safety of LDP in DKD treatment are lacking. METHODS: We have designed a double-blind, placebo-controlled, randomized trial. After a 2-week run-in period, 124 eligible participants with DKD will be assigned to either the experimental or the control group in a 1:1 ratio. Patients in the experimental group will receive LDP, while patients in the control group will receive a matched placebo. As the basic treatment in the 2 groups, metformin hydrochloride sustained-release tablets, for blood glucose control, and irbesartan tablets, for blood pressure regulation, will be provided. All participants will undergo 4 weeks of treatment and 12 weeks of follow-up. The primary outcome is the change in 24 hours urinary protein levels, measured from the baseline to the end of the treatment phase (week 24). The secondary outcomes to be assessed include the change in serum creatinine and estimated glomerular filtration rate, urinary albumin excretion rate, improvement of TCM syndromes and symptoms, fasting blood glucose and postprandial 2-hour blood glucose, blood lipids (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, from baseline to weeks 12 and 24. DISCUSSION: The results of this study will provide high-quality evidence of the effects of LDP in DKD treatment, which will provide an alternative treatment strategy in patients with DKD.

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.

Evaluation of clinical efficacy of integrated traditional Chinese and Western medicine in the treatment of acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a common disease in critically ill patients that has a high incidence and mortality rate worldwide. At present, there is no specific treatment for ARDS. Traditional Chinese medicine has been shown to have good potential in preventing and treating ARDS, especially in reducing the dosages of Western medicines and therefore, adverse drug reactions. The purpose of this study is to compare the clinical efficacy of integrated Chinese and Western medicine to that of Western medicine alone in the treatment of ARDS. METHODS: We are proposing a prospective, multicenter, randomized, double-blind, placebo-controlled study in which 110 eligible patients would be enrolled and randomly divided into a Western medicine treatment group and an integrated Chinese and Western medicine treatment group. After 2 weeks of interventions and 1 year of follow-up, the clinical efficacy and safety of Jiawei qianyang dan in ARDS patients would be observed. The outcomes measured would include the Traditional Chinese medicine symptom score, the oxygenation index (PɑO2/FiO2), extravascular pulmonary water index, duration of mechanical ventilation, number of ICU hospitalization days, and the 28-day mortality rate for the 2 groups before and after treatment. The all-cause mortality rate, respiratory failure mortality rate, and readmission rate after 1 year of follow-up will be statistically analyzed and safety will be evaluated. DISCUSSION: In this study, we aim to demonstrate the greater clinical efficacy of integrated traditional Chinese and Western medicine in the treatment of ARDS compared to that of Western medicine alone. In order to do this, we hope to provide evidence for the clinically supportive effect of the Jiawei qianyang dan in the treatment of ARDS and therefore demonstrate a more effective treatment.