[Analysis of clinical research features and outcome indexes of traditional Chinese medicine intervention in septic kidney injury].

This study aims to systematically review the clinical features and outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) intervention in septic kidney injury and provide a reference for optimizing clinical study design and building the core outcome set(COS) of TCM treatment of septic kidney injury. Computer searches were conducted on PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed to find published RCT of TCM intervention in septic kidney injury in the past five years, extract the basic characteristics, intervention measures, outcome indicators, and other data of included studies, and conduct descriptive analysis. 53 RCTs were included, and the sample size was mostly concentrated in 60-80 cases, with abdominal infection being the most common(15 articles, 83.3%) and the TCM syndrome of blood stasis being the most frequent(9 articles, 50.0%). The frequency of intervention methods from high to low were TCM decoction(28 articles, 52.8%), Chinese patent medicine(22 articles, 41.5%), and combined TCM therapy(3 articles, 7.5%); the intervention time of the trial was more than 7 d(34 articles, 69.4%). The risk of bias in included studies was unclear. A total of 84 outcome indicators were involved, which were divided into 9 fields, including 63 physical and chemical tests(305 times, 72.2%), 4 kinds of disease degree(48 times, 11.6%), 4 kinds of clinical effective rate(15 times, 3.6%), 1 kind of quality of life(1 time, 0.2%), 2 kinds of economic evaluation(14 times, 3.3%), 1 kind of TCM disease(9 times, 2.1%), 2 kinds of long-term prognosis(16 times, 3.8%), 2 kinds of safety events(6 times, 1.4%), and 5 other indicators(8 times, 0.7%). The cumulative frequency was 422 times, among which the outcome indicators with higher frequency were inflammatory factors(42 articles, 79.2%) and markers of renal function and kidney injury(40 articles, 75.5%). Only 1(1.9%) of the included articles mentioned primary and secondary outcome indicators, and 6 articles(11.3%) mentioned safety events, 13 articles(24.5%) mentioned economic assessment. The RCT quality of TCM intervention in septic renal injury was generally low, and the reference standards for sepsis, kidney injury, and TCM syndrome diagnosis were not uniform. There are some problems in outcome indicators, such as unclear distinction between primary and secondary indicators, neglect of endpoint indicators, lack of application of TCM characteristic indicators, and insufficient attention to safety events and economic assessment. It is suggested that the quality of clinical research methodology should be improved in the future, and the COS should be constructed to provide high-level evidence-based evidence for TCM intervention in septic kidney injury.

Bu-Fei Yi-Shen Granules Reduce Acute Exacerbations in Patients with GOLD 3-4 COPD: A Randomized Controlled Trial.

Purpose: Chronic obstructive pulmonary disease (COPD) is a disease characterized by frequent acute exacerbations (AEs), especially in severe and very severe cases. We aimed to evaluate the efficacy and safety of Bu-fei Yi-shen granules (BYGs) for COPD. Patients and Methods: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of 348 COPD patients with GOLD 3-4 COPD. The patients were randomly assigned into experimental or control groups in a 1:1 ratio. Patients in the experimental group were prescribed BYG, while those in the control group were administered a placebo, orally, twice daily, with 5 days on and 2 days off per week for 52 weeks. The outcomes included AEs, pulmonary function, clinical signs and symptoms, dyspnea scores (mMRC), quality of life scores, and a 6-minute walk test (6MWT). Results: A total of 280 patients completed the trial, including 135 patients in the experimental group and 145 in the control group. Compared to the control group, significant differences were observed in frequencies of AEs (mean difference: -0.35; 95% CI: -0.61, -0.10; P = 0.006) and AE-related hospitalizations (-0.18; 95% CI: -0.36, -0.01; P = 0.04), 6MWD (40.93 m; 95% CI: 32.03, 49.83; P < 0.001), mMRC (-0.57; 95% CI: -0.76, -0.37; P < 0.001), total symptoms (-2.18; 95% CI: -2.84, -1.53; P < 0.001), SF-36 (11.60; 95% CI: 8.23, 14.97; P < 0.001), and mCOPD-PRO (-0.45; 95% CI: -0.57, -0.33; P < 0.001) after treatment. However, there were no significant differences in mortality, pulmonary function, and mESQ-PRO scores (P > 0.05). No obvious adverse events were observed. Conclusion: BYG, as compared to a placebo, could significantly reduce the frequencies of AEs and AE-related hospitalizations for GOLD 3-4 COPD patients. Clinical symptoms, treatment satisfaction, quality of life, and exercise capacity improved. There was no significant improvement in mortality and pulmonary function.

Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear. OBJECTIVE: The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment. MAIN OUTCOME MEASURES: The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George's Respiratory Questionnaire for IPF (SGRQ-I) score. RESULTS: The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: -3.30 days; 95% CI, -6.300 to -0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: -0.67; 95% CI: -0.89 to -0.44; P < 0.001) and SGRQ-I score (between-group difference: -10.36; 95% CI: -16.483 to -4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: -0.67; 95% CI: -0.91 to -0.43; P < 0.001) and SGRQ-I (between-group difference: -10.28; 95% CI, -15.838 to -4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant. CONCLUSION: KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.

Metabolomic profiling combined with network analysis of serum pharmacochemistry to reveal the therapeutic mechanism of Ardisiae Japonicae Herba against acute lung injury.

Introduction: Acute lung injury (ALI) is a common and devastating respiratory disease associated with uncontrolled inflammatory response and transepithelial neutrophil migration. In recent years, a growing number of studies have found that Ardisiae Japonicae Herba (AJH) has a favorable anti-inflammatory effect. However, its serum material basis and molecular mechanism are still unknown in ALI treatment. In this study, metabolomics and network analysis of serum pharmacochemistry were used to explore the therapeutic effect and molecular mechanism of AJH against lipopolysaccharide (LPS)-induced ALI. Methods: A total of 12 rats for serum pharmacochemistry analysis were randomly divided into the LPS group and LPS + AJH-treated group (treated with AJH extract 20 g/kg/d), which were administered LPS (2 mg/kg) by intratracheal instillation and then continuously administered for 7 days. Moreover, 36 rats for metabolomic research were divided into control, LPS, LPS + AJH-treated (5, 10, and 20 g/kg/d), and LPS + dexamethasone (Dex) (2.3 × 10-4 g/kg/d) groups. After 1 h of the seventh administration, the LPS, LPS + AJH-treated, and LPS + Dex groups were administered LPS by intratracheal instillation to induce ALI. The serum pharmacochemistry profiling was performed by UPLC-Orbitrap Fusion MS to identify serum components, which further explore the molecular mechanism of AJH against ALI by network analysis. Meanwhile, metabolomics was used to select the potential biomarkers and related metabolic pathways and to analyze the therapeutic mechanism of AJH against ALI. Results: The results showed that 71 serum components and 18 related metabolites were identified in ALI rat serum. We found that 81 overlapping targets were frequently involved in AGE-RAGE, PI3K-AKT, and JAK-STAT signaling pathways in network analysis. The LPS + AJH-treated groups exerted protective effects against ALI by reducing the infiltration of inflammatory cells and achieved anti-inflammatory efficacy by significantly regulating the interleukin (IL)-6 and IL-10 levels. Metabolomics analysis shows that the therapeutic effect of AJH on ALI involves 43 potential biomarkers and 14 metabolic pathways, especially phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism pathways, to be influenced, which implied the potential mechanism of AJH in ALI treatment. Discussion: Our study initially elucidated the material basis and effective mechanism of AJH against ALI, which provided a solid basis for AJH application.

LncRNA PROX1 antisense RNA 1 promotes PD-L1-mediated proliferation, metastasis, and immune escape in colorectal cancer by interacting with miR-520d.

It was recently found that lncRNA PROX1 antisense RNA 1 (PROX1-AS1) manifested oncogenicity in a variety of malignancies. This work intended to investigate the molecular mechanisms of PROX1-AS1 in colorectal cancer (CRC) development and immune evasion. In this study, both PROX1-AS1 and PD-L1 expressions were lifted in CRC tissues and cells. PROX1-AS1 interference restrained CRC cell proliferation, migration, invasion, as well as CD8 + T-lymphocyte apoptosis, but increased the cytotoxicity and percentage of CD8 + T lymphocytes. The inhibitory effects of PROX1-AS1 inhibition on CRC progression and immune escape were positively related to PD-L1 suppression. PROX1-AS1 absorbed miR-520d to upregulate PD-L1 expression. PROX1-AS1 facilitated CRC progression and immune escape by targeting miR-520d. Furthermore, PROX1-AS1 deletion impaired CRC tumor growth in vivo . To sum up, this study affirmed that PROX1-AS1 could absorb miR-520d to upregulate PD-L1 in CRC, thereby promoting tumor progression and immune escape.

Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway.

BACKGROUND: Effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) demonstrates positive effects on stable chronic obstructive pulmonary disease (COPD). PURPOSE: To investigate the mechanisms of ECC-BYF III on COPD rats from the aspect of airway epithelial cell senescence. METHODS: COPD model rats (Sprague-Dawley rat) were treated with ECC-BYF III for 8 weeks, and the efficacy was evaluated. Cigarette smoke extract (CSE)-induced senescence model of airway epithelial cells was treated with ECC-BYF III, and related enzymes and proteins involved in oxidative stress and mitophagy were detected. RESULTS: ECC-BYF III markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including the reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 levels, increase of the level in total superoxide dismutase (T-SOD), and decease in the p21 level in the airways. Furthermore, ECC-BYF III suppressed p16 and p21 expressions and senescence-associated ß-galactosidase (SA-ß-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF III upregulated mitophagy-related proteins, including the co-localizations of TOM20 and LC3B, PINK1 and PARK2, and improved mitochondrial function by upregulating mitochondrial mitofusin (MFN)2 and reducing dynamin-related protein 1 (DRP1) expression. ECC-BYF III enhanced the activities of T-SOD and GSH-PX by up-regulating NRF2, thus inhibiting oxidative stress. After intervention with NRF2 inhibitor, the regulation effects of ECC-BYF III on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed. CONCLUSIONS: ECC-BYF III exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through the activation of NRF2 signaling.

Efficacy and safety of Jin-shui Huan-xian granule for idiopathic pulmonary fibrosis: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND AND RATIONALE: Idiopathic pulmonary fibrosis is a critical disease with a poor prognosis. Although different studies have been conducted for the treatment of idiopathic pulmonary fibrosis, limited treatments are available. Jin-shui Huan-xian granule (JHG), which is a Chinese medicine herbal compound, has shown promising efficacy in reducing frequencies of acute exacerbations, improving exercise capacity the quality of life of patients with idiopathic pulmonary fibrosis. This study is to evaluate the efficacy and safety of JHG for IPF. SUBJECTS AND METHODS: This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 312 idiopathic pulmonary fibrosis patients will be enrolled and randomly allocated to one of the two groups with 1:1. After a 2-week washout period, 52-week treatment will also be performed for all the patients. Patients in the experimental group and the control group will be given JHG and JHG placebo, respectively. Outcome measures including acute exacerbations, pulmonary function, dyspnea, exercise capacity, and quality of life will be evaluated in this study. DISCUSSION: Based on our previous study, it is hypothesized that JHG will reduce acute exacerbations; improve exercise capacity, pulmonary function, and quality of life; and delay the disease progression-free. High-level evidence-based support for TCM in IPF will also be obtained in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04187690. Register on December 11, 2019.

Peimine ameliorates pulmonary fibrosis via the inhibition of M2-type macrophage polarization through the suppression of P38/Akt/STAT6 signals.

Peimine, a bioactive substance isolated from Chinese medicine Fritillaria, can potentially suppress pulmonary fibrosis (PF); however, its therapeutic mechanism remains unclear. Recent evidence suggests the participation of M2-type macrophages in the pathogenesis of PF. The present study aimed to investigate the effect of peimine on a bleomycin (BLM)-induced PF rat model and the underlying mechanism of this effect. After BLM administration, peimine was administered to rats from day 29 to day 42, with pirfenidone (PFD) as a positive control. H&E and Masson's trichrome stain were used to analyze histological changes. Q-PCR and western blotting were used to measure mRNA levels and protein levels, respectively. High-throughput RNA sequencing (RNA-seq) technology detected the differentially expressed genes (DEGs) regulated by peimine. Our results revealed that peimine treatment significantly ameliorated BLM-induced PF by suppressing histological changes and collagen deposition. In addition, peimine decreased the number of M2 macrophages and the expression of profibrotic factors. RNA-seq results showed that DEGs regulated by peimine in IL-4-induced macrophages were mainly associated with immune system processes, the PI3K/Akt pathway, and the MAPKs pathway. Then, immunofluorescence assay and western blot results demonstrated that peimine treatment suppressed the expression of p-p38 MAPK and p-Akt (s473) and also inhibited the nuclear translocation of p-STAT6. In conclusion, the present study demonstrated that peimine has a protective effect on PF through the suppression of M2 polarization of macrophages by inhibiting the STAT6, p38 MAPK, and Akt signals.

Network pharmacology combined with pharmacodynamics revealed the anti-inflammatory mechanism of Tanreqing capsule against acute-exacerbation chronic obstructive pulmonary disease.

Acute-exacerbation chronic obstructive pulmonary disease (AECOPD) is mainly associated with acute respiratory tract infection. In recent years, a growing number of studies have found that Tanreqing capsule (TRQ) has a favorable anti-inflammatory effect. In this study, we used network pharmacology and pharmacodynamics to explore the molecular mechanism and effects of TRQ in AECOPD treatment. To further understand the molecular mechanism of TRQ in AECOPD treatment, we used the network pharmacology to predict components of TRQ, TRQ-related targets, AECOPD-related targets, and pathways. In addition, we used the cigarette-smoke/lipopolysaccharide -induced AECOPD experimental model in Sprague-Dawley rats (72 rats randomly divided into six groups [n = 12 each]: control, model, high-TRQ [TRQ-H], medium-TRQ [TRQ-M], low-TRQ, and dexamethasone [Dex]) to evaluate the therapeutic effects of TRQ and to verify the network pharmacology. We found that 59 overlapping targets based on component-and AECOPD-related targets were frequently involved in the advanced glycation end product-receptor for advanced glycation end product signaling pathway in diabetic complications, the phosphatidylinositol-3-kinase-protein kinase B signaling pathway, and the hypoxia-inducible factor 1 signaling pathway, which might play important roles in the anti-inflammatory mechanism of TRQ in AECOPD treatment. Moreover, TRQ groups exerted protective effects against AECOPD by reducing the infiltration of inflammatory cells. Meanwhile, TRQ-M and TRQ-H groups significantly downregulated or upregulated the expression of tumor necrosis factor, interleukin (IL) 6, C-reactive protein, IL10, and serum amyloid A, as key targets in network pharmacology, in the serum and bronchoalveolar lavage fluid to achieve anti-inflammatory efficacy. Our study showed that TRQ had better anti-inflammatory efficacy against AECOPD, and initially elucidated its molecular mechanism. Moreover, our study also provides a new strategy to explore effective mechanism of TRQ against AECOPD; and further studies are needed to validate the biological processes and pathways of TRQ against AECOPD.

Systematic characterization of the components and molecular mechanisms of Jinshui Huanxian granules using UPLC-Orbitrap Fusion MS integrated with network pharmacology.

Jinshui Huanxian granules (JSHX) is a clinical Chinese medicine formula used for treating pulmonary fibrosis (PF). However, the effective components and molecular mechanisms of JSHX are still unclear. In this study, a combination approach using ultra-high performance liquid chromatography-Orbitrap Fusion mass spectrometry (UPLC-Orbitrap Fusion MS) integrated with network pharmacology was followed to identify the components of JSHX and the underlying molecular mechanisms against PF. UPLC-Orbitrap Fusion MS was used to identify the components present in JSHX. On the basis of the identified components, we performed target prediction using the SwissTargetPrediction database, protein-protein interaction (PPI) analysis using STRING database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using Metascape and constructed a component-target-pathway network using Cytoscape 3.7.2. Molecular docking technology was used to verify the affinity between the core components and targets. Finally, the pharmacological activities of three potentially bioactive components were validated in transforming growth factor ß1 (TGF-ß1)-induced A549 cell fibrosis model. As a result, we identified 266 components, including 56 flavonoids, 52 saponins, 31 alkaloids, 10 coumarins, 12 terpenoids and 105 other components. Of these, 90 validated components were predicted to act on 172 PF-related targets and they exhibited therapeutic effects against PF via regulation of cell migration, regulation of the mitogen-activated protein kinase (MAPK) cascade, reduction of oxidative stress, and anti-inflammatory activity. Molecular docking showed that the core components could spontaneously bind to receptor proteins with a strong binding force. In vitro, compared to model group, hesperetin, ruscogenin and liquiritin significantly inhibited the increase of α-smooth muscle actin (α-SMA) and fibronectin (FN) and the decrease of e-cadherin (E-cad) in TGF-ß1-induced A549 cells. This study is the first to show, using UPLC-Orbitrap Fusion MS combined with network pharmacology and experimental validation, that JSHX might exert therapeutic actions against PF by suppressing the expression of key factors in PF. The findings provide a deeper understanding of the chemical profiling and pharmacological activities of JSHX and a reference for further scientific research and clinical use of JSHX in PF treatment.

[Network Meta-analysis of heat-clearing and detoxifying Chinese medicine injections in treatment of acute exacerbation of chronic obstructive pulmonary disease].

This study aims to evaluate the efficacy and safety of heat-clearing and detoxifying Chinese medicine injections in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Randomized controlled trial(RCT) on the treatment of AECOPD with heat-clearing and detoxifying Chinese medicine injections were retrieved from 8 databases including CNKI and PubMed(from establishment to July 11, 2021). Related information in eligible articles was extracted, and the quality of the included articles was assessed by Cochrane collaboration's tool for assessing risk of bias. Stata SE 15.1 and ADDIS 1.16.6 were employed for data analysis. A total of 81 RCTs were screened out, involving 7 526 patients(3 782 in the experimental group and 3 744 in the control group). According to the statistical difference and network Meta-analysis, the injections are in the order of(1)Reduning Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in improving the effective rate,(2)Reduning Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in decreasing C-reactive protein(CRP),(3)Reduning Injection+conventional western medicine>Xiyanping Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in reducing white blood cell count(WBC),(4)Yuxingcao Injection+conventional western medicine>Reduning Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in lowering partial pressure of carbon dioxide(PaCO_2),(5)Yuxingcao Injection+conventional western medicine>Reduning Injection+conventional western medicine>Tanreqing Injection+conventional western medicine>Xiyanping Injection+conventional western medicine in improving partial pressure of oxygen(PaO_2), and(6)Qingkailing Injection+conventional western medicine>Tanreqing Injection+conventional western medicine in shortening mean hospital stay. In terms of safety, none of the five injections have serious adverse reactions. The five heat-clearing and detoxifying Chinese medicine injections are effective for AECOPD, but the mechanisms are different. Among them, Reduning Injection+conventional western medicine and Tanreqing Injection+conventional western medicine demonstrate better and more effects. Due to the differences in the quantity and quality of included studies, the conclusion needs to be further verified.

Enhanced Corrosion Resistance of Carbon Steel in Hydrochloric Acid Solution by Polyoxometalate-Estertin Derivatives.

The development of acid-resistant and efficient corrosion inhibitors is of great significance for metal protection in many industrial processes. In this work, eight cases of sandwich-type polyoxometalate (POM)-based inorganic-organic hybrids, namely, carboxyethyltin and transition metal (TM) cofunctionalized tungstoantimonates and tungstobismuthates, formulated as Na x K10-x [(SnR)2(TM(H2O)3)2(B-ß-SbW9O33)2]·mH2O and Na y K10-y [(SnR)2(TM(H2O)3)2(B-ß-BiW9O33)2]·nH2O (abbreviated as SbW9-TM-SnR and BiW9-TM-SnR; TM = Mn, Co, Ni, and Zn; m = 18, 24, 24, and 22; n = 30, 25, 20, and 21; SnR = Sn(CH2CH2COO)) are first used as green corrosion inhibitors for 20# carbon steel in 0.5-2.0 M HCl solutions. Weight loss and electrochemical experiments prove that the corrosion inhibition efficiency is all above 81% for these POM-based corrosion inhibitors at 150 mg L-1, and SbW9-Mn-SnR shows the highest efficiency of 96.9% at 150 mg L-1 after immersion in a 0.5 M HCl solution for 10 h. Scanning electron microscopy-energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy analyses show that these POM-based inhibitors form films on the carbon steel and the adsorption mechanism obeys the Langmuir adsorption model. The thermodynamic activation parameters were calculated, proving the occurrence of both chemical and physical adsorptions. The film-forming mechanism was also analyzed. This work provides guidance for synthesizing new lacunary POM-based materials to protect metals from corrosion in HCl pickling.

[Regularity of prescriptions for intermediate and advanced lung cancer based on latent structure combined with association rules].

The present study explored the regularity of prescriptions for the treatment of intermediate and advanced lung cancer to provide references for clinical medication. CNKI, Wanfang, VIP, and CBM were searched for the research papers on the treatment of lung cancer by Chinese medicine published from database inception to May 31, 2021. The relevant information of qualified papers was extracted to establish a database. The Chinese medicines with frequency >3% underwent analysis of the latent structure and association rules by Lantern 5.0 and SPSS Molder 14.1, respectively, and the prescription regularity in the treatment of intermediate and advanced lung cancer was analyzed based on the frequency description. A total of 713 papers were included, involving 327 Chinese medicines with a cumulative frequency of 12 794 and 106 prescriptions with a cumulative frequency of 824. The commonly used Chinese medicines were dominated by deficiency-tonifying, heat-clearing, phlegm-resolving, and cough/dyspnea-relieving drugs, such as Astragali Radix, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Ophiopogonis Radix, Poria, and Hedyotis Diffusa, which are cold, warm, and plain in nature and sweet, bitter, and pungent in flavor, and mainly act on lung, spleen, and stomach meridians. Commonly used prescriptions included Shashen Maidong Decoction, Liujunzi Decoction, and Baihe Gujin Decoction. The latent structure analysis revealed 32 latent variables and 65 hidden classes. Six comprehensive clustering models and 11 core prescriptions were obtained by professional knowledge inference. The common syndromes of intermediate and advanced lung cancer were inferred to be Qi and Yin deficiency in the lung, Qi deficiency in the lung and spleen, Yin deficiency in the liver and kidney, combined phlegm and stasis, phlegm-heat obstructing lung, and Qi stagnation and blood stasis. Forty-four strong associations were screened out by association rules analysis, including four pairwise strong associations(Polygonati Odorati Rhizoma→Ophiopogonis Radix, Polygonati Odorati Rhizoma→Glehniae Radix, Amomi Fructus→Atractylodis Macrocephalae Rhizoma, and Polygonati Rhizoma→Astragali Radix) and 40 triplet strong associations(such as Trichosanthis Radix+Glehniae Radix→Ophiopogonis Radix, Polygonati Odorati Rhizoma+Glehniae Radix→Ophiopogonis Radix, Trichosanthis Radix+Ophiopogonis Radix→Glehniae Radix, and Scutellariae Barbatae Herba+Codonopsis Radix→Hedyotis Diffusa). In the treatment of intermediate and advanced lung cancer, Qi-replenishing and Yin-nourishing drugs are mainly employed, assisted with cancer-resisting, toxin-removing, spleen-invigorating, phlegm/stasis-resolving, and blood-activating drugs based on syndrome differentiation. The roots were treated following the principles of tonifying lungs and replenishing the spleen, and symptoms following the principles of removing the toxin, dispelling stasis, and resolving phlegm.

Network pharmacology analysis uncovers the effect on apoptotic pathway by Bu-Fei formula for COPD treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: The Bu-Fei formula (BFF) has a positive effect on chronic obstructive pulmonary disease (COPD). However, its therapeutic mechanisms against COPD remain unknown. AIM OF THE STUDY: To explore BFF's therapeutic effect on COPD and pharmacological mechanisms. MATERIALS AND METHODS: First, the effect of BFF on rats with COPD was studied. Rats were randomly assigned to the blank, COPD, BFF treatment, and aminophylline (APL) treatment groups. From weeks 1-8, the COPD model was established by Klebsiella pneumoniae (KP) and cigarette smoke. Then, rats were given corresponding treatment for 8 weeks. The lung function of the rats was analyzed by whole-body plethysmography and pulmonary function testing, lung histopathology by electron microscopy and hematoxylin and eosin staining, and protein levels by immunohistochemistry. Next, the key components and targets of BFF in COPD were screened by network pharmacology analysis. Finally, the possible mechanism was verified through molecular docking and in vivo experiments. RESULTS: BFF significantly improved lung function and lung histopathology in COPD rats and inhibit inflammation and collagen deposition in lung tissues. Also, 46 bioactive compounds and 136 BFF targets related to COPD were identified; among them, 3 compounds (quercetin, luteolin, and nobiletin) and 6 core targets (Akt1, BCL2, NF-κB p65, VEGFA, MMP9, and Caspase 8) were the key molecules associated with the mechanisms of BFF. The target enrichment analysis suggested that BFF's mechanisms might involve the apoptosis-related pathway; this possibility was supported by the molecular docking data. Lastly, BFF was indicated to increase the expression of core target genes and the production of apoptosis-related proteins. CONCLUSIONS: BFF affects COPD by regulating the apoptosis-related pathways and targets.

The pharmacokinetic study of Tanreqing and the interaction with cefixime in rat model of pneumonia by validated UPLC-MS/MS.

Combining traditional Chinese medicine and chemical drugs with antimicrobial activities has become more popular, but there is insufficient relevant research on such combinations. The Tanreqing injection (TRQI), a Chinese compound medicine, exhibits therapeutic effects in treating upper respiratory tract infections, severe influenza, and pneumonia. This research investigates the pharmacokinetics of TRQI in pneumonia model rats and explores the effect of the antibiotic cefixime on its metabolism. The pneumonia model rats were randomly divided into six groups: low, medium, and high (3, 6, and 12 mL kg-1) dose TRQI group, and a medium dose TRQI combined with cefixime (14.4 mg kg-1) group, with the remainder two groups were control group. Blood samples were collected from the tail vein at different time points between 0 and 24 h after injection. A sensitive and quick method based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of the 13 TRQI components in the blood samples. The analytes were separated on an XBridge™C18 column (2.1 mm × 150 mm, 5 µm), with the flow phase consisting of methanol and 0.1% formic acid water at a flow rate of 0.3 mL/min. The assay method met the biological sample determination requirements, demonstrating good adaptability and practicability for application in the pharmacokinetic study of TRQI in pneumonia model rats. Moreover, the method was used successfully in the interaction study of TRQI with cefixime. The results indicated that co-administration results in a significant change in the pharmacokinetic parameters of the main TRQI components. However, the changes in the pharmacokinetic characteristics of multiple TRQI components were inconsistent. Thus, the results of this drug combination under different pathological conditions in clinical applications were unpredictable. Therefore, more attention should be paid to the combined use of cefixime and TRQI in clinical applications to avoid the risk of adverse drug reactions in future studies.

Effect of Yangqing Chenfei Formula on epithelial-mesenchymal transition in silicon dioxide-induced silicosis rats / 中国职业医学

@# Objective Yangqing Chenfei Formula - To investigate the effect of (YCF) on epithelial mesenchymal transition (EMT) Methods in lung tissues of silicosis model rats. Specific pathogen free adult male SD rats were randomly divided into control group, model group, tetrandrine group and YCF group, with eight rats in each group. The rats in the model group, tetrandrine group and YCF group were intratracheally injected with 1.00 mL of silica suspension with a mass concentration of 50.0 g/L, and the rats in the control group were given an equal volume of 0.9% sodium chloride solution. On the 15th day after modeling, the tetrandrine group was given tetrandrine at a dose of 27.0 mg/kg body weight, the YCF group was given YCF with a dose of 8.91 g/kg body weight, while both the control group and model group were given 2.00 mL 0.9% sodium chloride solution. Gavage wasperformed twice a day in the morning and evening for 14 days. On day 29 of the experiment, after evaluating the tidal volume, - functional residual volume (FRC) and vital capacity of rats in each group, lung tissues were collected, and hematoxylin eosin staining and Masson staining were performed to examine the histopathological changes, and the fibrosis score was evaluated. - - Hydroxyproline level was detected by colorimetry. The expression of type Ⅰ collagen (COL Ⅰ), type Ⅲ collagen (COL Ⅲ), - - - - - - E cadherin (E Cad), N cadherin (N Cad) and α smooth muscle actin (α SMA) protein was detected by immunohistochemistry. - The expression of epithelial cell adhesion molecule (EpCAM) and fibroblast specific protein 1 (FSP 1) was detected by Results immunofluorescence. The lung structure was intact and the alveolar structure was normal in the control group. The alveolar structure was destroyed, the alveolar wall was thickened, and cellular nodules were observed/n the model group. The lung tissue lesions of rats in the tetrandrine group and YCF group were reduced compared with that in the model group, and there was no difference in the degree of lesions between the two groups. The tidal volume, FRC and vital capacity of rats in model P< - P< group decreased (all 0.05), the relative expression of E Cad protein in lung tissue decreased ( 0.05), the fibrosis score and - - - - the level of hydroxyproline, the protein relative expression of COL Ⅰ, COL Ⅲ, N Cad and α SMA in lung tissue increased (all P< - 0.05), while the fluorescence intensity of EpCAM protein decreased, and that of FSP 1 protein increased compared with the P< control group. The tidal volume, FRC and vital capacity of rats in tetrandrine and YCF groups increased (all 0.05), the fibrosis - - - score and the level of hydroxyproline, the protein relative expression of COL Ⅰ, N Cad and α SMA in lung tissue decreased (all P< - P< 0.05), the relative expression of E Cad protein in lung tissues increased ( 0.05), while the EpCAM protein fluorescence - intensity increased and FSP 1 protein fluorescence intensity decreased compared with the model group. The relative expression - P< Conclusion of N Cad protein in lung tissues of YCF group was lower than that of the tetrandrine group ( 0.05). YCF can - improve the lung function, alleviate collagen deposition in lung tissues, and inhibit the epithelial mesenchymal transition in silicosis model rats, and then attenuates the progression of silicotic fibrosis.

[Study on the rule of acupoint selection in treatment of acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the characteristics and rule of clinical acupoint selection in treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: The clinical articles of acupuncture in treatment of AECOPD were retrieved from the databases of PubMed, EMbase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and SinoMed, from the date of establishment to July 15, 2020. The articles were screened in accordance with the inclusion and exclusion criteria, the prescriptions of acupuncture and the relevant information of the acupoints and meridians were extracted to establish the database. The data mining methods i.e. Apriori association rule analysis and cluster analysis were used to analyse the using frequency, involving meridians, acupoint distributions, association rules and cluster of selected acupoints. RESULTS: A total of 54 articles were included, 67 acupuncture prescriptions were extracted, 69 acupoints were involved and the total using frequency was 475 times. The top 5 acupoints in frequency were Danzhong (CV 17), Feishu (BL 13), Zusanli (ST 36), Fenglong (ST 40) and Dingchuan (EX-B1). The main involved meridians were bladder meridian of foot-taiyang, conception vessel, stomach meridian of foot-yangming and lung meridian of hand-taiyin. The acupoints were mainly distributed in chest and abdomen, waist and dorsum. The mainly selected special points were five-shu points, front-mu points, convergent points and back-shu points. Twenty strong association rules were summarized by association rule analysis, including Fenglong (ST 40)Þ Zusanli (ST 36), Fengmen (BL 12)Þ Danzhong (CV 17), Tianshu (ST 25)Þ Zhongwan (CV 12), Dingchuan (EX-B1)+ Feishu (BL 13) Þ Danzhong (CV 17), Fenglong (ST 40)+ Feishu (BL 13) Þ Zusanli (ST 36), etc. Five cluster groups were summarized by cluster analysis, i.e. ①Feishu (BL 13), ② Dingchuan (EX-B1) and Danzhong (CV 17), ③ Chize (LU 5), Lieque (LU 7) and Fengmen (BL 12), ④Zusanli (ST 36) and Fenglong (ST 40), ⑤Tianshu (ST 25), Guanyuan (CV 4) and Zhongwan (CV 12). CONCLUSION: The local acupoints and acupoints along meridians are the main acupuncture prescriptions for AECOPD, and the special points are the predominated selection. The acupoint compatibility embodies the therapeutic principle of "strengthening vital qi to eliminate pathogenic factors and considering both the root cause and symptoms".

Tiaobu Feishen therapy inhibits inflammation induced by cigarette smoke extracts in a human monocyte/macrophage cell line.

OBJECTIVE: To study the mechanistic effects of Tiaobu Feishen therapy (TBFS) on inflammation induced by cigarette smoke extract (CSE) in a human monocyte/macrophage cell line. METHODS: The human monocyte/macrophage cell line THP-1 was stimulated with 10 % CSE in the presence or absence of Bufei Yishen formula (BYF), Bufei Jianpi formula (BJF) and Yiqi Zishen formula (YZF). All formulations contained serum. Pro-inflammatory cytokines were measured in the supernatants using enzyme-linked immunosorbent assay. The activity of STAT3 DNA binding was detected using electrophoretic mobility shift assay and janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation was assessed using Western blotting. RESULTS: The results showed that BYF, BJF and YZF treatment strongly decreased the CSE-induced secretion of interleukin (IL)-6, IL-8, tumor necrosis factor-α and matrix metalloproteinase-9 by THP-1 cells. Furthermore, BYF, BJF and YZF treatment attenuated STAT3 DNA binding capacity and JAK2 and STAT3 were shown to be phosphorylated. CONCLUSION: The data revealed that BYF, BJF and YZF effectively inhibited a CSE-induced inflammatory response in THP-1 cells by limiting activation of the JAK2/STAT3 pathway.

Pharmacokinetics, tissue distribution and excretion of five rhubarb anthraquinones in rats after oral administration of effective fraction of anthraquinones from rheum officinale.

Rhubarb, a famous traditional Chinese medicine, shows a wide range of physiological activities and pharmacological benefits. Rhubarb anthraquinones are perceived as the pharmacologically active compounds of Rhubarb, and understanding metabolism of them is crucial to assure safety and effectiveness of clinical application. In this study, the pharmacokinetics, tissue distribution and excretion of five rhubarb anthraquinones (aloe-emodin, rhein, emodin, chrysophanol, physcion) were systematically investigated after oral administration of rhubarb extract to rats.An HPLC method was developed and validated for quantitation of five rhubarb anthraquinones in rat plasma, tissues, urine and faeces to investigate the Pharmacokinetic characteristics. The results showed that the proposed method was suitable for the quantification of five anthraquinones in plasma, tissue and excreta samples with satisfactory linear (r > 0.99), precision (<10%) and recovery (85.12-104.20%). The plasma concentration profiles showed a quick absorption with the mean Tmax of 0.42-0.75 h and t1/2 of 6.60-15.11 h for five anthraquinones. The analytes were widely distributed in most of the tissues. Approximately 0.13-10.59% and 28.47-81.14% of five anthraquinones were recovered in urine and faeces within 132 h post-dosing, which indicated the major elimination route was faeces excretion.In summary, this study lays a foundation for elucidating the pharmacokinetic rule of rhubarb anthraquinone and the important data can provide reliable scientific resource for further research.

Effective-constituent compatibility-based analysis of Bufei Yishen formula, a traditional herbal compound as an effective treatment for chronic obstructive pulmonary disease.

OBJECTIVE: Critical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF. METHODS: The active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi), 2 (Bushen), 3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory. An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of "Groups 1 to 4" according to their pharmacological activity. We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD). RESULTS: We identified 12 active constituents in BYF. The numbers of constituents in Groups 1 to 4 were 3, 2, 5 and 2, respectively. We identified the optimal ratios of effective constituents within each group. In Group 1, total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2. In Group 2, icariin:schisandrin B ratio was 100:12.5. In Group 3, nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4:30:6.25:0:0. In Group 4, paeoniflorin:paeonol ratio was 4:1. An orthogonal design was then used to establish the optimal ratios of Group 1, Group 2, Group 3 and Group 4 in ECC of BYF I. The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25. A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF. CONCLUSION: Based on the ECC of traditional Chinese medicine formula method, the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.