Small airway dysfunction in pneumoconiosis: a cross-sectional study.

BACKGROUND: Although several histological studies have documented airway inflammation and remodelling in the small airways of dust-exposed workers, little is known regarding the prevalence and risk factors of small airway dysfunction (SAD) in pneumoconiosis. The present study investigated the prevalence and characteristics of spirometry-defined SAD in pneumoconiosis and assessed the risk factors for associated with SAD. METHODS: A total of 1255 patients with pneumoconiosis were invited to participate, of whom 1115 patients were eligible for final analysis. Spirometry was performed to assess SAD using the following three indicators: maximal mid-expiratory flow and forced expiratory flow 50% and 75%. SAD was defined as at least two of these three indicators being less than 65% of predicted value. Logistic regression analyses were used to analyse the relationships between clinical variables and SAD. RESULTS: Overall, 66.3% of patients with pneumoconiosis had SAD, among never-smokers the prevalence of SAD was 66.7%. The proportion of SAD did not differ among the subtypes of pneumoconiosis. In addition, SAD was present across the patients with all stages of pneumoconiosis. Even among those with forced expiratory volume in 1 s (FEV1) ≥ 80% and FEV1/forced vital capacity ratio ≥ 70%, 40.8% of patients had SAD. Patients with SAD were older than patients without SAD, more likely to be women and heavy smokers. Importantly, patients with SAD had more severe airflow obstruction, air trapping, and diffusion dysfunction. All patients with both pneumoconiosis and chronic obstructive pulmonary disease had SAD. Based on multivariate analysis, overall, aged 40 years and older, female sex, heavy smoking, body mass index ≥ 25.0 kg/m2 and pneumoconiosis stage III were significantly associated with increased risk of SAD. Among the never smokers, risk factors for SAD included female sex, BMI ≥ 25.0 kg/m2, pneumoconiosis stage II and stage III CONCLUSION: Spirometry-defined SAD is one of the common functional abnormalities caused by occupational dust exposure and should be taken into account when monitoring respiratory health of workers to guide the early precautions and management in pneumoconiosis.

Cobalt-related interstitial lung disease or hard metal lung disease: A case series of Chinese workers.

Hard metal lung disease (HMLD) is rarely diagnosed and is caused by the occupational inhalation of hard metal dust, mainly cobalt. The diagnosis of HMLD is based on a thorough occupational dust exposure combined with clinical-radiological-histological findings. We present a series of four Chinese workers who had occupational exposure to cobalt acid lithium or cobalt and tungsten dust. Four patients all complained of intermittent cough, chest tightness, or shortness of breath on exertion. High-resolution computed tomography scans presented bilateral ground-glass attenuation, consolidations, and/or reticular opacities with diffuse small nodules. Histologic findings showed that interstitial inflammation and fibrotic lesions distributed peribronchioles. The infiltrations by macrophages as well as visible multinucleated giant cells indicated giant cell interstitial pneumonia (GIP). Cobalt was detectable in the lung tissues of two patients measured by inductively-coupled plasma mass spectrometry. The first patient was diagnosed with cobalt-related interstitial lung disease (ILD), while the others were HMLD. GIP is the classic pathology of cobalt-related ILD or HMLD. One of the patients showed spontaneous remission after the cessation of exposure, while the other three recovered within 6-32 weeks after avoiding occupational exposure and using corticosteroids. At follow-up, all four patients showed no recurrence. A multidisciplinary diagnostic panel including occupational cobalt exposure evaluation is beneficial to recognize cobalt-related ILD or HMLD and to indicate the necessity of prevention.

Rare cases of severe life-threatening lead poisoning due to accident or chronic occupational exposure to lead and manganese: Diagnosis, treatment, and prognosis.

BACKGROUND: Chronic long-term, low-dose environmental and occupational exposure to lead (Pb) has been extensively studied in large cohorts worldwide among general populations, miners, smelters, or battery workers. However, studies on severe life-threatening Pb poisoning due to accidental or chronic occupational exposure to Pb and manganese (Mn) were rarely reported. METHODS: We present one case of acute severe Pb poisoning and compare it with another severe chronic occupational exposure case involving Pb and Mn. A 27-year-old woman mistakenly took a large quantity of pure Pb powder as an herbal remedy; she developed abdominal colic, severe nausea, vomiting, fatigue, and cutaneous and sclera icterus. Laboratory tests showed her blood lead level (BLL) of 173.5 µg dL-1 and urinary lead level (ULL) of 1240 µg dL-1. The patient was diagnosed with acute Pb poisoning and acute liver failure. In another chronic exposure case, a 56-year-old man worked in a Pb and Mn smelting factory for 15 years. He was brought to the emergency room with severe nausea, vomiting, and paroxysmal abdominal colic, which was intolerable during the onset of pain. His BLL was 64.8 µg dL-1 and ULL was 38 µg dL-1, but his blood and urinary Mn levels were normal. The patient was diagnosed with chronic Pb poisoning. Both patients received chelation therapy with calcium disodium ethylene-diamine-tetraacetate (CaNa2EDTA). The woman with acute severe Pb intoxication recovered well and was discharged from the hospital after treatment, and the man who survived severe Pb poisoning was diagnosed with lung cancer. CONCLUSION: Clinical manifestations of acute and chronic severe Pb poisoning are different. Chelation therapy with CaNa2EDTA is proven to be an effective life-saving therapy in both cases by reducing BLL. Occupational exposure to both Pb and Mn does not appear to increase Mn neurotoxicity; however, the probability that co-exposure to Mn may increase Pb toxicity in the same patient cannot be excluded.

[Genetic analysis of a family affected with pulmonary hypertension secondary to hereditary hemorrhagic telangiectasia].

OBJECTIVE: To carry out genetic testing for a family affected with pulmonary hypertension (PH) as the initial sign of hereditary hemorrhagic telangiectasia (HHT). METHODS: High throughput sequencing was performed to detect potential mutation in the coding regions of endoglin (ENG), activin receptor-like kinase 1 (ACVRL1) and mothers against decapentaplegic homolog 4 (SMAD4) genes. RESULTS: A pathogenic heterozygous c.814C>T (p.Gln272Ter) mutation of the ACVRL1 gene was identified in the proband. Her mother and two sons have carried the same mutation. CONCLUSION: The c.814C>T (p.Gln272Ter) mutation of the ACVRL1 gene probably underlies the disease in this family. Genetic testing should be recommended to HHT patient, in particular those with pulmonary hypertension.

Serum concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: a case-control study.

BACKGROUND: Asbestosis and silicosis are progressive pneumoconioses characterized by interstitial fibrosis following exposure to asbestos or silica dust. We evaluated the potential diagnostic biomarkers for these diseases. METHODS: The serum concentrations of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and matrix metalloproteinase-2 (MMP-2), MMP-7, and MMP-9 were measured in 43 patients with asbestosis, 45 patients with silicosis, 40 dust-exposed workers (DEWs) without pneumoconiosis, and 45 healthy controls (HCs). Chest high-resolution computed tomography (HRCT) images were reviewed by experts blinded to the clinical data. According to the receiver operating characteristic (ROC) curve, the ideal level of each biomarker and its diagnostic sensitivity were obtained. RESULTS: The serum KL-6 and MMP-2 concentrations were highest in patients with asbestosis, particularly in comparison with those in DEWs and HCs (P<0.05). The serum SP-D concentration was significantly higher in patients with asbestosis than in patients with silicosis, DEWs, and HCs (P<0.01), whereas no significant difference was noted among patients with silicosis, DEWs, and HCs. No significant difference in the serum MMP-7 or -9 concentration was found among patients with asbestosis, patients with silicosis, DEWs, or HCs. Among patients with asbestosis, the serum KL-6 concentration was significantly correlated with the lung fibrosis scores on HRCT and negatively correlated with the forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted. The serum SP-D and MMP-2 concentrations were negatively correlated with the DLCO % predicted (all P<0.05). The order of diagnostic accuracy according to the ROC curve was KL-6, SP-D, and MMP-2 in patients with asbestosis alone and in the combination of both patients with asbestosis and those with silicosis. The combination of all three biomarkers may increase the possibility of diagnosing asbestosis (sensitivity, 93%; specificity, 57%) and both asbestosis and silicosis (sensitivity, 83%; specificity, 62%). CONCLUSIONS: KL-6, SP-D, and MMP-2 are available biomarkers for the adjuvant diagnosis of asbestosis and silicosis. The combination of all three biomarkers may improve the diagnostic sensitivity for asbestosis and silicosis.

Heavy metal poisoning caused by Chinese folk remedies in psoriasis patients: a retrospective analysis.

Psoriasis, characterized as a chronic relapsing disease with a protracted course, often drives patients to seek relief through Chinese folk remedies (CFR). Nonetheless, the complex compositions of these remedies frequently result in unintended adverse effects, notably various types of heavy metal poisoning. Our study involved an exhaustive collection and analysis of clinical data from psoriasis patients who developed heavy metal poisoning due to CFR usage, admitted to Beijing Chao-Yang Hospital from January 2011 to October 2023. Our analysis identified 44 cases of mercury poisoning, 17 of lead poisoning, 21 of arsenic poisoning, and 4 instances of mixed heavy metal poisoning. The folk remedies used ranged from fumigation and inhalation to skin application and oral administration. Distinct pathogenic characteristics were observed in each poisoning type. After treatment with metal chelating agents, all patients experienced a reduction in heavy metal levels in their bodies, accompanied by varying degrees of symptom alleviation. This study underscores the vital necessity of opting for formal, medically approved treatments for psoriasis, thereby avoiding the hazardous consequences of unregulated folk remedies that may lead to severe heavy metal poisoning.

Integrative transcriptomics and proteomics analysis reveal the protection of Astragaloside IV against myocardial fibrosis by regulating senescence.

Myocardial fibrosis (MF) is a pivotal pathological process implicated in various cardiovascular diseases, particularly heart failure. Astragaloside IV (AS-IV), a natural compound derived from Astragalus membranaceus, possesses potent cardioprotective properties. However, the precise molecular mechanisms underlying its anti-MF effects, particularly in relation to senescence, remain elusive. Thus, this study aimed to investigate the therapeutic potential and underlying molecular mechanisms of AS-IV in treating ISO-induced MF in mice, employing transcriptomics, proteomics, in vitro, and in vivo experiments. We assessed the positive effects of AS-IV on ISO-induced MF using HE staining, Masson staining, ELISA, immunohistochemical staining, transthoracic echocardiography, transmission electron microscopy, and DHE fluorescence staining. Additionally, we elucidated the regulatory role of AS-IV in MF through comprehensive transcriptomics and proteomics analyses, complemented by Western blotting and RT-qPCR validation of pertinent molecular pathways. Our findings demonstrated that AS-IV treatment markedly attenuated ISO-induced myocardial injury and oxidative stress, concomitantly inhibiting the release of SASPs. Furthermore, integrated transcriptomics and proteomics analyses revealed that the anti-MF mechanism of AS-IV was associated with regulating cellular senescence and the p53 signaling pathway. These results highlight AS-IV exerts its anti-MF effects not only by inhibiting oxidative stress but also by modulating senescence through the p53 signaling pathway.

Pulmonary sarcoid-like granulomatosis induced by aluminum dust: A case report and literature review.

Case report: We present a case of a 48-year-old woman with 27 months of exposure to aluminum dust and silica owing to polishing processing. The patient was admitted to our hospital with intermittent cough and expectoration. Chest high-resolution computed tomography showed diffuse ill-defined centrilobular nodules and patchy ground-glass opacities in bilateral lungs. A video-assisted thoracoscopic surgery biopsy demonstrated multiple isolated and confluent granulomas in an otherwise normal parenchyma without malignancy or signs of infection. Elemental analysis was performed on the grinding wheel powder in the workplace using an X-ray fluorescence spectrometric analyzer, showing 72.7% of Al2O3 and 22.8% of SiO2 as raw materials. She was diagnosed with aluminum-associated sarcoid-like granulomatous lung disease, rather than sarcoidosis, according to occupational exposure by a multidisciplinary panel. Conclusion: Occupational aluminum dust exposure may induce pulmonary sarcoid-like granulomatosis recognized by a multidisciplinary diagnostic panel.

Effect of pueraria on left ventricular remodelling in HFrEF: A systematic review and meta-analysis.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a prevalent cardiovascular disease globally, posing a significant burden on healthcare and society. Left ventricular remodelling is the primary pathology responsible for HFrEF development and progression, leading to increased morbidity and mortality. Pueraria, a traditional Chinese herbal medicine and food, is commonly used in China to treat HFrEF. Accumulating evidence suggests that pueraria can effectively reverse left ventricular remodelling in HFrEF patients. This meta-analysis aims to assess the impact of pueraria on left ventricular remodelling in HFrEF patients. METHODS: Eight electronic databases, including PubMed, EMBASE, Clinicaltrials.gov, Cochrane Library, Wanfang, CNKI, CQVIP, and CBM were searched for literature from inception to June 2023. All randomized controlled trials (RCTs) using pueraria in the treatment of HFrEF were included. The Cochrane Risk of Bias tool was utilized for RCTs' methodological evaluation, while Review Manager 5.4.1 was used to analyze the data. RESULTS: Nineteen RCTs with a total of 1,911 patients (1,077 males and 834 females) were identified. Meta-analysis indicated that combination medication of pueraria and conventional medicine (CM) was superior to the CM alone in raising left ventricular ejection fraction (LVEF; MD = 6.46, 95% CI, 4.88 to 8.04, P < 0.00001), and decreasing left ventricular end-diastolic diameter (LVEDD; MD = -4.78, 95% CI, -6.55 to -3.01, P < 0.00001), left ventricular end-Systolic diameter (LVESD; MD = -3.98, 95% CI, -5.98 to -1.99, P < 0.00001) and N-terminal pro-brain natriuretic peptide (NT-proBNP; MD = -126.16, 95% CI, -185.30 to -67.03, P < 0.0001). Besides, combination medication improved clinical efficacy rate (RR = 3.42, 95% CI, 2.54 to 4.59, P < 0.00001), 6-min walk test (6-MWT; MD = 65.54, 95% CI, 41.77 to 89.31, P < 0.00001), and TCM syndrome score efficacy (RR = 3.03, 95% CI, 1.57 to 5.83, P = 0.0009). Regarding safety, no difference was observed for adverse events (RR = 0.59, 95% CI, 0.22 to 1.54, P = 0.28). CONCLUSION: The use of pueraria combined with conventional medicine in HFrEF patients has superiority over conventional medicine alone in ameliorating cardiac function and reversing left ventricular remodeling. Moreover, combination medication has no increase in adverse drug events. Given some limitations, more prudence and high-quality clinical trials are needed in the future to verify the conclusions.

Progressive pulmonary fibrosis in myositis-specific antibody-positive interstitial pneumonia: a retrospective cohort study.

Objectives: Idiopathic inflammatory myopathy (IIM) frequently coexists with interstitial pneumonia (IP) and is commonly the initial or sole manifestation accompanied by positive myositis-specific autoantibodies (MSAs), even in the absence of meeting diagnostic criteria. This study aims to evaluate the proportion of progressive pulmonary fibrosis (PPF) and identify potential predictors influencing the progression of pulmonary fibrosis in patients with MSA-IP. Methods: This descriptive study employed a retrospective cohort design, enrolling patients diagnosed with interstitial pneumonia and positive MSAs at Beijing Chao-Yang Hospital in a sequential manner. Clinical data were systematically collected from the patients' medical records during regular follow-up visits conducted every 3 to 6 months. Cox regression analysis was utilized to identify independent predictors of PPF in patients with positive MSAs and interstitial pneumonia. Results: A total of 307 patients were included in the study, with 30.6% of them developing PPF during a median follow-up period of 22 months. Kaplan-Meier survival curves demonstrated a significantly lower survival in the PPF patients compared to the non-PPF patients (median 11.6 months vs. 31 months, p = 0.000). An acute/subacute onset of interstitial pneumonia (HR 3.231, 95%CI 1.936-5.392, p = 0.000), lower diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 6.435, 95%CI 4.072-10.017, p = 0.001), and the presence of diffuse alveolar damage (DAD) on high-resolution computed tomography (HRCT) (HR 8.679, 95%CI 1.974-38.157, p = 0.004) emerged as independent predictors of PPF. Notably, the implementation of triple therapy comprising glucocorticoids, immunosuppressants, and antifibrotic drugs was associated with a reduced risk of developing PPF (HR 0.322, 95%CI 0.115-0.899, p = 0.031). Conclusion: Approximately 30.6% of patients with MSA-IP may develop PPF within the follow-up period. Patients presenting with an acute/subacute onset of interstitial pneumonia, lower predicted DLCO SB% and evidence of DAD on HRCT are more susceptible to developing PPF. Conversely, the administration of triple therapy appears to serve as a protective factor against the development of PPF in patients with MSA-IP.

The incidence of malignancies in asbestosis with chrysotile exposure: a large Chinese prospective cohort study.

Background: Asbestos exposure is closely related to the occurrence and development of various malignancies. This prospective cohort study aimed to evaluate the incidence rate and potential risk factors in a cohort of asbestosis patients in China. Methods: The incidence of malignancies was determined in patients who had been exposed to chrysotile asbestos and diagnosed with asbestosis sequentially at Beijing Chaoyang Hospital from 1 January 2007 to 31 December 2019. Cox regression analyses were used to analyze the correlations between clinical variables and asbestosis combined with malignancies. Results: A total of 618 patients with asbestosis were identified, of whom 544 were eligible for analysis. Among them, 89 (16.36%) were diagnosed with various malignancies. The standardized incidence ratios (SIRs) of patients with asbestosis combined with malignancies were 16.61, 175, 5.23, and 8.77 for lung cancer, mesothelioma, breast cancer, and endometrial carcinoma, respectively. The risks of all malignancies and lung cancer increased with initial exposure before 17 years old, longer asbestos exposure, and smoking. Conclusions: The SIRs of patients with asbestosis-related malignancies were significantly increased in lung cancer, mesothelioma, breast cancer, and endometrial carcinoma in a hospital-based Chinese cohort. Smoking and the duration of asbestos exposure increased the risk of lung cancer.

Qige Huxin Formula Attenuates Isoprenaline-Induced Cardiac Fibrosis in Mice via Modulating Gut Microbiota and Protecting Intestinal Integrity.

Background: The composition and metabolic activities of gut microbiota are strongly interconnected with cardiac fibrosis (CF) and heart failure (HF). Qige Huxin formula (QHF), a traditional Chinese medicine (TCM) formulation originating from a classical Fangji Huangqi decoction, has been widely used to clinically treat HF for decades. However, it is still unclear whether QHF alleviates CF by modulating gut microbiota and intestinal integrity. Purpose: This study aimed to investigate the cardioprotective effects of QHF in isoprenaline-induced CF through modulating gut microbiota and intestinal integrity. Methods: Fifty mice were randomly divided into five groups after one week of acclimatization feeding: control group, model group, 2.56 g/kg/d group (low-dose QHF), 5.12 g/kg/d group (high-dose QHF), and meto group (15 mg/kg/d). The CF model was established by subcutaneously injecting the mice with isoprenaline (10 mg/kg/d for 14 days), followed by QHF treatment. The heart volume, cardiac weight index (CWI), serum myocardial enzymes, serum inflammatory cytokines, serum lipopolysaccharide, histopathology of the heart and colon tissues, ZO-1, and occludin of colon tissues were then measured. Fecal samples from mice were analyzed using 16S rRNA sequencing. Results: QHF treatment significantly reduced heart volume, CWI, and serum CK and CK-MB levels, attenuated cardiac histopathological alterations, and alleviated CF. QHF treatment also downregulated TNF-α, IL-1ß, and IL-6 in serum. Moreover, QHF treatment decreased the serum level of lipopolysaccharide and maintained intestinal integrity by upregulating ZO-1 and occludin. The 16S rRNA microbiota analysis revealed that QHF treatment increased the relative abundance of Marvinbryantia and Phascolarctobacterium. Conclusions: QHF treatment exerts cardioprotective effects through modulating gut microbiota, protecting intestinal integrity, and alleviating inflammation. This study shows that gut microbiota may enhance heart-gut interaction.

Toxic Nephropathy Secondary to Chronic Mercury Poisoning: Clinical Characteristics and Outcomes.

Introduction: Kidney disease secondary to mercury poisoning has not been well documented and is often misdiagnosed and mistreated. Methods: We performed a retrospective analysis of patients diagnosed with having mercury poisoning over a 6-year period between July 2013 and June 2019. Demographics, clinical measures, renal pathologic examinations, treatments, and outcomes were compared between patients with kidney disease and those without kidney disease. Results: Of the 172 patients with mercury poisoning, 46 (26.74%) had renal damage. Among the 46 patients, 41 (89.13%) presented nephrotic syndrome, and 5 (10.87%) showed proteinuria alone. The pathologic abnormality associated with kidney disease caused by mercury poisoning was mainly membranous nephropathy (18 of 35 patients, 51.43%). Among 41 patients with nephrotic syndrome, 25 were treated with chelation therapy alone and 12 with mercury chelation therapy and glucocorticoids. The remaining 4 patients were treated with chelation therapy, glucocorticoids, and immunosuppressive therapies. The overall effective rate was 97.5% (40 patients). There was no significant difference in complete remission rate among the 3 treatment methods (P < 0.05). Conclusion: The main clinical manifestation of kidney disease secondary to chronic mercury poisoning was nephrotic syndrome, which was reflected in pathologic examinations as membranous nephropathy. Kidney disease to chronic mercury poisoning is prone to misdiagnosis and missed diagnosis. Chelation therapy is the main treatment, and the prognosis is good. Patients with severe condition can be supplemented with glucocorticoid.

Yiqi Huayu decoction alleviates bleomycin-induced pulmonary fibrosis in rats by inhibiting senescence.

Overview: In treating pulmonary fibrosis (PF), traditional Chinese medicine (TCM) has received much attention, but its mechanism is unclear. The pharmacological mechanisms of TCM can be explored through network pharmacology. However, due to its virtual screening properties, it still needs to be verified by in vitro or in vivo experiments. Therefore, we investigated the anti-PF mechanism of Yiqi Huayu Decoction (YHD) by combining network pharmacology with in vivo experiments. Methods: Firstly, we used classical bleomycin (BLM)-induced rat model of PF and administrated fibrotic rats with YHD (low-, medium-, and high-dose). We comprehensively assessed the treatment effect of YHD according to body weight, lung coefficient, lung function, and histopathologic examination. Second, we predict the potential targets by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with network pharmacology. In brief, we obtained the chemical ingredients of YHD based on the UHPLC-MS/MS and TCMSP database. We collected drug targets from TCMSP, HERB, and Swiss target prediction databases based on active ingredients. Disease targets were acquired from drug libraries, Genecards, HERB, and TTD databases. The intersecting targets of drugs and disease were screened out. The STRING database can obtain protein-protein interaction (PPI) networks and hub target proteins. Molecular Complex Detection (MCODE) clustering analysis combined with enrichment analysis can explore the possible biological mechanisms of YHD. Enrichment analyses were conducted through the R package and the David database, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome. Then, we further validated the target genes and target proteins predicted by network pharmacology. Protein and gene expression detection by immunohistochemistry, Western blot (WB), and real-time quantitative PCR (rt-qPCR). Results: The results showed that high-dose YHD effectively attenuated BLM-induced lung injury and fibrosis in rats, as evidenced by improved lung function, relief of inflammatory response, and reduced collagen deposition. We screened nine core targets and cellular senescence pathways by UHPLC-MS/MS analysis and network pharmacology. We subsequently validated key targets of cellular senescence signaling pathways. WB and rt-qPCR indicated that high-dose YHD decreased protein and gene expression of senescence-related markers, including p53 (TP53), p21 (CDKN1A), and p16 (CDKN2A). Increased reactive oxygen species (ROS) are upstream triggers of the senescence program. The senescence-associated secretory phenotypes (SASPs), containing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß1 (TGF-ß1), can further exacerbate the progression of senescence. High-dose YHD inhibited ROS production in lung tissue and consistently reduced the SASPs expression in serum. Conclusion: Our study suggests that YHD improves lung pathological injury and lung function in PF rats. This protective effect may be related to the ability of YHD to inhibit cellular senescence.

Astragaloside IV Ameliorates Isoprenaline-Induced Cardiac Fibrosis in Mice via Modulating Gut Microbiota and Fecal Metabolites.

Aim: Gut microbiota is of crucial importance to cardiac health. Astragaloside IV (AS-IV) is a main active ingredient of Huangqi, a traditional edible and medicinal herb that has been shown to have beneficial effects on cardiac fibrosis (CF). However, it is still uncertain whether the consumption of AS-IV alleviates cardiac fibrosis through the gut microbiota and its metabolites. Therefore, we assessed whether the anti-fibrosis effect of AS-IV is associated with changes in intestinal microbiota and fecal metabolites and if so, whether some specific gut microbes are conducive to the benefits of AS-IV. Methods: Male C57BL-6J mice were subcutaneously injected with isoprenaline (ISO) to induce cardiac fibrosis. AS-IV was administered to mice by gavage for 14 days. The effects of AS-IV on cardiac function, myocardial enzyme, cardiac weight index (CWI), and histopathology of ISO-induced CF mice were investigated. Moreover, 16S rRNA sequencing was used to establish gut-microbiota profiles. Fecal-metabolites profiles were established using the liquid chromatograph-mass spectrometry (LC-MS). Results: AS-IV treatment prevented cardiac dysfunction, ameliorated myocardial damage, histopathological changes, and cardiac fibrosis induced by ISO. AS-IV consumption increased the richness of Akkermansia, Defluviitaleaceae_UCG-011, and Rikenella. AS-IV also modulated gut metabolites in their feces. Among 141 altered gut metabolites, amino acid production was sharply changed. Furthermore, noticeable correlations were found between several specific gut microbes and altered fecal metabolites. Conclusions: An increase of Akkermansia, Defluviitaleaceae_UCG-011, and Rikenella abundance, and modulation of amino acid metabolism, may contribute to the anti-fibrosis and cardiac protective effects of Astragaloside IV.

[Effect of oxygen therapy on the morphology of cardiac muscle, lung and liver in rats with acute hydrogen sulfide intoxication].

OBJECTIVE: To evaluate the effects of different oxygen therapy technique (different concentrations of normobaric oxygen and the hyperbaric oxygen) on the ultrastructure of cardiac muscle, lung and liver in rats with acute hydrogen sulfide intoxication. METHODS: One hundred healthy male Wistar rats were randomly divided into five groups: normal control group (A), poisoned group (B), oxygen therapy group (C), oxygen therapy group (D) and oxygen therapy group (E). After the exposure to 300 ppm H2S for 60 min in a static exposure tank (1 m3), the rats were treated with oxygen therapy, C, D and E groups were given 33% oxygen, 50% oxygen of atmospheric oxygen and hyperbaric oxygen therapy for 100 min, respectively. The rats in normal control group inhaled air under the same environment. After exposure and therapy, the tissues of lung, heart and liver were observed under light microscope and electron microscope. RESULTS: The results of light microscope examination showed that the broken and not well aligned cardiac myofilaments, cytoplasmic edema and pyknosis could be seen in group B. The well aligned and clear cardiac myofilaments appeared in group C, D and E. The alveolar hemorrhage, edema and inflammatory cells exudation could not be seen in group A. Alveolar epithelial cell edema, unsmooth alveolar edge and alveolar inflammatory cells exudation could be found in group B. The unsmooth alveolar septal borders and pulmonary edema could be seen occasionally in group C and D, the alveolar inflammatory cells exudation could not be seen in group E. The regular hepatic boards and the uniform hepatic cellular nuclei were found in group A. The disordered hepatic boards, widened cellular gaps and cytoplasmic edema could be seen occasionally in group B. The irregular hepatic boards and ballooning degeneration could be seen in group C and D. The regular hepatic boards and uniform cytoplasm could be found in group E. The results of electron microscope examination indicated that the mitochondrial swelling, autolyzing, fuzzy and breakage of myocardial cells were observed in group B; the clear mitochondrial structure appeared in group E. The apoptosis and organelle vacuole of alveolar epithelial cells could be observed in group B. The relatively normal nuclei of alveolar epithelial cells could be seen in group E. The lax cytoplast structure of hepatocytes, unclear nuclear membrane, lumped chromatin, slightly swelled mitochondria and phagosomes were observed in group B. However, no improved change was observed in group C, D and E. CONCLUSION: Hydrogen sulfide could induce the extensive and severe damage of myocardial mitochondria, alveolar epithelial cells and hepatocytes, the oxygen therapy in good time could reduce significantly the myocardial injury, and improve the lung injury to some extent. High-pressure oxygen therapy is better than the normobaric oxygen therapy.

Add-on effect of Chinese herbal medicine in the treatment of mild to moderate COVID-19: A systematic review and meta-analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic since its outbreak in Wuhan, China. It is an urgent task to prevent and treat COVID-19 effectively early. In China's experience combating the COVID-19 pandemic, Chinese herbal medicine (CHM) has played an indispensable role. A large number of epidemiological investigations have shown that mild to moderate COVID-19 accounts for the largest proportion of cases. It is of great importance to treat such COVID-19 cases, which can help control epidemic progression. Many trials have shown that CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 was superior to conventional therapy alone. This review was designed to evaluate the add-on effect of CHM in the treatment of mild to moderate COVID-19. METHODS: Eight electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Clinical Trials.gov website, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database and China Biology Medicine (CBM) were searched from December 2019 to March 2021 without language restrictions. Two reviewers searched and selected studies, and extracted data according to inclusion and exclusion criteria independently. Cochrane Risk of Bias (ROB) tool was used to assess the methodological quality of the included RCTs. Review Manager 5.3.0 software was used for statistical analysis. RESULTS: Twelve eligible RCTs including 1393 participants were included in this meta-analysis. Our meta-analyses found that lung CT parameters [RR = 1.26, 95% CI (1.15, 1.38), P<0.00001] and the clinical cure rate [RR = 1.26, 95%CI (1.16, 1.38), P<0.00001] of CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 were better than those of conventional therapy. The rate of conversion to severe cases [RR = 0.48, 95%CI (0.32, 0.73), P = 0.0005], TCM symptom score of fever [MD = -0.62, 95%CI (-0.79, -0.45), P<0.00001], cough cases [RR = 1.43, 95%CI (1.16, 1.75), P = 0.0006], TCM symptom score of cough[MD = -1.07, 95%CI (-1.29, -0.85), P<0.00001], TCM symptom score of fatigue[MD = -0.66, 95%CI (-1.05, -0.28), P = 0.0007], and CRP[MD = -5.46, 95%CI (-8.19, -2.72), P<0.0001] of combination therapy was significantly lower than that of conventional therapy. The WBC count was significantly higher than that of conventional therapy[MD = 0.38, 95%CI (0.31, 0.44), P<0.00001]. Our meta-analysis results were robust through sensitivity analysis. CONCLUSION: Chinese herbal medicine combined with conventional therapy may be effective and safe in the treatment of mild to moderate COVID-19. More high-quality RCTs are needed in the future.

Transcriptome analysis reveals the molecular mechanism of Yiqi Rougan decoction in reducing CCl4-induced liver fibrosis in rats.

BACKGROUND: Liver fibrosis develops from various chronic liver diseases, and there is currently a lack of specific treatment strategies. Yiqi Rougan decoction (YQRG) is a traditional Chinese medicine that has shown durative effects in the treatment of liver fibrosis; however, the mechanism associated with YQRG-related improvements in liver fibrosis remains to be experimentally determined. This study evaluated the therapeutic effect of YQRG on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and its molecular mechanism. METHODS: We used low-, medium-, and high-dose YQRG to treat CCl4-induced liver fibrosis in rats, followed by assessment of liver injury and fibrosis according to liver appearance, body weight, liver mass index, histopathologic examination, and serum testing. Additionally, we performed transcriptome analysis using RNA-sequencing (RNA-seq) technology, including cluster, Gene Ontology (GO), and pathway analyses, to identify differentially expressed genes (DEGs), and protein and gene expression were detected by immunofluorescence (IFC), western blot and real-time quantitative PCR. RESULTS: The results showed that YQRG effectively alleviated CCl4-induced liver injury and fibrosis in rats, including observations of improved liver function, decreased activity of hepatic stellate cells (HSCs), and decreased extracellular matrix (ECM) deposition. Moreover, we identified downregulated and upregulated DEGs in the model group relative to the control and YQRG-treated groups, with GO analysis revealing their enrichment in biological processes, such as endoplasmic reticulum stress (ERS), apoptosis, and autophagy. Furthermore, pathway analysis showed that YQRG treatment downregulated the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/AKT) signalling pathways and upregulated other signalling pathways, including those related to peroxisome proliferator-activated receptors(PPAR) and AMP-activated protein kinase(AMPK), with these findings subsequently verified experimentally. CONCLUSION: These findings showed that YQRG improved CCl4-induced liver fibrosis through multiple mechanisms and pathways, offering critical insight into the YQRG-related therapeutic mechanism and promoting further research into its potential application.

Add-On Effect of Honeysuckle in the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a global emergency since December 2019. Chinese herbal medicine plays an important role in the treatment of COVID-19. Chinese herbal medicine honeysuckle is an extremely used traditional edible and medicinal herb. Many trials suggest that honeysuckle has obtained a good curative effect for COVID-19; however, no systematic evaluation on the clinical efficacy of honeysuckle in the treatment of COVID-19 is reported. This study aimed to evaluate the efficacy and safety of Chinese herbal medicine honeysuckle in the treatment of COVID-19. Methods: Seven electronic databases (PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine) were searched to identify randomized controlled trials (RCTs) of honeysuckle for adult patients (aged ≥ 18 years) with COVID-19. The Cochrane Risk of Bias Tool was applied to assess the methodological quality of trials. Review Manager 5.3 software was used for data analysis. Results: Overall, nine RCTs involving 1,286 patients were enrolled. Our meta-analyses found that combination therapy of honeysuckle and conventional therapy was more effective than conventional therapy alone in lung computed tomography (CT) [relative risk (RR) = 1.24, 95% confidence interval (95%CI) (1.12, 1.37), P < 0.0001], clinical cure rate [RR = 1.21, 95%CI (1.12, 1.31), P < 0.00001], and rate of conversion to severe cases [RR = 0.50, 95%CI (0.33, 0.76), P = 0.001]. Besides, combination therapy can improve the symptom score of fever, cough reduction rate, symptom score of cough, and inflammatory biomarkers (white blood cell (WBC) count; C-reactive protein (CRP)) (P < 0.05). Conclusion: Honeysuckle combined with conventional therapy may be beneficial for the treatment of COVID-19 in improving lung CT, clinical cure rate, clinical symptoms, and laboratory indicators and reducing the rate of conversion to severe cases. Besides, combination therapy did not increase adverse drug events. More high-quality RCTs are needed in the future.