Exploring the efficacy and molecular mechanism of Danhong injection comprehensively in the treatment of idiopathic pulmonary fibrosis by combining meta-analysis, network pharmacology, and molecular docking methods.

BACKGROUND: Danhong injection, a compound injection of Chinese herbal medicine, has been widely used in idiopathic pulmonary fibrosis (IPF) at present as an adjuvant treatment. However, the clinical efficacy and molecular mechanism of IPF are still unclear. This study will evaluate and explore the clinical efficacy and molecular mechanism of Danhong injection in the treatment of IPF. METHODS: In meta-analysis, the computer was used to search 8 databases (PubMed, EMbase, CENTRAL, MEDLINE, CBM, CNKI, WanFang, and VIP) to collect the RCTs, and RevMan 5.3 and Stata 14.0 were used for statistical analysis. It has been registered on PROSPERO: CRD42020221096. In network pharmacology, the main chemical components and targets of the chemical components of Danhong injection were obtained in TCMSP and Swiss Target Prediction databases. The main targets of IPF were obtained through Gencards, Disgenet, OMIM, TTD, and DRUGBANK databases. The String platform was used to construct PPI networks. Cytoscape 3.8.2 was used to construct the "Danhong components - IPF targets-pathways" network. The molecular docking verification was conducted by Auto Dock. RESULTS: Twelve RCTs were finally included with a total of 896 patients. The meta-analysis showed that Danhong injection could improve the clinical efficiency ([OR] = 0.25, 95% CI [0.15, 0.41]), lung function, arterial blood gas analysis, inflammatory cytokines, and serum cytokines associated with pulmonary fibrosis of IPF patients, respectively (P < .05). The core active components of Danhong injection on IPF were Luteolin, Quercetin, and Kaempferol, and the core targets were PTGS2, AR, ESR1, PPARG, and RELA. Danhong injection mainly improved IPF through PD-L1 expression and PD-1 checkpoint path in cancer, pathways in cancer, PI3K-Akt signaling pathway, etc. CONCLUSION: These results provided scientific basis for the clinical use of Danhong injection for the treatment of IPF, and provided a new direction to explore the potential mechanism of action of Danhong injection.

Husband smoking is associated with Wife's thyrotropin abnormality: A population-based cohort study among Chinese reproductive-aged women.

OBJECTIVES: To comprehensively assess the association of husband smoking with wives' thyrotropin abnormality. METHODS: This population-based retrospective cohort study included 2 406 090 Chinese reproductive-aged women who had participated twice in the National Free Pre-pregnancy Checkups Project between 2010 and 2020. Multivariate-adjusted odds ratios and 95% confidence intervals for subnormal and supranormal thyrotropin were estimated according to the husband's smoking status. RESULTS: Husband smoking at the first visit was associated with a 17% (15%-20%) and 26% (24%-28%) increased odds of subnormal thyrotropin and supranormal thyrotropin respectively compared to participants in neither-smoker group. In non-smoking participants with normal thyrotropin levels at the first visit, the corresponding increased risk of subnormal thyrotropin and supranormal thyrotropin at the second visit were 15% (12%-18%) and 19% (16%-21%) in contrast to participants without husband-smoking exposure. In non-smoking participants with abnormal thyrotropin levels at their first visit, husband smoking cessation was associated with 27% (17%-35%) and 36% (31%-40%) reduced odds of subnormal thyrotropin and supranormal thyrotropin at the second visit compared with the participants whose husband still smoking at the second visit. CONCLUSION: Husband smoking was associated with wives' subnormal thyrotropin and supranormal thyrotropin, and cessation of husband smoking could reduce the odds of thyrotropin abnormality. Couple-focused smoking intervention should be developed to reduce the burden of asymptomatic thyroid disease in females.

A comprehensive comparison of the safety and efficacy of drugs in the treatment of idiopathic pulmonary fibrosis: a network meta-analysis based on randomized controlled trials.

OBJECTIVE: Randomized controlled trials(RCTs) of multiple drugs for Idiopathic pulmonary fibrosis(IPF) have been reported and achieved a certain degree of efficacy, however, the difference in safety and efficacy of them for IPF is not yet well understood. The aim of this network meta-analysis is to assess their safety and efficacy in the treatment of IPF and differences in this safety and efficacy comprehensively. METHODS: The PubMed, EMbase, CENTRAL and MEDLINE were retrieved to find out the RCTs of drugs in the treatment of IPF. The retrieval date is from construction to November 10, 2022. Stata 14.0 and RevMan 5.3 was used for statistical analysis. REGISTRATION NUMBER: CRD42023385689. RESULTS: Twenty-four studies with a total of 6208 patients were finally included, including RCTs of 13 drugs. The results of safety showed that there' s no difference in the incidence of SAEs of 13 drugs treated with IPF compared to placebo (P>0.05), and it's also found that Warfarin had a higher all-cause mortality for IPF than placebo (OR = 5.63, 95% CI [1.54 to 20.55]). SUCRA' s scatterplot showed that Pirfenidone, Nintedanib, Sildenafil and Imatinib were lower than placebo, and Warfarin, Ambrisentan and N-acetylcysteine were higher than placebo. The results of effectiveness showed that Nintedanib (MD = -0.08, 95% CI [-0.12 to -0.04]) improved FVC (L)absolute change from baseline in patients better than placebo, and Nintedanib (OR=1.81, 95% CI [1.23 to 2.66]), Pirfenidone (OR=1.85, 95%CI [1.26 to 2.71]) and Pamrevlumab (OR=4.11, 95% CI [1.25 to 13.58]) improved the proportion of patients with a decline in FVC ≥10% predicted better than placebo. SUCRA' s scatterplot showed that Pamrevlumab, Pirfenidone and Nintedanib were lower than placebo, and Warfarin and Ambrisentan were higher than placebo. CONCLUSION: Compared with other drugs, Nintedanib and Pirfenidone can significantly slow the decline of lung function in patients with IPF, and the safety is higher. Therefore, they can be further promoted in clinical practice. Warfarin and Ambrisentan shouldn't be used clinically for IPF as the safety and efficacy of them are poor compared to other drugs and placebo. Pamrevlumab may become important drugs for the treatment of IPF in the future.

QiShenYiQi pill inhibits atherosclerosis by promoting TTC39B-LXR mediated reverse cholesterol transport in liver.

BACKGROUND: Tetranucleotide repeat domain protein 39B (TTC39B) was found to combine with ubiquitin ligase E3, and promote the ubiquitination modification of liver X receptor (LXR), which led to the inhibition of reverse cholesterol transport and development of atherosclerosis. QiShenYiQi pill (QSYQ) is a modern Chinese patent drug for treating ischemic cardiovascular diseases, the underlying mechanism is found to promote the expression of LXR-α/ ATP-binding cassette transporter G5 (ABCG5) in the liver of atherosclerotic mice. PURPOSE: The aim of this study is to investigate the effect of QSYQ on TTC39B-LXR mediated reverse cholesterol transport in atherosclerotic mice. STUDY DESIGN AND METHODS: Male apolipoprotein E gene knockout mice (7 weeks old) were fed with high-fat diet and treated with low dose of QSYQ (QSYQ-l, 0.3 g/kg·d), high dose of QSYQ (QSYQ-H, 1.2 g/kg·d) and LXR-α agonist (LXR-A, GW3965 10 mg/kg·d) for 8 weeks. C57BL/6 J mice were fed with normal diet and used as negative control. Oil red O staining, HE staining, ELISA, RNA sequencing, western blot, immunohistochemistry, RT-PCR, cell culture and RNA interference were performed to analyze the effect of QSYQ on atherosclerosis. RESULTS: HE staining showed that QSYQ reduced the atherosclerotic lesion significantly when compared to the control group. ELISA measurement showed that QSYQ decreased serum VLDL and increased serum ApoA1. Oil Red O staining showed that QSYQ reduced the lipid content of liver and protect liver function. Comparative transcriptome RNA-sequence of liver showed that DEGs after QSYQ treatment enriched in high-density lipoprotein particle, ubiquitin ligase complex, bile secretion, etc. Immunohistochemical staining and western blot proved that QSYQ increased the protein expression of hepatic SR-B1, LXR-α, LXR-ß, CYP7A1 and ABCG5. Targeted inhibiting Ttc39b gene in vitro further established that QSYQ inhibited the gene expression of Ttc39b, increased the protein expression of SR-B1, LXR-α/ß, CYP7A1 and ABCG5 in rat hepatocyte. CONCLUSION: Our results demonstrated the new anti-atherosclerotic mechanism of QSYQ by targeting TTC39B-LXR mediated reverse cholesterol transport in liver. QSYQ not only promoted reverse cholesterol transport, but also improved fatty liver and protected liver function.

Association of vitamin D receptor gene polymorphism with the risk of sepsis: A systematic review and meta-analysis.

BACKGROUND: To investigate the association between sepsis and the vitamin D receptor (VDR) gene polymorphisms. METHODS: Databases including PubMed, Cochrane Library, EMbase, CNKI, Wanfang Data, and VIP Data were systematically searched. The association was assessed using odds ratios (ORs), and 95% confidence intervals (CIs). The statistical tests were performed using Review Manager 5.4. RESULTS: We identified a total of 5 studies. The relationship between VDR gene polymorphisms (Apa I, Bsm I, Taq I, and Fok I), and incidence of sepsis was investigated. The results of this meta-analysis showed that the allelic contrast model (F vs f, P = .03, OR = 0.65, 95% CI = 0.44-0.95), dominant genetic model (FF vs Ff + ff, P = .02, OR = 0.53, 95% CI = 0.30-0.91), and codominance genetic model (FF vs ff, P = .03, OR = 0.39, 95% CI = 0.16-0.91) of VDR Fok I locus increased the risk of sepsis, and the lack of association between the VDR Fok I gene polymorphism and the risk assessment of sepsis, based on the ethnic subgroup analysis, might be attributable to the small sample size. The risk of sepsis with Apa I, Bsm I, and Taq I did not appear to be correlated. CONCLUSION SUBSECTIONS: This meta-analysis revealed that the VDR Fok I polymorphism is closely associated with the susceptibility to sepsis, and patients with sepsis have lower 25-hydroxyvitamin D levels. VDR Fok I gene mutations may change the risk of sepsis.

Mechanism of Simiao Decoction in the treatment of atherosclerosis based on network pharmacology prediction and molecular docking.

To explore the molecular mechanism of Simiao Decoction (SMD) intervening atherosclerosis (AS). The main components and potential mechanisms of SMD remain unknown. This study aims to initially clarify the potential mechanism of SMD in the treatment of AS based on network pharmacology and molecular docking techniques. The principal components and corresponding protein targets of SMD were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the compound-target network was constructed by Cytoscape3.9.1. AS targets were searched on DrugBank, OMIM, and TTD databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a protein-protein interaction network. We further performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the targets. The molecular docking method was used to verify the interaction between core components of SMD and targets. We created the active compounds-targets network and the active compounds-AS-targets network based on the network database containing Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, DrugBank, OMIM, and TTD. We discovered that the therapy of AS with SMD involves 3 key substances-quercetin, kaempferol, and luteolin-as well as 5 crucial targets-ALB, AKT1, TNF, IL6, and TP53. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the shared targets involved a number of signaling pathways, including the advanced glycosylation end product-receptor of AGE signaling pathway in diabetic complications, Hepatitis B, Lipid and atherosclerosis, Chemical Carcinogenesis-Receptor Activation, and Pathways in Cancer. The molecular docking demonstrated that the binding energies of quercetin, kaempferol, and luteolin with 5 important targets were favorable. This study reveals the active ingredients and potential molecular mechanism of SMD in the treatment of AS, and provides a reference for subsequent basic research.

Ethnicity-specific association between TERT rs2736100 (A > C) polymorphism and lung cancer risk: a comprehensive meta-analysis.

The rs2736100 (A > C) polymorphism of the second intron of Telomerase reverse transcriptase (TERT) has been confirmed to be closely associated with the risk of Lung cancer (LC), but there is still no unified conclusion on the results of its association with LC. This study included Genome-wide association studies (GWAS) and case-control studies reported so far on this association between TERT rs2736100 polymorphism and LC to clarify such a correlation with LC and the differences in it between different ethnicities and different types of LC. Relevant literatures published before May 7, 2022 on 'TERT rs2736100 polymorphism and LC susceptibility' in PubMed, EMbase, CENTRAL, MEDLINE databases were searched through the Internet, and data were extracted. Statistical analysis of data was performed in Revman5.3 software, including drawing forest diagrams, drawing funnel diagrams and so on. Sensitivity and publication bias analysis were performed in Stata 12.0 software. The C allele of TERT rs2736100 was associated with the risk of LC (Overall population: [OR] = 1.21, 95%CI [1.17, 1.25]; Caucasians: [OR] = 1.11, 95%CI [1.06, 1.17]; Asians: [OR] = 1.26, 95%CI [1.21, 1.30]), and Asians had a higher risk of LC than Caucasians (C vs. A: Caucasians: [OR] = 1.11 /Asians: [OR]) = 1.26). The other gene models also showed similar results. The results of stratified analysis of LC patients showed that the C allele was associated with the risk of Non-small-cell lung carcinoma (NSCLC) and Lung adenocarcinoma (LUAD), and the risk of NSCLC and LUAD in Asians was higher than that in Caucasians. The C allele was associated with the risk of Lung squamous cell carcinoma (LUSC) and Small cell lung carcinoma(SCLC) in Asians but not in Caucasians. NSCLC patients ([OR] = 1.27) had a stronger correlation than SCLC patients ([OR] = 1.03), and LUAD patients ([OR] = 1.32) had a stronger correlation than LUSC patients ([OR] = 1.09).In addition, the C allele of TERT rs2736100 was associated with the risk of LC, NSCLC and LUAD in both smoking groups and non-smoking groups, and the risk of LC in non-smokers of different ethnic groups was higher than that in smokers. In the Asians, non-smoking women were more at risk of developing LUAD. The C allele of TERT rs2736100 is a risk factor for LC, NSCLC, and LUAD in different ethnic groups, and the Asian population is at a more common risk. The C allele is a risk factor for LUSC and SCLC in Asians but not in Caucasians. And smoking is not the most critical factor that causes variation in TERT rs2736100 to increase the risk of most LC (NSCLC, LUAD). Therefore, LC is a multi-etiological disease caused by a combination of genetic, environmental and lifestyle factors.

Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain.

Neuropathic pain (NeP) remains a significant clinical challenge owing to insufficient awareness of its pathological mechanisms. We elucidated the aberrant metabolism of the cerebral cortex in NeP induced by the chronic constriction injury (CCI) using metabolomics and proteomics analyses. After CCI surgery, the values of MWT and TWL markedly reduced and maintained at a low level. CCI induced the significant dysregulation of 57 metabolites and 31 proteins in the cerebral cortex. Integrative analyses showed that the differentially expressed metabolites and proteins were primarily involved in alanine, aspartate and glutamate metabolism, GABAergic synapse, and retrograde endocannabinoid signaling. Targeted metabolomics and western blot analysis confirmed the alterations of some key metabolites and proteins in endogenous pain-modulatory system. In conclusion, our study revealed the alterations of endocannabinoids system and purinergic system in the CCI group, and provided a novel perspective on the roles of endogenous pain-modulatory system in the pathological mechanisms of NeP.

QiShenYiQi pill inhibits atherosclerosis by promoting reverse cholesterol transport PPARγ-LXRα/ß-ABCA1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: QiShenYiQi pill (QSYQ), a Chinese compound medicine, originate from BuYangHuanWu decoction in the Qing dynasty, and has been used to treat ischemic cardiovascular diseases for more than two hundred years in China. Multi-central randomized double-blind controlled studies have proved that QSYQ has similar efficacy as enteric coated aspirin in the secondary prevention of myocardial infarction. AIM OF STUDY: The aim of study was to explore the effect of QSYQ on reverse cholesterol transport (RCT) pathway during atherosclerosis. MATERIALS AND METHODS: Eight-week-old male apoE-/- mice (on the gene background of C57BL/6J) were fed with a high-fat western diet and treated with low dose and high dose of QSYQ, as well as the positive control agent, liver X receptor-α (LXR-α) agonist GW3965. Eight weeks later, mice were sacrificed and the aorta was collected for atherosclerotic analysis. The aortic root was stained with Oil red O to evaluate the area of atherosclerotic lesion, and stained with immunohistochemistry to analyze the intra-plaque component and RCT protein in atherosclerotic plaque. The thoracic aorta was used to detect differentially expressed genes by comparative transcriptome RNA-seq and the protein expression of RCT pathway by western blotting. RESULTS: After eight weeks of treatment, we found that both of QSYQ and LXR-α agonist reduced atherosclerotic plaque area significantly, and decreased the intra-plaque component, including the lipid, the smooth muscle cell and the macrophage. Compared with the control group, there were 49 differentially expressed genes in low-dose QSYQ group, including 21 up-regulated genes and 28 down-regulated genes. The results of GO and KEGG analysis showed that the differentially expressed genes mainly concentrated in the negative regulation of lipid biosynthesis, positive regulation of lipid metabolism, cell response to lipids, negative regulation of lipid storage, fatty acid degradation, and glycerol ester metabolism. Both of QSYQ and LXR-α agonist reduced the protein expression of CD36 and increased the protein expression of PPARγ-LXRα/ß-ABCA1 in atherosclerotic plaque. CONCLUSION: The anti-atherosclerotic mechanism of QSYQ was involved in inhibiting lipid phagocytosis and promoting reverse cholesterol transport, therefore reducing lipid deposition and inflammatory cells in plaque.

Vitamin D can ameliorate premature ovarian failure by inhibiting neutrophil extracellular traps: A review.

The etiology of premature ovarian failure (POF) is mainly related to inflammatory diseases, autoimmune diseases, and tumor radiotherapy and chemotherapy; however, its specific pathogenesis has not been clarified. Vitamin D (VD), a fat-soluble vitamin, is an essential steroid hormone in the human body. Neutrophil extracellular traps (NETs) are meshwork structures that are formed when neutrophils are stimulated by inflammation and other factors and are closely associated with autoimmune and inflammatory diseases. Notably, VD inhibits NET formation and intervenes in the development of POF in terms of inflammatory and immune responses, oxidative stress, and tissue fibrosis. Therefore, this study aimed to theorize the relationship between NETs, VD, and POF and provide new ideas and targets for the pathogenesis and clinical treatment of POF.

PNPLA3 148M/M Is More Susceptible to Palmitic Acid-Induced Endoplasmic Reticulum Stress-Associated Apoptosis in HepG2 Cells.

Background: Patatin-like phospholipase domain-containing 3 (PNPLA3) is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD), and its rs738409 (I148M) polymorphism is associated with the occurrence and progression of NAFLD. Endoplasmic reticulum (ER) stress-related hepatocyte lipoapoptosis contributes to the progress of NAFLD. PNPLA3 is also known as a member of the calcium-independent phospholipase A2ε family, which can hydrolyze fatty acids to generate lysophosphatidylcholine (LPC) that induces ER stress-related hepatocyte lipoapoptosis. Whether the PNPLA3 risk genotype 148M/M is involved in more severe ER stress-associated lipoapoptosis is unclear. Methods: A PNPLA3148I knock-in HepG2 cell model was constructed based on HepG2 expressing PNPLA3 148M/M using the Cas9/sgRNA system. PNPLA3 148M/M, I/M, and I/I cells were treated with 0.3 mM palmitic acid (PA) for 24 h to induce lipid deposition. Cellular lipid deposition was detected by oil red staining. Apoptosis was observed by TUNEL. LPC was determined by ELISA, and the expression of PNPLA3, the ER stress marker Bip, molecules involved in the ER stress PERK/elF-2a pathway, and its downstream C/EBP homologous protein (CHOP)-mediated apoptotic pathway were detected by western blot. Results: The results showed no difference in PNPLA3 basal expression and basal hepatocyte lipid content between the three genotypes of cells. Lipid deposition and apoptosis were more severe in PNPLA3 148M/M and 148I/M cells than in I/I cells after PA treatment. PA-induced upregulation of protein expression of Bip, ER stress-responsive PERK pathway molecules p-PERK, p-eIF2α, CHOP, and CHOP-associated apoptotic molecules PUMA and Bax were more pronounced in PNPLA3 148M/M cells than in PNPLA3 148I/I cells. The basal LPC levels and the PA-treated increase of LPC levels in the cell culture supernatants did not differ between the three genotypic cells. Conclusion: PNPLA3 148M/M cells were more susceptible to PA-induced lipid deposition and ER stress-related apoptosis than 148I/I cells, and the proapoptotic susceptibility of PNPLA3 148M/M is independent of LPC.

Multi-phase attention network for face super-resolution.

Previous general super-resolution methods do not perform well in restoring the details structure information of face images. Prior and attribute-based face super-resolution methods have improved performance with extra trained results. However, they need an additional network and extra training data are challenging to obtain. To address these issues, we propose a Multi-phase Attention Network (MPAN). Specifically, our proposed MPAN builds on integrated residual attention groups (IRAG) and a concatenated attention module (CAM). The IRAG consists of residual channel attention blocks (RCAB) and an integrated attention module (IAM). Meanwhile, we use IRAG to bootstrap the face structures. We utilize the CAM to concentrate on informative layers, hence improving the network's ability to reconstruct facial texture features. We use the IAM to focus on important positions and channels, which makes the network more effective at restoring key face structures like eyes and mouths. The above two attention modules form the multi-phase attention mechanism. Extensive experiments show that our MPAN has a significant competitive advantage over other state-of-the-art networks on various scale factors using various metrics, including PSNR and SSIM. Overall, our proposed Multi-phase Attention mechanism significantly improves the network for recovering face HR images without using additional information.

Comparison of 4 kinds of traditional Chinese medicine injections to assist in improving clinical indicators of patients with idiopathic pulmonary fibrosis: A systematic review and network meta-analysis.

BACKGROUND: At present, apart from lung transplantation, no drugs can effectively treat idiopathic pulmonary fibrosis (IPF). Therefore, it is imperative to explore new drugs to control or treat it. Traditional Chinese medicine (TCM) injections have been widely used in the field of IPF, but there is no comparison of their efficacy in the assisted improvement of IPF. Therefore, the purpose of this study is to network meta-analyze the efficacy and safety of 4 kinds of commonly used TCM injections assisted by conventional treatment to improve the disease. METHODS: Used a computer to find the Randomized Controlled Trials (RCTs) from the 8 major databases (PubMed, EMbase, CENTRAL, MEDLINE, CBM, China National Knowledge Infrastructure, WanFang Database and VIP Chinese Science). Cochrane's risk assessment tool was used to evaluate the quality of the literature. The Grading of Recommendations Assessment, Development and Evaluation approach served to assess the certainty in the evidence of direct and indirect estimates. Revman5.3 (Review Manager (RevMan) Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.) and stata14.0 (Stata/SE 14.0 for Windows (64-bit). Revision Apr 22, 2015.Copyright 1985-2015 StataCorp LP). were used for Statistical analysis. Registration number: CRD42020220570. RESULTS: After layer-by-layer screening, 20 RCTs were finally included, which include a total of 1363 patients and 4 kinds of RCT of TCM injection (12 studies on Danhong injection, 5 studies on Ligustrazine injection, 2 studies on Huangqi injection and 1 study on Dazhu hongjingtian injection). The results showed: Clinical effective rate: Danhong Injection (Odds ratio [OR] = 3.94, 95% CI [2.34, 6.64], moderate certainty of evidence), Huangqi injection (OR = 3.40, 95% CI [1.38, 8.41], moderate certainty of evidence) and Ligustrazine injection (OR = 2.74, 95% CI [1.62, 4.64], moderate certainty of evidence) combined with conventional treatment had better curative efficacy than that of the conventional treatment group. SUCRA Ranking: Danhong (80.5) > Huangqi (68.5) > Ligustrazine (52.9) > Dazhu hongjingtian (44.3) > Conventional treatment (3.8); Forced Expiratory Volume In 1s/Forced vital capacity%: SUCRA Ranking: Danhong (80.0) > Ligustrazine (62.9) > Conventional treatment (2.1); Carbon monoxide diffusing capacity%: SUCRA Ranking: Ligustrazine (89.9) > Dazhu hongjingtian (63.4) > Danhong (44.9) > Conventional treatment (1.8); Partial pressure of Oxygen: SUCRA Ranking: Dazhu Hongjingtian (87.1) > Danhong (78.8) > Ligustrazine (34.0) > Conventional treatment (0.0); Partial pressure of carbon dioxide: SUCRA Ranking: Danhong (99.3) > Ligustrazine (50.3) > Conventional treatment (0.4). No obvious adverse reactions were found in all studies. CONCLUSION: The four TCM injections combined with conventional treatment can effectively improve the clinical indicators of patients with IPF, and the improvement effect of Danhong injection was more obvious.

Quantitative evaluation of precautions against the COVID-19 indoor transmission through human coughing.

In this work, we focus on the dispersion of COVID-19-laden droplets using the transient computational fluid dynamics (CFD) modeling and simulation of the coughing process of virus carriers in an enclosure room, aiming to set up the basic prototype of popular precautionary strategies, i.e., face mask, upward ventilation, protective screen, or any combination thereof, against the indoor transmission of COVID-19 and other highly contagious diseases in the future. A multi-component Eulerian-Lagrangian CFD particle-tracking model with user-defined functions is utilized under 8 cases to examine the characteristics of droplet dispersion concerning the mass and heat transfer, droplet evaporation, air buoyancy, air convection, air-droplet friction, and turbulent dispersion. The result shows that implementing upward ventilation is the most effective measure, followed by wearing face masks. Protective screens can restrict the movement of the coughing droplets (though it will not reduce viral load). However, applying protective screens arranged with lean can be counterproductive in preventing the spread of COVID-19 when it is inappropriately placed with ventilation. The soundest solution is the combination of the face mask and upward ventilation, which can reduce the indoor infectious concentration by nearly 99.95% compared with the baseline without any precautionary strategies. With the resumption of school and work in the post-epidemic era, this study would provide intelligence-enhancing advice for the masses and rule-makers to curb the pandemic.

Astragalus polysaccharide protects sepsis model rats after cecum ligation and puncture.

To investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on septic rats, the present project applied APS at concentrations of 400, 600, and 800 mg/kg/d to rats for prophylactic administration for 7 d, and a rat sepsis model was constructed by the cecum ligation and puncture (CLP) method. Forty-eight rats were divided into six groups of eight each. Each experiment was repeated at least three times. Rat serum levels of VD3, 25(OH)D3, 1,25(OH)2D3, IL-6, TNF-α, CRP, sICAM-1, corticosterone (CORT), and short-chain fatty acids (SCFAs) in each group were detected, and renal damage was observed by H&E. We also determined the protein expression of CYP27B1, CYP24A1, vitamin D receptor (VDR), steroidogenic acute regulatory protein (STAR), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), CYP21A2, CYP17A1, and CYP11B1. An operational taxonomic unit (OTU) was used to determine the gut microbiota diversity of septic rats after prophylactic administration and before modeling. Results revealed that APS markedly increased the contents of 25(OH)D3 and 1,25(OH)2D3 but greatly decreased those of TNF-α, IL-6, CRP, sICAM-1, and CORT. APS alleviated renal tubular dilation and vascular congestion in rat kidneys and substantially reduced renal cell apoptosis. Moreover, the expression of CYP24A1, VDR, CYP11B1, CYP21A2, CYP17A1, STAR, and 3ß-HSD in the kidneys of the H-APS group was substantially decreased compared to that of the model group, whereas CYP27B1 was markedly increased. GC-MS detection indicated a substantial increase in SCFAs and acetic acid content in the H-APS group versus model group. Through 16S sequencing, the abundance of genus and gut microbiota species increased in the APS groups compared to that of the control group. Taken together, APS increased the activity of the vitamin D axis, inhibited the production of inflammatory factors in the body, altered the structure of rat intestinal flora, and increased the amount of acetic acid and SCFAs in rats, thereby effectively hindering inflammation and organ damage in septic rats.

Increased frequency of angiotensin converting enzyme D allele in Chinese Han patients with idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

BACKGROUND: To explore the association between Angiotensin Converting Enzyme (ACE) insert(I)/defect(D) gene polymorphism and the susceptibility to idiopathic pulmonary fibrosis (IPF). METHODS: Searching PubMed, EMbase, CENTRAL, MEDLINE, CBM, China National Knowledge Infrastructure, WanFang Database and VIP Chinese Science database through a computer and collect the literature from China and foreign countries published before January 22, 2022. Screen the literatures and extract data such as first author, year of publication, diagnostic criteria and gene frequency, and draw a funnel chart and perform Begg's Test and Egger's test to evaluate publication bias. The influence analysis was performed for heterogeneous results and at the same time, the trial sequential analysis (TSA) was also conducted to confirm the robustness of the meta-analysis results. Registration number: CRD42021259341. RESULTS: There were a total of 4 literatures (4 studies conducted in the Chinese Han population), and a total of 292 IPF patients and 351 healthy controls were included in this study. The results showed that in the Chinese Han population, the ACE I/D gene polymorphism was associated with the susceptibility of IPF (D vs I: [odds ratio, OR] = 0.53, 95% confidence interval [95%CI] [0.42, 0.67], P < .00001; DD vs II: [OR] = 0.37, 95%CI [0.24, 0.57], P < .00001; DD vs II + ID:[OR] = 0.30, 95%CI [0.21, 0.43], P < .00001), and the angiotensin II (Ang Ⅱ) level of IPF patients was higher than that of the control group (mean difference [MD] = 14.29, 95%CI [11.20,17.37], P < .00001).The TSA also confirmed that D allele was closely related to the susceptibility of IPF. CONCLUSION: In the Chinese Han population, the D allele of the ACE I/D gene polymorphism is associated with the susceptibility of IPF.

T-SPOT with CT image analysis based on deep learning for early differential diagnosis of nontuberculous mycobacteria pulmonary disease and pulmonary tuberculosis.

OBJECTIVES: This study aimed to establish a diagnostic algorithm combining T-SPOT with computed tomography image analysis based on deep learning (DL) for early differential diagnosis of nontuberculous mycobacteria pulmonary disease (NTM-PD) and pulmonary tuberculosis (PTB). METHODS: A total of 1049 cases were enrolled, including 467 NTM-PD and 582 PTB cases. A total of 320 cases (160 NTM-PD and 160 PTB) were randomized as the testing set and were analyzed using T-SPOT combined with the DL model. The testing cases were first divided into T-SPOT-positive and -negative groups, and the DL model was then used to separate the cases into four subgroups further. RESULTS: The precision was found to be 91.7% for the subgroup of T-SPOT-negative and DL classified as NTM-PD, and 89.8% for T-SPOT-positive and DL classified as PTB, which covered 66.9% of the total cases, compared with the accuracy rate of 80.3% of T-SPOT alone. In the other two remaining groups, where the T-SPOT prediction was inconsistent with the DL model, the accuracy was 73.0% and 52.2%, separately. CONCLUSION: Our study shows that the new diagnostic system combining T-SPOT with DL based computed tomography image analysis can greatly improve the classification precision of NTM-PD and PTB when the two methods of prediction are consistent.

A Microneedle Patch with Self-Oxygenation and Glutathione Depletion for Repeatable Photodynamic Therapy.

Photodynamic therapy (PDT) has attained extensive attention as a noninvasive tumor treatment modality. However, the hypoxia in solid tumors, skin phototoxicity of "always on" photosensitizers (PSs), and abundant supply of glutathione (GSH) in cancer cells severely hampered the clinical applications of PDT. Herein, a self-oxygenation nanoplatform (denoted as CZCH) with GSH depletion ability was encapsulated into the hyaluronic acid microneedle patch (MN-CZCH) to simultaneously improve the biosafety and therapeutic efficacy of PDT. The Cu2+-doped porous zeolitic imidazolate framework incorporated with catalase (CAT) is capable of efficiently loading PS 2-(1-hexyloxyethyl)-2-divinylpyropheophorbic-a (HPPH). The CZCH intermingled MN patch (MN-CZCH) could effectively penetrate the stratum corneum, topically transport HPPH to the target tumor site, achieve a long tumor retention time, and enhance the efficacy of PDT via the simultaneously synergistic effect of CAT-catalyzed self-supplying O2 and Cu2+-mediated GSH depletion. Using traceable fluorescence (FL) imaging of the released HPPH from CZCH, the FL imaging-guided repeatable PDT can be achieved for enhanced antitumor efficacy. As a result, the MN-CZCH patch exhibited excellent therapeutic efficacy against melanoma with minimal toxicity, which has promising potential for cancer theranostics.

Bufei Decoction Improves Lung-Qi Deficiency Syndrome of Chronic Obstructive Pulmonary Disease in Rats by Regulating the Balance of Th17/Treg Cells.

Bufei decoction (BFD) has been applied to treat chronic obstructive pulmonary disease (COPD) for centuries as a recognized traditional Chinese herbal formula. However, mechanisms of BFD on COPD are unclear. This study conducts an inquiry into the underlying mechanisms of the therapeutic effect of BFD on COPD. A COPD rat model with qi deficiency in lungs was established through induction using cigarette and sawdust smoking combined with intratracheal instillation of lipopolysaccharide following BFD treatment for 28 days. Changes in Th17/Treg cells of COPD rats with the syndrome of lung qi deficiency after BFD administration were verified using pulmonary function, ELISA, flow cytometry, histopathology, and Western blotting assays. The findings showed that BFD protected COPD rats from decreased lung function and lung injury. BFD administration reduced proinflammatory cytokines IL-6 and IL-17 secretion, promoted inhibitory cytokines IL-10 and TGF-ß secretion, decreased Th17/Treg cell ratio, markedly downregulated the Th17 cell transcription factor ROR-γt expression, and upregulated transcription factor Foxp3 expression in Treg cells. We speculate that lung tonic soup improved pulmonary qi deficiency in rats with COPD by regulating the balance of Th17/Treg cells.

SIRT1 mediates nutritional regulation of SREBP-1c-driven hepatic PNPLA3 transcription via modulation of H3k9 acetylation.

BACKGROUND: Patatin-like phospholipase domain containing 3 (PNPLA3) is the main nonalcoholic fatty liver disease (NAFLD) susceptibility. Its expression is regulated tightly by nutritional and energy status, but the mechanism of epigenetic regulation of PNPLA3 gene by nutritional dietary factors has not been reported. Here, we investigated the effect and mechanism of Sirtuin 1 (SIRT1) regulated H3K9 deacetylation on PNPLA3 transcriptional expression in vivo and in vitro. METHODS: Mouse models of fasting/re-feeding transition and nonalcoholic fatty liver induced by high Sucrose diet were constructed; and HepG2 cells were treated with serum- and glucose-free medium or exposed to high glucose and high insulin, to generate fasting and high-glucose-induced lipid deposition cell states. Enrichment levels of histone H3K9 acetylation and sterol responsive element binding protein-1c (SREBP-1c) at the PNPLA3 promoter were observed by ChIP-qPCR. PNPLA3 gene expression was detected by real-time PCR; SIRT1 protein expression was detected by western blot. And lipid deposition was detected by Oil Red O. RESULTS: H3K9ac levels at SRE regions of PNPLA3 promoter were found to be decreased in mice during fasting and increase during refeeding, and increased in mice with NAFLD induced by high-sucrose diet. The change pattern of PNPLA3 promoter H3K9Ac physiologically (fasting/refeeding) and pathologically was consistent with that of PNPLA3 gene expression, but opposite to that of SIRT1 protein expression. In HepG2 cells, overexpression of SIRT1 inhibited high-glucose induced hyper-acetylation of H3K9 at PNPLA3 promoter, and silent expression of SIRT1 suppressed fasting-induced hypo-acetylation of H3K9. Overexpression of SIRT1 prevented basal and SREBP-1c-driven PNPLA3 gene expression and also prevented the endogenous binding of SREBP-1c to PNPLA3. CONCLUSIONS: We first preliminarily revealed SIRT1 may regulate PNPLA3 gene expression by affecting SREBP-1-driven transcription via acetylation modification of H3K9.