Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

Objective To investigate the mechanism of Guizhi Fuling Pills in the treatment of polycystic ovary syndrome(PCOS)and endometriosis(EMT).Methods TCMSP was utilized to obtain the active ingredients and related targets of the constituent Chinese medicines of Guizhi Fuling Pills.GeneCards,PharmGKB,and TTD databases were used to screen PCOS and EMT disease targets,respectively.The Venn R diagram was drawn after obtaining the intersecting targets of drugs and diseases using the Venn R package in R software,the drug-active ingredient-potential target interactions network diagram was made in Cytoscape,the intersecting target protein-protein interactions(PPI)network diagram was drawn in the STRING platform,and Cytoscape was used to optimize the PPI network and screen the core targets.R language was applied for Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and AutoDockTools was for molecular docking.Results A total of 85 active ingredients and 191 corresponding targets of Guizhi Fuling Pills were obtained,and 77 potential targets of Guizhi Fuling Pills for the treatment of PCOS and EMT.The core active ingredients of Guizhi Fuling Pills for PCOS and EMT were quercetin,β-sitosterol,kaempferol,hederagenin,baicalein,and the core targets were AKT1,EGFR,IL-6,TNF,and TP53.GO functional analysis yielded 2 020 biological process,34 cellular components,126 molecular functions,and KEGG enrichment analysis yielded 165 signaling pathways.Molecular docking showed that the core components in the formula docked well with the targets.Conclusion Guizhi Fuling Pills may regulate the signaling pathways of lipid and atherosclerosis,AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,and chemical carcinogenesis-receptor activation through quercetin,β-sitosterol,kaempferol,hederagenin,and baicalein,and act on AKT1,EGFR,IL-6,TNF,and TP53,thus treating PCOS and EMT with homotherapy for heteropathy.

Objective To explore the risk factors related to afterload mismatch(AM)after transcatheter mitral valve repair(MitraClip).Methods This was a retrospective cohort study.48 patients hospitalized in the Department of Cardiovascular Medicine,the First Affiliated Hospital of Sun Yat-sen University from December 2021 to December 2023,who underwent MitraClip due to severe mitral regurgitation(MR)were included.Preoperative clinical data,laboratory tests,and preoperative and postoperative color Doppler echocardiographic examination results of surgical patients were collected.AM was defined as the left ventricular ejection fraction(LVEF)decreased by 15％or more after surgery compared with the one before(dLVEF≤-15％).Patients were divided into AM group and non-AM group according to whether afterload mismatch occurred.Univariate and multivariate logistic regression were used to analyze the risk factors of postoperative AM.Results Among 48 patients who underwent MitraClip,14 of them(29.2％)developed afterload-mismatched.For those without AM,their overall LVEF was improved after the operation;for patients in both AM group and non-AM group,their overall left ventricular end-diastolic diameter(LVEDd),left ventricular end-diastolic diameter volume index(LVEDVi)was reduced compared with the preoperative ones.Univariate regression analysis showed that C-reactive protein levels(OR 1.98,95％CI 1.02-3.83),platelets(OR 2.22,95％CI 1.08-4.53),systemic immune inflammation index(OR 1.96,95％CI 1.03-3.71)were associated with an increased risk of AM in patients undergoing MitraClip(all P＜0.05),while those with larger right atrial diameter(OR 0.35,95％CI 0.13-0.93)or moderate to severe tricuspid regurgitation(OR 0.19,95％CI 0.05-0.81)were less likely to develop into AM(both P＜0.05),which is still satisfied after adjustment.Conclusions For patients who underwent MitraClip,C-reactive protein levels,platelets and systemic immune inflammation index(SII)are associated with an increased risk of afterload mismatched,while those with larger right atrial diameter or moderate to severe tricuspid regurgitation were less likely to develop into AM.

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

Collagen is a macromolecular protein constituting the extracellular matrix of animal connective tissue, which has been widely used and developed in fields of biomedicine, tissue engineering, food, and cosmetics. Due to its advantages such as abundant sources and good biocompatibility, low immunogenicity, and degradability, collagen can be used as a dressing or tissue engineering scaffold for wound repair. According to the source of materials, collagen can be divided into natural collagen and recombinant collagen. Natural collagen is mainly extracted directly from mammals and fish; recombinant collagen is obtained based on genetic engineering technology, and its sources include recombinant expression systems of microorganisms, animals, and plants. This paper summarizes the sources of collagen, and the roles, advantages, and disadvantages of different sources of collagen in wound repair, the particularity and superiority of collagen combined with three-dimensional printing technology in wound repair, the impact of market norms of China's collagen industry on the field of wound repair, and explains the precautions for the development of collagen-related products, aiming to provide new ideas for selecting a suitable source of collagen for wound repair.
Animals ; Collagen/metabolism* ; Wound Healing ; Tissue Engineering ; Tissue Scaffolds ; Cosmetics ; Mammals/metabolism*

Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

Animals ; Electrophoresis, Gel, Two-Dimensional ; Male ; Muscles ; Physical Conditioning, Animal ; Proteome ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19. METHODS: Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders. RESULTS: The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. CONCLUSIONS Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.
COVID-19 ; China/epidemiology* ; Cities ; Humans ; SARS-CoV-2