This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

Aim To investigate the effect of Toddalia asiatica(TA)on bone destruction in rheumatoid ar-thritis(RA)and its possible mechanism by network pharmacology and in vitro experiments.Methods The active components and targets of TA against RA bone damage were analyzed by network pharmacology.Mo-lecular docking was performed by using AutoDock and PyMOL software pairs.MC3T3-e1 cells were cultured in vitro,and the effect of Toddalia asiatica alcohol ex-tract(TAAE)on cell viability was detected by CCK-8,and appropriate drug concentration and intervention time were screened.The osteoblast model was induced by osteogenic induction medium,and the osteogenic differentiation was detected by ALP staining,activity detection and alizarin red staining.The expression of pathway-related proteins Wnt3a and β-catenin was de-tected by Western blot,and the pathway inhibitor DKK-1 was used to further verify whether TAAE regulated osteoblast differentiation through the Wnt/β-catenin signaling pathway.Results A total of 158 anti-RA bone destruction targets and 56 core targets were se-lected.The enrichment of KEGG signaling pathway mainly included cancer pathway,phosphatidylinositol 3-kinase/protein kinase B signaling pathway and cAMP signaling pathway.The results of CCK-8 showed that 1 g·L-1 TAAE could significantly improve cell survival rate.The results of ALP staining and ALP activity de-tection showed that TAAE could significantly increase the staining positive rate and ALP activity of cells in-duced by osteogenic induction medium.Western blot showed that TAAE could increase the expression of Wnt3a and β-catenin.The expression of these proteins decreased after DKK-1 inhibitors were used.Conclu-sion TAAE can regulate osteoblast differentiation through Wnt/β-catenin signaling pathway to treat os-teodestruction in rheumatoid arthritis.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective:To verify the clinical efficacy and safety of Qufeng Tongxuan method in treating low- and moderate-volume intracerebral hemorrhage at acute stage.Methods:A prospective, multicenter, randomized, double-blind, placebo-controlled study was performed; patients with low- and moderate-volume intracerebral hemorrhage at the basal ganglia and/or thalamus accepted treatment in 16 hospitals from September 2019 to April 2022 were enrolled. These patients were divided into experimental and control groups with a block randomized method by SAS software. Patients in control group were given conventional western medicine treatment; those in experimental group accepted Qufeng Tongxuan method (sequential therapy of Shexiang Huayu Xingnao granules and Zhilong Huoxue Tongyu granules) besides conventional western medicine treatment. NIHSS was used to assess neurological function before treatment and on 7 th, 14 th, 30 th, and 90 th d of treatment. Prognoses of these patients were assessed by modified Rankin scale (mRS) before treatment and on 180 th d of treatment. Brain CT was performed before treatment and on 7 th and 14 th d of treatment to calculate the hematoma volume. Before treatment and on 14 th d of treatment, changes of coagulation function, liver and kidney functions of the 2 groups were compared. Adverse reactions during treatment in the 2 groups were recorded. Results:No significant differences in NIHSS scores were noted between the 2 groups before treatment, on 7 th, 14 th, and 30 th d of treatment ( P>0.05); NIHSS scores in experimental group on 90 th d of treatment were signficantly lower than those in control group ( P<0.05); NIHSS scores in experimental group decreased gradually before treatment and on 7 th, 14 th, 30 th and 90 th d of treatment, with statistical significances ( P<0.05). No significant differences in mRS scores were noted between the 2 groups before treatment ( P>0.05); mRS scores in experimental group on 180 th d of treatment were signfciantly lower than those in control group ( P<0.05). No significant difference in hematoma volume was noted between the 2 groups before treatment and on 7 th and 14 th d of treatment ( P>0.05); both groups had gradually decreased hematoma volumes before treatment and on 7 th and 14 th d of treatment, respectively, with significant differences ( P<0.05); the volume difference of hematoma between 14 th d of treatment and before treatment in experimental group (6.42[4.10, 11.73]) was significantly higher than that in control group (4.00[1.25, 10.58], P<0.05). No significant differences in liver and kidney function indexes or coagulation function indexes were noted between the 2 groups before treatment and on 14 th d of treatment ( P>0.05). Adverse reaction incidence was 9.52% ( n=12) in experimental group and 10.34% ( n=12) in control group, without statistical difference ( P>0.05). Conclusion:Under premise of conventional western medicine treatment, Qufeng Tongxuan method can promote hematoma absorption and improve neurological deficit symptoms in low- and moderate-volume intracerebral hemorrhage at acute stage, without obvious adverse reactions.

Objective:To analyze and compare the policies and theoretical fundamental, the categories and amount of activities, benefits and influential factors of international and national physical activity guidelines for children, to provide theoretical and method guidance for the development and implementation of relevant guidelines. Methods:Six guidelines of physical activity for children issued by the World Health Organization (WHO), China, United States, Australia and Canada (2 sets) were included, analyzed and coded using International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY). The policy background, theories, evidence-based methods, recommended activities, activity volume, benefits and influential factors of the guidelines were discussed. Results:There were relevant backgrounds of health policies and theoretical fundamentals for the development of these guidelines. The recommended categories of physical activities involved the activities of fitness, skills and sports. The amount of activity all the guidelines recommended was at least 60 minutes of moderate to high intensity activity per day, and vigorous-intensity or musculoskeletal enhancement activities at least three times a week. Physical activities had benefit for children in the fields of development and maxima of functioning, promotion of activities and participation, formation of good habits of life, establishment of healthy lifestyles, and improvement of the relevant environmental factors. Conclusion:It is useful to analyze and compare the contents of guidelines of physical activities for children using framework, terminology and coding systems of ICF-CY. Both international and national guidelines of physical activity for children are developed in relevant health policies backgrounds and health-related theories. There are three types of physical activity for children aligning to ICF-CY: fitness, skills and sports. All guidelines recommended moderate to high level intensity of activity. Children can gain from physical activities for the development of exercise habits and active lifestyles. Accessible environments are recommended, including Products and Technology, Natural Environment and Human-Made Changes to Environment, Support and Relationships, Attitudes, and Services, Systems and Policies.

OBJECTIVETo investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS).

METHODSSixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2).

RESULTSCompared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05).

CONCLUSIONSInflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.

OBJECTIVETo evaluate the efficacy of periprostatic nerve block anesthesia (PPNB) for pain relief in transrectal ultrasound-guided systematic prostate biopsy (PBx).

METHODSWe reviewed the data of patients undergoing initial PBx at our center from November, 2013 to January, 2015. Only the patients with 12-core systemic PBx were included and 111 patients were eligible for this study, among whom 52 patients received PPNB and 59 did not. PPNB was achieved by an injection of 5 mL of 1% lidocaine at the angle between the seminal vesicle and base of the prostate on each side before biopsy. The DRE pain score, probe insert pain score, and biopsy pain score were assessed by visual analogue scale (VAS) immediately after the biopsy. The complications were recorded and evaluated immediately after and at 7 days after the biopsy.

RESULTSThe mean age, prostate volume, total prostate specific antigen (tPSA), free PSA (fPSA), and abnormal DRE were comparable between the 2 groups (P>0.05). Immediately after the biopsy, no difference was found between the 2 groups in DRE pain score (1.40±0.98 vs 1.39±0.91, P=0.102) or probe insert pain score (2.07±0.96 vs 2.03±0.90, P=0.960), but the biopsy pain score was significantly lower in PPNB group than in no PPNB group (2.54±1.42 vs 3.07±1.43, P=0.033). The incidence of the procedure-related complications was similar between the 2 groups (P>0.05).

CONCLUSIONPPNB can significantly lower the biopsy pain score in PBx without increasing the incidence of complications.

Biopsy ; Humans ; Lidocaine ; therapeutic use ; Male ; Nerve Block ; Pain ; prevention & control ; Pain Management ; methods ; Pain Measurement ; Prostate ; diagnostic imaging ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; diagnosis ; Ultrasonography

Objective To study the effect of p38MAPK on the activity and c-myc protein expression in rat acetaldehyde-induced hepatic stellate cell(HSC),and to investigate the alcoholic liver fibrosis related mechanism.Methods The different concentrations of SB203580 as the p38 specific blocker was adopted to conduct the intervention on rat acetaldehyde-induced HSC.The cellular mor-phological change was observed by the microscope.The cell proliferation was detected by MTT,the cell cycle was analyzed by flow cytometry(FCM),and the expression of c-myc protein was examined by the SABC method.Results (1)after acetaldehyde stimula-tion,HSC was increased in size and proliferated rapidly,but with the added SB203580 concentration increase,the cellular prolifera-tion was slowed down,the cells size was diminished and the deformed cells were increased.(2)The proliferation of acetaldehyde-in-duced HSC was inhibited by different doses of SB203580,and the higher concentration has the more significant inhibiting effect.(3) With the SB203580 concentration increase,the cells at the phase G0 and G1 were increased,while the cells at the phase S were de-creased,at the same time the expression positive rate of c-myc protein was decreased.Conclusion Blocking p38MAPK pathway ac-tivity could inhibit the proliferation of acetaldehyde-induced HSC,which may be related to the down-regulation of C-myc protein ex-pression and blocking the DNA synthesis in cells entering from G0/G1 phase to S phase.