Objective To develop a nutritional formula on enhancing the endurance of heavy load exercise,and evaluate its efficacy comprehensively.Methods Sixty C57BL/6J male mice were randomly divided into control group(CON group)and low-,medium-and high-dose nutritional formula groups(LDF,MDF and HDF groups),with 15 mice in each group.Each group received intervention with nutritional formula at corresponding dose for 2 weeks,and underwent adaptive training and heavy load exercise in the 1 st and 2nd weeks,respectively.Exhaustion exercise time,skeletal muscle antioxidant indicators(SOD,MDA,PC and GSH),fatigue related indicators(serum URA,LDH and LA),muscle glycogen,and serum exercise injury related indicators(ALT,AST,CK and CK-MB)were measured and detected in the mice,and comprehensive evaluation was conducted according to relevant evaluation standards.Results The LDF group,MDF group and HDF group had significantly prolonged running exhaustion time than the CON group(P＜0.05),with the HDF group showing the greatest improvement(P＜0.05).Compared with the CON group,the activities of SOD and GSH in the skeletal muscles were significantly increased(P＜0.05),while the levels of MDA and PC in skeletal muscles were obviously decreased in the 3 doses of nutritional formula groups(P＜0.05).PAS staining of the skeletal muscles displayed that the glycogen content was significantly increased in the MDF group and the HDF group than the CON group(P＜0.05),and the highest increase was observed in the HDF group(P＜0.05).Biochemical test revealed that the levels of LDH,LA,ALT,AST,CK,and CK-MB were remarkably lower in the 3 doses of nutritional formula groups than the CON group(P＜0.05).Conclusion The nutritional formula can significantly improve the endurance and skeletal muscle antioxidant capacity in mice under heavy load exercise,and has anti-fatigue and-injury protection effects.This nutritional formula can be used to support physical fitness during heavy load endurance exercise.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Aim To study the mechanism of action of licorice in alleviating cisplatin liver injury.Methods Forty-eight SD rats were randomly divided into a blank group,a model group,a positive control group and lico-rice administration groups(450,900 and 1 800 mg·kg-1).After 5 days of prophylactic administration,8 mg·kg-1 of cisplatin was injected intraperitoneally in-to the model,positive control,and licorice administra-tion groups to establish an acute liver injury model.LC-MS/MS untargeted metabolomics was used to ana-lyze the differential metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury.Re-sults PLS-DA score plots showed significant separa-tion of metabolomics samples.The analysis yielded 119 differential metabolites associated with cisplatin liver injury,of which 31 differential metabolites were signifi-cantly regressed after licorice intervention and were mainly involved in D-arginine and D-ornithine metabo-lism;parathyroid hormone synthesis,secretion,and ac-tion;tyrosine metabolism;biosynthesis of phenylala-nine,tyrosine,and tryptophan;β-alanine metabolism;and amino acid and nucleotide sugar metabolism.Con-clusions Metabolomics analysis indicates that licorice can alter the metabolic profile of cisplatin-induced he-patic injury rats,and its mechanism of action may be related to its improvement of the levels of differential metabolites and its involvement in the regulation of a-mino acid metabolism and other related pathways.

Aim To investigate the molecular mechanisms of alcohol extracts of Euphorbia fischeriana steud. against hepatocellular carcinoma (HCC) through a combination of network pharmacology analysis and experimental validation. Methods The active ingredients and targets of alcohol extracts of Euphorbia fischeriana steud. were determined through TCMSP, Swiss ADME, Swiss Target Prediction database and references. The databases DisGeNET and GeneCards were employed to screen potential HCC-related genes. Venny platform, STRING platform and Cytoscape software were applied to construct active ingredient-target-disease and protein-protein interaction (PPI) network maps. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the DAVID database. To assess the effects of Euphorbia fischeriana steud. alcohol extracts on BEL-7402 cells, the proliferation and apoptosis were detected by CCK-8, EdU and flow cytometry assays, and the related protein levels of JAK2/STAT3 pathway were analyzed by Western blot. Additionally, H22 hepatocellular carcinoma mouse model was used to evaluate the in vivo efficacy of Euphorbia fischeriana steud. alcohol extracts. Results A total of 916 HCC targeted genes, 30 active ingredients containing the related 567 potential targeted genes, and 115 intersection targets of disease and compounds were obtained. KEGG enrichment analysis identified JAK2/STAT3 signaling as a critical pathway. In vitro experiments showed the alcohol extracts of Euphorbia fischeriana steud. could inhibit proliferation, promote apoptosis and suppress JAK2/STAT3 signaling pathway in a dose-dependent manner in BEL-7402 cells. In addition, the alcohol extracts of Euphorbia fischeriana steud., either alone or in combination with sorafenib, dramatically blocked tumor growth in in vivo tests. Conclusions Euphorbia fischeriana steud. alcohol extracts have anti-cancer effects in HCC, and the molecular mechanisms may be connected to the regulation of JAK2/STAT3 signaling pathway.

OBJECTIVE: To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data. METHODS: Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS). RESULTS: This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24). CONCLUSION We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
Humans ; Escherichia coli/genetics* ; Escherichia coli Infections/epidemiology* ; Multilocus Sequence Typing ; Genotype ; Beijing ; Drug Resistance, Multiple, Bacterial/genetics* ; Anti-Bacterial Agents/pharmacology* ; Diarrhea ; Microbial Sensitivity Tests

OBJECTIVE: To analyze the clinical characteristics of patients with emergency in-hospital cardiac arrest (IHCA) in Kashgar, Xinjiang Uygur Autonomous Region and the factors affecting the success rate of cardiopulmonary resuscitation. METHODS: Retrospectively selected patients who had cardiac arrest and cardiopulmonary resuscitation in the emergency department of the People's Hospital of 6 counties and cities in Kashgar area from January 2019 to January 2022. The clinical data of all patients were collected, including gender, age, major underlying diseases, the beginning and duration of resuscitation, the number of electric defibrillation acute physiology and chronic health evaluation II (APACHE II). According to whether the resuscitation was successful, all patients were divided into successful resuscitation group and failed resuscitation group. The clinical characteristics of the two groups were compared. Then, the influencing factors of the success rate of cardiopulmonary resuscitation in IHCA patients were analyzed by binary Logistic regression. RESULTS: A total of 1 376 patients were enrolled, including 1 117 cases of failed resuscitation and 259 cases of successful resuscitation. The success rate of resuscitation was 18.82%. Compared with the resuscitation failure group, the patients in the successful resuscitation group were younger (age: 49.10±20.99 vs. 58.44±18.32), the resuscitation start time was earlier [resuscitation start time ≤ 5 minutes: 76.45% (198/259) vs. 66.61% (744/1 117)], the proportion of cardiovascular and cerebrovascular diseases was lower [cardiovascular disease: 49.42% (128/259) vs. 58.19% (650/1 117), cerebrovascular disease: 17.37% (45/259) vs. 21.58% (241/1 117)], the number of electric defibrillation was lower [times: 0 (0, 2) vs. 1 (0, 1)], the proportion of endotracheal intubation was more [80.31% (208/259) vs. 55.60% (621/1 117)], APACHE II score was lower (13.75±8.03 vs. 17.90±4.63), and the difference was statistically significant (all P < 0.01). Binary Logistic regression analysis showed that age, start time of resuscitation, ventilation mode and APACHE II score were protective factors affecting the success rate of cardiopulmonary resuscitation in patients with emergency IHCA [age: odds ratio (OR) = 0.982, 95% confidence interval (95%CI) was 0.973-0.991, P < 0.001; resuscitation start time ≤ 5 minutes: OR = 0.629, 95%CI was 0.409-0.966, P = 0.034; tracheal intubation assisted ventilation: OR = 0.243, 95%CI was 0.149-0.397, P < 0.001; low APACHE II score: OR = 0.871, 95%CI was 0.836-0.907, P < 0.001], while underlying diseases (cardiovascular diseases) are a risk factor affecting the success rate of cardiopulmonary resuscitation (OR = 1.190, 95%CI was 1.015-1.395, P = 0.036). CONCLUSIONS Age, resuscitation start time, ventilation mode, APACHE II score and major underlying diseases (cardiovascular diseases) have a greater impact on the success rate of resuscitation in IHCA patients. The above factors are conducive to improving or formulating more effective rescue strategies for IHCA patients, so as to achieve the purpose of improving the success rate of clinical treatment.
Humans ; Adult ; Middle Aged ; Aged ; Retrospective Studies ; Cardiopulmonary Resuscitation ; Heart Arrest/therapy* ; Electric Countershock ; Hospitals

Objective: To compare the differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all cause death, thromboembolic events, major bleeding events and composite endpoint in patients with nonvalvular atrial fibrillation. Methods: This is a retrospective cohort study. From the China Atrial Fibrillation Registry cohort study, the patients with atrial fibrillation who were>18 years old were randomly divided into CAS risk score group and CHA₂DS₂-VASc risk score group respectively. According to the anticoagulant status at baseline and follow-up, patients in the 2 groups who complied with the scoring specifications for anticoagulation were selected for inclusion in this study. Baseline information such as age and gender in the two groups were collected and compared. Follow-up was performed periodically to collect information on anticoagulant therapy and endpoints. The endpoints were all-cause death, thromboembolism events and major bleeding, the composite endpoint events were all-cause death and thromboembolism events. The incidence of endpoints in CAS group and CHA₂DS₂-VASc group was analyzed, and multivariate Cox proportional risk model was used to analyze whether the incidence of the endpoints was statistically different between the two groups. Results: A total of 5 206 patients with AF were enrolled, average aged (63.6±12.2) years, and 2092 (40.2%) women. There were 2 447 cases (47.0%) in CAS risk score group and 2 759 cases (53.0%) in CHA₂DS₂-VASc risk score group. In the clinical baseline data of the two groups, the proportion of left ventricular ejection fraction<55%, non-paroxysmal atrial fibrillation, oral warfarin and HAS BLED score in the CAS group were lower than those in the CHA₂DS₂-VASc group, while the proportion of previous diabetes history and history of antiplatelet drugs in the CAS group was higher than that in the CHA₂DS₂-VASc group, and there was no statistical difference in other baseline data. Patients were followed up for (82.8±40.8) months. In CAS risk score group, 225(9.2%) had all-cause death, 186 (7.6%) had thromboembolic events, 81(3.3%) had major bleeding, and 368 (15.0%) had composite endpoint. In CHA₂DS₂-VASc risk score group, 261(9.5%) had all-cause death 209(7.6%) had thromboembolic events, 112(4.1%) had major bleeding, and 424 (15.4%) had composite endpoint. There were no significant differences in the occurrence of all-cause death, thromboembolic events, major bleeding and composite endpoint between anticoagulation in CAS risk score group and anticoagulation in CHA₂DS₂-VASc risk score group (log-rank P =0.643, 0.904, 0.126, 0.599, respectively). Compared with CAS risk score, multivariable Cox proportional hazards regression models showed no significant differences for all-cause death, thromboembolic events, major bleeding and composite endpoint between the two groups with HR(95%CI) 0.95(0.80-1.14), 1.00(0.82-1.22), 0.83(0.62-1.10), 0.96(0.84-1.11), respectively. All P>0.05. Conclusions: There were no significant differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all-cause death, thromboembolic events, and major bleeding events in Chinese patients with non-valvular atrial fibrillation.
Adolescent ; Anticoagulants ; Atrial Fibrillation/drug therapy* ; Cohort Studies ; Female ; Hemorrhage/complications* ; Humans ; Male ; Retrospective Studies ; Risk Assessment ; Stroke/epidemiology* ; Stroke Volume ; Thromboembolism/etiology* ; Ventricular Function, Left

As a traditional Chinese medicinal material， Glycyrrhizae Radix et Rhizoma has been extensively used in various formulae. According to modern pharmacological research， it has anti-tumor， anti-inflammatory， anti-viral， liver-protecting， anti-heart failure， immunoregulatory， and anti-fibrosis effects. Caused by the interaction of various factors， cancer features complex pathogenesis. It is a global challenge and one of the main causes of death in China. Statistics show that the morbidity and mortality of malignant tumors have been on the rise， particularly for the young， which threaten the health of human beings. At the moment， radiotherapy and chemotherapy are the main countermeasures. Most clinical anti-tumor drugs demonstrate non-selective toxicity. To be specific， they damage normal cells while killing tumor cells， thus injuring vital organs. In addition， long-term medication will reduce the sensitivity of tumor cells. However， traditional Chinese medicine， which is characterized by treatment based on syndrome differentiation， multiple components， and multiple targets， is superior in the treatment of tumor. Studies have shown that the combination of anti-tumor drugs with Chinese medicine can not only enhance the anti-tumor effect but also alleviate toxicity. Therefore， it has been a research hotspot to develop anti-tumor drugs based on traditional Chinese medicine. In recent years， major headway has been made in the research on active ingreddients of Glycyrrhizae Radix et Rhizoma in anti-liver cancer， anti-breast cancer， anti-lung cancer， and anti-colon cancer and the combination with other drugs for anti-tumor. On this basis， we summarized the mechanisms of active ingredients of Glycyrrhizae Radix et Rhizoma in inducing apoptosis， interfering with cell cycle， inducing autophagy， inhibiting glycolysis， regulating immunity， and modulating miRNA and signaling pathways， as well as the combination with other drugs in anti-tumor efficiency， toxicity reduction， and sensitivity enhancement， hoping to lay a theoretical basis for the further development and clinical application of active ingredients of Glycyrrhizae Radix et Rhizoma.

OBJECTIVE: To explore the mechanism of F.nucleatum-induced pyroptosis in macrophages and the regulatory role of inflammasomes. METHODS: Lactate dehydrogenase (LDH) cytotoxicity assay and Hoechst 33342/PI double fluorescence staining were used to analyze cytolysis in F.nucleatum-infected macrophage RAW264.7 cells.The expressions of pyroptosis-related proteins caspase-1, GSDMD and IL-1β were determined using Western blotting.Inflammasome activation in the cells was analyzed by detecting the mRNA expressions of NLRP3, NLRC4, AIM2, and NLRP1 with qRT-PCR.RNA interference technique was used to knock down the key molecules involved in pyroptosis regulation in the macrophages, and the pyroptosis and necrosis rates of the cells following F.nucleatum infection were examined. RESULTS: The results of LDH cytotoxicity assay and double-fluorescence staining showed that F.nucleatum infection caused swelling and lytic cell death in RAW264.7 cells.F.nucleatum infection resulted in the activation of caspase-1 and GSDMD and upregulated IL-1β expression in a multiplicity of infection (MOI)-and time-dependent manner (P < 0.05).qRT-PCR revealed significantly increased expression of NLRC4 mRNA in the macrophages after F.nucleatum infection (P < 0.05).NLRC4 silencing by siRNA strongly inhibited the activation of caspase-1/GSDMD pathway and reduced cell death (P < 0.05) and IL-1β expression in F.nucleatum-infected cells. CONCLUSION NLRC4 inflammasome drives caspase-1/GSDMD-mediated pyroptosis and inflammatory signaling in F.nucleatum-infected macrophages, suggesting the potential of NLRC4 inflammasome as a therapeutic target for F.nucleatum infections.
Pyroptosis/genetics* ; Inflammasomes/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Macrophages/metabolism* ; RNA, Messenger/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*

Adventitia ; Humans ; Mitral Valve ; Mitral Valve Prolapse