ObjectiveThe primary objective of this study was to investigate the effects of carbohydrate intake order on post-exercise recovery and metabolic regulation under heat stress, particularly in models of exercise induced fatigue. Given the increasing significance of optimizing nutritional strategies to support performance in extreme environmental conditions, this study aimed to provide experimental evidence that contributes to a better understanding of how the sequence in which carbohydrates are consumed impacts exercise recovery, metabolic homeostasis, and fatigue alleviation in a high-temperature environment. MethodsA mouse model of exercise-induced fatigue was established under high-temperature (35°C) to simulate heat stress. The subjects were divided into 3 distinct groups based on their carbohydrate intake order: the “mixed intake” group (HOT_MIX), where all macronutrients (carbohydrates, proteins, and fats) were consumed in a balanced ratio; the “carbohydrate-first intake” group (HOT_CHO), where carbohydrates were consumed first followed by other macronutrients; the “carbohydrate-later intake” group (HOT_PRO), where proteins and fats were consumed prior to carbohydrates. Each group underwent a 7 d intervention period with daily intake according to their designated group. Exercise performance was assessed using rotarod retention time test, and biomarkers of muscle damage, such as lactate dehydrogenase (LDH), creatine kinase (CK), lactate (LD), alanine aminotransferase (ALT), and non-esterified fatty acids (NEFA), were measured. Furthermore, targeted metabolomics analyses were conducted to investigate metabolic shifts in response to different dietary strategies, and KEGG pathway enrichment analysis was employed to explore the biological mechanisms underlying these changes. ResultsThe findings demonstrated that the HOT_PRO group exhibited a significantly improved performance in the rotarod test, with a longer retention time compared to both the HOT_MIX and HOT_CHO groups (P<0.05). Additionally, this group showed significantly reduced levels of muscle damage markers such as LDH and CK, indicating that the carbohydrate-later intake strategy helped alleviate exercise-induced muscle injury. Metabolomic profiling of the HOT_PRO group showed marked increases in alanine, creatine, and flavin adenine dinucleotide (FAD), indicating shifts in amino acid metabolism and oxidative metabolism. Conversely, metabolites such as spermidine, cholesterol sulfate, cholesterol, and serine were significantly reduced in the HOT_PRO group, pointing to alterations in lipid and sterol metabolism. Further analysis of the differential metabolites revealed that these changes were primarily associated with key metabolic pathways, including glycine-serine-threonine metabolism, primary bile acid biosynthesis, taurine and hypotaurine metabolism, and steroid hormone biosynthesis. These pathways are essential for energy production, antioxidant defense, and muscle recovery, suggesting that the carbohydrate-later feeding strategy may promote metabolic homeostasis and improve exercise recovery by enhancing these critical metabolic processes. ConclusionThe results of this study support the hypothesis that consuming carbohydrates after proteins and fats during exercise recovery enhances metabolic homeostasis and accelerates recovery under heat stress. This strategy effectively modulates energy, amino acid, and lipid-related pathways, which are crucial for improving endurance performance and mitigating fatigue in high-temperature environments. The findings suggest that carbohydrate-later intake could be a promising nutritional strategy for athletes and individuals exposed to heat during physical activity. Furthermore, the study provides valuable insights into how different nutrient timing strategies can impact exercise recovery and metabolic regulation, paving the way for more personalized and effective nutritional interventions in extreme environmental conditions.

Etomidate reversibly blocks 11-β-hydroxylated steroid dehydrogenase inhibits the synthesis of cortisol by adrenal cells.This product is a special injection.When evaluating the quality and efficacy of the generic and the reference preparations,it should be based on pharmaceutical and non-clinical consistency and adopt a step-by-step research strategy,firstly,bioequivalence(BE)was studied.In bioequivalence study,the research type,dosage and method,bioequivalence evaluation,safety monitoring and pharmacodynamics(PD)evaluation should be considered and designed reasonably.Based on the pharmacokinetics(PK)characteristics of etomidate medium-long chain fat emulsion injection and the bioequivalence study of its generic drug before its domestic market,the general design requirements and relevant considerations for the bioequivalence study of this product were systematically discussed.The purpose is to provide useful reference and guidance for domestic research and development of generic drugs.

Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.

Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P＜0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P＞0.05).Compared with the control group,190 differential metabolites(VIP＞1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.

Aim To explore the effects of sirolimus on the growth and development of motor,vascular,nerv-ous,and immune systems through zebrafish models.Methods After 3 hours of fertilization of zebrafish embryos,different concentrations of sirolimus were add-ed to the growth environment,and the growth and de-velopment of the embryos was recorded.Transgenic ze-brafish models labeled with blood vessels,nerves or im-mune cells were used to compare the drug effects on the growth and development of those systems.Results At the concentration of 0.5 μmol·L-1,the hatching rate and the body length(P＜0.01)were significantly smaller than those of the control group,and movement was also significantly slowed down.Meanwhile,the length of axons of the nervous system,the development of intersegmental vessels,and the growth of immune cells were significantly delayed by drug treatment.But when the concentration was below 0.1 μmol·L-1,there was no statistically difference between the control group and the sirolimus group.Conclusions When the concentration of sirolimus exceeds a certain level,it can significantly slow down the growth and development of movement,blood vessels,nervous system and im-mune system of zebrafish.Therefore,in clinical prac-tice,it is important to monitor the blood concentration of sirolimus in children on time.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

Cannabinoid receptors are one of the most expressed G protein-coupled receptors in the central nervous system, which are potential drug targets for inflammation, pain and drug abuse. Cannabinoid receptors are composed of type 1 receptor (CB1R), type 2 receptor (CB2R) and other receptors, of which CB1R plays a vital role in regulating central memory, cognition, and motor function. Therefore, screening CB1R agonists has potential value in treating nervous system diseases. In this study, the intracellular loop 3 (ICL3) domain of CB1R was replaced with a circular-permutated enhanced green fluorescent protein (cpEGFP). After infecting HEK 293T cells with lentivirus particles, we obtained a stable cell line that was overexpressed human CB1R-cpEGFP after puromycin selection. The interaction between receptor agonists and CB1R led to the change of receptor conformation, resulting in de-protonation of the EGFP, and enhancing the fluorescence intensity. Therefore, active CB1R compounds could be verified by measuring the fluorescence intensity. Using CB1R agonist arachidonyl-2′-chloroethylamide (ACEA) as a positive control to evaluate the reliability of this model, studies have shown that ACEA could induce receptor activation and increase fluorescence intensity, while antagonist rimonabant inhibited receptor activation with unchanged fluorescence intensity. In conclusion, this study successfully constructed a fluorescent probe screening model for CB1R agonists.

OBJECTIVE: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). RESULTS: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. CONCLUSION HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli