Methamphetamine abuse is a major public health problem in the world,and in recent years,methamphetamine is also the most abused synthetic drug in China.The neurotoxic or addiction mechanism of methamphetamine has not been fully clarified,and there is still a lack of specific withdrawal methods and drugs for methamphetamine abuse.Mitochondria are not on-ly the organelles to which methamphetamine directly produces toxic effects,but also participate in regulating the neurotoxic damage process of methamphetamine.Mitochondrial quality is the regulatory basis for maintaining mitochondrial homeostasis and is regulated by three main mechanisms,which are mitochon-drial biogenesis,mitochondrial dynamic,and mitophagy.This review summarizes the research progress of mitochondrial quality control in methamphetamine-induced neurotoxicity,which may provide theoretical support for further research on the mechanism of methamphetamine neurotoxicity and development the mito-chondria-targeting drugs.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

AIM To investigate the clinical effects of Buyang Huanwu Decoction combined with Erlong Xizhu Acupuncture Method on elderly patients with stroke.METHODS Ninety-six patients were randomly assigned into control group(48 cases)for 1-month intervention of Erlong Xizhu Acupuncture Method,and observation group(48 cases)for 1-month intervention of both Buyang Huanwu Decoction and Erlong Xizhu Acupuncture Method.The changes in neurological function indices(NIHSS score,NDS score),Hcy,CysC,vascular endothelial function indices(ET-1,NO,vWF),intracranial hemodynamic indices(Vmean,R,DR),hemorheological indices(WBLSV,WBHSV,FIB,HCT,EAI)and prognosis assessment indices(mRS score,BI score)were detected.RESULTS After the treatment,the two groups displayed decreased neurological function indices,Hcy,CysC,ET-1,vWF,R,DR,hemorheological indices,mRS score(P＜0.05),and increased NO,Vmean,BI score(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the elderly patients with stroke,Buyang Huanwu Decoction combined with Erlong Xizhu Acupuncture Method can reduce serum Hcy,CysC levels,and improve vascular endothelial functions,intracranial hemodynamics,hemorheological indices,thus improve neurological functions and promote prognosis.

Objective To study the pharmacokinetic characteristics of the test formulation of compound lidocaine cream and reference formulation of lidocaine and prilocaine cream in Chinese healthy subjects and to evaluate whether there is bioequivalence between the two formulations.Methods A single-center,single-dose,randomized,open-label,two-period,two-sequence,crossover design was used.This study included 40 healthy subjects,and in each period,test formulation or reference formulation 60 g was applied to the skin in front of both thighs(200 cm2 each side,a total of 400 cm2)under fasting conditions,and the drug was left on for at least 5 h after application.The concentrations of lidocaine and prilocaine in plasma were determined using liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Pharmacokinetic parameters were calculated using WinNonlin 8.0 software to evaluate the bioequivalence of the two formulations.Results After the application of the test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream on both thighs of the subjects,the pharmacokinetic parameters of lidocaine in plasma were as follows:Cmax were(167.27±91.33)and(156.13±66.86)ng·mL-1,AUC0-t were(1 651.78±685.09)and(1 636.69±617.23)ng·mL-1·h,AUC0-∞ were(1 669.85±684.65)and(1 654.37±618.30)ng·mL-1·h,the adjusted geometric mean ratios were 104.49％,101.88％and 101.89％,respectively,with 90％confidence intervals of 98.18％-111.20％,97.80％-106.13％and 97.87％-106.07％,all within the range of 80.00％-125.00％.The pharmacokinetic parameters of prilocaine in plasma were as follows:Cmax were(95.66±48.84)and(87.52±39.16)ng·mL-1,AUC0-t were(790.86±263.99)and(774.14±256.42)ng·mL-1·h,AUC0_m were(807.27±264.67)and(792.84±254.06)ng·mL-1 h,the adjusted geometric mean ratios were 107.34％,103.55％and 102.98％,respectively with 90％confidence intervals of 101.69％-113.31％,99.94％-107.30％and 99.65％-106.43％,all within the range of 80.00％-125.00％.Conclusion The test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream are bioequivalent.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

OBJECTIVE: This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children. METHODS: School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables. RESULTS: Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status. CONCLUSION Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.
Humans ; Child ; Nutritional Status ; Cross-Sectional Studies ; Iodine ; Sodium Chloride, Dietary/analysis* ; China ; Water

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Male ; Humans ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism* ; DNA-Binding Proteins/metabolism* ; Prolyl Hydroxylases/metabolism* ; Hypoxia ; Prostatic Neoplasms/pathology* ; Glycolysis ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Line, Tumor ; DNA Helicases/metabolism*

Aim To predict the targets of Modified Danggui Shaoyao San ( MDSS) in the treatment of chronic atrophic gastritis ( CAG) based on network pharmacology and vertify the results based on experim-ention. Methods TCMSP, SWISS TARGETS, GENE CARDS and OMIM databases were used to screen the therapeutic targets of MDSS for CAG. STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets. Metascape database was used for GO analysis and KEGG enrichment pathways. And molecular docking was used for target validation. CAG rat model was pre¬pared by N-methyl-N'-nitroso-N-nitroguanidine free drink combined with sodium salicylate gastric lavage. The pathology of rat gastric mucosa was observed by hematoxylin-eosin staining,and the ultrastructure of ep¬ithelial cells was observed by transmission electron mi-croscopy. The serum IL-6 and IL-10 content was detected by enzyme-linked immunosorbent assay, and the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in rats was detected by qPCR and Western blot. Results MDSS acted on 189 targets, mainly involved in response to oxidative stress and apoptotic signaling pathway. KEGG analysis related to pathways in cancer and JAK-STAT signaling pathway. The experimental results showed that the MDSS could improve the degree of atrophy of gastric mucosa in CAG rats and improve the status of epithelial cells, down-regulate the serum IL-6 content of CAG rats, up-regulate the IL-10 content, and reduce the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in gastric mucosa with statistical significance. Conclusions MDSS treats CAG through multiple active ingredients, targets, and pathways, the mechanism of which may be related to the inhibition of the JAK2/STAT3 signaling pathway.