The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the in vitro metabolism and products of 2-MDCK. The results indicate that 2-MDCK undergoes various metabolic reactions, including dehydrogenation, deamination, hydroxylation, and demethylation, leading to the formation of eight metabolites. By conducting actual testing on hair samples from 2-MDCK abusers, the existence of six metabolites was confirmed. Comparing the metabolic products in the liver microsomal in vitro model, M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption. Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau. Negative hair samples were provided by laboratory volunteers, and all samples were obtained with the informed consent of the volunteers. These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites, as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class. This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

The present study identified chemical constituents of Honghua Xiaoyao Tablet (HXT) and explored its biological connotation and characteristics on the premenstrual syndrome (PMS) treatment from the "disease-syndrome-symptom" association network. UHPLC-Q Exactive Orbitrap HRMS technology was applied to analyze the chemical constituents in HXT. According to the composition principles, the compatible herbs of HXT were divided into the Shugan Jieyu group, Huoxue Tiaojing group and Yiqi Jianpi group. The candidate targets of the corresponding prescriptions of HXT efficacy groups were collected from the Pharmmapper database and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0. The gene set related to the clinical symptoms included in Traditional Chinese and Western Medicine diagnosis and treatment standards were obtained from SoFDA, GeneCards, DisGeNET, MalaCards and literature published. The "HXT candidate targets-PMS (liver depression, Qi stagnation, and blood stasis syndrome) genes" network was constructed based on the gene interaction information, and further, the core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes (KEGG) for exploring the therapeutic advantages in PMS treatment of HXT efficacy groups, which were further verified experimentally in vitro. A total of 109 components from HXT were identified, including 20 components from Shugan Jieyu group enriched in the neurological system, estrogen regulation, and "immune-inflammation" related pathways, 77 components from Huoxue Tiaojing group enriched in the blood-circulation system, "immune-inflammation" and estrogen regulation related pathways and 30 components from Yiqi Jianpi group regulating immune inflammation, digestive system, and hormone levels. The biochemical indicator detection demonstrated that both the levels of 5-HT and DA in the hypothalamus tissues and the levels of E₂, NO, VEGF and RLN in the uterine tissues of PMS model rats were lower than those in controls, which the levels of OT, PROG, IL-6, IL-1β and TNF-α in the uterine tissues were increased in PMS group, which were all reversed by the administration of HXT, indicating that this prescription may regulate the synthesis and secretion of estrogen, intervene in neurotransmitter synthesis and signal transduction, reverse the imbalance of "immune-inflammation", and regulate digestive system function through various biological pathways, exerting the liver-smoothing, Qi-regulating, blood-activating and spleen-tonifying comprehensive effects, leading to alleviating the "neuroendocrine-endocrine-immune" system and blood-circulation disorders. The relevant results may provide a reference for clarifying the advantages and efficacy of HXT in treating PMS with liver stagnation, Qi stagnation, and blood stasis syndrome, and exploring its therapeutic advantages. The animal experiment of this study was approved by the Ethics Committee of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (approval number: 2023B248).

Objective To compare the short- to mid-term outcomes of aortic valve plasty (AVP) and Ross surgery in children with severe aortic valve disease. Methods The patients (aged<18 years) with severe aortic valve disease who underwent AVP (an AVP group) or Ross surgery (a Ross group) at the Department of Cardiovascular Surgery, West China Hospital from January 2019 to September 2023 were retrospectively included. We compared perioperative and follow-up data between the groups. Results A total of 48 pediatric patients were included, including 28 males and 20 females, with an average age of (9.3±4.5) years. There were 25 patients in the AVP group, and 23 in the Ross group. Leaflet thinning (15/25, 60.0%) and leaflet extension (10/25, 40.0%) were the most common strategies used in the AVP group, while root replacement technique (12/23, 52.2%) and subcoronary technique (10/23, 43.5%) were the most frequently used strategies in the Ross group. There was no in-hospital death. The median follow-up time was 16.0 (7.0, 30.0) months. Peak flow velocity of the aortic valve was higher in the AVP group [2.0 (1.4, 2.9) m/s vs. 1.2 (1.0, 1.5) m/s, P<0.001], while there was no statistical difference in the postoperative aortic valve regurgitation severity between the two groups (P=0.127). During follow-up, the overall reoperation rate and aortic valve reoperation rate were similar between the AVP group and the Ross group (8.0% vs. 13.0%, P=0.922; 8.0% vs. 0.0%, P=0.266). The rate of recurrent aortic valve disease was higher in the AVP group (52.0% vs. 4.3%, P<0.001), while further analysis failed to recognize any risk factors. Conclusion AVP and Ross procedure show similar perioperative safety, survival and reoperation rate. The rate of recurrent aortic valve disease is higher in the AVP group, but further investigations are needed to confirm the causes.

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.
Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China/epidemiology* ; Diseases in Twins/genetics* ; Hyperlipidemias/genetics* ; Metabolic Diseases ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

Objective: To investigate the prospective association of physical activity with all-cause, cardiovascular disease (CVD), and chronic kidney disease (CKD) mortality in CKD patients in China. Methods: Cox proportional hazard models were used to evaluate the association of total, domain-specific, and intensity-specific physical activity with the risk of all-cause, CVD, and CKD mortality based on data from the baseline survey of China Kadoorie Biobank. Results: During a median follow-up of 11.99 (11.13, 13.03) years, there were 698 deaths in 6 676 CKD patients. Compared with the bottom tertile of total physical activity, participants in the top tertile had a lower risk of all-cause, CVD, and CKD mortality, with hazard ratios (HRs) (95%CIs) of 0.61 (0.47-0.80), 0.40 (0.25-0.65), and 0.25 (0.07-0.85), respectively. Occupational, commuting, and household physical activity were negatively associated with the risk of all-cause and CVD mortality to varying degrees. Participants in the top tertile of occupational physical activity had a lower risk of all-cause (HR=0.56, 95%CI: 0.38-0.82) and CVD (HR=0.39, 95%CI: 0.20-0.74) mortality, those in the top tertile of commuting physical activity had a lower risk of CVD mortality (HR=0.43, 95%CI: 0.22-0.84), and those in the top tertile of household physical activity had a lower risk of all-cause (HR=0.61, 95%CI: 0.45-0.82), CVD (HR=0.44, 95%CI: 0.26-0.76) and CKD (HR=0.03, 95%CI: 0.01-0.17) mortality, compared with the bottom tertile of corresponding physical activity. No association of leisure-time physical activity with mortality was observed. Both low and moderate-vigorous intensity physical activity were negatively associated with the risk of all-cause, CVD and CKD mortality. The corresponding HRs (95%CIs) were 0.64 (0.50-0.82), 0.42 (0.26-0.66) and 0.29 (0.10-0.83) in the top tertile of low intensity physical activity, and the corresponding HRs (95%CIs) were 0.63 (0.48-0.82), 0.39 (0.24-0.64) and 0.23 (0.07-0.73) in the top tertile of moderate-vigorous intensity physical activity. Conclusion: Physical activity can reduce the risk of all-cause, CVD, and CKD mortality in CKD patients.
Humans ; Exercise ; Motor Activity ; Cardiovascular Diseases ; China ; Renal Insufficiency, Chronic

Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.
Animals ; Mice ; Depression ; Eukaryotic Initiation Factor-4E/metabolism* ; MicroRNAs/metabolism* ; Neurons/metabolism* ; Stroke/metabolism*

Objective 聽 聽To evaluate the mid-term outcomes between tricuspid valve detachment (TVD) and non-detachment (NTVD) for ventricular septal defect (VSD). Methods 聽 聽 The patients who underwent perimembranous VSD repair in the Department of Cardiovascular Surgery, West China Hospital from 2015 to 2020 were included. According to the surgical method, the patients were divided into a TVD group and a NTVD group. The clinical data of the two groups were compared. Results 聽 聽 Totally 538 patients were included in the study. There were 240 patients in the TVD group, including 121 males and 119 females, with an average age of 3.85卤8.42 years and an average weight of 14.12卤12.97 kg. There were 298 patients in the NTVD group, including 149 males and 149 females, with an average age of 4.42卤9.36 years and an average weight of 14.87卤12.51 kg. There was no statistical difference in the age, weight, sex, preoperative New York Heart Association (NYHA) classification or tricuspid regurgitation (TR) degree between the two groups (P>0.05). Median follow-up was 30 (23, 40) months in the TVD group, and 29 (23, 41) months in the NTVD group (P=0.600). After operation, one patient in each group developed third-degree atrioventricular block and recovered to sinus rhythm before discharge (P=0.848). No pacemaker was needed. There was no statistical difference in the length of stay (P=0.054), mortality (P=1.000), in-hospital reoperation (P=0.199), or follow-up reoperation (P=0.505). More than 98% of patients in both groups had postoperative TR less than moderate (P=0.926). At the last follow-up, only 7 (2.9%) patients in the TVD group were detected trivial residual shunting, and 14 (4.7%) in the NTVD group (P=0.289). No one needed to have reoperation because of residual VSD. The TVD group showed less TR during the follow-up (P=0.019). Conclusion     TVD is an alternative technique which can be safely used in the closure of VSD, especially in technologically mature medical center. Appropriate tricuspid valve detachment for those hard-to-expose VSDs does not result in poorer tricuspid valve function or higher risk of atrioventricular block, and might reduce the incidence of residual shunting.

Objective     To search for the key microRNAs (miRNAs) involved in myocardial fibrosis in hypertrophic cardiomyopathy, and to further explore the mechanisms involved in the regulation of myocardial fibrosis. Methods    Forty-two patients with hypertrophic cardiomyopathy diagnosed and treated surgically in West China Hospital of Sichuan University from January 2014 to June 2018 were selected, including 29 males and 13 females, with a median age of 46 (15-69) years. In the myocardial tissue of patients with hypertrophic cardiomyopathy with different degrees of fibrosis, miRNAs with significantly different expression were screened and further verified at the cellular level. By regulating the expression of the target miRNAs, the expressions of fibrosis-related proteins and target genes were detected respectively. Finally, the target-binding relationship was verified by dual-luciferase reporter gene detection. Results    miR-484 was up-regulated in severely fibrotic myocardial tissue and activated cardiac fibroblasts. After cardiac fibroblasts were activated by TGF-β1, the expression of miR-484 was significantly up-regulated, the expression of fibrosis-related proteins (CollagenⅠ, α-SMA) increased, and the expression of the target gene HIPK1 decreased (P<0.05). After inhibiting the expression of miR-484 by transfection of miR-484 antagomir, the expression of fibrosis-related proteins decreased, while expression of HIPK1 was up-regulated (P<0.05). The detection of dual luciferase reporter gene showed that the luciferase activity of the transfected WT-miRNA-484 mimics group was lower than that of the control group (P<0.05). Conclusion    miR-484 is a pro-fibrotic miRNA that participates in the process of myocardial fibrosis by negatively regulating the expression of HIPK1. It can be used as a regulatory target to provide a therapeutic strategy for myocardial fibrosis.

Objective: To describe the distribution characteristics of type 2 diabetes in twins in Chinese National Twin Registry (CNTR), provide clues and evidence for revealing the influence of genetic and environmental factors for type 2 diabetes. Methods: Of all twins registered in the CNTR during 2010-2018, a total 18 855 twin pairs aged ≥30 years with complete registration information were included in the analysis. The random effect model was used to describe the population and area distribution characteristics and concordance of type 2 diabetes in twin pairs. Results: The mean age of the subjects was (42.8±10.2) years, the study subjects included 10 339 monozygotic (MZ) twin pairs and 8 516 dizygotic (DZ) twin pairs. The self-reported prevalence rate of type 2 diabetes was 2.2% in total population and there was no sighificant difference between MZ and DZ. Intra-twin pairs analysis showed that the concordance rate of type 2 diabetes was 38.2% in MZ twin pairs, and 16.0% in DZ twin pairs, the difference was statistically significant (P<0.001). The concordance rate of type 2 diabetes in MZ twin parts was higher than that in DZ twin pairs in both men and women, in different age groups and in different areas (P<0.05). Further stratified analysis showed that in northern China, only MZ twin pairs less than 60 years old were found to have a higher concordance rate of type 2 diabetes compared with DZ twin pairs (P<0.05). In southern China, the co-prevalence rate in male MZ twin pairs aged ≥60 years was still higher than that in DZ twin pairs (P<0.05). Conclusion: The twin pairs in this study had a lower self-reported prevalence of type 2 diabetes than the general population. The study results suggested that genetic factors play a role in type 2 diabetes prevalence in both men and women, in different age groups and in different areas, however, the effect might vary.
Adult ; China/epidemiology* ; Diabetes Mellitus, Type 2/genetics* ; Diseases in Twins/genetics* ; Female ; Humans ; Male ; Middle Aged ; Registries ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

Objective: To describe the distribution characteristics of coronary heart disease in adult twins recruited from Chinese Twin Registry (CNTR), and provide clues and evidence for the effect of genetic and environmental influences on coronary heart disease. Methods: By using the data of CNTR during 2010-2018, a total of 34 583 twin pairs aged ≥18 years who completed questionnaire survey and had related information were included in the current study to analyze the population and area distribution characteristics of coronary heart disease. Random effect models were used to compare the differences between groups. The concordane rate of coronary heart disease were calculated respectively in monozygotic (MZ) twin pairs and dizygotic (DZ) twin pairs to estimate the heritability. Results: The twin pairs included in this analysis were aged (34.2±12.4) years. The overall prevalence rate of coronary heart disease in twin pairs was 0.7%. Twin pairs who were women, older, obese and lived in northern China had higher prevalence of coronary heart disease (P<0.05). Intra-pair analysis in the same-sex twin pairs found that the concordane rate of coronary heart disease was higher in MZ twin pairs (25.3%) than in DZ twins (7.4%), and the difference was statistically significant (P<0.001). The overall heritability of coronary heart disease was 19.3% (95%CI: 11.8%-26.8%). Stratified by gender, age and area, the concordane rate was still higher in MZ twin pairs than in DZ pairs. Participants who were women, aged 18-30 years or ≥60 years and lived in northern China had a higher heritability of coronary heart disease. Conclusion: The distribution of coronary heart disease in twin pairs differed in populations and areas. The prevalence of coronary heart disease was affected by genetic factors, but the effect varied with age, gender and area.
Adolescent ; Adult ; China/epidemiology* ; Coronary Disease/genetics* ; Diseases in Twins/genetics* ; Female ; Humans ; Male ; Twins, Dizygotic ; Twins, Monozygotic/genetics*