Selenoproteins, as the active form of selenium, play an important role in various physiological and pathological processes, such as anti-oxidation, anti-tumor, immune response, metabolic regulation, reproduction and aging. Although the expression level of selenoproteins in adipose tissue is significantly influenced by dietary selenium intake, it is closely related to the homeostasis of adipose tissue. In this review, we summarized the role of selenoproteins in the physiological function of adipose tissue and the pathogenesis of obesity in recent years, in order to provide a rationale for developing potential therapeutic agents for the treatment of obesity and related metabolic diseases.
Selenoproteins/metabolism* ; Adipose Tissue/physiology* ; Obesity/metabolism* ; Humans ; Animals ; Selenium

Salvia miltiorrhiza is a perennial herb of the genus Salvia(Lamiaceae). As one of the earliest medicinal plants to undergo molecular biology research, it has gradually become a model plant for molecular biology of medicinal plants. With the gradual analysis of the genome of S. miltiorrhiza and the biosynthetic pathways of its main active components tanshinone and salvianolic acids, the transcriptional regulation mediated by transcription factors and related regulatory proteins has gradually become a new research focus. Due to the lack of scientific and unified naming of transcription factors and different research indexes in different literature, this paper systematically sorted out the transcription factors in different literature with the genomes of DSS3 from selfing for three generations and bh2-7 from selfing for six generations as reference. In total, 73 transcription factors and related regulatory proteins belonging to 13 gene families were identified. The effects of overexpression or gene silencing experiments on tanshinone and salvianolic acids were also analyzed. This study unified the identified transcription factors, which laid a foundation for further constructing the regulatory networks of secondary metabolites and insect or stress resistance and improving the quality of medicinal materials by using global transcriptional regulation engineering.
Salvia miltiorrhiza/chemistry* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Transcription Factors/metabolism* ; Abietanes/metabolism*

OBJECTIVE: To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells. METHODS: K562 cells were treated with ginsenoside-Rg5 and imatinib. Cell survival was detected by CCK-8 assay, and IC₅₀ were calculated separately for each drug. Based on the value of IC₅₀ of ginsenoside-Rg5 and imatinib, an appropriate concentration gradient was selected for the combination. The synergistic effect of the two drug was analyzed using the online software synergy finder. The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy. RESULTS: Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dosedependent manner(r =-0.991， r =-0.942). The synergy score ZIP >10 was measured by Synergy Finder online software, indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells. The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96% and 8.13%, respectively, while the rate increased to 21.35% with the combination of two drugs, the apoptosis rate in the combination group was higher than that in the single-drug group ( P <0.05). The proportion of K562 cells in the G₀/G₁ phase was significantly increased with the combined treatment of two drugs( P <0.05). The protein expression levels of p-PI3K, p-AKT, p-mTOR in K562 cells treated with the combination were significantly decreased, with noticeable downregulation of BCL-2 and upregulation of BAX, leading to a decreased Bcl-2/BAX ratio, while no significant changes were observed in the non-phosphorylated forms of PI3K, AKT, and mTOR proteins. CONCLUSION The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis, and the mechanism may act through PI3K/AKT/mTOR signaling pathways.
Humans ; Ginsenosides/pharmacology* ; Imatinib Mesylate ; K562 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction/drug effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism* ; Drug Synergism ; Apoptosis/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Proliferation/drug effects*

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

  Objective  To investigate the occurrence of chronic postsurgical pain (CPSP) among patients with preoperative COVID-19, and further analyze the risk factors for CPSP.  Methods  This study was a ambispective cohort study, with subjects from a completed cohort study with follow-up. We included the clinical data of the patients with preoperative COVID-19 who underwent surgery at Peking Union Medical College Hospital from December 1, 2022 to February 28, 2023. Follow-up was conducted up to 6 months postoperatively, with the primary outcome being CPSP. Multivariate Logistic regression analysis was used to analyze the correlation between COVID-19-related exposure indicators and CPSP.  Results  A total of 4117 surgical patients were included, all of whom had preoperative COVID-19. Among them, 4002 cases had mild symptoms during the acute phase, 62 cases had severe symptoms, and 53 cases were critically ill. At 6th month postoperatively, 1298 cases (31.53%) had long COVID-19 syndrome, and the incidence of CPSP was 5.59% (95% CI: 4.88%-6.28%). After adjusting for confounding factors including age, gender, comorbidities, anesthesia method, and type of surgery, multivariate Logistic regression analysis revealed that critically ill COVID-19 during the acute phase (aOR=3.35, 95% CI: 1.48-7.62, P < 0.001) and presence of long COVID-19 syndrome postoperatively (aOR=2.50, 95% CI: 1.90-3.29, P < 0.001) were associated with CPSP.  Conclusions  It is clear for the first time that critically ill COVID-19 during the acute phase and the presence of long COVID-19 syndrome postoperatively are the risk factors for CPSP among patients with preoperative COVID-19.

Objective:To analyze the expression of silent information regulator 2-related enzyme 1 (SIRT1) and its relationship with chondrocyte apoptosis in patients with Kashin-Beck disease (KBD).Methods:Twenty patients with KBD were selected as the KBD group from Guide County, Qinghai Province, and 40 healthy subjects matched by age and sex were selected as the control group. Fasting elbow venous blood of the study subjects was collected, and peripheral blood mRNA levels of SIRT1 and selenoprotein genes [glutathione peroxidase (GPX) 2, GPX3, thioredoxin reductase (TXNRD) 1, TXNRD3, iodothyronine deiodinase Ⅰ (DIO1), and selenophosphate synthetase 2 (SPS2)] were detected by real-time PCR. The correlation between SIRT1 expression and selenoprotein genes in peripheral blood of KBD patients was analyzed by curve fitting method. Meanwhile, normal human chondrocytes cultured in vitro were divided into control group (without any treatment), resveratrol (RES) group (to verify the activation effect of RES on SIRT1), tert-butyl hydroperoxide (tBHP) injury group (oxidative injury model of chondrocyte), and RES protection group (tBHP injury after RES pre protection). The mRNA levels of SIRT1, selenoprotein genes, and apoptosis-related genes [B lymphoblastoma-2 gene (BCL2), BCL2-associated X protein (BAX), nuclear transcription factor κB (NF-κB) p65, and tumor suppressor gene P53] in each group of cells were detected by real-time PCR. Results:In the population study, the peripheral blood SIRT1 mRNA level in the KBD group (1.12 ± 0.38) was lower than that of control group (1.87 ± 0.97), and the difference was statistically significant ( t = 3.31, P = 0.002). According to curve fitting analysis, the mRNA levels of GPX3, TXNRD1, and TXNRD3 in peripheral blood of KBD group increased with the increase of SIRT1 mRNA level ( R2 = 0.48, 0.66, 0.95, P < 0.001). The level of DIO1 mRNA showed a trend of decreased first and then increased with the increase of SIRT1 mRNA level ( R2 = 0.51, P = 0.024). The mRNA levels of GPX2 and SPS2 showed no significant change trend with the increase of SIRT1 mRNA level ( R2 = 0.16, 0.12, P = 0.064, 0.114). In cell studies, compared with the control group (1.00 ± 0.10), the SIRT1 mRNA level in the RES group (1.79 ± 0.07) was higher ( P < 0.05). Compared with tBHP injury group, the RES protection group had higher mRNA levels of selenoprotein genes GPX3, TXNRD1, TXNRD3, and DIO1 ( P < 0.05); the mRNA levels of apoptosis-related genes BAX, P53 and the ratio of BAX/BCL2 were lower, while the mRNA levels of BCL2 and NF-κB p65 were higher ( P < 0.05). Conclusions:KBD patients have low expression of SIRT1. And RES activation of SIRT1 may enhance the antioxidant capacity of chondrocyte by up-regulating the expression of selenoprotein genes, thus inhibiting chondrocyte apoptosis.

Objective:To investigate the role of oxidative stress and silent information regulator 2 homolog 1 (SIRT1) in cartilage injury in Kashin-Beck disease (KBD) by evaluating the level of oxidative stress and the effect of oxidative injury on SIRT1 expression in patients with KBD.Methods:In May 2017, Twenty patients with KBD were selected from Guide County of Qinghai Province as the KBD group, and 40 healthy subjects were selected as the control group, 5 ml elbow venous blood was collected, centrifuged, and the upper plasma was retained. The glutathione peroxidase (GPX) activity and reactive oxygen species (ROS) level were determined by enzyme linked immunosorbent assay (ELISA), and SIRT1 mRNA level was determined by real-time fluorescence quantitative PCR (RT-qPCR). Meanwhile, 150 μmol/L tert-butyl hydroperoxide (tBHP) was selected to damage chondrocytes; and different concentrations of sodium selenite (Na 2SeO 3) were used to intervene in chondrocytes to detect cell viability, and appropriate concentration of Na 2SeO 3 was selected for pre protection. Total RNA and DNA of chondrocytes were extracted. The mRNA levels of SIRT1, DNA methyltransferase 1 (DNMT1), and the DNA methylation level in the SIRT1 promoter region were determined by RT-qPCR. At the same time, Hoechst 33342 staining was used to detect chondrocyte apoptosis. Results:The plasma GPX activity [(35.48 ± 8.82) U/g·Hb] in KBD group was lower than that in control group [(40.43 ± 6.68) U/g·Hb, t = - 2.43, P = 0.018], and the ROS level [(577.10 ± 96.92) U/ml] was higher than that in control group [(526.44 ± 62.63) U/ml, t = 2.13, P = 0.043]. GPX activity was positively correlated with SIRT1 mRNA level ( r s = 0.44, P = 0.005), while ROS level was negatively correlated with SIRT1 mRNA level ( r s = - 0.39, P = 0.006). After 48 hours of treatment with 150 μmol/L tBHP (tBHP injury group), the survival rate of chondrocytes decreased to (55.27 ± 2.96)%; and the survival rate of chondrocytes pre-protected with 0.10 μg/ml Na 2SeO 3 (selenium protection group) was significantly higher than that of tBHP injury group ( P < 0.05). Compared with control group, the SIRT1 mRNA level of chondrocytes in tBHP injury group was significantly decreased; while the DNA methylation level in the SIRT1 promoter region, DNMT1 mRNA level and cell apoptosis rate were significantly increased ( P < 0.05). Compared with tBHP injury group, the selenium protection group had higher levels of SIRT1 mRNA in chondrocytes, lower levels of DNA methylation in the SIRT1 promoter region, DNMT1 mRNA, and cell apoptosis rate ( P < 0.05). The apoptosis rate was negatively correlated with SIRT1 mRNA level ( r s = - 0.78, P = 0.004), and positively correlated with the DNA methylation level in the SIRT1 promoter region ( r s = 0.76, P = 0.006). Conclusions:KBD patients have increased levels of oxidative stress, which may be associated with low expression of SIRT1. Oxidative injury may down-regulate SIRT1 expression and promote chondrocytes apoptosis by catalyzing DNA methylation in the SIRT1 promoter region.

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.