ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVE: This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age. METHODS: In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. RESULTS: The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. CONCLUSION In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans ; Female ; Vitamin D/blood* ; Adult ; Middle Aged ; Polymorphism, Single Nucleotide ; Adolescent ; Young Adult ; China ; Biomarkers/blood* ; Bone Remodeling/genetics* ; Vitamin D-Binding Protein/genetics* ; Procollagen/blood* ; Osteocalcin/blood* ; Peptide Fragments/blood* ; East Asian People

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 prevalence of sexual drug use in men who have sex with men (MSM) in Chengdu and analyze the relationship between depression and sexual drug use.Methods:A total of 1 277 MSM were recruited between November 2021 and May 2022. Questionnaire was used to collect information about their demographic characteristics, depression status and sexual drug use behavior. Univariate and multivariate logistic regression models were used to analyze the relationship between depression and sexual drug use.Results:In the 1 277 MSM, assessment identified 503 mild depression cases (39.4%), 196 moderate depression cases (15.3%) and 171 severe depression cases (13.4%) and 444 MSM (34.8%) reported sexual drug use in the past 6 months. Multivariate logistic regression models showed that compared with non-depression, mild depression (a OR=1.67,95% CI:1.24-2.23), moderate depression (a OR=1.50,95% CI: 1.02-2.19) and severe depression (a OR=1.56,95% CI:1.04-2.32) were positively associated with sexual drug use. Conclusions:The prevalence of depression and sexual drug use were high in MSM in Chengdu. There was a positive correlation between depression and sexual drug use. It is necessary to pay close attention to depression and sexual drug use and conduct targeted intervention in MSM.

Objective:To investigate the prevalence of sexual drug use in men who have sex with men (MSM) in Chengdu and analyze the relationship between depression and sexual drug use.Methods:A total of 1 277 MSM were recruited between November 2021 and May 2022. Questionnaire was used to collect information about their demographic characteristics, depression status and sexual drug use behavior. Univariate and multivariate logistic regression models were used to analyze the relationship between depression and sexual drug use.Results:In the 1 277 MSM, assessment identified 503 mild depression cases (39.4%), 196 moderate depression cases (15.3%) and 171 severe depression cases (13.4%) and 444 MSM (34.8%) reported sexual drug use in the past 6 months. Multivariate logistic regression models showed that compared with non-depression, mild depression (a OR=1.67,95% CI:1.24-2.23), moderate depression (a OR=1.50,95% CI: 1.02-2.19) and severe depression (a OR=1.56,95% CI:1.04-2.32) were positively associated with sexual drug use. Conclusions:The prevalence of depression and sexual drug use were high in MSM in Chengdu. There was a positive correlation between depression and sexual drug use. It is necessary to pay close attention to depression and sexual drug use and conduct targeted intervention in MSM.

Cardiovascular and cerebrovascular diseases, usually result from atherosclerosis, has the highest mortality rate globally. Lipid metabolism disorder is the main cause of atherosclerotic cardiovascular and cerebrovascular diseases, which not only lead to acute diseases such as myocardial infarction, stroke, acute pancreatitis, but also chronic kidney disease. In recent years, the advancement of gene therapy technologies has provided novel means for lipid metabolism study, and has also made it possible to cure patients with congenital lipid metabolism abnormalities. Adeno-associatd virus has a wide host range, high safety, low immunogenicity, and especially the ability of long-term stable expression in vivo, making it the preferred delivery tool for gene therapy of monogenic genetic diseases. Alipogene triprivec, also known as Glybera, was approved by the European Medicines Agency in 2012. It is the first gene therapy drug that uses recombinant AAV1 vector to directly deliver a highly active LPL protein S447X mutant to muscle cells for the treatment of patients with hereditary LPL deficiency. To enhance the targeted transduction efficiency of AAV carriers, recombinantAAV8.TBG.hLDLR utilizes the tissue tropsim of AAV8 to liver, meanwhile utilizes a liver specific thyroxine binding globulin promoter to control gene transcription, thereby achieving liver cell specific high expressionof human low-density lipoprotein receptors (LDLR). In patients with familial hypercholesterolemia,AAV8.TBG.hLDLR treatment effectively lower the level of plasma LDL for a long time, thus preventing the occurrence of atherosclerosis.Proprotein convert subunit kexin 9 (PCSK9) is secreted by liver cells. PCSK9 binds and transports LDLR to lysosomes for degradation, preventing the circulation and regeneration of LDLR, leading to accelerated degradation of LDLR and finally resulting in the accumulation of low-density lipoprotein cholesterol in plasma. Using AAV to deliver Cas9 of Staphylococcus aureus and gRNA targeting the Pcsk9 gene can knock out Pcsk9 in mouse liver, leading to a long-term significant decrease in plasma cholesterol levels in mice. Hepatocyte specific angiopoietin related protein 3 (Angptl3) is an endogenous inhibitor of LPL. Using the AAV9 mediated AncBE4max system and the dCas9 mediated single base gene editing system to introduce early termination codons, the knockout of Angptal3 in liver cells was achieved with an average knockout efficiency of 63.3%. After 2-4 weeks of administration in mice, the Angptl3 protein was completely undetectable in the peripheral blood, and serum triglycerides and total cholesterol decreased by 58% and 61%, respectively. Ring finger containing protein 130 (RNF130) is an E3 ubiquitin ligase. Research has shown that overexpression of RNF130 using AAV2/8 leads to ubiquitination degradation and redistribution of LDLR on the cell membrane, significantly reducing LDLR expression on liver cells and increasing plasma LDLC levels, while knocking out Rnf130 gene using the AAV-CRISPR system results in the opposite effect. This AAV mediated RNF130 function study proves that RNF130 is a posttranslational regulatory protein of LDLR and plays an important role in the regulation of serum LDLC. As mentioned above, recently, various lipid-lowering gene therapy drugs carried by different serotypes of adeno-associated virus have been applied in clinic or are undergoing clinical trials, and adeno-associated virus has emerging to be an important tool for lipid metabolism research.This article reviews the new progress of adeno-associated virus vectors in lipid metabolism study and lipid-lowering gene therapy.

Objective To establish a method to identify an unknown substance based on the combined use of gas chromatography-quadrupole time-of-flight mass spectrometry(GC-QTOF-MS),ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q/Orbitrap HRMS)and nuclear magnetic resonance(NMR)techniques.Methods The unknown substance was dissolved in methanol and was detected by GC-QTOF-MS and UPLC-Q/Orbitrap HRMS,and was dissolved in methanol-d4 to be detected by NMR.Results The main characteristics ion peaks of components with retention time of 9.67 min in GC-QTOF-MS measured were 84.080 8,110.999 7,128.107 0(base peak),138.994 7,etc.The protonated molecular ion peak m/z in UPLC-Q/Orbitrap HRMS was 268.109 3.It was inferred that the unknown substance was an analog of the syn-thetic cathinone substance 2-methyl-1-[4-(methylthio)phenyl]-2-morpholinopropan-1-one(MTMP)by comparing the mass spectrum information and molecular structure of MTMP.NMR analysis confirmed it as a novel N-morpholine substituted synthetic cathinone substance 1-(4-chlorophenyl)-2-methyl-2-morpholinopropan-1-one(CMMP).Conclusion The method established in this study can be used for structural confirmation of CMMP.

A triplex RT-qPCR assay with human genes as internal references was established for detection of the Dengue and Zika viruses(DENV and ZIKV,respectively).The conserved regions of the four serotypes of DENV,along with the NS1 gene of ZIKV and the human β-actin gene,which is stably ex-pressed in various human tissues,were targeted by three sets of specific primers and probes.Standard plasmids for four se-rotypes of DENV,ZIKV,and β-actin were constructed as pos-itive controls.Optimal reaction conditions were determined through an L9(34)orthogonal experiment.The specificity,sensitivity,and coverage of the assay were verified and evalua-ted clinically,and the consistency was evaluated against a com-mercial kit for detection of DENV.The triplex RT-qPCR assay established exhibited no non-specific cross reactions with 12 similar arboviruses.The detection sensitivity for DENV and ZIKV were 2.99 and 2.18 copies/μL,respectively,and the intra-group and inter-group repeatability coefficients of variation were within 1.5％.As compared to the commercial kit,the proposed assay obtained positive results for 13 epidemic strains of DENV.Bland-Altman consistency analysis confirmed that the consistency of the detection results of clinical positive samples between the commercial kit and the proposed assay was 92.59％.The highly specific and sensitive triplex RT-qPCR assay with internal references is an effective tool for early and rapid differential identification of DENV and ZIKV.

Objective:To observe the impacts of using heated and humidified gas sources for delivery room resuscitation on the short-term outcomes of extremely preterm infants.Methods:A retrospective study was conducted on 231 extremely preterm infants admitted to the neonatal intensive care unit of Shenzhen Maternity & Child Healthcare Hospital, the First School of Clinical Medicine, Southern Medical University, from January 2020 to December 2022. The infants were divided into two groups based on whether heated and humidified gas sources were used during delivery room resuscitation: the heated and humidified group (103 cases) and the non-heated and humidified group (128 cases). Independent sample t-tests, Chi-square tests, and Mann-Whitney U tests were used to compare general conditions and short-term outcomes between the groups. Multivariate logistic regression analysis was used to assess the impact of using heated and humidified gas sources during delivery room resuscitation on the short-term outcomes of extremely preterm infants. Results:Compared to the non-heated and humidified group, the heated and humidified group had a lower incidence of intubation resuscitation [28.2% (29/103) vs. 41.4% (53/128), χ 2=4.38], moderate to severe bronchopulmonary dysplasia (BPD)/death [22.3% (23/103) vs. 39.1% (50/128), χ 2=7.39] and low rectal temperature upon admission (<36.7 ℃) [57.3% (59/103) vs. 79.7% (102/128), χ 2=13.57], while the rectal temperature upon admission was higher [36.3 ℃ (36.0-36.7 ℃) vs. 35.9 ℃ (35.5-36.3 ℃), U=－5.05], with all differences being statistically significant (all P<0.05). After adjusting for gender, gestational age, mode of delivery, amniotic fluid condition, weight on admission, maternal premature rupture of membranes, assisted reproductive technology, and full course of prenatal steroid use, multivariate logistic regression analysis showed that the use of heated and humidified gas sources during delivery room resuscitation could increase the hospital admission rectal temperature ( β=0.46, 95% CI: 0.28-0.64), and decrease the risks of severe BPD/death ( aOR=0.39, 95% CI: 0.20-0.75), and low rectal temperature upon admission ( aOR=0.29, 95% CI: 0.16-0.55)(all P<0.05). Compared to the non-heated and humidified group, the heated and humidified group showed no statistically significant differences in the use of pulmonary surfactant [37.9% (39/103) vs. 43.8% (56/128), χ 2=1.45], incidence of stage Ⅲ or higher necrotizing enterocolitis [2.0% (2/103) vs. 5.5% (7/128), χ 2=2.06], grade Ⅲ or higher intracranial hemorrhage [2.9% (3/103) vs. 3.9% (5/128), χ 2=0.22], and retinopathy of prematurity requiring surgical treatment [3.9% (4/103) vs. 10.2% (13/128), χ 2=3.60] (all P>0.05). Conclusion:The use of heated and humidified gas sources during resuscitation of extremely preterm infants can reduce the risk of moderate to severe BPD/death, help maintain warmth during resuscitation, and do not adversely affect other short-term outcomes.