Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Objective To observe the efficacy of Asini Corii Colla for the treatment of women with pregnancy anemia induced by β-thalassemia and its effect on the expression of early growth response 2(EGR2).Methods Transcriptome sequencing(RNA-seq)was performed firstly.Twenty pregnant women with β-thalassemia were randomly assigned to the treatment group and the control group at the proportion of 3:1.There were 15 cases allocated to the treatment group,one case fell off during the trial,and eventually 14 cases were included.The control group had 5 cases.The treatment group was given Asini Corii Colla powder orally,and the control group had no intervention.The course of treatment covered 4 weeks.The peripheral blood of the two groups of pregnant women was sampled before and after treatment for RNA-seq analysis,and then the candidate targets were defined.Subsequently,a prospective clinical randomized controlled trial(RCT)was conducted.A total of 41 pregnant women with β-thalassemia were randomly assigned to the treatment group(24 cases)and the control group(17 cases)at the proportion of 3:2.The treatment group was treated with Asini Corii Colla powder orally,and the control group was treated with the simulant of Asini Corii Colla Powder orally.The course of treatment covered 4 weeks.The hematological parameters of the two groups of pregnant women were detected before and after treatment,and the mRNA and protein expression levels of candidate targets were detected by real-time polymerase chain reaction(real-time PCR)and western blotting respectively.Results(1)The results of RNA-seq analysis showed that EGR2 expression of patients with genotype βCD41-42(-TTCT)/βN in the treatment group was significantly up-regulated after treatment(log2 FC=1.915;Padj=9.84E-03),and EGR2 was named as the candidate target.(2)The results of RCT showed that after treatment,there was no significant difference in the average hemoglobin(Hb)concentration between the two groups of pregnant women with β-thalassemia(P＞0.05),but the average Hb of the patients with genotypeβCD41-42(-TTCT)/βN in the treatment group increased by(6.54±4.74)g/L,which was significantly higher than that of other genotypes of pregnant women with β-thalassemia(P＜0.05).The expression levels of EGR2 Mrna and protein in peripheral blood of the patients with genotypeβCD41-42(-TTCT)/Βn in the treatment group were significantly increased after treatment(P＜0.05).The pre-and post-treatment difference of Hb concentration in the two groups of pregnant women withβ-thalassemia was positively correlated with pre-and post-treatment difference of EGR2 Mrna level and EGR2 protein level,and the correlation coefficients were 0.701 and 0.683,respectively(P＜0.001).Conclusion The pregnant women with thalassemia of genotype Βcd41-42(-TTCT)/Βn can achieve satisfactory efficacy after oral administration of Asini Corii Colla.Its curative effect for improving anemia may be related to the transcriptional regulation of globin genes through up-regulating EGR2 expression,activating RNA polymerase Ⅱ promoter,and promoting nucleic acid binding.

OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on renal function after laparoscopic radical nephrectomy. METHODS: We reviewed the clinical data of 282 patients with renal cell carcinoma (RCC), who underwent laparoscopic radical nephrectomy (LRN) in the Department of Urology, Third Medical Center of PLA General Hospital from November, 2020 and June, 2022.According to whether DEX was used during the operation, the patients were divided into DEX group and control group, and after propensity score matching, 99 patients were finally enrolled in each group.The incidence of acute kidney injuries were compared between the two groups.Serum creatinine (sCr) data within 3 months to 1 year after the operation were available in 51 patients, including 26 in DEX group and 25 in the control group, and the incidence of chronic kidney disease (CKD) was compared between the two groups. RESULTS: After propensity score matching and adjustment for significant covariates, there were no significant differences in postoperative levels of sCr, cystatin C (CysC), β2-microglobulin (β2-MG), hemoglobin (Hb), or C-reactive protein (CRP), extubation time, incidence of AKI, or length of hospital stay between the two groups (P>0.05).The intraoperative urine volume was significantly higher in DEX group than in the control group (P < 0.05).A significant correlation between AKI and CKD was noted in the patients (P < 0.05).The incidence of CKD did not differ significantly between the two groups (P>0.05). CONCLUSION DEX can not reduce the incidence of AKI or CKD after LRN.
Humans ; Dexmedetomidine ; Incidence ; Propensity Score ; Renal Insufficiency, Chronic/epidemiology* ; Kidney Neoplasms/surgery* ; Nephrectomy/adverse effects* ; Laparoscopy/adverse effects* ; Acute Kidney Injury/prevention & control* ; Retrospective Studies

OBJECTIVE: To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis. METHODS: Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched. RESULTS: A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways. CONCLUSIONS Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.
Echinococcosis/genetics* ; Gene Expression Profiling ; Humans ; MicroRNAs/metabolism* ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; T-Lymphocytes, Regulatory ; TOR Serine-Threonine Kinases/genetics* ; Th17 Cells ; Transcription Factors/genetics*

Objective: To investigate the influencing factors of HBV intrauterine transmission and their interaction effects by integrating logistic regression model and Chi-squared automatic interaction detector (CHAID) decision tree model. Methods: A total of 689 pairs of HBsAg-positive mothers and their neonates in the obstetrics department of the Third People's Hospital of Taiyuan from 2007 to 2013 were enrolled, and the basic information of mothers and their neonates were obtained by questionnaire survey and medical record review, such as the general demographic characteristics, gestational week and delivery mode. HBV DNA and HBV serological markers of the mothers and newborns were detected by fluorescence quantitative PCR and electrochemiluminescence immunoassay respectively. The CHAID decision tree model and unconditional logistic regression analysis were used to explore the factors influencing HBV intrauterine transmission in neonates of HBsAg-positive mothers. Results: Among the 689 neonates, the incidence of HBV intrauterine transmission was 11.47% (79/689). After adjusted for confounding factors, the first and second logistic multivariate analysis showed that cesarean delivery was a protective factor for HBV intrauterine transmission (OR=0.25, 95%CI: 0.14-0.43; OR=0.27, 95%CI: 0.15-0.46); both models indicated that maternal HBeAg positivity and HBV DNA load ≥2×10⁵ IU/ml before delivery were risk factors of HBV intrauterine transmission (OR=3.89, 95%CI: 2.32-6.51; OR=3.48, 95%CI: 2.12-5.71), respectively. The CHAID decision tree model screened three significant factors influencing HBV intrauterine transmission, the most significant one was maternal HBeAg status, followed by delivery mode and maternal HBV DNA load. There were interactions between maternal HBeAg status and delivery modes, as well as delivery mode and maternal HBV DNA load before delivery. The rate of HBV intrauterine transmission in newborns of HBeAg-positive mothers by vaginal delivery increased from 19.08% to 29.37%; among HBeAg-positive mothers with HBV DNA ≥2×10⁵ IU/ml, the rate of HBV intrauterine transmission increased to 33.33% in the newborns by vaginal delivery. Conclusions: Maternal HBeAg positivity,maternal HBV DNA ≥2×10⁵ IU/ml and vaginal delivery could be risk factors for HBV intrauterine transmission in newborns. Interaction effects were found between maternal HBeAg positivity and vaginal delivery, as well as vaginal delivery and high maternal HBV DNA load. Logistic regression model and the CHAID decision tree model can be used in conjunction to identify the high-risk populations and develop preventive strategies accurately.
DNA, Viral/genetics* ; Decision Trees ; Female ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B virus/genetics* ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Logistic Models ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology*

Objective: To investigate the type, length, and CG loci of HBV DNA CpG islands in HBsAg positive maternal C genotype and its relationship with intrauterine HBV transmission, so as to provide a new perspective for the study of intrauterine transmission of HBV. Methods: From June 2011 to July 2013, HBsAg-positive mothers and their newborns who delivered in the obstetrics and gynecology department of the Third People's Hospital of Taiyuan were collected. Epidemiological data were collected through face-to-face questionnaires and electronic medical records. Serum HBV markers and serum HBV DNA were detected by electrochemiluminescence and quantitative fluorescence PCR, respectively. Intrauterine transmission of HBV was determined by positive HBsAg and/or HBV DNA in femoral venous blood before injection of HBV vaccine/Hepatitis B immunoglobulin within 24 h of birth. A total of 22 mothers and their newborns with HBV DNA load ≥10⁶ IU/ml in intrauterine transmission were selected as the intrauterine transmission group, and 22 mothers with HBV DNA load ≥10⁶ IU/ml without intrauterine transmission were chosen as the control group by random seed method. The distribution prediction of CpG islands of HBV DNA in 39 mothers with genotype C by HBV DNA sequencing was analyzed. Results: Among 39 mothers with HBV C genotype, 19 were in the intrauterine transmission group, and 20 were in the control group. The HBV DNA of 39 patients with genotype C traditional CpG island Ⅱ and Ⅲ, while the control group had traditional CpG island Ⅰ and novel CpG island Ⅳ and Ⅴ. The length of CpG island Ⅱ and Ⅲ and the number of CG loci of CpG island Ⅱ in the intrauterine transmission group differed from those in the control group (P<0.05). The CpG island Ⅱ length ≥518 bp and the number of CG loci ≥40 in the intrauterine transmission group (11/19) were significantly higher than those in the control group (2/20) (P<0.05). The length of CpG island Ⅱ and the number of CG loci in the X gene promoter region (Xp region) were higher than those in the control group (P<0.05). In the HBV intrauterine transmission group, most of maternal (12/19) HBV DNA CpG island Ⅱ completely covered the Xp region, which was significantly higher than that in the control group (5/20), and the number of HBV DNA Xp region CG loci was higher than that in the control group (P<0.05). Conclusions: The distribution of maternal C genotype HBV DNA CpG islands is related to intrauterine transmission. The length of CpG island Ⅱ and the number of CG sites may increase the risk of intrauterine transmission of HBV.
Biomarkers ; CpG Islands ; DNA, Viral/genetics* ; Female ; Hepatitis B ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious

OBJECTIVE: To study the risk factors and treatment for neutropenia of late newborns (NLN). METHODS: Related clinical data were collected from the preterm infants and critically ill neonates who were admitted to the neonatal intensive care unit from July 2019 to January 2020. A total of 46 newborns with a blood absolute neutrophil count (ANC) of < 1.5×10 RESULTS: Among the 46 neonates in the NLN group, 29 had a gestational age of < 32 weeks, 14 had a gestational age of 32-37 weeks, and 3 had a gestational age of > 37 weeks. There was no significant difference between the two groups in the incidence rates of gestational hypertension, premature rupture of membranes > 18 hours and intrauterine distress, 5-minute Apgar score, the duration of positive pressure ventilation, the incidence rate of early-onset sepsis, and the type of initially used antibiotics ( CONCLUSIONS The risk of NLN increases with the presence of late-onset sepsis and the increase in the duration of antibiotic use. NLN is generally a benign process. G-CSF appears to be safe and effective for NLN with severe disease conditions or severe reduction in ANC.
Granulocyte Colony-Stimulating Factor ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Leukocyte Count ; Neutropenia ; Risk Factors ; Sepsis

OBJECTIVE: To analyze the characteristics of the age at peak height velocity and peak height velocity of primary and middle school students in Zhongshan City, Guangdong Province, and to explore the law of the sudden increase in adolescent height in this area, and to understand the law of height growth spurt in adolescence by longitudinal tracking of the height of children and adolescents in Zhong-shan City. METHODS: Based on the physical examination database of primary and middle school students in Zhongshan City, Guangdong Province from 2005 to 2016, individuals who had been continuously tracked for more than 6 times were selected as research samples. SITAR model was used to fit the height data of the sample population, and the age at peak height velocity and peak height velocity were calcula-ted. RESULTS: A total of 49 579 subjects were included in this study, including 26 524 boys and 26 008 urban students. The median follow-up ages of boys and girls were 7.74 and 7.72 years, respectively. The boy's height spurt peak age was (12.72±0.89) years, and later than the girls at the age of (10.98±0.95) years (t=207.639, P < 0.001), the boy's height spurt peak velocity of (10.12±1.49) cm/year, higher than the girls of (8.35±1.12) cm/year (t=150.826, P < 0.001). The gender differences of height spurt peak age and height spurt peak speed in urban and rural students were consistent with the whole sample. The height surge peak age of urban male students was earlier than that of rural male students, and the height surge peak speed of urban female students was lower than that of rural female students. CONCLUSION The peak age of the surge of girls was earlier than that of boys, but the peak rate of the surge of girls was lower than that of boys, the peak age of urban students was earlier than that of rural students, but the peak rate of urban boys was lower than that of rural boys in Guangdong Province.
Adolescent ; Body Height ; Child ; Female ; Humans ; Male ; Rural Population ; Sex Factors ; Students