BACKGROUND: Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients. However, the association of joint changes in antihypertensive medication use and healthy lifestyle index (HLI) with BP control among hypertension patients is seldom reported, which needs to provide more evidence by prospective intervention studies. We examined the association of antihypertensive medication use and HLI with BP control among employees with hypertension in China based on a workplace-based multicomponent intervention program. METHODS: Between January 2013 and December 2014, a cluster randomized clinical trial of a workplace-based multicomponent intervention program was conducted in 60 workplaces across 20 urban areas in China. Workplaces were randomly divided into intervention (n = 40) and control (n = 20) groups. Basic information on employees at each workplace was collected by trained professionals, including sociodemographic characteristics, medical history, family history, lifestyle behaviors, medication status and physical measurements. After baseline, the intervention group received a 2-year intervention to achieve BP control, which included: (1) a workplace wellness program for all employees; (2) a guidelines-oriented hypertension management protocol. HLI including nonsmoking, nondrinking, adequate physical activity, weight within reference range and balanced diet, were coded on a 5-point scale (range: 0-5, with higher score indicating a healthier lifestyle). Antihypertensive medication use was defined as taking drug within the last 2 weeks. Changes in HLI, antihypertensive medication use and BP control from baseline to 24 months were measured after the intervention. RESULTS: Overall, 4655 employees were included (age: 46.3 ± 7.6 years, men: 3547 (82.3%)). After 24 months of the intervention, there was a significant improvement in lifestyle [smoking (OR = 0.65, 95% CI: 0.43-0.99; P = 0.045), drinking (OR = 0.52, 95% CI: 0.40-0.68; P < 0.001), regular exercise (OR = 3.10, 95% CI: 2.53-3.78; P < 0.001), excessive intake of fatty food (OR = 0.17, 95% CI: 0.06-0.52; P = 0.002), restrictive use of salt (OR = 0.26, 95% CI: 0.12-0.56; P = 0.001)]. Compare to employees with a deteriorating lifestyle after the intervention, those with an improved lifestyle had a higher BP control. In the intervention group, compared with employees not using antihypertensive medication, those who consistent used (OR = 2.34; 95% CI: 1.16-4.72; P = 0.017) or changed from not using to using antihypertensive medication (OR = 2.24; 95% CI: 1.08-4.62; P = 0.030) had higher BP control. Compared with those having lower HLI, participants with a same (OR = 1.38; 95% CI: 0.99-1.93; P = 0.056) or high (OR = 1.79; 95% CI: 1.27~2.53; P < 0.001) HLI had higher BP control. Those who used antihypertensive medication and had a high HLI had the highest BP control (OR = 1.88; 95% CI: 1.32-2.67, P < 0.001). Subgroup analysis also showed the consistent effect as the above. CONCLUSION These findings suggest that adherence to antihypertensive medication treatment and healthy lifestyle were associated with a significant improvement in BP control among employees with hypertension.

Refractory prolactinoma is the most common pituitary neuroendocrine tumor.Dopamine receptor agonists(DA)are the primary choice for drug treatment.Most patients with prolactinomas respond well to DA.However,a minority of prolactinomas patients still show resistance to DA.Although drug-resistant and refractory prolactinomas are rare in clinical practice,their treatment is extremely challenging.Even a combination of drug therapy,multiple surgeries,and radiotherapy may not yield satisfactory outcomes.Therefore,standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved.In the clinical management of refractory prolactinomas,it is often necessary to consider the patient's condition comprehensively,replace other types of DA,or consider surgery,radiotherapy,and immunotherapy,which requires multidisciplinary diagnosis and treatment.This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy,surgery,and radiotherapy treatments for refractory prolactionmas,aiming to provide new ideas for basic research,clinical diagnosis and treatment.

This study aims to explore the molecular regulation mechanism of the differential accumulation of flavonoids in the leaves and roots of Sarcandra glabra. Liquid chromatography-mass spectrometry(LC-MS) and high-throughput transcriptome sequencing(RNA-seq) were employed to screen out the flavonoid-related differential metabolites and differentially expressed genes(DEGs) encoding key metabolic enzymes. Eight DEGs were randomly selected for qRT-PCR verification. The results showed that a total of 37 flavonoid-related differential metabolites between the leaves and roots of S. glabra were obtained, including pinocembrin, phlorizin, na-ringenin, kaempferol, leucocyanidin, and 5-O-caffeoylshikimic acid. The transcriptome analysis predicted 36 DEGs associated with flavonoids in the leaves and roots of S. glabra, including 2 genes in the PAL pathway, 3 genes in the 4CL pathway, 2 genes in the CHS pathway, 4 genes in the CHI pathway, 2 genes in the FLS pathway, 1 gene in the DFR pathway, 1 gene in the CYP73A pathway, 1 gene in the CYP75B1 pathway, 3 genes in the PGT1 pathway, 6 genes in the HCT pathway, 2 genes in the C3'H pathway, 1 gene in the CCOAOMT pathway, 1 gene in the ANR pathway, 1 gene in the LAR pathway, 2 genes in the 3AT pathway, 1 gene in the BZ1 pathway, 2 genes in the IFTM7 pathway, and 1 gene in the CYP81E9 pathway. Six transcription factors, including C2H2, bHLH, and bZIP, were involved in regulating the differential accumulation of flavonoids in the leaves and roots of S. glabra. The qRT-PCR results showed that the up-or down-regulated expression of the 8 randomly selected enzyme genes involved in flavonoid synthesis in the leaves and roots of S. glabra was consistent with the transcriptome sequencing results. This study preliminarily analyzed the transcriptional regulation mechanism of differential accumulation of flavonoids in the leaves and roots of S. glabra, laying a foundation for further elucidating the regulatory effects of key enzyme genes and corresponding transcription factors on the accumulation of flavonoids in S. glabra.
Metabolome ; Gene Expression Regulation, Plant ; Flavonoids ; Gene Expression Profiling ; Transcriptome ; Transcription Factors/metabolism*

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

OBJECTIVE: The mode of human immunodeficiency virus (HIV) transmission via injection drug use (IDU) still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi. METHODS: We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data. RESULTS: Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs. CONCLUSION HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces. Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.
Humans ; HIV-1/genetics* ; HIV Infections ; Drug Users ; Phylogeny ; Bayes Theorem ; China/epidemiology* ; Genotype

Objective: Schizophrenia is a complex and devastating psychiatric disorder with a strong genetic background. However, much uncertainty still exists about the role of genetic susceptibility in the pathophysiology of schizophrenia. TEA domain transcription factor 1 (TEAD1) is a transcription factor associated with neurodevelopment and has modulating effects on various nervous system diseases. In the current study, we performed a case–control association study in a Northeast Chinese Han population to explore the characteristics of pathogenic TEAD1 polymorphisms and potential association with schizophrenia. Methods: We recruited a total of 721 schizophrenia patients and 1,195 healthy controls in this study. The 9 single nucleotide polymorphisms (SNPs) in the gene region of TEAD1 were selected and genotyped. Results: The genetic association analyses showed that five SNPs (rs12289262, rs6485989, rs4415740, rs7113256, and rs1866709) were significantly different between schizophrenia patients and healthy controls in allele or/and genotype frequencies. After Bonferroni correction, the association of three SNPs (rs4415740, rs7113256, and rs1866709) with schizophrenia were still evident. Haplotype analysis revealed that two strong linkage disequilibrium blocks (rs6485989-rs4415740-rs7113256 and rs16911710-rs12364619-rs1866709) were globally associated with schizophrenia. Four haplotypes (C-C-C and T-T-T, rs6485989-rs4415740-rs7113256; G-T-A and G-T-G, rs16911710-rs12364619-rs1866709) were significantly different between schizophrenia patients and healthy controls. Conclusion The current findings indicated that the human TEAD1 gene has a genetic association with schizophrenia in the Chinese Han population and may act as a susceptibility gene for schizophrenia.

Objective: To estimate the prevalence, awareness, treatment and control rate of hypertension among young and middle-aged population in China. Methods: The analysis was based on the results of 2012-2015 China Hypertension Survey, which was a cross-sectional stratified multistage random sampling survey. A total of 229 593 subjects were included in the final analysis. The data including sex, age, living in urban and rural areas, prevalence of hypertension, history of stroke, family history of coronary heart disease and drinking, physical examination, heart rate were collected. Hypertension was defined as mean systolic blood pressure (SBP) ≥140 mmHg (1 mmHg=0.133 kPa), and (or) diastolic blood pressure (DBP) ≥90 mmHg, and (or) self-report a history of hypertension, and (or) use of antihypertensive medicine within 2 weeks before survey. Prehypertension was defined as SBP between 120-139 mmHg, and (or) DBP between 80-89 mmHg. Control of hypertension was considered for hypertensive individuals with SBP<140 mmHg and DBP<90 mmHg. The prevalence of prehypertension, hypertension, awareness, treatment, control rate were calculated, and the control rate among those with antihypertensive medication was also calculated. Results: The prevalence of prehypertension and hypertension was 43.8% (95%CI: 42.3%-45.4%), and 22.1% (95%CI: 20.8%-23.3%), respectively. The prevalence of prehypertension and hypertension was significantly higher among male than female across different age groups. The awareness, treatment, control rate of hypertension and control rate among treated hypertensive participants were 43.8%, 33.2%, 16.7%, and 40.2%, respectively. The prevalence was higher, and the control rate was lower among individuals with higher heart rate. Conclusion: The prevalence of prehypertension and hypertension among young and middle-aged population is high, the awareness, treatment and control rate need to be further improved in this population. The prevention and treatment of hypertension should be strengthened in the future to improve the control rate of hypertension in China.
Middle Aged ; Male ; Female ; Humans ; Antihypertensive Agents/therapeutic use* ; Prehypertension/epidemiology* ; Prevalence ; Cross-Sectional Studies ; Hypertension/drug therapy* ; Blood Pressure ; China/epidemiology*

OBJECTIVE: To observe the effect of electroacupuncture (EA) on pain behavior, synovial inflammatory response and demyelination of saphenous nerve in the rats modeled with knee osteoarthritis (KOA) and explore the effect mechanism of EA for reliving allodynia. METHODS: Eighty-four male SD rats were randomly divided into a control group, a model group and an EA group, 28 rats in each one. Intra-articular injection of sodium monoiodoacetate (MIA) was administered in right knee joint of each rat in the model group and the EA group to establish the KOA model. In the EA group, separately, on day 5, 7 and 9 after modeling, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave (2 Hz/15 Hz), 1 mA in current intensity, for 30 min in one intervention, once a day, and 3 interventions were required. On the 9th day after modeling, the weight-bearing rate was calculated for the affected limbs of the rats in each group, the synovial morphological changes were observed using HE and Masson staining, flow cytometry was adopted to detect the synovial immunocyte counts, and MSD multi-spot assay was used to detected the synovial inflammatory cytokine content. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was observed in each group and the ultrastructure of the saphenous nerve was observed under transmission electron microscopy. RESULTS: On the 9th day after modeling, compared with the control group, the weight-bearing rate of the affected limb was reduced (P<0.01), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis occurred in the affected limb; the counts of synovial CD11b⁺ cells and M1 macrophages (CD11b⁺CD86⁺) were increased (P<0.01), the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, IL-10 and IL-13 in the synovial tissue were elevated (P<0.01, P<0.05) for the rats of the model group. Compared with the model group, the weight-bearing rate of the affected limb was increased (P<0.05), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis were mitigated, the counts of CD11b⁺ cells and M1 macrophages (CD11b⁺CD86⁺) in the synovial tissue, and the contents of TNF-α and IL-6 were reduced (P<0.01, P<0.05) in the EA group. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was reduced in the model group when compared with the control group (P<0.01), and it was increased in the EA group when compared with the model group (P<0.05). Besides, in the model group, obviously, the myelin sheath structure was destroyed, the myelin layer was disintegrated and loosened, the axon was extruded or the layer thicken and cracked. Compared with the model group, the injury of saphenous nerve was alleviated remarkably in the EA group. CONCLUSION The intervention with EA may attenuate the synovial inflammatory response and the injury of saphenous nerve in the affected limb of the rat with KOA, so that the spontaneous pain during the synovial inflammatory response stage and allodynia at the later stage are relieved.
Male ; Rats ; Animals ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; Hyperplasia ; Cytokines ; Pain/etiology*

Objective To evaluate the effects of early exercise intervention in patients who have undergone primary isolated valve surgery. Methods Forty patients scheduled for mitral, aortic, and/or tricuspid valve surgery were allocated to receive a supervised exercise intervention consisting of cycling for 3 min/d at the bedside after operation (intervention group, n=20, mean age [49.05±3.728] years) or to receive no exercise intervention (control group, n=20, mean age [47.95 ± 3.214] years). Oxygen saturation (SpO2) was measured by pulse oximetry continuously before and after the 6-minute walk test. Psycho-educational counseling was provided, and patients were assessed using standard patient questionnaires. Results The arterial SpO2 level increased significantly in the intervention group after exercise compared with the control group (P<0.05). Heart rate returned to baseline in the intervention group postoperatively and was significantly lower than that in the control group (P<0.05). Conclusions A small amount of supervised cycling exercise at the bedside is a safe activity that may improve peripheral arterial SpO2 and reduce heart rate to the baseline level following longer distance walk before discharge in patients who have undergone isolated valve surgery.

To provide experimental basis and theoretical guidance for further research on the molecular mechanism of notoginsenoside R_1(NGR_1) in the treatment of depression, the present study analyzed the potential mechanism of NGR_1 in the treatment of depression through network pharmacology and verified it by molecular docking and animal experiments. PharmMapper, SwissTargetPrediction, and GeneCards were used to predict the related targets of both NGR_1 and depression to obtain the potential targets of NGR_1 in the treatment of depression. The database for annotation, visualization and integrated discovery(DAVID) was used for GO functional annotation and KEGG pathway enrichment analysis to screen the possible mechanisms of NGR_1 exerting antidepressant effect. Cytoscape 3.9.0 was adopted to construct a protein-protein interaction(PPI) network, and the topological analysis was performed to obtain the core targets. The binding activity of NGR_1 to core targets was tested by molecular docking. The depression model was prepared by injecting lipopolysaccharide(LPS) into the lateral ventricle in mice, and intervened with NGR_1. The antidepressant effect of NGR_1 was detected by behavioral tests and RT-qPCR. The results showed that by network pharmacology, 56 common targets of NGR_1 and depression were predicted, and GO enrichment analysis determined 13 related biological processes, mainly involving G protein-coupled receptor signaling pathway, positive regulation of transcription from RNA polymerase Ⅱ promoter, cytokine-mediated signaling pathway, gene expression, apoptosis, cell proliferation, and signal transduction. In addition, KEGG pathway enrichment analysis identified ten potential pathways, including neuroactive ligand-receptor interaction signaling pathway, lipid and atherosclerosis signaling pathway, cAMP signaling pathway, PI3 K-AKT signaling pathway, and lipid and atherosclerosis signaling pathway. PPI analysis revealed that the core targets included CASP3, VEGFA, IGF1, STAT3, MAPK1, PPARG, MTOR, MAPK14, NR3 C1 and AR, and molecular docking demonstrated that NGR_1 had desirable binding activity to these target proteins. In animal experiments, the results showed that NGR_1 improved the disease behavior of depressed mice, significantly inhibited the neuroinflammatory response(reducing the mRNA expression of Iba-1, TNF-α, IL-1β, and IL-6), and regulated the mRNA expression of lipid and atherosclerosis signaling pathway-related targets(CASP3, STAT3, MAPK1 and MAPK14). This indicated that the antidepressant mechanism of NGR_1 may be related to the regulation of lipid and atherosclerosis signaling pathway. In conclusion, network pharmacology was used to reveal the core targets and pathways of NGR_1, and some of them were verified in animal experiments, which provided the basis for in-depth exploration on the mechanism of NGR_1 in the treatment of depression.
Mice ; Animals ; Caspase 3 ; Animal Experimentation ; Mitogen-Activated Protein Kinase 14 ; Network Pharmacology ; Molecular Docking Simulation ; Antidepressive Agents/pharmacology* ; Lipopolysaccharides ; Atherosclerosis ; RNA, Messenger ; Drugs, Chinese Herbal/pharmacology*