OBJECTIVE: To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes. METHODS: A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents. RESULTS: The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (P_interaction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis. CONCLUSION Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.
Humans ; Male ; Middle Aged ; Aged ; Female ; Metformin/adverse effects* ; Diabetes Mellitus, Type 2/drug therapy* ; Cohort Studies ; Ischemic Stroke/complications* ; Prospective Studies ; Hypoglycemic Agents/adverse effects* ; Stroke/prevention & control* ; Retrospective Studies

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

OBJECTIVE: To explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci. METHODS: A questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke. RESULTS: A total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033). CONCLUSION Decreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.
Aged ; Genome-Wide Association Study ; Humans ; Ischemic Stroke ; Middle Aged ; Sleep/genetics* ; Stroke/genetics* ; Surveys and Questionnaires

In recent years, the real-world studies (RWS) have attracted extensive attention, and the real-world evidence (RWE) has been accepted to support the drug development in China and abroad. However, there is still a lack of standards for the evaluation of the quality of RWE. It is necessary to formulate a quality evaluation and reporting specification for RWE especially in traditional Chinese medicine (TCM). To this end, under the guidance of China Association of Chinese Medicine, the Quality Evaluation and Reporting Specification for Real-World Evidence of Traditional Chinese Medicine (QUERST) Group, including 24 experts (clinical epidemiologists, clinicians, pharmacologists, ethical reviewer and statisticians), was established to develop the specification. This specification contains the listing of classification of RWS design and RWE, the general principles and methods of RWE quality evaluation (26 tools or scales), 25 types of bias in RWS, the special considerations in evaluating the quality of RWE of TCM, and the 19 reporting standards of RWE. This specification aims to propose the quality evaluation principles and key points of RWE, and provide guidance for the proper use of RWE in the development of TCM new drugs.
Medicine, Chinese Traditional ; China

Aim To explore the effeet of salidroside (SAL) on proliferation of osteoblasts and its possible mechanism by using mouse primary osteoblasts ( MOB) as the research object.Methods Alkaline phosphatase ( ALP) staining was used to identify the extracted primary cells.MTT was used to detect the effect of SAL on the proliferation.RT-PCR, Western blot, ELISA were used to investigate the molecular mechanism of SAL.Results The extracted cells generated black-brown deposits by ALP staining, which were shown to be osteoblasts clearly.SAL promoted the pro liferation of MOB.Meanwhile, SAL could up-regulate the mRNA and protein expression levels of hypoxia-inducible factor-lcx ( HIF-1 ex), vascular endothelial growth factor ( VEGF ) , angiopoietin-like protein 4 (ANGPTL4) and interleukin 6 ( IL-6 ) , which were down-regulated by using the HIF-lex blocker YC-1.Conclusions SAL could promote the proliferation of MOB through HIF-1 a/VEGF, ANGPTL4, IL-6 signaling pathway.

BACKGROUNDPatients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.

METHODSParticipants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.

RESULTSIn total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis.

CONCLUSIONSHemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Adult ; Aged ; China ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Renal Dialysis ; adverse effects ; mortality ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate the protective effects of high-dose ulinastatin on the vital organs in patients undergoing total arch replacement for type A aortic dissection.

METHODSBetween September 2014 and March 2016, 66 patients with type A aortic dissection underwent total arch replacement at our center. Thirty-six of the patients received ulinastatin treatment at 300 000 U/8 h from admission to 3 days postoperatively and at 300 000 U/2 h during cardiopulmonary bypass surgery (UTI group), and the other 30 patients did not receive perioperative ulinastatin treatment (control group). The surgical data and blood biochemistry profiles on days 1, 3, and 5 postoperatively were compared between the two groups, and the postoperative ICU stay, re-operation for bleeding, ventilation for over 7 days, ultrafiltration for postoperative renal failure, tracheotomy, incidences of pulmonary and neurological complications and hospital death were also compared.

RESULTSs The operating time, cardiopulmonary bypass time, ACP time, cardiac arrest time, the lowest rectal temperature and frequency of bilateral and unilateral antegrade selective cerebral perfusion were similar between the two groups (P>0.05). Compared with those in the control group, patients in UTI group had lower lactate, S-100 and neuron specific enolase levels on the first postoperative day and higher OI on the 1st, 3rd, and 5th postoperative days (P<0.05), but serum creatinine, blood urea nitrogen, total bilirubin, and alanine aminotransferase levels were comparable between the two groups (P>0.05). No significant differences were found in the frequency of re-operation for bleeding, ultrafiltration for renal failure, tracheotomy, neurological complications or hospital death after the operation between the two groups, but the patients in UTI group had a shorter ICU time, a less frequent long-term ventilation and a lower incidence of pulmonary infection (P<0.05).

CONCLUSIONHigh-dose ulinastatin offers protection on pulmonary function and lowers the specific brain injury markers in patients with type A aortic dissection after total arch replacement, but its protective effects on brain is uncertain.

Aneurysm, Dissecting ; surgery ; Aorta, Thoracic ; surgery ; Aortic Aneurysm, Thoracic ; surgery ; Body Temperature ; Brain ; drug effects ; Cardiopulmonary Bypass ; Cerebrovascular Circulation ; Glycoproteins ; therapeutic use ; Humans ; Incidence ; Lactic Acid ; blood ; Lung ; drug effects ; Perfusion ; Phosphopyruvate Hydratase ; blood ; Postoperative Period ; Protective Agents ; therapeutic use ; S100 Proteins ; blood ; Time Factors

The methylcytosine dioxygenases TET proteins (TET1, TET2, and TET3) play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA (valproic acid)-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neuronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demonstrated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells. Furthermore, we revealed that TET1 could positively regulate srGAP3 expression independent of its catalytic activity, and srGAP3 is required for TET-mediated neuronal differentiation of Neuro2a cells. The results presented here may facilitate better understanding of the role of TET proteins in neuronal differentiation, and provide a possible therapy target for neuroblastoma.
Animals ; Catalytic Domain ; Cell Differentiation ; drug effects ; physiology ; Cell Line, Tumor ; DNA-Binding Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Enzyme Inhibitors ; pharmacology ; GTPase-Activating Proteins ; genetics ; metabolism ; Immunohistochemistry ; Mice ; Microscopy, Fluorescence ; Neuroblastoma ; metabolism ; pathology ; Protein Isoforms ; antagonists & inhibitors ; genetics ; metabolism ; Proto-Oncogene Proteins ; antagonists & inhibitors ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; metabolism ; Valproic Acid ; pharmacology

A pot experiment was conducted to study effect of drought stress on leaf physiological characteristics and growth of one year old Stellaria dichotoma seedlings. The result showed that plant height and shoot dry weight significantly decreased with decrease in soil water content; however, root length and root dry weight increased at light drought stress and decreased at severe drought stress. The result also showed that with the decrease of soil water content, proline content in S. dichotoma leaves decreased then increase, while solube protein content decreased. Activities of SOD and POD in S. dichotoma leaves significantly decreased as soil water content decreased, while activity of CAT significantly decreased at severe drought stress. Membrane permeability in S. dichotoma leaves increased, while MDA content decreased then increased as soil water decreased. These results suggest that S. dichotoma had osmotic stress resistance ability and reactive oxygen scavenging capacity at light drought stress, which caused S. dichotoma growth was no inhibited at a certain extent drought stress.
Droughts ; Plant Leaves ; enzymology ; growth & development ; metabolism ; Plant Proteins ; metabolism ; Plant Roots ; enzymology ; growth & development ; metabolism ; Proline ; metabolism ; Seedlings ; enzymology ; growth & development ; metabolism ; Stellaria ; enzymology ; growth & development ; metabolism ; Water ; metabolism

To analyze the genetic characterization of epidemic rubella virus strains isolated in Liaoning from 2007-2012, a total of 145 rubella virus strains were isolated using Vero/Slam cell line from the patients' throat swabs during rubella outbreaks and sporadics cases in Liaoning Province from 2007 to 2012. Fragments of 945 nucleotides containing 1E gene from 145 rubella virus isolates were amplified by RT-PCR, the PCR products were sequenced and analyzed. Based on the 739 nucleotides of 1E gene, the phylogenetic trees were constructed with 32 WHO rubella reference strains of 13 genotypes downloaded from GenBank and 145 rubella virus strains. The results showed that the 145 rubella virus strains in 2007 -2012 belonged to genotype 1E, nucleotide acids and amino acids similarities were 97.2%-100.0% and 97.6%-100.0%, respectively. Compared to the 1E reference strains(Rvi/ Dezhou.CHN/02, RVi/MYS/01), the nucleotide acids and amino acids similarities were 96.6%-99.2% and 98.2%-100.0%, respectively except for one amino acid change (Val246-Ala246) of RVi/Shenyang. Liaoning. CHN/13.11/13, and Asp262-Asn262 of RVi/Shenyang. Liaoning. CHN/13.11/4 and RVi/Liaoyang. Liaoning. CHN/26. 11/2. there had no change found in the important antigenic epitope sites, the hemagglutination inhibition and neutralization epitopes of the other rubella viruses. All the 145 strains isolated had the same amino acid change (Leu338--Phe338) in E1 protein. These findings suggested that genotype 1E of rubella virus was the predominant genotype in Liaoning province. the rubella prevailed in recent six years was mainly caused by rubella viruses genotype 1E with multi-transmission routes.
Amino Acid Sequence ; China ; epidemiology ; Epidemics ; Genotype ; Humans ; Molecular Sequence Data ; Phylogeny ; Rubella ; epidemiology ; virology ; Rubella virus ; classification ; genetics ; isolation & purification ; Sequence Alignment ; Viral Envelope Proteins ; chemistry ; genetics