OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

OBJECTIVE: To explore the effect of thoracic paravertebral anesthesia (TPVB) on prognosis of patients undergoing resection of lung cancer. METHODS: This study was conducted among the patients undergoing surgical resection of primary lung cancer under general anesthesia or TPVB combined with general anesthesia (TPVB+GA) between January, 2017 and May, 2018.The patients were enrolled in TPVB+GA group and GA group (control group) using a propensity score matching (PSM) method at the ratio of 1:2 based on their baseline characteristics.The clinical parameters, 5-year overall survival (OS), progression-free survival (PFS) and intraoperative dosage of opioids were compared between the two groups to assess the impact of TPVB on prognosis of the patients. RESULTS: Forty-seven patients were enrolled in TPVB+GA group and 94 in the control group.Kaplan-Meier survival analysis showed a significantly prolonged PFS in the patients with TPVB+GA (log-rank P=0.034), with an odds ratio (OR) of 0.45(95%CI: 0.33-0.89).Consistently, univariate and multivariate Cox regression analyses identified TPVB as an independent protective prognostic factor for patients with lung cancer resection (P=0.002, OR=0.33, 95%CI: 0.16-0.66).Cox regression analyses indicated that a lower intraoperative dose of remifentanil was significantly correlated with a longer PFS of the patients following lung cancer resection (P=0.017, OR=0.47, 95%CI: 0.25-0.87).Chi-square test confirmed that TPVB, but not general anesthesia, significantly reduced intraoperative dose of remifentanil, indicating a possible synergistic effect of TPVB with opioids to affect the survival of the patients. CONCLUSION TPVB can prolong the survival time and improve the prognosis of the patients undergoing surgical resection of lung cancer.
Humans ; Remifentanil ; Pain, Postoperative ; Nerve Block/methods* ; Analgesics, Opioid ; Prognosis ; Lung Neoplasms/surgery*

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult ; Anti-HIV Agents/adverse effects* ; Antiretroviral Therapy, Highly Active ; China ; Drug Therapy, Combination ; HIV Infections/drug therapy* ; HIV-1 ; Humans ; Maleimides ; Peptides ; Ritonavir/therapeutic use* ; Treatment Outcome ; Viral Load

Objective To evaluate the risk of hepatitis B virus(HBV) infection among preschool children who were the non-responders to hepatitis B vaccine in future. Methods A prospective cohort study was conducted. Children aged 2 to 5 years were selected from 64 kindergartens.These children were inoculated three doses of hepatitis b vaccine at 0, 1 and 6 months after birth. Hepatitis B surface antigen (HBsAg)and Hepatitis B surface antibody (anti-HBs)were detected during the period from March to May 2015. The children who were HBsAg negative were enrolled in the study. The subjects were divided into exposure group (anti-HBs negative) and control group (anti-HBs positive) . The follow-up began on June 1, 2015 and ended on June 1, 2016. Serum HBsAg of children in the cohort was then collected and detected from June 1 to 30, 2016. At the end of the study, the HBsAg positive rates between two groups were compared. Results 83 children who received hepatitis B vaccine again during the follow-up period were excluded from 1 907 non-responders. The actual number in non-responders group was 1 824. 151 children were lost at the end of the study. The actual number of follow-up was 1 673 and 5 children were found to be positive for HBsAg and the infection rate was 0.30% (5/1673). In the respondent goup, 2 054 were enrolled and followed. Finally, 140 children were lost and none of the remaining 1 914 people were HBsAg positive at the end of the study. HBsAg positive rate was higher in the non-responder group than in the responder group (P=0.023). Conclusion There is a risk of HBV infection in the children who are non-responders to hepatitis B vaccine in future.

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.
Aged ; China ; epidemiology ; Chlorides ; blood ; Coronary Artery Disease ; blood ; diagnosis ; mortality ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Sodium ; blood

Objective:To explore the relationship between single nucleotide polymorphism (SNP) rs4977574 in CDKN2B-AS1 gene and female premature coronary artery disease (pCAD) occurrence. Methods: Our research included 2 groups: pCAD group, n=226 consecutive patients≤65 years of age and Control group, n=79 subjects with matched age,without CAD. The genotype of CDKN2B-AS1 SNP rs4977574 was detected by SNaPshot. Blood levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), uric acid (UA), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) were examined; relationships between rs4977574 polymorphism and the above parameters were assessed. Results: Compared to Control group, pCAD group had increased blood levels of TG, UA, FPG and HbA1c, P<0.05. With adjusted age, body mass index (BMI), relevant disease history and risk factors, elevated HbA1c (HbA1c>6.2%) obviously increased the risk of female pCAD occurrence (OR=3.35, 95%CI 1.41-8.00, P=0.006). The genotype and allele frequency of rs4977574 were different between pCAD group and Control group, P<0.05. Compared to Control group, pCAD group had the higher frequency of G allele(OR=1.24, 95%CI 1.05-1.48, P=0.019); further analysis found that rs4977574 polymorphism was related to high HbA1c. Compared to AA genotype, GG+GA genotype had the increased incidence of high HbA1c(OR=2.08, 95%CI 1.11-3.89, P=0.022). Conclusion: CDKN2B-AS1 SNP rs4977574 was related to female pCAD occurrence and it was also related to high HbA1c.

Tripterygium wilfordii has complex chemical components. To study and summarize the advance in studies on the anti-inflammatory and immunoregulatory activities and toxicology of known monomers of T. wilfordii, the pertinent literatures related to the studies on the pharmacology, toxicology and pharmacokinetics of T. wilfordii over past 30 years were searched. According to the findings, more than ten anti-inflammatory and immunoregulatory monomers were found in T. wilfordii. The pharmacology and toxicology of wilforidine, triptolidenol, triptonide, demethylzeylasteral shall be further studied.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Humans ; Immunologic Factors ; pharmacology ; Plant Extracts ; pharmacokinetics ; pharmacology ; Tripterygium ; chemistry

BACKGROUNDTraumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide. Therefore, we investigated the role of AG490 in regulating brain oedema, expression of CD40 and neurological function after TBI.

METHODSSprague Dawley rats (n = 240) were randomly divided into a sham operation group, TBI+saline group and TBI+AG490 (JAK/STAT inhibitor) group. Members of each group were euthanized at 6, 12, 24 or 72 hours after injury. Neurological severity score (NSS) was used to evaluate the severity of neurological damage. Brain water was quantitated by wet/dry weight method. The expression of CD40 was assessed by flow cytometry.

RESULTSIn both the TBI+saline group and the TBI+AG490 group, the brain water content was elevated after TBI, reached a peak at 24-hour and remained high for the rest of the period investigated; the expression of CD40 reached a peak 24 hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours. Elevations in the level of CD40, degree of brain edema and NSS after TBI were significantly reduced in TBI+AG490 group.

CONCLUSIONInhibition of the JAK/STAT signalling pathway reduces brain oedema, decreases the expression of CD40 and exerts neuroprotective effects after TBI.

Animals ; Brain Edema ; metabolism ; Brain Injuries ; drug therapy ; CD40 Antigens ; analysis ; Flow Cytometry ; Janus Kinases ; metabolism ; Male ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; STAT Transcription Factors ; metabolism ; Tyrphostins ; therapeutic use

BACKGROUNDThe synovial fluid concentrations of adiponectin are significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA). Accumulating evidence suggests that adiponectin may be an inducer of inflammation in arthritis, but the mechanism remains unclear. The objectives of this study were to compare the expression levels of adiponectin receptors in rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF), evaluate the roles of adiponectin receptors in adiponectin-induced prostaglandin E(2) (PGE(2)) production, and then investigate the effects of a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX)-2-selective inhibitor on adiponectin-induced PGE(2) release.

METHODSThe expressions of adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA and protein in synovial fibroblasts from seven patients with RA and eight patients with OA undergoing total knee replacement were evaluated by real-time polymerase chain reaction, immunofluorescence microscopy and Western blotting analysis. Adiponectin-induced PGE(2) production was detected by enzyme-linked immunosorbent assay. RNA interference against the AdipoR1 and AdipoR2 genes was performed to investigate the effects of the adiponectin receptors on adiponectin-induced PGE(2) production in both RASF and OASF.

RESULTSAdipoR1 and AdipoR2 mRNA and protein were expressed by both RASF and OASF. Compared with OASF, RASF exhibited higher levels of AdipoR1, but there was no significant difference for AdipoR2. Adiponectin induced the production of PGE(2) by the synovial fibroblasts in a concentration-dependent manner, and this was more obvious in RASF. RNA interference showed that the difference may be mediated by the diverse distribution of AdipoR1. The adiponectin-induced PGE(2) production was efficiently relieved by the NSAID and COX-2-selective inhibitor.

CONCLUSIONThe present findings suggest that AdipoR1 may mediate the difference in adiponectin-induced PGE(2) production in RASF and OASF.

Adiponectin ; pharmacology ; Arthritis, Rheumatoid ; metabolism ; Blotting, Western ; Cells, Cultured ; Dinoprostone ; metabolism ; Female ; Fibroblasts ; drug effects ; metabolism ; Humans ; Immunoassay ; Male ; Microscopy, Fluorescence ; Middle Aged ; Osteoarthritis ; metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Receptors, Adiponectin ; genetics ; metabolism ; Synovial Membrane ; cytology

OBJECTIVETo explore the effect of acupuncture-drug compound anesthesia on immune function in patients with extracorporeal circulation undergoing cardiac surgery.

METHODSThirty cases undergoing cardiac surgery which included atrial septal defect neoplasty, ventricular septal defect neoplasty, mitral valve replacement and pulmonary valve coarctotomy were randomly divided into group A and group B, 15 cases in each group. Group A was given general anesthesia plus acupuncture at Neiguan (PC 6), Lieque (LU 7) and Yunmen (LU 2), and group B was given simple general anesthesia. Tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interleukin-10 (IL-10) levels before and after surgery were compared.

RESULTSThe level of TNF-alpha was increased and the levels of IL-2 and IL-10 in the serum were decreased in both groups after extracorporeal circulation for 2 h and 24 h, and the ranges of all changes were more less in group A (all P < 0.05).

CONCLUSIONCompared with simple general anesthesia, acupuncture-drug compound anesthesia can improve immune suppression partially in the perioperative periods under the same conditions of controlling anesthesia degree.

Acupuncture Analgesia ; Adult ; Anesthesia, General ; Cardiac Surgical Procedures ; Female ; Heart Diseases ; blood ; immunology ; surgery ; Humans ; Inflammation Mediators ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Male ; Middle Aged ; Perioperative Care ; Tumor Necrosis Factor-alpha ; blood ; Young Adult