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Non-O1/non-O139 Vibrio cholerae (NOVC) are increasingly being recognized as causes of sporadic cases of gastroenteritis and extra-intestinal invasive infections, such as bacteremia as well as skin and wound infections in immunosuppressed hosts. However, oral infections caused by these microorganisms have rarely been reported. We present a case of oral infection caused by NOVC in a patient undergoing chemoradiotherapy after esophagectomy for esophageal cancer. The patient recovered well after antibiotic treatment. The isolate from the patient was screened for phenotypic and genetic characteristics with reference to their major virulence genes. Our report provides supporting evidence for oral infection due to NOVC in a patient with esophageal cancer and suggests that some putative accessory virulence factors may be crucial in the pathogenicity of this strain. To the best of our knowledge, this is the first documented case of oral infection due to NOVC.

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio may carry additional information and has been suggested as a better predictor for atherosclerosis progression and cardiovascular disease (CVD) than LDL-C and HDL-C alone. Therefore, we aim to explore the association between LDL-C/HDL-C ratio and high carotid intima-media thickness (CIMT) risk in a large Cohort in Beijing, China. This cohort study included 13,612 adults without high CIMT at first entry and who attended the baseline examination and at least one follow-up annual examination between 2009 and 2016. We used multivariable Cox regression to estimate hazard ratios (HR) with their 95% confidence intervals (CI) for the association between LDL-C/HDL-C ratio and risk of high CIMT. During 37,912 person-years of follow-up, 1996 (1268 men and 728 women) developed high CIMT. Compared with the first quartile of LDL-C/HDL-C ratio, the risk of high CIMT was significantly increased for the fourth quartile of LDL-C/HDL-C ratio (HR = 1.51, 95% CI: 1.29-1.78). We observed a significant association between LDL-C/HDL-C ratio and high CIMT risk comparing LDL-C/HDL-C ratio >2.78 with LDL-C/HDL-C ratio ≤2.78 and significant dose-response relationship between LDL-C/HDL-C ratio and risk of high CIMT. The restricted cubic spline showed a significant nonlinear association between LDL-C/HDL-C ratio and the risk of high CIMT (pnon-linearity = 0.009). We identify a significant association between LDL-C/HDL-C ratio and the risk of high CIMT in the Chinese Cohort study. Future studies are needed to evaluate the effectiveness of reducing LDL-C/HDL-C ratio treatment on the development of high CIMT.

Objective: This study aims to investigate the effect of optimized ultrafiltration on perioperative electrolytes, acid–base balance, and pulmonary function during cardiopulmonary bypass (CPB) in infants with low body weight (under 10 kg), using traditional balanced ultrafiltration and modified ultrafiltration.Methods: A total of 30 children who underwent surgical correction for congenital heart disease in Changzhou Children's Hospital between January 2018 and December 2019 were randomly divided into two groups. In the treatment group, ultrafiltration pre-treatment was carried out with blood-containing priming fluid prior to CPB. Balanced ultrafiltration was performed during the operation, and optimized and modified ultrafiltration were conducted before closing and extubation. In the control group, traditional balanced ultrafiltration was used during the operation, and a modified ultrafiltration combination was used before closing and extubation. Indexes such as blood gas analysis and electrolytes were measured perioperatively, and pulmonary function was observed.Results: No deaths were reported in either group. The ventilator-assisted breathing time was shorter in the treatment group than in the control group (P < 0.05). The indexes of the treatment group were closer than those of the control group to the optimal physiological values. The concentrations of potassium ion (K+), lactate (Lac), and blood glucose (Glu) decreased, and there was significant difference between the two groups (P < 0.05) at the end of CPB. Hemoglobin (Hb) and hematocrit (HCT) in the treatment group increased (P < 0.01). Alveolar-arterial differences for oxygen (A-aDO2) and respiratory index (RI) increased significantly in both groups after operation. Children in the treatment group began to recover lung function earlier than children in the control group. Both A-aDO2 and RI were lower in the treatment group than in the control group at each time point after operation (P < 0.05).Conclusion: Optimizing and modifying the traditional ultrafiltration combination method can effectively shorten the ultrafiltration time, reduce the adverse impacts of the ultrafiltration technique, and improve the lung function of infants after operation.

Background This comprehensive meta-analysis aimed to combine data from different studies and to estimate the association between FKBP5 polymorphisms and depression. Methods We performed a meta-analysis of observational studies. An electronic search was conducted on four databases for articles published before July 1, 2020. Results A total of 5125 patients with depression and 8399 controls from 16 independent studies were included in the analysis. The results showed that FKBP5 rs1360780 was associated with the risk of depression in the codominant model (CT vs. CC; OR = 1.10, 95% CI = 1.00-1.20, P = .04); rs4713916 polymorphism was associated with depression in the codominant model (AG vs. GG; OR = 1.19, 95% CI = 1.05-1.34, P = .008) and recessive model (AA vs. AG + GG; OR = 0.74, 95% CI = 0.56-0.99, P = .04); a significant association between rs3800373 and depression was found in the codominant genetic model (AC vs. AA; OR = 1.18, 95% CI = 1.05-1.34, P = .007) and dominant model (CC + AC vs. AA; OR = 1.15, 95% CI = 1.03-1.30, P = .02); there was no significant association of FKBP5 rs9470080 or rs9296158 with depression in any genetic model (P > .05). No publication bias was observed in our analysis. Moreover, sensitivity analyses demonstrated the Zobel's study significantly affected the heterogeneity for rs4713916 and rs3800373. Conclusions FKBP5 rs1360780 was associated with an increased risk of depression in the codominant model. We also found that rs4713916 and rs3800373 were involved in depression, rs4713916 was positively associated with depression in the codominant model and recessive model, and rs3800373 was related to an elevated risk of depression in the codominant model and dominant model.

Liping Yang,1,2 Zhaomin Liu,2 Wenhua Ling,2 Li Wang,1 Changyi Wang,1 Jianping Ma,1 Xiaolin Peng,1 Jianying Chen3 1Center for Chronic Disease Control, Nanshan, Shenzhen, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Internal Medicine Department, BaiYun Hospital, GuangZhou, GuangDong Province, People’s Republic of ChinaCorrespondence: Liping YangCenter for Chronic Disease Control, NanShan, ShenZhen 518000, People’s Republic of ChinaTel +86-755-26403300Email yanglp6@mail2.sysu.edu.cnBackground: Insulin-like growth factor binding protein-4 (IGFBP-4) fragments have been shown to be associated with cardiometabolic diseases. Anthocyanins as a subgroup of natural polyphenols could have benefits on treating cardiometabolic diseases. The aim of this study was to examine the effects of purified anthocyanins on serum IGFBP-4 fragments and glycemic control in patients with fasting hyperglycemia.Methods: A set of 121 participants with elevated fasting glucose (≥ 5.6 mmol/L), who were originally randomly assigned to anthocyanins (320 mg/day) or placebo groups, were included in this study. Serum IGFBP-4 fragments, fasting and postload glucose, insulin, and C-peptide after a three-hour oral glucose tolerance test (OGTT) were measured at baseline and at the end of 12 weeks.Results: Compared with placebo, anthocyanins increased serum IGFBP-4 fragments (net change 8.33 ng/mL, 95% CI [1.2, 15.47], p=0.023) and decreased fasting glucose (− 0.4 mmol/L [− 0.71, -0.1], p=0.01), 2-hour C-peptide (− 1.02 ng/mL [− 1.99, − 0.04], p=0.041) and the 3-hour area under the curve (AUC) of C-peptide (− 2.19 [− 4.11, − 0.27], p=0.026). No other significant difference in parameters for glycemic control and insulin resistance was observed.Conclusion: Anthocyanins supplementation for 12 weeks improved serum IGFBP-4 fragments and decreased fasting glucose and postload C-peptide in patients with fasting hyperglycemia. Further studies are needed to confirm our findings and clarify the potential mechanism.Trial Registration: ClinicalTrials.gov, NCT02689765. Registered on 6 February 2016, https://clinicaltrials.gov/ct2/show/NCT02689765.Keywords: IGFBP-4 fragments, anthocyanin, oral glucose tolerance test, insulin resistance, C-peptide

Aim The aim of this study is to investigate the sex-specific association between the ZJU index and risk of fatty liver disease in a large Chinese cohort. Methods A total of 28 729 adults without fatty liver disease at baseline and who completed at least one follow-up of annual examinations between 2009 and 2016 were included in this study. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for fatty liver disease risk associated with the ZJU index. Results During a median follow-up of 3.01 years, 7373 developed fatty liver disease. There were significant associations between the ZJU index and fatty liver disease for women and men with increasing HRs as the quartiles increase across Q2-Q4, corresponding HRs (95% CIs) in M3 were 2.28 (1.98-2.64), 3.52 (3.07-4.04), and 4.87 (4.24-5.59) for women and 2.44 (2.17-2.75), 4.18 (3.73-4.68), and 6.23 (5.56-6.98) for men. The association between the ZJU index and fatty liver disease risk remained significant in all the subgroups except that of T2DM and abdominal obesity subgroups for men. However, the association became nonsignificant when comparing Q3 and Q2 of the ZJU index with reference in the subgroups of T2DM for men, and nonsignificant when comparing Q3 of the ZJU index with reference in the subgroups of participants with T2DM and abdominal obesity for women. Conclusion The ZJU index was significantly associated with the risk of fatty liver disease in Chinese population. It will be better to keep body mass index, alanine aminotransferase, aspartate aminotransferase, triglyceride, and fasting plasma glucose at a normal level for preventing fatty liver disease.

Background Epidemiological studies have suggested that adiponectin is associated with the development of insulin resistance and type 2 diabetes. This study first examined the effect of purified anthocyanins, a group of dietary flavonoids, on serum adiponectin in patients with prediabetes and newly diagnosed diabetes. Methods A total of 160 patients with prediabetes (n = 90) or newly diagnosed diabetes (n = 70) were randomly assigned to either the anthocyanins group or the placebo group for 12 weeks of intervention. Serum adiponectin, a set of biomarkers related to glucolipid metabolism, anthropometric parameters, dietary intake and physical activity were measured before and after intervention. Results Anthocyanins increased serum adiponectin compared with placebo (net change 0.46 µg/mL, 95% CI [0.03, 0.90], p = 0.038) in the subjects with newly diagnosed diabetes. No significant difference in the change in adiponectin was observed between the two groups either in the overall subjects (0.02 µg/mL [− 0.32, 0.36], p = 0.906) or in prediabetes (− 0.35 µg/mL [− 0.85, 0.16], p = 0.174). Anthocyanins also decreased fasting glucose (− 0.5 mmol/L [− 1, − 0.04], p = 0.035) in the subjects with newly diagnosed diabetes, but no such change was observed in those with prediabetes. Conclusions Anthocyanins supplementation for 12 weeks improved serum adiponectin and fasting glucose in patients with newly diagnosed diabetes, but not in patients with prediabetes. Trial registration ClinicalTrials.gov, NCT02689765. Registered on 6 February 2016, https://clinicaltrials.gov/ct2/show/NCT02689765.

BACKGROUND The association of ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C ratio) change trajectory with risk of type 2 diabetes mellitus (T2DM) remains unknown. The aim of this study was to evaluate the association between risk of T2DM and TG/HDL-C ratio change trajectory. METHODS A total of 18 444 participants aged 18-80 years old were included in this cohort study. Linear regression and quadratic regression models were used to determine the TG/HDL-C ratio change trajectory. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TG/HDL-C ratio change trajectory and probability of T2DM. RESULTS T2DM developed in 714 participants during a median follow-up of 5.74 years (92 076.23 person-years of follow-up). After adjusting for baseline potential confounders, odds of T2DM were greater for participants with the increasing, U-shape, bell-shape, and other shape change vs decreasing change (adjusted OR [aOR] 2.01, 95% CI 1.42-2.81; 1.56, 1.15-2.13; 1.60, 1.17-2.20; and 1.49, 1.13-2.00, respectively). The results were robust in the sensitivity analyses on excluding baseline participants with T2DM. Moreover, the associations remained significant with male sex, age

Background Treatment of pulmonary tuberculosis (TB) requires at least six months and is compromised by poor adherence. In the directly observed therapy (DOT) scheme recommended by the World Health Organization, the patient is directly observed taking their medications at a health post. An alternative to DOT is video-observed therapy (VOT), in which the patients take videos of themselves taking the medication and the video is uploaded into the app and reviewed by a health care worker. We developed a comprehensive TB management system by using VOT that is installed as an app on the smartphones of both patients and health care workers. It was implemented into the routine TB control program of the Nanshan District of Shenzhen, China. Objective The aim of this study was to compare the effectiveness of VOT with that of DOT in managing the treatment of patients with pulmonary TB and to evaluate the acceptance of VOT for TB management by patients and health care workers. Methods Patients beginning treatment between September 2017 and August 2018 were enrolled into the VOT group and their data were compared with the retrospective data of patients who began TB treatment and were managed with routine DOT between January 2016 and August 2017. Sociodemographic characteristics, clinical features, treatment adherence, positive findings of sputum smears, reporting of side effects, time and costs of transportation, and satisfaction were compared between the 2 treatment groups. The attitudes of the health care workers toward the VOT-based system were also analyzed. Results This study included 158 patients in the retrospective DOT group and 235 patients in the VOT group. The VOT group showed a significantly higher fraction of doses observed (P85% of their doses observed, while only 16.4% (26/158) of the DOT patients had >85% of their doses observed. All patients were cured without recurrences. The VOT management required significantly (P Conclusions Implementation of the VOT-based system into the routine program of TB management was simple and it significantly increased patient adherence to their drug regimens. Our study shows that a comprehensive VOT-based TB management represents a viable and improved evolution of DOT.

Background The discordance of the low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with alterative lipid parameters may explain the inconsistent association of CIMT with the LDL-C/HDL-C ratio. Therefore, this study aimed to explore the associations between LDL-C/HDL-C ratio discordance with alternative lipid parameters and elevated carotid intima-media thickness (CIMT) risk in a large cohort in Beijing, China. Methods In total, 13,612 adults who didn’t have elevated CIMT at baseline and who participated in at least one follow-up of annual examination between 2009 and 2016 were included in this cohort study. A multivariable Cox regression model was utilized to evaluate the associations of discordance of the LDL-C/HDL-C ratio with TC, TGs, LDL-C and HDL-C with elevated CIMT risk. Results During 37,999 person-years of follow-up, 2004 individuals (1274 men and 730 women) developed elevated CIMT. Among individuals with normal TC and TGs, 16.6 and 15.2% individuals had a discordantly high LDL-C/HDL-C ratio, respectively, and the risk of elevated CIMT increased by 1.54 (95% CI 1.33, 1.77) and 1.53 (95% CI 1.33, 1.76), respectively, comparing to individuals with a concordantly low LDL-C/HDL-C ratio. A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with LDL-C and HDL-C (P Conclusions A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with TC, TGs, LDL-C and HDL-C Even a low LDL-C/HDL-C ratio with discordantly high LDL-C and normal HDL-C could also significantly increase CIMT risk. Individuals should maintain both the LDL-C/HDL-C ratio and LDL-C at normal levels to prevent elevated CIMT.

The MTHFR gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) – a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the MTHFR promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age- and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect MTHFR promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, MTHFR promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic (ROC) curve to determine whether MTHFR promoter methylation levels can predict IS. The mean MTHFR methylation levels in case group (8.10 ± 6.14) were significantly lower than those in control group (17.44 ± 3.16; p < 0.05). MTHFR promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels

BACKGROUND The study aimed to investigate the associations of baseline serum albumin level and its dynamic change with type 2 diabetes mellitus (T2DM) risk in a large Chinese cohort study. METHODS This cohort study included 30 442 adults without T2DM at first entry, who completed at least one follow-up of annual examinations between 2009 and 2016. Serum albumin level was measured at baseline and at every annual check-up. The dynamic change in serum albumin level (∆ALB) was calculated by subtracting serum albumin level at baseline from that at the last follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox regression models. RESULTS During 7 years of follow-up, we identified 1634 T2DM events. From the lowest to the highest quartile of serum albumin level, adjusted HRs (95% CI) were 1.00 (reference), 0.96 (0.94, 1.01), 0.98 (0.95, 1.02) and 0.88 (0.85, 0.98), respectively. As compared with stable change in serum albumin (-0.2 ≤ ∆ALB

In mainland China, the clinical, epidemiological and genetic features of non-O1/non-O139 Vibrio cholerae (NOVC) bacteraemia have been scarcely investigated. Herein, we describe a patient with NOVC bacteraemia diagnosed in our hospital and present a retrospective analysis of literature reports of 32 other cases in China, detailing the clinical epidemiology, antibiotic resistance and molecular characteristics of isolates. Most patients were male (84.8%; median age, 53 years) and had predisposing factors, such as cirrhosis, malignant tumours, blood diseases and diabetes. In addition to fever, gastroenteritis was the most frequent presenting symptom. The mortality rate during hospitalisation was 12.1%. NOVC bacteraemia cases were more common in June–August, with the majority in coastal provinces and the Yangtze River basin. Only 42.4% of cases were attributed to consumption of marine (aquatic) products. Tetracycline, third-generation cephalosporins, and fluoroquinolones were the most effective antimicrobial agents, and the highest frequencies of resistance were recorded for ampicillin/sulbactam (37.5%), amoxicillin/clavulanic acid (33.3%), ampicillin (29.2%) and sulfamethoxazole (20%). Multi-drug resistant isolates were not detected. Limited data indicate that ctxAB and tcpA genes were absent in all NOVC isolates but other putative virulence genes (hlyA, toxR, hap and rtxA) were common. Ten multilocus sequence types were identified with marked genetic heterogeneity between different isolates. As clinical manifestations of NOVC bacteraemia may vary widely, and isolates exhibit genetic diversity, clinicians and public health experts should be alerted to the possibility of infection with this pathogen because of the high prevalence of liver disease in China.

Background. Conflicting findings have been reported regarding the sex-specific association between serum uric acid (SUA) level and type 2 diabetes mellitus (T2DM) risk, and no study has explored the association between the change in hyperuricemia status and T2DM risk. The study was aimed at exploring the sex-specific association of baseline SUA and changes in hyperuricemia status with T2DM risk. Methods. We included 37,296 eligible adults without T2DM at the first examination who attended the baseline examination and at least one follow-up annual examination. Cox and logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) for T2DM risk associated with baseline SUA and the change in hyperuricemia status, respectively. Results. During a median follow-up of 3.09 years, of 37,296 eligible adults, 2,263 developed T2DM. Compared with the first SUA quartile, higher quartiles were associated with an increased risk of T2DM in women (HR 1.78, 95% CI 1.17-2.71 for Q3 and 1.93, 1.27-2.93 for Q4; Ptrend<0.001) but not in men. Compared with women with a persistent normal SUA level at baseline and the last follow-up, T2DM risk increased significantly among those whose SUA status changed from normal at baseline to hyperuricemia at the last follow-up (OR 1.71, 95% CI 1.12-2.55) and those with persistent hyperuricemia at baseline and the last follow-up (OR 2.37, 95% CI 1.60-3.46). However, for men, a nonsignificant association was found between the change in hyperuricemia status and T2DM risk. Conclusions. Baseline SUA and the change in hyperuricemia status were associated with T2DM risk only among women. The findings suggest the importance of monitoring SUA levels and maintaining them within a normal range for preventing or reducing incident T2DM in Chinese women.

Activation of HIV-1 reservoirs and induction of anti-HIV-1 T cells are critical to control HIV-1 rebound after combined antiretroviral therapy (cART). Here we evaluated in humanized mice (hu-mice) with persistent HIV-1 infection the therapeutic effect of TLR3 agonist and a CD40-targeting HIV-1 vaccine, which consists of a string of 5 highly conserved CD4+ and CD8+ T cell epitope-rich regions of HIV-1 Gag, Nef, and Pol fused to the C-terminus of a recombinant anti-human CD40 antibody (αCD40.HIV5pep). We show that αCD40.HIV5pep vaccination coadministered with poly(I:C) adjuvant induced HIV-1-specific human CD8+ and CD4+ T cell responses in hu-mice. Interestingly, poly(I:C) treatment also reactivated HIV-1 reservoirs. When administrated in therapeutic settings in HIV-1-infected hu-mice under effective cART, αCD40.HIV5pep with poly(I:C) vaccination induced HIV-1-specific CD8+ T cells and reduced the level of cell-associated HIV-1 DNA (or HIV-1 reservoirs) in lymphoid tissues. Most strikingly, the vaccination significantly delayed HIV-1 rebound after cART cessation. In summary, the αCD40.HIV5pep with poly(I:C) vaccination approach both activates replication of HIV-1 reservoirs and enhances the anti-HIV-1 T cell response, leading to a reduced level of cell-associated HIV-1 DNA or reservoirs. Our proof-of-concept study has significant implication for the development of CD40-targeting HIV-1 vaccine to enhance anti-HIV-1 immunity and reduce HIV-1 reservoirs in patients with suppressive cART.

The city of Shenzhen has recently experienced extraordinary economic growth accompanied by a huge internal migrant influx. We investigated the local dynamics of tuberculosis (TB) epidemiology in the Nanshan District of Shenzhen to provide insights for TB control strategies for this district and other rapidly developing regions in China. We analyzed the age-specific incidence and number of TB cases in the Nanshan District from 2011 to 2016. Over all, the age-standardized incidence of TB decreased at an annual rate of 3.4%. The incidence was lowest amongst the age group 0–14 and showed no increase in this group over the six-year period (P = 0.587). The fastest decreasing incidence was among the 15–24 age group, with a yearly decrease of 13.3% (β = 0.867, P β = 1.131, P

Hyponatremia is the most common electrolyte disorder in hospitals. Many medical illnesses, including congestive heart failure, liver failure, renal failure and pneumonia, may be associated with hyponatremia. In addition, hyponatremia in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) was first reported in 1993. The evidence suggests that severe hyponatremia is associated with increased morbidity and mortality in human immunodeficiency virus (HIV)/AIDS patients; however, the incidence of hyponatremic syndrome in HIV/AIDS patients remains very high in clinical practice, as almost 40% of HIV/AIDS inpatients in Xinjiang, a developing region of China, are hyponatremic. A method for identifying the pathogenesis and therapeutic treatments for hyponatremia in HIV/AIDS patients is needed. This review focuses on the clinical and pathophysiological aspects of hyponatremia and highlights the causes, presentation and treatment recommendations for hyponatremic patients with HIV/AIDS.

Background The treatment failure and reinfection rates among syphilis patients are high, and relevant studies in China are limited. The aim of this study was to detect the rates of treatment failure and reinfection after syphilis treatment and to explore the potential associated factors. Methods We conducted a longitudinal cohort study in a sexually transmitted disease clinic, the Department of Dermatology and Venereology in Nanshan Center for Chronic Disease Control. Serological testing was performed at baseline and throughout the 2-year follow-up for syphilis patients. To identify potential predictors of treatment outcomes, multivariate logistics analyses were utilized to compare the demographic and clinical characteristics of patients with serological failure/reinfection to those with serological cure/serofast. Results From June 2011 to June 2016, a total of 1133 patients were screened for syphilis. Among the 770 patients who completed the 2-year follow-up, 510 first-diagnosed patients were included in the final analysis. Multivariate logistics analysis revealed the stage of syphilis (secondary syphilis VS. primary syphilis: adjusted odds ratio, 3.50; 95% confidence interval, 1.11-15.47; p = 0.04), HIV status (positive VS. negative: adjusted odds ratio, 3.06; 95% confidence interval, 1.15-8.04; p = 0.02) and frequency of condom use (always use VS. never use: adjusted odds ratio, 0.28; 95% confidence interval 0.08-0.75; p = 0.02) were significantly associated with the serological outcome. Conclusions The clinical implications of our findings suggest that it is very important to perform regular clinical and serologic evaluations after treatment. Health counseling and safety education on sex activity should be intensified among HIV-infected patients and secondary syphilis patients after treatment.

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUCkidney/AUCplasma = 0.586 ± 0.072), clearly indicating that nanopar...

In biological research, alignment of protein sequences by computer is often needed to find similarities between them. Although results can be computed in a reasonable time for alignment of two sequences, it is still very central processing unit (CPU) time-consuming when solving massive sequences alignment problems such as protein database search. In this paper, an optimized protein database search method is presented and tested with Swiss-Prot database on graphic processing unit (GPU) devices, and further, the power of CPU multi-threaded computing is also involved to realize a GPU-based heterogeneous parallelism. In our proposed method, a hybrid alignment approach is implemented by combining Smith–Waterman local alignment algorithm with Needleman–Wunsch global alignment algorithm, and parallel database search is realized with compute unified device architecture (CUDA) parallel computing framework. In the experiment, the algorithm is tested on a lower-end and a higher-end personal computers equipped with GeForce GTX 750 Ti and GeForce GTX 1070 graphics cards, respectively. The results show that the parallel method proposed in this paper can achieve a speedup up to 138.86 times over the serial counterpart, improving efficiency and convenience of protein database search significantly.

Despite the efficient suppression of HIV-1 replication that can be achieved with combined antiretroviral therapy (cART), low levels of type I interferon (IFN-I) signaling persist in some individuals. This sustained signaling may impede immune recovery and foster viral persistence. Here we report studies using a monoclonal antibody to block IFN-α/β receptor (IFNAR) signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. We discovered that effective cART restored the number of human immune cells in HIV-1-infected hu-mice but did not rescue their immune hyperactivation and dysfunction. IFNAR blockade fully reversed HIV-1-induced immune hyperactivation and rescued anti-HIV-1 immune responses in T cells from HIV-1-infected hu-mice. Finally, we found that IFNAR blockade in the presence of cART reduced the size of HIV-1 reservoirs in lymphoid tissues and delayed HIV-1 rebound after cART cessation in the HIV-1-infected hu-mice. We conclude that low levels of IFN-I signaling contribute to HIV-1-associated immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a potential strategy to enhance immune recovery and reduce HIV-1 reservoirs in individuals with sustained elevations in IFN-I signaling during suppressive cART.

This study aims to investigate the association between serum creatinine and risk of type 2 diabetes mellitus (T2DM) based on a cohort analysis and meta-analysis of cohort studies.We enrolled 41 439 participants aged ≥18 years without T2DM at baseline, who had ≥2 health examinations based on an ongoing prospective cohort in Beijing. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs. For the meta-analysis, cohort studies reporting risk estimates for the serum creatinine-T2DM association were included. A random-effects model was used to calculate summary relative risks (RRs) and restricted cubic splines to model the dose-response association.During a mean follow-up of 3.54 years, 1867 developed T2DM. Low serum creatinine was associated with increased risk of T2DM; adjusted HRs (95% CIs) across sex-specific quartiles were 1.45 (1.24, 1.71), 1.19 (1.02, 1.39), 1.07 (0.92, 1.24), and 1.00 (reference). The association was significant for both sexes and individuals with overweight or obesity. In the meta-analysis of six cohort studies (including the current study) involving 115 767 participants and 5370 T2DM events, the pooled RR was 1.61 (95% CI 1.35, 1.92), comparing the lowest with the highest category of serum creatinine. We found a linear association between serum creatinine and T2DM risk (PThe cohort study and meta-analysis provide further evidence supporting the negative association between serum creatinine and T2DM risk in a linear dose-response pattern.背景: 本研究旨在通过队列研究和纳入队列研究的meta分析, 探讨血肌酐与2型糖尿病(Type 2 diabetes mellitus, T2DM)风险之间的关联。 方法: 本研究纳入了41439名年龄≥18岁, 在基线时未患有T2DM, 且进行了2次以上健康体检在北京的参与者。采用Cox比例风险回归来估计风险比(hazard ratios, HRs)和95%置信区间(confidence intervals, CIs)。Meta分析纳入的研究为报道血肌酐与T2DM关联的风险估计的队列研究。采用随机效应模型估计相对危险度(Relative risk, RR), 限制性立方样图拟合剂量-反应关系。 结果: 在平均3.54年的随访中, 有1867例T2DM新发病例。血肌酐过低明显增加了患T2DM的风险；性别特定的四分位数(Q1-Q4)的校正HR(95% CI)为1.45(1.24, 1.71), 1.19(1.02, 1.39), 1.07(0.92, 1.24)和1.00(参照组)。该关联在不同性别和超重/肥胖者中均显着相关。Meta分析共纳入6项队列研究(包括本研究), 共包含115,767名参与者和5,370例T2DM病例。将最低与最高的血肌酐水平进行比较, RR为1.61(95% CI 1.35, 1.92)。血肌酐和T2DM风险之间呈线性关联(P

Combination antiretroviral therapy (cART) effectively suppresses HIV-1 replication and enables HIV‑infected individuals to live long, productive lives. However, the persistence of HIV-1 reservoirs of both T and myeloid cells with latent or low-replicating HIV-1 in patients under cART makes HIV-1 infection an incurable disease. Recent studies have focused on the development of strategies to activate and purge these reservoirs. Bromodomain and extraterminal domain proteins (BETs) are epigenetic readers involved in modulating gene expression. Several bromodomain inhibitors (BETi) are reported to activate viral transcription in vitro in HIV-1 latency cell lines in a P-TEFb (CDK9/cyclin T1)-dependent manner. Little is known about BETi efficacy in activating HIV-1 reservoir cells under cART in vivo. Here we report that a BETi (I-BET151) efficiently activated HIV-1 reservoirs under effective cART in humanized mice in vivo. Interestingly, I-BET151 during suppressive cART in vivo activated HIV-1 gene expression only in monocytic cells and not in CD4+ T cells. We further demonstrate that BETi preferentially enhanced HIV-1 gene expression in monocytic cells rather than in T cells and that whereas CDK9 was involved in activating HIV-1 by I-BET151 in both monocytic and T cells, CDK2 enhanced HIV-1 transcription in monocytic cells but inhibited it in T cells. Our findings reveal a role for CDK2 in differential modulation of HIV-1 gene expression in myeloid cells and in T cells and provide a novel strategy to reactivate monocytic reservoirs with BETi during cART. IMPORTANCE Bromodomain inhibitors have been reported to activate HIV-1 transcription in vitro, but their effect on activation of HIV-1 reservoirs during cART in vivo is unclear. We found that BETi (I-BET151) treatment reactivated HIV-1 gene expression in humanized mice during suppressive cART. Interestingly, I-BET151 preferentially reactivated HIV-1 gene expression in monocytic cells, but not in CD4 T cells, in cART-treated mice. Furthermore, I-BET151 significantly increased HIV-1 transcription in monocytic cells, but not in HIV-1-infected CD4 T cells, via CDK2-dependent mechanisms. Our findings suggest that BETi can preferentially activate monocytic HIV-1 reservoir cells and that a combination of reservoir activation agents targeting different cell types and pathways is needed to achieve reactivation of different HIV-1 reservoir cells during cART.

IntroductionBrachial-ankle pulse wave velocity (ba-PWV), as a simple and easily measured marker of arterial stiffness, has not been prospectively explored for its role in type 2 diabetes mellitus (T2DM) risk among the general population. This study aimed to explore the association between baseline ba-PWV value and new-onset T2DM among Chinese adults.Research design and methodsUsing data from Xiaotangshan Hospital, we conducted a prospective cohort study among those who underwent annual or biennial health check-up examinations and who had their ba-PWV measured from 2009 to 2016. We explored the risk of new-onset T2DM across ba-PWV tertiles using Cox proportional-hazards regression analysis.ResultsOf 6122 adults (68.9% male; mean age: 51.0 (SD 13.0) years) without T2DM and with ba-PWV measured at baseline, 599 participants developed T2DM during an average of 3.8 (SD 2.3) years of follow-up. After multivariable adjustment, ba-PWV was positively related to T2DM risk (p for trend=0.008). Compared with the lowest ba-PWV tertile, the HRs and their 95% CIs were 1.57 (1.18 to 2.10) for the second and 1.66 (1.24 to 2.22) for the third tertile. The risk across ba-PWV tertiles increased steadily from 1000 cm/s to 1400 cm/s and then reached a plateau. Subgroup analyses indicated a significantly higher risk among those aged ConclusionsOur findings suggest that ba-PWV might be a useful and independent predictor of new-onset T2DM with ba-PWV ranging between 1000 cm/s and 1400 cm/s, especially among younger individuals and current smokers.

ObjectiveMetabolic syndrome (MetS) is a notable risk factor of coronary heart disease (CHD). However, there are differences in the methods used to define MetS. The purpose of this study was to determine which MetS definition most fully reflects the 10-year probability of CHD based on the Framingham risk algorithm.DesignCross-sectional study.SettingData were obtained from the China Health and Nutrition Survey and the Influencing Factors of Chronic Diseases Survey conducted among residents of Nanshan District in Shenzhen, China.ParticipantsIn total, 1721 participants aged 20–80 years were included in this study.MethodsMetS was diagnosed according to the criteria of the National Cholesterol Education Program’s Adult Treatment Panel (revised NCEP-ATP III), the International Diabetes Federation (IDF) and the Chinese Diabetes Society (CDS). The NCEP-ATP III algorithm was used to calculate the Framingham risk score, and the Framingham risk score was used to define the probability of developing CHD within 10 years either as low (20%). Chi-square tests with or without the Bonferroni correction were used to compare the differences in the distribution of the 10-year estimated risk of developing CHD among the three definitions.ResultsCompared with the other definitions, the revised NCEP-ATP III criteria identified more participants (30.96%, 95% CI 28.8% to 33.2%) as having MetS, while the CDS criteria showed the highest 10-year probability of developing CHD. The 10-year probability of developing CHD in the participants with MetS was significantly higher than that in the participants without MetS (CDS: χ2=157.65, revised ATP III: χ2=45.17, IDF: χ2=306.15, all p2=72.83; IDF: χ2=63.60; CDS: χ2=23.84; all pConclusionsThis study demonstrates the differences in the prevalence and distribution of the 10-year estimated risk of developing CHD based on the definition of MetS. A significant finding of this study is that the MetS definitions have better performance for men than for women. Further studies in China, especially longitudinal studies, are needed to determine which definition of MetS is best suited for predicting CHD risk.

The combination antiretroviral therapy (cART) effectively suppresses HIV-1 infection and enables HIV-infected individuals to live long productive lives. However, the persistence of HIV-1 reservoir cells with latent or low-replicating HIV-1 in patients under cART make HIV-1 infection an incurable disease. Recent studies have focused on the development of strategies such as epigenetic modulators to activate and purge these reservoirs. Bromodomain inhibitors (BETi) are epigenetic modulating compounds able to activate viral transcription in HIV-1 latency cell lines in a positive transcription elongation factor b (P-TEFb)-dependent manner. Little is known about the efficacy of activating HIV-1 reservoir cells under cART by BETi in vivo. In this study, we seek to test the potential of a BETi (I-BET151) in activating HIV-1 reservoir cells under effective cART in humanized mice in vivo. We discover that I-BET151 efficiently activates HIV-1 transcription in monocytic cells, but not in CD4+T cells, during suppressive cART in vivo. We further reveal that HIV-1 proviruses in monocytic cells are more sensitive to I-BET151 treatment than in T cells in vitro. Finally, we demonstrate that I-BET151-activated viral transcription in monocytic cells is dependent on both CDK2 and CDK9, whereas only CDK9 is involved in activation of HIV-1 by I-BET151 in T cells. Our findings indicate a role of myeloid cells in HIV-1 persistence, and highlights the limitation of measuring or targeting T cell reservoirs alone in terms of HIV-1 cure, as well as provides a potential strategy to reactivate monocytic reservoirs during cART.IMPORTANCEIt has been reported the low level of active P-TEFb critically contributes to the maintenance of HIV-1 latency or low-replication in HIV-1 reservoir cells under cART. Bromodomain inhibitors are used to activate HIV-1 replication in vitro but their effect on activation of the HIV-1 resevoirs with cART in vivo is not clear. We found that BETi (I-BET151) treatment reactivated HIV-1 gene expression in humanized mice during suppressive cART. Interestingly, I-BET151 preferentially reactivated HIV-1 gene expression in monocytic cells, but not in CD4 T cells. Furthermore, I-BET151 significantly increased HIV-1 transcription in monocytic cells, but not in latently infected CD4 T cells, via CDK2-dependent mechanisms. Our findings suggest that BETi can preferentially activate monocytic HIV-1 reservoir cells, and a combination of latency reversal agents targeting different cell types and pathways is needed to achieve reactivation of different HIV-1 reservoir cells during cART.

Immunodeficient mice reconstituted with human immune tissues and cells (humanized mice) are relevant and robust models for the study of HIV-1 infection, immunopathogenesis, and therapy. In this study, we performed a comprehensive comparison of human immune reconstitution and HIV-1 infection, immunopathogenesis and therapy between immunodeficient NOD/Rag2−/−/γc−/− (NRG) mice transplanted with human HSCs (NRG-hu HSC) and mice transplanted with HSCs and thymus fragments (NRG-hu Thy/HSC) from the same donors. We found that similar human lymphoid and myeloid lineages were reconstituted in NRG-hu HSC and NRG-hu Thy/HSC mice, with human T cells more predominantly reconstituted in NRG-hu Thy/HSC mice, while NRG-hu HSC mice supported more human B cells and myeloid cells reconstitution. HIV-1 replicated similarly and induced similar T cell depletion, immune activation, and dysfunction in NRG-hu HSC and NRG-hu Thy/HSC mice. Moreover, combined antiretroviral therapy (cART) inhibited HIV-1 replication efficiently with similar persistent HIV-1 reservoirs in both models. Finally, we found that blocking type-I interferon signaling under cART treatment transiently activated HIV-1 reservoirs, enhanced T cell recovery and reduced HIV-1 reservoirs in both HIV-1 infected NRG-hu HSC and NRG-hu Thy/HSC mice. In summary, we report that NRG-hu Thy/HSC and NRG-hu HSC mice support similar HIV-1 infection and similar HIV-1 immunopathology; and HIV-1 replication responds similarly to cART and IFNAR blockade therapies. The NRG-hu HSC mouse model reconstituted with human HSC only is sufficient for the study of HIV-1 infection, pathogenesis, and therapy.

To identify transmitted and acquired HIV-1 drug resistance mutations in Xinjiang, China, we collected the peripheral blood of 50 treated and 50 treatment-naive HIV-1-infected individuals in this region. We successfully amplified 36 reverse transcriptase and 42 protease gene sequences of HIV-1 from 51 individuals and identified mutations associated with resistance to reverse transcriptase (RT) and protease (PR) inhibitors (RTIs and PIs) according to Stanford Drug Resistance Database. Among the drug-treated individuals, the results showed that K103N in the RT region was the most frequent mutation, found in 67% (6/9) of the cases, followed by M184V with 56% (5/9). Five individuals had both nucleoside and non-nucleoside reverse transcriptase inhibitor resistance mutations after more than 12 months of treatment. Among the untreated individuals, 33% (9/27) were found to harbor drug resistance mutations in the RT gene. K103N occurred at the highest rate, accounting for 22% (6/27), followed by P225H (7%) and Y188L (4%). Neither of the two groups showed any major resistance mutations to PIs. Our study revealed that the prevalence of drug resistance was relatively high in Xinjiang and that K103N occurred at the highest rate. These results suggest that it is important to carry out HIV drug resistance testing, especially for the K103N mutation in the RT region, before and during the treatment process. This study may help to guide ART strategies in the Xinjiang region.

The direct link between sustained type I interferon (IFN-I) signaling and HIV-1–induced immunopathogenesis during chronic infection remains unclear. Here we report studies using a monoclonal antibody to block IFN-α/β receptor 1 (IFNAR1) signaling during persistent HIV-1 infection in humanized mice (hu-mice). We discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. Thus, IFN-Is suppress HIV-1 replication during the chronic phase but are not essential for HIV-1–induced aberrant immune activation. Surprisingly, IFNAR blockade rescued both total human T cell and HIV-specific T cell numbers despite elevated HIV-1 replication and immune activation. We showed that IFNAR blockade reduced HIV-1–induced apoptosis of CD4+ T cells. Importantly, IFNAR blockade also rescued the function of human T cells, including HIV-1–specific CD8+ and CD4+ T cells. We conclude that during persistent HIV-1 infection, IFN-Is suppress HIV-1 replication, but contribute to depletion and dysfunction of T cells.

OBJECTIVES: The aim of this study was to compare the expression levels of serum miRNAs in diabetic retinopathy and type 2 diabetes mellitus. METHODS: Serum miRNA expression profiles from diabetic retinopathy cases (type 2 diabetes mellitus patients with diabetic retinopathy) and type 2 diabetes mellitus controls (type 2 diabetes mellitus patients without diabetic retinopathy) were examined by miRNA-specific microarray analysis. Quantitative real-time polymerase chain reaction was used to validate the significantly differentially expressed serum miRNAs from the microarray analysis of 45 diabetic retinopathy cases and 45 age-, sex-, body mass index- and duration-of-diabetes-matched type 2 diabetes mellitus controls. The relative changes in serum miRNA expression levels were analyzed using the 2-ΔΔCt method. RESULTS: A total of 5 diabetic retinopathy cases and 5 type 2 diabetes mellitus controls were included in the miRNA-specific microarray analysis. The serum levels of miR-3939 and miR-1910-3p differed significantly between the two groups in the screening stage; however, quantitative real-time polymerase chain reaction did not reveal significant differences in miRNA expression for 45 diabetic retinopathy cases and their matched type 2 diabetes mellitus controls. CONCLUSION: Our findings indicate that miR-3939 and miR-1910-3p may not play important roles in the development of diabetic retinopathy; however, studies with a larger sample size are needed to confirm our findings.

Objective—A child safety restraint (CSR) is an effective measure to reduce the risk of child injury from traffic collisions. This study aims to explore knowledge, attitudes and behaviors regarding CSR in a Chinese population. Methods—A cross-sectional survey regarding CSR use was conducted from April to May 2014 in Shenzhen Municipality. Respondents were parents who had at least one child 0 to 6 years of age and simultaneously owned a car. These parents provided a self-report of demographic characteristics as well as information about their knowledge, attitudes and behaviors toward CSR use. Results—Most respondents had a fair level of knowledge about CSR with higher mean knowledge scores demonstrated among the respondents who were male, had an advanced degree, a higher income, owned an expensive car, had an older child, drove frequently with children and routinely drove greater distances with children. Meanwhile, most respondents had a more positive attitude toward CSR use with a higher mean attitude score among those who had an advanced degree, owned an expensive car, drove frequently with children and routinely drove a greater distance with children. However, some myths regarding CSR use also existed (e.g., parents can effectively protect their children in a car collision by holding them, they are not required to purchase the CSR for child safety if there is no mandatory provision by law, among others). Among 3768 respondents who had at least one child and a car, 27.8% (1047) had a CSR, and 22.9% (864) used the CSR. A logistic regression model showed the likelihood of CSR ownership to be higher if respondents drove frequently or greater distances and was dependent on both the educational level of the respondents and the age of the children. The frequency of CSR use increased as the age of children decreased (P = 0.0274). The respondents with CSR ownership and those with frequent use of CSR had higher mean knowledge and mean attitude scores. Conclusions—This observational study found that although the majority of respondents had fair levels of knowledge and positive attitudes, they had lower rates of CSR ownership and use. Therefore, efforts at developing opportunities to expand public awareness of CSR use should be made to improve child passenger safety practices and eliminate child injury caused by traffic collisions.

OBJECTIVES: Cystathionine β-synthase is a major enzyme in the metabolism of plasma homocysteine. Hyperhomocysteinemia is positively associated with hypertension and stroke. The present study was performed to examine the possible effects of Cystathionine β-synthase promoter methylation on the development of hypertension and stroke. METHODS: Using quantitative methylation-specific PCR, we determined the Cystathionine β-synthase methylation levels in 218 healthy individuals and 132 and 243 age- and gender-matched stroke and hypertensive patients, respectively. The relative changes in Cystathionine β-synthase promoter methylation were analyzed using the 2- ΔΔCt method. The percent of the methylated reference of Cystathionine β-synthase was used to represent the Cystathionine β-synthase promoter methylation levels. RESULTS: In this study, the Cystathionine β-synthase promoter methylation levels of hypertensive and stroke participants were both higher than that of the healthy individuals (median percentages of the methylated reference were 50.61%, 38.05% and 30.53%, respectively, all p

Summary Aims Hyperhomocysteinemia (HHcy) is known to increase the risk of many diseases. Factors influencing HHcy in healthy and hypertensive subjects remain under-researched. Methods A large population-based study was conducted in 60 communities from Shenzhen, China. Responses to standardized questions on lifestyle factors and blood samples were collected from all participants after a 12-h overnight fast. Multiple linear and multivariate logistic regressions were used to explore risk factors for HHcy. Results were then compared to those from a systematic review of English-language articles listed in Pubmed, EBSCOhost, Web of Science, Embase and Cochrane libraries that investigated HHcy risk factors in healthy and hypertensive subjects. Results A total of 1586 healthy (Male/Female = 642/944) and 5935 hypertensive subjects (Male/Female = 2928/3007) participated in our population-based study. In logistic regression analyses, age, BMI and creatinine (Cr) were risk factors, while being female, fruit intake and physical activity were protective factors for HHcy in healthy subjects. In hypertensive subjects, seven [age, smoking, salt intake, systolic blood pressure (SBP), uric acid, triglycerides (TG), and Cr] and four [female, fruit intake, total cholesterol (TC), and glucose] factors were associated with higher and lower HHcy respectively. The review of 71 studies revealed that potential risk factors for Hcy included nutritional, physiologic, lifestyle habits, ethnicity, genetics, interactions between gene–environment, gene–gene, gene–nutritional, environment–environment, nutritional–nutritional. Conclusion Our study indicates the potential importance of increasing folic acid and vitamin B supplementation, daily fruit and vegetable intake, regular exercise and refraining from tobacco smoking and alcohol consumption as preventive strategies for Hcy.