Association of plasma advanced glycation end-products and their soluble receptor with type 2 diabetes among Chinese adults.

AIMS: Population-based evidence regarding circulating advanced glycation end-products (AGEs) and the risk of type 2 diabetes (T2D) is conflicting and insufficient. We aimed to examine the association of plasma AGEs and plasma soluble receptors for AGEs (sRAGE) with T2D. MATERIALS AND METHODS: We conducted a hospital-based case-control study including 1072 pairs (53.9 ± 9.7 years, 56.0% male) of newly diagnosed T2D and age- and sex-matched controls. We further performed a nested case-control study within an ongoing prospective cohort consisting of 127 incident T2D cases and 381 well-matched controls (62.2 ± 5.1 years, 71.7% male). Plasma AGEs were detected using liquid chromatography-tandem mass spectrometry, and plasma sRAGE was measured by enzyme-linked immunosorbent assay. Conditional logistic regression was used to evaluate the association of plasma AGEs and sRAGE concentrations with T2D. RESULTS: Higher plasma AGEs and lower sRAGE concentrations were associated with higher odds of T2D. The multivariable-adjusted odds ratios of T2D comparing the highest with the lowest quartile levels were 3.28 (95% CI: 2.14, 5.02) for plasma AGEs and 0.25 (95% CI: 0.16, 0.39) for plasma sRAGE. Participants in the highest quartile of plasma AGEs and the lowest quartile of sRAGE concentrations had the greatest odds of T2D. The positive association of AGEs and inverse association of sRAGE with T2D risk was confirmed in the replication-nested case-control study. CONCLUSIONS: Increased circulating AGEs and decreased sRAGE concentrations were associated with elevated T2D risk. Our findings may have implications for the strategies of T2D prevention and management.

Low frequency of repetitive trans-spinal magnetic stimulation promotes functional recovery after spinal cord injury in mice through inhibiting TGF-ß1/Smad2/3 signaling pathway.

Spinal cord injury (SCI) remains a worldwide challenge due to limited treatment strategies. Repetitive trans-spinal magnetic stimulation (rTSMS) is among the most cutting-edge treatments for SCI. However, the mechanism underlying rTSMS on functional recovery is still unclear. In this study, 8-week-old C57BL/6J female mice were used to design SCI models followed by treatment with monotherapy (1 Hz rTSMS or LY364947) or combination therapy (rTSMS + LY364947). Our results showed obvious functional recovery after monotherapies compared to untreated mice. Immunofluorescence results demonstrated that rTSMS and LY364947 modulate the lesion scar by decreasing fibrosis and GFAP and possess the effect on neural protection. In addition, rTSMS suppressed inflammation and the activation of TGFß1/Smad2/3 signaling pathway, as evidenced by markedly reduced TGF-ßRⅠ, Smad2/3, and p-Smad2/3 compared with untreated mice. Overall, it was confirmed that 1 Hz rTSMS promotes SCI recovery by suppressing the TGFß1/Smad2/3 signaling, revealing a novel pathological mechanism of 1 Hz rTSMS intervention, and may provide potential targets for clinical treatment.

High-fat diet induces sarcopenic obesity in natural aging rats through the gut-trimethylamine N-oxide-muscle axis.

INTRODUCTION: The lack of suitable animal models for sarcopenic obesity (SO) limits in-depth research into the disease. Emerging studies have demonstrated that gut dysbiosis is involved in the development of SO. As the importance of microbial metabolites is starting to unveil, it is necessary to comprehend the specific metabolites associated with gut microbiota and SO. OBJECTIVES: We aimed to investigate whether high-fat diet (HFD) causes SO in natural aging animal models and specific microbial metabolites that are involved in linking HFD and SO. METHODS: Young rats received HFD or control diet for 80 weeks, and obesity-related metabolic disorders and sarcopenia were measured. 16S rRNA sequencing and non-targeted and targeted metabolomics methods were used to detect fecal gut microbiota and serum metabolites. Gut barrier function was evaluated by intestinal barrier integrity and intestinal permeability. Trimethylamine N-oxide (TMAO) treatment was further conducted for verification. RESULTS: HFD resulted in body weight gain, dyslipidemia, impaired glucose tolerance, insulin resistance, and systemic inflammation in natural aging rats. HFD also caused decreases in muscle mass, strength, function, and fiber cross-sectional area and increase in muscle fatty infiltration in natural aging rats. 16S rRNA sequencing and nontargeted and targeted metabolomics analysis indicated that HFD contributed to gut dysbiosis, mainly characterized by increases in deleterious bacteria and TMAO. HFD destroyed intestinal barrier integrity and increased intestinal permeability, as evaluated by reducing levels of colonic mucin-2, tight junction proteins, goblet cells and elevating serum level of fluorescein isothiocyanate-dextran 4. Correlation analysis showed a positive association between TMAO and SO. In addition, TMAO treatment aggravated the development of SO in HFD-fed aged rats through regulating the ROS-AKT/mTOR signaling pathway. CONCLUSION: HFD leads to SO in natural aging rats, partially through the gut-microbiota-TMAO-muscle axis.

Allocation of emergency medical resources for epidemic diseases considering the heterogeneity of epidemic areas.

Background: The resources available to fight an epidemic are typically limited, and the time and effort required to control it grow as the start date of the containment effort are delayed. When the population is afflicted in various regions, scheduling a fair and acceptable distribution of limited available resources stored in multiple emergency resource centers to each epidemic area has become a serious problem that requires immediate resolution. Methods: This study presents an emergency medical logistics model for rapid response to public health emergencies. The proposed methodology consists of two recursive mechanisms: (1) time-varying forecasting of medical resources and (2) emergency medical resource allocation. Considering the epidemic's features and the heterogeneity of existing medical treatment capabilities in different epidemic areas, we provide the modified susceptible-exposed-infected-recovered (SEIR) model to predict the early stage emergency medical resource demand for epidemics. Then we define emergency indicators for each epidemic area based on this. By maximizing the weighted demand satisfaction rate and minimizing the total vehicle travel distance, we develop a bi-objective optimization model to determine the optimal medical resource allocation plan. Results: Decision-makers should assign appropriate values to parameters at various stages of the emergency process based on the actual situation, to ensure that the results obtained are feasible and effective. It is necessary to set up an appropriate number of supply points in the epidemic emergency medical logistics supply to effectively reduce rescue costs and improve the level of emergency services. Conclusions: Overall, this work provides managerial insights to improve decisions made on medical distribution as per demand forecasting for quick response to public health emergencies.

Evaluation of BCAS1-positive immature oligodendrocytes after cerebral ischemic stroke and SVD.

Ischemic cerebrovascular disease is an important cause of physical disability and dementia. Oligodendrocytes (OLGs), which differentiate from oligodendrocyte precursor cells (OPCs), are crucial for remyelination of the damaged brain and functional recovery. Breast carcinoma amplified sequence 1 (BCAS1) has recently been shown to be highly expressed in newly formed pre-myelinating oligodendrocytes (pre-mOLGs), while its expression level is reduced in mature OLGs. In this study, we analyzed BCAS1 expression by immunohistochemical analysis of human post-mortem brain tissue from six stroke patients (death within 2 months after stroke onset) and eight small vessel disease (SVD) patients. Control post-mortem brain tissue was from eight age-matched patients without any obvious central nervous system (CNS) pathology. The Olig2 expression in the area corresponding to the same section of the BCAS1-stained slice was analyzed to determine the total oligodendrocyte lineage. The percentage of differentiating OPCs in the oligodendrocyte lineage was calculated as the ratio of BCAS1+ to Olig2+ cells (BCAS1+/Olig2+). The stroke and SVD cases showed demyelination with decreased expression of myelin basic protein (MBP, a mature OLG marker). The stroke cases showed significantly increased numbers of early-stage BCAS1+ cells with an immature morphology and Olig2+ cells (pan-oligodendrocyte lineages) in the peri-infarct areas in both the cortex and white matter, but showed no increase in the number of late-stage BCAS1+ cells with a mature morphology. In contrast, the SVD cases showed no significant increase in Olig2+ and BCAS1+ cells. These results indicated that remyelination dysfunction could be attributed to insufficient maturation of OPCs in stroke and impaired recruitment of OPCs in SVD.

Environmental exposure to perchlorate, nitrate and thiocyanate, and thyroid function in Chinese adults: A community-based cross-sectional study.

BACKGROUND: Evidence on environmental exposure to perchlorate, nitrate, and thiocyanate, three thyroidal sodium iodine symporter (NIS) inhibitors, and thyroid function in the Chinese population remains limited. OBJECTIVE: To investigate the associations of environmental exposure to perchlorate, nitrate, and thiocyanate with markers of thyroid function in Chinese adults. METHODS: A total of 2441 non-pregnant adults (mean age 50.4 years and 39.1% male) with a median urinary iodine of 180.1 µg/L from four communities in Shenzhen were included in this cross-sectional study. Urinary perchlorate, nitrate, thiocyanate, and thyroid profiles, including serum free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), and thyroid stimulating hormone (TSH), were measured. Generalized linear model was applied to investigate the single-analyte associations. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to examine the association between the co-occurrence of three anions and thyroid profile. RESULTS: The median levels of urinary perchlorate, nitrate, and thiocyanate were 5.8 µg/g, 76.4 mg/g, and 274.1 µg/g, respectively. After adjusting for confounders, higher urinary perchlorate was associated with lower serum FT4, TT4, and TT3, and higher serum FT3 and TSH (all P < 0.05). Comparing extreme tertiles, subjects in the highest nitrate tertile had marginally elevated TT3 (ß: 0.02, 95% CI: 0.00-0.04). Each 1-unit increase in log-transformed urinary thiocyanate was associated with a 0.04 (95% CI: 0.02-0.06) pmol/L decrease in serum FT3. The WQS indices were inversely associated with serum FT4, TT4, and FT3 (all P < 0.05). In the BKMR model, the mixture of three anions was inversely associated with serum FT4, TT4, and FT3. CONCLUSIONS: Our study provides evidence that individual and combined environmental exposure to perchlorate, nitrate, and thiocyanate are associated with significant changes in thyroid function markers in the Chinese population with adequate iodine intake.

Study on the Localization of Fangcang Shelter Hospitals During Pandemic Outbreaks.

In the event of pandemic, it is essential for government authority to implement responses to control the pandemic and protect people's health with rapidity and efficicency. In this study, we first develop an evaluation framework consisting of the entropy weight method (EWM) and the technique for order preference by similarity to ideal solution (TOPSIS) to identify the preliminary selection of Fangcang shelter hospitals; next, we consider the timeliness of isolation and treatment of patients with different degrees of severity of the infectious disease, with the referral to and triage in Fangcang shelter hospitals characterized and two optimization models developed. The computational results of Model 1 and Model 2 are compared and analyzed. A case study in Xuzhou, Jiangsu Province, China, is used to demonstrate the real-life applicability of the proposed models. The two-stage localization method gives decision-makers more options in case of emergencies and can effectively designate the location. This article may give recommendations of and new insights into parameter settings in isolation hospital for governments and public health managers.

Optimizing COVID-19 vaccine allocation considering the target population.

Vaccine allocation strategy for COVID-19 is an emerging and important issue that affects the efficiency and control of virus spread. In order to improve the fairness and efficiency of vaccine distribution, this paper studies the optimization of vaccine distribution under the condition of limited number of vaccines. We pay attention to the target population before distributing vaccines, including attitude toward the vaccination, priority groups for vaccination, and vaccination priority policy. Furthermore, we consider inventory and budget indexes to maximize the precise scheduling of vaccine resources. A mixed-integer programming model is developed for vaccine distribution considering the target population from the viewpoint of fairness and efficiency. Finally, a case study is provided to verify the model and provide insights for vaccine distribution.

Association of Sleep Patterns and Lifestyles With Incident Hypertension: Evidence From a Large Population-Based Cohort Study.

Background: Adherence to a healthy lifestyle (no smoking, consuming a healthy diet, engaging in physical activity, and maintaining a healthy weight) is recommended in current guidelines for hypertension prevention. However, evidence regarding the association between sleep behaviors, independently and jointly with traditional lifestyle factors, and the risk of hypertension is limited. Methods: This prospective study included 165,493 participants who are free of hypertension at baseline from the UK Biobank. Sleep behaviors, including chronotype, sleep duration, insomnia, snoring, and daytime sleepiness were used to construct a healthy sleep score. We also derived a healthy lifestyle score based on smoking status, diet quality, physical activity, and body mass index (BMI). Cox proportional hazards regression models and competing risk analyses were used to estimate the associations of the healthy sleep score and healthy lifestyle score with the risk of hypertension. The population attributable risk percent (PAR%) was estimated for increased cases of hypertension due to poor adherence to a healthy sleep pattern or a healthy lifestyle. Results: A total of 10,941 incident hypertension cases were documented during a median of 11.8 years of follow-up. The multivariable-adjusted hazard ratio (HR) for hypertension was 0.58 [95% confidence interval (CI): 0.52, 0.65] for participants with a sleep score of 5 compared with 0-1, and 0.48 (95% CI: 0.43, 0.54) for participants with a lifestyle score of 4 compared with those who scored 0. For joint association, those with a poor sleep pattern and a poor lifestyle had the highest risk of hypertension [HR: 2.41 (95% CI: 2.12, 2.74)]. PAR% was 14.7% (95% CI: 12.3%, 17.1%), 20.1% (95% CI: 17.6%, 22.6%), and 31.7% (95% CI: 27.6%, 35.6%) for poor adherence to a healthy sleep pattern, a healthy lifestyle, and the combination of a healthy sleep pattern and a healthy lifestyle. Conclusion: Both a healthy sleep pattern and a healthy lifestyle were associated with a lower risk of hypertension, and the benefits of adhering to a healthy sleep pattern complement the well-established lifestyle for the optimal primary prevention of hypertension. These findings support the current perspective that a healthy sleep pattern is an important part of a healthful and productive lifestyle for hypertension prevention.

Higher Levels of Urinary Thiocyanate, a Biomarker of Cruciferous Vegetable Intake, Were Associated With Lower Risks of Cardiovascular Disease and All-Cause Mortality Among Non-smoking Subjects.

Background: Epidemiologic studies on cruciferous vegetable (CV) intake and cardiovascular disease (CVD) were inconclusive. Objective: To investigate the associations of urinary thiocyanate, a biomarker of CV intake, with CVD and all-cause mortality among non-smoking adults. Methods: This prospective cohort study comprised 10,489 non-smoking adults (weighted mean age, 46.8 years; 43.4% male) from the National Health and Nutrition Examination Survey 2001-2014. Non-smokers were defined as subjects with serum cotinine < 3 ng/mL. Urinary thiocyanate was measured with ion chromatography tandem mass spectrometry at baseline, and CVD and all-cause mortality were identified through linkage to National Death Index until December 31, 2015. Cox proportional hazards model was applied to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD and all-cause mortality. Results: A total of 800 deaths, of which 136 died of CVD, were ascertained within a median 7.8 years of follow-up. Urinary thiocyanate was positively correlated with total CV intake among non-smoking adults (r s = 0.088, P < 0.001). Comparing extreme quartiles, the multivariate-adjusted HRs for CVD and all-cause mortality were 0.50 (95% CI: 0.29-0.85) and 0.75 (95% CI: 0.60-0.92), respectively. Each 1 µg/g creatinine increment of log-transformed urinary thiocyanate was associated with a 25% (HR: 0.75; 95% CI: 0.62-0.91) reduced CVD mortality risk and 12% (HR: 0.88; 95% CI: 0.81-0.96) reduced all-cause mortality risk. The documented inverse associations persisted in sensitivity analyses. Conclusion: Increased levels of urinary thiocyanate, a candidate biomarker of CV intake, were associated with low risks of CVD and total mortality among non-smoking adults. This prospective biomarker-based study provided further evidence to support the cardiovascular benefits of CVs.

A Resilient, Non-neuronal Source of the Spatiotemporal Lag Structure Detected by BOLD Signal-Based Blood Flow Tracking.

Recent evidence has suggested that blood oxygenation level-dependent (BOLD) signals convey information about brain circulation via low frequency oscillation of systemic origin (sLFO) that travels through the vascular structure ("lag mapping"). Prompted by its promising application in both physiology and pathology, we examined this signal component using multiple approaches. A total of 30 healthy volunteers were recruited to perform two reproducibility experiments at 3 Tesla using multiband echo planar imaging. The first experiment investigated the effect of denoising and the second was designed to study the effect of subject behavior on lag mapping. The lag map's intersession test-retest reproducibility and image contrast were both diminished by removal of either the neuronal or the non-neuronal (e.g., cardiac, respiratory) components by independent component analysis-based denoising, suggesting that the neurovascular coupling also comprises a part of the BOLD lag structure. The lag maps were, at the same time, robust against local perfusion increases due to visuomotor task and global changes in perfusion induced by breath-holding at the same level as the intrasession reliability. The lag structure was preserved after time-locked averaging to the visuomotor task and breath-holding events, while any preceding signal changes were canceled out for the visuomotor task, consistent with the passive effect of neurovascular coupling in the venous side of the vasculature. These findings support the current assumption that lag mapping primarily reflects vascular structure despite the presence of sLFO perturbation of neuronal or non-neuronal origin and, thus, emphasize the vascular origin of the lag map, encouraging application of BOLD-based blood flow tracking.

[Application of homologous conduits with valves in the treatment of complex congenital heart disease with insufficient pulmonary blood flow in children].

OBJECTIVE: To investigate the effects of homologous conduits with valves in the treatment of complex congenital heart disease with insufficient pulmonary blood flow in children. METHODS: Homologous conduits with valves were used in the right ventricular outflow tract reconstruction among 212 pediatric patients with complex congenital heart disease with insufficient pulmonary blood flow, aged 2.6 (0.5 - 15). The patients were followed up for 2.6 years (6 months to 7 years) and underwent echocardiography to assess the degree of pulmonary insufficiency and calcification of blood vessel. RESULTS: The success rate of operation was 96.5% (204/212). The ratio of right ventricle to aortic pressure was less then 0.55. During the follow-up, echocardiography showed valvular regurgitation and calcification of the blood vessel in 34 patients, 23 (11.2%) being mild, 7 (3.42%) being moderate, and 4 (1.96%) being sever. 170 patients did not show obvious pulmonary insufficiency. CONCLUSION: Application of homologous conduits with valves in the treatment of complex congenital heart disease with insufficient pulmonary blood flow in children shows excellent early results in preventing pulmonary insufficiency.

Transcatheter closure of postoperative residual ventricular septal defects using Amplatzer-type perimembranous VSD occluders.

OBJECTIVES: The reoperations of postoperative residual ventricular septal defects (VSDs) are associated with higher risks. Our aim is to assess the efficacy and safety of transcatheter closure of postoperative residual VSDs using perimembranous VSD occluders. METHODS: Twenty-one patients with residual VSDs underwent transcatheter closure in our center from January 2005 to January 2012. The study population consisted of 9 males and 12 females whose ages ranged from 1.9 to 54 years (median age, 8.7 years). Eighteen cases had perimembranous VSD repair previously, 3 cases had tetralogy of Fallot surgical treatment. All patients had signs of left ventricle volume overload (Qp/Qs ≥ 1.5). Two types of perimembranous VSD occluders, symmetric and asymmetric, were used in 14 and 7 cases, respectively. The diameter of residual VSDs ranged from 4-16 mm (mean, 7.8 mm). The waist size of occluders ranged from 6-18 mm. RESULTS: There were 0 deaths and 1 serious adverse event. Intravascular hemolysis occurred in 1 patient (4.8%), lasted for 7 days, and recovered with therapy. A trivial intraprosthetic residual shunt was observed in 2 patients (9.5%) after the procedure and 1 patient (4.8%) at 6 months. Two patients (9.5%) had transient left anterior hemiblock and recovered within the first week after the procedure. At the latest follow-up, no atrioventricular block and new-onset aortic regurgitation occurred. CONCLUSIONS: Transcatheter closure is a feasible and safe management option for patients with postoperative residual VSDs and obviates the need for a second surgery and cardiopulmonary bypass.

Unidirectional monovalve homologous aortic patch for repair of ventricular septal defect with pulmonary hypertension.

BACKGROUND: Severe pulmonary hypertension is a common complication of congenital cardiac defects with large left to right shunt, and the closure of a large ventricular septal defect (VSD) with elevated pulmonary vascular resistance (PVR) is associated with significant morbidity and mortality. A unidirectional monovalve homologous aortic patch was designed to close the large VSD with severe pulmonary hypertension in an effort to decrease the morbidity and mortality. METHODS: Twenty-seven patients (mean age, 15.0 +/- 5.6 years) with large VSD with severe pulmonary hypertension (pulmonary vascular resistance, 15.2 +/- 3.8 Wood units) were repaired with a unidirectional monovalve homologous aortic patch. According to body surface area and the preoperative arterial oxygen saturation, the monovalve homologous aortic patches were fenestrated on the aortic wall with a diameter of 4 to 8 mm. RESULTS: Two patients died of pulmonary hypertensive crisis and cardiac arrest postoperatively. All of the survival patients were followed up (5 months to 10 years) and the cardiopulmonary function was well improved with no late death. Obvious opening and closing of the monovalve was detected by early postoperative echocardiography in seven patients. A small amount of right to left shunt was detected in three patients three months after operation, and in two of them the shunt still existed three years after operation. CONCLUSIONS: Closure of a large VSD in patients with severe pulmonary hypertension could be performed with low morbidity and mortality when a unidirectional monovalve homologous aortic patch was used and the long-term result was satisfactory.