Roux-en-Y Gastric Bypass Surgery for the Prevention of Long-term Renal Function Damage in Type 2 Diabetes: A Clinical Study.

Objective: Type 2 diabetes mellitus (T2DM) is strongly associated with obesity, a significant risk factor for the occurrence and progression of chronic kidney disease. In recent years, weight loss surgery has become an important treatment option for diabetes. This study examined whether Roux-en-Y gastric bypass surgery, a new metabolic bariatric surgery approach, can effectively reduce the risk of long-term renal impairment in individuals with type 2 diabetes. Methods: In a cohort study, 60 individuals suffering from both obesity and type 2 diabetes were stratified and randomly divided into 2 groups based on gender and weight. The control group (30 cases) received internal medicine treatment; the observation group (30 cases) received Roux-en-Y gastric bypass surgery. The study compared the changes in glycated hemoglobin, fasting blood glucose, fasting insulin, fasting C-peptide, postprandial 2-hour blood glucose, postprandial 2-hour insulin, postprandial 2-hour C-peptide, weight, waist circumference, and BMI before and at 6, 12, and 18 months after treatment. Kidney function-related indicators such as urinary protein excretion, microalbuminuria, and creatinine clearance were also compared. Results: There were no significant differences in the above indicators between the 2 groups before treatment (P > .05). After 6, 12, and 18 months of treatment, the levels of glycated hemoglobin, fasting blood glucose, fasting insulin, fasting C-peptide, postprandial 2-hour blood glucose, postprandial 2-hour insulin, postprandial 2-hour C-peptide, weight, waist circumference, and BMI were significantly decreased compared to before treatment (P < .05). Urinary protein excretion and microalbuminuria decreased, while creatinine clearance increased after 6, 12, and 18 months of surgery (P < .05). The differences in indicators between the 2 groups at each point after surgery were statistically significant (P < .05). Conclusion: Roux-en-Y gastric bypass surgery was more effective than medical treatment in treating type 2 diabetes and mitigating long-term kidney function damage. These findings confirm the clinical utility of Roux-en-Y gastric bypass surgery in these conditions, indicating its potential for generalization and reference.

Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases.

The phenomenon of an aging population is advancing at a precipitous rate. Alzheimer's disease and Parkinson's disease are two of the most common age-associated neurodegenerative diseases, both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures. Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles, including the clearance of macromolecular waste and the trafficking of immune cells. Notably, aquaporin 4-mediated glymphatic transport, crucial for maintaining neural homeostasis, becomes disrupted during the aging process and is further compromised in the pathogenesis of Alzheimer's disease and Parkinson's disease. Functional meningeal lymphatic vessels, which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes, are integral in bridging the central nervous system with peripheral immune responses. Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease. This review meticulously explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders. It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.

High-Q adiabatic micro-resonators on a wafer-scale ion-sliced 4H-silicon carbide-on-insulator platform.

A 4H-silicon carbide-on-insulator (4H-SiCOI) has emerged as a prominent material contender for integrated photonics owing to its outstanding material properties such as CMOS compatibility, high refractive index, and high second- and third-order nonlinearities. Although various micro-resonators have been realized on the 4H-SiCOI platform, enabling numerous applications including frequency conversion and electro-optical modulators, they may suffer from a challenge associated with spatial mode interactions, primarily due to the widespread use of multimode waveguides. We study the suppression of spatial mode interaction with Euler bends, and demonstrate micro-resonators with improved Q values above 1 × 105 on ion-sliced 4H-SiCOI platform with a SiC thickness nonuniformity less than 1%. The spatial-mode-interaction-free micro-resonators reported on the CMOS-compatible wafer-scale 4H-SiCOI platform would constitute an important ingredient for the envisaged large-scale integrated nonlinear photonic circuits.

Decreased miR-451a in cerebrospinal fluid, a marker for both cognitive impairment and depressive symptoms in Alzheimer's disease.

Background: Alzheimer's disease (AD) patients are often accompanied by depressive symptoms, but its underlying mechanism remains unclear. The present study aimed to explore the potential role of microRNAs in the comorbidity of AD and depression. Methods: The miRNAs associated with AD and depression were screened from databases and literature and then confirmed in the cerebrospinal fluid (CSF) of AD patients and different ages of transgenic APP/PS1 mice. AAV9-miR-451a-GFP was injected into the medial prefrontal cortex (mPFC) of APP/PS1 mice at seven months, and four weeks later, a series of behavioral and pathological analyses were performed. Results: AD patients had low CSF levels of miR-451a, which was positively correlated with the cognitive assessment score, but negatively with their depression scale. In the mPFC of APP/PS1 transgenic mice, the miR-451a levels also decreased significantly in the neurons and microglia. Specific virus vector-induced overexpression of miR-451a in the mPFC of APP/PS1 mice ameliorated AD-related behavior deficits and pathologies, including long-term memory defects, depression-like phenotype, ß-amyloid load, and neuroinflammation. Mechanistically, miR-451a decreased the expression of neuronal ß-secretase 1 of neurons through inhibiting Toll-like receptor 4/Inhibitor of kappa B Kinase ß/ Nuclear factor kappa-B signaling pathway and microglial activation by inhibiting activation of NOD-like receptor protein 3, respectively. Conclusion: This finding highlighted miR-451a as a potential target for diagnosing and treating AD, especially for those with coexisting symptoms of depression.

Correcting for bias due to mismeasured exposure history in longitudinal studies with continuous outcomes.

Epidemiologists are often interested in estimating the effect of functions of time-varying exposure histories in relation to continuous outcomes, for example, cognitive function. However, the individual exposure measurements that constitute the history upon which an exposure history function is constructed are usually mismeasured. To obtain unbiased estimates of the effects for mismeasured functions in longitudinal studies, a method incorporating main and validation studies was developed. Simulation studies under several realistic assumptions were conducted to assess its performance compared to standard analysis, and we found that the proposed method has good performance in terms of finite sample bias reduction and nominal confidence interval coverage. We applied it to a study of long-term exposure to PM 2.5 $\text{PM}_{2.5}$ , in relation to cognitive decline in the Nurses' Health Study Previously, it was found that the 2-year decline in the standard measure of cognition was 0.018 (95% CI, -0.034 to -0.001) units worse per 10 µ g/m 3 $\mu \text{g/m}^3$ increase in PM 2.5 $\text{PM}_{2.5}$ exposure. After correction, the estimated impact of PM 2.5 $\text{PM}_{2.5}$ on cognitive decline increased to 0.027 (95% CI, -0.059 to 0.005) units lower per 10 µ g/m 3 $\mu \text{g/m}^3$ increase. To put this into perspective, effects of this magnitude are about 2/3 of those found in our data associated with each additional year of aging: 0.044 (95% CI, -0.047 to -0.040) units per 1 year older after applying our correction method.

Effects of exercise training in hypoxia versus normoxia on fat-reducing in overweight and/or obese adults: A systematic review and meta-analysis of randomized clinical trials.

Objective: Fat loss theory under various oxygen conditions has been disputed, and relevant systematic review studies are limited. This study is a systematic review and meta-analysis to assess whether hypoxic exercise training (HET) leads to superior fat-reducing compared with normoxic exercise training (NET). Methods: We searched PubMed, Web of Science, CNKI, ProQuest, Google Scholar, Cochrane Library, and EBSCOhost from inception to June 2022 for articles comparing the effects of hypoxic and normoxic exercise on body composition indicators, glycometabolism, and lipometabolism indicators in obese and overweight adults. Only randomized controlled trials (RCTs) were included. The effect sizes were expressed as standardized mean difference (SMD) and 95% confidence intervals (CI). Between-study heterogeneity was examined using the I 2 test and evaluated publication bias via Egger's regression test. The risk of bias assessment was performed for each included trial using Cochrane Evaluation Tool second generation. The meta-analysis was performed by using R 4.1.3 and RevMan 5.3 analytic tools. Results: A total of 19 RCTs with 444 subjects were analyzed according to the inclusion and exclusion criteria. Among them, there were 14 English literature and five Chinese literature. No significant difference in body composition (SMD -0.10, 95% CI -0.20 to -0.01), glycometabolism and lipid metabolism (SMD -0.01, 95% CI -0.13 to -0.10) has been observed when comparing the HET and NET groups. We only found low heterogeneity among trials assessing glycometabolism and lipometabolism (I 2 = 20%, p = 0.09), and no publication bias was detected. Conclusion: The effects of HET and NET on fat loss in overweight or obese people are the same. The application and promotion of HET for fat reduction need further exploration.

Bayesian network mediation analysis with application to the brain functional connectome.

The brain functional connectome, the collection of interconnected neural circuits along functional networks, facilitates a cutting-edge understanding of brain functioning, and has a potential to play a mediating role within the effect pathway between an exposure and an outcome. While existing mediation analytic approaches are capable of providing insight into complex processes, they mainly focus on a univariate mediator or mediator vector, without considering network-variate mediators. To fill the methodological gap and accomplish this exciting and urgent application, in the article, we propose an integrative mediation analysis under a Bayesian paradigm with networks entailing the mediation effect. To parameterize the network measurements, we introduce individually specified stochastic block models with unknown block allocation, and naturally bridge effect elements through the latent network mediators induced by the connectivity weights across network modules. To enable the identification of truly active mediating components, we simultaneously impose a feature selection across network mediators. We show the superiority of our model in estimating different effect components and selecting active mediating network structures. As a practical illustration of this approach's application to network neuroscience, we characterize the relationship between a therapeutic intervention and opioid abstinence as mediated by brain functional sub-networks.

Drainage of senescent astrocytes from brain via meningeal lymphatic routes.

Recent progress on the central lymphatic system has greatly increased our understanding of how the brain maintains its own waste homeostasis. Here, we showed that perivascular spaces and meningeal lymphatic vessels form a functional route for clearance of senescent astrocytes from the aging brain. Blocking meningeal lymphatic drainage by ligation of the deep cervical lymph nodes impaired clearance of senescent astrocytes from brain parenchyma, subsequently increasing neuroinflammation in aged mice. By contrast, enhancing meningeal lymphatic vessel diameter by a recombinant adeno-associated virus encoding mouse vascular endothelial growth factor-C (VEGF-C) improved clearance of senescent astrocytes and mitigated neuroinflammation. Mechanistically, VEGF-C was highly expressed in senescent astrocytes, contributing themselves to migrate across lymphatic vessels along C-C motif chemokine ligand 21 (CCL21) gradient by interacting with VEGF receptor 3. Moreover, intra-cisternal injection of antibody against CCL21 hampered senescent astrocytes into the lymphatic vessels and exacerbated short memory defects of aged mice. Together, these findings reveal a new perspective for the meningeal lymphatics in the removal of senescent astrocytes, thus offering a valuable target for therapeutic intervention.

Incorporating Information on Control Diseases Across Space and Time to Improve Estimation of the Population-level Impact of Vaccines.

BACKGROUND: The synthetic control method evaluates the impact of vaccines while adjusting for a set of control time series representing diseases that are unaffected by the vaccine. However, noise in control time series, particularly in areas with small counts, can obscure the association with the outcome, preventing proper adjustments. To overcome this issue, we investigated the use of temporal and spatial aggregation methods to smooth the controls and allow for adjustment of underlying trends. METHODS: We evaluated the impact of pneumococcal conjugate vaccine on all-cause pneumonia hospitalizations among adults ≥80 years of age in 25 states in Brazil from 2005 to 2015. Pneumonia hospitalizations in this group indicated a strong increasing secular trend over time that may influence estimation of the vaccine impact. First, we aggregated control time series separately by time or space before incorporation into the synthetic control model. Next, we developed distributed lags models (DLMs) to automatically determine what level of aggregation was most appropriate for each control. RESULTS: The aggregation of control time series enabled the synthetic control model to identify stronger associations between outcome and controls. As a result, the aggregation models and DLMs succeeded in adjusting for long-term trends even in smaller states with sparse data, leading to more reliable estimates of vaccine impact. CONCLUSIONS: When synthetic control struggles to identify important prevaccine associations due to noise in control time series, users can aggregate controls over time or space to generate more robust estimates of the vaccine impact. DLMs automate this process without requiring prespecification of the aggregation level.

Ultrasonic cardiogram and MiRNA-21 analysis of cardiac dysfunction in patients with cardiac arrest following cardiopulmonary resuscitation.

PURPOSE: To explore correlations between the serum level of miRNA-21 expression and cardiac dysfunction severity after cardiopulmonary resuscitation (CPR) using ultrasonic cardiogram. METHODS: Thirty-nine patients with cardiopulmonary arrest receiving successful CPR and forty-one healthy participants were recruited in the study. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunochemiluminometric assays was used to examine the serum miRNA-21 level and the concentration of cardiac troponins T and I, respectively. Indices of Electrocardiogram (ECG) and cardiac dysfunction measured by ultrasound of patients in the case group were used to assess cardiac function after CPR. Furthermore, the correlation between the serum level of miRNA-21 expression and severity of cardiac dysfunction was analyzed by Spearman correlation analysis. RESULTS: As compared to the control group, the serum level of miRNA-21 expression, as well as cardiac troponin T and I levels in the case group were significantly higher (p = 0.000). The miRNA-21 expression level in the patients at IV grade of cardiac function were substantially higher than patients at III grade (p = 0.015). There was no significant difference in level of cardiac troponins T and I between patients at III grade and patients at IV grade (p > 0.05). Further, Spearman correlation analysis revealed that the level of miRNA-21 expression was negatively correlated with cardiac function index in the ultrasound imaging: E peak, E/A value, LVEF and LVEDD (r = 0.617, 0.535, 0.612, 0.573, P = 0.012, 0.009, 0.008, 0.011), but was positively correlated with the level of cardiac troponins T and I (r = 0.546,0.582, P = 0.006,0.007) and the severity of cardiac dysfunction (r = 0.859, p < 0.05). CONCLUSION: The level of miRNA-21 is higher after CPR is closely related to the severity of cardiac dysfunction that is measured by ultrasound, suggesting that it may serve as a potential biomarker.

Resveratrol attenuates neurological deficit and neuroinflammation following intracerebral hemorrhage.

Resveratrol (RESV) improves histopathological and behavioral outcomes in diseases of the central nervous system. However, to the best of our knowledge, there have been no studies investigating its neuroprotective effects on secondary brain injury following intracerebral hemorrhage (ICH). The aim of the present study was to evaluate the neuroprotective function of resveratrol following ICH. Male Sprague-Dawley rats were randomly divided into 3 groups: Sham, ICH and ICH+RESV groups. Rats underwent ICH and received an intraperitoneal injection of RESV daily. Rotarod and open field tests were performed to evaluate improvements in motor disturbance pre- and post-surgery. Rats were sacrificed following the final behavioral test; subsequently, neuron injury and cell death in the hippocampus and microglia activation in the cortex were determined using Nissl staining and ionized calcium binding adaptor molecule 1 immunofluorescence staining, respectively. Compared with the ICH group, rats treated with resveratrol for 2 weeks performed significantly better in behavioral tests. Furthermore, less neural damage in the hippocampus and decreased activation of microglia was observed in the ICH+RESV group. The results of the present study therefore indicate that resveratrol may alleviate secondary brain injury following ICH.