Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy.

AIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR. METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed. RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples. CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.

FGF17 protects cerebral ischemia reperfusion-induced blood-brain barrier disruption via FGF receptor 3-mediated PI3K/AKT signaling pathway.

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients.

A comparative analysis of 375 patients with lateral and medial medullary infarction.

BACKGROUND: Few studies have compared the etiology and clinical features between pure lateral medullary infarction (LMI) and pure medial medullary infarction (MMI). METHODS: All patients included were hospitalized at The First Affiliated Hospital and The Second Affiliated Hospital of Wenzhou Medical University from January 2015 to July 2020. Their risk factors, clinical manifestation, stroke mechanisms and short-term prognosis were analyzed retrospectively. RESULTS: Among the 387 patients enrolled, 266 (68.7%) had LMI, 109 (28.2%) had MMI, and 12 (3.1%) (nine men and three women) had LMI plus MMI. We analyzed the 375 patients of LMI and MMI. The average ages of LMI and MMI were 59.4 years and 62.69 years, respectively. Univariate analysis and multivariable logistic regression was used to investigate the existing risk factors of MMI relative to LMI. Prior infarction, poor glycemic control, and atherosclerosis were more frequently associated with MMI than with LMI. The clinical manifestation was significantly different between LMI and MMI. We used modified Rankin Scale (mRS) score as the short-term prognostic evaluation criteria, and MMI appeared worse than LMI. CONCLUSIONS: This study reveals that: (1) patients with MMI are older than those with LMI; (2) prior infarction, poor glycemic control, and atherosclerosis are independent risk factors of MMI than that of LMI; (3) the clinical manifestations of LMI and MMI are heterogeneous; (4) short-term prognosis of MMI is worse than LMI.

The underlying mechanism of enhanced methane production using microbial electrolysis cell assisted anaerobic digestion (MEC-AD) of proteins.

Anaerobic digestion (AD) is a promising technology capable of converting waste matter into bio-energy. Recent studies have reported that microbial electrolysis cell assisted anaerobic digestion (MEC-AD) is an effective system for methane production from organic waste, via enhanced electron transfer. However, little is known about the effects of applied voltage on the AD of proteins. Herein, the mechanism of MEC-AD on protein digestion was investigated using varying concentrations of bovine serum albumin (BSA) as the protein substrate (500 mg/L, 4 g/L, and 20 g/L BSA). Experimental results showed that the applied voltage can not only enhance the methane production rate from 23.8% to 45.6% at low and medium organic loading (BSA concentration of 500 mg/L and 4 g/L), but also improve the methanogenesis efficiency increased by 225.4% at high BSA concentration (20 g/L) with the applied voltage of 0.6 V compared to that with open circuit. Mechanism explorations revealed that the applied voltage significantly enhanced the acidogenesis and methanogenesis processes in the AD of proteins. Microbial community characterization showed that with the applied voltage, the abundance of fermentative bacteria increased by 46.7 % at the anode, while, the abundance of Methanobacterium at the cathode increased from 10.4 to 84.3%, indicating the methanogenesis pathway transformed from acetoclastic to hydrogenotrophic. External circuit electron transfer calculations demonstrated that only 10% of the produced methane could be attributed to direct interspecies electron transfer (DIET). From a thermodynamic perspective, the applied external voltage led to a reduction in the cathodic potential to -0.9 V, which is beneficial for enhanced methane production via mediated interspecies electron transfer (MIET) by enrichment of hydrogenotrophic methanogens. The findings reported here reveal the previously unrecognized contribution of proteins to MEC-AD, while also furthering our understanding of the role of applied voltage in the MEC-AD process.

Clinical activity changes in the neurology department of Wenzhou during the COVID-19 pandemic: an observational analysis.

OBJECTIVE: To explore the activity changes in neurology clinical practice that have occurred in tertiary public hospitals during the COVID-19 pandemic. METHODS: Outpatient and inpatient data from the neurology department were extracted from the electronic medical record system of three tertiary Grade A hospitals in Wenzhou. Data were analyzed across 5 months following the beginning of the pandemic (from January 13 to May 17) and compared with the same period in 2019. Data on reperfusion therapy for acute infarction stroke were extracted monthly from January to April. RESULTS: The number of outpatients declined from 102,300 in 2019 to 75,154 in 2020 (26.54%), while the number of inpatients in the three tertiary Grade A hospitals decreased from 4641 to 3437 (25.94%). The latter trend showed a significant drop from the 3rd week to the 7th week. The number of patients in these hospitals decreased significantly, and a significant drop was seen in the neurology department. As usual, stroke was the most common disease observed; however, anxiety/depression and insomnia increased dramatically in the outpatient consultation department. CONCLUSIONS: The results of our study revealed the effects of the COVID-19 pandemic in the clinical practice of neurology in Wenzhou during the outbreak. Understanding the pandemic's trends and impact on neurological patients and health systems will allow for better preparation of neurologists in the future.

A cross-sectional survey on occupational stress and associated dyslipidemia among medical staff in tertiary public hospitals in Wenzhou, China.

INTRODUCTION: Occupational stress is considered to be a harmful physical and emotional response to an individual's psychological and/or physiological state in the work environment and is highly prevalent among medical staff. However, few epidemiological studies have investigated occupational stress in medical staff. Our study aims to explore the characteristics of occupational stress and its relationship with dyslipidemia in Chinese medical staff at tertiary hospitals and establish the basis for future preventive strategies. METHODS: A cross-sectional study was conducted in three tertiary public hospitals in Wenzhou City, Zhejiang Province, China. Data were collected using random sampling procedures to examine demographic characteristics and job-related data. The participants completed the Occupational Stress Inventory-Revised (OSI-R) questionnaires and serum lipids tests. Partial correlation analysis was conducted to explore the relationship between occupational stress and dyslipidemia. RESULTS: A total of 1,176 medical staff responses to questionnaires were obtained. The occupational stress levels of medical staff were higher than those of normative populations, while their coping resources were lower. Most of the subscales of occupational stress demonstrated higher results for doctors and males than for nurses and females with crude analyses. Each subscale of OSI-R was found to be associated with a different type of blood lipid level. CONCLUSIONS: The occupational stress level of medical staff in tertiary public hospitals in Wenzhou was high, and occupational stress may contribute to dyslipidemia. An investigation into occupational stress levels and their association with dyslipidemia in this population could draw more attention to medical staff in tertiary public hospitals.

Predictors of the Prevalence of Dyslipidemia and Influencing Factors for Young Health Examination Cohort: A Cross-Sectional Survey.

Objectives: The objective of this study was to estimate the prevalence of dyslipidemia and associated influencing factors in young adults in the southeastern coastal area of China. Methods: This study adopted a cross-sectional survey and included 7,859 young people who underwent examinations at three hospitals in Wenzhou, Zhejiang Province, China. All subjects completed a questionnaire in the form of face-to-face interviews and underwent anthropometric measurements and biochemical tests. The continuous data are presented as the means ± standard deviations and were compared using Student's t-tests. The categorical variables are presented as proportions. The influencing factors associated with dyslipidemia were evaluated through a multivariate logistic regression. Results: The prevalence of dyslipidemia among young adults aged 18-45 years in the southeastern coast of China was high with 7.1, 15.0, 22.9, and 4.0% for high-total cholesterol (TC), high-triglyceride (TG), low-high-density lipoprotein cholesterol (HDL-C), and high-low-density lipoprotein cholesterol (LDL-C). Among those with dyslipidemia, a statistically significant difference in sex was observed, and all types of dyslipidemia were associated with smoking and alcohol consumption. However, those with high-TG, high-LDL, and low-HDL levels did not significantly differ in education level or occupation. The presence of dyslipidemia was significantly associated with increased age, the male sex (OR: 1.85, 95% CI: 1.39-2.21), smoking (OR: 2.02, 95% CI: 1.98-2.13), alcohol consumption (OR: 1.33, 95% CI: 1.16-1.63), overweight or obesity (OR: 2.01, 95% CI: 1.79-2.41), and intellectual work (OR: 1.36, 95% CI: 1.11-1.72). Conclusion: The prevalence of dyslipidemia among young adults aged 18-45 years in the southeastern coast of China was high. To prevent dyslipidemia at an early age, it is essential to conduct effective intervention programs targeting risk factors and to implement routine screening programs.

Predictors of Health-Related Quality of Life and Influencing Factors for COVID-19 Patients, a Follow-Up at One Month.

OBJECTIVE: To survey the health-related quality of life (HRQoL) and its influencing factors among patients with COVID-19 in their first medical follow up. METHODS: All patients diagnosed with COVID-19 were discharged from 12 hospitals in Wenzhou, Zhejiang from Jan 17, 2020 to Mar 20, 2020. Prospectively collected and analyzed data included demographics, clinical symptoms, comorbidity, and chest CT imaging features at the first follow up, 1 month after discharge. All patients underwent the HRQoL evaluation with the Chinese version of Short-Form 36-item questionnaire (SF-36) as well as a general condition questionnaire. Factors associated with SF-36 were constructed using linear regression. Predictors of impaired physical component summary (PCS) and a mental component summary (MCS) were identified by logistic regression. RESULTS: SF-36 demonstrated a significant difference in HRQoL in patients with COVID-19, except in physical function (PF), when compared to the general Chinese population (p<0.05). The multiple linear regressions demonstrated that age was negatively associated with PF, role physical (RP), but positively associated with vitality (VT) (p<0.05). PF, bodily pain (BP), and role-emotional (RE) were negatively associated with the female sex (p<0.05). For mental health, the clinical subtypes were significant associated factors (p < 0.05). Length of stay (LOS) was strongly negatively associated with RE and RP, and positively associated with VT (p< 0.05). Logistical regression revealed that non-obese overweight (OR 3.71) and obesity (OR 3.94) were risk factors for a low PCS and female sex (OR 2.22) was a risk factor for a low MCS. CONCLUSIONS: Health-related quality of life was poor among COVID-19 patients at the 1 month follow-up. Patients suffered from significant physical and psychological impairment. Therefore, prospective monitoring of individuals exposed to SARS-CoV-2 is needed in order to fully understand the long-term impact of COVID-19, as well as to inform prompt and efficient interventions to alleviate suffering.

The Synergistic Roles of the Chronic Prenatal and Offspring Stress Exposures in Impairing Offspring Learning and Memory.

In Alzheimer's disease (AD), extensive experimental studies have demonstrated a negative impact of chronic stress during various stages of life (including prenatal phase) on some aspects of AD pathology. Nevertheless, presently, few studies have been involved in the learning and memory impairments, as well as neuropathology elicited by the chronic prenatal stress (CPS) and the chronic offspring stress (COS) exposures simultaneously, particularly for the adult male APPswe/PS1dE9 murine offspring. Therefore, the aim of the present study was to investigate the influence of CPS on learning and memory impairments induced by COS in 6-month-old male APPswe/PS1dE9 offspring mice and the related mechanism. Our study firstly demonstrates that 14-day exposure to CPS could exacerbate the learning and memory impairments, as well as neuropathological damages in the CA3 regions of the hippocampus and cortex neurons, which is induced by the 28-day exposure to COS in 6-month-old male APPswe/PS1dE9 offspring mice. In addition, CPS could potentiate the production of AßPP, Aß42, and corticosterone in 6-month-old male APPswe/PS1dE9 offspring that also suffer COS. In conclusion, our novel findings strongly implicate the synergistic roles of the CPS and COS exposures in impairing offspring learning and memory. Moreover, CPS potentiating the production of Aß42 might be mediated by glucocorticoids through increasing the expression of APP and BACE1 gene.