Objective: The diabetic autonomic neuropathy is one of the most common complications in type 2 diabetes mellitus (T2DM), especially gastrointestinal autonomic neuropathy (GAN), which occurs in up to 75% of patients. The study aimed to investigate the gut microbiota composition, structure, and function in T2DM patients with GAN (T2DM_GAN) and set up a link between gut microbiota and clinical characteristics of patients.Methods: DNA was extracted from fecal samples of three groups using the kit method: healthy volunteers (n = 19), the patients with T2DM (n = 76), and T2DM_GAN (n = 27). Sequencing of 16S ribosomal DNA was performed using the MiSeq platform.Results: According to the clinical data, higher age, lower triglyceride, and lower body mass index were the main features of patients with T2DM_GAN. The gut microbiota analysis showed that Bacteroidetes, Firmicutes, and Proteobacteria constituted the three dominant phyla in healthy individuals. In addition, the gut microbiota structure and function of T2DM_GAN patients were clearly different from that of T2DM patients. T2DM patients were characterized by Fusobacteria, Fusobacteriia, Fusobacteriales, Fusobacteriaceae, Fusobacterium, Lachnoclostridium, and Fusobacterium_mortiferum. Those gut microbiota may be involved in carotenoid and flavonoid biosyntheses. Relatively, the Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Escherichia-Shigella, Megasphaera, Escherichia_coli, and Megasphaera_elsdenii were characteristic in the T2DM_GAN patients. Those may be involved in bacterial invasion of epithelial cells and pathogenic Escherichia coli infection.Conclusions: GAN exacerbated gut microbiota dysbiosis in adult patients with T2DM. The findings indicated that phyla Fusobacteria and class Gammaproteobacteria were closely related to the occurrence of T2DM. Especially the latter may promote T2DM_GAN.

Previous studies examining associations between subclinical hypothyroidism (SCH) with in vitro fertilization (IVF) outcome indicate some benefits of levothyroxine (LT4) treatment. But IVF outcomes in treated SCH women whose serum Thyroid Stimulating Hormone (TSH) concentration did and did not exceed 2.5 mIU/L before the IVF cycle has not been studied thoroughly. In this study, we performed a prospective cohort study with 270 treated subclinical hypothyroidism patients undergoing their first IVF retrieval cycle at a single cite. SCH in women receiving LT4 replacement with a basal TSH level between 0.2-2.5mIU/L displayed a similar rate of clinical pregnancy (47.4% vs 38.7%, P = .436), miscarriage (7.4% vs 16.7%, P = .379) and live birth (43.9% vs 32.3%, P = .288) compared to women with a basal TSH level between 2.5-4.2 mIU/L. Strictly controlled TSH (less than 2.5 mIU/L) before IVF may have no effect on the pregnancy rate in LT4 treated SCH women.

Background: Alzheimer’s disease (AD) is an age-progressive neurodegenerative disorder that affects cognitive function. There have been several functional connectivity (FC) strengths; however, FC density needs more development in AD. Therefore, this study wanted to determine the alternations in resting-state functional connectivity density (FCD) induced by Alzheimer’s and mild cognitive impairment (MCI). Methods: One hundred and eleven AD patients, 29 MCI patients, and 73 healthy controls (age- and sex-matched) were recruited and assessed using resting-state functional magnetic resonance imaging (MRI) scanning. The ultra-fast graph theory called FCD mapping was used to calculate the voxel-wise short- and long-range FCD values of the brain. We performed voxel-based between-group comparisons of FCD values to show the cerebral regions with significant FCD alterations. We performed Pearson’s correlation analyses between aberrant functional connectivity densities and several clinical variables with adjustment for age and sex. Results: Patients with cognition decline showed significantly abnormal long-range FCD in the cerebellum crus I, right insula, left inferior frontal gyrus, left superior frontal gyrus, left inferior frontal gyrus, and right middle frontal gyrus. The short-range FCD changed in the cerebellum crus I, left inferior frontal gyrus, left superior occipital gyrus, and right middle frontal gyrus. The long- and short-range functional connectivity in the left inferior frontal gyrus was positively correlated with Mini-mental State Examination (MMSE) scores. Conclusions: FCD in the identified regions reflects mechanism and compensation for loss of cognitive function. These findings could improve the pathology of AD and MCI and supply a neuroimaging marker for AD and MCI.

Objective: The objective ofthis study was to assess the association between thyroid hormone (TH) levels in follicular fluid (FF) and serum and to determine whether THs impact assisted reproductive technology (ART) outcomes.Methods: This study enrolled 299 women undergoing ART. Blood samples were drawn on the day of human chorionic gonadotrophin (HCG) administrationand analysed for thyroid-stimulating hormone (TSH), thyroxine(T4), triiodothyronine(T3),free T4 (fT4),free T3(fT3), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) levels. FF was obtained on the oocyte pick up (OPU) day and analysed forTSH, T4, T3, fT4, fT3, TPOAb, TgAb and estradiol levels.Results: (1) There were significant positive correlations between serum and FF TH and thyroid autoantibody levels. Statistically significant differences were discovered in serum and FF levels of TSH (p ≤ 0.001), T4 (p ≤ 0.001), T3 (p ≤ 0.001), TPOAbs (p ≤ 0.001) and TGAbs (p = 0.021).(2) Serum T4 levels [121.9(104.8,140.8) vs 114.1(98.6,130.6) nmol/l,p = 0.026], serum fT4 levels[(19.0(17.7,21.8) vs 18.6(17.0,20.1) pmol/l,p = 0.026], serum T4/T3 ratios [62.5 (55.7, 66.2) vs 59.4 (53.4, 64.9),p = 0.029], FF fT4 levels [19.0(17.5,21.3) vs 18.1(16.8,19.9) pmol/l,p = 0.009] and FF T4/T3 ratios [52.6 (46.4, 57.3) vs 50.0 (43.7, 53.1),p = 0.004] were significantly higher in the successful pregnancy group than the implantation failure group.(3) Spearman’s rank correlation analysis revealed positive associations of both the FF T4/T3 ratio and serum TSH levels with the numbers of retrieved oocytes (total or MII) and embryos (fertilized, cleavage, and good quality).Conclusions: TH levels in FF are strongly correlated with those in serum on the HCG day, and THs on the HCG day may affect ART outcomes.

BACKGROUND The lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility. AIM To evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight. METHODS Ninety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People’s Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs. RESULTS Fasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL. CONCLUSION Heterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Objectives: Patients with type 1 diabetes (T1D) face unique challenges in glycaemic control due to the complexity and uniqueness of the dietary structure in China, especially in terms of postprandial glycaemic response (PPGR). This study aimed to establish a personalized model for predicting PPGR in patients with T1D.Materials and methods: Data provided by the First People’s Hospital of Yunnan Province, 13 patients with T1D, were recruited and provided with an intervention for at least two weeks. All patients were asked to wear a continuous glucose monitoring (CGM) device under free-living conditions during the study period. To tackle the challenge of incomplete data from wearable devices for CGM measurements, the GAIN method was used in this paper to achieve a more rational interpolation process. In this study, patients’ PPGRs were calculated, and a LightGBM prediction model was constructed based on a Bayesian hyperparameter optimisation algorithm and a random search algorithm, which integrated glucose measurement, insulin dose, dietary nutrient content, blood measurement and anthropometry as inputs.Results: The experimental outcomes revealed that the PPGR prediction model presented in this paper demonstrated superior accuracy (R=0.63) compared to both the carbohydrate content only model (R=0.14) and the baseline model emulating the standard of care for insulin administration (R=0.43). In addition, the interpretation of the model using the SHAP method showed that blood glucose levels at meals and blood glucose trends 30 minutes before meals were the most important features of the model.Conclusion: The proposed model offers a heightened precision in predicting PPGR in patients with T1D, so it can better guide the diet plan and insulin intake dose of patients with T1D.