The relationship between dietary patterns and premature coronary heart disease (CHD), as well as the underlying proteomic mechanisms, remains incompletely understood. Using data from the Global Burden of Disease (GBD) 2021 study, we calculated the population attributable fraction (PAF) to derive weights for dietary factors and constructed a dietary score specific to premature CHD. This score was evaluated in 14 134 UK Biobank participants with proteomics data. Protein associations with the dietary score and incident premature CHD were assessed using multivariable linear regression and Cox proportional hazards models under strict dual-filtering criteria. Statistical mediation analysis was performed to explore whether proteins may partially account for the observed diet-CHD association. A higher GBD dietary score was associated with a reduced risk of premature CHD. Individuals in the highest quintile (Q5) of the dietary score exhibited a 47.0% lower risk compared with those in the lowest quintile (Q1) (HR: 0.530; 95% CI: 0.350-0.803). From 134 robust proteins identified via stringent intersection analysis as associated with both diet and premature CHD, 133 showed statistical evidence of mediation, with proportions ranging from -3.8% to 27.6%. A higher GBD dietary score is associated with a reduced risk of premature CHD, with proteins potentially mediating this relationship.

BackgroundSocial isolation is a key modifiable risk factor for cognitive decline, yet its mediating mechanisms are not fully understood.ObjectiveThis study examines depression and systemic inflammation (neutrophil-to-lymphocyte ratio, NLR) as mediators between social isolation and domain-specific cognitive impairments.MethodsUsing cross-sectional data from 1272 adults aged ≥60 (NHANES 2011-2014), we constructed a social isolation index (0-4) incorporating marital status, living arrangements, functional limitations, and social participation barriers. Cognition was assessed via Alzheimer's Disease Word Learning Test (CERAD-WL) (verbal memory), Animal Fluency (executive function), Digit Symbol Substitution Test (processing speed), and composite Z-scores. Mediation analyses with PHQ-9 depression scores and NLR controlled for sociodemographic, lifestyle, and clinical factors.ResultsSevere social isolation (score = 3) showed dose-response associations with cognitive impairment, particularly in processing speed (DSST β = -11.66, p < 0.01) and global cognition (Z-score β = -0.59, p < 0.01). Depression accounted for about 14.5-20.3% of the association with executive function and processing speed, and NLR explained 25.4% of verbal memory problems. Significant direct effects persisted post-mediation (e.g., CERAD-WL β = -0.519; DSST β = -2.374, p < 0.001), suggesting unmeasured pathways.ConclusionsSocial isolation was associated with cognition through tripartite mechanisms: depression-linked processing speed/executive dysfunction, inflammation-mediated verbal memory decline, and direct neurobiological effects. Integrated interventions targeting social connectivity and depression are clinically prioritized over anti-inflammatory strategies. Findings emphasize domain-specific vulnerabilities requiring precision approaches for isolated older adults.

Skeletal muscle insulin resistance (IR) is a critical deficiency in IR pathophysiology that substantially affects overall metabolic health. Skeletal muscle is mechanically sensitive since its structure and function are significantly influenced by factors such as mechanical stretching and tissue stiffness. These mechanical stimuli can cause adaptive changes that enhance muscle performance and resilience. In this review, we discuss the current state of skeletal muscle IR research from the perspective of mechanomedicine. We also systematically and comprehensively present the evolution of mechanomedicine in addressing skeletal muscle IR by various disciplines, including biomechanics, mechanobiology, mechanodiagnosis, and mechanotherapy. The goal of the review is to provide important theoretical insights and practical methods for elucidating the pathogenesis of IR and to advance diagnostic and therapeutic approaches informed by mechanomedicine.

Purpose:In this study, we used arterial spin labeling (ASL) to explore altered cerebral blood flow perfusion in Parkinson's disease (PD) patients with anxiety and assessed the relationship between anxiety and perfusion in various brain regions to determine the pathophysiologic basis for the occurrence of anxiety in patients with PD. Materials and methods:Seventy-three patients with PD who were treated at China-Japan Friendship Hospital from September 2023 to November 2024 were enrolled: 36 PD patients with anxiety (PD-A) and 37 PD patients without anxiety (PD-NA); in addition, 37 healthy volunteers were recruited as healthy controls (HCs). All the subjects underwent three-dimensional T1-weighted imaging (3D-T1WI) and pseudo-continuous arterial spin labeling (pCASL) sequential scans via 3.0-T MRI, and cerebral blood flow (CBF) values were obtained from the whole brain. Independent samples t tests and non-parametric Mann-Whitney U tests were applied to test the differences in the CBF values of each brain region between the PD and HC groups, and between the PD-A and PD-NA groups. The relationships between CBF values and anxiety scores in the PD group were also investigated. Results:CBF values in the bilateral frontal lobes, parietal lobes, temporal lobes, occipital lobes, substantia nigra, striatum, caudate nuclei, left pallidum, and bilateral cerebellum were lower in the PD group than in the HC group (P < 0.05). Compared with those in the PD-NA group, the CBF values of the bilateral frontal lobes, temporal lobes, left putamen and left pallidum were lower in the PD-A group (P < 0.05). CBF values in the left frontal lobe (r = -0.265, P = 0.024), right frontal lobe (r = -0.283, P = 0.015), left temporal lobe (r = -0.287, P = 0.014), and right temporal lobe (r = -0.275, P = 0.019) were negatively correlated with Hamilton Anxiety Scale (HAMA) scores in PD patients. Conclusion:The development of PD-A may be associated with dysfunctional brain perfusion in multiple brain regions, notably the bilateral frontal lobes, temporal lobes, left putamen, and left pallidum. Abnormal CBF in these brain regions may serve as a neuroimaging marker for early PD-A diagnosis. Using ASL to identify perfusion changes in core regions may advance our understanding of the pathophysiological mechanisms underlying PD-A.

This study developed a mobile health-based early identification model for postpartum depression (PPD) and evaluated its effectiveness in community postpartum visits. A randomized controlled trial included 102 postpartum women (intervention: n=54; control: n=48). The intervention group used the "Maternal Love Guardian" app, integrating clinical risk factors and digital phenotyping (behavioral, emotional, cognitive, and voice data) to stratify PPD risk. Primary outcomes included detection rates, model performance, and intervention adherence. The model achieved 90.0% sensitivity and 84.1% specificity (AUC=0.871) at 3 weeks postpartum. The intervention group had significantly shorter PPD identification time (11.8 vs. 26.9 days, P<0.001) and higher early intervention rates (25.9% vs. 8.3%, P=0.019). Digital phenotyping revealed key differences in sleep, step count, social activity, and speech rate in PPD cases. At 12 weeks, symptom improvement was faster (4.3 vs. 6.9 weeks, P=0.009), and mother-infant interaction scores improved (77.8 vs. 72.1, P=0.033). Community providers reported 23% reduced consultation time (P<0.001). Cost-effectiveness was favorable (8,924 RMB per QALY). The mobile health model enhances PPD detection, accelerates intervention, and improves outcomes efficiently.

Background:Gestational diabetes mellitus (GDM), a prevalent metabolic complication during pregnancy, has a global prevalence of approximately 14%. Its onset is closely associated with insulin resistance, insufficient compensatory function of β - cells, and abnormal placental function. Epidemiological studies have indicated that type 2 diabetes is an independent risk factor for breast cancer. However, the association between GDM and the risk of breast cancer remains controversial. Objective:This systematic review and meta-analysis aim to comprehensively evaluate the association between GDM and the risk of breast cancer and explore its underlying mechanisms. Methods:This study systematically searched PubMed, Web of Science, Scopus, EMBASE, and the Cochrane Library databases, covering the period from establishing each database until April 14, 2025. Two researchers extracted relevant data and assessed the quality of included studies using the Newcastle-Ottawa Scale. The study evaluated inter-study heterogeneity using the I² statistic. Based on the magnitude of heterogeneity, fixed-effect or random-effect models were employed to calculate the pooled hazard ratio (HR) and its corresponding 95% confidence interval (CI). Additionally, subgroup analyses, sensitivity analyses, funnel plot analyses, and publication bias assessments were performed. All data analyses were conducted using STATA 17 software. Results:The overall analysis revealed no significant association between GDM and breast cancer risk (HR=1.03, 95%CI: 0.92-1.15). However, subgroup analysis revealed significant regional heterogeneity: within the regional subgroups, North American results showed an association between GDM and a reduced breast cancer risk (HR=0.89, 95%CI: 0.84-0.95), whereas Asian findings suggested an association with an increased risk (HR=1.23, 95%CI: 1.15-1.31). No significant associations were observed in subgroups based on study design (cohort/case-control) or follow-up duration (short-term/long-term). Sensitivity analysis demonstrated robust results, and there was no publication bias in this study. Conclusion:In summary, there is no significant association between GDM and breast cancer risk overall. However, notable regional heterogeneity exists: in the North American subgroup, GDM is associated with a reduced risk of breast cancer, while in the Asian subgroup, GDM is significantly associated with an increased risk of breast cancer. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251032589.

Atrial fibrillation (AF) is the most prevalent arrhythmia in clinical practice, and obesity serves as a significant risk factor for its development. The underlying mechanisms of obesity-related AF remain intricate and have yet to be fully elucidated. We have identified FPR2 as a potential hub gene involved in obesity-related AF through comprehensive analysis of four transcriptome datasets from AF patients and one transcriptome dataset from obese individuals, and its expression is up-regulated in both AF and obese individuals. Interestingly, ANXA1, the endogenous ligand of FPR2, was found to exhibit differential expression with AF and obesity. Specifically, it was observed to be down-regulated in AF patients but up-regulated in obese individuals. The susceptibility to AF in obese mice induced by high-fat diet (HFD) was increased following with the FPR2 blocker Boc-2.The administration of exogenous ANXA1 active peptide chain Ac2-26 can mitigate the susceptibility to AF in obese mice by attenuating atrial fibrosis, lipid deposition, oxidative stress injury, and myocardial cell apoptosis. However, this protective effect against AF susceptibility is reversed by AAV9-shAMPK-mediated AMPK specific knockdown in the myocardium. The vitro experiments demonstrated that silencing ANXA1 exacerbated lipid deposition, oxidative stress injury, and apoptosis induced by palmitic acid (PA) in cardiomyocytes. Additionally, Ac2-26 effectively mitigated myocardial lipid deposition, oxidative stress injury, and apoptosis induced by PA. These effects were impeded by FPR2 inhibitors Boc-2 and WRW4. The main mechanism involves the activation of AMPK by ANXA1 through FPR2 in order to enhance fatty acid oxidation in cardiomyocytes, thereby ultimately leading to a reduction in lipid accumulation and associated lipotoxicity. Our findings demonstrate that the ANXA1-FPR2 axis plays a protective role in obesity-associated AF by alleviating metabolic stress in the atria of obese mice, thereby emphasizing its potential as a promising therapeutic target for AF.

Objective: Anxiety symptoms are persistent in Parkinson's disease (PD), but the underlying neural substrates are still unclear. In the current study, we aimed to explore the underlying neural mechanisms in PD patients with anxiety symptoms. Methods: 42 PD-A patients, 41 PD patients without anxiety symptoms (PD-NA), and 40 healthy controls (HCs) were recruited in the present study. All the subjects performed 3.0T fMRI scans. The fractional amplitude of low-frequency fluctuation (fALFF) analysis was used to investigate the alterations in neural activity among the three groups. A Pearson correlation analysis was performed between the altered fALFF value of the PD-A group and anxiety scores. Results: Compared with HCs, PD-A patients had higher fALFF values in the left cerebellum, cerebellum posterior lobe, bilateral temporal cortex, and brainstem and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, and left inferior parietal lobule. Moreover, between the two PD groups, PD-A patients showed higher fALFF values in the right precuneus and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, left inferior parietal lobule, and left occipital lobe. Furthermore, Pearson's correlation analysis demonstrated that the right precuneus and left caudate were correlated with the Hamilton Anxiety Rating Scale scores. Conclusion: Our study found that anxiety symptoms in PD patients may be related to alterations of neurological activities in multiple brain regions. Furthermore, these may be critical radiological biomarkers for PD-A patients. Therefore, these findings can improve our understanding of the pathophysiological mechanisms underlying PD-A.

Global cerebral ischemia can elicit rapid innate neuroprotective mechanisms that protect against delayed neuronal death. Brain-derived 17β-estradiol (BDE2), an endogenous neuroprotectant, is synthesized from testosterone by the enzyme aromatase (Aro) and is upregulated by brain ischemia and inflammation. Our recent study revealed that G1, a specific G-protein-coupled estrogen receptor 1 (GPER) agonist, exerts anti-inflammatory and anti-apoptotic roles after global cerebral ischemia (GCI). Herein, we aimed to elucidate whether G1 modulates the early inflammatory process and the potential underlying mechanisms in the ovariectomized rat hippocampal CA1 region. G1 was found to markedly reduce pro-inflammatory (iNOS, MHCII, and CD68) and to enhance anti-inflammatory (CD206, Arginase 1, IL1RA, PPARγ, and BDNF) markers after 1 and 3 days of reperfusion after GCI. Intriguingly, the neuroprotection of G1 was blocked by the Aro inhibitor, letrozole. Conversely, the GPER antagonist, G36, inhibited Aro-BDE2 signaling and exacerbated neuronal damage. As a whole, this work demonstrates a novel anti-inflammatory role of GPER, involving a synergistic mediation with BDE2 during the early stage of GCI.

Tau protein hyperphosphorylation and formation of intracellular neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of Alzheimer's disease (AD) and positively correlated with the severity of AD symptoms. NFTs contain a large number of metal ions that play an important role in regulating tau protein phosphorylation and AD progression. Extracellular tau induces primary phagocytosis of stressed neurons and neuronal loss by activating microglia. Here, we studied the effects of a multi-metal ion chelator, DpdtpA, on tauinduced microglial activation and inflammatory responses and the underlying mechanisms. Treatment with DpdtpA attenuated the increase in the expression of NF-xB and production of inflammatory cytokines, IL-16, IL-6 and IL-10, in rat microglial cells induced by expression of human tau40 proteins. Treatment with DpdtpA also suppressed tau protein expression and phosphorylation. Moreover, treatment with DpdtpA prevented tauinduced activation of glycogen synthase kinase-36 (GSK-36) and inhibition of phosphatidylinositol-3-hydroxy kinase (PI3K)/AKT. Collectively, these results show that DpdtpA can attenuate tau phosphorylation and inflammatory responses of microglia by regulating the PI3K/AKT/GSK-36 signal pathways, providing a new option to alleviate neuroinflammation for the treatment of AD.& COPY; 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

In the “treat all” era, the high rate of late HIV diagnosis (LHD) worldwide remains an impediment to ending the HIV epidemic. In this study, we analyzed LHD in newly diagnosed people living with HIV (PLWH) and its impact on HIV transmission in Northeast China. Sociodemographic information, baseline clinical data, and plasma samples obtained from all newly diagnosed PLWH in Shenyang, the largest city in Northeast China, between 2016 and 2019 were evaluated. Multivariate logistic regression analysis was performed to identify risk factors associated with LHD. A molecular network based on the HIV pol gene was constructed to assess the risk of HIV transmission with LHD. A total of 2882 PLWH, including 882 (30.6%) patients with LHD and 1390 (48.2%) patients with non-LHD, were enrolled. The risk factors for LHD were older age (≥ 30 years: p < .01) and diagnosis in the general population through physical examination (p < .0001). Moreover, the molecular network analysis revealed that the clustering rate (p < .0001), the fraction of individuals with ≥ 4 links (p = .0847), and the fraction of individuals linked to recent HIV infection (p < .0001) for LHD were significantly or marginally significantly lower than those recorded for non-LHD. Our study indicates the major risk factors associated with LHD in Shenyang and their limited contribution to HIV transmission, revealing that the peak of HIV transmission of LHD at diagnosis may have been missed. Early detection, diagnosis, and timely intervention for LHD may prevent HIV transmission.

BackgroundPrevious studies have revealed alteration of functional connectivity (FC) in Parkinson's disease patients with anxiety (PD-A), but local brain activities associated with anxiety in Parkinson's disease (PD) patients remain to be elucidated. Regional homogeneity (ReHo) analysis was employed to investigate alterations of regional brain activities in PD-A patients. MethodsResting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 42 PD-A patients, 41 PD patients without anxiety (PD-NA), and 40 age-and gender-matched healthy control (HC) subjects. ReHo analysis was used to investigate the synchronization of neuronal activities in brain regions in the three groups. The relationship between ReHo value and anxiety score in the PD-A group was also investigated. ResultsParkinson's disease patients with anxiety showed increased ReHo values in the bilateral frontal lobes, caudate nucleus, and anterior cingulate gyrus [Gaussian random field (GRF) correction, voxel size p < 0.01, cluster size p < 0.05], compared with PD-NA patients and HC subjects, but the ReHo values of the right cerebellar hemisphere and posterior cerebellar lobe decreased (GRF correction, voxel size p < 0.01, cluster size p < 0.05). The increased ReHo values of the right superior frontal gyrus (r = 0.633, p = 0.001) and anterior cingulate gyrus (r = 0.45, p = 0.01) were positively correlated with anxiety scores in PD-A patients. ConclusionThe development of PD-A may be associated with dysfunctional local activities in multiple brain regions, including the frontal cortex, cerebella, basal ganglia, and limbic system. Abnormal ReHo values in these brain regions may serve as neuroimaging markers for the early diagnosis of PD-A. The results suggest that using ReHo analysis to identify functional changes in core regions may advance our understanding of the pathophysiological mechanisms underlying PD-A.

A method of judging potential sports injury posture using three-dimensional image analysis is proposed. The potential sports injury posture judgment analysis is carried out on the three-dimensional posture image of the movement, and the three-dimensional image analysis is introduced to analyze and locate the sports injury. An advanced scientific research project to capture the overall motion posture; use the smoothness parameter to design and implement a college sports training management decision-making system, improve the system application performance, increase by 12.0%, improve the quality of college sports training management decision-making, increase by 20.0%, extract 3D image points Cloud features; based on radial functions, collect and generate complete motion injury poses.

目的:研究帕金森病伴焦虑(PDA)患者静息状态下局部脑功能的变化.方法:对26例PDA患者及26例年龄性别相匹配的健康受试者进行静息态功能磁共振扫描,计算并比较其大脑局部一致性(Reho)的差异.结果:静息状态下,与正常被试组相比,PDA患者Reho升高的脑区包括左侧额中回(簇体积140,t=4.7754),左侧壳核(簇体积70,t=4.7754),左侧角回(簇体积68,t=3.7362);Reho减低脑区包括左侧小脑半球(簇体积98,t=-4.1288),右侧小脑半球(簇体积98,t=-4.1300),以上所有脑区升高或降低的Reho均存在统计学差异(均P＜0.05,簇体积＞54,AlphaSim多重比较校正).结论:静息状态下,PDA患者多个脑区Reho存在变化.

Daytime nap is associated with the risk of atherosclerotic cardiovascular disease (ASCVD). However, the contribution of platelet to the association of daytime nap with ASCVD remains unclear. We analyzed the mediation effect of abnormal platelet indices on the association between daytime nap and 10-year ASCVD risk. The participants of this study were 2445 adults aged 30 to 74 years without ASCVD from the baseline Wuhan residents (n = 3053) of the Wuhan-Zhuhai (WHZH) Cohort Study. Participants completed the questionnaire and physical examination (including blood pressure, height, weight, and blood biochemical indicators). We assessed the association of daytime nap or nocturnal sleep duration with 10-year ASCVD risk and mediation effects of platelet indices on the associations using generalized linear models (GLM). Individuals with daytime nap duration of 30 or 60 min had a 1.37- (95%CI: 1.05, 1.78) or 1.44- (95%CI: 1.17, 1.78) fold increased risk of 10-year ASCVD compared with non-nappers. As compared with non-nappers, MPV values or MPV/PLT ratio mediated 15.29% or 6.18% of the association of daytime nap duration of 30 min with 10-year ADCVD risk as well as 19.21% or 7.61% of the association of daytime nap duration of 60 min with 10-year ADCVD risk (all p < .05). Platelet might partially contribute to increased 10-year ASCVD risk in individuals with daytime nap duration of 30 or 60 min.

Identification of molecules specific to the retinal neovasculature will promote antiangiogenic therapy with enhanced targeting ability. The specificity of phage-displayed peptide GX1 (a cyclic 7-mer peptide motif CGNSNPKSC) to gastric cancer neovasculature has been extensively confirmed both in vitro and in vivo. To investigate the potential application of GX1 in antiangiogenic therapy targeting retinal angiogenesis-related diseases, we performed immunohistochemistry and immunofluorescence analyses. GX1 demonstrated positive staining in the retinal neovasculature in an oxygen-induced mouse model of retinopathy (OIR) as well as in rat retinal microvasculature endothelial cells (RMECs), confirming the major role of the GX1 receptor during retinal angiogenesis. Dimeric GX1 was synthesized to increase the binding affinity to the GX1 receptor, and the antiangiogenic effects were examined in RMECs in vitro and the retinal neovasculature in the OIR in vivo. Cell proliferation was evaluated using a Cell Counting Kit-8 (CCK-8) assay, revealing that compared with the GX1 monomer, dimeric GX1 significantly inhibited RMEC proliferation (P < 0.05). This finding may be attributed to the enhanced (P < 0.05) apoptosis induced by dimeric GX1 in RMECs based on results obtained from TUNEL, flow cytometric and cell cycle analyses. In RMECs, in vitro cell migration and tube formation were significantly inhibited following exposure to dimeric GX1. Intravitreal administration of dimeric GX1 resulted in a greater reduction in the retinal neovascularization in vivo than administration of the GX1 monomer (P < 0.05). In conclusion, dimeric GX1 showed greater inhibition of angiogenesis than monomeric GX1 and could be a promising agent for antiangiogenic therapy in retinal angiogenesis-related diseases.

Background: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function. Methods: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender-and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer's disease, Parkinson's syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models. Results: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19-1.93) or NNO (OR: 1.50, 95%CI: 1.16-1.93) levels as well as in the second tertile of urinary n-ary sumation Sigma Nic level (OR: 1.43, 95%CI: 1.13-1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or n-ary sumation Sigma Nic and the risk of cognitive impairment. Conclusions: Urinary levels of OHCotGluc, NNO or n-ary sumation Sigma Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.

Purpose: To study the risk factors of gestational diabetes mellitus (GDM) heterogeneity, and to evaluate the correlation between the risk factors and obesity. Methods: We performed a case-control study of 452 women with GDM and 516 women with normal glucose tolerance (NGT) at the first and second trimester. We defined GDM women as GDM-resistance subtype, GDM-dysfunction subtype, and GDM-mixed subtype, according to their simultaneous insulin-release test with predominant insulin-sensitivity defect, insulin-secretion defect, or both defects. Results: We found that higher maternal age, family history of diabetes, the elevated level of fasting blood glucose in the first trimester (>= 5.1 mmol/L) were risk factors of all GDM subtypes. Pre-pregnancy overweight/obesity and the increased gestational weight gain (GWG) in the first-trimester are risk factors of the GDM-resistance subtype. Indicators including younger age at first menstruation, the elevated levels of alanine aminotransferase (ALT), total bile acid (TBA), triglyceride (TG), and the decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors of the GDM-resistance subtype. However, the associations between those risk factors and GDM-resistance subtype attenuated after adjusted by pre-pregnancy body mass index (pre-BMI) and gestational weight gain (GWG) in the first trimester. Nonalcoholic fatty liver disease (NAFLD) and the improved level of TG are independent risk factors for the GDM-resistance subtype and the GDM-mixed subtype, respectively. Conclusion: Women with GDM exhibited heterogeneity based on glycemic physiology and their risk factors are not all the same. Some obesity-related risk factors are specific to the GDM-resistance subtype, which are mediated by pre-pregnancy overweight/obesity and the elevated GWG the first-trimester.

Neuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.