This study aimed to explore the potential classification and influencing factors of post-traumatic stress disorder (PTSD) in intensive care unit (ICU) patients receiving mechanical ventilation to prov Show more
This study aimed to explore the potential classification and influencing factors of post-traumatic stress disorder (PTSD) in intensive care unit (ICU) patients receiving mechanical ventilation to provide a theoretical basis for formulating targeted intervention measures. A total of 229 patients on mechanical ventilation who were hospitalized in the intensive care unit of a Class III Grade A hospital in Zunyi from August 2023 to July 2024 were selected as research participants using a purposive sampling method. The General information questionnaire, Eysenck Personality Questionnaire Revised, Short Scale for Chinese (EPQ-RSC), Simplified Coping Style Questionnaire (SCSQ), Perceived Social Support Scale (PSSS), and Hospital Anxiety and Depression Scale (HADS) were used to assess the patients within 7 days after discharge from the ICU. One month after extubation, a cross-sectional survey was conducted using the Impact of Event Scale-Revised (IES-R). Latent profile analysis (LPA) was used to analyze the latent subtypes of PTSD, and univariate analysis and a disordered multivariate logistic regression model were used to evaluate the influencing factors associated with different types of PTSD. A total of 215 valid questionnaires were collected, and the effective recovery rate was 93.89%. The incidence of PTSD was 14.9% (95% CI: 10.12%-19.64%). There were three latent categories of PTSD among the ICU patients on mechanical ventilation: the "low-stress group" (56.8%, PTSD symptoms among mechanically ventilated ICU survivors manifest in three distinct profiles. Our findings strongly recommend early psychological screening, particularly focusing on anxiety and depression levels and patients' educational background. Medical staff should formulate targeted intervention plans based on the characteristics of different patient categories to lower the level of PTSD in patients. Show less
The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relations Show more
The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relationships and underlying mechanisms. Genetic variants related to lipid profiles and targets for lipid modification were sourced from the Global Lipids Genetics Consortium. Summary data for 10 cardiometabolic diseases were compiled from both discovery and replication data sets. Expression quantitative trait loci data from relevant tissues were employed to evaluate significant lipid-modifying drug targets. Comprehensive analyses including colocalization, mediation, and bioinformatics were conducted to validate the results and investigate potential mediators and mechanisms. Significant causal associations were identified between lipids, lipid-modifying drug targets, and various cardiometabolic diseases. Notably, genetic enhancement of LPL (lipoprotein lipase) was linked to reduced risks of myocardial infarction (odds ratio [OR] The study substantiates the causal role of lipids in specific cardiometabolic diseases, highlighting LPL as a potent drug target. The effects of LPL are suggested to be influenced by changes in glucose and blood pressure, providing insights into its mechanism of action. Show less
Inhibition of branched-chain ketoacid dehydrogenase kinase (BDK or BCKDK), a negative regulator of branched-chain amino acid (BCAA) metabolism, is hypothesized to treat cardio-metabolic diseases. From Show more
Inhibition of branched-chain ketoacid dehydrogenase kinase (BDK or BCKDK), a negative regulator of branched-chain amino acid (BCAA) metabolism, is hypothesized to treat cardio-metabolic diseases. From a starting point with potential idiosyncratic toxicity risk, modification to a benzothiophene core and discovery of a cryptic pocket allowed for improved potency with 3-aryl substitution to arrive at PF-07328948, which was largely devoid of protein covalent binding liability. This BDK inhibitor was shown also to be a BDK degrader in cells and in vivo rodent studies. Plasma biomarkers, including BCAAs and branched-chain ketoacids (BCKAs), were lowered in vivo with enhanced pharmacodynamic effect upon chronic dosing due to BDK degradation. This molecule improves metabolic and heart failure end points in rodent models. PF-07328948 is the first known selective BDK inhibitor candidate to be examined in clinical studies, with Phase 1 single ascending dose data showing good tolerability and a pharmacokinetic profile commensurate with once-daily dosing. Show less
Cadmium (Cd) contamination in plants and soil poses significant risks to livestock, particularly sheep. Cd exposure often leads to severe gastrointestinal diseases in sheep that are difficult to treat Show more
Cadmium (Cd) contamination in plants and soil poses significant risks to livestock, particularly sheep. Cd exposure often leads to severe gastrointestinal diseases in sheep that are difficult to treat. Milk-derived exosomes, particularly those from sheep milk (SM-Exo), have shown potential in treating gastrointestinal disorders, though their efficacy in Cd-induced colitis remains unclear. In this study, we investigated the therapeutic potential of SM-Exo in a Cd-induced colitis model. Hu sheep were exposed to Cd, and their fecal microbiota were collected to prepare bacterial solutions for fecal microbiota transplantation (FMT) in mice. The changes in gut microbiota and gene expression were analyzed through microbiome and transcriptomics. Our results showed that prior to treatment, harmful bacteria (e.g., Show less
Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which a Show more
Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which are responsible for transporting lipids to peripheral tissues. The cellular mechanisms that regulate ApoB and B-lp production, secretion, transport, and degradation remain to be fully defined. In humans, elevated levels of vascular B-lps play a causative role in cardiovascular disease. Previously, we have detailed that human B-lp biology is remarkably conserved in the zebrafish using an Show less
Type 2 diabetes (T2D) is a chronic metabolic disorder that has high comorbidity with mental disorders. The genetic relationships between T2D and depression are far from being well understood. We perfo Show more
Type 2 diabetes (T2D) is a chronic metabolic disorder that has high comorbidity with mental disorders. The genetic relationships between T2D and depression are far from being well understood. We performed genetic correlation, polygenic overlap, Mendelian randomization (MR) analyses, cross-trait meta-analysis, and Bayesian colocalization analysis to assess genetic relationships between T2D and depression, in the forms of major depressive disorder (MDD) and depressed affect (DAF). Then, the summary data-based MR (SMR) analysis was performed to prioritize genes contributing to MDD and to T2D from functional perspective. MDD-driven signaling pathways were constructed to understand the influence of MDD on T2D at the molecular level. T2D has positive genetic correlations both with MDD (r Our study points out that depression, in the forms of MDD and DAF, may increase the risk of T2D. Analysis of underlying genetic variation and the molecular pathways, connecting depression and T2D, indicate that the pathophysiological foundations of these two conditions have a notable overlap. Show less
Ischemia-reperfusion (IR) and adriamycin (also named doxorubicin, DOX)-induced acute myocardial injuries have a significant impact on health, causing serious economic and medical burdens. Therefore, w Show more
Ischemia-reperfusion (IR) and adriamycin (also named doxorubicin, DOX)-induced acute myocardial injuries have a significant impact on health, causing serious economic and medical burdens. Therefore, we need to explore and identify drugs with potential therapeutic value for treating I/R- and DOX-induced myocardial injury. In the present study, we explored the therapeutic potential of FGF4 for I/R and DOX-induced myocardial injury. We found that FGF4 showed good improvement in acute cardiac injury. However, due to the short half-life of FGF4, we further prepared a myocardial-targeted FGF4-sustained release nanoliposome (named FGF4-NANO-IMTP). We investigated the effect of FGF4-NANO-IMTP on myocardial injury caused by I/R and DOX. Show less
The causal relationship between the familial hypercholesterolemia (FH) and intestinal vascular diseases was unnoticed. This study aims to investigate the cause-and-effect relationship of FH with risk Show more
The causal relationship between the familial hypercholesterolemia (FH) and intestinal vascular diseases was unnoticed. This study aims to investigate the cause-and-effect relationship of FH with risk of intestinal vascular diseases in human. A Mendelian randomization (MR) analysis was performed by extracting summary-level datasets for FH or FH concurrently with ischemic heart disease (IHD) and intestinal vascular diseases from the FinnGen study including 329,115, 316,290 and 350,505 individuals. The inverse-variance weighted (IVW) method and the weighted median method were applied to analyze the causal relationships between FH or FH concurrently with IHD and the risk of intestinal vascular diseases. Cochran's Q statistic method and MR-Egger regression were used to assess heterogeneity and pleiotropy. The IVW method demonstrated that FH was significantly associated with higher odds of intestinal vascular diseases [OR (95%CI): 1.22 (1.03, 1.45)] ( In conclusion, FH was causally positive-associated with the increased risk of intestinal vascular diseases, revealing a potential unfortunate outcome for FH. Therefore, patients with FH should pay closely attention to the risk of intestinal vascular diseases. Our study may provide evidence for new diagnostic and therapeutic strategies in clinical practices. Show less
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from Show more
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from colorectal cancer (CRLM) remain poorly understood. Here we show that patients with CRLM whose liver metastases (LM) exhibited tumor fibrosis (Fibrosis+ LM) had significantly worse progression-free survival (P = 0.025) and overall survival (P = 0.008). Single-cell RNA sequencing revealed that the tumor microenvironment of the Fibrosis+ LM was characterized by T cells with an exhausted phenotype, macrophages displaying a profibrotic and suppressive phenotype and fibrosis-promoting fibroblasts. Further investigation highlighted the pivotal role of VCAN_eCAF in remodeling the tumor fibrosis in the tumor microenvironment of Fibrosis+ LM, emphasizing potential targetable interactions such as FGF23 or FGF3-FGFR1. Validation through multiplex immunohistochemistry/immunofluorescence and spatial transcriptomics supported these findings. Here we present a comprehensive single-cell atlas of tumor fibrosis in LM, revealing the intricate multicellular environment and molecular features associated with it. These insights deepen our understanding of tumor fibrosis mechanisms and inform improved clinical diagnosis and treatment strategies. Show less
Infantile hemangioma (IH) is a common benign vascular tumor in infants, often requiring intervention due to potential functional impairment and cosmetic concerns. Propranolol, a nonselective β-adrener Show more
Infantile hemangioma (IH) is a common benign vascular tumor in infants, often requiring intervention due to potential functional impairment and cosmetic concerns. Propranolol, a nonselective β-adrenergic receptor blocker, is the first-line therapy for IH, yet its mechanisms remain incompletely elucidated. This prospective study investigated the systemic angiogenic protein profile changes in response to propranolol in 14 treatment-naïve IH infants compared to 14 healthy controls using antibody array analysis. We identified twenty-six angiogenic proteins significantly downregulated in pretreatment IH patients compared to healthy controls. After 3 months of propranolol treatment, six proteins including HB-EGF, TGFα, ANGPTL4, Follistatin, Tie-1 and PLGF were significantly upregulated. Bioinformatic enrichment analysis revealed that these proteins are involved in key biological processes and signaling pathways, including epithelial cell proliferation, angiogenesis regulation, VEGF signaling, ERBB-EGFR axis, Ras-MAPK, and PI3K-Akt pathways. These results suggest that propranolol treatment is associated with a rebalancing of dysregulated angiogenic proteins in IH, through modulating both pro- and anti-angiogenic factors to rebalance vascular homeostasis. Our study provides novel insights into the systems-level pharmacological actions of propranolol and proposes potential biomarkers for treatment response evaluation. Show less
Altered levels of human plasma metabolites have been implicated in the etiology of bipolar disorder (BD). However, the causality between metabolites and the disease was not well described. We performe Show more
Altered levels of human plasma metabolites have been implicated in the etiology of bipolar disorder (BD). However, the causality between metabolites and the disease was not well described. We performed a bidirectional metabolome-wide Mendelian randomization (MR) analysis to evaluate the potential causal relationships between 871 plasma metabolites and BD. We used DrugBank and ChEMBL to evaluate whether related metabolites are potential therapeutic targets. Finally, Bayesian colocalization analysis was performed to identify shared genomic loci BD and identified metabolites. Our MR results showed that six metabolites were significantly associated with a reduced risk of BD, including arachidonate (20:4n6) (OR: 0.90, 95% CI: 0.84-0.95) and sphingomyelin (d18:2/24:1, d18:1/24:2) (OR: 0.92, 95% CI: 0.87-0.96), while five metabolites were significantly associated with an increased risk of BD, including 1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) (OR: 1.09, 95% CI: 1.05-1.13). However, our reverse MR analysis showed that BD was not associated with the levels of any metabolite. Additionally, the leave-one-out analysis revealed SNPs within chromosome 11 loci harboring MYRF, FADS1, and FADS2 as ones with the potential to influence partial causal effects. Druggability evaluation showed that 10 of the BD-related metabolites, such as sphingomyelin and cytidine, have been targeted by pharmacologic intervention. Colocalization analysis highlighted one colocalized region (chromosome 11q12) shared by 11 metabolites and BD and pointed to some genes as possible players, including FADS1, FADS2, FADS3, and SYT7. Our study supported a causal role of plasma metabolites in the susceptibility to BD, and the identified metabolites may provide a new avenue for the prevention and treatment of BD. Show less
Colorectal cancer (CRC) is one of the leading causes of cancer-related death, and most CRCs arise from colorectal adenomas. Early detection and removal of precancerous lesions during the adenoma-carci Show more
Colorectal cancer (CRC) is one of the leading causes of cancer-related death, and most CRCs arise from colorectal adenomas. Early detection and removal of precancerous lesions during the adenoma-carcinoma sequence can significantly reduce CRC risk. However, current clinical practice lacks rapid, noninvasive screening tools for reliable adenoma detection. Proteomic analysis was performed on serum samples from patients with inflammatory polyps (non-neoplastic), patients with adenomas, and healthy controls to identify key differentially expressed proteins capable of distinguishing adenoma patients. The alterations in these candidate proteins were further validated by ELISA to evaluate their potential as diagnostic biomarkers for colorectal adenoma. In two independent cohorts, we identified two candidate biomarkers, apolipoprotein A4 (APOA4) and filamin A (FLNA), through a multi-step selection process involving ANOVA p-value screening, sparse partial least squares discriminant analysis (sPLS-DA), and LASSO regression analysis. These candidates were subsequently validated in a third cohort using ELISA. The ELISA results for APOA4 were discordant with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) findings. In contrast, FLNA levels measured by ELISA showed a progressive decrease from healthy controls to patients with inflammatory polyps and further to those with adenomas. We propose FLNA as a potential biomarker for the diagnosis of colorectal adenomas. The areas under the ROC curves exceeded 0.7 for both key clinical comparisons: 0.810 for adenomas versus healthy controls, and 0.734 for adenomas versus inflammatory polyps. Overall, this study not only enhances our understanding of the serum proteome in colorectal adenoma but also identifies FLNA as a promising biomarker for its clinical diagnosis. Show less
Oxymatrine is an alkaloid with the property of immunomodulation. Recent studies have demonstrated that oxymatrine inhibits experimental autoimmune encephalomyelitis (EAE), an animal model of multiple Show more
Oxymatrine is an alkaloid with the property of immunomodulation. Recent studies have demonstrated that oxymatrine inhibits experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by promoting the production of interferon-β (IFN-β). However, the mechanism through which oxymatrine regulates the production of IFN-β remains unclear. The aim of this study was to investigate the pharmacological effects and related molecular mechanisms of oxymatrine in the treatment of EAE through in vivo and in vitro experiments. Oxymatrine alleviated neurological dysfunction, demyelination, and inflammation in EAE mice. It reduced microglia/macrophage infiltration and polarization, lowered pro-inflammatory cytokine levels (iNOS, TNF-α), and enhanced the expression of IL-10 and IL-27. Additionally, oxymatrine upregulated the STING/TBK1/IRF3 signaling pathway in EAE mice, promoting IFN-β production by microglia. Similarly, in LPS-induced BV2 cells, oxymatrine suppressed inflammatory factors and activated the STING/TBK1/IRF3 pathway to enhance IFN-β production. Notably, treatment with the STING inhibitor, C176, reversed these effects in both EAE mice and LPS-induced BV2 cells, confirming the pathway's critical role in the mechanism of oxymatrine therapy. Oxymatrine promotes IFN-β production in microglia by upregulating the STING/TBK1/IRF3 signaling pathway, thereby alleviating the neurological dysfunction of EAE and reducing pathological and inflammatory events. This study identifies a novel anti-EAE mechanism of oxymatrine: promoting IFN-β production in microglia by activating the STING/TBK1/IRF3 pathway. However, it lacks clinical sample verification. If validated later, oxymatrine may provide a more economical, convenient endogenous IFN-β induction regimen for MS patients. Show less
Atherosclerosis (AS) remains a leading cause of cardiovascular morbidity and mortality, characterized by intricate interactions between immune dysregulation and lipid metabolism abnormalities-identify Show more
Atherosclerosis (AS) remains a leading cause of cardiovascular morbidity and mortality, characterized by intricate interactions between immune dysregulation and lipid metabolism abnormalities-identifying key mediators in its pathogenesis is critical for improving diagnostics and therapies. This study focuses on Transmembrane Protein 106A (TMEM106A) to clarify its role and clinical relevance in AS progression. Public transcriptomic datasets (GSE43292, GSE100927, GSE28829) were analyzed to assess TMEM106A expression and diagnostic value; single-cell RNA-seq data (GSE159677) defined its cellular localization. Immune infiltration (ssGSEA, Cibersort, xCell) and CellChat (intercellular communication) analyses explored its immune associations. TMEM106A was significantly upregulated in AS samples across datasets, with strong diagnostic efficacy (AUC 0.80-0.95). Single-cell analysis confirmed its specific enrichment in macrophages, with functional links to immune-related pathways. TMEM106A promoted macrophage infiltration, foam cell formation, oxidative stress, and inflammatory responses, while regulating PLCB2 in chemokine signaling; silencing TMEM106A alleviated these pro-atherosclerotic effects. TMEM106A contributes to AS progression by modulating macrophage-mediated immune responses and chemokine signaling, as validated in experimental models. These findings support its potential as a clinically relevant biomarker and promising therapeutic target for AS intervention. Show less
The present case report presents the diagnostic challenges of pediatric diffuse low-grade glioma (pDLGG) with oligodendroglioma-like features. The patient, an 11-year-old girl, presented with refracto Show more
The present case report presents the diagnostic challenges of pediatric diffuse low-grade glioma (pDLGG) with oligodendroglioma-like features. The patient, an 11-year-old girl, presented with refractory epilepsy and brain imaging did not provide a clear diagnosis. Intraoperatively, the tumor appeared gray-yellow to gray-red, with moderate texture and unclear borders, consistent with LGG. Postoperative pathology showed diffuse infiltrative growth of the tumor, with pleomorphic cell morphology and oligodendroglioma-like gliocyte proliferation. Staining was positive for markers such as glial fibrillary acidic protein and Olig-2. Genomic analysis revealed BRAF V600E, fibroblast growth factor receptor (FGFR)1 and FGFR4 mutations, but no IDH mutations or other related mutations. The final diagnosis was pDLGG with alterations in the MAPK pathway. The present case underscores the importance of molecular and histological features in the diagnosis of pDLGG, especially when clinical and imaging characteristics are atypical, as molecular diagnostics provide key insights for disease classification. Show less
GATA2 establishes transcriptomes governing hematopoietic stem/progenitor cell development. In progenitors, GATA2 represses inflammatory genes (Il6st and Il6ra) encoding IL6ST/GP130 and IL6RA receptor Show more
GATA2 establishes transcriptomes governing hematopoietic stem/progenitor cell development. In progenitors, GATA2 represses inflammatory genes (Il6st and Il6ra) encoding IL6ST/GP130 and IL6RA receptor subunits mediating IL-6 signaling. While IL6ST heterodimerizes with IL6RA, IL-11, IL-27, oncostatin M, and leukemia inhibitory factor receptors, IL6RA heterodimerizes exclusively with IL6ST to confer IL-6 signaling. As GATA2-dependent repression is not well understood, we devised a multi-omics strategy to elucidate mechanisms underlying repression and applied the approach to the cytokine/chemokine receptor gene family. Identifying accessible distal and intronic chromatin sites in GATA2-deficient (GATA2 Show less
Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac h Show more
Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac hypertrophy. SMURF2 (SMAD-specific E3 ubiquitin ligase 2) is an important member of NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) family of HECT E3 ubiquitin ligases. In this study we investigated the regulatory role of SMURF2 in cardiac hypertrophy. Experiment models were established in mice by transverse aortic constriction (TAC) in vivo, as well as in neonatal rat cardiomyocytes (NRCMs) by treatment with angiotensin II (Ang II, 1 μM) in vitro. We showed that the expression levels of SMURF2 were significantly elevated in cardiac tissues from patients with cardiac hypertrophy and the two experiment models. In NRCMs, SMURF2 knockdown or treatment with a specific SMURF2 inhibitor heclin (8 μM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, evidenced by reduced mRNA levels of Anp, Bnp and β-Mhc as well as cell surface. Prophylactic or therapeutic administration of heclin (10 mg·kg Show less
Post-hemorrhagic hydrocephalus (PHH) is a neurological disease that primarily affects premature infants and involves infiltration of blood into the brain's ventricles followed by excessive accumulatio Show more
Post-hemorrhagic hydrocephalus (PHH) is a neurological disease that primarily affects premature infants and involves infiltration of blood into the brain's ventricles followed by excessive accumulation of cerebrospinal fluid (CSF), leading to ventricular enlargement and increased intracranial pressure. The precise mechanisms driving PHH development and persistence are incompletely understood and lack disease-modifying treatments. Using a mouse model of PHH, we have identified transcriptomic, proteomic, and cellular features of PHH involving neuroimmune and neurovascular alterations recapitulating those reported in human disease. Improvement upon a lysophosphatidic acid (LPA)-induced PHH mouse model was combined with unbiased proteomic and single-nucleus transcriptomics that identified microglial molecular pathways propagating PHH. Pharmacological depletion of microglia in vivo significantly reduced PHH-associated ventriculomegaly. These data identify microglial and neurovascular elements in the development of PHH, implicating them as other potentially tractable therapeutic targets beyond LPA receptors, towards developing medical treatments for PHH. Show less
The association between gut microbes and Alzheimer's disease (AD) has not been entirely elucidated. We aimed to demonstrate the association between gut microbes and AD and to further investigate the p Show more
The association between gut microbes and Alzheimer's disease (AD) has not been entirely elucidated. We aimed to demonstrate the association between gut microbes and AD and to further investigate the pathogenesis of microbes with a causal relationship to AD. Mendelian randomization analyses were used to determine the significant causal relationship between gut microbes and AD. Protein-protein interaction (PPI) network was used to identify the hub genes. Functional enrichment analysis was used to reveal the pathogenesis theoretically between gut microbes and AD. In the present study, a total of 32 microbes were identified that were significantly associated with AD. Subsequently, DLGAP2, NRXN3, NEGR1, NTNAP2, MYH9, and SCN3A were identified as hub genes. The genes NRXN3, NEGR1, and NTNAP2 were enriched in the cell adhesion molecules (CAMs) signaling, and the taxons of gut microbes that corresponded to these were Show less
Pheochromocytomas and paragangliomas (PPGLs) exhibit the highest degree of heritability among all human tumors, yet the genetics of urinary bladder paragangliomas (UBPGLs) remains poorly understood. T Show more
Pheochromocytomas and paragangliomas (PPGLs) exhibit the highest degree of heritability among all human tumors, yet the genetics of urinary bladder paragangliomas (UBPGLs) remains poorly understood. The present study aims to examine the characteristics of a cohort of Chinese patients with UBPGLs, focusing particularly on genetics. The study included 70 Chinese patients with UBPGLs from 15 centers in China, 240 patients with non-head and neck PGLs (non-HNPGLs) outside the urine bladder, and 16 Caucasian patients with UBPGLs. Tumor DNA samples were sequenced by next generation sequencing. All identified pathogenic variants (PVs) were confirmed by Sanger sequencing. Among the 70 Chinese patients, PVs were identified in 38 cases: 23 in cluster 1 A (13 SDHB, 1 SDHD, 1 SDHA, 4 IDH1, 2 SLC25A11, and 2 FH), 4 in cluster 1B (3 EPAS1 and 1 EGLN1), and 11 in cluster 2 genes (7 HRAS, 1 FGFR1, 2 NF1, and 1 H3F3A). Compared with other non-HNPGLs, UBPGLs had more PVs in cluster 1 A genes (32.9% vs. 14.2%, p < 0.001), but fewer in cluster 1B (5.7% vs. 19.2%, p = 0.002) and cluster 2 genes (15.7% vs. 42.5%, p < 0.001). PVs in SDHB (18.6%) was the most common in Chinese patients with UBPGLs, followed by HRAS (10.0%). No PVs was found in 45.7% of all UBPGLs. PVs in HRAS, SLC25A11, EPAS1, and FH were also identified in Caucasians with UBPGLs. Chinese patients with UBPGLs have a diverse genetic profile. PVs in cluster 1 A genes underlie nearly 1/3 of patients, highlighting the importance of genetic testing. Diverse germline and somatic PVs are also present in Caucasian patients with UBPGLs. Show less
Women diagnosed with PCOS exhibit a high prevalence of obstructive sleep apnea (OSA). This study aims to assess risk factors of OSA among patients with PCOS. This retrospective study included 126 pati Show more
Women diagnosed with PCOS exhibit a high prevalence of obstructive sleep apnea (OSA). This study aims to assess risk factors of OSA among patients with PCOS. This retrospective study included 126 patients with PCOS who were categorized into an OSA group (n = 30) and a non-OSA group (n = 96) according to the apnea-hypopnea index (AHI). A control group comprised 72 patients without PCOS who presented during the same period for infertility due to fallopian tube, pelvic, or male factors. Patients with PCOS A multivariate logistic regression model was used to analyze independent risk factors for OSA in the PCOS group. Patients with PCOS had significantly higher AHI values and elevated values for various physical indicators, including body mass index (BMI) and neck, waist, and hip circumferences; prolactin (PRL); fasting plasma glucose (FPG); insulin (FINS); triglycerides (TG); homeostasis model assessment of insulin resistance (HOMA-IR); 2-hour postprandial glucose (2-hPG) and insulin (2-hINS); AHI; and oxygen desaturation index (ODI). Conversely, levels of high-density lipoprotein cholesterol (HDL-C) and lowest oxygen saturation (LSaO OSA in PCOS patients is linked to metabolic indicators. High neck circumference and BMI levels were independent risk factors, highlighting the need for OSA in routine PCOS screening, particularly in the context of metabolic dysregulation. Show less
Mercury (Hg) is a widespread environmental pollutant with known neurotoxic and cardiometabolic effects, and its influence on lipid metabolism during childhood remains insufficiently understood. Mitoch Show more
Mercury (Hg) is a widespread environmental pollutant with known neurotoxic and cardiometabolic effects, and its influence on lipid metabolism during childhood remains insufficiently understood. Mitochondrial dysfunction is proposed as a potential mechanism linking Hg exposure to metabolic disruption. Mitochondrial DNA copy number (mtDNA-CN) is regarded as an indicator of mitochondrial biogenesis and functional capacity, where lower levels generally suggest mitochondrial damage or dysfunction. In contrast, ribosomal DNA (rDNA) and relative telomere length (RTL) reflect genomic stability and cellular aging. This study investigated the associations between blood Hg levels and serum lipid profiles in children and adolescents and assessed the mediating roles of mtDNA-CN, rDNA, and RTL. A cross-sectional study was performed among 352 children and adolescents aged 6–17 years in eastern China. Blood Hg levels were determined using inductively coupled plasma mass spectrometry (ICP-MS), and serum lipid markers, namely total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were assessed along with the genomic indicators such as mtDNA-CN, rDNA, and RTL. Multivariable linear regression and mediation analyses were conducted. Higher Hg levels were significantly related with increased TC (β = 0.144, Hg exposure in children and adolescents is linked to an atherogenic lipid profile, potentially through mitochondrial dysfunction. MtDNA-CN appears to be a sensitive molecular mediator of Hg-induced lipid disturbances, which highlights the relevance of mitochondrial health in early-life environmental epidemiology and cardiovascular risk prevention. The findings support early prevention strategies and environmentally focused health policies that reduce toxicant exposure and thus promote long-term cardiometabolic health in young populations. Show less
This study explored latent mental health profiles among adolescents in southwestern China and the association with emotional regulation using the dual-factor model framework. 1,682 junior middle schoo Show more
This study explored latent mental health profiles among adolescents in southwestern China and the association with emotional regulation using the dual-factor model framework. 1,682 junior middle school students completed the LPA revealed three profiles: Troubled (31.51%, high negative symptoms/low well-being), complete mental health (61.30%, low negative symptoms/high well-being), and more troubled (7.19%, severe negative symptoms/extremely low well-being). Cognitive reappraisal positively predicted complete mental health (vs. Troubled; Three distinct profiles emerged, differing from the traditional dual-factor model. Cognitive reappraisal protects mental health, while expressive suppression correlates with poorer outcomes, highlighting the need for targeted interventions promoting cognitive reappraisal. Show less
Hypertriglyceridemia, characterized by increased triglyceride (TG) concentrations, is considered the most important risk factor for cardiometabolic disorders, including dyslipidemia, atherosclerotic c Show more
Hypertriglyceridemia, characterized by increased triglyceride (TG) concentrations, is considered the most important risk factor for cardiometabolic disorders, including dyslipidemia, atherosclerotic cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD). Recently, the angiopoietin-like protein (ANGPTL) family, which comprises ANGPTL1 to ANGPTL8, was confirmed to play an important role in modulating lipoprotein lipase (LPL) activity. However, understanding of the underlying mechanisms remains limited. Importantly, emerging evidence has linked several transcriptional and post-transcriptional factors to the potential alteration of TG metabolism via ANGPTL proteins. This review focused on the similarities and differences in the expression, structural features, and modulatory profile of three ANGPTLs: ANGPTL3, ANGPTL4, and ANGPTL8. In addition, the regulatory functions of those three ANGPTLs in modulating LPL were summarized to provide potential therapeutic and clinical strategies for hypertriglyceridemia and its related cardiometabolic disorders. Show less
This study aims to investigate the molecular differences and commonalities between systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) by analyzing RNA-sequencing (RNA-seq) data. By focusi Show more
This study aims to investigate the molecular differences and commonalities between systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) by analyzing RNA-sequencing (RNA-seq) data. By focusing on differentially expressed genes and enriched pathways, the investigation seeks to identify unique biomarkers, shared pathways, and potential therapeutic targets for these autoimmune diseases. This study involved 10 patients with SSc and 24 with SLE who did not receive immunosuppressants. RNA-seq data from patients with SSc and SLE were analyzed using DESeq2 to identify differentially expressed genes. Functional and pathway enrichment analyses were conducted and comparative analyses were performed. We identified 2055 differentially expressed genes (DEGs) between patients with SSc and controls. Notably, the expression of the shared gene RGS5 was significantly downregulated in both SLE and SSc, with a more pronounced downregulation in SSc. Additionally, the expression of the key transcription factor EGR1 was upregulated in SSc, whereas that of BLK, ITGAM, and IFNG was upregulated in SLE. Network analysis identified hub genes-AP3D1, FTX, USP47, CUX1, ZC3H4, CAND1, INTS1, TRNT1, MTERF1, and SETD1B-that may play critical roles in the progression of both SLE and SSc. These findings suggest that RGS5 could serve as a shared biomarker for vascular dysfunction, while EGR1 and BLK may represent therapeutic targets in SSc and SLE. Overall, this analysis enhances understanding of distinct and overlapping gene expression signatures in SSc and SLE, providing a foundation for future targeted treatment strategies and requiring further validation in larger cohorts. Show less