👤 Lili Ping

Gene-environment interactions play a critical role in shaping phenotypic heterogeneity in complex psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is a key genetic regulator of stress-sensitive neuroplasticity. Yet, how We conducted a case-control study including 93 patients with first-episode schizophrenia (SZ) and 64 healthy controls. Childhood trauma exposure was assessed using the Childhood Trauma Questionnaire (CTQ), and symptom dimensions were evaluated with the Positive and Negative Syndrome Scale (PANSS). Three Patients with SZ exhibited significantly higher CTQ scores across all trauma subtypes compared with controls (all These findings demonstrate that Show less

Accurate classification of intestinal polyps is crucial for preventing colorectal cancer but is hindered by visual similarity among subtypes and endoscopic variability. While deep learning aids in diagnosis, single-modal models face efficiency-accuracy trade-offs and ignore pathological semantics. We propose a multimodal framework that integrates endoscopic images with structured pathological descriptions to bridge this gap. We propose LPA-Tuning CLIP, which incorporates three key innovations: replacing CLIP's instance-level contrastive loss with cross-modal projection matching (CMPM) with ID loss to explicitly optimize intraclass compactness and interclass separation through label-aware image-text similarity matrices; introducing structured clinical semantic templates that encode WHO diagnostic criteria into hierarchical text prompts for consistent pathology annotations; and developing medical-aware augmentation that preserves lesion features while reducing domain shifts. The experimental results demonstrate that our proposed method achieves an accuracy of 85.8% and an F1 score of 0.862 on the internal test set, establishing a new state-of-the-art performance for intestinal polyp classification. This study proposes a multimodal polyp classification paradigm that achieves 85.8% accuracy on three-subtype classification via endoscopic image-pathology text joint representation learning, outperforming unimodal baselines by 8.7% and a multimodal baseline by 4.3%. Show less

To investigate the relation of glycemic and lipid metabolism with brain structure and cognitive function in people with diabetes, so as to improve cognitive function in these individuals. Based on the UK Biobank, 26,394 patients, who were diagnosed with diabetes by doctors between 2006 and 2010, were included in the study. The demographic information, clinical data of glycemic and lipid metabolism and cognitive function (brain MRI and cognitive function scores) were collected. Multiple linear regression and non-restricted cubic spline analyses were used to investigate the relations of glycemic and lipid metabolism with brain structure and cognitive function. In this study, the mean age of people with diabetes (containing 39 % females) was 59.58 ± 7.21 years. Higher random blood glucose (β = -0.116, p < 0.001) and glycosylated hemoglobin (HbA1c) (β = -0.062, p = 0.051) were associated with a smaller brain volume. Higher HbA1c (β = 0.036, p < 0.001; β = 0.023, p = 0.021) was related with worse cognitive function. Further analysis showed that HbA1c < 6.5 % had a protective effect on cognitive function, and HbA1c = 6.5 %∼8.5 % and >8.5 % was unrelated and negatively related with cognitive function, respectively. Different types of lipids had varying effects on cognitive function. Higher total cholesterol (TC) (β = 0.125, p = 0.008), low density lipoprotein-cholesterol (LDL-C) (β = 0.086, p = 0.025), and ApoB (β = 0.092, p = 0.026) were associated with more significant brain structural abnormalities. Conversely, triglyceride (TG) = 0.75∼8.0 mmol/L was positively correlated with cognitive function (β = -0.036, p < 0.001; β = -0.044, p < 0.001; β = 0.058, p = 0.001), and higher ApoA (β = -0.032, p < 0.001; β = -0.033, p < 0.001; β = 0.047, p = 0.004) was associated with better cognitive function. The age-stratified analysis revealed that the impact of lipids on cognitive function was age-dependent. TC and LDL-C were related to brain structural abnormalities in the 55-60 age group, while TG had a stronger protective effect on cognitive function in older adults, particularly those aged 65-70 years. In people with diabetes, higher HbA1c (>8.5 %), as well as elevated TC, LDL-C, and ApoB, are associated with worse brain structure and cognitive function. Conversely, HbA1c < 6.5 % and elevated TG within the range of 0.75∼8.0 mmol/L have a protective effect on cognitive function, and the later exhibited more evident impact in older adults. To prevent or delay the onset of dementia in people with diabetes, it may be necessary to intensify glycemic control, targeting an HbA1c level of <6.5 %. Additionally, the age-specific lipid-lowering strategies shall be considered, with more flexible triglyceride-lowering goals for elderly patients. Show less

CLN3 disease is a rare fatal juvenile neurodegenerative lysosomal storage disease. Challenges in tracking underlying disease biology have hindered the identification of effective therapeutic targets and the ability to execute clinical trials in this rare disease. While diagnostic biomarkers are readily available, biomarkers that reflect the underlying core lysosome dysfunction are lacking. In the present study, CLN3 Show less

Lipolysis in white adipose tissue (WAT) provides fatty acids as energy substrates for thermogenesis to increase energy expenditure. Syndecan-4 (Sdc4) is a transmembrane proteoglycan bearing heparan sulfate chains. Although single nucleotide polymorphisms (SNPs) of the Sdc4 gene have been identified linking to metabolic syndromes, its specific function in adipose tissue remains obscure. Here, we show that Sdc4 serves as a regulator of lipid metabolism and adaptive thermogenesis. Sdc4 expression and shedding are elevated in the white adipose tissue (WAT) of diet-induced obese mice. Adipocyte-specific deletion of Sdc4 promotes lipolysis and WAT browning, thereby raising whole-body energy expenditure to protect against diet-induced obesity. Mechanistically, fibroblast growth factor 2 (FGF2) is a paracrine factor that maintains energy homeostasis. Elevated shed Sdc4 concentrates and delivers FGF2 to fibroblast growth factor receptor 1 (FGFR1) on adipocytes, which in turn suppresses lipolysis by reducing hormone-sensitive lipase (HSL) activity, thus exaggerating adipose tissue dysfunction upon high-fat diet induction. Sdc4-deficient adipocytes show higher lipolytic and thermogenic capacity by enhancing HSL phosphorylation and UCP1 expression. Overall, our study reveals that adipocyte-derived shed Sdc4 is a novel suppressor of lipolysis, contributing to decreased energy expenditure, thus exaggerating obesity. Targeting shed Sdc4 is a potential therapeutic strategy for obesity. Show less

This investigation aimed to evaluate the efficacy and safety of rosuvastatin in treating moderate to severe metabolic associated fatty liver disease (MAFLD). This prospective, open-label, randomized study included non-diabetic participants with metabolic syndrome and intrahepatocellular lipid (IHCL) levels >10 %, as determined by proton magnetic resonance spectroscopy ( Thirty-two participants completed the study. Rosuvastatin resulted in a significant absolute (△IHCL: 7.61 ± 4.51 vs. 1.54 ± 5.33, p = 0.002) and relative reduction in IHCL (△IHCL%: -42.28 ± 24.90 % vs. -8.91 ± 31.93 %, p = 0.003) compared to the control. Reduction in IHCL correlated significantly with decreases in low-density lipoprotein cholesterol (LDL-C) (r = 0.574, p < 0.01), apolipoprotein B (ApoB) (r = 0.660, p < 0.001), and free fatty acids (FFA) (r = 0.563, p = 0.005). No significant safety differences were observed between groups. Rosuvastatin significantly reduced hepatic steatosis in individuals with moderate to severe MAFLD and metabolic syndrome over 52 weeks, while maintaining a favorable safety profile. Show less

It remains unclear whether lipid profiles and lipid-lowering medications are causally related to peripheral arterial disease (PAD). Explain whether there is a causal relationship between lipid status and lipid-lowering drugs and PAD. In this two-sample Mendelian randomization (MR) analysis, we assessed the causal relationship between lipid traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), total cholesterol (TC), and LDL-associated genetic variants (HMGCR, NPC1L1, PCSK9, APOB), and the risk of PAD using genetic variants associated with these lipid markers. The study analyzed data from 1,654,960 individuals derived from the Global Lipid Genetics Consortium and the UK Biobank, ensuring a robust and comprehensive genetic insight into the effects of lipid dysfunction on PAD. We found genetically predicted associations between HDL-C (OR: 0.83, 95% CI: 0.83-0.77), LDL-C (OR: 1.29, 95% CI: 1.12-1.50), TC (OR: 1.14, 95% CI: 1.01- 1.29), TG (OR: 1.16, 95% CI: 1.04-1.24), APOB (OR: 1.31, 95% CI: 1.16-1.48), and APOA1 (OR: 0.84, 95% CI: 0.77-0.97), and the risk of PAD. In addition, inhibition of PCSK9 was associated with a reduced risk of PAD (OR: 0.68, 95% CI: 0.57-0.79, P<0.001), while no association between the other three gene proxies of LDL inhibition including HMGCR (OR: 1.21, 95% CI: 0.87-1.69, P=0.250), NPC1L1 (OR: 0.77, 95% CI: 0.44-1.33, P=0.344), and APOB (OR: 1.01, 95% CI: 0.87-1.26, P=0.890), and the risk of PAD were found. Based on genetic evidence, dyslipidemia is an important risk factor for PAD. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may be an effective strategy for the treatment of PAD. Show less

To explore the diagnosis value of inflammatory markers and cytokines in neonatal sepsis. In this retrospective analysis, 90 cases of neonatal sepsis admitted to our hospital from April 2019 to April 2021 were included in the observation group, and 70 healthy neonates who received routine physical examinations in our hospital during the same period were recruited as the control group. Comparison and analysis of inflammatory markers and cytokines levels between the two groups were performed on days 1, 3, and 7 after the onset. Flow cytometry was used to measure the white blood cells (WBCs) and percentage of neutrophils (N%), immunoturbidimetry was used to determine C-reactive protein (CRP), immunochromatographic analysis was used to determine procalcitonin (PCT) in plasma, and the enzyme-linked immunosorbent assay was used to determine interleukin-27 (IL-27), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor- Compared with healthy controls, neonatal sepsis resulted in significantly higher levels of WBC, N%, PCT, and CRP on days 1, 3, and 7 after onset. The levels of WBC, N%, and PCT were continuously decreased from day 1 to day 7, while the levels of CRP were increased on day 1 and day 3 but declined on day 7 ( Neonatal sepsis was associated with fluctuating levels of WBC, N%, PCT, CRP, IL-27, IL-6, IL-10, and TNF- Show less

Cancer cells undergo significant lipid metabolic reprogramming to ensure sufficient energy supply for survival and progression. However, how cancer cells integrate lipid metabolic signaling with cancer progression is not well understood. In the present study, we demonstrated that C/EBPδ, a critical lipid metabolic regulator, is a TGF-β1 downstream gene and promotes lung adenocarcinoma metastasis. Importantly, C/EBPδ caused significant oscillations in both lipid metabolic and epithelial to mesenchymal transition (EMT) gene networks. Mechanistically, we demonstrated that C/EBPδ recruited oncogene NCOA3 to transcriptionally activate Slug, a canonical EMT transcription factor, which in turn induced oxLDL receptor-1 (Lox1) expression and enhanced oxLDL uptake to promote cancer metastasis, which could be blocked with LOX1 neutralizing antibody. In summary, our results unveiled a previously unappreciated interplay between lipid metabolic and metastatic program, as well as the existence of a pivotal C/EBPδ-Slug-Lox1 transcription axis to promote oxLDL levels and cancer metastasis. Show less

Metanephric adenoma is a rare, benign renal neoplasm with occasional misdiagnosis. However, its molecular characterization is not fully understood. In this study, we use the hybrid capture-based Next-Generation Sequencing to sequence a panel of 295 well-established oncogene or tumor suppressor genes in 28 cases of MA patients in China. Novel clinicopathological markers associated with the mitogen-activated protein kinase (MAPK) pathway in metanephric adenoma were detected by immunohistochemistry. It was found that except for BRAF (22/28) mutations (c.1799 T > A, p.V600E), NF1 (6/28), NOTCH1 (5/28), SPEN (5/28), AKT2 (4/28), APC (4/28), ATRX (3/28), and ETV4 (3/28) mutations could also be detected. Meanwhile, a novel and rare gene fusion of STARD9-BRAF, CUX1-BRAF, and LOC100507389-BRAF was detected in one MA patient. In addition, although MEK phosphorylation was normally activated, the phosphorylation level of ERK was low in metanephric adenoma cases. Highly expressed p16 and DUSP6 may have contributed to these results, which maintained MA as a benign renal tumor. This study provides novel molecular and pathological markers for metanephric adenoma, which could improve its diagnosis and increase the understanding of its pathologic mechanism. Show less

Increasing evidence shows that diabetes causes cardiac dysfunction. We hypothesized that a glucagon-like peptide-1 analogue, liraglutide, would attenuate cardiac dysfunction in diabetic rats. Twenty-four Sprague Dawley (SD) rats were divided into 2 groups fed either a normal diet (normal, n = 6) or a high-fat diet (HFD, n = 18) for 4 weeks. Then, the HFD rats were injected with streptozotocin (STZ) to create a diabetic rat model. Diabetic rats were divided into 3 subgroups receiving vehicle (diabetic, n = 6), a low dose of liraglutide (Llirag, 0.2 mg/kg/day, n = 6) or a high dose of liraglutide (Hlirag, 0.4 mg/kg/day, n = 6). Metabolic parameters, systolic blood pressure, heart rate, left ventricular (LV) function, and whole genome expression of the heart were determined. Diabetic rats developed insulin resistance, increased blood lipid levels and oxidative stress, and impaired LV function, serum adiponectin, NO. Liraglutide improved insulin resistance, serum adiponectin, NO, heart rate and LV function and reduced blood triglyceride, total cholesterol levels and oxidative stress. Moreover, liraglutide increased heart Show less

To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). Seven single-nucleotide polymorphisms (rs3764261 in The following polymorphisms were statistically associated with HDL-C level after adjusting for age, gestational week, pre-pregnancy BMI and state of GDM or HOMAIR: (i) rs3764261 (b = -0.055 mmol/L, 95% CI -0.101 to -0.008, Several risk alleles found to be related to HDL-C in GWAS are also associated with HDL-C levels in pregnant Chinese Han women and these risk loci contribute additively to low HDL-C levels. Show less

Hyperlipidemia has unique adverse effects on pregnant women and their offspring. The underlying genetic factors related to lipid levels in pregnant populations need more studies. This study aimed to investigate the relationship between 6 single-nucleotide polymorphisms (SNPs) and plasma lipid levels during pregnancy. A total of 2060 pregnant women were recruited. Fasting plasma lipids were measured in the third trimester of pregnancy. Six SNPs (rs1260326 in GCKR, rs1800775 in CETP, rs515135 in APOB, rs1800588 in LIPC, rs964184 in ZPR1, and and rs4420638 in APOC1 of each participant were genotyped using TaqMan allelic discrimination assays. The relationships between the 6 loci and plasma lipids were analyzed using a multiple linear regression method. Two variants, rs1260326 (β = 0.220, 95% confidence interval [CI] = 0.148-0.291; P = 2.048 × 10 Loci found by genome-wide association studies to be associated with plasma lipid levels in the general population were also related to lipid levels in the third trimester of pregnancy. This finding implies that changes to lipid profiles during gestation may be associated with SNPs of lipid-related genes. Variants of lipid-related genes are important predictors for estimating lipid concentrations during the pregnancy. Show less

Yin-deficiency-heat (YDH) syndrome is a concept in Traditional Chinese Medicine (TCM) for describing subhealth status. However, there are few efficient diagnostic methods available for confirming YDH syndrome. To explore the novel method for diagnosing YDH syndrome, we applied iTRAQ to observe the serum protein profiles in YDH syndrome rats and confirmed protein levels by ELISA. A total of 92 differentially expressed proteins (63 upregulated proteins and 29 downregulated proteins), which were mainly involved in complement and coagulation cascades and glucose metabolism pathway, were identified by the proteomic experiments. Kininogen 1 (KNG1) was significantly increased ( Show less