Objective: To explore the relationship of family function with sleep and externalizing problem behaviors of preschool children, so as to provide a guidance for externalizing problem prevention and intervention among preschool children. Methods: From October 2023 to January 2024, a convenience sampling method was used to select 5 138 preschool children from kindergartens in 8 districts of Wuhan City, Hubei Province. Parents completed the survey for Family Adaptability and Cohesion Scale, children s sleep habits and Child Behavior Checklist (CBCL). Spearman correlation analysis was used to examine the correlation of family function with scores of sleep quality and externalizing problem behaviors among preschool children. A mediation model analysis and bootstrap test were conducted to further investigate the mediating role of sleep quality between family function and externalizing problem behaviors. Mplus 8.7 software was used for latent profile analysis of family function. Results: The reported rates of poor sleep quality and externalizing problem behaviors among preschool children were 11.8% ( n =607), 20.0% ( n =1 026). The relevant analysis results showed that family function was negatively correlated with sleep quality and externalizing problem behaviors ( r = -0.20, -0.23), and sleep quality was positively correlated with externalizing problem behaviors ( r =0.27) ( P <0.01). The mediation effect test showed that family function negatively predicted externalizing problem behaviors ( β =-0.079) and sleep quality ( β = -0.075), while sleep quality positively predicted externalizing problem behaviors ( β =0.215) ( P <0.01). The latent profile analysis results showed that family function could be classified into 4 categories: high family function group (23.01%), upper middle family function group (44.65%), moderate family function group (26.24%) and low family function group (6.11%). Compared to high family function, the other three categories significantly positively predicted externalizing problem behaviors, and the mediating effects of sleep quality on different categories of family function were statistically significant [upper middle family function: mediation effect value was 0.022 (95% CI =0.004-0.041) and direct effect value was 0.329 (95% CI =0.263-0.396); middle family function: mediation effect value was 0.087 (95% CI =0.063-0.115) and direct effect value was 0.491 (95% CI =0.416-0.565); low family function: mediation effect value was 0.144 (95% CI =0.107-0.185) and direct effect 0.621 (95% CI =0.503-0.740)] ( P < 0.05 ). Conclusion Family function negatively predicts the externalizing problem behaviors of preschool children, and sleep quality plays a partial mediating role.

Objective: To explore the association between maternal lipid levels during pregnancy and the risk of overweight and obesity in offspring at 3 years of age, providing scientific evidences for the prevention and control of childhood obesity. Methods: A total of 2 432 mother-child pairs with maternal lipid tests during pregnancy and offspring s physical growth data at 3 years of age were included from the Borin in Guangzhou Cohort Study up to September 2021. Lipid indicators, including high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), triglycerides (TG), and total cholesterol (TC), were measured at 13-19 +6 weeks (mid pregnancy) and 32-39 +6 weeks (late pregnancy). Children s body mass index (BMI) Z score were calculated according to the World Health Organization s growth standards for children under 5 years old. The lipid Z score were divided into four quartiles: Q 1, Q 2, Q 3 and Q 4. Linear regression was used to analyze the relationship between maternal lipid levels during pregnancy and offspring’s BMI Z score at 3 years of age. Poisson regression with a robust error variance was employed to evaluate the association between maternal lipid levels during pregnancy and the at risk of overweight and obesity in offspring at 3 years of age, after adjusting for maternal age at conception, education level, parity, pre pregnancy BMI and gestational diabetes mellitus. Results: There was a statistically significnt difference in the detection rate of overweight and obesity risk among children with different mothers s pre pregnancy BMI ( χ 2=22.85, P <0.05). Linear regression analysis showed that TG levels in late pregnancy were positively related to BMI Z score ( β=0.10, 95%CI=0.02-0.18, P <0.05). Poisson regression with a robust error variance indicated that, compared with the Q 1 group of TC, the Q 4 group of TC in mid pregnancy was associated with an increased risk of overweight and obesity in offspring at 3 years of age ( RR=1.59, 95%CI =1.04-2.44); compared with the Q 1 group of TG, the Q 4 group of TG during late pregnancy increased the risk of overweight and obesity in offspring at 3 years of age ( RR=1.79, 95%CI =1.02-3.12) (both P <0.05). Conclusions Maternal serum TC level during mid pregnancy can increase the risk of overweight and obesity in offspring at 3 years of age. Maternal serum TG levels during late pregnancy is positively correlated with BMI and the risk of overweight and obesity in offspring at 3 years of age.

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Purpose To explore the clinicopathological characteristics of atypical spindle cell lipomatous tumour(ASLT).Methods The clinical pathology,immunopheno-type,and molecular characteristics of 8 ASLTs diagnosed and treated in Fujian Cancer Hospital from 2020 to 2023 were col-lected.The histological morphology,immunophenotype and mo-lecular characteristics of 8 ASLTs were evaluated by HE stai-ning,immunohistochemistry and FISH.Clinicopathological fea-tures of 8 ASLTs were analyzed with literature review.Results Mixed distribution of spindle cells and adipocytes in different proportions was seen in all 8 cases,with no or mild cell atypia and no necrosis.Immunophenotypically,8 ASLTs were CD34 and S-100 positive to varying degrees,RB was negative,MDM2 and CDK4 were negative or focus positive,and Ki67 prolifera-tion index was low.FISH showed MDM2 amplification was nega-tive in 6 cases.Conclusion ASLT is a newly named benign adipose-derived tumor subtype with unique morphology,immu-nophenotype,and molecular characteristics.It has a good prog-nosis.Correct diagnosis can avoid clinical over-treatment.

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

BACKGROUND:Inflammation and oxidative stress contribute to the barriers of regeneration in chronic wound.Oxymatrine has various biological activities,such as anti-oxidation,anti-inflammation and so on,which may have the potential effect of promoting wound healing. OBJECTIVE:To investigate the effect of oxymatrine on wound healing and the protective effect on H2O2-induced oxidative stress injury in human keratinoid cell line HaCaT cells. METHODS:(1)In vivo experiment:Hyaluronic acid methacryloyl hydrogels containing 0,0.05,0.1,0.2 g/L oxymatrine were prepared.A full-layer skin defect model with a diameter of 12 mm was made in the back of 75 diabetic mice and randomly divided into five groups for intervention,with 15 mice in each group.The wounds of the model group were bandaged and fixed.The wounds of the hydrogel group were covered with hyaluronic acid methacryloyl hydrogel.The wounds of the low-dose,moderate-dose and high-dose oxymatrine groups were covered with hyaluronic acid methacryloyl hydrogel containing 0.05,0.1,and 0.2 g/L oxymatrine,respectively,and then bandaged and fixed after light curing.Relevant indicators were detected within 14 days.(2)In vitro experiment:Human keratinocyte line HaCaT was divided into five groups.The normal group was cultured conventionally.H2O2 group and low-,moderate-and high-concentration oxymatrine groups were treated with H2O2 for 4 hours,and then the medium was replaced with medium containing 0,0.05,0.1,and 0.2 g/L oxymatrine,respectively,and the relevant indexes were detected after 24 hours of culture. RESULTS AND CONCLUSION:(1)In vivo experiment:Compared with the model group,the wound healing rate of mice in the hydrogel group had no significant change.The wound healing rate of mice in the low-,moderate-and high-dose oxymatrine group was increased at 7 and 14 days after treatment(P<0.05).Pathological observation of wound section 14 days after treatment showed that compared with the model group,the thickness of regenerated epidermal layer,the number of microvessels,and collagen deposition in the moderate-and high-dose oxymatrine groups were increased(P<0.05).Western blot assay analysis of wound samples 7 days after surgery showed that compared with the model group,the protein expressions of tumor necrosis factor α and interleukin 6 in the moderate-and high-dose oxymatrine groups were decreased(P<0.05).(2)In vitro experiment:CCK8 assay,EdU and Ki67 staining showed that compared with the H2O2 group,the cell proliferation ability of the moderate-and high-concentration oxymatrine groups was significantly increased(P<0.05).Compared with the H2O2 group,mitochondrial membrane potential was increased(P<0.05)and reactive oxygen species content was decreased(P<0.05)in the moderate-and high-concentration oxymatrine groups.Western blot assay results showed that compared with the H2O2 group,the expression levels of Nrf2 nuclear protein,Nrf2 total protein,HO-1 protein,and superoxide dismutase 1 protein were increased in the high-concentration oxymatrine group(P<0.05).(3)These findings confirm that oxymatrine can alleviate oxidative stress damage in HaCat cells and accelerate wound healing by upregulating the levels of Nrf2 and HO-1 protein.

BackgroundDiabetes distress is highly prevalent and has adverse impacts in adolescent patients with type 1 diabetes. However， the related factors of diabetes distress in adolescents with type 1 diabetes are not clear. ObjectiveTo identify the factors associated with diabetes distress in adolescents with type 1 diabetes using Meta-analysis， and to provide a scientific evidence for effective prevention and improvement of diabetes distress in adolescents with type 1 diabetes. MethodsOn December 1， 2022， a computerized search was conducted on databases including PubMed， Cochrane Library， Web of Science， Embase， CNKI， Wanfang Data， VIP and China Biomedical Literature Database， and studies relevant to diabetes distress in adolescents with type 1 diabetes were systematically included. Quality assessment of cross-sectional and cohort studies was carried out using criteria defined by the Agency for Healthcare Research and Quality （AHRQ） and Newcastle-Ottawa Scale （NOS）. Then the included studies were pooled in a Meta-analysis using Revman 5.3. ResultsA total of 22 studies were included， involving 6 442 adolescents with type 1 diabetes. Meta-analysis denoted that the occurrence of diabetes distress among adolescents with type 1 diabetes was correlated with age （r=0.094，95% CI： 0.042~0.145）， HbA1c （r=0.291， 95% CI： 0.248~0.335）， trait anxiety （r=0.585， 95% CI： 0.526~0.639）， depressive symptoms （r=0.635， 95% CI： 0.590~0.676）， resilience （r=-0.410， 95% CI： -0.528~-0.276） and parents' diabetes distress （r=0.462， 95% CI： 0.421~0.501）. ConclusionFactors including age， HbA1c， trait anxiety， depressive symptoms， resilience and parents' diabetes distress are correlated with diabetes distress in adolescents with type 1 diabetes. ［Funded by Sichuan Science and Technology Program （number， 24KJPX0034）］

Objective:To explore the intolerable uncertainty level and its related factors in female patients re-ceiving in vitro fertilization and embryo transfer.Methods:A total of 503 female patients receiving in vitro fertiliza-tion and embryo transfer in a tertiary reproductive hospital in Shandong province were selected.Theywere assessed with a self-designed general information questionnaire,the Intolerance of Uncertainty scale-12(IUS-12),Fertility Problem Inventory(FPI,including social concern,sexual concern,relationship concern,need for parenthood,and re-jection of childfree lifestyle),and Hospital Anxiety and Depression Scale(HADS).Results:The score of IUS-12 was 28(13,60).Multiple stepwise regression analysis showed that having children,having anxiety symptoms,the scores of social concern,sexual concern and need for parenthood were positively associated with IUS-12 scores(β=0.11,0.19,0.21,0.13,0.25),and rejection of childfree lifestyle was negatively associated with IUS-12 scores(β=-0.18).Conclusion:It suggests that the unbearable uncertainty of women receiving in vitro fertilization and embryo transfer is related to whether they have children,social concerns,sexual concerns,need for parenthood,and rejection of childfree lifestyle.

Objective:To elucidate the cytopathological characteristics,molecular subtypes,and clinical prognoses of metastatic breast car-cinoma with serosal effusions.Methods:Seventeen cases that included effusion cytology and clinical data were retrospectively analyzed.Two patients were diagnosed between April 2016 and September 2023 at the Suzhou Ninth Hospital Affiliated to Soochow University,and 15 patients were diagnosed at The First Affiliated Hospital of Soochow University.Cytopathological characteristics,molecular subtypes,and prognoses were analyzed.Results:The cytopathological features of metastatic breast carcinoma in serosal effusions were as follows:1)In-vasive ductal carcinoma:one cell type was relatively densely arranged in nests or colored spheres,which displayed an elevated nuclear/cyto-plasmic ratio,irregular nuclear membrane,and cytoplasmic mucin vacuoles.The other cell type was tiled,single scattered,and varied in size and shape,with enlarged nuclei and elevated nuclear/cytoplasmic ratio.2)Invasive lobular carcinoma:cells were scattered and uniform in size and shape.The nuclei had a relatively regular shape,but displayed an elevated nuclear-to-cytoplasmic ratio.Among the 17 breast can-cer cases,6 had transitioned in molecular subtyping,including 1 case from Luminal A to triple-negative type,1 case from Luminal B to hu-man epidermal growth factor receptor 2(HER-2)-overexpressing type,and 4 cases from Luminal B to triple-negative type.Conclusions:The cytopathological characteristics of serous effusion cells combined with immunocytochemical staining and fluorescence in situ hybridization(FISH)suggest that it is important to determine the origin and molecular typing of tumor cells.This provides an important basis for precise clinical treatment and prognosis.