BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

Abstract Improving the coping ability of parents of adolescents with non-suicidal self-injury (NSSI) can help reduce the frequency of NSSI, improve the quality of life of adolescents with NSSI, and alleviate the physical and psychological burden on their parents. The review summarizes the concept and significance of parental coping ability among adolescents with NSSI, as well as the current status of research and intervention strategies in China and abroad, with the aim of providing a reference for relevant research.

ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology， animal experiments， and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 （CCK-8） assay was adopted to observe the effects of different volume fractions （5%， 10%， 15%， and 20%） of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells， and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma （5%， 10%， 15%， and 20%） on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-， medium-， and high-dose （4.63， 9.25， 18.5 g·kg^-1） Huangqi Xiayuxue decoction and sorafenib （20 mg·kg^-1） groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention， hematoxylin-eosin （HE） staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay was employed to detect cell apoptosis. Immunohistochemistry （IHC） was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 （PI3K/Akt/FoxO1） signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology， among which tumor protein p53 （TP53）， Akt1， and signal transducer and activator of transcription 3 （STAT3） were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation， as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group， all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells （P<0.01）. The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma （P<0.01）. Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume， promoted tumor cell apoptosis in the high-dose group， up-regulated the protein and mRNA levels of Bax and Caspase-3， down-regulated the protein and mRNA levels of Bcl-2， and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway （P<0.05， P<0.01）. ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.

ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology， animal experiments， and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 （CCK-8） assay was adopted to observe the effects of different volume fractions （5%， 10%， 15%， and 20%） of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells， and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma （5%， 10%， 15%， and 20%） on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-， medium-， and high-dose （4.63， 9.25， 18.5 g·kg^-1） Huangqi Xiayuxue decoction and sorafenib （20 mg·kg^-1） groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention， hematoxylin-eosin （HE） staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay was employed to detect cell apoptosis. Immunohistochemistry （IHC） was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 （PI3K/Akt/FoxO1） signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology， among which tumor protein p53 （TP53）， Akt1， and signal transducer and activator of transcription 3 （STAT3） were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation， as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group， all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells （P<0.01）. The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma （P<0.01）. Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume， promoted tumor cell apoptosis in the high-dose group， up-regulated the protein and mRNA levels of Bax and Caspase-3， down-regulated the protein and mRNA levels of Bcl-2， and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway （P<0.05， P<0.01）. ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.

ObjectiveTo investigate the effects of Liuwei Dihuangwan on mammalian target of rapamycin （mTOR）-mediated synaptic plasticity in the prefrontal cortex-hippocampus circuit in the rat model of valproic acid （VPA）-induced autism spectrum disorder （ASD） and to explore its potential mechanism for reducing behavioral abnormalities in ASD rats. MethodsThirteen SD pregnant rats were randomized into the VPA group （10 rats） and the control group （3 rats）. On gestational day 13， the VPA group was intraperitoneally injected with VPA solution （600 mg·kg^-1）， while the control group was injected with an equal volume of normal saline. Male pups of 21 days old from both groups underwent behavioral tests to screen the ASD model rats （32 rats）. These rats were then randomly assigned to the model （distilled water）， vitamin D （1 480 U·kg^-1）， low-dose （0.75 g·kg^-1） Liuwei Dihuangwan， and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan groups， and normal male pups were selected as the blank group （distilled water）， with 8 rats in each group. Each group was treated with the corresponding drug or an equal volume of distilled water via gavage daily. After drug administration， behavioral tests were conducted again， followed by anesthesia and tissue collection. Nissl staining was carried out to observe the morphological changes of neurons in the prefrontal cortex and hippocampus. Transmission electron microscopy was used to observe changes in hippocampal synaptic structure. Immunohistochemistry and Western blot were employed to determine the expression of mTOR， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the prefrontal cortex， as well as synaptophysin-1 （SYP-1）， postsynaptic density 95 （PSD95）， and N-methyl-D-aspartate receptors （NMDARs） in the hippocampus. ResultsCompared with the control group， the model group exhibited severe growth retardation and developmental deformities， with abnormal behavioral performance and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus. Compared with the model group， all treatment groups showed reduced behavioral abnormalities and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus， with the most significant effects in the high-dose Liuwei Dihuangwan group. Immunohistochemistry and Western blotting results showed that compared with the control group， the model group exhibited significantly increased protein levels and phosphorylation ratios of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex （P<0.05， P<0.01）， and decreased protein levels of SYP-1 and PSD95 and increased protein level of NMDARs in the hippocampus （P<0.01）. Compared with those in the model group， the protein levels of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex decreased in the vitamin D and high-dose Liuwei Dihuangwan groups （P<0.05）， and the p-mTOR/mTOR， p-Akt/Akt， and p-PI3K/PI3K ratios in the prefrontal cortex declined in the vitamin D group （P<0.05）. The high-dose Liuwei Dihuangwan group showed a reduction in p-PI3K/PI3K ratio （P<0.05）. The protein level of SYP-1 and PSD95 in the hippocampus increased in the vitamin D， low-dose Liuwei Dihuangwan， and high-dose Liuwei Dihuangwan groups （P<0.05， P<0.01）， while the protein level of NMDARs decreased in the vitamin D and high-dose Liuwei Dihuangwan groups （P<0.01）. ConclusionLiuwei Dihuangwan significantly reduces VPA-induced ASD-like behaviors and enhances the regeneration and repair of neurons in the prefrontal cortex and synaptic structures in the hippocampus by downregulating of PI3K/Akt/mTOR expression in the prefrontal cortex， upregulating SYP-1 and PSD95 expression in the hippocampus， and inhibiting NMDARs expression.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is currently the most prevalent chronic liver disease worldwide， and its disease spectrum encompasses simple steatosis， metabolic-associated steatohepatitis， hepatic fibrosis， liver cirrhosis， and hepatocellular carcinoma. Recent studies have shown that hepatic macrophages play an important regulatory role in the development and progression of MAFLD. Hepatic macrophages mainly consist of resident Kupffer cells and monocyte-derived macrophages， which participate in the pathophysiological processes of the disease by regulating inflammatory response， lipid metabolism， fibrogenic process， and cell death pathways. This article summarizes the diversity and functional plasticity of hepatic macrophages in MAFLD， reviews their interactions with hepatocytes and gut microbiota， elaborates on the core mechanism of hepatic macrophages and related signaling pathways in the progression of MAFLD， and further discusses novel therapeutic strategies targeting hepatic macrophages. An in-depth understanding of the mechanism of action of hepatic macrophages in MAFLD may provide a crucial theoretical basis for developing precise therapeutic approaches for this disease.

To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.