ObjectiveTo investigate whether visceral fat area （VFA） is an independent risk factor for significant liver fibrosis in patients with nonalcoholic fatty liver disease （NAFLD） based on clinical data， and to establish an effective diagnostic model. MethodsA total of 222 NAFLD patients who attended Department of Hepatology， Guangdong Provincial Hospital of Traditional Chinese Medicine， from January 2021 to April 2025 were enrolled， and according to liver stiffness measurement （≥8 kPa or not）， they were divided into significant fibrosis group and non-significant fibrosis group. Propensity score matching （PSM） was performed at a ratio of 1∶1 to balance the baseline data between the two groups. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was used to determine the correlation of VFA and other indicators with significant liver fibrosis； univariate and multivariate logistic regression analyses were used to identify whether VFA was an independent risk factor for significant liver fibrosis in NAFLD patients， and the receiver operating characteristic （ROC） curve was plotted to assess the predictive performance of related indicators. ResultsA total of 45 patients with significant liver fibrosis and 177 patients without significant liver fibrosis were enrolled， and after PSM， 90 patients （45 pairs） were finally included in analysis. Compared with the non-significant fibrosis group， the significant fibrosis group had significantly higher levels of body mass index （BMI）， fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， uric acid （UA）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， controlled attenuation parameter （CAP）， and VFA， as well as a significantly higher proportion of patients with visceral fat obesity or three or more metabolic risk factors （all P<0.05）. VFA， BMI， AST， and HbA1c were strongly correlated with significant liver fibrosis （all r>0.5， all P <0.05）， and ALT， GGT， UA， FBG， and CAP were significantly positively correlated with significant liver fibrosis （r=0.3　—　0.5， all P<0.05）. VFA （odds ratio ［OR］=1.040， 95% confidence interval ［CI］： 1.018　—　1.062， P<0.05）， FBG （OR=2.372， 95%CI： 1.199　—　4.691， P<0.05）， and AST （OR=1.032， 95%CI： 1.003　—　1.058， P<0.05） were independent risk factors for significant liver fibrosis in NAFLD patients. The new diagnostic model based on VFA， FBG， and AST （with an area under the ROC curve ［AUC］ of 0.907） had a significantly better performance than aspartate aminotransferase-to-platelet ratio index （AUC=0.834）， fibrosis-4 （AUC=0.660）， triglyceride-glucose index （AUC=0.656）， and NAFLD fibrosis score （AUC=0.768） in predicting significant liver fibrosis in NAFLD patients （all P<0.05）. ConclusionVFA is an independent risk factor for significant liver fibrosis in NAFLD patients， and the noninvasive diagnostic model based on VFA， FBG， and AST can effectively predict the onset of significant liver fibrosis in NAFLD patients.

ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus （T2DM） and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function， while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized， double-blind， placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine （TCM） group （54 cases） or the control group （56 cases）. Patients in the TCM group received Jianpi Qinghua Granules， while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention， blood glucose fluctuations were assessed using the following parameters： time in the target blood glucose range （TIR）， mean daily blood glucose （MBG）， standard deviation of mean daily blood glucose （SDBG）， mean amplitude of glycemic excursions （MAGE）， coefficient of variation of blood glucose （CV）， glycated hemoglobin （HbA1c） achievement rate， fasting plasma glucose （FPG）， and 2 hour postprandial glucose （2 hPG）. Skeletal muscle mass was measured by dual-energy X-ray absorptiometry （DXA）， while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally， pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention， ensuring comparability. After treatment， compared to the control group， the TCM group showed a significant increase in TIR （P<0.01）. While the SDBG and CV decreased， and MBG and MAGE increased in the TCM group， these differences were not statistically significant. Notably， the TCM group exhibited significant reductions in 2 hPG （P<0.01） and HbA1c （P<0.05）， though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group （χ²=45.498， P<0.01）. In terms of skeletal muscle mass and function， the TCM group demonstrated a significant increase in handgrip strength （P<0.01） and a significant reduction in the 5-time sit-to-stand duration （P<0.05）. However， although body fat percentage increased， leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat， these changes were not statistically significant. For pancreatic islet function， the TCM group showed significant reductions in fasting insulin （FINS） and homeostasis model assessment of insulin resistance （HOMA-IR） （P<0.01）. Additionally， the TCM syndrome score in the TCM group was significantly reduced （P<0.01）. ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function， improving pancreatic islet function， and ameliorating related TCM syndromes.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

Ischemic stroke(IS) is a complex pathological process involving multiple cellular and molecular mechanisms and it is characterized by high mortality, high disability, and high recurrence. In recent years, the incidence of IS in China has been increasing year by year, and it has a trend of occurring in increasingly young individuals. Herb pairs are the smallest unit of traditional Chinese medicine(TCM) compatibility and an important part of TCM compounding, and the research on them is of great significance in guiding the clinical medication. Pharmacological studies have confirmed that certain herb pairs can exert anti-ischemic effects through various pathways such as reducing inflammation, alleviating oxidative stress, protecting the nervous system, and promoting neovascularization. By reviewing the relevant articles in the past decade, this paper probes into the combination rules, modern experimental studies, and combination ratios of the commonly used herb pairs from the etiology and pathogenesis of IS and summarizes 18 commonly used and deeply studied herb pairs, with a view to providing reference for the application, research, and development of clinical medicines.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Ischemic Stroke/metabolism* ; Medicine, Chinese Traditional

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.