Objective To investigate the association between physical activity levels and blood lipids among college freshmen, and to provide scientific evidence for the health management of college freshmen. Methods An electronic questionnaire survey on physical activity was conducted on freshmen of a university, and fasting blood biochemical indicators were detected. The International Physical Activity Questionnaire (IPAQ) short form was used to evaluate the physical activity levels of the participants. Dyslipidemia was defined as an abnormality in any one of the following serum lipid parameters: total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or non-high-density lipoprotein cholesterol. Binary logistic regression and stratified analyses were employed to explore the relationship between physical activity and blood lipids. Results A total of 3 401 participants were included, with an average age of 18.45 ± 0.92 years, and 60.5% were female. The prevalence of dyslipidemia was 17.7%, with a higher rate among males (22.1%) than females (14.8%). After adjusting for confounding factors related to blood lipids, high-intensity physical activity was negatively associated with the risk of elevated LDL-C among males (OR = 0.36, 95% CI: 0.13–0.99, P = 0.049). Conclusion Among freshmen at a medical college in Hubei Province, high-intensity physical activity is negatively associated with the risk of elevated LDL-C in males, but this association needs to be further confirmed by larger prospective cohort studies.

[摘 要] 目的：构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒（DPM），探讨其对三阴性乳腺癌（TNBC）细胞4T1及其小鼠移植瘤的治疗效果。方法：通过物理吸附法制备 DPM 纳米颗粒，利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞，细胞实验分为对照组、超声辐照组（US组）、DPM治疗组（DPM组）和DPM治疗联合超声辐照组（DPM + US组），用CCK-8法检测细胞活性，免疫荧光法检测高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的表达，WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型，分为四组，处理同细胞实验，测量肿瘤体积，免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ（HIF-1ɑ）蛋白的表达，TUNEL法检测细胞凋亡，流式细胞术检测免疫细胞活化情况，对主要器官进行H-E染色，以评估纳米材料的体内安全性。结果：DPM呈梭形，平均粒径（268 ± 3.302）nm，电位（33.1 ± 0.87）mV。细胞实验中，DPM联合超声辐照可明显抑制4T1细胞的增殖（P < 0.001），提高4T1细胞中ROS水平（P < 0.001），诱导4T1细胞CRT表达上调（P < 0.001），HMGB1从细胞核中移至细胞质，激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加（均P < 0.001）]。体内实验中，DPM联合超声辐照可显著抑制4T1细胞移植瘤生长（P < 0.001）并促进免疫细胞表型转化（P < 0.001），抑制移植瘤组织中Ki-67、HIF-1α蛋白表达（均P < 0.01），谷胱甘肽（GSH）产生（P < 0.01），促进CRT、HMGB1蛋白表达、ROS产生（P < 0.001），对主要器官结构无明显影响。结论： DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长，诱导抗肿瘤免疫应答，且对主要器官无明显毒性。

Objective: To evaluate the clinical efficacy and safety of micro-percutaneous nephrolithotomy (microPCNL) using Needle-perc in the oblique supine-lithotomy position for treating 1—2 cm lower-pole stones (LPSs)，by comparing it with flexible ureteroscopic lithotripsy (FURL)，so as to identify an effective surgical method for LPSs. Methods: We retrospectively analyzed the clinical data of 56 patients with isolated LPSs of 1—2 cm treated in our hospital during Jan.and Dec.2023.Patients were divided into two groups based on the treatment method：FURL (n=31) and microPCNL (n=25).General information and perioperative data were compared between the two groups. Results: All operations were successfully completed.The operation time was shorter in the microPCNL group than in the FURL group \[(46.5±10.1) min vs.(73.5±18.9) min，P<0.001\].Stone-free rate (SFR) was 92.0% in the microPCNL group and 71.0% in the FURL group (P=0.026).There were no significant differences in the average fall of hemoglobin level，serumc creatinine change level，hospitalization time and postoperative fever between the two groups. Conclusion: MicroPCNL in oblique supine-lithotomy position is a safe and effective treatment for 1-2 cm LPSs，with a higher SFR compared to FURL.

Objective:To explore the clinical efficacy of health management programs for elderly patients with comorbid diabetes and coronary heart disease, to provide suggestions for health management of elderly patients with comorbid diabetes and coronary heart disease.Methods:A randomized controlled trial was conducted. A total of 72 elderly patients with comorbid diabetes and coronary heart disease from different communities who visited the Fenglin Street Community Health Service Center, Xuhui District, Shanghai, from January to June 2023 were selected by convenient sampling method. They were divided into control group and experimental group by random number method, with 36 cases in each group. The control group used the routine health management program, the experimental group used the health management program for elderly patients with comorbid diabetes and coronary heart disease. The clinical indicators (glycated hemoglobin, body mass index, etc), self-management abilities (including those of elderly patients with diabetes and those with coronary heart disease), and quality of life were compared between the two groups.Results:There were 14 males and 22 females in the control group, with an age of (73.67 ± 5.97) years; there were 21 males and 15 females in the experimental group, with an age of (73.33 ± 5.63) years. After intervention, the glycated hemoglobin of patients in the experimental group was (7.03 ± 0.64)%, while that of the control group was (7.42 ± 0.72)%. The difference between the two groups was statistically significant ( t=-2.49, P<0.05).The scores of self-management ability of elderly patients with diabetes and elderly patients with coronary heart disease in the experimental group were (22.66 ± 4.69) and (98.28 ± 13.54) points, which were significantly higher than (20.56 ± 4.05) and (93.00 ± 8.01) points in the control group, the differences were statistically significant ( t=2.03, 2.01, both P<0.05). The score of energy in the experimental group was (35.56 ± 8.68) points, which was higher than that of the control group (28.75 ± 15.18) points, the difference was statistically significant ( t=2.34, P<0.05). Conclusions:Health management programs for elderly patients with comorbid diabetes and coronary heart disease can significantly improve patients′ blood glucose control and enhance their self-management abilities for diabetes and coronary heart disease. However, further validation is needed to improve patients′ blood lipid control level and quality of life.

OBJECTIVE To establish a clinical comprehensive evaluation framework for direct oral anticoagulants （DOACs） in the prevention of cancer-associated venous thromboembolism （CAVTE）， providing a methodological reference for the rational prevention and treatment of CAVTE as well as for the formulation and adjustment of macro-management strategies for anticoagulant drugs. METHODS Through literature retrieval， evaluation indicators were collected and organized to establish a preliminary indicator pool. The selection of evaluation indicators was carried out through two rounds of Delphi surveys using average score of indicator importance≥3.5 and a coefficient of variation （CV） ＜0.25 as the screening criteria. Analytic hierarchy process （AHP） was employed to finalize the indicator weights. RESULTS The authority levels （C）r of the two rounds of expert consultations were 0.877 and 0.943， with CV of 0.24 and 0.18， respectively. The Kendall concordance coefficients were 0.331 and 0.535 （P＜0.05）. After expert validation， six primary indicators and forty-six secondary indicators were finalized for inclusion in the evaluation framework. The primary indicators and their weightings， ranked in descending order， were as follows：“ effectiveness” （38.86%）， “safety” （38.86%），“ cost-effectiveness” （10.67%），“ accessibility” （5.51%），“ suitability” （3.48%）， and “innovation” （2.64%）. The secondary indicators exhibited a weight range from 0.02% to 20.25%， with the top five secondary indicators being：“ incidence of intracranial hemorrhage” （20.25%）， “reduction in all-cause mortality” （15.29%）， “decrease in the incidence of pulmonary embolism” （8.82%）， “reduction in the incidence of deep vein thrombosis” （7.25%）， and “drug contraindications” （4.74%）. CONCLUSIONS This study has established an authoritative， scientific， and reliable comprehensive clinical evaluation framework for the use of DOACs in the prevention of CAVTE.

Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL