ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Polygonatum sibiricum， as a traditional Chinese medicine with both medicinal and edible properties， has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs， tonifying the spleen and benefiting Qi， and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system， effectively enhancing and improving the morphology and function of immune organs， stimulating the proliferation and activation of immune cells， and regulating the secretion and release of immune factors， thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum， there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore， this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years， and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects： including increasing the organ index of the spleen and thymus， increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells， improving intestinal flora imbalance， regulating the quantity and proportion of T lymphocyte subsets， increasing the level of immunoglobulin， promoting the proliferation of macrophages， enhancing the activity of natural killer cells， increasing the number of white blood cells， and promoting the maturation of dendritic cells， providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum， and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

OBJECTIVES: To explore the mechanism by which Tougu Xiaotong Capsule (TXC) promotes chondrogenic differentiation and cartilage repair in mice with osteoarthritis (OA). METHODS: Fifty 8-week-old male C57BL mice were randomly divided into normal control group, cartilage damage (induced by subchondral ring-shaped drilling) model group and TXC treatment groups at low, moderate and high doses (184, 368 and 736 mg/kg, respectively). Saline (in normal control and model groups) and TXC were administered after modeling by daily gavage for 6 consecutive weeks. The changes of cartilage damage in the mice were assessed by measuring thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) and using micro-CT, modified safranine O and fast green staining, HE staining, and qPCR. Primary cultures of mouse synovial mesenchymal stem cells (SMSCs) with lentivirus vector transfection for interfering CXCL12, TXC treatment, or both for 24 h were examined for chondrogenic differentiation using immunofluorescence staining, scratch assay, immunocytochemistry, and Western blotting. RESULTS: In mouse models with cartilage damage, TXC treatment at the moderate dose significantly alleviated joint pain, promoted cartilage repair, and upregulated the mRNA expression levels of CXCL12, GDF5, collagen II, aggrecan, Comp and Sox9 in the cartilage tissue. In primary mouse SMSCs, CXCL12 knockdown resulted in significant reduction of GDF5 protein expression, migration ability and Sox9 protein expression, and these changes were obviously reversed by TXC treatment. CONCLUSIONS TXC promotes chondrogenic differentiation of mouse SMSCs to promote repair of cartilage damage in mice by activating the CXCL12/GDF5 pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Osteoarthritis/metabolism* ; Male ; Growth Differentiation Factor 5/metabolism* ; Mice, Inbred C57BL ; Mice ; Chemokine CXCL12/metabolism* ; Signal Transduction/drug effects* ; Cell Differentiation/drug effects* ; Cartilage, Articular/drug effects* ; Mesenchymal Stem Cells/cytology*

Objective: To analyze the prevalence trends and associated factors of overweight and obesity among children and adolescents in Macao from 2005 to 2020, so as to provide evidence for developing health promotion strategies. Methods: Data were obtained from the Macao Citizen Physical Fitness Monitoring Database for the years 2005, 2010, 2015, and 2020 for participants aged 6-22 years. The χ 2 test was employed to analyze trends in detection rates, while univariate and multivariate Logistic regression analyses were conducted to identify influencing factors. Results: The overweight rate among Macaos children and adolescents increased from 10.4% in 2005 to 14.8% in 2020. The obesity rate rose from 6.8% to 12.1%, with the total detection rate increasing from 17.2% to 26.9%, and the differences were statistically significant ( χ 2 trend =46.7, 87.5, 145.9, P <0.01). Notably, the overweight/obesity rate among boys showed rapid growth ( χ 2 trend = 118.6, P <0.01), while girls exhibited a declining inflection point in 2020. Multivariate Logistic regression analysis revealed that children and adolescents with the following characteristics faced higher risks of overweight/obesity: a physical education performance score of 3 points (overweight: OR=2.34, 95%CI =1.10-4.96; obesity: OR=2.39, 95%CI =1.19-4.81), paternal obesity (overweight: OR=2.07, 95%CI =1.38-3.11; obesity: OR=1.51, 95%CI = 1.01-2.27), and maternal obesity (overweight: OR=1.69, 95%CI =1.08-2.63; obesity: OR=1.77, 95%CI =1.16- 2.71 ) ( P <0.05). Conversely, lower risks were observed in those who performed appropriate warm-up activities before exercise (obesity: OR=0.37, 95%CI =0.15-0.95), participated in two academic/non-sports extracurricular classes (obesity: OR=0.46, 95%CI =0.24-0.88), and reported moderate physical exertion during extracurricular exercise (obesity: OR=0.60, 95%CI =0.36-0.98) ( P <0.05) . Conclusions Overweight and obesity among Macao s children and adolescents remain severe, particularly among boys, while girls show early signs of improvement. It is recommended to establish a multi-sectoral collaborative prevention and control system to reduce childhood and adolescent obesity.

Objective:To evaluate the preventive effects of transcutaneous electrical acupoint stimulation (TEAS) on chronic pain after lumbar spine surgery.Methods:This was a secondary analysis conducted on the studies assessing the effect of TEAS on gastrointestinal function in patients undergoing lumbar spinal surgery. Fifty lumbar spinal stenosis patients of either sex, aged 50-75 yr, with a body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status cassification Ⅰ or Ⅱ, with expected operation time≥3 h, undergoing lumbar spinal surgery under general anesthesia, were enrolled and assigned into 2 groups ( n=25 each) using a random number table method: control group (C group) and TEAS group. In group C, stimulating electrodes were placed at the non-acupoint parts of the limbs, but no electrical stimulation was applied. In group TEAS, the bilateral Neiguan (PC6), Hegu (L14), Zusanli (ST36), Shangjuxu (ST37) and Xiajuxu (ST39) were stimulated with disperse-dense waves at a frequency of 2/100 Hz. The intensity of stimulation was the maximum current that patients could tolerate. The intervention was performed once a day for 30 min per session at 30 min prior to anesthesia induction and on postoperative days 1-7. Telephone follow-ups were conducted at 3, 6 and 12 months after surgery to record the occurrence of postoperative moderate-to-severe lower back pain and leg pain (Numerical Rating Scale score ≥4), and the Oswestry Disability Index (ODI) value and four-item neuropathic pain questionnaire scores. The pain-related medical visits and usage of nonsteroidal anti-inflammatory drugs were also recorded after surgery. Results:Three patients in each group were lost to follow-up. Compared with group C, the incidence of chronic low back pain was significantly decreased at 6-12 months after surgery, the ODI value and four-item neuropathic pain questionnaire scores were decreased at 12 months after surgery ( P<0.05), ODI value difference reached the minimal clinically important difference, the proportion of patients requiring medical visits due to postoperative pain and usage rate of nonsteroidal anti-inflammatory drugs were decreased at 6-12 months after surgery ( P<0.05), and no significant change in the incidence of chronic moderate-to-severe leg pain was found at each time period after surgery in group TEAS( P>0.05). Conclusions:TEAS can prevent the occurrence of chronic lower back pain and improve functional impairment in patients undergoing lumbar spine surgery.

Objective Chronic atrophic gastritis(CAG)is often accompanied by intestinal flora disorder and intestinal symptoms,forming the phenomenon of"stomach disease involving intestine".This study explored the dynamic correlation between intestinal symptoms and qi-stagnation degree in patients with CAG qi-stagnation syndrome and analyzed the characteristics of gut microbiota from the perspective of"spleen-stomach system serving as the pivotal hub of qi movement"in TCM.Methods According to the syndrome element differentiation method,410 patients with CAG were divided into four groups:non-qi-stagnation group,mild qi-stagnation group,moderate qi-stagnation group and severe qi-stagnation group.Correlation analysis and 16S intestinal flora sequencing technology were used to analyze the correlation and differential flora between the degree of CAG qi-stagnation and intestinal symptoms.Results Patients with CAG qi-stagnation syndrome were often accompanied by intestinal symptoms such as frequent flatulence,poor defecation and alternating loose-constipated stools.The frequency of cases was significantly positively correlated with the degree of qi-stagnation"non-mild-moderate-severe"(P<0.05).There was a difference in the abundance of gut microbiota between the four groups of CAG qi-stagnation none,mild,moderate and severe.The relative abundance of Streptococcus,Subdoligranulum,Eubacterium_coprostanoligenes_group and Haemophilus was positively correlated with the degree of qi-stagnation.The relative abundance of Ruminococcus_torques_group and Butyricicoccus showed a negative correlation,and Haemophilus was statistically significant among the four groups(P<0.05).Conclusion This study can provide clinical evidence and micro-mechanism for the connotation of"gastrointestinal co-morbidities"and"different diseases with the same syndrome",which may open up new ideas for clinical diagnosis and treatment.

Traditional Chinese medicine(TCM)is an ancient medical system distinctive and effective in treating cancer,depression,coronavirus disease 2019(COVID-19),and other diseases.However,the relatively abstract diagnostic methods of TCM lack objective measurement,and the complex mechanisms of action are difficult to comprehend,which hinders the application and internationalization of TCM.Recently,while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research,the rise of machine learning(ML)has significantly enhanced their inte-gration with TCM.This article introduces representative methodological cases in quality control,mechanism research,diagnosis,and treatment processes of TCM,revealing the potential applications of ML technology in TCM.Furthermore,the challenges faced by ML in TCM applications are summarized,and future directions are discussed.

Objective To explore the mechanism by which Tougu Xiaotong Capsule(TXC)promotes chondrogenic differentiation and cartilage repair in mice with osteoarthritis(OA).Methods Fifty 8-week-old male C57BL mice were randomly divided into normal control group,cartilage damage(induced by subchondral ring-shaped drilling)model group and TXC treatment groups at low,moderate and high doses(184,368 and 736 mg/kg,respectively).Saline(in normal control and model groups)and TXC were administered after modeling by daily gavage for 6 consecutive weeks.The changes of cartilage damage in the mice were assessed by measuring thermal withdrawal latency(TWL)and mechanical withdrawal threshold(MWT)and using micro-CT,modified safranine O and fast green staining,HE staining,and qPCR.Primary cultures of mouse synovial mesenchymal stem cells(SMSCs)with lentivirus vector transfection for interfering CXCL12,TXC treatment,or both for 24 h were examined for chondrogenic differentiation using immunofluorescence staining,scratch assay,immunocytochemistry,and Western blotting.Results In mouse models with cartilage damage,TXC treatment at the moderate dose significantly alleviated joint pain,promoted cartilage repair,and upregulated the mRNA expression levels of CXCL12,GDF5,collagen II,aggrecan,Comp and Sox9 in the cartilage tissue.In primary mouse SMSCs,CXCL12 knockdown resulted in significant reduction of GDF5 protein expression,migration ability and Sox9 protein expression,and these changes were obviously reversed by TXC treatment.Conclusion TXC promotes chondrogenic differentiation of mouse SMSCs to promote repair of cartilage damage in mice by activating the CXCL12/GDF5 pathway.

Abstract To investigate the effects of exercise on gut microbiota(GM) among children with autism spectrum disorder(ASD)，the review provides an in depth summary of the three core biological pathways through which exercise modulates the GM: repairing the integrity of the intestinal barrier to inhibit lipopolysaccharide mediated neuroinflammation; optimizing key metabolites, such as short chain fatty acids, to reshape gut-brain communication; synergistically regulating the tryptophan-kynurenine metabolic pathway and vagus nerve signaling to balance neurotransmitters. These interconnected pathways not only alleviate gastrointestinal discomfort but also provide a solid biological foundation for improving the core behavioral symptoms of ASD, such as social deficits and repetitive behaviors. Future research should focus on establishing standardized exercise intervention protocols, validating the efficacy of these key biological pathways using multi omics approaches, and exploring combined intervention strategies. The results of corollary studies will provide a more robust scientific basis for precision rehabilitation of children with ASD.