BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

Background Air pollution remains a critical public health issue, with persistent exposure to air pollutants continuing to pose significant health risks. Currently, research investigating the association between air pollution and myocardial infarction mortality in Shenzhen remains inadequate. Objective To quantitatively assess the association between air pollutants and myocardial infarction mortality in residents. Methods Based on the mortality surveillance system of Shenzhen Center for Disease Control and Prevention, we conducted a time-stratified case-crossover study of 10089 permanent residents who died from myocardial infarction in Shenzhen between 2013 and 2022. Using residential address information, we obtained individual-level exposure data for air pollutants from the China High Air Pollutants dataset and meteorological factors from the China Meteorological Administration Land Data Assimilation System. A time-stratified case-crossover study design was employed to construct a conditional logistic regression model to assess the association between short-term exposure to air pollutants and myocardial infarction mortality. The exposure-response relationship was visualized, and a comprehensive health risk assessment was performed. Results This study included a total of 10 089 cases of myocardial infarction deaths in Shenzhen. The median [interquartile range (IQR)] concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃) in Shenzhen from 2013 to 2022 were 24.59 (20.19) μg·m⁻³, 42.85 (28.42) μg·m⁻³, 8.53 (3.39) μg·m⁻³, 29.47 (13.56) μg·m⁻³, 0.77 (0.27) mg·m⁻³, and 86.53 (51.39) μg·m⁻³, respectively. The moving average concentrations of PM_2.5 and PM₁₀ over the current day and the previous 2 days (lag02) showed the highest risk of myocardial infarction mortality, with an odds ratio (OR) and 95% confidence interval (95%CI) of 1.004 (1.001, 1.007) and 1.004 (1.002, 1.006), respectively. At lag05, SO₂ demonstrated the strongest association with the risk of myocardial infarction mortality, with an OR (95%CI) of 1.042 (1.019, 1.065). The exposure-response relationships of PM_2.5, PM₁₀, and SO₂ with myocardial infarction mortality were approximately linear, whereas NO₂ exhibited a nonlinear relationship. At lag05, the highest risk of myocardial infarction mortality associated with NO₂ exposure was observed when the NO₂ concentration was ≤21.92 μg·m⁻³, with an OR (95% CI) of 1.024 (1.003, 1.046). The health risk assessment indicated that, using the WHO Air Quality Guidelines as the reference, the local PM_2.5 and NO₂ exposure led to an excess mortality of 398 and 298 cases, respectively. The sensitivity analysis revealed that after adjusting for O₃ and restricting the study period to 2013—2019, the effect estimates for PM_2.5, PM₁₀, NO₂, and SO₂ on myocardial infarction mortality slightly increased. Conclusion Short-term exposure to air pollutants, including PM_2.5, PM₁₀, NO₂, and SO₂, could increase the risk of myocardial infarction mortality. This study provides important scientific evidence for environmental health risk assessment and environmental management in Shenzhen.

Objective: To systematically review the development and changes in mental health policies within the National Outline for Children s Development in China from 1992 to 2030, providing a reference basis for future formulation of mental health policies among children and adolescent in China. Methods: Based on the four editions of the National Outline for Children s Development in China across different periods from 1992 to 2030, word frequency analysis was used to reveal shifts in policy priorities, and an internationally recognized framework for adolescent health policy analysis was applied to conduct a textual review. Results: Word frequency analysis revealed that the term "psychological" appeared 6 times in the National Outline for Children s Development in China (2001-2010) but increased to 20 times in the National Outline for Children s Development in China (2021-2030) (abbreviated as the National Outline of 2021), while the term "health" rose from 4 times in the National Outline for Children s Development Plan in China in the 1990s to 68 times in the National Outline of 2021. The scope of mental health policy interventions expanded to encompass five key areas:health, safety, education, welfare and legal protection. Textual analysis highlighted that the policies of the National Outline for Children s Development in China were demand driven, prioritized vulnerable groups and continuously broadened their coverage, emphasizing sustainability and appropriateness, and monitoring/evaluation mechanisms. By 2023, 42.3% of primary schools and 64.8% of secondary schools employed full time mental health education teachers. However, the National Outline for Children s Development in China lacked direct evidence of children and adolescents participation in policy formulation, and publicly available mental health data disaggregated by age and gender remained limited. Conclusion Mental health policies of children and adolescents in China have evolved from nonexistence to gradual refinement, yet institutionalized channels for youth involvement in policy development and evaluation remain insufficient, and transparency in age and gender specific mental health data needs improvement.

OBJECTIVE: To summarize the research progress of suture augmentation (SA) in anterior cruciate ligament (ACL) reconstruction. METHODS: A comprehensive review of recent literature about SA in ACL reconstruction at home and abroad was conducted. The efficacy of SA in ACL reconstruction was evaluated by examining the definition, biomechanics, and histological studies of SA, along with its clinical application status in ACL reconstruction. RESULTS: SA demonstrates significant advantages in enhancing the biomechanical stability of ACL grafts, reducing the risk of re-rupture, and accelerating postoperative recovery. Specifically, SA improves graft stiffness, ultimate failure strength, and cyclic stability, thereby diminishing the risk of early postoperative failure and joint instability. Histologically, it fosters remodeling and tendon-bone integration through early load-sharing mechanisms; however, stress shielding may interfere with natural remodeling processes, warranting further attention. Clinically, SA reduces graft failure rates and the need for revision surgeries, markedly improving knee joint stability and functional recovery in young patients. Nevertheless, its impact on graft maturation and potential complications remains controversial. CONCLUSION Despite the many advantages of SA in ACL reconstruction, future endeavors should focus on optimizing tensioning techniques, developing bioactive materials, and conducting large-scale randomized controlled trials to further elucidate its clinical value and scope of applicability, providing a more reliable solution for ACL reconstruction.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Biomechanical Phenomena ; Anterior Cruciate Ligament/surgery* ; Anterior Cruciate Ligament Injuries/surgery* ; Suture Techniques ; Sutures ; Tendons/transplantation* ; Joint Instability/prevention & control* ; Knee Joint/surgery*

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Objective:To analyze the effect of depressive state on Alzheimer's disease(AD)mice,3xTg-AD mice were stimulated with chronic social frustration stress(CSDS)and chronic mild unpredictable stress(CUMS),to estab-lish an early AD-induced depression mouse model,and to detect cognitive and behavioral changes,activation of micro-glia in the hippocampus and neuronal loss.Methods:Three-month-old mice were subjected to 8-day stress stimulation alternately,the depressive state of the mice was evaluated by behavior,the evaluation criteria were formulated,and the cognitive behavior was detected and analyzed,and the hippocampal brain tissue sections were stained with immunofluo-rescence to observe the deposition of β-amyloid(Aβ)and the aggregation of microtubule-associated protein(tau),mi-croglia activation and neuronal loss.Results:Depression-related behavioral results showed that the CSDS+CUMS group had depression-related phenotypes.Cognitive-behavioral testing showed that the new object recognition index of the mice in the CSDS+CUMS group was significantly reduced(P＜0.05),and the Morris water maze showed that the spatial memory ability of the CSDS+CUMS group was significantly reduced(P＜0.05),but there was no obvious fear memory loss in the CSDS+CUMS group in the conditioned fear experiment.The results of immunofluorescence staining showed that Aβ deposition appeared in the hippocampus at 4 months of age,the activated microglia increased(P＜0.001),and a certain degree of neuronal loss appeared in the CSDS+CUMS group(P＜0.001);At 8 months of age,the CSDS+CUMS group showed tau protein aggregation early.Conclusion:We established a model of AD-induced de-pression in AD mice,in which 3xTg-AD mice experienced early decline in learning memory and increased AD-related pathological deposition of neurons in the hippocampus,accompanied by microglial activation and neuronal loss.

Myelodysplastic syndrome (MDS) is a malignant hematologic tumor, which is currently difficult to cure. The theory of Xuanfu was proposed by Liu Wansu, which is unique in the clinical evidence of Chinese medicine and is less frequently applied to hematological diseases. The application of Xuanfu theory in myelodysplastic syndrome provides new ideas for the treatment of the disease. The abnormal flow of Qi, blood and fluids caused by the occlusion of the Xuanfu is the cause of toxic stasis obstruction, which is the pathogenesis of toxic stasis obstruction. Thus, the method of dispersion of Bone from Xuanfu, the external treatment of Xuanfu, and regulation of liver qi and Xuanfu help to return to normal of opening and closing function of Xuanfu, and release toxic stasis. In this paper, we analyzed the evidence of toxin-stasis obstruction in myelodysplastic syndrome from the theory of Xuanfu, aiming to provide a feasible theoretical basis for clinical treatment of the disease.

Refeeding syndrome(RFS)has a high incidence among critically ill patients and significantly impacts the re-covery and prognosis of the patients.In this paper,we reviewed the literature on the risk factors and risk prediction models for RFS,finding the risk factors of RFS included patient-related,treatment-related factors and disease-related factors and the risk prediction models encompassed risk stratification model,risk score models and the Logistic regression models.It was concluded from the review that early assessment was crucial to preventing the occurrence of RFS.However,there was still a lack of reliable RFS risk prediction models with good predictive performance.It was found as well that it was crucial for the prevention of RFS to attach importance to nutritional and serological indicators and other factors.It was expected to be a necessity to conduct prospec-tive and multicenter studies to develop a risk prediction model for predicting RFS for ICU patients.Our review provides a refer-ence for early assessment and intervention for critically ill patients with RFS.

ObjectiveTo investigate the clinicopathological features， diagnosis and treatment methods， and prognosis of gallbladder sarcomatoid carcinoma （GBSC）. MethodsA retrospective analysis was performed for the clinical data of 16 patients with GBSC who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2015 to April 2023， including general information， clinical manifestations， imaging features， pathological features， and treatment modality， and follow-up was performed for all patients. The Kaplan-Meier method was used to perform the survival analysis and plot the survival curve， and the Log-rank test was used for comparison between groups. ResultsAmong the 16 patients， there were 6 male patients and 10 female patients， with a mean age of 62.9±8.4 years. The main clinical manifestations were right upper abdominal pain in 13 patients （81.3%）， nausea in 5 patients （31.3%）， abdominal distension in 4 patients （25.0%）， poor appetite in 3 patients （18.8%）， weakness in 2 patients （12.5%）， fever in 2 patients （12.5%）， and jaundice in 1 patient （6.3%）， and 3 patients were asymptomatic and were found to have this disease by physical examination. Of all patients， 81.3% （13/16） were in the advanced stage （stage Ⅲ/Ⅳ） at the time of initial diagnosis. Histopathological examination showed that some cancer cells were spindle-shaped under the microscope， with marked nuclear division and noticeable heteromorphism. Immunohistochemistry showed a positive expression rate of 100% （16/16） for Vimentin， AE1/AE3， and CK8/18， and Ki-67 proliferation index was highly expressed in 81.3% （13/16） of the patients （≥50%）， with a median of 70% （range 20%‍ ‍—‍ ‍90%）. All 16 patients underwent surgical treatment， with radical surgery in 11 patients and palliative surgery in 5 patients， among whom 9 received R0 resection， 2 received R1 resection， and 5 received R2 resection， and 7 patients received adjuvant therapy after surgery. Effective follow-up was achieved for all 16 patients， with a follow-up time of 0.5‍ ‍—‍ ‍26.0 months and a median follow-up time of 11.0 months. By the end of follow-up， 2 patients survived and 14 patients died due to tumor recurrence or metastasis， with a median survival time of 10.0 months， and the 1- and 2-year cumulative survival rates after surgery were 31.3% and 8.3%， respectively. The prognostic analysis showed that TNM stage （χ²=6.727， P=0.009）， surgical approach （χ²=7.508， P=0.006）， margin condition （χ²=7.934， P=0.005）， and adjuvant therapy （χ²=4.608， P=0.032） were associated with the prognosis of patients. ConclusionThe clinical manifestations of GBSC lack specificity， and a confirmed diagnosis relies on immunohistochemical analysis. Most patients are in the advanced disease at the time of initial diagnosis and tend to have a poor prognosis. There are currently no targeted therapies for this disease， and radical surgery with negative margins and adjuvant therapy can improve the survival rate of patients.