Angiogenesis， as a core mechanism for maintaining tissue perfusion and repairing ischemic injury， plays a crucial role in ischemic diseases such as coronary heart disease and peripheral arterial disease. Traditional Chinese medicine（TCM）， with its advantages of multi-target and synergistic regulation， provides a unique perspective for therapeutic angiogenesis. Based on this， this article intends to delve into the synergistic effects of key signaling pathways， including vascular endothelial growth factor（VEGF）/VEGF receptor（VEGFR）， Notch， phosphoinositide 3-kinase/ protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR）， and angiopoietin/endothelial TEK tyrosine kinase（Ang/Tie2）， and elucidate the driving mechanisms of endothelial cell metabolic reprogramming and exosome-mediated intercellular communication within this process. Based on existing literature， it summarizes the microenvironment-dependent and bidirectional regulatory characteristics of natural active components of TCM（such as terpenes， tanshinones， and flavonoids） on angiogenesis. Furthermore， it systematically discusses how classical TCM formulas achieve blood vessel formation and functional maturation by protecting the neurovascular units， recruiting pericytes， and remodeling the microenvironment. Current evidence highlights the advantages of multi-target synergy and temporal regulation in TCM， but also reveals challenges such as high heterogeneity and a lack of functional evaluations and high-quality clinical trials. Future efforts should integrate multi-omics to decipher network mechanisms， optimize formula compatibility， and conduct multicenter studies to promote the development of innovative preparations. This review highlights the academic value of TCM in angiogenesis， provides an evidence base for treating ischemic diseases， and supports multidisciplinary integration and innovation.

Objective To analyze survival outcomes and influencing factors among patients with colorectal cancer in Yunnan Province. Methods Clinical data were retrospectively collected from 4 892 patients with colorectal cancer. Survival data were obtained through follow-up. Overall survival (OS) was calculated by using the Kaplan-Meier method. Univariate analysis was performed by applying the log-rank test. Meanwhile, multivariate analysis employed the Cox proportional hazards regression model. Results The 1-, 3-, 5-, and 10-year OS rates for the entire cohort were 91.90%, 74.40%, 64.40%, and 28.70%, respectively. Univariate analysis revealed that age, ethnicity, region, differentiation grade, TNM stage, clinical stage, metastatic status, histological type, and treatment modality (chemotherapy, radiotherapy, and surgery) were associated with patient prognosis (all P<0.05). Multivariate analysis identified age (HR=1.250), region (HR=1.262), differentiation grade (HR=0.761), clinical stage (HR=3.128), and treatment modality (chemotherapy, HR=0.644; radiotherapy, HR=1.605; surgery, HR=0.384) as independent factors affecting survival prognosis in patients with colorectal cancer (all P<0.001). Conclusion Age, region, clinical stage, and treatment modality are independent factors influencing survival among patients with colorectal cancer in Yunnan Province. In clinical practice, these factors should be integrated to develop individualized prevention and treatment strategies, thereby improving patient outcomes.

Immune-stimulating antibody drug conjugate (ISAC) can not only effectively solve the defects of stimulator of interferon genes (STING) agonists by coupling antibodies with STING agonists through the targeting of antibodies, but also play a synergistic role with antibodies to further improve the efficacy of STING agonists. This review first provides a concise overview of the current research landscape of ISACs and STING agonists, systematically elaborates on evolving trends in STING agonist development, and subsequently summarizes the mechanistic advances in STING ISAC research. Special emphasis is placed on representative STING ISAC candidates in preclinical/clinical development. Finally, the future directions of STING ISACs are critically discussed with perspectives and recommendations, aiming to provide theoretical insights and practical guidance for future investigations.

This study employed the drug affinity responsive target stability (DARTS) technique to investigate the molecular mechanism of the antipsychotic drug penfluridol against melanoma, revealing the biological pathway to exert its effect on the HSPA6/p53/p21 signaling axis. Experiments such as the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell colony formation ability assay confirmed that penfluridol could significantly downregulate the expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) in melanoma A375 and B16 cells, induce cell cycle arrest in the G1 phase, and thus inhibit the proliferation of melanoma cells. Meanwhile, the results of Western blot, Hoechst 33342 staining and Annexin V-FITC/PI double staining experiments showed that penfluridol could significantly downregulate the expression of Bcl-2 and upregulate the expression of Bax and cleaved caspase-3, inducing cell apoptosis. Further, the DARTS technique was used to identify heat shock 70 kD protein 6 (HSPA6) as the key target bound by penfluridol. Penfluridol activates the p53/p21 pathway by upregulating HSPA6. Knocking down HSPA6 reverses not only the activation of the p53/p21 pathway mediated by penfluridol but also the associated cell cycle arrest and apoptosis. Animal experiments on tumor-bearing mice also confirmed that knocking down HSPA6 could reverse the in vivo anti-tumor activity of penfluridol. This study clarified that penfluridol can inhibit the progression of melanoma by targeting HSPA6 to activate the p53/p21 signaling axis, providing a new perspective for the repositioning of antipsychotic drugs in cancer treatment.

This study aimed to investigate the effect of atractylenolide I (Atr-I) on myocardial mitochondrial function in mice with dilated cardiomyopathy (DCM) by regulating the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. Sixty SPF-grade male cTnT R141W transgenic DCM mice were randomly divided into the DCM group, Atr-I low-dose group (60 mg/kg), Atr-I high-dose group (240 mg/kg), captopril group (0.01 g/kg), and Atr-I high-dose+cGAS/STING pathway activator 5,6-dimethylxanthenone-4-acetic acid (DMXAA) group, with 12 mice in each group. Additionally, 12 male C57BL/6J mice were used as the control group. All mice were administered via oral gavage once daily for 8 weeks. Cardiac function was assessed using the Vevo 770 ultrasound system; myocardial pathology was examined via HE staining; mitochondrial ultrastructure in cardiomyocytes was observed using transmission electron microscopy; the proportion of cardiomyocytes without reduced mitochondrial membrane potential was detected using JC-1 staining; reactive oxygen species (ROS) content in myocardial tissue was measured using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining; adenosine triphosphate (ATP) content in myocardial tissue was determined using a commercial kit; and Western blot was performed to detect the protein expression levels of mitofusin-2 (MFN2), dynamin-related protein 1 (DRP1), cGAS, STING, interferon-β (IFN-β), CXC chemokine ligand 10 (CXCL10), and interleukin-6 (IL-6) in myocardial tissue. The aim was to observe the effect of Atr-I on myocardial mitochondrial function in DCM mice. The results showed that low- and high-dose Atr-I (60 mg/kg, 240 mg/kg) intervention improved cardiac function, alleviated cardiomyocyte hypertrophy and disordered muscle fiber arrangement, ameliorated mitochondrial ultrastructure in cardiomyocytes, reduced ROS content and the protein expression levels of DRP1, cGAS, STING, IFN-β, CXCL10, and IL-6 in myocardial tissue, and increased the proportion of cardiomyocytes without reduced mitochondrial membrane potential, as well as ATP content and MFN2 protein expression in myocardial tissue. However, DMXAA attenuated the beneficial effects of high-dose Atr-I on myocardial mitochondrial function in DCM mice. In conclusion, Atr-I may improve myocardial mitochondrial function in DCM mice by inhibiting the cGAS/STING pathway.

Objective: To explore the dynamic developmental trajectories of college students class belongingness during their college years and its longitudinal predictive effects on depressive symptoms, so as to provide targeted insights for precise campus psychological interventions. Methods: In October 2021 (T1), a total of 4 720 college students from a university in Shandong Province were selected by cluster sampling method and followed up for 3 years. Surveys were conducted annually (T2: October 2022, T3: October 2023, T4: October 2024). The Class Belongingness Scale and Patient Health Questionnaire-9 (PHQ-9) were used to assess students class belongingness and depressive symptoms. Latent growth mixture modeling was employed to identify trajectories of class belonging, and multinomial Logistic regression analysis was used to examine the predictive effects of these trajectory classes on depressive symptoms. Results: Mean scores of class belongingness across T1-T4 were (73.24±11.95, 74.76±12.25, 75.25±12.38, 77.64±11.63), and the scores of depressive symptoms were [1.00 (0, 5.00), 0 (0, 3.00), 0 (0, 2.00), 0 (0, 2.00)]. The developmental trajectories of class belongingness were categorized into three types: the high-starting ascending group ( 56.61 %), the low-starting descending group (11.91%), and the medium-starting stable group (31.48%). Multinomial Logistic regression analysis showed that, compared to the medium-starting stable group, the high-starting ascending group had a lower probability of developing mild depressive symptoms ( OR=0.27, 95%CI =0.15-0.47) and moderate or above depressive symptoms ( OR=0.29, 95% CI = 0.14-0.60) (both P <0.05). Conversely, the low-starting descending group had a higher probability of developing mild depressive symptoms ( OR=2.31, 95%CI =1.65-3.22) and moderate or above depressive symptoms ( OR=7.49, 95%CI = 3.82-14.69) (both P <0.05). Conclusion Declining trajectory of class belongingness is a risk factor for depressive symptoms, while sustained upward trend may mitigate such risks.

Objective: To explore the longitudinal association between weight trajectories and physical fitness test composite scores among primary school students, so as to provide empirical evidence for school based weight management and physical health promotion. Methods: A total of 2 112 students from a primary school in Beijing who participated in physical fitness assessments annually from 2008 to 2023 were included and classified into different body weight trajectory groups based on body mass index (BMI) threshold: "normal/overweight-obese". Group based trajectory model was used to identify distinct weight trajectories. Generalized estimating equation and Cox regression were used to analyze the associations between weight trajectories and changes in physical fitness test scores, as well as event risks. Robustness checks were conducted. Results: The prevalence of overweight and obesity among primary school students was 26.50%. BMI showed a significant negative correlation with physical fitness composite scores ( r=-0.19, P <0.01). Four types of weight trajectories were identified: persistent normal group (64.5%, 1 362), persistent overweight- obese group (18.2%, 385), normal to overweight-obese group (14.0%, 296), and overweight-obese to normal group (3.3%, 69). Compared to the persistent normal group, both the normal to overweight-obese and persistent overweight-obese groups showed significantly higher risks of failing the physical fitness test ( HR =4.23, 4.60), and the speed of achieving excellent was slower ( HR = 0.52, 0.40) (all P <0.05). Robustness tests confirmed the stability of the findings. Conclusions Body weight trajectories have a long term impact on physical fitness performance among primary school students. Students with persistent or progressive overweight-obese trajectories have limited score improvement and a higher risk of failure; primary school students with persistent or progressive overweight and obesity should be a key focus.

ObjectiveTo investigate the effects of prostaglandin E₂ （PGE₂） microinjection into the median preoptic nucleus （MnPO） on core body temperature in female mice， and to clarify its underlying mechanism. MethodsMicroinjection cannula were implanted into the MnPO of female mice using stereotaxic surgery.Subsequently， a multi-channel temperature acquisition system was used to simultaneously monitor rectal and brown adipose tissue （BAT） temperatures before and after intra-MnPO injections of different reagents.To investigate the thermoregulatory effects of the microinjection of PGE₂ into the MnPO， 12 female C57BL/6 mice were randomly divided into a saline group （n=6） and a PGE₂ group （n=6）， which were injected with 0.1 μL saline and PGE₂ （2.8 mmol/L）， respectively.To determine whether E-series prostaglandin receptor （EP）1， EP3， and EP4 receptors mediate the thermoregulatory effects of PGE₂， 15 female C57BL/6 mice were randomly divided into 3 groups （n=5 per group）.Mice in each group first received an injection of 0.1 μL PGE2 （2.8 mmol/L） into the MnPO. After their body temperature returned to baseline levels， they were subsequently injected with a mixture of either EP1， EP3 or EP4 antagonist （ant） （20 mmol/L） + PGE2 （2.8 mmol/L）. ResultsCompared with baseline level， the rectal temperature （P<0.01） and BAT temperature （P<0.001） of female mice both increased significantly after microinjection of PGE₂ into the MnPO.Compared with the saline group， the increases in rectal temperature （P<0.001） and BAT temperature （P<0.000 1） were significantly greater in the PGE₂ group of mice.Furthermore， following the injection of PGE₂ into MnPO， the increase in BAT temperature was found to be significantly greater than that in rectal temperature in mice （P<0.001）.Compared to the administration of PGE₂ alone， co-injection of an EP3 ant + PGE₂ into the MnPO of mice resulted in a significantly smaller increase in both rectal temperature （P<0.001） and BAT temperature （P<0.001）.In contrast， the increases in rectal and BAT temperatures following MnPO injection of either EP1 ant + PGE₂ or EP4 ant + PGE₂ were not statistically significant （P>0.05）. ConclusionInjection of PGE₂ into the MnPO elevates BAT and core body temperature in female mice via the EP3 receptor.

ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

ObjectiveTo investigate the incidence and influencing factors of posttraumatic stress disorder （PTSD） three months after a traffic accident， and to explore the role of social support and coping strategies. MethodsA total of 117 individuals exposed to trauma following road traffic accidents were recruited. General demographic and clinical information was collected within one week， and the hamilton anxiety rating scale （HAMA）， the hamilton depression rating scale-24 （HAMD-24）， the social support rating scale （SSRS）， and the simplified coping style questionnaire （SCSQ） were administered. A 3-month follow-up was subsequently conducted， during which PTSD symptoms were assessed using the post-traumatic stress disorder checklist for DSM-5 （PCL-5）. Participants were divided into a PTSD group and a non-PTSD group according to whether PTSD occurred. Between-group comparisons were performed using the Mann-Whitney U non-parametric test or the χ² test， as appropriate. Spearman correlation analysis was used to examine the associations between general characteristics and PCL-5 scores. Binary Logistic regression was applied to identify factors influencing PTSD， and receiver operating characteristic （ROC） curve analysis was conducted to evaluate the diagnostic value of the SCSQ and SSRS. ResultsDuring the 3-month follow-up of the 117 trauma-exposed individuals， 17 cases developed PTSD， with a higher proportion of females （70.59%）. Between-group comparisons showed that， compared with the PTSD group， the non-PTSD group had higher scores for positive coping， objective support， and subjective support （P<0.05）， and lower scores for negative coping， HAMA， HAMD， and PCL-5 （P<0.05）. Correlation analysis indicated that female gender， negative coping， and higher HAMA and HAMD scores were associated with greater PTSD severity. Logistic regression analysis demonstrated that educational level （OR=1.715， 95% CI： 1.020-2.883， P=0.042） and negative coping （OR=1.590， 95% CI： 1.003-2.522， P=0.048） were risk factors for PTSD， whereas objective support （OR=0.646， 95% CI： 0.451-0.925， P=0.017） was a protective factor. The ROC analysis showed that the total SCSQ score and its negative and positive coping dimensions， the total SSRS score and its subjective and objective support dimensions， as well as their combined use， all demonstrated good discriminative ability in distinguishing between the PTSD and non-PTSD groups. ConclusionThe results suggest that individuals who are female， with higher HAMA and HAMD scores after a motor vehicle accident， and those with lower social support and negative coping strategies， should be given particular attention. Early interventions for these individuals may reduce the incidence of PTSD.