ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg^-1）and high-dose（28.86 g·kg^-1） ZJSP groups， and the metformin group （0.25 g·kg^-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription （ZJSP） on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy （DCM）， with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase （AMPK）/forkhead box protein O1 （FoxO1）/cluster of differentiation 36 （CD36） signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin （STZ） while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group， the low-dose（14.43 g·kg^-1）and high-dose（28.86 g·kg^-1） ZJSP groups， and the metformin group （0.25 g·kg^-1）， with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks， fasting blood glucose （FBG） and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin （FINS） and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin （HE） staining， and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of AMPK， FoxO1， and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK， p-AMPK， FoxO1， p-FoxO1， and CD36. ResultsCompared with the control group， the model group showed significantly increased levels of FBG and FINS （P<0.01）， elevated levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.01）， and significantly decreased left ventricular ejection fraction （EF） and fractional shortening （FS） values （P<0.01）. HE staining revealed marked cardiomyocyte hypertrophy， disarray， and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased， while FoxO1 and CD36 mRNA expressions were significantly increased （P<0.01）. The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced， while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased （P<0.01）. Compared with the model group， all treatment groups exhibited significantly reduced FBG （P<0.01）， decreased FINS and blood lipid levels （TG， TC， LDL-C） （P<0.05， P<0.01）， improved cardiac function （P<0.05）， noticeable amelioration of myocardial histopathological morphology and lipid deposition， increased AMPK mRNA expression （P<0.01）， with significantly downregulated FoxO1 and CD36 mRNA expressions （P<0.01）， elevated p-AMPK/AMPK protein expression levels in myocardial tissue （P<0.05）， significantly decreased p-FoxO1/FoxO1 ratios （P<0.01）， and downregulated CD36 protein expression levels （P<0.05， P<0.01）. ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice， and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

Retinal microcirculatory disorder is a key factor in the occurrence and development of diabetic retinopathy （DR）， and also an important link in the prevention and treatment of DR. The theory of "Gaozhuo" holds that the microcirculatory disorder in DR is based on the deficiency of spleen Qi and is characterized by the obstruction caused by "Gaozhuo" and blood stasis. The deficiency of spleen Qi is an essential precondition for the endogenous formation and accumulation of Gaozhuo， while Gaozhuo invasion is the direct cause of microcirculatory disorders in DR. The deficiency of spleen Qi and the endogenous formation of Gaozhuo mean the process in which glucose metabolism dysfunction induces an excessive production of inflammatory factors and lipid metabolites. The obstruction caused by "Gaozhuo" and blood stasis is the direct pathogenesis of microcirculatory disorders in DR， encompassing two stages： Gaozhuo obstruction and turbidity and stasis stagnation. Gaozhuo obstruction and turbidity and stasis stagnation represent the process in which inflammatory factors and lipid metabolites damage the retinal microcirculation and induce thrombosis， thus mediating microcirculatory disorders. Turbidity and stasis stagnation and blood extravasation outside the vessels reveal the progression to microvascular rupture and hemorrhage resulting from the microcirculatory disorders. According to the pathogenesis evolution of the theory of "Gaozhuo"， microcirculatory disorders in DR can be divided into deficiency of spleen Qi with Gaozhuo obstruction， deficiency of spleen Qi with turbidity and stasis stagnation， and turbidity and stasis stagnation with blood extravasation outside the vessels. Clinically， treatment principles should focus on strengthening the spleen and benefiting Qi， resolving turbidity， and dispersing stasis. Different syndrome patterns should be addressed with tailored therapies， such as enhancing the spleen and benefiting Qi while regulating Qi and reducing turbidity， strengthening the spleen and benefiting Qi while resolving turbidity and dispelling stasis， and strengthening the spleen and resolving turbidity while removing stasis and stopping bleeding. Representative prescriptions include modified Wendantang， modified Buyang Huanwutang， modified Danggui Buxuetang， Zhuixue Mingmu decoction， Tangmuqing， Shengqing Jiangzhuo Tongluo Mingmu prescription， Danhong Huayu decoction， and Yiqi Yangyin Huoxue Lishui formula.

[摘 要] 目的：探讨同源异型盒蛋白D11（HOXD11）对Ki-67的转录调控作用及其对喉鳞状细胞癌（LSCC）细胞恶性生物学行为的影响和机制。方法：结合高通量测序数据，通过GEO、UALCAN数据库分析HOXD11在LSCC中差异表达。收集2022年1月至2025年1月联勤保障部队第九八〇医院手术切除的60例LSCC患者的癌及癌旁组织标本，以及人LSCC细胞系AMC-HN-8、TU-177、TU-686和人正常喉上皮细胞（HNLEC），构建敲低或过表达HOXD11的细胞系，将细胞分为对照组、HOXD11敲低组及HOXD11过表达组。通过RT-qPCR法检测HOXD11和Ki-67基因在LSCC组织和细胞中mRNA表达水平，免疫组织化学（IHC）法分析两者在LSCC组织中的蛋白表达及分布，WB法进一步验证蛋白差异表达。采用MTS、克隆形成实验及Transwell实验分别检测敲低或过表达HOXD11对LSCC细胞增殖、迁移与侵袭的影响。通过双萤光素酶报告基因实验和染色质免疫沉淀（ChIP）实验验证HOXD11对Ki-67启动子活性的调控作用。结果：GEO和UALCAN数据库分析表明，HOXD11在LSCC中高表达（P < 0.01）。在LSCC组织中HOXD11和Ki-67 mRNA和蛋白表达均显著高于癌旁组织（均P < 0.01），同时，两者表达水平之间存在正相关（r = 0.26，P < 0.05）；LSCC细胞系中HOXD11 mRNA表达显著高于HNLEC（均P < 0.01）。敲低HOXD11显著抑制LSCC细胞的增殖、迁移和侵袭能力（均P < 0.01），而过表达HOXD11则促进细胞的这些恶性生物学行为（均P < 0.01）。双萤光素酶报告基因实验及ChIP实验均证实，HOXD11可直接结合到Ki-67启动子区上，调控其表达（P < 0.01）。回复实验显示，过表达Ki-67可部分逆转敲低HOXD11对LSCC细胞增殖、迁移与侵袭的抑制作用（均P < 0.01）。结论：HOXD11在LSCC组织及细胞系中均呈高表达，其机制在于通过直接调控Ki-67的转录活性，从而增强LSCC细胞的增殖、迁移及侵袭能力。

Objective: To explore the consistency between self perceived body size and body mass index (BMI) evaluation among medical students, and analyze their association with depressive symptoms, so as to provide scientific evidence for psychological intervention targeting medical students. Methods: From September to November 2022, a convenient cluster sampling method was employed to select 1 850 college students from two universities in Hefei, Anhui Province, and Nanjing, Jiangsu Province. The Patient Health Questionnaire-9 (PHQ-9) was used to assess their depressive symptoms. Chi-square test was applied to compare the rates of depressive symptoms among medical students with different demographic characteristics. Kappa consistency test was performed to evaluate the consistency between self-perceived body size and BMI evaluation. Generalized linear models with binomial distribution and Logit link were constructed to analyze the associations of self-perceived body size and consistency between self-rated and BMI evaluation with depressive symptoms, as well as gender differences in these associations. Results: A total of 40.7 % of medical students overestimated or underestimated their body size. Specifically, the underestimation rate was 20.5% in males and 4.9 % in females, while the overestimation rate was 12.7% in males and 40.5% in females, the distribution of consistency in the misclassification rate of body self-perception between males and females was statistically significant ( χ 2=221.54, P ＜0.01). The overall consistency between self perceived body size and BMI evaluation was low for both males and females, with Kappa values of 0.518 and 0.281 respectively (both P <0.01). After adjusting for confounding variables, generalized linear model analyses showed that medical students with self perceived obesity and body size overestimation had higher risks of depressive symptoms ( OR =1.62, 1.26, both P ＜0.05). Stratified analyses by gender revealed that girls with self perceived overweight and obesity had higher risks of depressive symptoms in female students ( OR =1.43, 1.66, both P <0.05), whereas no statistically significant associations among boys ( OR =0.84, 1.86, both P >0.05). Girls with body size overestimation had a higher risk of depressive symptoms ( OR=1.20, P ＜ 0.05), with no significant association in boys ( OR=1.00, P >0.05). Conclusions Differences exist related between self perceived body size and BMI evaluation among medical students. Self perceived obesity and body size overestimation are related factors to depressive symptoms.

Objective: To systematically review the effect of physical activity (PA) on health related quality of life (HRQoL) among children and adolescents and the magnitude of association, so as to provide an evidence based support for optimizing health promotion strategies for children and adolescents. Methods: Medline (PubMed), EMBASE, the Cochrane Library, SCIELO, PEDro, CNKI, Wanfang and VIP databases were searched to collect literature on PA and HRQoL in children and adolescents, which were published up to January 1, 2025. Cochrane ROB tool and specific evaluation system were used to assess literature quality, Stata 16.0 software was used for Meta analysis. For descriptive studies, correlation( r ) and 95% confidence interval( CI ) were used as effect indicators, and the inverse variance method was used to merge the data. Standardized mean difference( SMD ) and 95% CI were used to calculate the combined effect size of intervention studies. Results: A total of 22 studies involving 27 303 healthy children and adolescents were included, including 9 descriptive studies and 13 intervention studies. The results of descriptive analysis showed that PA level was positively correlated with HRQoL ( r =0.27, 95% CI =0.21-0.32, P <0.01). The analysis of intervention studies showed that PA had significant effects on overall HRQoL ( SMD =0.10, 95% CI =0.05-0.16), physical functioning ( SMD =0.16, 95% CI =0.08-0.23), and mental functioning ( SMD =0.17, 95% CI =0.10-0.25)( P <0.01). Subgroup analysis found that the effects of physical activity on overall HRQoL, physiological function, and psychological function in children and adolescents were maximized when the intervention duration was less than 6 months ( SMD =0.13, 0.18, 0.20), the frequency was≥5 times per week ( SMD =0.13, 0.19, 0.24) and there was a supplementary plan( SMD =0.10, 0.18, 0.23)( P <0.01). Conclusion PA is an important factor affecting the HRQoL of healthy children and adolescents, and the systematic PA intervention has a effect on improving the HRQoL.

In recent years, mesenchymal stem cell-derived exosomes (MSC-EXO) have garnered increasing attention in the field of stomatology and have become an established research area in biomedical research. This article reviews the engineering of exosomes derived from mesenchymal stem cells and their application in the field of stomatology, in order to provide new ideas for the development of stomatology. Exosomes are nanoscale membrane vesicles secreted by cells and contain a variety of proteins, RNAs, lipids, and other biomolecules. They are transported through the circulatory system and can interact with other cells to regulate their biological behavior and participate in a variety of physiological and pathological processes. In the treatment of oral diseases, exosomes have shown great potential due to their natural biological activity and versatility. However, studies have found that relying solely on the function of natural exosomes may not fully meet the complex clinical requirements. Therefore, the concept of engineered exosomes has emerged. Engineered exosomes can be modified by bioengineering technology to enhance their targeting, allowing them to reach the lesion site more accurately. At the same time, engineered exosomes can also be surface modified or loaded internally to carry specific therapeutic molecules, such as drugs, gene editing tools or signaling molecules to improve the therapeutic effect. In addition, this engineered treatment can also confer greater stability to exosomes, making them better able to resist clearance by the immune system when circulating in the body, extending their half-life, and improving the effectiveness of treatment. Although engineered exosomes have attracted extensive attention in the fields of stomatology and other fields, their application is still mainly in the stage of basic research. To promote the clinical application of engineered exosomes, it is necessary to provide more sufficient evidence of biocompatibility and clarify their therapeutic effect and mechanism.

Animal models combining disease and syndrome are important research tools to explore the nature of traditional Chinese medicine (TCM) syndromes. At present, the construction and evaluation methods of animal models have preliminarily established the foundation for standardized development. Qi-yin deficiency syndrome is a common type of TCM syndrome in cardiovascular diseases. It is an important pathogenic factor causing the onset, pathological damage, and chronic nature of cardiovascular diseases, as well as triggering other illnesses. The establishment of an animal model of cardiovascular disease with the characteristics of Qi-yin deficiency, along with an objective and standardized evaluation system, has become an important part of modern cardiovascular disease research. In recent years, research on the construction and evaluation of animal models of heart Qi-yin deficiency syndrome has increased, but the construction methods and evaluation criteria vary. Compared with other animal models, the literature is limited, lacking statistics and overall analysis. Therefore, based on the scientific connotation of heart Qi-yin deficiency syndrome, this article systematically reviews the evaluation system of its animal model, covering multidimensional methods such as macroscopic characterization assessment, physicochemical indicators and objective evaluation, and syndrome differentiation based on prescriptions. The specific model construction strategies are described, including single-factor induction methods (sleep deprivation, chronic intermittent hypoxia, arterial occlusion, high-salt feeding) and the compound-factor induction methods (sleep deprivation combined with drug method, chronic intermittent hypoxia combined with drug method, exhaustive swimming combined with drug method). Meanwhile, application examples of each model in the research are listed, the existing problems in the current model construction and evaluation are analyzed, and optimization directions are proposed, such as promoting the compound factor induction strategy and improving the objectivity of the evaluation criteria. This article aims to provide theoretical references for constructing an animal model of heart Qi-yin deficiency syndrome that conforms to TCM characteristics, and thereby laying a scientific foundation for the prevention and treatment of cardiovascular diseases with TCM.

Objective To discuss the application of ultrasound multimodal diagnostic mode combined with ultrasonic precision interventional technology in differentiating the benign from malignant solid breast masses.Methods A total of 396 patients who underwent breast surgery at the Wuwei Cancer Hospital of China from May 2021 to July 2023 were enrolled in this study.Within 2 weeks before surgery,multimodal ultrasound examination(including two-dimensional ultrasound,color Doppler ultrasound,elastic ultrasound,breast three-dimensional ultrasound,and contrast-enhanced ultrasound)and ultrasound-guided needle biopsy were performed in all patients.The consistency between the results of multimodal ultrasound examination,ultrasound-guided needle biopsy,combination diagnosis and the postoperative pathological diagnoses was analyzed.Results Of the 396 patients with solid breast mass,malignant lesion was seen in 237(59.85％)and benign lesion was seen in 159(40.15％).The sensitivity of multimodal ultrasound in diagnosing benign and malignant solid breast masses was 77.64％(184/237),the specificity was 90.57％(144/159),the positive predictive value was 92.46％(184/199),the negative predictive value was 73.10％(144/197),the accuracy was 82.83％(328/396),and the consistency with the postoperative pathological diagnosis was 0.656.The sensitivity of ultrasound-guided needle puncture in diagnosing benign and malignant solid breast masses was 94.51％(224/237),the specificity was 100.00％(159/159),the positive predictive value was 100.00％(224/224),the negative predictive value was 92.44％(159/172),the accuracy was 96.72％(383/396),and the consistency with the postoperative pathological diagnosis was 0.933.The sensitivity of multimodal ultrasound combined with ultrasound-guided needle puncture in diagnosing benign and malignant solid breast masses was 100.00％(228/228),the specificity was 94.64％(159/168),the positive predictive value was 96.20％(228/237),the negative predictive value was 100.00％(159/159),the accuracy was 97.73％(387/396),and the consistency with the postoperative pathological diagnosis was 0.937.Conclusion The ultrasound multimodal diagnostic mode and ultrasonic precision interventional technology can be used in differentiating the benign from malignant solid breast masses with high diagnostic accuracy.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.