Exercise, as a non-pharmacological intervention, holds a pivotal role in metabolic regulation, neuroplasticity, and immune homeostasis maintenance. However, human exercise studies are constrained by ethical limitations in tissue sampling, especially for key organs such as muscles and the brain. Meanwhile, rodent models like mice exhibit physiological differences in exercise patterns and metabolic rates from human. Despite these challenges, approximately 70% of human and mouse genes are conserved, providing a molecular basis for cross-species comparisons. This paper leverages the GEPREP database, which integrates human and mouse exercise transcriptomic data from multiple platforms, to conduct a comprehensive cross-species analysis of exercise-induced gene expression patterns. We employ a stringent data standardization process, including the conversion of orthologous genes and the filtering of low-expressing genes, to ensure the accuracy and reliability of the analysis. A mixed-effects model is utilized to assess differential gene expression across multiple cohorts, identifying genes that are significantly upregulated or downregulated in response to exercise. The analysis reveals a complex pattern of gene expression, with a significant number of genes showing conserved responses between humans and mice, particularly in acute aerobic exercise, where genes such as ATF3, PPARGC1A, and ANKRD1 are commonly upregulated. These genes are implicated in muscle stress response, metabolic regulation, and muscle adaptation, highlighting the shared molecular pathways activated by exercise across species. However, the study also uncovers substantial species-specific differences in gene expression, especially in chronic aerobic exercise, where the number of divergently regulated genes increases. These differences suggest that while some fundamental biological processes are conserved, the specific regulatory mechanisms and gene expression patterns can vary significantly between humans and mice. Functional enrichment analysis further reveals that conserved genes are involved in muscle development, inflammation regulation, and energy metabolism, while species-specific genes are associated with ion transport, extracellular matrix (ECM) organization, and muscle contraction, indicating the multifaceted impact of exercise on skeletal muscle function. The findings emphasize the importance of considering species-specific differences when interpreting results from animal models and translating them to human health applications. The study highlights the need for a more nuanced understanding of the molecular underpinnings of exercise-induced adaptations and underscores the value of cross-species comparative analyses in uncovering the evolutionary and functional basis of these responses. Future research should focus on integrating multi-omics data and expanding the analysis to include other tissues to provide a more comprehensive view of the systemic effects of exercise. Additionally, the development of species-specific gene editing models and the validation of key genes in exercise physiology will further enhance our understanding of the evolutionary logic behind exercise interventions. This study not only provides valuable insights into the molecular mechanisms of exercise-induced adaptations but also underscores the necessity of validating findings from animal models in human cohorts to ensure the reliability and applicability of translational research in exercise science. By addressing these aspects, the study aims to bridge the gap between basic research and clinical applications, ultimately contributing to the development of personalized exercise prescriptions and interventions that can effectively promote health and prevent diseases.

AIM: To analyze the mechanism of Usher syndrome(USH)caused by Adgrv1 gene variation through the Hedgehog(Hh)signaling pathway.METHODS: Based on Adgrv1 gene variant mice(Adgrv1-/-), taking wild type(WT)C57BL/6 mice as controls, the expression of Adgrv1 gene and the structure of retina and cell cilia were analyzed by qRT-PCR, HE, transmission electron microscopy, and immunofluorescence. Additionally, the changes of key factors in the Hh signaling pathway caused by Adgrv1 gene variation were observed.RESULTS: The Adgrv1 gene was expressed in both the retina and primary cultured lung fibroblasts of Adgrv1-/- mice, but the expression levels were significantly decreased. The Adgrv1 gene variation can cause dissolution of the outer disc membrane of the retinal photoreceptors and significantly shorten the cilia length in primary lung fibroblasts. In the Hh signaling pathway, the expression of Ptch1 and Gli genes of Adgrv1-/- was significantly reduced, while the expression of PKA genes was increased.CONCLUSION:The Adgrv1 gene variation leads to shortened cell cilia and dissolution of the outer disc membrane of the retinal photoreceptors, resulting in retinitis pigmentosa, which is related to decreased expression of PTCH1 and GLI1 proteins in the Hh pathway.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.

Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.

Outer membrane vesicles (OMVs) are nanoscale vesicles secreted by Gram-negative bacteria. As a unique bacterial secretion, OMV secretion can help bacteria maintain the outer membrane stability or remove harmful substances. Studies have shown that local separation of outer membrane and peptidoglycan layers led by abnormalities in outer membrane protein function, abnormal structure or excessive accumulation of LPS, and erroneous accumulation of phospholipids in the outer leaflet, which can all lead to bacterial outer membrane protrusion and eventually bud formation of OMVs. Since OMVs are mainly composed of bacterial outer membrane and periplasmic components, the pathogen associated molecular patterns (PAMPs) on their surface can trigger strong immune responses. For example, OMVs can recruit and activate neutrophils, polarize macrophages to secrete large amounts of inflammatory factors. More importantly, OMVs can act as adjuvants to induce dendritic cell (DC) maturation to enhance adaptive immune response in the body. At the same time, OMVs are derived from bacteria, which make it easy to modify. The methods by genetic engineering and others can improve their tumor targeting, give them new functions, or reduce their immunotoxicity, which is conducive to their application in tumor therapy. OMVs not only induce apoptosis or pyroptosis of tumor cells, but also regulate the host immune system, which makes OMVs themselves have a certain killing effect on tumors. In addition, the tendency of neutrophils to inflammatory tumor sites and the formation of neutrophil extracellular traps enable OMVs to target tumor sites, and the suitable size and the characteristic that they are easily taken up by DCs give OMVs a certain lymphatic targeting ability. Therefore, OMVs are often employed as excellent drug or vaccine carriers in tumor therapy. This review mainly discusses the biological mechanism of OMVs, the regulatory effects of OMVs on immune cells, the functional modification strategies of OMVs, and their research progress in tumor therapy.

Objective To investigate the baseline clinical characteristics,ascending aortic root anatomical characteristics,and related factors of the surgical strategy of patients with new-onset conduction disturbance(NOCD)after transcatheter aortic valve replacement(TAVR)with self-expanding valve(SEV)implantation.Methods A retrospective study was conducted on 245 patients who underwent TAVR at the Xiamen Cardiovascular Hospital Xiamen University between December 2014 and November 2022.According to the inclusion and exclusion criteria,167 patients with SEV implantation during surgery were continuously included.They were divided into tricuspid aortic valve group(TAV group,113 cases)and bicuspid aortic valve group(BAV group,54 cases)according to aortic valve morphology.The TAV group was divided into NOCD group(43 cases)and non NOCD group(70 cases)according to postoperative electrocardiogram characteristics.The BAV group was divided into NOCD group(16 cases)and non NOCD group(38 cases).Collect clinical data such as preoperative electrocardiogram and ascending aortic root CT angiography from patients.Results The right-non valvular calcification quantification(P=0.005)in the non-NOCD group was significantly greater than that in the NOCD group,but the aortic angle(P=0.002)was smaller in TAV patients.Multivariate analysis suggested that the risk of NOCD after TAVR is reduced by 2.6％for every 10 mm3 increase in right-non valvular calcification in patients(OR 0.974,P=0.039),the risk of postoperative NOCD nearly 7.3％for every degree increase in aortic angulation(OR 1.073,P=0.003).In BAV patients the increase of the risk of NOCD after TAVR is nearly 3.3％for every l ms increase in preoperative PR interval(OR 1.033,P=0.041),the risk of NOCD is reduced by 6.6％for every 10 mm3 increase in calcification quantification in the right coronary valve area(OR 0.934,P=0.013).Conclusions In TAV patient,right-non valvular calcification may have a protective effect on the cardiac conduction system,but a larger aortic angle increases the risk of NOCD.In BAV patients,a longer preoperative PR interval is a risk factor for NOCD,and the right coronary valve area may protect the cardiac conduction system.

Objective:To investigate effects of mesalazine(MS)on proliferation,apoptosis and inflammatory injury of cell model of ulcerative colitis(UC)induced by lipopolysaccharide(LPS),as well as transforming growth factor-β1(TGF-β1)/Smad signaling pathway effect in this study.Methods:Human colonic epithelial cells NCM-460 cultured in vitro were induced UC model by LPS,and divided into Con group(no treatment),LPS group(1 mg/L LPS),MS group(0.1,0.2,0.4 mg/L MS+1 mg/L LPS)and inhibitor group(10 μmol/L TGF-β1/Smad signaling pathway inhibitor LY2109761+0.2 mg/L MS+1 mg/L LPS).Cell morphology,proliferation,apoptosis and levels of inflammatory factors and TGF-β1/Smad pathway-related markers were examined by inverted microscope,EdU assay,Hoechst 33258 staining,ELISA and Western blot.Results:LPS treatment highly induced cell proliferation rate and Smad7 pro-tein level compared with Con group,while apoptotic cells,inflammatory factors TNF-α and IL-6,soluble interleukin-2 receptor(sIL-2R)release,as well as TGF-β1,p-Smad2,p-Smad3 protein expressions were increased;the above effects induced by LPS was reversed by MS in a dose-dependent manner(P<0.05).Compared with 0.2 mg/L MS group,NCM-460 cells proliferation rate and Smad7 expression were increased,while apoptotic cells,TNF-α and IL-6,sIL-2R releases,and TGF-β1,p-Smad2,p-Smad3 protein expressions were decreased(P<0.05).Conclusion:MS can attenuate LPS-induced apoptosis and inflammatory injury in NCM-460 cells,and this protection was possibly through suppressing TGF-β1/Smad signaling pathway.

Objective:The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center.Methods:According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022.Results:The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas.Conclusions:The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.