ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure （CHF） and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction （TAC）. Eight of the 50 SD rats were randomly selected as the sham group， and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model， trimetazidine （6.3 mg·kg^-1）， and Yiqi Wenyang Huoxue Lishui components （60 mg·kg^-1 total saponins of Astragali Radix， 10 mg·kg^-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma， 190 mg·kg^-1 aqueous extract of Lepidii Semen， and 100 mg·kg^-1 cinnamaldehyde） groups. The rats were administrated with corresponding agents by gavage， and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg^-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide （NT-ProBNP）， hypersensitive troponin（cTnI）， creatine kinase （CK）， lactate dehydrogenase （LD）， free fatty acids （FFA）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The colorimetric assay was employed to measure the levels of adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta （ATP5D）， glucose transporter 4 （GLUT4）， and carnitine palmitoyltransferase-1 （CPT-1）. The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ. ResultsCompared with the sham group， the model group showed a loosening arrangement of cardiac fibers， fracture and necrosis of partial cardiac fibers， inflammatory cells in necrotic areas， massive blue fibrotic tissue in the myocardial interstitium， increased collagen fiber area and myocardial fibrosis， destroyed mitochondria， myofibril disarrangement， sparse myofilaments， and fractured and reduced cristae. In addition， the rats in the model group showed declined ejection fraction （EF） and fractional shortening （FS）， risen left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs）， elevated levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， lowered level of SOD， down-regulated protein levels of GLUT4 and CPT-1， decreased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and declined levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. Compared with the model group， the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue， risen EF and FS， declined LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs， lowered levels of NT-ProBNP， cTnI， CK， MDA， FFA， and LD， elevated level of SOD， up-regulated protein levels of GLUT4 and CPT-1， increased activities of Na⁺-K⁺-ATPase， Ca²⁺-Mg²⁺-ATPase， and respiratory complexes Ⅰ-Ⅳ， and elevated levels of ATP5D， ATP， ADP， and AMP （P<0.05， P<0.01）. ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function， reduce myocardial injury， regulate glucose and lipid metabolism， optimize the utilization of substrates， and alleviate the damage of mitochondrial structure and function， thus improving the energy metabolism of the myocardium in the rat model of CHF.

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

Objective To compare the long-term survival outcomes of patients with T_1-2N₀M₀ duodenal neuroendocrine tumor (DNET) after endoscopic resection (ER) or surgical resection (SR). Methods Patients diagnosed with T_1-2N₀M₀ DNET between January 1, 2004, and December 31, 2015, were extracted from the SEER database. Kaplan-Meier survival curve and log-rank test were used to compare overall survival (OS) rate and cancer-specific survival (CSS) rate between patients undergoing ER or SR. Propensity score matching (PSM) was used to reduce grouping differences, and multivariate Cox regression was used to analyze factors affecting OS and CSS before and after PSM. Results A total of 656 patients were included, with 457 in ER group and 199 in SR group. Before PSM, there was no significant difference in the 5-year OS rate between the ER and SR groups (88.9% vs 89.6%), but there was a significant difference in the 5-year CSS rate (99.3% vs 96.9%, P＝0.017). Before PSM, multivariate Cox regression analysis showed advanced age was an independent risk factor for decreased OS (P＜0.001). After PSM, there was no significant difference between the ER group (n＝187) and SR group (n＝187) in 5-year OS rate (90.2% vs 88.9%) or CSS rate (98.9% vs 96.7%). After PSM, multivariate Cox regression also showed advanced age was an independent risk factor for decreased OS, while resection method was not an independent factor for OS or CSS. Conclusions There is no significant difference in OS or CSS after endoscopic treatment and surgical treatments for patients with T_1-2N₀M₀ DNET, and advanced age is an independent factor for OS.

Abstract The construction of autism spectrum disorders (ASD) specialty cohorts in China is still in its infancy, and the cost effectiveness is insufficient when relying on diagnostic and treatment processes of child health care to collect ample and high quality data. After 2000, the United States Simons Foundation s ASD Research Initiative, the Early ASD Risk Longitudinal Investigation (EARLI), and the British ASD Study of Infant Siblings (BASIS), which have been built based on Internet recruitment, have provided new insight for the construction of large sample ASD specialty cohorts in China. Future research can further explore and optimize the methods of Internet recruitment, and establish a more comprehensive and accurate ASD specialty cohorts.

A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

Taxifolin (Tax) has been proved to be a medicinal edible substance with protective effects against alcoholic liver injury, however, its poor hydrophilicity and permeability have hindered the clinical application of Tax. In this study, we prepared taxifolin-phosphatidylcholine/sodium deoxycholate/PVP-K30 micells (Tax-MLs). Box-Behnken test was used to obtain the optimal preparation process, and Tax-MLs were characterised by transmission electron microscopy and fourier transform infrared spectroscopy. Physicochemical parameters such as proximate micelle concentration, equilibrium solubility and oil-water partition coefficient were determined, and the release pattern of Tax-MLs was investigated by in vitro digestion simulation. Alcoholic liver injury model to explore the in vivo efficacy of Tax-MLs. The results showed that the average particle size, polydispersity index (PDI) and zeta potential of Tax-MLs were 36.90 ± 4.57 nm, 0.194 ± 0.01 and -32.6 ± 0.35 mV, respectively, and the uniform size and distribution of Tax-MLs were observed by transmission electron microscopy. The formation of Tax-MLs was proved by differential scanning calorimetry and fourier transform infrared spectroscopy. In terms of physicochemical properties, the solubility of Tax-MLs in water increased by 92.02 times compared with Tax, and its oil-water partition coefficient in water increased from 0.43 to 1.14, which proved that Tax-MLs could improve its solubility and permeability. The in vivo pharmacodynamic results showed that compared with the Tax group, Tax-MLs low, medium and high dose groups showed a significant reduction in liver indices and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05), and enhanced the activities of superoxide dismutase (SOD) and glutathione (GSH), and lowered the levels of malondialdehyde (MDA) more significantly in the hepatic tissues. Tax-MLs effectively improved drug solubility and permeability, and enhanced the protective effect against alcoholic liver injury. Animal experiments were conducted with approval from the Animal Ethics Committee of Changchun University of Traditional Chinese Medicine (approval number: 2023601).

BACKGROUND:Ca2+expression in astrocytes has been found to be closely related to cognitive function,and the Ca2+signaling pathway regulated by inositol 1,4,5-trisphosphate receptors(IP3R2)and ryanodine receptor(RYR)2 receptors has become a hot spot in the study of cognitive disorder-related diseases. OBJECTIVE:To investigate the expression of Ca2+signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning,and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning. METHODS:C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group.An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group,and the same amount of air was inhaled in the control group.Behavioral and neuronal changes,astrocyte specific marker glial fibrillary acidic protein,IP3R2,RYR2 receptor and Ca2+concentration in astrocytes of the two groups were detected using Morris water maze,hematoxylin-eosin staining,western blot,immunofluorescence double labeling and Ca2+fluorescence probe at 21 days after modeling. RESULTS AND CONCLUSION:In the Morris water maze,the escape latency of the experimental group was significantly longer than that of the control group(P<0.05).Hematoxylin-eosin staining results showed that in the experimental group,the number of hippocampal pyramidal cells decreased,the cell structure was disordered,and the nucleus was broken and dissolved.Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus,and the expressions of IP3R2,RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group(P<0.05).Western blot analysis showed that the expressions of IP3R2,RYR2,and glial fibrillary acidic protein in the hippocampus of the experimental group were increased(P<0.05).Ca2+concentration in hippocampal astrocytes increased significantly in the experimental group(P<0.05).To conclude,astrocytes may affect Ca2+signals by mediating IP3R2 and RYR2 receptors,then impair the cognitive function of mice with carbon monoxide poisoning,and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.

Objective: To analyze respiratory syncytial virus(RSV) outbreaks surveillance results and the epidemiological characteristics in kindergarten and school in Shenzhen during 2017-2023 , so as to provide a scientific reference for control and prevention of RSV. Methods: Epidemiological data and surveillance results of RSV outbreaks in kindergarten and school from 2017 to 2023 were collected for descriptive analyses. Results: A total of 31 RSV outbreaks were identified in kindergarten and school in 2017-2023 in Shenzhen, 346 cases were reported, the average incidence rate was 22.02%. The most annual RSV outbreaks were reported in 2020 with 14 outbreaks, followed by 8 outbreaks in 2023. A total of 64.52% of RSV outbreaks were identified in kindergarten with rest occurring in primary school or middle school. The greatest monthly count of outbreak was 18 (58.06%) in September, followed by 3 outbreaks (9.68%) in March and October. A total of 244 swab samples were collected, 169 samples were positive for respiratory viruses, the positive rate was 69.26%, 121 samples were positive for RSV,from 31 respiratory syncytical virus outbreaks 57 and samples were positive for other respiratory viruses(9 samples were positive for two respiratory viruses). A toral of 14(45.16%) outbreaks are caused by RSV alone, 17 outbreaks (54.84%) were caused by RSV and other respiratory viruses. Conclusions Most RSV outbreaks in kindergarten and school are reported after 2020 in Shenzhen, most RSV outbreaks occur in kindergarten, peak seasons of RSV outbreaks are autumn and spring.