OBJECTIVE To investigate the effects and potential mechanism of Panax notoginseng saponins （PNS） on gastric mucosal injury and inflammatory response in rats with chronic atrophic gastritis （CAG） via the stem cell factor（SCF）/cellular tyrosine kinase receptor（c-kit） signaling pathway. METHODS Male SD rats were used to establish a CAG rat model through intragastric administration of N -methyl- N ′-nitro- N -nitrosoguanidine combined with an irregular diet. Successfully modeled rats were randomly divided into a model group， positive control-vitacoenzyme group （Positive group， 250 mg/kg）， PNS low- and high-dose groups （PNS-L and PNS-H groups， 9， 18 mg/kg）， and high-dose PNS+SCF/c-kit inhibitor group （PNS-H+ISCK03 group， 18 mg/kg+47 mg/kg）， with 8 rats in each group. Additionally， 8 healthy rats were selected as a control group. After the final administration， the activities of serum gastrin （GAS）， motilin （MTL） and pancreatic polypeptide （PP）， as well as the levels of tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and IL-8 in gastric mucosal tissues， were measured in each group. Pathological changes of the gastric mucosal and ultrastructure of the epithelial cells were observed， and gastric mucosal atrophy was scored. Cell apoptosis in gastric mucosal tissues and the expressions of proliferating cell nuclear antigen （PCNA）， nuclear factor-κB p65 （NF-κB p65）， SCF and c-kit were detected. RESULTS Compared with the control group， the model group showed significantly increased inflammatory cell infiltration in the gastric mucosal， extensive epithelial cell detachment， severe ultrastructural damage， and significantly elevated or up-regulated gastric mucosal atrophy score， TNF-α and IL-8 levels in gastric mucosal， cell apoptosis rate， and NF-κB p65 protein expression. Meanwhile， serum levels of GAS and MTL， PP activity， the level of IL-10 in gastric mucosal tissue， and protein expressions of PCNA and SCF， as well as the phosphorylation level of c-kit， were significantly decreased or down-regulated （ P ＜0.05）. Compared with the model group， Positive， PNS-L and PNS-H groups exhibited markedly improved pathological changes in the gastric mucosal and significant amelioration of the quantitative indicators， with the PNS-H group showing significantly better improvement than the PNS-L group （ P ＜0.05）. However， ISCK03 significantly reversed the ameliorative effects of high-dose PNS on the above indicators in rats （ P ＜0.05）. CONCLUSIONS PNS improves gastric mucosal injury in CAG rats by reducing the inflammatory response and promoting gastric mucosal repair； these effects may be related to the activation of the SCF/c-kit signaling pathway.

Mitochondria, functioning not only as the central hub of cellular energy metabolism but also as semi-autonomous organelles, orchestrate cellular fate decisions through their endogenous mitochondrial DNA (mtDNA), which encodes core components of the electron transport chain. Emerging research has identified microRNAs localized within mitochondria, termed mitochondria-located microRNAs (mitomiRs). Recent studies have revealed that mitomiRs are transcribed from nuclear DNA (nDNA), processed and matured in the cytoplasm, and subsequently transported into mitochondria. mitomiRs regulate mtDNA through diverse mechanisms, including modulation of mtDNA expression at the translational level and direct binding to mtDNA to influence transcription. Aberrant expression of mitomiRs leads to mitochondrial dysfunction and contributes to the pathogenesis of metabolic diseases. Restoring mitomiR expression to physiological levels using mitomiRs mimics or inhibitors has been shown to improve mitochondrial function and alleviate related diseases. Consequently, the regulatory mechanisms of mitomiRs have become a major focus in mitochondrial research. Given that mitomiRs are located in mitochondria, targeted delivery strategies designed for mtDNA can be adapted for the delivery of mitomiRs mimics or inhibitors. However, numerous intracellular and extracellular barriers remain, highlighting the need for more precise and efficient delivery systems in the future. The regulation of mtDNA expression mediated by mitomiRs not only expands our understanding of miRNA functions in post-transcriptional gene regulation but also provides promising molecular targets for the treatment of mitochondrial-related diseases. This review systematically summarizes recent research progress on mitomiRs in regulating mtDNA expression and discusses the underlying mechanisms of mitomiRs-mtDNA interactions. Additionally, it provides new perspectives on precision therapeutic strategies, with a particular emphasis on mitomiRs-based regulation of mitochondrial function in mitochondrial-related diseases.

Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.

Aim To evaluate the toxicity and mecha-nism of Epimedium sagittatum(Sieb.et Zucc.)Maxim aqueous extract(ESMAE)on HepaRG cells based on serum toxicology.Methods MTT assay was used to detect the activity of HepaRG cells after treatment with the serum containing ESMAE from SD rats.Western blot was used to detect the effects of the serum contai-ning drug on the expression of endoplasmic reticulum stress-related proteins(PERK,eIF-2α,ATF-4,GRP78,CHOP)and pyroptosis related proteins(NL-RP1,caspase-1,cleaved caspase-1,GSDMD,GSDMD-N).MTT assay was used to detect the activity of Hep-aRG cells after treatment with the liver homogenate containing ESMAE from SD rats.Results Twenty percent serum containing drug significantly decreased the viability of HepaRG cells,with the cells exhibiting swelling,rupture,and vesicle-like pyroptosis.The ex-pression levels of endoplasmic reticulum stress-related proteins PERK,eIF-2α,ATF-4,GRP78,and CHOP significantly increased.The expression levels of pro-teins involved in the NLRP1-mediated classical pyrop-tosis pathway were significantly increased.Finally the liver homogenate containing drug decreased the cell ac-tivity,and cells exhibited swelling,rupture,and vesicle-like pyroptosis.Conclusions After administration of ESMAE,the serum containing drug and the liver ho-mogenate containing drug of rats show toxicity to Hep-aRG cells,and can induce endoplasmic reticulum stress and activate the NLRP1/caspase-1/GSDMD pyroptosis pathway in HepaRG cells.

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.

New quality productivity is a strategic engine for promoting high-quality development and is an inherent requirement and important focus for enhancing new driving forces and building national advantages.The cultivation of innovative talents and technological innovation are key to the development of new quality productivity.Laboratory animal science is a comprehensive interdisciplinary subject that integrates multiple disciplines including biology,medicine,pharmacy,and biomedical engineering.Teaching and research of laboratory animal science not only promotes the creation of innovative talent teams by cultivating innovative consciousness,thinking,spirit,and operational abilities,but also promotes the development of cutting-edge technologies and the transformation of disruptive research result in the fields of basic research and clinical translation of biomedicine,thus providing important guarantees for China's scientific and technological progress and innovative development.

Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.

High altitude heart disease(HAHD)is a chronic mountain sickness in which the body is exposed to high altitude(＞2 500 m)hypobaric hypoxia environment for a long time.HAHD has high morbidity and poor prognosis,and pulmonary hypertension is the main causative mechanism for its develop-ment.The phosphodiesterase-5 inhibitor sildenafil has become a hot drug for the treatment of pulmonary hypertension.This paper reviews the progress of HAHD and discusses the mechanism of action and effectiveness of sildenafil in the treatment of HAHD,with a view to providing a basis for the treatment of HAHD with sildenafil.