BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

Ground-glass nodules (GGNs) are common imaging manifestation in the early screening of lung adenocarcinoma. With the widespread use of low-dose computed tomography (LDCT) in lung cancer screening, the detection rate of GGNs has significantly increased. According to the presence or absence of a solid component, GGNs are mainly classified into pure ground-glass nodules (pGGNs) and mixed ground-glassnodules (mGGNs), which differ in their natural course and biological behavior. In general, pGGNs tend to progress more slowly, whereas mGGNs are more likely to develop invasive features. The vast majority of pGGNs remain stable for years, but some pGGNs and mGGNs may show an increase in size or in the solid component. The "indolence" observed on the surface of GGNs hides complex genomic, metabolic, and immune changes, which are difficult to capture with traditional image-based data. In recent years, multi-omics analysis, radiomics, and artificial intelligence models have provided new tools for identifying high-risk GGNs. However, there is still controversy over the clinical generalizability, interpretability, and standardization of these models. Furthermore, there is no consensus on whether surgical resection is required. This article reviews the molecular mechanisms, metabolic, and immune microenvironment changes involved in the progression of GGNs, discusses the advantages and limitations of imaging prediction models, and combines domestic and international guidelines and survival studies to explore the controversial points in follow-up and surgical strategies, aiming to provide references for the personalized management of GGNs.

Basket trial, as an innovative clinical trial design concept, marks the transformation of medical research from the traditional large-scale and single-disease treatment to the precise and individualized treatment. By gradually incorporating the Bayesian method during development, the trial design becomes more scientific and reasonable and increases its efficiency. The fundamental principle of the Bayesian method is the utilization of prior knowledge in conjunction with new observational data to dynamically update the posterior probability. This flexibility enhances the basket trial's capacity to effectively adapt to variations during the research process. Consequently, it enables researchers to dynamically adjust research strategies based on accumulated data and improve the predictive accuracy regarding treatment responses. In addition, the design concept of the basket trial aligns with the traditional Chinese medicine(TCM) principle of "homotherapy for heteropathy". The principle of "homotherapy for heteropathy" emphasizes that under certain conditions, different diseases may have the same treatment. Similarly, basket trials allow using a uniform trial design across multiple diseases, offering enhanced operational and significant practical value in the realm of TCM, particularly within the context of syndrome-based disease research. By introducing basket trials, the design of TCM clinical studies will be more scientific and yield higher-quality evidence. This study systematically categorized various Bayesian methods and models utilized in basket trials, evaluated their strengths and weaknesses, and identified their appropriate application contexts, so as to offer a practical guide for designing basket trials in the realm of TCM.
Bayes Theorem ; Humans ; Medicine, Chinese Traditional/methods* ; Research Design ; Clinical Trials as Topic/methods* ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective To analyze trend changes of disease burden of hypertensive nephropathy (HTN) between 2012 and 2023 in Chongqing, and to provide the suggestion for HTN prevention and treatment. Methods Death cases of HTN from Chongqing death registration data between 2012 and 2023 were analyzed to calculate indicators such as mortality, age standardization mortality rate (ASMR), rate of years of life lost (YLL) and Average years of life lost. The mortality of HTN between male and female, urban and rural were compared by Chi-square test. The trend change was explained by average annual percent of change (AAPC). Results The mortality and standardized mortality of HTN in Chongqing decreased from 5.44/100 000 and 3.13/100 000 in 2012 to 2.76/100 000 and 1.07/100,000 in 2023 respectively. The average annual percent change (AAPC) was -5.41% and -8.35% respectively, and the differences in the change trends were statistically significant (P<0.01). The mortality and standardized mortality of HTN in males and females decreased with AAPC of 5.50%, 8.07%, 5.27% and 8.69% respectively, and the differences in the change trends were all statistically significant (all P< 0.05). From 2012 to 2014, 2019 and 2021, the mortality rate of HTN in rural areas was higher than that in urban areas (all P < 0.05). The mortality and standardized mortality of HTN in rural areas decreased with AAPC of 6.58% and 9.46% respectively, and the differences in the change trends were all statistically significant (all P<0.05). The rate of YLL and standardized YLL of HTN in Chongqing decreased from 96.02/100 000 and 60.42/100 000 in 2012 to 44.98/100 000 and 21.49/100 000 in 2023 respectively. The AAPC was -5.83% and -7.80% respectively, and the differences in the change trends were statistically significant (both P < 0.05). AYLL of HTN were 17.88 years in 2012, and it was 17.08 years in 2023. There were no statistically significant differences in the changes (both P > 0.05). The standardized AYLL of HTN in rural areas increased at an average annual rate of 1.14%, and the difference was statistically significant (P < 0.05). Conclusion The mortality and YLL rate of HNT in Chongqing was lower than it in China. Moreover, its trend was decreased. It should be strengthened early screening and healthy management of HNT.

Objective:To explore the correlation between body mass index (BMI) and the risk of multiple myeloma (MM).Methods:A two-sample Mendelian randomization (MR) analysis was utilized. The data were obtained from genome-wide association study (GWAS) datasets in the IEU OpenGWAS database. The dataset number for exposure factor BMI was ieu-a-2, involving 339 224 mixed populations (males and females) and containing 2 555 511 single nucleotide polymorphisms (SNP); the dataset number for outcome factor MM was ieu-b-4957, involving 372 617 European populations (601 MM patients and 372 016 healthy individuals), containing 8 615 746 SNP; the BMI and MM reference genomes were both HG19/GRCh37 provided by the Genetic Investigation of Anthropometric Traits (GIANT) collaborative organization. From dataset ieu-a-2, 79 SNP significantly associated with BMI were selected as instrumental variables ( F > 10), and then validated in the outcome factor dataset (ieu-b-4957), with missing SNP excluded, resulting in 76 retained instrumental variables. MR analyses were performed using the inverse variance weighted (IVW), MR-Egger regression, weighted median method, simple mode method, and weighted mode method. Sensitivity analyses were conducted using the Cochran Q test, MR-Egger regression intercept and leave-one-out approach. Results:IVW results showed a positive correlation between BMI and the risk of MM ( OR = 1.001, 95% CI: 1.000-1.002, P = 0.012), which was supported by the MR-Egger method ( OR = 1.003, 95% CI: 1.000-1.005, P = 0.022). The sensitivity analyses results showed that neither the MR-Egger intercept (intercept = -4.336×10 -5, P = 0.158) nor the heterogeneity test (IVW: Q = 82.02, P = 0.271) found significant heterogeneity or horizontal pleiotropy, indicating high robustness of the results. Conclusions:BMI may be a potential risk factor for the development of MM.

Objective:To explore the clinical efficacy of the splenic vessel-oriented anatomical plane priority strategy in Da Vinci robotic Kimura distal pancreatectomy.Methods:A retrospective analysis was conducted on 26 patients who underwent robotic-assisted distal pancreatectomy at Zhejiang Provincial People’s Hospital from January 2019 to September 2024. The cohort included 7 male and 19 female patients, aged (49.3±16.7) years. Surgical outcomes, including operative time, intraoperative blood loss, postoperative complications, and hospital stay, were analyzed, and surgical techniques were summarized.Results:All 26 patients successfully completed the surgery. Pathological diagnoses included 5 cases of intraductal papillary mucinous neoplasm, 5 serous cystadenomas, 1 pancreatic neuroendocrine tumor, 6 solid pseudopapillary neoplasms, 4 mucinous cystic neoplasms, and 5 neuroendocrine tumors. The maximum tumor diameter was (2.3±1.1) cm, and the operative time was (183.2±77.4) min. The spleen preservation rate was 100% (26/26). Intraoperative blood loss was 50.0 (17.5, 125) ml, and postoperative hospital stay was (10.1±3.7) d. No Clavien-Dindo grade III or higher complications occurred. The post-operative pancreatic fistula (POPF) rate was 53.8% (14/26), including 38.5% (10/26) biochemical leak and 15.3% (4/26) grade B POPF, with no grade C POPF.Conclusion:The splenic vessel-oriented anatomical plane priority strategy in robotic-assisted spleen-preserving distal pancreatectomy (Kimura technique) is safe and feasible, significantly improving the spleen preservation rate.

Objective To analyze the effects of tyrosinase on choroidal and retinal thickness and blood flow changes in guinea pigs,and to explore the role of tyrosinase in the development and progression of myopia.Methods A total of 30 three-week-old male tri-colored guinea pigs and 10 albino guinea pigs were selected and divided into four groups:control group(tri-colored hyperopic guinea pigs,with no intervention),albino group(albino myopic guinea pigs,with no inter-vention),myopia group(tri-colored myopic guinea pigs,with no intervention),and injection group[tri-colored hyperopic guinea pigs,injected with tyrosinase inhibitor(6 250 μg·L-1),100 μL per day].The experiment lasted for 4 weeks.The refractive status and axial length(AL)of the guinea pigs in each group were measured,along with ocular biometric param-eters related to axial length[anterior chamber depth,aqueous humor depth(AQD),central corneal thickness,lens diame-ter,vitreous chamber depth(VCD)].Optical coherence tomography was used to measure the retinal thickness,choroidal thickness(ChT),and choroidal blood perfusion(ChBP)in different regions of the guinea pigs.The tyrosinase activity in the vitreous and retina of guinea pigs in each group was measured.The expression levels of neurotransmitters in the vitre-ous and retina of guinea pigs in each group were detected.Results The differences in refractive status between the albi-no group and the control group at 0,2,and 4 weeks of the experiment were statistically significant(F=8.972,P＜0.05).At the 4th week of the experiment,the refractive status of the injection group was lower than that of the control group,and the AL was greater than that of the control group,with statistically significant differences(both P＜0.05).Further analysis of AL-related biometric parameters revealed that only AQD and VCD were associated with the changes in AL of guinea pigs in each group.At the 0th week of the experiment,the average retinal thickness of the control group was greater than that of the albino group,with a statistically significant difference(t=-9.007,P＜0.000 1).Moreover,the differences in reti-nal thickness in the outer retina across different directions and time points were statistically significant(all P＜0.05).The differences in retinal thickness between the control and albino groups were mainly concentrated in the outer retina.The ChT of the albino group was less than that of the control group,with a significant difference between groups(F=4.809,P=0.030).The ChBP of the control group was significantly higher than that of the albino group at 0,2,and 4 weeks of the experiment(all P＜0.05).At the 4th week of the experiment,the tyrosinase activity in the vitreous of the injection,albi-no,and myopia groups was lower than that of the control group,with statistically significant differences(all P＜0.05).The differences in neurotransmitters between the albino and control groups were mainly concentrated in the vitreous.In the retina,the ornithine level in the myopia group was higher than that in the albino and control groups,and the tryptophan levels in the myopia and control groups were higher than that in the albino group,with statistically significant differences(all P＜0.05).Conclusion Tyrosinase plays a crucial role in the development of myopia,regulating the development of refractive status by influencing the physiological properties of the retina and choroid.

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.