1.Effects of human umbilical cord blood platelet-rich plasma,mononuclear cells,and mesenchymal stem cells in repairing thin endometrium in rats
Yanli MU ; Anchun HU ; Wenchi XU ; Panpan CHEN ; Hao CHEN ; Shuyun ZHAO ; Guanyou HUANG ; Xiaojuan CHEN
Chinese Journal of Tissue Engineering Research 2026;30(1):78-92
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.
2.Effects of human umbilical cord blood platelet-rich plasma,mononuclear cells,and mesenchymal stem cells in repairing thin endometrium in rats
Yanli MU ; Anchun HU ; Wenchi XU ; Panpan CHEN ; Hao CHEN ; Shuyun ZHAO ; Guanyou HUANG ; Xiaojuan CHEN
Chinese Journal of Tissue Engineering Research 2026;30(1):78-92
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.
3.Trend change of the mortality and disease burden of hypertensive nephropathy in Chongqing in 2012-2023
Xianbin DING ; Yan JIAO ; Rui DING ; Biao KANG ; Hao MU ; Jie XU ; Ting CHEN ; Jiawei XIE
Journal of Public Health and Preventive Medicine 2025;36(6):43-47
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.
4.Exploration of basket trial design with Bayesian method and its application value in traditional Chinese medicine.
Si-Cun WANG ; Mu-Zhi LI ; Hai-Xia DANG ; Hao GU ; Jun LIU ; Zhong WANG ; Ya-Nan YU
China Journal of Chinese Materia Medica 2025;50(3):846-852
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
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Humans
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Medicine, Chinese Traditional/methods*
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Research Design
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Clinical Trials as Topic/methods*
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Drugs, Chinese Herbal/therapeutic use*
5.The Valvular Heart Disease-specific Age-adjusted Comorbidity Index (VHD-ACI) score in patients with moderate or severe valvular heart disease.
Mu-Rong XIE ; Bin ZHANG ; Yun-Qing YE ; Zhe LI ; Qing-Rong LIU ; Zhen-Yan ZHAO ; Jun-Xing LV ; De-Jing FENG ; Qing-Hao ZHAO ; Hai-Tong ZHANG ; Zhen-Ya DUAN ; Bin-Cheng WANG ; Shuai GUO ; Yan-Yan ZHAO ; Run-Lin GAO ; Hai-Yan XU ; Yong-Jian WU
Journal of Geriatric Cardiology 2025;22(9):759-774
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.
6.The impact of femoral resection on the prognosis of patients with soft tissue sarcoma of the thigh involving cortical bone
Hao QU ; Keyi WANG ; Haochen MU ; Yaling JIANG ; Jiahao ZHANG ; Xin HUANG ; Nong LIN ; Zhaoming YE
Chinese Journal of Orthopaedics 2025;45(10):630-639
Objective:To investigate the prognostic effect of femoral resection on patients with soft tissue sarcoma of the thigh with cortical bone involvement.Methods:This retrospective study included patients with soft tissue sarcoma of the thigh diagnosed and treated in the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to December 2021. Patients were divided into two groups based on whether femoral resection and reconstruction were performed with 20 in the resection group and 86 in the non-resection group. Propensity score matching (PSM) was used to control confounding variables. Overall Survival, recurrence free survival, metastasis free survival, and postoperative functional outcomes were compared between groups before and after PSM. Cox proportional hazards regression was used to identify risk factors for death, recurrence, and metastasis.Results:Before PSM, the 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 46.7% and 36.7% in the resection group, compared to 69.7% and 60.3% in the non-resection group without significant differences ( P>0.05). However, the 5-year metastasis-free survival (MFS) rate was significantly lower in the resection group (40.0%) compared to the non-resection group (73.1%) ( P=0.021). After PSM, the 5-year OS, RFS, and MFS in the resection group were 46.7%, 36.7%, and 35.9%, respectively, compared to 45.0%, 39.4%, and 67.7% in the non-resection group, with no significant differences ( P>0.05). The median postoperative MSTS functional score after PSM was significantly lower in the resection group 23(18, 25) points than in the non-resection group 26.5(24.3, 27.8) points ( U=43.000, P=0.007). Multivariate Cox regression analysis identified grade III histology ( HR=3.794, P=0.002) and tumor involvement angle around the femur greater than 180° ( HR=2.729, P=0.030) as independent risk factors for death. Age over 55 years ( HR=4.185, P=0.015), tumor diameter greater than 8 cm ( HR=4.290, P=0.014), and involvement of the intermuscular compartment ( HR=3.794, P=0.017) were associated with increased risk of local recurrence. Grade III histology ( HR=3.848, P=0.006) and involvement of the intermuscular compartment ( HR=2.500, P=0.045) were associated with distant metastasis. Conclusion:For patients with thigh soft tissue sarcoma involving femoral cortex involvement but no medullary cavity invasion, bone resection did not improve survival, recurrence or metastasis compared with patients in non-resection group. A relatively more conservative surgical approach may be advisable to preserve limb function without compromising oncological prognosis.
7.The therapeutic effects of newly formulated Tadalafil tablets on rats with pathological cardiac hypertrophy through regulation of NF-κB signaling pathway
Xue-di ZHANG ; Ye-ding SONG ; Li-mei LI ; Hao-yan CHEN ; Hua-sui CUI ; Zheng-gang ZHAO ; Zi-jian ZHAO ; Yun-ping MU ; Fang-hong LI
Chinese Pharmacological Bulletin 2025;41(8):1485-1492
Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P<0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P<0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.
8.Correlation between body mass index and risk of multiple myeloma: a two-sample Mendelian randomization study
Fangshuo FENG ; Lanting LIU ; Lugui QIU ; Mu HAO
Journal of Leukemia & Lymphoma 2025;34(5):291-295
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.
9.Specific extraction and analysis of synthesized proteins from mesenchymal stem cells transplanted into the ischemic heart
Wan-Er LU ; Ying DAI ; Mu-Han TANG ; Kang WEI ; Shu-Jia CHEN ; Huai HUANG ; Jing LIN ; Hao-Rong PENG ; Li-Xuan ZHOU ; Dun-Zheng HAN
Medical Journal of Chinese People's Liberation Army 2025;50(8):991-998
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.
10.The diagnostic accuracy and safety of CT-guided percutaneous lung biopsy in ≥80 years patients
Journal of Interventional Radiology 2025;34(4):414-417
Objective To evaluate the diagnostic accuracy and clinical safety of CT-guided percutaneous lung biopsy in ≥80 years patients.Methods A total of 400 patients who underwent CT-guided percutaneous lung biopsy were enrolled in this study.There were 79 patients aged ≥80 years(≥80 group)and 321 patients aged<80 years(<80 group).The diagnostic accuracy and complications of CT-guided percutaneous lung biopsy were compared between the two groups.Multivariate logistic regression analysis was used to assess the relevant risk factors for the occurrence of complications in patients aged ≥80 years.Results No statistically significant differences in the incidence of complications(including pneumothorax,pulmonary hemorrhage,hemoptysis,etc.)existed between the two groups(P>0.05).In ≥80 group and<80 group,the diagnostic accuracy was 97.47%and 97.51%respectively,the sensitivity was 97.10%and 97.17%respectively,both the specificity and positive predictive value were 100%,and the negative predictive value was 83.33%and 82.61%respectively,the differences in the above indexes between the two groups were not statistically significant(all P>0.05).In ≥80 group,the lesion size and the number of intraoperative needle direction adjustments were the independent risk factors for causing pulmonary hemorrhage(OR=0.429,9.429,P<0.05).Conclusion For 80 years patients,CT-guided percutaneous lung biopsy is clinical safe with high diagnostic accuracy.The incidence of complications and diagnostic accuracy of CT-guided percutaneous lung biopsy in patients aged ≥80 years are not significantly different from those in patients aged<80 years.


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