1.Mechanical stress regulates apoptosis in vascular smooth muscle cells
Fei XU ; Jinqiang YAN ; Shoudong CHAI
Chinese Journal of Tissue Engineering Research 2025;29(5):1064-1072
		                        		
		                        			
		                        			BACKGROUND:With the development of biomechanics,its research into cardiovascular diseases has become more and more extensive.By studying the mechanical properties of blood vessels,the pathogenesis of cardiovascular diseases such as atherosclerosis and restenosis can be effectively revealed and new ideas and methods can be developed for the treatment of cardiovascular diseases. OBJECTIVE:To review the research status of apoptosis of vascular smooth muscle cells induced by mechanical stress and search for potential target molecules and signaling pathways for clinical treatment,thereby improving the clinical treatment effect on cardiovascular diseases such as atherosclerosis and restenosis. METHODS:We searched the literature in CNKI,PubMed and ScienceDirect databases from January 1992 to May 2023.The search terms were"vascular smooth muscle cell,mechanical stress,shear stress,stretch stress,apoptosis"in Chinese and English.Finally,63 articles were included for review and analysis. RESULTS AND CONCLUSION:Physiological and pathological apoptosis of vascular smooth muscle cells is an adaptive remodeling in response to the changes in vascular mechanics.Vascular smooth muscle cells in different parts have different mechanical stimuli and their pathogenesis is also different.Low shear stress,physiological shear stress and high shear stress directly interact with surface molecules,receptors and proteins of vascular smooth muscle cells to regulate apoptosis-related signaling molecules and inhibit cell proliferation,thus regulating the apoptosis of vascular smooth muscle cells.In this part,the research on promoting proliferation is not summarized.Low stretch stress,physiological stretch stress and high stretch stress can all cause apoptosis of vascular smooth muscle cells,but it is still controversial.There are many mechanoreceptors(such as integrins and receptor tyrosine kinases)on the surface of vascular smooth muscle cells,which can transform mechanical signals into intracellular chemical signals(such as the Hippo pathway),activate the apoptosis signals of vascular smooth muscle cells and regulate the apoptosis of vascular smooth muscle cells.In short,different mechanical stimuli start a variety of signal pathways and regulate the apoptosis of vascular smooth muscle cells through various signal molecules.For example,shear stress affects Fas/FasL and Akt pathways mainly by stimulating prostaglandin secretion and transforming growth factors.Strech stress mainly regulates the YAP pathway and Notch pathway through Yes-related proteins.At different times or intensities,these molecules may play opposite two-way roles.For example,when mouse vascular smooth muscle cells are stretched at 10%physiological tension for 1 hour,cell proliferation increases.However,the proliferation of human vascular smooth muscle cells can decrease after 12 hours of stretching.Clinically,the key molecules of mechanical transduction can be disturbed by searching for key molecules that interfere with mechanical transduction at their critical time points of action.
		                        		
		                        		
		                        		
		                        	
2.The Difficulties and Methodological Suggestions for the Recommendation Formation of Clinical Practice Guidelines of Traditional Chinese Medicine
Yicheng GAO ; Rui CAO ; Zhihan LIU ; Yuting FENG ; Qianyun CHAI ; Minjing LUO ; Ruyu XIA ; Yutong FEI
Journal of Traditional Chinese Medicine 2024;65(3):251-255
		                        		
		                        			
		                        			Currently, there are many difficulties in formulating recommendations of traditional Chinese medicine (TCM) clinical practice guidelines. This paper analyzed and summarized the unique or prominent difficult issues in the formulation of recommendations faced by TCM guidelines, such as experts' professional background and experience bringing about the preferance from the academic emotion, inconsistency between different academic schools making it difficult to reach consensus, lack of guiding principles of the decision weight of different dimensions for recommendations. Therefore, methodological suggestions have been put forward, including organizing parallel TCM and western medicine consensus group, improving the method of combining TCM and western medicine paradigm, attaching great importance to the evidence-based governance of academic schools, and promoting the research on different dimensions for recommendation formulation, which may provide a methodological reference for the guideline development. 
		                        		
		                        		
		                        		
		                        	
3.Development and validation of a prognostic nomogram for locally advanced renal cell carcinoma patients after surgery
Fei LI ; Xiaodong WEN ; Hongqiang CHAI ; Ming WU ; Lei PANG
Journal of Modern Urology 2024;29(4):334-341
		                        		
		                        			
		                        			【Objective】 To construct a nomogram survival prediction model for patients with locally advanced renal cell carcinoma based on SEER database (n=7893), so as to provide reference for future prognosis study. 【Methods】 Case data were downloaded from the SEER database, and divided into the experimental group and validation group with a ratio of 7∶3 by simple randomization.The clinical information was analyzed, independent risk factors influencing prognosis were screened, and the overall survival (OS) and tumor-specific survival (CSS) were mapped.Model performance was evaluated using consistency index, area under the receiver operating characteristic curve (AUC), internal and external validation, and calibration curves. 【Results】 Patients’ age, tumor size, disease progression tpye, TNM stage, number of positive lymph nodes, marital status and pathological type were significantly correlated with OS and CSS (P<0.01).Based on the above predictors, the internal verification AUC of the 1-, 3- and 5- year OS nomogram model was 0.809, 0.721 and 0.715, respectively.The internal validation AUC of the nomogram model for 1-, 3- and 5- year CSS was 0.802, 0.745 and 0.735, respectively.The external validation AUC of the OS nomogram model was 0.792, 0.628 and 0.620 at 1, 3 and 5 years, respectively, and the external validation AUC of CSS was 0.943, 0.803 and 0.737 at 1.3 and 5 years, respectively, showing good model differentiation and accuracy. 【Conclusion】 The prediction performance of the nomogram model is good, and it can provide reference for individualized treatment.
		                        		
		                        		
		                        		
		                        	
4.Effect of thermal insulation measures on intervention of perioperative hypothermia in patients undergoing abdominal surgery:a network meta-analysis
Ya JI ; Fei CHAI ; Liping ZHOU ; Pingping YU ; Yi WANG
Modern Clinical Nursing 2024;23(8):81-90
		                        		
		                        			
		                        			Objective To evaluate the effectiveness of different thermal insulation measures on intervention of perioperative hypothermia in patients undergoing abdominal surgery,through a network Meta-analysis.Methods A systematic search through online databases was conducted from the inception of the databases to August 2023.Databases of CNKI,VIP,Wan Fang Data,SinoMed,PubMed,the Cochrane Library,Web of Science and Embase were searched to retrieve randomly controlled trials(RCTs)in the effectiveness of different thermal insulation measures on perioperative hypothermia in patients undergoing abdominal surgery.According to the inclusion and exclusion criteria,two researchers independently screened the retrieved literatures,extracted data and evaluated the quality of acquired data.Revman 5.4,R 4.3.1 and Stata17.0 were used for the network meta-analysis of the acquired data.Results A total of 26 RCTs were included,involving 9 thermal insulation measures that involved with 2 414 patients.Meta-analysis showed that an inflatable blanket combined with warmed intravenous infusion achieved the best effectiveness in maintaining the perioperative core temperature of the patients with abdominal surgery.An inflatable blanket combined with warmed peritoneal lavage fluid achieved the best effectiveness in reduction of the incidence of perioperative hypothermia and shivering.Conclusion This study shows that a combination of inflatable blanket with warmed peritoneal lavage fluid/warmed intravenous infusion can achieve the best effectiveness on intervention of perioperative hypothermia in patients undergoing abdominal surgery.
		                        		
		                        		
		                        		
		                        	
5.Clinicopathological characteristics of the CD8+T lymphocytes infiltration and its mechanism in distinct molecular subtype of medulloblastoma
Xiaodong CHAI ; Ziwen SUN ; Haishuang LI ; Liangyi ZHU ; Xiaodan LIU ; Yantao LIU ; Fei PEI ; Qing CHANG
Journal of Peking University(Health Sciences) 2024;56(3):512-518
		                        		
		                        			
		                        			Objective:To investigate the characteristics of the CD8+T cells infiltration from the 4 sub-types in medulloblastoma(MB),to analyze the relationship between CD8+T cells infiltration and prog-nosis,to study the function of C-X-C motif chemokine ligand 11(CXCL11)and its receptor in CD8+T cells infiltration into tumors and to explore the potential mechanism,and to provide the necessary clinico-pathological basis for exploring the immunotherapy of MB.Methods:In the study,48 clinical MB sam-ples(12 cases in each of 4 subtypes)were selected from the multiple medical center from 2012 to 2019.The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString Pan-Cancer 10360?Panel(NanoString Technologies).Immunohistochemistry(IHC)staining of formalin-fixed,paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8+T cells in the MB four subtypes.Through bioinformatics analysis,the relation-ship between CD8+T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated.The expression of CXCR3 receptor on the surface of CD8+T cells in MB was verified by double immunofluorescence staining,and the under-lying molecular mechanism of CD8+T cells infiltration into the tumor was explored.Results:The charac-teristic index of CD8+T cells in the WNT subtype of MB was relatively high,suggesting that the number of CD8+T cells in the WNT subtype was significantly higher than that in the other three subtypes,which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus(GEO)database analysis by using R2 online data analysis platform.And the increase of CD8+T cells infiltration was posi-tively correlated with the patient survival.The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes.Immunofluorescence staining showed the presence of CXCL11 receptor,CXCR3,on the surface of CD8+T cells,suggesting that the CD8+T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3.Conclusion:The CD8+T cells infiltrate more in the WNT subtype MB than other subtypes.The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system,and the patients with more infiltration of CD8+T cells in tumor have better prognosis.This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8+T cells infiltration in MB,and give a new potential therapeutic target for the future immunotherapy of MB.
		                        		
		                        		
		                        		
		                        	
6.Expression level of serum UBE2C and TRIM27 in patients with endometrial cancer and their correlation with pathological parameters
Fei CHAI ; Zhenwen CHEN ; Hongyan LIU ; Su LI ; Yuanyuan GONG ; Yingying ZHAO
The Journal of Practical Medicine 2024;40(13):1808-1813
		                        		
		                        			
		                        			Objective To investigate the expression level of serum ubiquitin-conjugating enzyme 2C(UBE2C)and tripartite motif-containing protein 27(TRIM27)in patients with endometrial cancer(EC)and their correlation with pathological parameters.Methods A total of 96 EC patients from March 2020 to March 2023 were selected as EC group;65 patients with endometrial atypical hyperplasia(EAH)as EAH group,and 80 healthy subjects as the control group.Enzyme linked immunosorbent assay was applied to analyze the expression level of serum UBE2C and TRIM27.The relationship between serum UBE2C,TRIM27,and pathological data was analyzed;receiver operating characteristic was applied to evaluate the predictive value of serum UBE2C and TRIM27 level for EC.Results The level of serum UBE2C and TRIM27 of EC patients was obviously higher than that in healthy subjects(P<0.05),and was correlated with tumor diameter,tumor differentiation,lymph node metastasis,FIGO stage,muscle layer invasion depth,cervical involvement,estrogen receptor expression,and progestogen receptor expression(P<0.05).There was positive correlation between serum UBE2C and TRIM27(r=0.475,P<0.001);and the level of serum UBE2C and TRIM27 was positively correlated with tumor diameter,lymph node metastasis,FIGO stage,and depth of musclular invasion,but negatively with tumor differentiation,estrogen receptor expression,and progestogen receptor expression(P<0.05).The combination of UBE2C and TRIM27 had obviously higher AUC in evaluating EC than single detection(ZUBE2C-combination=3.406,P<0.001,ZTRIM27-combination=3.285,P=0.001).Conclusion The expression level of UBE2C and TRIM27 in serum of EC patients is up-regulated,which is closely related to pathological parameters.The level of serum UBE2C and TRIM27 can provide reference for early diagnosis of EC.
		                        		
		                        		
		                        		
		                        	
7.Mechanism of ginsenoside Rg1 inhibiting the proliferation and metastasis of tongue squamous cell carcinoma
Xue LI ; Sha-Fei ZHAI ; Xin-Yang MA ; Dan-Yang WANG ; Juan CHAI ; Fang ZHOU ; Jia ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1888-1892
		                        		
		                        			
		                        			Objective To investigate the inhibitory effect of Ginsenosides Rg1(GS-Rg1)on the proliferation and metastasis of tongue squamous cell carcinoma(TSCC),and its related mechanisms of action.Methods TSCC cells were treated with GS-Rg1 at concentrations of 1.25,2.5,5.0 and 10.0 μmol·L-1 for 48 hours.The proliferation ability of cells at different concentrations was measured by cell counting kit-8(CCK-8)experiment,and the IC5ovalue of GS-Rg1 at CAL-27 for 48 hours was calculated.TSCC cells CAL-27 were divided into control group and GS-Rg1 group.The control group and GS-Rg1 group were treated with 0.9%NaCl and IC50concentration of GS-Rg1 for 48 hours,respectively.The cell cycle distribution of each group was detected by flow cytometry,and the cell metastasis ability of each group was detected by Transwell experiment.Construct TOP/FOP Flash plasmid,transfect control group and GS-Rg1 group,and detect the effect of GS-Rg1 effect on wnt/β-catenin signaling pathway activity in TSCC cell CAL-27 using luciferase assay.Using wnt/β-catenin pathway inhibitor XAV939 treated GS-Rg1 group cells(XAV939+GS-Rg1 group),and wnt/β-catenin pathway activator HLY78 was used to treat GS-Rg1 group cells(HLY78+GS-Rg1 group)and detect changes of wnt/β-catenin signaling pathway activity,the cell proliferation ability,cell cycle distribution,and metastasis ability in XAV939+GS-Rg1 group,HLY78+GS-Rg1 group and GS-Rg1 group.The expression of wnt/β-catenin signaling pathway related proteins β-catenin,and its downstream cell cycle related proteins cellular myelocytomatosis oncogene(cMYC),Cyclin dependent kinase 4(CDK4),andcyclinD1,as well as metastasis related proteins E-cadherin,N-cadherin and matrix metalloproteinase 2(MMP-2)were detected by Western blotting in each group of cells.Results GS-Rg1 significantly inhibited the proliferation ability of TSCC cells CAL-27(P<0.05),and the IC50value of GS-Rg1 on CAL-27 was(5.46±1.58)μmol·L-1.The ratio of GO/G1 phase cells in the control group and GS-Rg1 group were(60.65±2.16)%and(71.20±2.38)%,respectively;the number of cell transmembrane penetration were 87.33±7.51 and 50.67±3.21,respectively;the luciferase activity were 1.00±0.02 and 0.35±0.06,respectively.Compared with the control group,the GS-Rg1 group showed cell cycle arrest in GO/G1 phase,decreased cell metastasis ability,and the activity of wnt/β-catenin signaling pathway decreased(P<0.05,P<0.01).Compared with the GS-Rg1 group,the activity of the wnt/β-catenin signaling pathway was decreased,cell proliferation ability and metastasis ability was decreased(P<0.05),while the number of GO/G1 phase cells was increased(P<0.05),the expression of β-catenin,cMYC,CDK4,cyclinD1,E-cadherin and MMP-2 proteins were decreased(P<0.05),while the expression of N-cadherin protein increased in XAV939+GS-Rg1 group cells.However,the result were opposite in the HLY78+GS-Rg1 group of cells.Conclusion GS-Rg1 downregulates wnt/β-catenin signaling pathway inhibits the proliferation and metastasis ability of TSCC cells.
		                        		
		                        		
		                        		
		                        	
8.Research Ideas and Methods for Standardization of Traditional Chinese Medicine Syndrome Differentiation
Mingjing LUO ; Qianyun CHAI ; Yuting FENG ; Yicheng GAO ; Ruyu XIA ; Yaqi WANG ; Jianping LIU ; Yutong FEI
Journal of Traditional Chinese Medicine 2023;64(24):2505-2510
		                        		
		                        			
		                        			Syndrome differentiation and treatment is a unique mode of diagnosis in traditional Chinese medicine (TCM). The establishment of scientific and standardized syndrome diagnosis standards is an important link to evaluate the clinical efficacy of TCM objectively and systematically, and also a prerequisite for the promotion and development of TCM to obtain international recognition. This article reviewed the basic modes and existed problems of the current syndrome diagnosis criteria, and proposed to construct a multidimensional core information set integrating the minimized core symptoms, the artificial intelligence signs, the multi-modal laboratory indicators, and multi-omics specific markers, so as to present syndrome characteristics from multiple perspectives systematically. This paper also described the basic mode, constructure, as well as the process and methodology to be adopted in the establishment of the standardized diagnostic research method. The core information set of diagnostic symptoms not only took into account the specificity of the disease, but also improved the inconsistency due to the complexity and subjectivity of the syndrome differentiation, thereby providing a methodological basis for the standardization of TCM syndrome differentiation in clinical research. 
		                        		
		                        		
		                        		
		                        	
9.Age-adjusted Charlson comorbidity index predicts mortality in patients with acute type A aortic dissection
Wendan WANG ; Lei WANG ; Chen CHAI ; Xiaowei ZHANG ; Fei LV ; Suting ZHONG ; Tiantian WANG ; Long WU ; Zehai TANG
Chinese Journal of Emergency Medicine 2023;32(1):76-81
		                        		
		                        			
		                        			Objective:To evaluate the predictive value of age-adjusted Charlson comorbidity index (ACCI) for in-hospital mortality and 1-year mortality in patients with acute type A aortic dissection (ATAAD).Methods:This was a retrospective cohort study, and the clinical data of ATAAD patients admitted to Wuhan Union Hospital from January 1, 1999 to December 31, 2018 were collected for analysis. All the patients were confirmed by computed tomography angiography or magnetic resonance imaging of the aorta and the onset time was less than 14 days. Patients who survived at discharge were followed up to obtain 1-year survival information. The ACCI score was calculated for patients based on their comorbidities and age at admission, and they were divided into three groups of 0, 1 and ≥2 according to the ACCI score. The in-hospital mortality and 1-year mortality of the three groups were compared. Logistic regression analysis was applied to determine the independent predictors for in-hospital mortality and 1-year mortality.Results:Among 1 133 ATAAD patients, 383, 357 and 393 patients had ACCI score of 0, 1, and ≥2, respectively. The in-hospital mortality and 1-year mortality of patients with ACCI score ≥2 were significantly higher than those of patients with ACCI score of 0 (25.4% vs. 17.0%, 30.0% vs. 19.6%, both P<0.05). Multivariate Logistic regression analysis showed that ACCI score ≥2 was an independent risk factor for in-hospital mortality ( OR=1.670, 95% CI: 1.176-2.370, P=0.004) and 1-year mortality ( OR=1.762, 95% CI: 1.264-2.456, P<0.001). Age (per 10-year increase) and cerebrovascular diseases were independent risk factors for in-hospital mortality and 1-year mortality, while diabetes mellitus was a protective factor for in-hospital mortality. Conclusions:ACCI can predict the in-hospital mortality and 1-year mortality of ATAAD patients, and patients with ACCI score ≥2 have a poorer prognosis.
		                        		
		                        		
		                        		
		                        	
10.Prevalence, patterns and prognosis of multimorbidity among middle-aged and elderly inpatients with chronic obstructive pulmonary disease.
Jia CUI ; Yan Fei GUO ; Ya Qi TONG ; Di CHAI ; Tie Ying SUN
Chinese Journal of Preventive Medicine 2023;57(5):701-709
		                        		
		                        			
		                        			Objective: To explore the characteristics, patterns of multimorbidity and the impact on quality of life and the prognosis of middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD). Methods: This is a cross-sectional study. From January 2012 to December 2021, 939 middle-aged and elderly COPD patients hospitalized in Beijing Hospital were selected by the convenient sampling method. The basic data of patients and the date of 16 common chronic diseases were collected. Patterns of multimorbidity were depicted by cluster analysis. Generalized linear regression model and logistic regression were used to evaluate the multimorbidity patterns and their prognosis. Results: At least one multimorbidity existed among 93.40% of COPD patients, and the median number of multimorbidity was 3. The top five multimorbidity among the patients were hypertension (57.93%, 544/939), coronary heart disease (33.76%,317/939), heart failure (31.95%,300/939), hyperlipidemia (31.63%,297/939) and arrhythmia (27.37%,257/939). Four multimorbidity patterns were identified, cardiometabolic and metabolic multimorbidity, kidney disease multimorbidity, respiratory-digestive-tumor multimorbidity and other multimorbidity. Cardiometabolic and metabolic multimorbidity was most common (590/939, 62.83%). Compared with non-cardiometabolic and metabolic multimorbidity, the incharge ADL score of patients with this multimorbidity decreased by 7 points (95%CI:-11.22- -3.34), Correspondingly, patients with kidney disease multimorbidity decreased by 14 points (95%CI:-24.12- -3.30) on the incharge score. The presence or absence of kidney disease multimorbidity had the greatest impact on discharge score, which was reduced by 12 points in comparison with patients without this multimorbidity (95%CI:-22.43- -2.40). ICU admission is mostly affected by the presence of cardiometabolic and metabolic multimorbidity (OR=2.44, 95%CI: 1.51-3.92) and kidney disease multimorbidity (OR=2.58, 95%CI: 1.01-6.60). The risk of death is the highest for cardiometabolic and metabolic multimorbidity (OR=2.24, 95%CI: 1.19-4.21). Conclusion: Multimorbidity is common in COPD patients. The most common pattern is cardiometabolic and metabolic multimorbidity. Cardiometabolic and metabolic multimorbidity and kidney disease multimorbidity significantly affect the quality of life and often associate with a poor prognosis.
		                        		
		                        		
		                        		
		                        			Aged
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		                        			Middle Aged
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		                        			Humans
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		                        			Multimorbidity
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		                        			Inpatients
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		                        			Prevalence
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		                        			Cross-Sectional Studies
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		                        			Quality of Life
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		                        			Pulmonary Disease, Chronic Obstructive/epidemiology*
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		                        			Chronic Disease
		                        			
		                        		
		                        	
            
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