1.Establishment of a LASSO-Logistic Regression-based Risk Prediction Model for Early Recurrence of Siewert Ⅱ/Ⅲ Adenocarcinoma of Esophagogastric Junction Post-Surgery
Zuyu ZHANG ; Hong WEI ; Qian LIU ; Yaoqiang WANG ; Xueyan FAN ; Ruiying LUO ; Changjiang LUO
Medical Journal of Peking Union Medical College Hospital 2024;15(3):604-615
To investigate the risk factors for early relapse after curative resection of Siewert type Ⅱ/Ⅲ adenocarcinoma of esophagogastric junction (AEG) and construct a visual predictive model. A retrospective analysis was conducted on the clinicopathological data of patients diagnosed with Siewert type Ⅱ/Ⅲ AEG who underwent curative resection at the Second Hospital of Lanzhou University from January 2016 to March 2021. The samples were randomly divided into a training group and a validation group in a 7∶3 ratio. The LASSO-Logistic regression method was used to select variables predictive of early recurrence of Siewert type Ⅱ/Ⅲ AEG and construct a predictive model for early recurrence. The model was validated through 1000 bootstrap resampling. Receiver operating characteristic (ROC) curves were drawn, and area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to evaluate the model's stability. According to the inclusion and exclusion criteria of this study, a total of 320 Siewert type Ⅱ/Ⅲ AEG patients were included, with 122 experiencing recurrence within two years. LASSO-Logistic regression analysis revealed AJCC staging, degree of differentiation, CA199, CEA, NLR, and tumor maximum diameter as independent predictive factors for early recurrence of Siewert type Ⅱ/Ⅲ AEG. A predictive model was constructed with these factors and depicted as a nomogram. For the training group, the AUC of the ROC curve was 0.836(95% CI: 0.785-0.887), with a sensitivity of 81.4% and a specificity of 85.6%;for the validation group, the AUC was 0.812(95% CI: 0.711-0.912), with a sensitivity of 80.6% and a specificity of 87.7%. Calibration curves for both the training and validation groups displayed curves close to the reference line, indicating high model stability. The DCA curve showed that the model provided a good net benefit with threshold probabilities between 0.05 and 0.75. A multivariate model developed using LASSO-Logistic regression could predict early relapse in patients with Siewert type Ⅱ/Ⅲ AEG, which may be instrumental in assessing patient prognoses and in guiding postoperative surveillance and management for patients with Siewert type Ⅱ/Ⅲ AEG.
2.GNMT inhibits intrauterine adhesion fibrosis through TGF-β1/Smad3 signaling pathway and its mechanism
Hong GU ; Jia WANG ; Wenwen ZHANG ; Xiao YANG ; Xiyue HUANG ; Yingfeng ZHANG ; Yanhua MAO ; Changjiang LI ; Qiuhong CHEN ; Jinglin HUANG ; Qi LIU ; Ling WEI ; Congcong SUN
Journal of Army Medical University 2024;46(18):2110-2120
Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6~8 weeks old and weighing from 180~220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.
3.Research progress in TWEAK and its receptor functions in cardiovascular diseases
Changjiang HONG ; Quanliang LI ; Yuan ZHANG
Military Medical Sciences 2016;40(2):158-161
Tumor necrosis factor-like weak inducer of apoptosis ( TWEAK ) is a member of the superfamily .TWEAK binds to its receptor [ fibroblast growth factor-inducible 14 ( Fnl4 ) and the serum level of soluble CD 163 ( sCD163 ) ] and regulates many cellular activities via associated signal pathways ,including proliferation,migration,differentiation,apoptosis, angiogenesis and inflammation ,which play a significant role in the formation and development of cardiovascular diseases , such as atherosclerosis , heart failure , cardiomyopathy , and peripheral vascular disease .This review summarizes functions of TWEAK and its receptor in cardiovascular diseases .
4.Repeated sub-acute stent thrombosis: a case report.
Jing DAI ; Shuzheng LYU ; Xiantao SONG ; Hong LIU ; Rui TIAN ; Xin CHEN ; Changjiang GEI ; Yuan ZHOU ; Feng XU
Chinese Journal of Cardiology 2014;42(3):254-255
Aged
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Humans
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Male
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Stents
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adverse effects
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Thrombosis
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etiology
5.Synergistic effect of atorvastatin and probucol on severity of coronary lesion in patients with borderline coronary lesion
Changjiang GE ; Shuzheng Lü ; Hong LIU ; Lixia FENG ; Xiantao SONG ; Xin CHEN ; Kang MENG ; Fei YUAN ; Fengqing JI ; Yong HUO
Chinese Journal of Emergency Medicine 2012;21(3):277-281
Objective To study the changes of plasma cystatin C level (PcyC),and evaluate the effects of the joint use of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline lesion of coronary artery.Methods One hundred and thirty consecutive patients with borderline coronary lesion assessed by quantitative coronary angiography were enrolled into borderline coronary lesion group (BCL),and another 136 subjects without coronary lesion were enrolled as controls (CTR).And in the meantime,the subjects in BCL group were randomized (closed envelope method) into routine treatment subgroup ( RTT,n =60),and combined treatment subgroup in which patients were treated with atorvastatin 20 mg plus probucol 1.0 g daily in addition to routine medication ( CBT,n =70) for 6 months.There were no statistical differences in basic clinical features between two subgroups.PcyC,high-sensitive C-reactive protein (hs-CRP),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol ( HDL-C ) and triglycerides (TG) were determined.Of them,104 patients in BCL group rechecked by coronary angiography.Comparison of biomarkers carried out between two groups by using a number of independent-sample t-test and analysis of variance.For enumeration data,chi-square test was used to compare mean values of biomarkers between groups. P < 0.05 was considered statistically significant.Results PcyC levels were significantly higher in BCL group than those in CTR group ( P < 0.05 ).Compared with RTT subgroup,levels of PcyC,TC,LDL-C,TG and hs-CRP were more significantly decreased in CBT subgroup (P < 0.05,P < 0.01 ).Moreover,there was a trend of slight decrease in the mean percent of stenosis (MPS) of coronary artery with borderline lesion in RTT subgroup treated for 6 months,whereas more marked decrease in the MPS of coronary artery with borderline coronary lesion in CBT subgroup treated for 6 months ( P > 0.05 ; P < 0.05 ).Conclusions Cystatin C plays an important role in the pathogenesis of coronary artery,and PcyC is associated with severity of coronary lesion,the combination of atorvastatin and probucol decreases the PcyC level,and it may be the treatment of choice for borderline lesion of coronary artery.
6.The correlation between the OATP1B1 521T > C genetic polymorphism and essential hypertension
Lili YE ; Jian QIU ; Shujin ZHAO ; Changjiang HONG ; Fei XIAO ; Yuhai ZOU
Chinese Journal of Primary Medicine and Pharmacy 2012;19(5):646-648
Objective To study the relationship between the OATP1B1 521T > C genetic polymorphism and essential hypertension.Methods 164 essential hypertension subjects and 159 normotensive subjects were detected by the TaqMan-MGB probe real-time fluorescence quantitative PCR,and the results were compared with those of DNA sequencing.Results The frequencies of T/C genotype and C allele of OATP1B1 521T > C gene of the essential hypertension subjects were obviously lower than those of the normotensive subjects(T/C genotype:0.16 vs 0.25,P <0.05 ;C allele:0.10 vs 0.17,P <0.05),The difference was significant.Binary logistic stepwise regression analysis was used for evaluatine the risk factors of essential hypertension,there was significant relationship between OATP1 B1 52IT > C gene polymorphism and essential hypertension.Conclusion The SLCO1 B1 521T > C variant was common in Chinese essential hypertension population,but the difference of frequency of SLCO1B1 52IT > Cmuton between the essential hypertension patients and the normotensive controls was of obviously statistical significance,which indicates that the SLCO1B1521T > C variant maybe associate with essential hypertension.
7.Therapeutic effect and security of triple antiplatelet with Cilostazol in the elderly after drug-eluting stent implantation
Rui TIAN ; Shuzheng LV ; Hong LIU ; Fei YUAN ; Xin CHEN ; Huagang ZHU ; Xiantao SONG ; Yuan ZHOU ; Changjiang GE
Chinese Journal of Geriatrics 2012;31(3):185-188
Objective To evaluate the therapeutic effect and security of triple antiplatelet with cilostazol in the elderly after drug-eluting stent implantation and compare it with double antiplatelet treatment. Methods 234 elderly patients with coronary disease were randomly divided into two groups.118 cases in the triple antiplatelet group were treated with clopidogrel (300 or 600 mg/d) and aspirin(100 mg/d) in addition with cilostazol(200mg/d) from pre surgery to 6 month after surgery,then received double antiplatelet treatment.116 cases in the double antiplatelet group were treated with Aspirin(100 mg/d) and clopidogrel(300 or 600 mg/d),then clopidogrel was ceased after 1 year and used only Aspirin. The main parameters during follow up included all-cause death,major adverse cardiovascular events (MACE) and major adverse cardiac and cerebrovascular event (MACCE),the secondary parameters during follow- up were recurrence of angina pectoris,myocardial infarction,revascularization and hemorrhage within 2 years. Results The recurrence of angina pectoris and revascularization were found in 1 case (0.85%) and 1 case(0.85%) respectively in the triple antiplatelet group,while 8 cases(6.90%) and 8 cases (6.90%) in the double antiplatelet group,with significant difference between the two groups(both x2 =4.27,P<0.05).All cause death,myocardial infarction,cerebral apoplexy and hemorrhage were not found in the triple antiplatelet group,while 1 case of death,1 case with myocardial infarction,1 case with apoplexy and no hemorrhage appeared in the double antiplatelet group,with no significant difference between the two groups(P>0.05).Conclusions The triple antiplatelet added with cilostazol in the elderly after drug eluting stent implantation may decrease the recurrence of angina pectoris and revascularization with higher security.
8.Human Bop is a novel BH3-only member of the Bcl-2 protein family.
Xiaoping ZHANG ; Changjiang WENG ; Yuan LI ; Xiaoyan WANG ; Chunsun JIANG ; Xuemei LI ; Youli XU ; Quan CHEN ; Lei PAN ; Hong TANG
Protein & Cell 2012;3(10):790-801
One group of Bcl-2 protein family, which shares only the BH3 domain (BH3-only), is critically involved in the regulation of programmed cell death. Herein we demonstrated a novel human BH3-only protein (designated as Bop) which could induce apoptosis in a BH3 domain-dependent manner. Further analysis indicated that Bop mainly localized to mitochondria and used its BH3 domain to contact the loop regions of voltage dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane. In addition, purified Bop protein induced the loss of mitochondrial transmembrane potential (Δψm) and the release of cytochrome c. Furthermore, Bop used its BH3 domain to contact pro-survival Bcl-2 family members (Bcl-2, Bcl-X(L), Mcl-1, A1 and Bcl-w), which could inhibit Bop-induced apoptosis. Bop would be constrained by pro-survival Bcl-2 proteins in resting cells, because Bop became released from phosphorylated Bcl-2 induced by microtubule-interfering agent like vincristine (VCR). Indeed, knockdown experiments indicated that Bop was partially required for VCR induced cell death. Finally, Bop might need to function through Bak and Bax, likely by releasing Bak from Bcl-X(L) sequestration. In conclusion, Bop may be a novel BH3-only factor that can engage with the regulatory network of Bcl-2 family members to process intrinsic apoptotic signaling.
Amino Acid Sequence
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Animals
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Apoptosis
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Cell Line
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Cell Survival
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Humans
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Mice
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Mitochondria
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metabolism
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Mitochondrial Membranes
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metabolism
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Molecular Sequence Data
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Protein Structure, Tertiary
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Protein Transport
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Proto-Oncogene Proteins c-bcl-2
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chemistry
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metabolism
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Signal Transduction
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Time Factors
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Voltage-Dependent Anion Channel 1
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metabolism
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bcl-2 Homologous Antagonist-Killer Protein
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metabolism
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bcl-2-Associated X Protein
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metabolism
9.Clinical significances of plasma cystatin C levels in patients with coronary artery diseases
Changjiang GE ; Fang REN ; Shuzheng Lü ; Hong LIU ; Xiantao SONG ; Xin CHEN ; Kang MENG ; Xiaofan WU ; Fei YUAN ; Zening JIN ; Hong LI ; Fengqing JI
Chinese Journal of Emergency Medicine 2010;19(3):273-276
Objective To evaluate the relationship between plasma cystatin C concentration (PcyC) and coronary artery diseases (CAD). Method A total of 126 subjects with CAD evidenced by coronary angiography admitted from April 2007 to March 2009 were divided into three groups: stable angina pectoris (SAPs, n = 34),unstable angina pectoris (UAPs, n = 56) and acute myocardial infarction (AMIs, n = 36), according to the diag-nostic criteria of CAD set by WHO. Another 34 subjects without CAD were taken as controls. There were no statis-tical differences in demographics among four groups. Serum lipids profile, uric acid (UA), PcyC and high-sensi-tive C-reactive protein (hs-CRP) were determined. And in the meantime, all patients were followed up for six months and adverse cardiovascular events were recorded. Comparisons were made between groups with a number of independent-sample t -tests. Data were processed with analysis of variance to test the differences in means among four groups, and the means were compared with chi-square test. Statistical significance was established at a P val-ue of less than 0.05. Results Cystatin C levels were significantly higher in UAPs than that in SAPs and in controls (P < 0.05), but were much lower than that in AMIs (P < 0.05). And much higher concentration of hs-CRP was found in UAPs (P < 0.05) and in AMIs (P < 0.01). Cystatin C was positively and significantly corre-lated with age, hs-CRP, WBC, creatinine and UA (r > 0, P < 0.05), whereas a significantly negative correla-tion with high-density lipoprotein cholesterol was found (r = - 0.227, P < 0.05). These coefficients were obvi-ously high for creatinine (r = + 0. 612), and WBC (r = + 0.459). During the period of six-month follow-up, 26 patients with adverse cardiovascular events were found, and had significantly higher cystatin C levels than 22 con-trols at admission (P < 0.01). Conclusions Cystatin C plays a pivotal role in the course of CAD, and the PcyC is a strong predictor for the risk of cardiovascular events.
10.The effect of surface free energy parameters of diamond-like carbon films deposited on medical polyethylene terephthalate on bacterial adhesion.
Jin WANG ; Changjiang PAN ; Peng LI ; Yongxiang LENG ; Junying CHEN ; Guojiang WAN ; Ping YANG ; Hong SUN ; Nan HUANG
Journal of Biomedical Engineering 2006;23(2):342-345
Diamond-like carbon (DLC) films were deposited by acetylene plasma immersion ion implantation-deposition (PIII-D) on biomedical polyethylene terephthalate (PET). The capacities of Staphylococcus aureus (SA), Staphylococcus epidermidis (SE), Escherichia coli (EC), Pseudomonas aeruginosa (PA) and Candida albicans (CA) for adhesion to PETs are quantitatively determined by the plate counting and Gamma-ray counting of 125I radio labeled bacteria in vitro. The results indicate that the capacities of five types of bacteria for adhesion to PETs are all suppressed by C2H2 PIII-D (P<0.05). The surface energy components of the various substrates and bacteria are calculated based on measurements in water, formamide and diiodomethane and Lifshitz-van del Waals/acid-base approach (LW-AB). The surface free energies obtained are used to calculate the interfacial free energies of adhesion (deltaF(adh)) of five kinds of bacteria on various substrates, and the results show that it is energetically unfavorable for bacterial adhesion to the DLC films already deposited on PET by C2H2 PIII-D.
Bacterial Adhesion
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drug effects
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physiology
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Carbon
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chemistry
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Coated Materials, Biocompatible
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chemistry
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Diamond
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chemistry
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Escherichia coli
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drug effects
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Heart Valve Prosthesis
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microbiology
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Materials Testing
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Polyethylene Terephthalates
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chemistry
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Staphylococcus aureus
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drug effects
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Staphylococcus epidermidis
;
drug effects

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