Objective To analyze the risk factors for the occurrence of coronary slow flow(CSF)and to construct a predictive nomogram for the occurrence of CSF.Methods Totally 103 patients with CSF diagnosed by CAG examination were recorded as the CSF group.A total of 121 patients with normal blood flow in the same period were selected as the con-trol group.The following data of the two groups were collected:age,gender,smoking history,drinking history,body mass index(BMI),blood pressure,past medical history and other basic information,blood potassium,blood sodium,blood phosphorus,blood magnesium,urea nitrogen,creatinine,uric acid,blood glucose,albumin,globulin,creatine ki-nase,creatine kinase isoenzyme,triglycerides,total cholesterol,free fatty acids,low-density lipoprotein(LDL),high-density lipoprotein(HDL),lipoproteins,leukocytes,monocytes,lymphocytes,neutrophils,hemoglobin,red blood cells,red blood cell volume,red blood cell width,hematocrit,platelets,platelet volume,platelet distribution width,D-dimer and other laboratory test information,end-diastolic volume(EDV),end-systolic volume(ESV),stroke volume(SV),ejection fraction(EF),fractional shortening(FS)and other cardiac ultrasound examination results,the percentage of adjacent RR intervals≥50 ms(PNN50),mean standard deviation of normal RR intervals per 5 min(SDNNI),stan-dard deviation of average RR interval(SDNN),root mean square difference of consecutive normal RR intervals(RMS-SD),standard deviation of the mean of all NN intervals within 5 min(SDANN),standard deviation of adjacent NN inter-vals(SDSD),triangular index(TI)and other indexes related to heart rate variability.The indexes with statistical differ-ences in univariate analysis were included in least absolute shrinkage and selection operator(LASSO)regression and multi-variate Logistic regression analysis using the"glmnet"package of R statistical software to screen characteristic variables and analyze the risk factors for CSF.The"rms"package of R statistical software was used to construct a prediction nomo-gram for CSF.The ROC curve of the nomogram was drawn to evaluate the discrimination of the nomogram.The calibration curve was used to evaluate the consistency of the nomogram.The clinical decision curve was used to evaluate the clinical value of the nomogram.Results There were statistically significant differences in the smoking history,hypertension,systolic blood pressure,diastolic blood pressure,BMI,uric acid,blood sugar,triglycerides,total cholesterol,LDL,HDL,lymphocytes,EDV,ESV,EF,FS,PNN50,RMSSD,SDSD,SDNN,SDANN,age,blood sodium,blood magne-sium,neutrophils,red blood cell width,D-dimer,and TI between the CSF group and the control group(all P<0.05).The results of LASSO regression and multivariate Logistic regression analysis showed that smoking,systolic blood pres-sure,triglycerides,lymphocytes,SDNN,and EF were independent risk factors for the occurrence of CSF(all P<0.05).Based on this,a prediction nomogram for the occurrence of CSF was constructed,and the nomogram had good discrimina-tion,consistency,and clinical value.Conclusions Smoking,systolic blood pressure,triglycerides,lymphocytes,SDNN,and EF are independent risk factors for the occurrence of CSF.The prediction nomogram constructed based on the above risk factors has a high predictive value for the occurrence of CSF.
Objective To observe the changes in vitamin D receptor(VDR)gene polymorphisms and serum 25-hy-droxyvitamin D(25(OH)D)levels in patients with Parkinson's disease(PD),and to analyze their correlations with the on-set of PD and their predictive efficiency on the onset of PD in order to clarify the significance of VDR gene polymorphisms and changes in serum 25(OH)D levels.Methods Totally 178 PD patients(PD group)and 185 healthy subjects(control group)during the same period were included.PCR and DNA sequencing methods were used to detect the genotyping of VDR gene FokI(rs2228570)and BsmI(rs1544410)sites,and enzyme-linked immunosorbent assay was used to detect pe-ripheral serum 25(OH)D.The above indicators between the two groups were compared.Multivariate Logistic regression was used to analyze the independent risk factors for the onset of PD;ROC was used to analyze the predictive efficacy of vita-min D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels for the onset of PD.Results The frequencies of T allele and TT genotype of FokI site in the PD group were 48.6%and 25.3%respectively,and 37.7%and 15.1%in the control group,respectively.Comparing the two groups,χ2 were 8.516 and 10.383,respectively,and P were 0.004 and 0.001,respectively.There were no statistically significant differences in the alleles or genotypes of the BsmI locus between the PD group and the control group(all P>0.05).The serum 25(OH)D level in the PD group was(16.06±6.04)ng/mL,and that in the control group was(19.22±6.32)ng/mL(t=-4.873,P=0.000).The serum 25(OH)D levels of patients with TC type and CC type in the PD group were lower than those in the control group(t=-3.093,3.329,respectively;P= 0.002,0.001,respectively).When the serum 25(OH)D levels were consistent,patients with genotypes TT and TC were 2.527 and 1.888 times more likely to develop PD than patients with genotype CC,respectively(all P<0.05).When the genotypes were consistent,patients with deficient serum 25(OH)D level were 1.918 times more likely to develop PD than those with sufficient level(P<0.05).As for genotype TT patients with 25(OH)D deficiency,and genotype TC patients with 25(OH)D deficiency,their risks of developing PD were 4.818 and 3.822 times that of genotype CC patients with sufficient 25(OH)D,respectively(all P<0.05).The AUC under ROC of FokI locus genotype TT in predicting the onset of PD was 0.610,95%CI was 0.532-0.687,the diagnostic cut-off value was 0.502,the sensitivity was 74.5%,and the specificity was 47.4%;The AUC under the ROC of lack of serum 25(OH)D level in predicting the onset of PD was 0.576,the 95%CI was 0.517-0.635,the diagnostic cut-off value was 0.466,the sensitivity was 72.5%,and the specificity was 42.7%,re-spectively;the AUC under ROC of genotype TT combined with serum 25(OH)D deficiency in predicting the onset of PD was 0.693,95%CI was 0.588-0.798,the sensitivity was 64.2%,and the specificity was 74.5%,respectively.Conclu-sions The frequencies of the T allele and TT genotype at the FokI site of the VDR gene are high,and the serum 25(OH)D level is low;the T allele at the FokI site and vitamin D deficiency can promote the occurrence of PD individually or together,and both of them have poor predictive efficiency for the risk of PD onset.
Objective To investigate the clinical value of joint detection of six tumor markers in patients with colorectal cancer. Methods Eighty?six patients with colorectal cancer were included in the study group,86 healthy subjects were selected as the control group at the same period. The difference of tumor markers in different groups,tumor stages and prognosis were compared. Results The levels of carcinoembryonic antigen (CEA),carbohydrate antigen 19?9 (CA19?9),carbohydrate antigen 242 (CA242),carbohydrate antigen 72?4 ( CA72?4) , carbohydrate antigen 125 ( CA125 ) and carbohydrate antigen 50 ( CA50 ) in study group were significantly higher than those in the control group (CEA: (22. 5±6. 2)μg/L vs. (2. 2±1. 0)μg/L;CA19?9:(95. 7±27. 3) U/ml vs. (17. 1±9. 5) U/ml;CA242:(29. 5±8. 3) U/ml vs. (6. 0±2. 7) U/ml;CA72?4:(21. 6 ±5. 1) U/ml vs. (3. 6±1. 2) U/ml;CA125:(95. 4±32. 8) U/ml vs. (18. 9±8. 4) U/ml;CA50:(51. 8±20. 6)μg/L vs. (8. 3±3. 7)μg/L,t=29. 98,25. 22,24. 97,31. 86,20. 95,19. 27,P<0. 05). Among the single index detections,the sensitivity and negative predictive value of CA72?4 were the highest ( 61. 6%, 68. 3%) , the specificity of CA19?9 was the highest( 91. 9%) ,the positive predictive value of CEA was the highest ( 80. 4%) . The sensitivity,positive predictive value and negative predictive value of the joint detection were all higher than those in each single index detection (80. 3%,87. 3%,74. 1%). The levels of CEA,CA19?9,CA242,CA72?4, CA125 and CA50 in patients with stage III and IV were significantly higher than those in patients with stageⅠandⅡ(CEA:(32. 7±7. 1)μg/L vs. (15. 9±4. 4)μg/L;CA19?9:(127. 8±33. 7) U/ml vs. (52. 5±13. 8) U/ml;CA242:(40. 3±12. 7) U/ml vs. (23. 5±8. 6) U/ml;CA72?4:(37. 6±10. 2) U/ml vs. (13. 6±4. 1) U/ml;CA125:(128. 9±38. 4) U/ml vs. (59. 7±12. 8) U/ml;CA50:(88. 3±23. 7)μg/L vs. (41. 8±15. 6)μg/L,t=13. 04,13. 32,7. 11,14. 06,10. 99,10. 64,P<0. 05) . The levels of CEA,CA19?9,CA242,CA72?4,CA125 and CA50 in the recurrent metastasis group were significantly higher than those in the non?recurrent metastasis group ( CEA:( 37. 7 ± 8. 6 ) μg/L vs. ( 3. 8 ± 1. 7 ) μg/L;CA19?9:( 110. 5 ± 29. 4 ) U/ml vs. ( 25. 5 ± 13. 8 ) U/ml;CA242:( 33. 6 ± 10. 3 ) U/ml vs. ( 15. 5 ± 6. 6 ) U/ml;CA72?4:( 33. 1 ± 15. 3 ) U/ml vs. ( 9. 3 ± 3. 0 ) U/ml;CA125:(113. 4±31. 7) U/ml vs. (28. 7±7. 8) U/ml;CA50:(55. 4±14. 6)μg/L vs. (16. 8±9. 6)μg/L,t=29. 04,18. 31,9. 86,11. 47,19. 28,14. 65,P<0. 05) . Conclusion The joint detection of six markers can further improve the sensitivity, positive predictive value and negative predictive value of diagnosis, and can provide a more reliable basis for the auxiliary diagnosis of colorectal cancer.
Objective To observe the expression changes of hsa_circ_0131457 in the pancreatic cancer tissues,and to investigate the effects of hsa_circ_0131457 overexpression on the proliferation,apoptosis,migration,invasion and other biological behaviors of pancreatic cancer cells.Methods Seven cases of pancreatic cancer tissues and 7 cases of matched normal adjacent normal tissues were collected from pancreatic cancer cells PANC-1,SW1990,CFPAC-1,and normal pancreatic duct epithelial cells HPDE6-C7 in the logarithmic growth phase.The expression of hsa_circ_0131457 was detected by real-time fluorescence quantitative PCR.The pancreatic cancer cells with the lowest expression of hsa_circ_0131457 were divided into the overexpression group and control group,which were transfected with hsa_circ_0131457 over-expression plasmid and control plasmid by liposome transfection method,respectively.After transfection,OD values of cells in the two groups were detected by CCK-8 method at 0,24,48,72 and 96 h,apoptosis rate was detected by TUNEL staining method,cell migration distance was recorded by cell scratch test,and the number of transmembrane cells was re-corded by Transwell chamber test.The relative expression levels of apoptosis-related protein cyclin D2(CCND2)and cy-clin dependent kinase 4(CDK4)were detected by Western blotting.Results The relative expression levels of hsa_circ_0131457 in the pancreatic cancer tissues and adjacent normal tissues were 0.011±0.017 and 2.084±2.287,with statisti-cally significant difference(P＜0.05).The relative expression levels of hsa_circ_0131457 in PANC-1,SW1990 and CF-PAC-1 cells were 0.123±0.110,0.159±0.082 and 0.141±0.129,respectively;all of them were lower than that of nor-mal pancreatic ductal epithelial cells(1.174±0.839)(all P＜0.05).Therefore,the pancreatic cancer cells PANC-1 with the lowest expression of hsa_circ_0131457 was used for follow-up study.There were no significant differences in OD values between the two groups at 0 and 24 h(all P＜0.05),and the OD values of the overexpression group were lower than those of the control group at 48,72 and 96 h(all P＜0.05).The apoptosis rate of the overexpression group was higher than that of control group,the cell migration distance was shorter and the number of transmembrane cells was smaller than those of the control group(all P＜0.05).The relative expression levels of CCND2 and CDK4 protein in the overexpression group were higher than those in the control group(all P＜0.05).Conclusions The expression of hsa_circ_0131457 decreases in both pancreatic cancer tissues and cells.Overexpression of hsa_circ_0131457 can inhibit the proliferation,migration and inva-sion of pancreatic cancer cells,and promote apoptosis by up-regulating the expression of CCND2 and CDK4.
目的 观察冠心病患者经皮冠状动脉介入治疗(PCI)前后的心肌灌注情况,并探讨其与近期预后的关系.方法 选取经冠脉造影检查确诊的冠心病患者102例,均行PCI手术.患者分别于术前及术后3个月,应用PHILIPS EPIQ 7C超声诊断仪进行实时心肌超声造影(RTMCE)检查评价心肌灌注情况,记录前壁、下壁、侧壁曲线上升平台期的平均斜率(β)、心肌显峰强度(A)、局部心肌血流量(MBF).记录患者PCI术后6个月心血管不良事件(MACE)发生情况,采用Logistic多因素回归分析术后3个月RTMCE参数对冠心病患者PCI术后6个月发生MACE的影响,绘制其预测冠心病患者PCI术后6个月发生MACE的受试者工作特征(ROC)曲线,比较其预测价值.结果 患者PCI术后3个月前壁、下壁、侧壁的β、A、MBF均较术前升高(P均＜0.05).102例冠心病患者PCI术后6个月发生MACE 15例(14.7%).发生MACE者术后3个月前壁、下壁、侧壁的β、A、MBF均低于未发生MACE者(P均＜0.05).Logistic回归分析结果显示,术后3个月β、A、MBF降低均是冠心病患者PCI术后6个月发生MACE的独立危险因素(P均＜0.05).曲线下面积:侧壁A＞下壁β＞侧壁MBF＞侧壁β＞下壁A＞前壁A＞前壁β＞前壁MBF＞下壁MBF;当侧壁A≤8.75 dB时,其预测冠心病患者PCI术后6个月发生MACE的敏感度为86.67%、特异度为73.56%.结论 冠心病患者PCI术后心肌灌注情况改善,其前壁、下壁、侧壁RTMCE参数β、A、MBF均升高,上述指标降低与患者术后6个月MACE的发生有关,侧壁A对于患者近期预后具有较高的预测价值.
Objective To investigate the improvement effect of extracts from Berberis heteropoda Schrenk total an-thocyanins(BHSTA)on liver fibrosis mice and its mechanism.Methods Forty mice were randomly divided into the nor-mal control group,model control group,low-dose BHSTA group,high-dose BHSTA group,and silybin group,with 8 mice in each group.The hepatic fibrosis models were established by intraperitoneal injection of CCl4 oil in all groups except the normal control group.Mice in the low-dose BHSTA group,high-dose BHSTA group and silybin were given 10 and 40 mg/kg BHSTA solution and 1 μg/10 g silybin by intragastric administration,respectively,while mice in the normal control group and model control group were given equal volume of distilled water by intragastric administration,once a day,for 4 weeks.The body mass of each group was recorded within 4 weeks,and the mice were killed 4 weeks later.The liver index was calculated,and the pathological changes of liver tissues were observed after HE and Masson staining.The serum ala-nine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected by automatic biochemical analyzer.The expression levels of superoxide dismutase(SOD),glutathione peroxidase(GSH)and malondialdehyde(MDA)in liver tis-sues were detected by modified hydroxylamine hydrochloride method.The relative expression levels of NOD-like receptor heat protein domain associated protein 3(NLRP3)and its downstream target gene apoptosis-associated microprotein(ASC),Caspase-1,and interleukin-1β(IL-1β)proteins in the nucleus of liver tissues were detected by Western blotting.Results With the extension of intervention time,the body mass of mice in all groups showed an increasing trend.At the 4th week of group treatment,the body mass of mice in the normal control group,silybin group,high-dose BHSTA group,low-dose BHSTA group and model control group decreased successively,and significant difference was found between ev-ery two groups(all P＜0.05).Compared with normal control group,liver index in the other groups increased,especially in the model control group(all P＜0.05).In the normal control group,the hepatic lobule structure was intact,the hepatic cells were normal,and no inflammatory cell infiltration and collagen fiber hyperplasia were found in the sink area.In the model control group,most of the hepatic sinuses disappeared,moderate or severe edema changes were observed in hepato-cytes,and multiple balloon-like and fatty degeneration were observed,accompanied by multiple inflammatory cell infiltra-tion and a large number of collagen fiber hyperplasia in the portal area.Hepatocyte balloon-like degeneration,inflammato-ry cell infiltration and collagen fiber hyperplasia in the low-dose BHSTA group,high-dose BHSTA group and silybin group were reduced in comparison with those of the model control group.Compared with the normal control group,the expression levels of AST,ALT and MDA in serum and SOD and GSH in liver increased in the model control group,while the expres-sion levels of SOD and GSH in liver decreased(all P＜0.05).Compared with the model control group,the expression lev-els of AST,ALT and MDA in serum decreased in the low-dose BHSTA group,high-dose BHSTA group and silybin group,while the expression levels of SOD and GSH in liver increased.Among them,the decrease in the expression levels of se-rum AST,ALT and MDA in liver tissues was more significant in the high-dose BHSTA group and silybin group,while the increase in the expression levels of SOD and GSH in liver tissues was more significant in the silybin group(all P＜0.05).Compared with the normal control group,the relative expression levels of NLRP3,ASC,Caspase-1 and IL-1β in the liver tissues of the other four groups increased,and the increase was the most significant in the model control group(all P＜0.05).Conclusion BHSTA can protect the liver of mice with hepatic fibrosis,and its mechanism may be related to re-ducing oxidative stress and inhibiting NLRP3 inflammasome-related pathway.
Objective To explore the the effect and possible mechanism of heat stress at different rewarming time on the damage of human skeletal muscle cells(HSKMC).Methods HSKMC in the logarithmic growth phase were divided into the heat stress group and control group.Cells in the control group were cultured normally,and the heat stress models were established in the heat stress group and then were rewarmed in 37℃and 5%CO2 cell incubator for 0,6,12 and 24 h,respectively.The cell survival rate was detected by CCK-8,the cell ultrastructure was observed by transmission elec-tron microscopy,TRPV4 protein was detected by Western blotting,and TRPV4 mRNA was detected by real-time fluores-cence quantitative PCR.HSKMC in the logarithmic growth phase were randomly divided into the HS group,GSK+HS group,HC+HS group,and NC group.Cells in the NC group were cultured normally,and the heat stress models were es-tablished in the other three groups,and the rewarming time was 12 h.Cells in the GSK+HS group and HC+HS group were given TRPV4 agonist GSK1016790A(500 nmol)and TRPV4 inhibitor HC-067047(5 μmol)at 0.5 h before heat stress,and Ca2+ level was detected by flow cytometry.Results Compared with the control group,the survival rate of cells in heat stress group decreased after rewarming for 0,6,12 and 24 h(P＜0.05).With the extension of rewarming time,the survival rate of cells in the heat stress group decreased successively,and significant difference was found between these two groups(all P＜0.05).Compared with the control group,ultrastructural changes were observed in the cells in the heat stress group after rewarming for 0 and 6 h,which were mainly manifested as cell swelling,enlarged volume,cytoplasmic vacuolation,obvious mitochondrial swelling,degranulation,double ridge loss,widening of perinuclear space,nucleus condensation and contraction,and interruption of some envelope continuity.After rewarming for 12 and 24 h,the cells in the heat stress group even showed nucleolysis and disappearance,nucleus fragmentation,chromatin boundary aggrega-tion,and cytoplasmic structure disintegration and granulation.Compared with the control group,the relative expression levels of TRPV4 mRNA and protein in heat stress group increased after rewarming for 0,6,12 and 24 h(all P＜0.05).The levels of intracellular Ca2+ in the NC group,HC+HS group,HS group and GSK+HS group increased successively,and significant difference was found between groups(all P＜0.05).Conclusions Heat stress can reduce HSKMC survival rate and damage HSKMC structure.The longer rewarming time after heat stress,the greater the damage to HSKMC cells.The mechanism may be related to the promotion of TRPV4 expression and its mediated Ca2+ influx.
肠道菌群是一种复杂的、动态的生态系统,对维持肝脏正常生理功能至关重要,且与肝癌的发生发展密切相关.研究证实,肠道菌群会影响肝癌的治疗效果,与肝切除术后复发、术后感染等并发症的发生有关.肠道菌群会影响患者对免疫治疗的反应,肠道菌群及其代谢产物可以影响索拉非尼的疗效,减轻靶向治疗后的不良反应.此外,肠道菌群具有提高肝癌化疗敏感性的作用,同时也会影响放疗的效果和不良反应的发生.通过益生菌、中医药等调节肠道菌群可能是一种肝癌辅助治疗的新策略,对于开发新的诊疗模式和个性化治疗有着重要意义.
抑郁症是一种以显著而持久的心境低落、兴趣和愉快感缺乏以及精力减退为主要临床表现的心境障碍.其中,负性自动思维是面对压力个人信息处理偏差的结果,通常会表现出各种各样的认知错误,同时也体现出对自我、未来以及世界的消极想法,被认为在抑郁症的发病中占有重要地位.导致抑郁症负性自动思维的影响因素主要包括神经生物学因素、环境因素、人格因素,其中神经生物学因素主要包括基因变异(小脑素1、合成营养因子β1)、单胺类神经递质(多巴胺、5-羟色胺、去甲肾上腺素)改变、某些脑区(外侧眶额、颞叶皮层和前额叶)功能变化、脑结构(海马区和海马旁回)改变、认知控制网络异常等,环境因素包括家庭因素和社会因素,人格因素主要指特定的人格特质,如高能力紧张、低自我力量、低自我接纳、易于内疚、元情绪能力低等.对抑郁症负性自动思维的危险因素进行总结归纳,可为进一步探究抑郁症的发病机制以及更好地评估和干预抑郁症提供依据.
Objective To investigate the effect of aspirin in relieving skin rashes induced by epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)in mice and the possible mechanism.Methods Fifty male Balb/c mice were randomly divided into the control group,model group,and high-dose,medium-dose,and low-dose aspirin groups,with 10 mice in each group.The skin rash models were established by administering the EGFR-TKI erlotinib to the mice in all the groups except the control group.After successful modeling,the mice in the high-,medium-,and low-dose aspirin groups were given aspirin at doses of 1.13,0.75,and 0.38 mg per mouse,respectively,while the mice in the control group were given distilled water at 100 mg/kg,all by gavage,once a day,for a total of 30 days.All the mice were moni-tored for feeding,drinking,urination,defecation,and mental status as well as pruritus and other skin conditions.The skin moisture level was measured using a skin moisture analyzer,and skin inflammation was scored.After the mice were sacrificed,the back skin was taken for observing the pathological changes with HE staining,and serum levels of tumor ne-crosis factor-α(TNF-α)and interleukin-1β(IL-1β)were determined by ELISA.Results In the control group,the skin and general conditions were normal;the mice in the model and low-dose aspirin groups developed skin rashes,scabs,and desquamation on the back,and began to have reduced food intake,increased water intake,increased urination,and re-duced defecation since the first week,accompanied by anxiety and back scratching;compared with the model group,the medium-and high-dose aspirin groups showed significant improvements in skin rashes,scabs,and desquamation,and gradually returned to normal dieting since the second week.Only the model group had mild pruritus,while the other groups did not have any pruritus.No abnormal changes were found in any epidermal layer of the skin tissues in the control group;the model group showed epidermal thickening and substantial inflammatory cell infiltration in the dermis;the high-dose and medium-dose aspirin groups showed slight epidermal thickening and mild inflammatory cell infiltration in the su-perficial dermis,while the low-dose aspirin group had a larger number of inflammatory cells in the superficial dermis;the levels of inflammation in the three aspirin groups were all lower than that in the model group.There was no significant dif-ference in the skin moisture level between the groups(P＜0.05).The rash site,desquamation,exudation,skin thickening score,and serum levels of TNF-α and IL-1β were as follows:the control group＜the high-dose aspirin group＜the medium-dose aspirin group＜the low-dose aspirin group and model group(all P＜0.05).Conclusion Aspirin can alleviate EG-FR-TKI-induced skin rashes in mice,possibly through reducing serum TNF-α and IL-1β levels and thereby inhibiting in-flammatory response.
结直肠癌(CRC)患者约占全球所有新发肿瘤患者的10%,健康人群患CRC的风险为4%～5%,是肿瘤相关死亡的常见原因之一.目前筛查CRC的方法很多,如结肠镜、肿瘤标志物、影像学、微环境、病理学等,但是都有其不足之处.近年来随着深度学习、机器学习算法(ML)、硬件水平和数据库的提升,人工智能(AI)技术迎来第三次发展热潮,将ML与CRC的筛查方法相结合,能有效提高其敏感度及特异度,减少人工检测所带来的失误.目前研究显示,基于结肠镜检查、肿瘤标志物、影像学检查、肠道微环境、病理学检查的ML预测模型可以提高CRC筛查的准确性,减少不必要的人为错误,在提高效率的同时也减少了不必要的劳动浪费.ML有很多种预测模型,每个模型都有其自身的优势,我们要根据目标的不同特点进行合理选择,以提高CRC的筛查效果.
Objective To explore the inhibitory effect of Danyu formula on foam cell formation in rat aortic endothe-lial cells(RAECs)induced by oxidized low-density lipoprotein(Ox-LDL)and its possible mechanism.Methods RAECs were randomly divided into the control group,model group,low-dose Danyu formula group,medium-dose Danyu formula group,and high-dose Danyu formula group,and atorvastatin group.Except for the control group,RAECs in the rest of the five groups were treated with 200 μg/mL Ox-LDL for 72 h,and the low-,medium-,and high-dose Danyu formu-la groups and the atorvastatin group were treated with 50,100,and 200 μg/L Danyu formula solution and 300 μg/L atorv-astatin,respectively.After 24,48,and 72 h of treatment,the cell proliferation ability was detected by CCK-8.The foam formation was observed by oil red O staining in the cells treated for 72 h in each group.The protein levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),malondialdehyde(MDA),and superoxide dismutase(SOD)in the cell superna-tant were measured by ELISA.The reactive oxygen species(ROS)content was determined by the 2-hydroxyethylfluoresce-in oxidation fluorescence reaction.The relative mRNA expression levels of protein tyrosine kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)were detected by real-time fluorescence quantitative PCR.The relative protein expression levels of JAK2,p-JAK2,STAT3,and p-STAT3 were determined by Western blotting,and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 were calculated.Results Compared with the control group,the OD values of the model group decreased at the same time points(all P＜0.05).Compared with the model group at the same time points,the OD values of the high-dose Danyu formula group and the atorvastatin group increased,and the OD values of the medium-dose Danyu formula group increased at 48 and 72h(all P＜0.05).The control group cells did not exhibit foam formation,while the cells in the model group showed obvious foam formation.Compared with the model group,the foam formation in the atorvastatin group and the high-,medium-,and low-dose Danyu formula groups improved,with the high-dose Danyu formula group and the atorvastatin group showing the most significant improvement,almost approaching the control group.Compared with the control group,the levels of TNF-α,IL-6,ROS,JAK2 mRNA expression,STAT3 mRNA expression,p-JAK2/JAK2,p-STAT3/STAT3,and MDA in the cell supernatant of the model group increased,while the expression of SOD in the cell supernatant decreased(all P＜0.05).Compared with the model group,the levels of TNF-α,IL-6,ROS,JAK2 mRNA expression,STAT3 mRNA expression,p-JAK2/JAK2,p-STAT3/STAT3,and MDA in the cell supernatant of the atorvastatin group and the high-,medium-,and low-dose Danyu formula groups decreased,while the expression of SOD in the cell supernatant increased,with the most significant changes in the atorvastatin group and the high-dose Danyu formula group(all P＜0.05).There were no significant differences in the relative protein expression levels of JAK2 or STAT3 among these groups(all P＞0.05).Conclusion The high-dose,medium-dose,and low-dose Danyu formula can inhibit foam formation in Ox-LDL-induced RAECs,with the significant effect in the high-dose Danyu formula,and its mechanism may be related to the inhibition of inflammatory reaction,oxidative stress response,and JAK2/STAT3 signal-ing pathway.
目的 观察胃癌组织中长链非编码核糖核酸CHRF(lncRNA CHRF)、微小RNA-489(miR-489)的表达变化,探讨其与患者病情严重程度、上皮间质转化(EMT)、预后的关系.方法 选择行根治性手术治疗的胃癌患者63例,术中留取胃癌组织和癌旁组织样本.采用实时荧光定量PCR法检测胃癌组织和癌旁组织lncRNA CHRF、miR-489相对表达量,采用Western blotting法检测EMT相关蛋白E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentine)、Snail蛋白相对表达量,比较不同临床特征的胃癌患者癌组织lncRNA CHRF、miR-489表达,分析lncRNA CHRF、miR-489与E-cadherin、Vimentine、Snail的相关性;术后随访3年,比较lncRNA CHRF、miR-489高低表达患者的3年生存率,COX回归模型分析其对患者预后的影响.结果 与癌旁组织比较,胃癌组织lncRNA CHRF及Vimentine、Snail蛋白相对表达量均升高,miR-489及E-cadherin蛋白相对表达量均降低(P均＜0.05).TNM分期为Ⅲ期、有淋巴结转移、低/未分化的胃癌患者癌组织lncRNA CHRF表达分别高于TNM分期为Ⅰ/Ⅱ期、无淋巴结转移、高/中分化者,miR-489表达分别低于TNM分期为Ⅰ/Ⅱ期、无淋巴结转移、高/中分化者(P均＜0.05).胃癌组织lncRNA CHRF与E-cadherin表达呈负相关关系,与Vimentine、Snail表达呈正相关关系(r分别为-0.539、0.497、0.522,P均＜0.05);胃癌组织miR-489与E-cadherin表达呈正相关关系,与Vimentine、Snail表达呈负相关关系(r分别为0.512、-0.506、-0.508,P均＜0.05).胃癌组织lncRNA CHRF高表达者3年生存率为55.56%(15/27),低表达者为86.11%(31/36),两者比较P＜0.05;胃癌组织miR-489高表达者3年生存率为93.33%(28/30),低表达者为54.55%(18/33),两者比较P＜0.05.胃癌组织lncRNA CHRF表达升高及miR-489表达降低是影响胃癌患者预后的独立危险因素(P均＜0.05).结论 胃癌组织lncRNA CHRF表达升高、miR-489表达降低,二者参与了EMT的发生,并与患者的病情严重程度及预后有关.
目的 探讨多普勒超声辅助跟骨外侧动脉定位方法在跟骨骨折患者扩大L形切口切开复位内固定手术中的应用效果.方法 选择跟骨骨折患者24例,随机分为超声组和对照组,每组12例.两组均行扩大L形切口切开复位内固定手术治疗,超声组术前通过多普勒超声确定跟骨外侧动脉体表定位点.记录两组手术时间、术中C臂透视次数、术中出血量、骨折愈合时间,两组术前及术后3、12个月行跟骨侧位X线片检查并测量Bohler角、Gissane角;比较两组术后1、3、12个月的疼痛视觉模拟评分(VAS),术后3、12个月的美国足踝外科学会(AOFAS)评分,以及术后并发症发生率.结果 超声组手术时间短于对照组(P＜0.05).两组术中透视次数、术中出血量、骨折愈合时间比较差异均无统计学意义(P均＞0.05).与同组术前比较,两组术后3、12个月Bohler角、Gissane角均升高(P均＜0.05);两组术后3、12个月Bohler角、Gissane角比较差异均无统计学意义(P均＞0.05).两组术后1、3、12个月VAS及术后3、12个月AOFAS评分比较差异均无统计学意义(P均＞0.05).超声组术后发生皮缘坏死1例(8.3%);对照组术后发生皮缘坏死3例、感染1例,并发症发生率为33.3%;超声组术后并发症发生率低于对照组(P＜0.05).结论 跟骨骨折患者扩大L形切口切开复位内固定手术治疗前通过多普勒超声定位标记跟骨外侧动脉有助于缩短手术时间、减少术后并发症的发生.
慢性肾脏病(CKD)是严重影响公众健康的一种疾病,随着肾功能损害的加重,患者病死率及心血管事件发生率均升高,但是目前尚缺乏有效延缓CKD进展的措施.肾纤维化是CKD向终末期肾病进展的共同途径,早期肾纤维化以不均匀分布、局部聚集的"纤维化生态位"为主,伴随中性粒细胞、单核/巨噬细胞、淋巴细胞浸润等.中性粒细胞参与肾纤维化的机制报道较多的是中性粒细胞胞外诱捕网(NETs),NETs的形成往往会伴随中性粒细胞的溶解性死亡,表现为细胞膜破裂、核脱落、核膜解体等.单核/巨噬细胞主要是M2型单核/巨噬细胞参与肾纤维化的发生,其通过复杂的信号通路,激活成纤维细胞及间充质转化来参与ECM合成,从而促进肾纤维化的发展.T淋巴细胞作为细胞免疫中的主要效应细胞,在纤维化的发展过程中兼具双重作用,这其实与T淋巴细胞的不同亚型有关.对中性粒细胞、单核/巨噬细胞、淋巴细胞在肾纤维化过程中的相关机制进行总结,可为肾纤维化的诊断和治疗提供依据.
青蒿素类药物可通过多种机制发挥抗肿瘤作用,但该类药物存在半衰期短、稳定性差和生物利用度低等缺点,限制了其治疗效果.与游离药物相比,负载青蒿素类药物的纳米递送系统不仅可提高药物的溶解度和稳定性,延长体内循环时间,还可增强药物运输的肿瘤靶向性,具有更显著的抗肿瘤效果.目前,青蒿素类药物的纳米递送体系包括脂质体、纳米粒、纳米结构脂质载体、聚合物胶束、囊泡、自微乳以及纳米前药等,每种纳米递送体系均具有各自的优点及待改进之处,对其进行总结可为其在抗肿瘤治疗中的应用提供参考.
脓毒症是一种由病原微生物侵入机体后引起大量炎症因子释放,导致免疫系统紊乱,进而影响多个器官的一种全身炎症反应综合征.脓毒症引起的心肌损伤(SIMI)是导致脓毒症患者死亡的主要原因之一.目前传统治疗SIMI的药物疗效依旧不乐观,临床上尚未出现SIMI治疗完全有效的药物.近年来,大量的基础研究提示某些植物化学或生物活性类药物显示出强大的SIMI治疗效果.植物化学物质主要包括多酚类化合物、萜类以及皂苷类、生物碱类等,可通过减轻炎症反应、减弱氧化应激、改善代谢等来发挥预防及治疗SIMI的作用.生物活性物质主要包括激素、细胞因子、维生素和生物色素等,可以针对相应抗炎靶点或通路来下调炎症因子表达或抑制细胞死亡,从而改善SIMI.还有一些其他药物,如抗组胺药、抗心绞痛药和镇痛类药等,也显示出强大的治疗效果,可为SIMI的治疗提供新的研究方向.
目的 探讨皮下注射亮丙瑞林辅助腹腔镜手术治疗子宫内膜异位症的临床效果及其对患者阴道灌洗液中炎症、血管生成相关指标的影响.方法 选择子宫内膜异位症患者110例,随机分为观察组和对照组,每组55例.两组均进行腹腔镜手术,对照组术后给予米非司酮片口服,25 mg/次,1次/天,治疗12周;观察组术后首次月经来潮时给予注射用醋酸亮丙瑞林微球3.75 mg皮下注射,每隔4周注射1次,共注射3次.比较两组的临床疗效及不良反应发生情况,采用ELISA法检测两组治疗前及治疗后12周阴道灌洗液中的白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、白细胞介素8(IL-8)、肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)等炎症相关指标,以及可溶性血管内皮生长因子1(sFlt-1)、趋化因子配体2(CCL2)、胰岛素样生长因子Ⅰ(IGF-Ⅰ)、基质金属蛋白酶9(MMP-9)、抗子宫内膜抗体(EMAb)等血管生成相关指标.结果 观察组显效28例、有效25例、无效2例,总有效率为96.36%,对照组分别为17、30、8例及85.45%,两组总有效率比较P＜0.05.与治疗前比较,两组治疗12周阴道灌洗液IL-1β、IL-6、IL-8、TNF-α及IFN-γ水平均降低,且观察组降低更明显(P均＜0.05).与治疗前比较,两组治疗12周阴道灌洗液sFlt-1水平升高而CCL2、IGF-Ⅰ、MMP-9、EMAb水平均降低,且观察组变化更明显(P均＜0.05).两组不良反应发生率比较P＞0.05.结论 皮下注射亮丙瑞林辅助腹腔镜手术治疗子宫内膜异位症的临床疗效较好、安全性较高,同时有助于抑制患者阴道内的炎症反应及异常血管生成.
Objective To study the effects of Dendrobium huoshanense polysaccharide(DHP)on dyskinesia,neu-ronal damage,and senescence of astrocytes in mice with Parkinson's disease(PD).Methods Forty male C57BL/6 mice were randomly divided into the NC group,MOD group,DHP100 group,and DHP350 group,with 10 mice in each group.PD mouse models were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the MOD,DHP100 and DHP350 groups.After the models were established,the DHP100 and DHP350 groups were given 100 mg/kg and 350 mg/kg of DHP by gavage of 0.5 mL,once a day,for 2 weeks,respectively.The motor abil-ity of each group was evaluated by the passing time of balance beam,the hanging time of suspension,and the staying time of rotating rod test;the fluorescence expression of mouse midbrain nigral tyrosine hydroxylase(TH)and astrocyte nuclear fibrillar protein B1(Lamin B1)was detected by immunofluorescence;the relative expression of midbrain Lamin B1,inter-leukin-1β(IL-1β),and interleukin-6(IL-6)proteins was detected by Western blotting,and the expression of midbrain p16INK4a and matrix metalloproteinase 3(MMP-3)mRNA was detected by real-time fluorescence quantitative PCR.Mouse astrocytes C8-D1A cells were divided into three groups.Cells in the normal group were cultured with serum-free DMEM medium,and cells in the model group were treated with 0.6 mmol/L 1-methyl-4-phenylpyridine ion(MPP+)for 24 h,while the cells in the DHP group were pretreated with 8 μg/mL DHP for 12 h and then were treated with 0.6 mmol/L MPP+ for 24 h.The cell supernatant of the three groups was collected as the conditioned culture medium to act on human neuro-blastoma cells(SH-SY5Y).The survival rate of SH-SY5Y cells,cell cycle ratio,positive rate of β-galactosidase(β-gal),and telomerase activity of the three groups were compared.Results Compared with the NC group,the staying time,hanging time and the number of TH-positive neurons in the midbrain and the relative expression of Lamin B1 protein de-creased in the MOD group,and the passing time and the relative expression levels of IL-1β,IL-6 protein and p16INK4a and MMP-3 mRNA increased(all P＜0.05).Compared with the MOD group,the staying time,hanging time,the number of TH-positive neurons and the relative expression levels of Lamin B1 protein in the DHP100 group and DHP350 group in-creased,while the passing time,IL-1β protein and MMP-3 mRNA relative expression levels decreased,and moreover,the changes in the staying time,passing time,IL-1β protein and MMP-3 mRNA relative expression levels were more signif-icant in the DHP350 group(all P＜0.05).The relative expression levels of IL-6 protein and p16INK4a mRNA in the DHP350 group were lower than those in the MOD group and DHP100 group,and the fluorescence expression levels of Lamin B1 in nigra astrocytes in the MOD group were lower than those in the NC group,DHP100 group and DHP350 group(all P＜0.05).After the addition of cell-conditioned medium,the survival rates of SH-SY5Y cells in the normal,DHP and model groups decreased sequentially,with statistically significant difference between groups(all P＜0.05).Compared with the normal group,the proportion of cells in the G0/G1 phase and the positive rate of β-gal increased,and the proportion of cells in the S phase and telomerase expression decreased in the model group(all P＜0.05);compared with the model group,the proportion of cells in the G0/G1 phase and the positive rate of β-gal decreased,and the proportion of cells in the S phase and telomerase expression increased in the DHP group(all P＜0.05).Conclusion DHP can alleviate the dyskinesia of PD mice,and the mechanism may be related to inhibiting the senescence of astrocytes,thus alleviating the damage of neu-rons and exerting neuroprotective effect.
目的 探讨血清铁蛋白、基质金属蛋白酶9(MMP-9)及阴道分泌物B族链球菌(GBS)检测在胎膜早破致绒毛膜羊膜炎诊断中的应用.方法 选取胎膜早破致绒毛膜羊膜炎孕妇96例作为观察组,另选取同期无绒毛膜羊膜炎的胎膜早破孕妇96例作为对照组.两组入院后,采用放射免疫技术检测血清铁蛋白,ELISA法检测血清MMP-9,细菌培养及菌落鉴定阴道分泌物GBS阳性情况.采用Logistic回归分析血清铁蛋白、MMP-9及阴道分泌物GBS阳性对胎膜早破致绒毛膜羊膜炎的影响,绘制上述指标诊断胎膜早破致绒毛膜羊膜炎的受试者工作特征(ROC)曲线,分析其单独及联合检测的诊断效能.结果 观察组血清铁蛋白、MMP-9水平及阴道分泌物GBS阳性率均高于对照组(P均＜0.05).血清铁蛋白、MMP-9水平升高及阴道分泌物GBS阳性是胎膜早破致绒毛膜羊膜炎发生的独立危险因素[OR(95%CI)分别为2.536(1.397～4.602)、3.505(2.501～4.913)、3.572(2.398～5.321),P均＜0.01].血清铁蛋白、MMP-9及阴道分泌物GBS阳性单独及联合诊断胎膜早破致绒毛膜羊膜炎的ROC曲线下面积分别为0.729、0.820、0.568、0.950,敏感度分别为61.46%、81.25%、19.79%、79.19%,特异度分别为77.08%、73.96%、93.75%、97.92%.结论 胎膜早破致绒毛膜羊膜炎患者血清铁蛋白、MMP-9水平及阴道分泌物GBS阳性率均升高,与胎膜早破患者发生绒毛膜羊膜炎有关,联合检测有助于诊断.
