目的 探讨重症感染患者使用替加环素抗感染治疗后对凝血功能的影响.方法 收集徐州医科大学附属医院ICU 2018年10月～2021年1月符合条件的73例患者资料,按照替加环素维持剂量分为正常剂量组(50 mg q12h)和超剂量组(100 mg q12h),汇总两组患者的年龄、诊断、凝血功能指标和疾病转归等数据并进行分析.结果 正常剂量组替加环素可显著延长患者APTT、PT,降低FIB,超剂量组使用替加环素后,除了显著延长患者APTT、PT、降低FIB以外,TT也显著延长.相比正常剂量组,超剂量组FIB水平更低.两组对患者PLT均无显著影响.结论 替加环素对ICU重症感染患者的凝血功能存在一定影响,在使用替加环素抗感染治疗的过程中,应严密监测凝血功能指标的变化,对于已有凝血功能障碍或者出血风险高的患者应谨慎使用.

目的 通过分析JAK2 rs10119004基因多态性对伏立康唑血药谷浓度(Cmin)及临床治疗效果的影响,为伏立康唑治疗重症监护室(ICU)侵袭性真菌感染个体化方案的制定提供参考.方法 利用PCR及Sanger测序方法检测JAK2 rs10119004位点的基因型,同时应用液相色谱串联质谱(LC-MS/MS)法检测伏立康唑血药谷浓度(Cmin),分析各基因型患者Cmin的特点及不同基因型患者用药后疗效及不良反应发生情况.结果 70例患者伏立康唑Cmin为0.12～12.23 mg/L,平均3.07(1.92,5.48)mg/L.70例患者JAK2 rs10119004位点基因型共3种:野生未突变型G/G 25例,杂合子突变型G/A 32例,纯合子突变型A/A 13例.不同Cmin和不同基因型分组患者的治疗有效率及不良反应发生率差异无统计学意义.不同年龄(Age)、血浆白蛋白(ALB)水平和JAK2 rs10119004基因型患者,其伏立康唑Cmin存在差异;将具有统计学意义的影响因素纳入多元回归模型,得到回归方程C1=7.479+0.048×Age-0.233×ALB+1.405×X1(X1:G/A=1,非G/A=0);C2=7.479+0.048×Age-0.233×ALB+1.208×X2(X2:A/A=1,非A/A=0).结论 JAK2 rs10119004基因型可影响ICU侵袭性真菌感染患者伏立康唑的Cmin.

孟鲁司特是常见的治疗儿童哮喘和过敏性鼻炎的药物,于1998年被批准上市,作为白三烯受体拮抗剂,通过拮抗白三烯活性(白三烯可刺激黏液分泌,增加血管通透性,促进黏膜水肿形成)发挥作用,起到减少呼吸道黏液分泌、降低血管通透性和嗜酸性粒细胞聚集、促进呼吸道恢复通畅等作用.

目的 探讨重症监护室患者伏立康唑血药浓度对药物疗效和不良反应的影响.方法 收集2019年1月～2019年11月在重症监护室使用伏立康唑的患者资料,测定达稳态后伏立康唑的血药浓度.结果 60例患者平均血药浓度(3.99±2.94)mg/L,34例血药浓度在正常范围内.不同性别、年龄的药物浓度差异无统计学意义(P>0.05).33例使用伏立康唑治疗后有好转,平均血药浓度为(4.26±3.11)mg/L,未好转组平均血药浓度为(3.66±2.75)mg/L.60例患者的主要不良反应为肝功能异常,平均血药浓度为(3.75±3.10)mg/L.结论 重症监护室患者伏立康唑血药浓度个体差异大,需密切监测血药浓度,指导合理用药.

目的 观察CYP2C19?3位点不同基因型重症侵袭性真菌感染(IFI)患者接受常规剂量伏立康唑治疗时的血药浓度,并进行疗效对比.方法 接受伏立康唑抗真菌治疗的重症IFI患者70例,用药第3天清晨用药前采集肘静脉血,抗凝存放.取抗凝全血,提取DNA并进行PCR扩增后,采用Sanger测序法检测CYP2C19?3位点基因型,依据测序结果将患者分为GG组、GA组、AA组.取抗凝全血,使用超高效液相色谱仪及Xevo TQS三重四级杆串联质谱仪检测患者伏立康唑血药浓度.70例患者伏立康唑常规剂量治疗1周及以上,然后评估治疗效果和不良反应,计算治疗有效率、不良反应发生率.结果 70例患者中,CYP2C19?3位点GG型60例、GA型10例,未检测到AA基因型.GG组患者伏立康唑血药浓度为(3.58±2.84)mg/L,GA组为(5.80±2.16)mg/L,两组相比,P<0.05.GG组患者伏立康唑治疗有效率为55.00％(33/60),不良反应发生率为26.67％(16/60);GA组患者伏立康唑治疗有效率为90.00％(9/10),不良反应发生率为40.00％(4/10);两组伏立康唑治疗有效率相比,P<0.05;两组不良反应发生率相比,P>0.05.结论 CYP2C19?3位点GA基因型重症IFI患者的伏立康唑血药浓度、治疗有效率均高于GG型重症IFI患者.

目的 探讨临床药师干预对ICU患者万古霉素血药浓度监测的影响.方法 收集2018年1月～2019年1月期间ICU患者使用万古霉素并行血药浓度监测的临床资料,将首次浓度监测结果 分为未达标组、达标组和超标组,探讨影响血药浓度结果的因素.对于未达标组和超标组,临床药师将剂量调整建议告知临床医生,分析临床药师干预后采血时机的合理性和血药浓度的达标率.结果收集到病例139例,首次血药浓度监测达标率(30.9％)较低.其中,浓度达标患者43例,为未干预组.未达标和超标组共96例,临床药师建议调整剂量的患者为56例,为干预组.未干预组采血时机合理率为41.9％,干预组采血时机合理率为73.2％,与未干预组相比,二者差异有统计学意义(P<0.05).干预组第二次血药浓度结果达标率为68％,较首次血药浓度监测达标率有所增加.结论 ICU万古霉素浓度监测达标率较低,临床药师干预能够促进临床合理规范采血时机,提高血药浓度监测的准确性.

目的 对某院消化内科氨基酸注射液用药进行分析,对临床药师干预前后的效果进行比较,为进一步规范氨基酸注射液的临床应用提供参考.方法 采用回顾性分析的方法,对某院2017年1～7月及2018年同期的氨基酸注射液用药进行归纳和分析,具体包括适应证、输注方式及滴注速度等方面,并对临床药师干预前后的效果进行比较.结果 某院消化内科氨基酸注射液使用存在不足,主要表现在无适应证用药、输注方式错误及滴注速度过快等,在临床药师的干预下,合格率有所提高.结论 临床药师在保证氨基酸注射液合理使用方面发挥重要的作用.

AIM To explore the correlation between genetic variants of isocitrate dehydrogenase 2 (IDH2) and ten-eleven-translocation protein 2 (TET2) and cytarabine sensitivity in European (CEU) and African (YRI) populations in order to promote personalized medicine.METHODS Cell lines derived from persons of CEU ancestry or YRI ancestry from international HapMap project were cultured,and then exposed to cytarabine in different concentration (1,5,40,80 μ mol ·L-1) for 72 h.Percent cell survival values and cytarabine sensitivity depicted by the lower area under the survival curve (AUC) were determined by Alamar Blue assay.The AUC of cytarabine was calculated using the trapezoidal rule.Genotyping of IDH2 and TET2 was conducted by Taqman PCR assay.RESULTS Within CEU population samples,the AUC of cytarabine in IDH2 rs2970356 mutant CG/GG genotype carriers and rs2970358 mutant AG/GG genotype carriers were significantly lower than that in IDH2 rs2970356 CC genotype carriers and rs2970358 AA genotype carriers (rs2970356:CG/GG vs.CC,P ＜ 0.05;rs2970358:AG/GG vs.AA,P ＜ 0.05).There was no SNP in TET2 in CEU population associated with cytarabine sensitivity depicted by lower AUC.Within YRI population samples,the AUC of cytarabine in IDH2 rs2970356 mutant CC/CG genotype carriers,and in TET2 rs2454206 and rs11248047 mutant AG/GG genotype carriers were significantly lower than that in IDH2 rs2970356 GG genotype carriers,TET2 rs2454206 and rs11248047 AA genotype carriers (rs2970356:CG/GG vs.CC,P ＜ 0.05;rs2454206:AG/GG vs.AA,P ＜ 0.05;rs11248047:AG/GG vs.AA,P ＜ 0.05).CONCLUSION The cytarabine sensitivity might be influenced by gene polymorphism of IDH2 and TET2 in YRI populations,and only by gene polymorphism of IDH2 in CEU populations.

OBJECTIVE:To investigate the correlation of XRCC1 rs25487 polymorphism with the occurrence of lung cancer. METHODS:A total of 208 patients with primary lung cancer of Han nationality in Northern Jiangsu selected from the Affiliated Hospital of Xuzhou Medical University during Sept. 2015-Jul. 2016 were included in lung cancer group. A total of 214 healthy volunteers of the hospital underwent physical examination were included in control group. PCR-RFLP was used to detect the genotypes at XRCC1 rs25487 locus,and Logistic regression model was used to evaluate the correlation of genotypes with the occurrence of lung cancer. RESULTS:There was no statistical significance in the distribution of age and gender between 2 groups (P＞0.05). The proportion of smoker in lung cancer group was significantly higher than control group,with statistical significance(P＜0.05). AA,AG and GG genotypes were detected at rs25487 locus of XRCC1 gene. The frequency of AA,AG and GG genotype were 43.5%,41.1%and 15.4% in control group and 28.8%,48.6% and 22.6% in lung cancer group,respectively. The frequencies of genotypes in 2 groups were in line with Hardy-Weinberg equilibrium(P＞0.05),but there was statistical significance in genotype distribution between 2 groups(P＜0.05). Compared with AA genotype,the risk of lung cancer in individuals carrying AG genotype increased by 2.265 fold [OR＝2.265,95%CI(1.299,3.950),P＝0.040;after corrected with gender,age and smoking history OR＝2.309,95%CI(1.274, 4.185),P＝0.006],with statistical significance. The risk of lung cancer in individuals carrying GG genotype increased by 1.310 fold [OR＝1.310,95%CI(0.771,2.228),P＝0.318;after corrected OR＝1.429,95%CI(0.811,2.518),P＝0.217],without statistical significance. CONCLUSIONS:rs25487 locus mutant heterozy-gosity of XRCC1 gene is risk factor of lung cancer in Han nationality from Northern Jiangsu,and smoking can increase the risk of lung cancer.

Objective To analyze the risk factors and pathogens characteristics of stroke-associated pneumonia in neurological intensive care unit (NICU) of Affiliated Hospital of Xuzhou Medical University ("our hospital" for short),so as to provide evidence for antimicrobial drug choice.Methods Clinical data of 154 patients with stroke from January 2016 to June 2017 in our hospital.The multivariate Logistic regression analysis was used to analyze the risk factors of stroke-associated pneumonia,and the main pathogenic bacteria and drug resistance statistically.It was studied that how to carry out effective anti-infective therapy on the main pathogens.Results Multivariate regression analysis showed significant differences (P ＜ 0.05) in several factors such as age≥ 65 years,diabetes,dysphagia,hyperglycemia,hypoproteinemia,and high leukocyte count.The main pathogens were G-bacteria 59.09％ in proportion,the top three major pathogens were Klebsiella pneumoniae,Staphylococcus aureus and Pseudomonas aeruginosa.The main pathogens showed severe multidrug resistance.G-bacteria were more sensitive to Tigecycline,Amikacin and so on.Staphylococcus aureus was more sensitive to Vancomycin,Linezolid,Tigecycline,Amikacin and Cotrimoxazole.Conclusion Risk factors of stroke-associated pneumonia in NICU of our hospital include advanced age,diabetes,dysphagia,hyperglycemia,hypoproteinemia,and high leukocyte count,etc.G-bacteria were the main pathogens.The main pathogens show severe multidrug resistance.Amikacin,Tigecycline can be used as the preferred antibacterial drugs,MRSA infection can also choose Vancomycin,Linezolid and other antibacterial drugs.

患者，女，67岁。因“血糖升高20年，咳嗽、咯痰、喘憋1月，加重10d”于2015年7月2日入院。患者20年前行子宫切除术时发现血糖升高，伴口渴、多饮、多尿、多食、体质量下降，无明显视物模糊、四肢麻木，无尿中泡沫增多，给予消渴丸等口服降糖药治疗，血糖控制差。6年前无明显诱因渐感双下肢麻木不适，3年前出现视物模糊，具体诊疗经过不详。1个月前受凉后出现咳嗽、咯痰，痰为黄色黏痰，不易咯出，伴有咽痛不适，胸闷、憋气、呼吸困难，无明显发热，给予抗感染等对症支持治疗无效。10d 前上述症状加重，不能平卧，伴有双下肢水肿，全身乏力不适，未予诊治。否认高血压、脑血管病等慢性疾病史，否认肝炎、结核病史及密切接触史，否认食物及药物过敏史。诊断为2型糖尿病、心房颤动、肺部感染。入院后给予阿司匹林联合氯吡格雷抗血小板，去乙酰毛花苷、托拉塞米、二羟丙茶碱强心、利尿、平喘，头孢哌酮舒巴坦抗感染，胰岛素降糖，环磷腺苷葡胺营养心肌等治疗。7月13日早晨出现血尿，颜色鲜红，给予持续膀胱冲洗。7月16日患者出现持续肉眼血尿，血栓弹力图示阿司匹林抑制率100%，氯吡格雷抑制率95%，给予停用氯吡格雷、阿司匹林，输注红细胞、血小板、血浆等。7月23日未再出现血尿，给予拔尿管。经系统治疗后，患者无胸闷、憋喘，无血尿等，病情平稳，予以出院。

Objective To investigate the correlation between PPAR-δ gene polymorphisms,type 2 diabetes mellitus and metabolic indicators in Chinese Han population of Huaihai area.Methods The subjects were divided into case group(200 patients with type 2 diabetes mellitus)and control group(200 healthy people).The PPAR-δ gene polymorphisms in all subjects were detected with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method.Heigh,weight,waist circumference(WC),hip circumference(HC),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FPG),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)were measured,and the body mass index(BMI)and waist to hip ratio(WHR)were calculated in all subjects.Results There were no significant differences of the genotype frequency and allete frequency at PPAR-δ-87T/C site between two groups(P>0.05).There were significant differences of weight and BMI between different genotypes in patients with type 2 diabetes mellitus(P<0.05).The weight of cases with CC genotype was significantly higher than that of case with TT genotype,the BMI of cases with CC genotype was significantly higher than that of case with TT and TC genotypes(P<0.05 or P<0.01).There were no significant differences of other indexes among cases with 3 different genotypes(P>0.05).Conclusion There may be not the obvious correlation between the polymorphisms of PPAR-δ-87T/C and type 2 diabetes mellitus for Han redidents in Huaihai area,but PPAR-δ-87T/C gene polymorphisms may be associated with the obesity of patients with type 2 diabetes mellitus.

Objective To investigate the correlation between KCNQ1 gene polymorphism and type 2 diabetes mellitus(T2DM) in Chinese Han population in Huaihai region.Methods 200 T2DM inpatients and outpatients admitted to the Department of Endocrinology of the Affiliated Hospital of Xuzhou Medical College were selected as case group and 200 healthy people underwent physical examinations in the same region and period were selected as control group.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method was used to detect gene polymorphisms in the two groups.Results(1) In the control group,the genotypes of CC,CT and TT in KCNQ1 rs2237892 accounted for 36.0%(72/200),51.0%(102/200) and 13.0%(26/200) respectively and the allele frequencies of C and T were 61.5%(246/400) and 38.5%(154/400) respectively.In the case group,the genotype frequencies of CC,CT and TT were 47.5%(95/200),44.0%(88/200) and 8.5%(17/200) respectively and the allele frequencies of C and T were 69.5%(278/400) and 30.5%(122/400).The genotype distribution and allele frequencies in KCNQ1 rs2237892 between the two groups showed statistically significant differences(P0.05).(2) The genotype distributions and allele frequencies in KCNQ1 rs151290 between the two groups showed no statistically significant differences(P0.05).Conclusion KCNQ1 rs2237892 polymorphism may be associated with the incidence of type 2 diabetes mellitus among Chinese Han population in Huaihai region.The polymorphism of KCNQ1 rs151290 may have nothing to do with the incidence of type 2 diabetes mellitus in Chinese Han population in Huaihai region.

目的 通过多巴胺β羟化酶(DβH)基因rs1611115、rs1108580多态性位点的筛查,探索DβH基因多态性与中国淮海地区汉族人群儿童注意力缺陷多动障碍(ADHD)的相关性.方法 采用病例-对照研究,应用聚合酶链反应限制性片段长度多态性(PCR-RFLP)分析技术,对入选的50例汉族注意缺陷多动障碍患儿及50例正常儿童的rs1611115、rs1108580位点的基因型进行检测,利用ELISA法检测DβH活性.结果 rs1611115位点3种基因型比较,差异无统计学意义(χ2=0.434,P=0.805);等位基因之间比较差异也无统计学意义(χ2=0.385,P=0.535).rs1108580位点的3种基因型比较,差异有统计学意义(χ2=7.062,P=0.029),但等位基因之间比较,差异无统计学意义(χ2=2.000,P=1.157).结论 淮海地区ADHD患儿中存在rs1611115及rs1108580位点突变基因,但单个rs1611115位点可能与ADHD疾病无关.rs1108580突变位点单独存在时并不起作用,只有它处于纯合状态时才与ADHD相关.

【Objective】 To investigate the correlation between TCF7L2 gene polymorphism and type 2 diabetes mellitus in Chinese Han population from Huaihai region. 【Methods】 The TCF7L2 gene polymorphisms of 200 type 2 diabetes mellitus patients (case group) and 200 healthy people (control group) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). 【Results】 TCF7L2 rs12255372 genotype frequency and allele frequency revealed that there were no significant difference between type 2 diabetes and health people (P 0.05). Logistic regression analysis, regardless on single factor or multifactors such as: age, sex and blood pressure, did not suggest that the various genotypes of TCF7L2 rs12255372 were risk factors of type 2 dibetes (P 0.05). 【Conclusions】 No relevance between the gene polymorphisms of TCF7L2 rs12255372 and T2DM in Chinese Han population from Huaihai region has been observed.

目的 探讨一氧化氮合酶1转接蛋白(NOS1AP)基因多态性与中国淮海地区汉族人群2型糖尿病发病风险的关系.方法 采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法对200例2型糖尿病患者(病例组)和200例健康人群(对照组)进行NOS1AP基因多态性检测.结果 病例组NOS1AP rs12742393位点CC基因型和C等位基因频率均高于对照组(P<0.05),C等位基因显著增加2型糖尿病的遗传风险性(OR=1.662,95%CI=1.089~2.535,P=0.018).结论 NOS1AP rs12742393位点多态性可能与中国淮海地区汉族人群2型糖尿病的发病相关,C等位基因可能是2型糖尿病的遗传风险因子.

Oxidative stress has been shown to play an important role in the development and progression of diabetic nephropathy, and the formation of reactive oxygen species (ROS) is a direct consequence of hyperglycaemia. We hypothesized that hyperglycaemia-induced ROS can activate the transforming growth factor-β1 (TGF-β1)-phosphoinositide 3-kinase (PI3K)-Akt-FoxO3a signalling pathway, negatively regulating expression of manganese superoxide dismutase (MnSOD), which promotes excessive ROS generation and accelerates the pathological process of diabetic nephropathy. In vitro, in rat mesangial cells, high glucose (30 mmol l(-1)), but not equimolar mannitol, stimulated ROS production, upregulated the levels of TGF-β1, increased the phosphorylated Akt/total Akt and phosphorylated FoxO3a/total FoxO3a protein ratios, altered the subcellular localization of FoxO3a and reduced the levels of MnSOD expression. These high-glucose-induced changes further promoted the generation of ROS. In vivo, in db/db mice treated with an inhibitor of TGF-β1 (SB431542) or PI3K (LY294002), the levels of phosphorylated Akt and phosphorylated FoxO3a in the kidney cortices were decreased, the level of MnSOD expression was increased and the level of the lipid peroxidation end-product, malondialdehyde, was reduced. We conclude that overproduction of ROS induced by a high glucose concentration decreases the expression of MnSOD via the PI3K-Akt-FoxO3a pathway and further aggravates oxidative stress in diabetic nephropathy.