Abstract Early complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including graft-versus-host disease (GVHD) and viral reactivation, remain major causes of post-transplant morbidity, but whether immune perturbations precede these events remains unclear. We performed longitudinal TCRβ repertoire profiling in 108 allo-HSCT recipients and their corresponding donors at baseline and three early post-transplant time points to characterize immune reconstitution dynamics. Reduced baseline TCR diversity was most strongly associated with subsequent Epstein–Barr virus (EBV) reactivation, whereas cytomegalovirus (CMV) reactivation was more closely linked to post-transplant repertoire remodeling characterized by clonal expansion and reduced donor–recipient repertoire similarity. Sequence-based predictive modeling demonstrated meaningful discrimination, with fusion models achieving area under the curve (AUC) values of 0.745 for CMV, 0.819 for EBV, and 0.834 for GVHD. Temporal analyses further revealed complication-specific predictive windows. These findings indicate that major post-transplant complications are preceded by detectable immune perturbations and support the potential utility of TCR repertoire monitoring for early risk stratification after transplantation.

Background and Objective:The bone marrow microenvironment is closely related to normal hematopoiesis and hematologic tumors. Adipocytes are an important part of the bone marrow microenvironment, in which they can release free fatty acids (FFAs) through lipolysis and secrete adipocytokines, etc., and participate in normal hematopoiesis, which is closely related to the occurrence and treatment of hematological tumors. In this review, we aim to discuss how bone marrow adipocytes (BMAs) can influence the proliferation, apoptosis, and chemotherapy resistance of cancer cells by reprogramming lipid metabolism and the secretion of various adipocytokines. Methods:Studies from 2000 to July 2024 were reviewed from PubMed, Springer Link, and the Web of Science using the keywords bone marrow microenvironment, adipocytes, lipid metabolism, adipocytokines, hematological tumor, cancer, and their combinations. Unreliable articles such as those that are old and have a low impact factor are excluded, and there is no restriction on language. Key Content and Findings:Adipocytes can regulate the proliferation and differentiation of hematopoietic stem cells (HSCs) by secreting inflammatory factors and adipocytokines to maintain hematopoietic homeostasis. Adipocytes can also stimulate and accelerate the occurrence and progression of hematological tumors by secreting adipocytokines and mediating the reprogramming of lipid metabolism. Moreover, abundant adipocytes in bone marrow can protect tumor cells by physically blocking and/or secreting cytokines, leading to chemotherapy resistance. Conclusions:Therefore, the targeted inhibition of related lipid metabolism pathways and adipocytokines might be a potential therapeutic target for hematological tumors, which would be helpful to inhibit tumor growth and correct chemotherapy resistance.

目的:探讨微小核糖核酸-122(MicroRNA-122,miR-122)、胰岛素抵抗指数(Insulin Resistance of Homeostasis Model Assessment,HOMA-IR)水平的表达与妊娠期糖尿病(Gestational Diabetes Mellitus,GDM)及妊娠结局的关系.方法:选取孕 24～32 周GDM孕妇 52 例作为观察组,口服葡萄糖耐量试验(Oral Glucose Tolerance Test,OGTT)正常的孕 24～32 周孕妇 45 例作为对照组,比较两组糖代谢指标、HOMA-IR水平及血清和胎盘中miR-122 水平;根据GDM患者妊娠结局(若出现流产、早产、巨大儿、死胎、死产、胎儿畸形、新生儿呼吸窘迫综合征及新生儿死亡等任一情况均归为不良结局组),将 52 例GDM患者分为结局良好组 34 例和不良结局组 18 例,比较两组上述指标;分析miR-122 水平与HOMA-IR的相关性.结果:两组年龄、分娩孕周、孕次、产次、孕前等一般资料比较,差异无统计学意义(P＞0.05);观察组空腹血糖、胰岛素水平、HOMA-IR及血清和胎盘miR-122 水平均高于对照组(P＜0.05).不良结局组HOMA-IR及血清和胎盘miR-122 表达水平均高于结局良好组(P＜0.05).经Pearson相关分析结果显示,GDM患者血清及胎盘 miR-122 水平均与 HOMA-IR 呈正相关(P＜0.05).结论:GDM 患者伴有明显的胰岛素抵抗,miR-122 在GDM患者体内呈高水平表达,且其高水平表达与胰岛素抵抗有关,并可影响妊娠结局,这可能是GMD临床诊断和治疗GMD的潜在靶点.

目的 探讨补体C1q/肿瘤坏死因子相关蛋白5(CTRP5)与妊娠糖尿病(GDM)的关系.方法 选取2020年6月至2021年6月郑州大学第二附属医院孕检的孕妇172名,按是否患有GDM将其分为对照组(80名)和GDM组(92例).比较两组年龄、孕龄、孕前体重指数(BMI)、产前BMI、血压、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、空腹血糖(FBG)、葡萄糖负荷2 h血糖、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、稳态模型胰岛素抵抗(HOMA-IR)指数、CTRP5和脂肪甘油三酯脂肪酶(ATGL).分析CTRP5与各指标的相关性,并通过logistic回归模型分析CTRP5与GDM的关系.结果 GDM组孕前BMI、产前BMI、TC、TG、FBG、葡萄糖负荷2 h血糖、HbA1c、FINS、HOMA-IR指数均高于对照组,ATGL、CTRP5均低于对照组,差异有统计学意义(P＜0.05).CTRP5与孕前BMI、产前BMI、TC、TG、FBG、HbA1c、葡萄糖负荷2 h血糖、FINS、HOMA-IR指数呈负相关(r＜0,P＜0.05),与ATGL呈正相关(r＞0,P＜0.05).logistic回归模型分析结果显示,校正孕前BMI、产前BM1、TC、TG、FBG、HbA1c、葡萄糖负荷2 h血糖、FINS、HOMA-IR指数后,CTRP5仍为GDM发生的独立影响因素(P＜0.05).结论 CTRP5是GDM的影响因素,可能与胰岛素抵抗和糖脂代谢有关.

目的 探讨补体C1q肿瘤坏死因子相关蛋白1(CTRP1)促炎反应在糖尿病合并周围神经病变(DPN)发生中的作用.方法 选取2017-08—2020-11在郑州大学第二附属医院就诊的单纯2型糖尿病(T2DM)患者58例(T2DM组),DPN患者58例(DPN组)和60例健康体检者(HC组)为研究对象.采用酶联免疫吸附试验(ELISA)检测血清中脂肪因子CTRP1,炎症相关因子TNF-α、IL-1β、IL-6及炎症趋化因子MCP-1水平.结果 DNP组空腹血糖和糖化血红蛋白均显著高于T2DM组,且DNP组CTRP1、TNF-α和MCP-1也显著高于T2DM组.Pearson相关性分析和Logistic回归分析显示,CTRP1、TNF-α和MCP-1与DNP的发生密切相关,且是DPN的独立影响因素.而CTRP1相关性分析显示,血清CTRP1水平与TNF-α和MCP-1均呈正相关.结论 T2DM患者高表达的CTRP1可能通过促炎反应上调炎症因子TNF-α和炎症趋化因子MCP-1的表达,诱导DPN的发生.

目的:探讨妊娠期糖尿病(GDM)对胎盘组织脂代谢的影响及相关分子改变.方法:选择30例GDM孕妇和30例正常孕妇为研究对象,采用实时荧光定量PCR法检测胎盘组织中SNARE复合体相关基因[囊泡相关蛋白23(SNAP23)、突触融合蛋白4(STX4)、靶膜相关蛋白2(VAMP2)]及其正性调节因子Unc-18c的哺乳动物同源物(Munc18c)、脂肪酸β氧化限速酶肉碱棕榈酰转移酶1(CPT1)和促脂滴形成蛋白围脂滴蛋白2(PLIN2)mRNA表达水平,分析脂代谢相关基因表达与糖脂代谢指标的相关性.结果:GDM孕妇血TG水平和新生儿体重高于正常孕妇,其胎盘组织中脂肪含量也较正常孕妇升高(P<0.05).GDM孕妇胎盘中SNAP23、Munc18c和CPT1 mRNA表达水平较正常孕妇降低(P<0.05).GDM孕妇OGTT空腹血糖水平分别与SNAP23、Munc18c和CPT1 mRNA表达水平呈负相关(r=-0.549、-0.714、-0.572,P<0.05);而TG水平与Munc18c呈负相关(r=-0.788,P=0.029),与PLIN2呈正相关(r=0.577,P=0.015).GDM组新生儿体重与Munc18c和CPT1 mRNA表达水平均呈正相关(r=0.610、0.578,P<0.05);脂代谢相关基因中,SNAP23分别与Munc18c、CPT1和PLIN2 mRNA表达水平呈正相关(r=0.514、0.672、0.579,P<0.05),而Munc18c与CPT1 mRNA表达水平呈正相关(r=0.563,P=0.035).结论:GDM可加重母体脂代谢紊乱导致胎盘脂质蓄积,脂代谢相关基因SNAP23、Munc18c和CPT1协同参与胎盘组织脂肪酸氧化代谢下降,促进胎盘脂质蓄积.

目的 探讨脂肪因子CTRP1与脂肪三酰甘油脂酶(ATGL)、内皮脂肪酶(EL)和脂蛋白相关磷脂酶A2(Lp-PLA2)与2型糖尿病合并脑梗死发病的关系.方法 选取2018-12—2020-10郑州大学第二附属医院确诊的2型糖尿病患者36例、合并脑梗死患者36例及健康体检者34例为研究对象.采用酶联免疫吸附法检测血清CTRP1、ATGL、EL和Lp-PLA2水平,结合相关临床资料分析CTRP1及相关脂代谢酶与2型糖尿病患者脑梗死的相关性.结果 2型糖尿病合并脑梗死组TC和TG均显著高于对照组(TC:P<0.01和TG:P=0.047),而HDL-C较对照组明显下降(P=0.037),合并脑梗死患者的TC水平较单纯糖尿病患者显著升高(P<0.01).2型糖尿病合并脑梗死组CTRP1水平较高,2型糖尿病组和对照组依次下降(P<0.01).合并脑梗死组ATGL水平较对照组和2型糖尿病组显著降低(与糖尿病组比较,P=0.007;与对照组比较,P=0.005).合并脑梗死组EL和Lp-PLA2水平较对照组和糖尿病组均显著升高(EL:与糖尿病组比较,P<0.01;与对照组比较,P<0.01;Lp-PLA2:与糖尿病组比较,P=0.018;与对照组比较,P<0.01).血清CTRP1与EL和Lp-PLA2均呈正相关(EL:r=0.64,P<0.01;Lp-PLA2;r=0.37,P=0.026).结论 脂肪因子CTRP1可能通过刺激调节脂代谢酶EL和Lp-PLA2的水平,诱发/加重2型糖尿病患者脑梗死的发生,可作为评估脑梗死发生的高危因素之一.

目的 探讨妊娠期糖尿病(GDM)和/或非酒精性脂肪肝(NAFLD)的危险因素及三酰甘油葡萄糖(TyG)指数的诊断价值.方法 选取2018年6月～2019年9月郑州大学第二附属医院(以下简称“我院”)产检并分娩的孕妇,将患GDM孕妇分为GDM组(137例),患NAFLD孕妇为NAFLD组(70例),GDM合并NAFLD孕妇为复杂组(73例),并选取同期来我院产检的健康孕妇为正常组(73名).比较妊娠24～28周时空腹血糖(FBG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇酯(HDL-C)、低密度脂蛋白胆固醇酯(LDL-C)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、血尿酸(SUA),计算稳态模型胰岛素抵抗指数(HOMA-IR)及TyG指数等.结果 GDM组FBG、HbA1c、HOMA-IR、TyG指数高于正常组;NAFLD组ATL、SUA、TG、HOMA-IR、TyG指数高于正常组;复杂组ATL、SUA、TG、FBG、HbAh、HOMA-IR、TyG指数高于正常组及GDM组,FBG、HbA1c、HOMA-IR、TyG指数高于NAFLD组,差异均有统计学意义(均P＜0.05).GDM组、NAFLD组、复杂组FINS、巨大儿发病率高于正常组,差异有统计学意义(P＜0.05).Pearson相关分析显示,TyG指数与HOMA-IR及HbA1c呈正相关(r=0.473、0.472,P＜0.001).logistic回归分析显示,FBG(OR=1.707,95％CI:1.202～2.424,P=0.003),TG(OR=1.386,95％CI: 1.031～1.862,P=0.031)为GDM孕妇并发NAFLD的危险因素.ROC曲线显示HOMA-IR、TyG指数对GDM和/或NAFLD的发生均有诊断价值.结论 GDM合并NAFLD的孕妇IR及代谢紊乱严重,FBG、TG参与GDM孕妇NAFLD的发生,临床上应重视并采取有效的控制措施.TyG指数可初步识别IR,并评估血糖水平.

目的 观察贝前列素钠联合前列地尔对老年早期糖尿病肾病(DN)患者NOD样受体蛋白3(NLRP3)炎症小体表达的影响.方法 将老年DN患者142例按随机数字表法分为试验组71例及对照组71例.2组均接受降糖、优质低蛋白饮食和对症治疗.对照组给予前列地尔,每天10μg,静脉滴注,试验组前2周给予前列地尔,后2周给予贝前列素钠,每次40μg,每天3次,口服.2组均治疗4周.治疗前后,比较2组肾功能指标、氧化应激指标、NLRP3、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶-1(Caspase-1)、白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18),并记录2组治疗期间药物不良反应发生情况.结果 治疗后,试验组和对照组NLRP3 mRNA分别为18.01±0.91,22.37±1.06,ASC mRNA分别为19.98±0.85,23.59±1.02,Caspase-1 mRNA分别为20.42±0.95,23.91±1.04,NLRP3蛋白分别为0.28±0.03,0.39±0.06,ASC蛋白分别为0.32±0.04,0.48±0.07,Caspase-1蛋白分别为0.30±0.05,0.41±0.08,差异均有统计学意义(均P<0.01).试验组和对照组的IL-18分别为(16.50±1.97)和(21.71±2.45)pg·mL-1,IL-1β分别为(7.59±2.33),和(12.37±3.24)pg·mL-1,超氧化物歧化酶(SOD)分别为(55.48±9.78),(46.20±7.36)U·mg-1,谷胱甘肽过氧化物酶(GSH-Px)分别为(169.29±18.40),(140.59±13.62)kU·L-1,丙二醛(MDA)分别为(6.90±1.40),(9.96±2.28)mmol·mg-1,尿蛋白排泄率(UAER)分别为(64.40±7.40),(91.59±9.48)mmol·L-1,血肌酸酐(Scr)分别为(91.90±8.09),(120.47±10.60)μmol·L-1,尿足细胞标志蛋白(PCX)分别为(1.47±0.28),(2.62±0.39)mg·mL-1,亮氨酸氨基肽酶(LAP)分别为(8.41±1.69),(11.61±2.48)mg·mL-1,差异均有统计学意义(均P<0.05).试验组和对照组的药物不良反应发生率分别为4.63％(4例/71例),11.27％(8例/71例),差异无统计学意义(P>0.05).结论 贝前列素钠联合前列地尔能够有效降低老年DN患者降低尿蛋白,改善肾功能,疗效显著,其机制与改善机体氧化应激状态、抑制NALP3炎症信号通路的活化及其介导的炎症反应密切相关.

Objective: To explore the relationship between driver gene mutation (JAK2, MPL and CALR) and disease type in BCR-ABL negative myeloproliferative neoplasms (MPNs) including primary myeloid fibrosis (PMF), essential thrombocytosis (ET) and polycythemia vera (PV). Methods: A total of 32 MPN related genes were detected by high-throughput sequencing in 156 MPN patients. The relationships between disease type and patients' general performance, the characteristics of driver gene mutations, concomitant gene mutations were analyzed. Results: In the population with JAK2 V617F positive mutation, the proportion of patients over 60 years old in PMF was higher than that with ET or PV. By high-throughput sequencing, 22 concomitant gene mutations were detected in 46 patients with JAK2, MPL or CALR mutations, including 4 (8.3%) in PV, 20 (29.4%) in ET, and 22 (55.0%) in PMF. DNMT3A mutation was detected only in patients with PV, while splicing factor related genes including SF3B1, SRSF2 and U2AF1 were only accompanied by PMF. According to the variation allele frequency (VAF) value of JAK2 V617F mutation, the VAF value associated with PV was the highest (68.15%), followed by PMF (37.7%) and ET (23%). However, there were significant differences in the incidence of JAK2 V617F homozygous among 3 different diseases. In patients with JAK2 mutation, the proportion of other gene mutations in PV and ET was significantly lower than that in PMF. Conclusions: Under the condition of common driver gene mutations (JAK2, MPL and CALR), patients' age, VAF value and homozygous state, concomitant gene mutations are closely related to different disease type. These correlations help to improve clinical understanding of disease characteristics and risk assessment.

目的 探讨人巨细胞病毒感染与妊娠期糖尿病的相关性.方法 回顾性分析2018.6～2019.6在郑州大学第二附属医院门诊常规孕前检查、建立围产期档案并住院分娩的338例孕妇的临床资料,根据是否有妊娠期糖尿病分为GDM组(n=156)和NGT组(n=182).比较2组孕妇产前空腹血糖、糖化血红蛋白、血脂水平,并比较2组间HCMV感染的阳性率.结果GDM孕妇的FPG、HbA1c水平明显高于健康孕妇(FPG:4.90±0.60 vs.4.35±0.47,P<0.01;HbA1c:5.42±0.35 vs.5.05±0.33,P<0.01).GDM孕妇的TC、TG、LDL水平也较健康孕妇高(TC:6.21±1.23 vs.5.85±1.34,P=0.018;TG:3.21±2.32 vs.2.74±0.92,P=0.041;LDL:3.93±1.14 vs.3.46±0.88,P<0.01),且差异有统计学意义.GDM孕妇总体HCMV IgM阳性率高于健康孕妇[9例(5.77％)vs.2例(1.10％)],且差异有统计学意义(P=0.016).GDM孕妇中,未被感染即HCMV IgG(-)/IgM(-)所占比例为2例(1.28％),而健康孕妇未被感染的比例为12例(6.59％),两组间差异有统计学意义(P=0.015).HCMV活动性感染即HCMV IgG(+)/IgM(+)在GDM孕妇中的比例高于健康孕妇[7例(4.49％)vs.1例(0.55％)],且差异有统计学意义(P=0.027).结论 HCMV感染可能通过加重糖脂代谢紊乱和炎症导致GDM的发生和发展.

Diabetic retinopathy is one of the major complications of diabetes and the main cause to lead to blindness for diabetic patients. However, the exact mechanisms involved in the progression of diabetic retinopathy are not completely known. Herein, we demonstrated a novel role of miR-221-3p in the microvascular dysfunction in diabetic retinopathy. MiR-221-3p expression was found to be substantially upregulated in the retina samples of diabetic rats. Besides, ganglion cell layer, inner nuclear layer, outer nuclear layer, and retinal pigment epithelium layer of diabetic rats expressed higher miR-221-3p than the matched areas of normal rats. High glucose-treated retinal microvascular endothelial cells RF/6A and HRECs exhibited higher miR-221-3p than that in normal condition. MiR-221-3p inhibition could alleviate the retinal vascular leakage induced by diabetes in vivo as evaluated by Evans blue leakage assay, and reduce the proliferation, accelerate the apoptosis development, and inhibit the migration capacity of high glucose-treated RF/6A cells in vitro, while miR-221-3p overexpression partially enhanced the detrimental effects. By bioinformatics analysis and luciferase reporter assay, we identified that TIMP3 is the direct target of miR-221-3p. TIMP3 overexpression counteracted the effect of miR-221-3p on the vessel leakage and endothelial cell function. In conclusion, this study highlights the negative role of miR-221-3p in the microvascular dysfunction in diabetic retinopathy by targeting TIMP3, representing a potential therapeutic target for human diabetic retinopathy.

Objective:To investigate the relationship between gene mutation characteristics, mutation burden and general condition, disease subtype and karyotype of patients with myelodysplastic syndrome (MDS), and its clinical value.Methods:High-throughput sequencing was used to detect 65 blood tumor-related genes in 191 MDS patients and 9 secondary acute myelocytic leukemia patitents(SAML), and to analyze the characteristics of abnormal genes, mutation burden, as well as the relationship with disease subtypes, chromosome karyotypes and age.Results:Mutations were found in 148 patients (77.5%), including 47 abnormal genes and 186 mutation sites. And gene mutations were found in 9 SAML patients, the number of mutations was significantly higher than that in MDS patients (χ 2=11.911, P=0.018). Among the abnormal genes, the mutation frequency of U2AF1 (37.3%) and ASXL1 (41.6%) were higher, and there were significant differences in mutation burden among different abnormal genes ( F=91.946, P<0.001). There were differences in the number of gene mutations among different subtypes of MDS, and the number of EB-2 gene mutations was the highest (2.2±1.5). In SLD, MLD, EB-1 and EB-2, the proportion of carrying ≥ 3 mutations increased gradually (χ 2=52.471, P=0.037). TP53 mutation was associated with abnormal karyotype (r φ=0.177, P=0.019), especially with complex karyotype (r φ=0.440, P<0.001), while NPM1 mutation is associated with normal karyotype (r φ=0.173, P=0.024). The number of mutations carried by patients under 30 years old was the least, and the number of mutations increased with the increase of age. The number of mutations was the most in patients aged 60 to 79 years old ( P=0.017), and the mutation frequency of epigenetic related genes increased with the increase of age ( P=0.041). Conclusions:The mutation characteristics and mutation load of MDS-related genes are closely related to clinical factors such as disease subtype, chromosome karyotype and patient age.

Although TRPC6 expression is shown to be significantly elevated in a rat model diabetic nephropathy (DN), its expression and role in human DN are unclear. We thus explored the role of TRPC6 in the pathophysiology of tubular epithelial cell injury following DN. HK-2 cells were cultured in a high-glucose medium to induce a DN cell model. Ad-TRPC6 and TRP6 siRNA were transfected to overexpress and knock down TRPC6. We found that TRPC6 expression was significantly upregulated in DN tissues and cells. TRPC6 siRNA inhibited cell proliferation and promoted cell apoptosis in HK-2 cells treated with high glucose, whereas Ad-TRPC6 showed the opposite effect. Furthermore, Ad-TRPC6 significantly promoted release of IL-8 and IL-6. Subsequent experiments demonstrated that the signaling pathway of nuclear factor of activated T cells (NFAT) was activated by Ad-TRPC6 and deactivated by TRPC6 siRNA. The NFAT signaling inhibitor, FK-506, eliminated the effect of TRPC6 on HK-2 cells. These results suggest that TRPC6 was upregulated in DN and could promote cell proliferation and inflammation by inhibiting the NFAT signaling pathway in tubular epithelial cells.

PBL教学法是以问题为导向,以学生为中心的教学方式.教学过程中以问题为引导,调动学生学习的自主性,通过学生寻找问题的过程,学习问题所涉及的知识,从而提高学习的效率和课堂授课的效果.糖尿病是临床医学生所必修的内科学中的重要部分,本研究通过课堂效果、笔试成绩和问卷调查三种手段对比PBL教学与传统教学的优劣,结果发现PBL教学在教学过程中能够充分调动学生学习的主动性和积极性,教学效果明显优于传统教学,提示PBL教学在糖尿病教学中具有很好的应用价值.

C1qTNF-related protein 1 (CTRP1) is independently associated with type 2 diabetes. However, the relationship between CTRP1 and insulin resistance is still not established. This study aimed to explore the role of CTRP1 under the situation of insulin resistance in adipose tissue. Plasma CTRP1 level was investigated in type 2 diabetic subjects (n = 35) and non-diabetic subjects (n = 35). The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored. Our data showed that Plasma CTRP1 was higher and negative correlation with insulin resistance in diabetic subjects (r = -0.283, p = 0.018). Glucose utilisation test revealed that the glucose utilisation rate of mature adipocytes was improved by CTRP1 in the presence of insulin. CTRP1 was not only related to IRS-1 protein, but also negatively correlated with IRS-1 Ser1101 phosphorylation (r = -0.398, p = 0.031). Furthermore, Phosphorylation levels of IRS-1 Ser1101 were significantly lower after incubation with 40 ng/mL CTRP1 in mature adipocytes than those with no intervention (p < 0.05). There was no significant correlation between CTRP1 and other IRS-1 serine sites (Ser302, Ser307, Ser612, Ser636/639, and Ser789). Collectively, our results suggested that CTRP1 might improve insulin resistance by reducing the phosphorylation of IRS-1 Ser1101, induced in the situation of insulin resistance as a feedback adipokine.

Objective To observe the changes of heart rate variability(HRV)in patients with type 2 diabetes mellitus(T2DM),coronary heart disease(CHD),or T2DM and CHD,and its relationship with the index of cardiac structure function.Methods We chose 33 cases of patients with T2DM and CHD(T2DM combined with CHD group),32 patients with T2DM(T2DM group),32 patients with CHD(CHD group),and 31 cases of healthy controls(control group).The 24-hour dynamic electrocardiogram and echocardiography were performed to analyze the correlation of the time domain index of HRV,circadian variation and HRV index with cardiac structure function index.Results From comparing the four groups,the T2DM combined with CHD group had the highest incidence of HRV decrease,but the CHD group and T2DM group had no significant difference in the incidence of HRV decrease.HRV index of the T2DM combined with CHD group had no significant difference between awake state and sleeping state,but in the control group,every index of sleeping state was significantly higher than that of the awake state.Compared with the T2DM group and CHD group,left ventricular ejection fraction(LVEF)and E/A of the T2DM combined with CHD group decreased,but left ventricular end-diastolic diameter(LVEDD)and LA increased.Standard deviation of R-R intervals(SDNN)was negatively correlated with LA and LVEDD,but was positively correlated with LVEF and E/A.SDANN was negatively correlated with LVEDD,but was positively correlated with LVEF and E/A.SDNN index and LVEF was positively correlated.rMSSD was positively correlated with LVEF and E/A.Conclusions Patients with T2DM and CHD have the most serious autonomic nerve damage,and the heart rate variation of circadian rhythm is vanished.HRV can reflect the severity of the cardiac remodeling and cardiac function damage.

Aim: To investigate the relationship of endoplasmic reticulum stress ,TRAF2,Caspase-12 and the gestation-al diabetes mellitus(GDM).Methods: A total of 60 healthy female SD rats were randomly allocated into four groups : preg-nant group with high fat and sugar diet (HP),virgin group with high fat and sugar diet(HV),pregnant group with normal di-et(NP),virgin group with normal diet(NV).Fasting blood glucose(FBG),fasting serum insulin(FINS),and blood lipid of each group were tested in the late pregnancy , then the insulin resistance index(HOMA-IR) was calculated.The morpholog-ical changes in pancreatic tissue were observed using HE staining ,the apoptosis of islet cells was detected by TUNEL ,and the expression of GRP78 was tested by immunohistochemistry, the expressions of TRAF2 and Caspase-12 were tested by Western blot.Results: Pregnancy and high fat and sugar diet could increase FBG ,FINS,HOMA-IR,blood lipid synergisti-cally(P <0.05).At the 21st day during pregnancy, pancreatic tissue appeared different degree of atrophy ,islet cells de-creased significantly,pyknosis and karyorrhexis could be seen in HP group .Pregnancy, high fat and high sugar diet were the main factors for increasing the GRP78, TRAF2, Caspase-12 expressions in rat pancreatic tissue , and they had synergis-tic effect(P <0.05).Conclusion: Pregnancy and high fat and sugar diet are involved in ERS ;ERS might be involved in the development of GDM through inducing islet cell apoptosis by TRAF 2-Caspase-12 signaling pathway.

目的:探讨Egr-1是否参与妊娠期糖尿病(GDM)大鼠肝脏糖异生.方法:45只健康SD雌性大鼠随机分为正常饮食非孕鼠组(NC组)、正常饮食孕鼠组(NGT组)、高脂高糖饮食孕鼠组(GDM组),每组15只.妊娠第21天,应用全自动生化检测仪检测空腹血糖(FPG),ELISA法测定空腹胰岛素(FINS)、空腹胰高血糖素(FHGF),并计算胰岛素抵抗指数(HOMA-IR).应用RT-PCR检测肝脏组织中Egr-1和PEPCK、G-6-Pase mRNA表达水平.结果:与NC组比较,NGT组、GDM组大鼠HOMA-IR、FHGF和肝脏组织中Egr-1、PEPCK、G-6-Pase mRNA表达水平均升高(P均＜0.05);与NGT组比较,GDM组大鼠HOMA-IR、FHGF和肝脏组织中Egr-1、PEPCK、G-6-Pase mRNA表达水平均升高(P均＜0.05).在GDM组大鼠中,肝脏Egr-1的表达与FHGF、PEPCK和G-6-Pase的表达均呈正相关(r=0.855、0.975和0.897,P均＜0.05).结论:Egr-1通过影响胰高血糖素调控的肝脏糖异生参与GDM的发病.

软骨发育不全综合征（ chondrodysplasia syndrome，CHD）为某种原因引起的骨－软骨发育不良综合征，临床上较少见。鉴于目前我国普通民众经济状况及临床工作者对该病仍显贫乏的认知，CHD的诊断多依靠患者身高、体型及X线片，并无分子水平的诊断“金标准”。我院今年接诊1例疑似该病患儿，除常规辅助检查外，还对患儿成纤维细胞生长因子受体3（ FGFR3）基因突变情况进行了分析，从而明确了该病的诊断。现将该病例报告如下。