矮小症是指在相似环境下,儿童的身高处于正常的同种族、同年龄、同性别的人群身高均值 2 个标准差(–2SD)以下或第 3 百分位以下,其发病率为 2％ ～ 8％,不同国家及地区稍有差异[1].矮小症病因复杂,诊疗难度大,需转化医学与精准医学相结合的诊疗模式.随着精准医疗的发展,个性化治疗和临床研究越来越离不开生物样本的支持,生物样本库资源及其临床数据库受到广泛重视[2-4].

Objective:To investigate the predictive power of basal luteinizing hormone (LH) level for central gonadal activation states in girls.Methods:A total of 343 girls who developed secondary sex characteristics before the age of 8 years old and were hospitalized in the Affiliated Hospital of Jining Medical University from February 2015 to August 2022 were included in this study. The general clinical data were collected and the gonadotropin-releasing hormone analogue (GnRHa) stimulation test was performed. Based on the peak of LH in the GnRHa stimulation test, these girls were categorized into three groups: premature thelarche (PT), partial central precocious puberty (CPP), and complete CPP. The Logistic regression was used to clarify the independent correlation factors of PT and complete CPP. Receiver operating characteristic (ROC) curve was applied to compare the predictive power of the independent factors for PT and complete CPP.Results:Basal LH level showed significant differences between PT, partial CPP, and complete CPP groups with quartiles of 0.06(0.01, 0.16)U/L, 0.30(0.12, 0.56)U/L, and 1.50(0.72, 2.83)U/L, respectively. The difference between the three groups was meaningful in statistic (H=164.74, P<0.01). Age, basal LH, estradiol level, and uterine volume were independent influential factors of PT. Basal LH, estradiol level, and uterine volume were independent influential factors for complete CPP. Basal LH level was the best predictor for PT and complete CPP with AUCs of 0.874 and 0.878, respectively. The optimal cut-points of basal LH level for predicting PT and complete CPP were 0.185 U/L (sensitivity 83.90%, specificity 75.90%) and 0.435 U/L (sensitivity 80.50%, specificity 84.10%), respectively.Conclusion:Basal LH level is a valuable predictor of central gonadal activation states in girls, and can be used as an early screening index for CPP.

目的 通过对2013年2月-2018年1月在济宁医学院附属医院诊治,来自鲁西南地区的195例矮小症儿童行外周血染色体核型检查,分析矮小症的遗传病因.方法 对年龄3 ～16岁的195例矮小症儿童,培养外周血淋巴细胞行染色体核型分析.结果 在195例染色体核型中,异常染色体核型25例,占12.8％.其中染色体多态性8例,包括染色体缢痕1例、随体增加1例、异染色质区增加3例、臂间倒位2例及平衡易位1例;性染色体异常16例,包括Turner综合征14例,45,X/46,X,del(Y)核型1例,Y染色体长度变异1例;性反转1例(46,XY女性).结论 染色体异常是引起儿童矮小症的主要原因之一,常规遗传学检查可为部分矮小儿童明确病因,为临床诊疗提供科学依据.

Objective To study single nucleotide polymorphisms of COL11A2 gene in the growth plate and identify the correlation with the growth hormone deficiency (GHD).Methods Using the MALDI-TOF MS methods,the COL11A2 gene single nucleotide polymorphism loci (SNP) genotyping were detected in 229 cases of GHD children and 314 children with normal control group.And then the differences between the two groups with the SNP loci genotype frequency and allele frequency and genotype distribution of explicit and implicit model frequency were analyzed.Results The COL11A2 gene loci rs9368758 was associated with the occurrence of GHD (P=0.012).The allele of G in rs9368758 gene loci was a risk factor for GHD,the risk of GHD which would increase 1.71 times (P=0.02,OR=1.71.95 ％CI=1.11～2.65).The allele of A was a protection factors for GHD,which would reduce the risk of GHD in 0.63 times (P=0.02,OR=0.63,95％CI=0.43～0.92).Conclutions There is a correlation between COL11A2 gene loci rs9368758 and GHD.The allele of G in rs9368758 gene loci are GHD susceptible factors of the disease.A allele is GHD protective factors of the disease,which carriers are not easy to suffer from GHD.

目的 系统评价矮小症患儿生长激素受体外显子3多态性与重组人生长激素疗效的相关性.方法 计算机检索Pubmed、EMbase、The CNKI、CBM、The Cochrane Library等中英文数据库,搜集有关应用重组人生长激素治疗生长激素缺乏症、特发性矮小症、Turner综合征、小儿胎龄儿的相关文献.根据Cochrane系统评价方法,进行文献资料收集、质量评价、数据提取,最后采用Revman 5.3软件以及stata12.0软件进行Meta分析.结果 最终纳入1 7篇文献,Meta分析结果显示:rhGH治疗1年后,d3-GHR基因型身高生长速度明显高于GHRf1型,(MD=-0.75,95％CI(-0.96,-0.55),P＜0.00001);而d3-GHR基因型身高标准差积分也同样高于GHRf1基因型(MD=-0.10SDS,95％CI(-0.18,-0.01),P=0.04).结论 在短期治疗中,d3-GHR基因型与rhGH助长效应具有一定相关性.

目的 探讨可溶性鸟苷酸环化酶激活剂Cinaciguat对2型糖尿病大鼠血管并发症的干预作用.方法 雄性SD大鼠28只,8只采用普通饲料喂养者为对照组,20只高脂饲料喂养4周后给予小剂量链脲佐菌素腹腔注射制备2型糖尿病大鼠模型,16只大鼠造模成功并随机分为模型组和干预组各8只.继续饲养12周,干预组给予Cinaciguat 7 μg/(kg·d)腹腔注射,模型组和对照组大鼠给予等量质量分数0.1％ DMSO腹腔注射,疗程均为2周.测定各组大鼠血清空腹血糖、糖化血红蛋白、碱性磷酸酶、钙、磷、一氧化氮和一氧化氮合酶水平,并对胸主动脉行组织病理学检查.结果 模型组大鼠血清碱性磷酸酶活性[(886.63±527.08)u/L]明显高于干预组[(564.17±475.89)u/L]和对照组[(139.00±32.29)u/L],干预组高于对照组,差异有统计学意义(P＜0.01);模型组一氧化氮水平[(43.20±7.49)μmol/L]、一氧化氮合酶活性(12.23±2.32) u/mL]明显低于干预组[(49.18±8.38)μmol/L、(17.43±4.27)u/mL]和对照组[(62.23±10.04)μmol/L、(24.90±5.39)u/mL](P＜0.05),干预组低于对照组(P＜0.05);干预组和模型组空腹血糖[(24.89±4.79)、(24.60±4.42) mmol/L]及糖化血红蛋白[(11.38±0.61)％、(12.13±0.78)％]水平明显高于对照组[(5.02±0.65) mmol/L、(4.60±0.51)％](P＜0.01),模型组与干预组比较差异无统计学意义(P＞0.05);对照组、模型组与干预组大鼠血清钙[(1.75±0.17)、(1.89±0.50)、(1.97±0.52) mmol/L]和磷[(2.48±0.12)、(2.85±0.19)、(2.62±0.09) mmol/L]水平比较差异均无统计学意义(P＞0.05);组织病理检查结果显示对照组大鼠胸主动脉内膜连续、光滑,中膜平滑肌细胞走行清晰、无增生;模型组大鼠胸主动脉血管壁增厚,中膜平滑肌细胞增生且排列不规则;干预组大鼠胸主动脉壁较为完整、连续,中膜平滑肌细胞稍有增生,排列较规则,走行无明显异常.结论 Cinaciguat能有效改善2型糖尿病大鼠的抗氧化能力,为2型糖尿病血管并发症干预治疗提供了新思路和依据.

Objective To investigate the role of oxidative stress in the mechanism of diabetic peripheral neuropa-thy (DPN) and to analyze the risk factors for the development of DPN. Methods Fifty DPN patients and 27 patients diag-nosed with type 2 diabetes mellitus (T2DM) without DPN (NDPN) were enrolled into this study. The clinical data of pa-tients, including systolic pressure (SBP), diastolic pressure (DBP), body mass index (BMI), triglyceride (TG), total choles-terol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), Hemoglobin A1C (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPG), fasting C peptide (FC-P), 2-hour C peptide (2hC-P) were recorded and analyzed. Total antioxidant capacity (T-AOC), Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were examined to evaluate the level of oxidative stress. The risk factors with statistical significance were subjected to multiple Logistic regression analysis to screen for the risk factors for DPN. Results There was no signif-icant difference in sex, BMI, SBP, DBP, 2hPG, FC-P, TC, HDL-C, LDL-C, HbA1c, T-AOC between the 2 groups of pa-tients (P > 0.05), while age, duration of DM, FPG, TG, 2hC-P, SOD, MDA were statistically different (P < 0.05). By multi-factor Logistic regression analysis, age, TG, 2hC-P, MDA came into the regression equation;MDA and SOD cor-related with the TCSS score (P< 0.05). Conclusion Age, TG, 2hC-P, MDA levels are the independent risk factors for DPN, The decrease of SOD level and increase of MDA are interrelated with DPN, and the levels of SOD and MDA are as-sociated with the degree of functional nerve damage. Oxidative stress plays an important role in the pathogenesis of DPN.

目的观察二甲双胍对3T3-L1脂肪细胞瘦素、肿瘤坏死因子-α（TNF-α）表达与分泌量的影响,探讨二甲双胍降低体重、改善脂代谢的作用机制。方法 3T3-L1前脂肪细胞分化成熟后分别予不同浓度及作用时间的二甲双胍干预,采用RT-PCR法检测细胞内瘦素、TNF-αmRNA的表达,ELISA法测定培养基内瘦素、TNF-α的分泌量。结果二甲双胍抑制3T3-L1脂肪细胞瘦素、TNF-α的表达与分泌,呈时间与剂量依赖性。结论二甲双胍抗肥胖,改善脂代谢的作用可能与改善瘦素、TNF-α抵抗状态有关。

Objective To observe the effects of metformin on the expression and secretion of leptin and tumor necrosis factor(TNF-α) in 3T3-L1 adipocytes,and to explore its mechanism in anti-obesity and lipid metabolism improvement.Methods The 3T3-L1 preadipocytes were cultured and differentiated into adipocytes,then incubated with metformin at different concentrations and durations.Leptin and TNF-α mRNA expressions were assayed by RT-PCR.The supernate contents of leptin and TNF-α were detected by ELISA.Results Metformin functioned to inhibit the leptin and TNF-α mRNA expressions and secretions in 3T3-L1 adipocytes in a concentration-and time-dependent manner.Conclusion The function of metformin in anti-obesity and lipid metabolism improvement may be related with its improvement in leptin and TNF-α sensitivity.

目的 探讨乙型肝炎病毒HBV-DNA含量与血清标记物HBeAg、谷丙转氨酶(ALT)的相关性及其对肝病患者诊断、预后的意义.方法 采用酶联免疫吸附实验(ELISA)法检测523例乙肝患者血清学标记物(HBV-M),其血清学模型包括以下四种组合,A组:HBsAg(+)、HBeAg(+)、HBcAb(+)(大三阳);B组:HBsAg(+)、HBeAb(+)、HBcAb(+)(小三阳);C组HBsAg(+)、HBcAb(+);D组:HBsAb(+)、HBeAb(+)、HBcAb(+);并选取65例HBsAg(-)、HBsAb(-)HBeAg(-)、HBeAb(-)、HBcAb(+)正常人(E组)作为对照.实时荧光定量PCR(FQ-PCR)检测血清中HBV-DNA含量,同时采用酶法测定血清ALT水平.结果 A组HBV-DNA阳性率为92.55%,明显高于B组78.97%(x2=189.60,P<0.001)和C组50.98%(x2=234.15,P<0.001),A、D、C三组ALT水平均高于对照组(P<0.001,P<0.001,P<0.001);Log HBV-DNA与HBeAg S/CO之间存在正相关性(r=0.418,P<0.001),而ALT与Log HBV-DNA及HBeAg S/CO之间均无相关性.结论 HBV-DNA含量与乙肝病毒e抗原具有显著相关性,HBV-M和HBV-DNA定量检测并联合ALT水平对于临床乙肝病毒感染、复制及临床治疗有重要意义.