月经周期中内源性大麻素与性激素和促性腺激素的相关性研究分析

目的分析月经周期中不同时期正常女性血浆中N-花生四烯酸氨基乙醇(AEA)的水平变化及其与性激素和促性腺激素的相关性。方法选择2015年5~10月因输卵管梗阻或男方因素到本院生殖医学科就诊并欲行IVF助孕、月经周期和排卵正常的育龄妇女为研究对象。根据实验目的分为横断面研究组(79例)和纵向研究组(10例),检测AEA在两组女性月经周期中不同时期的变化,以及AEA与FSH、LH、E2、P之间的相关性。结果横断面研究组中早卵泡期、晚卵泡期、排卵期和黄体期AEA水平分别为(9.71±0.86)ng/ml、(10.61±1.05)ng/ml、(12.24±0.73)ng/ml和(7.46±0.71)ng/ml。排卵期AEA水平最高,黄体期最低(P0.05)。纵向研究组4个时期AEA水平分别(8.76±0.91)ng/ml、(11.61±1.28)ng/ml、(13.85±1.18)ng/ml、(8.50±1.08)ng/ml,排卵期AEA水平最高,黄体期最低(P0.05)。横断面研究组和纵向研究组各个时期的AEA水平比较均无显著性差异(P0.05)。AEA与FSH、LH、E2之间存在显著的正相关(P0.05),与P水平则无显著相关性(P=0.067)。结论正常女性血浆内AEA的浓度随月经周期的变化而变化,且与性激素和促性腺激素呈明显相关。但AEA与FSH、LH、E2、P之间的具体作用机制,有待进一步研究。     

2型糖尿病患者绝经期骨密度与甲状旁腺素、雌激素相关性研究

目的 观察2型糖尿病妇女绝经期骨密度与甲状旁腺素、雌激素相关性研究.方法 测定绝经期2型糖尿病妇女伴骨质疏松（A）组及绝经期2型糖尿病妇女无骨质疏松（B）组的左侧髋部股骨颈、大转子、华氏三角区、及腰椎L2～L4正侧位的骨密度和血清中骨代谢指标,如：骨钙素、碱性磷酸酶、钙、磷、甲状旁腺素、雌二醇、Ⅰ型胶原羧基末端终肽（β-CTx）的浓度,对骨密度与多个变量之间的关系进行相关分析,并对（A）组血清中的甲状旁腺素、雌二醇、骨钙素、β-CTx与不同部位的骨密度之间的关系进行多元逐步回归分析.结果绝经期2型糖尿病妇女（B）组的腰椎、大转子、华氏三角区、股骨颈等骨密度指标明显低于对照组（A）（P＜0.05）;2型糖尿病绝经期妇女血清中雌二醇水平与腰椎L2～L4骨密度呈正相关（P＜0.032）;甲状旁腺素水平与股骨颈骨密度呈负相关（P＜0.034）.结论 绝经期2型糖尿病患者甲状旁腺素和雌激素水平与骨密度密切相关,分别可以用于预测骨质疏松发生的不同部位.     

肾移植后血清白细胞介素2、可溶性白细胞介素2受体和白细胞介素6的监测

动态监测６０例肾移植患者术后２个月内血清白细胞介素２（ＩＬ－２）、可溶性ＩＬ－２受体（ｓＩＬ－２Ｒ）和白细胞介素６（ＩＬ－６）的变化。结果发现发生急性排斥反应时，上述细胞因子的升高较临床诊断提早数天，并且显著高于环孢素Ａ肾中毒组；对甲泼尼龙敏感的排斥反应，抗排斥治疗数天后上述因子下降到排斥前水平。提示肾移植术后动态监测患者血清ＩＬ－２、ｓＩＬ－２Ｒ和ＩＬ－６有助于急性排斥反应的早期诊断、鉴别诊断、及时治疗和甲泼尼龙抗排斥的疗效评价。     

Renal segmental tubular response to salt during the normal menstrual cycle

BACKGROUND: It has been suggested that women gain weight and develop peripheral edema during the luteal phase of the menstrual cycle because they tend to retain sodium and water. However, there is actually no clear evidence for physiological, cyclic variations in renal sodium handling during the menstrual cycle. We prospectively assessed the changes in segmental renal sodium handling occurring during the menstrual cycle in response to changes in salt intake. METHODS: Thirty-five normotensive women were enrolled. Seventeen women were randomized and studied in the follicular and 18 in the luteal phases of their menstrual cycle. All women were assigned at random to receive a low (40 mmol/day) or a high (250 mmol/day) sodium diet for seven days on two consecutive menstrual cycles. Renal sodium handling and hemodynamics were measured at the end of each diet period. RESULTS: The changes in sodium intake induced comparable variations in sodium excretion in both phases of the menstrual cycle. In the follicular phase, the increase in salt intake was associated with no change in renal hemodynamics, an increased fractional excretion of lithium (FELi) and a decreased fractional distal reabsorption of sodium (FDRNa), suggesting that sodium reabsorption is reduced both in the proximal and the distal tubules. In contrast, in the luteal phase, the renal response to salt was characterized by a significant renal vasodilation and a marked salt escape from the distal nephron, compared to the women investigated in the follicular phase (P < 0.01). Sodium reabsorption by the proximal nephron was not reduced as indicated by the unchanged FELi. CONCLUSIONS: These results show that the segmental renal handling of sodium differs markedly in the two phases of the menstrual cycle. They suggest that the female hormones modulate the renal handling of sodium at the proximal and distal segments of the nephron in young normotensive women.     

Urinary glycosaminoglycan excretion during the menstrual cycle in normal young women

PURPOSE: We investigated whether the menstrual cycle affects urinary glycosaminoglycan (GAG) excretion in normal young women. MATERIALS AND METHODS: Urine samples from 10 healthy women 19 to 21 years old were collected daily during the whole menstrual cycle. Concentration of total urinary GAG was assessed as mug hexuronic acid per mg creatinine. Proportions of sulfated GAG species were determined by agarose gel electrophoresis. RESULTS: Mean excretion values +/- SD for period days 4 to 13 and 15 to 28 of the cycle were significantly different (0.445 +/- 0.041 vs 0.356 +/- 0.035 microg/mg, p <0.001). Correlation between values for the first and second halves of the cycle showed that this difference was consistent irrespective of individual variations in GAG excretion (r = 0.9757, p <0.001). Proportions of urinary sulfated GAG did not change during the cycle. CONCLUSIONS: Excretion of total urinary GAG during the normal menstrual cycle of young women has a biphasic pattern with significantly higher values occurring in the first half of the cycle. This variation implies modulation by estrogens and consequently it should be considered when comparing the GAG concentration in urine samples from women of childbearing age.     

骨桥蛋白在人正常月经周期子宫内膜的表达

目的研究骨桥蛋白(osteopontin,OPN)在人正常月经周期子宫内膜的表达。方法采用免疫组织化学法对51例人正常月经周期子宫内膜OPN蛋白质进行定位和定量检测,Western blotting法测定增殖期及分泌期OPN蛋白水平,采用逆转录-聚合酶链反应(RT-PCR)方法检测18例人正常月经周期子宫内膜增殖期及分泌期OPN mRNA的表达。结果OPN蛋白质主要分布在正常子宫内膜腺上皮细胞,增殖早期、中期无表达,增殖晚期出现,分泌中期、晚期表达最强。月经期子宫内膜腺上皮细胞表达较强。OPN mRNA表达分泌期强于增殖期(P<0.05)。Western blotting检测结果显示正常子宫内膜组织中存在OPN蛋白,分泌期含量较高。结论OPN蛋白质及mRNA在正常子宫内膜中的表达呈现明显周期依赖性。分泌中、晚期表达增强提示其可能参与胚胎着床。     

正常月经周期中内皮素变化规律的研究

目的 :探讨健康育龄妇女正常月经周期中血浆及子宫内膜内皮素 ( ET)的变化 ,ET和卵巢甾体激素的相关性。方法 :对 3 8名正常月经周期妇女分别于增殖早、中期 ,分泌中、晚期 ,取 4次静脉血 ,应用放射免疫方法测定血浆 ET、雌激素 ( E2 )、孕激素 ( P)含量 ,其中 2 7名妇女选择某一期 ,采血同时取内膜测定子宫内膜 ET含量。结果 :正常月经周期各阶段血浆 ET水平无明显差异。子宫内膜组织 ET,分泌中、晚期 ( 3 .90± 1 .3 0 pg/mg)显著高于增殖早、中期 ( 2 .76± 1 .2 5 pg/mg) ( P<0 .0 5 )。无论是血浆 ET还是子宫内膜组织 ET均与雌、孕激素之间无明显相关性。结论 :子宫内膜中的 ET可能通过自分泌和 (或 )旁分泌机制参与子宫出血的调节 ,并与月经的始动有关。     

正常月经周期子宫内膜瘦素和瘦素受体的表达

目的　探讨瘦素和瘦素受体系统在正常月经周期子宫内膜表达特点及其意义。　方法　应用免疫组织化学方法检测 60例正常月经周期子宫内膜瘦素和瘦素长受体蛋白的表达。原位杂交技术测定 2 5例子宫内膜瘦素和瘦素长受体mRNA。　结果　瘦素蛋白在子宫内膜腺体和间质呈阳性或强阳性表达 ,月经周期各期间无显著差异 ;瘦素长受体蛋白在子宫内膜间质中呈弱阳性或阴性表达 ,月经周期各期间无显著差异 ;瘦素长受体蛋白在子宫内膜腺体的表达分泌期显著高于增殖期 (P <0 .0 0 1 )。瘦素和瘦素长受体mRNA在增殖期和分泌期子宫内膜的腺体和间质中均呈阳性表达。　结论　瘦素长受体蛋白在分泌期子宫内膜腺体表达增强 ,有可能在孕卵着床过程中发挥作用     

层粘连蛋白、纤粘连蛋白、IV型胶原在人月经周期子宫内膜中的表达

目的　研究细胞外基质蛋白层粘连蛋白 (LN)、纤粘连蛋白 (FN)和IV型胶原 (IVCL)在正常人月经周期子宫内膜中的表达。　方法　采用免疫组织化学方法检测 4 9例正常月经周期子宫内膜中LN、FN、IVCL蛋白的表达。　结果　LN主要分布于腺上皮及腔上皮基底膜 ,分泌中期表达最强。FN主要分布于间质 ,腔上皮及腺上皮基底膜也均有表达 ,分泌中期含量丰富。IVCL在腺上皮基底膜的表达分泌中期最强 ,在间质的表达分泌早期最强 ,分泌中、晚期表达逐渐减弱。LN、FN、IVCL在血管基底膜上均有表达 ,无周期性变化。　结论　LN、FN、IVCL在月经周期子宫内膜中的表达随月经周期而变化。     

Human myeloma cells promote the recruitment of osteoblast precursors: mediation by interleukin-6 and soluble interleukin-6 receptor.

Multiple myeloma is associated with the development of osteolytic bone disease characterized by a disruption to normal bone resorption and bone formation. Although studies have shown that myeloma cells produce factors that promote bone resorption little data are available examining the mechanism of decreased bone formation or the factors that mediate this effect. In the present study we describe a novel in vitro coculture system in which to investigate the effect of myeloma cells on osteoblast recruitment and differentiation. Under appropriate conditions mesenchymal stem cells were shown to differentiate into colonies of cells, a proportion of which show characteristics of osteoblasts, in that they express alkaline phosphatase activity and stain positively for collagen and calcium. The addition of the human myeloma cells JJN-3, RPMI-8226, or NCI-H929 to these cultures stimulated a significant increase in the total number of colonies (p < 0.005) and the proportion of osteoblastic colonies (p < 0.005). Media conditioned by these cells also were able to promote the formation of both total and osteoblastic colonies (p < 0.005). The addition of an antibody against the interleukin-6 receptor (IL-6R) blocked myeloma cell and myeloma cell-conditioned media induced osteoblast recruitment (p < 0.01). Furthermore, media conditioned by myeloma cells incubated with phorbol ester, which promotes IL-6R shedding, or a metalloproteinase inhibitor, which inhibits IL-6R shedding, were able to stimulate (p < 0.005) and inhibit osteoblast recruitment (p < 0.005), respectively. In addition, soluble IL-6R (sIL-6R) and IL-6 together, but not alone, were able to promote osteoblastic colony formation (p < 0.01). Taken together these data show that myeloma cells promote osteoblast recruitment by release of sIL-6R from myeloma cells.     

Normalization of intraoperative parathyroid hormone does not predict normal postoperative parathyroid hormone levels

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values. METHODS: Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals. RESULTS: Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values. CONCLUSIONS: Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.     

Angiogenesis of Uterus during menstrual cycle

ＡｎｇｉｏｇｅｎｅｓｉｓｏｆｕｔｅｒｕｓｄｕｒｉｎｇｍｅｎｓｔｒｕａｌｃｙｃｌｅＷａｎｇＪｉｅｄｏｎｇ（王介东）ＩｎｔｒｏｄｕｃｔｉｏｎＡｎｇｉｏｇｅｎｅｓｉｓ，ｔｈｅｆｏｒｍａｔｉｏｎｏｆｎｅｗｃａｐｉｌ－ｌａｒｉｅｓｆｒｏｍｅｘｉｓｔｉｎｇｂｌｏ...     

Plasma soluble interleukin-2 receptor levels during and after upper abdominal surgery

Soluble interleukin-2 (IL-2) receptor (sIL-2R) is reported to be up-regulated in inflammatory disorders. Although sIL-2R may modulate perioperative inflammatory responses, it remains unclear whether upper abdominal surgery affects plasma sIL-2R levels. We evaluated the influence of major abdominal surgery on plasma sIL-2R levels. Ten patients scheduled for upper abdominal surgery received anaesthesia with isoflurane, nitrous oxide, and epidural block. Plasma sIL-2R and IL-6 levels were determined at pre-anaesthesia, 0, 2, and 4 hours during surgery, and on postoperative days 1 (POD1) and 3 (POD3). The plasma levels of sIL-2R decreased significantly and achieved their minimum value at 4 hours (677.0 +/- 125.3 pg/ml, P < 0.01 compared to pre-anaesthesia value; 924.5 +/- 178.8 pg/ml, 95% confidence interval = 122.2-550.4). The plasma sIL-2R levels increased on POD1 (1336.5 +/- 174.0 pg/ml) and POD3 (1629.0 +/- 262.8 pg/ml), and reached a level significantly higher than the baseline (P < 0.05 and P < 0.001, 95% confidence interval = 93.4-730.6 and 402.8-1006.2, respectively). The plasma sIL-2R levels on POD3 significantly correlated with the peak IL-6 levels (r = 0.67, P < 0.05). The plasma sIL-2R levels on POD3 correlated with the amount of intraoperative bleeding (r = 0.66, P < 0.05). In conclusion, we found that major abdominal surgery induces characteristic changes in plasma soluble IL-2 receptor levels.     

甲状旁腺素联合雌二醇对大鼠骨质疏松的影响

目的探讨甲状旁腺素联合雌二醇对骨质疏松的影响及其作用机制,为临床用药提供理论依据。方法选取100只雌性SD大鼠随机分为5组:假手术组、去势组、甲状旁腺素组、雌二醇组、联合用药组,每组20只。首先构建去卵巢大鼠骨质疏松性动物模型,然后分别进行骨组织骨密度(bone mineral density,BMD)测定、骨代谢相关生化指标检测、骨代谢标志物检测、骨形态结构变化观察。结果去势组腰椎和股骨BMD、股骨最大载荷和刚度及血清Ca、P水平均较假手术组显著降低(P0. 05),而联合用药组上述指标均较去势组显著增高(P0. 05)。去势组血清ALP、COL-I、OC、OPG水平均较假手术组显著增高(P0. 05),而联合用药组上述指标均较去势组显著降低(P0. 05)。去势组骨小梁少见,细小稀疏,小梁间断裂分离,排列疏松紊乱;而联合用药组骨组织结构较完整,骨小梁形态结构较规整,数量多,致密均匀,连续性好呈网状。结论甲状旁腺素联合雌二醇可调节维持骨质疏松性骨代谢,增加骨密度,改善生物力学性能和骨组织病理形态学,促进骨形成,抑制骨吸收,具有骨保护作用。     

Hyperphosphatemia modestly retards parathyroid hormone suppression during calcitriol-induced hypercalcemia in normal and azotemic rats

BACKGROUND/AIMS: In in vitro studies, a high phosphate concentration has been shown to directly stimulate parathyroid hormone (PTH) secretion in a normal calcium concentration and to reduce PTH suppression in a high calcium concentration. In hemodialysis patients during dialysis-induced hypercalcemia, the effect of hyperphosphatemia on PTH secretion was less than in vitro studies. Our goal was to determine whether hyperphosphatemia retards PTH suppression during calcitriol-induced hypercalcemia in azotemic rats with hyperparathyroidism. METHODS: Rats underwent a two-stage 5/6 nephrectomy or sham operations. After surgery, rats received a high phosphate diet (P 1.2%, Ca 0.6%) for 4 weeks to induce hyperparathyroidism and then were placed on a normal diet (P 0.6%, Ca 0.6%) for two additional weeks to normalize serum calcium values in azotemic rats. At week 7, rats were divided into five groups and before sacrifice received at 24-hour intervals, three doses of calcitriol (CTR) or its vehicle. The five groups and dietary phosphate content were: group 1--normal renal function (NRF) + 0.6% P + vehicle; group 2--NRF + 0.6% P + CTR; group 3--renal failure (RF) + 0.6% P + vehicle; group 4--RF + 1.2% P + CTR; and group 5--RF + 0.6% P + CTR. RESULTS: In the two CTR-treated groups with marked hypercalcemia (groups 2 and 5), 15.52 +/- 0.26 and 15.12 +/- 0.13 mg/dl, respectively, stepwise regression showed that hyperphosphatemia retarded PTH suppression. When the two azotemic groups treated with CTR (groups 4 and 5) were combined to expand the range of serum calcium values, stepwise regression showed that hypercalcemia suppressed and hyperphosphatemia modestly retarded PTH suppression. Similarly, in groups 4 and 5 combined, correlations were present between PTH and both serum calcium (r = -0.70, p < 0.001) and serum phosphate (r = 0.64, p = 0.001). CONCLUSIONS: Hypercalcemia and high doses of calcitriol markedly reduced PTH secretion in azotemic rats despite severe hyperphosphatemia. Even though hyperphosphatemia did retard PTH suppression during hypercalcemia, its effect was small.     

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study

Background

To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease.

Methods

PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome).

Results

Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5–86.6%), median intravesical pressure at maximal capacity was 30 cmH₂O (range 10–107 cmH₂O), and median compliance was 3.93 ml/cmH₂O (range 0.05–30.3 ml/cmH₂O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases.

Conclusions

Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.     

IL-18及IL-18结合蛋白在人正常月经周期子宫内膜的表达

目的探讨白细胞介素(IL)18及IL18结合蛋白(IL18BP)在人正常月经周期子宫内膜上的表达。方法取因子宫肌瘤或子宫脱垂行全子宫切除术的患者子宫内膜,按月经周期和子宫内膜形态学检查结果分为增生期和分泌期2组,每组10例。免疫组织化学法检测子宫内膜的IL-18及IL-18BP表达;实时定量聚合酶连锁反应(qRT-PCR)检测子宫内膜IL-18及IL-18BP mRNA的表达。结果 IL-18、IL-18BP在人增生期和分泌期子宫内膜中均有表达,且随着月经周期其表达呈现时空性变化。IL18在增生期表达于腔上皮、腺上皮细胞膜及基质细胞,与增生期相比,分泌期基质细胞IL18的阳性表达显著降低(MOD值0.33±0.07 vs.0.52±0.12,P0.05),而IL18BP的表达则显著增加(MOD值0.33±0.20 vs.0.10±0.07,P0.05)。qRT-PCR结果显示,在增生期和分泌期子宫内膜标本均有IL18和IL18BP mRNA表达,与增生期相比,分泌期IL18表达显著下降(P0.05),IL18BP表达显著增强(P0.05),IL18BP/IL18比值显著增高(P0.05)。结论 IL18和IL18BP在整个月经周期人子宫内膜上均有表达,且其表达呈现时空性的变化,可能与月经周期过程中子宫内膜的崩解修复有关。