I型胶原吡啶交联终肽(ICTP)在骨肿瘤诊断中的临床研究

目的 检测良性骨肿瘤、恶性骨肿瘤患者及正常对照组血清中的I型胶原吡啶交联终肽(ICTP)活性，以评价ICTP在良恶性骨肿瘤诊断和鉴别诊断中的价值。方法 选取2005~2010年本院骨肿瘤科收治的78例恶性骨肿瘤患者，设为A组，其中49例为原发性恶性骨肿瘤、10例为继发性恶性骨肿瘤、19例为骨转移性肿瘤患者,另选43例良性骨肿瘤患者为B组，同时，设52例同龄正常人为C组，均采用酶免疫测定(EIA)方法测定他们血清中的ICTP活性。结果 B组患者血清ICTP活性为(6.75±3.34) μg/L，C组血清ICTP活性为(4.68±2.91) μg/L,A组患者血清ICTP活性为(14.84±8.49)μg/L，其中，原发性恶性骨肿瘤患者、继发性恶性骨肿瘤、骨转移性肿瘤患者的血清ICTP活性分别为(17.47±10.86)μg/L、(8.02±6.19) μg/L、(8.14±5.45) μg/L. A组中三类患者的血清ICTP活性与B组，C组相比差异均有统计学差异(P<0.05)，B组患者与C组相比差异无统计学差异(P>0.05)。而A组中原发性恶性骨肿瘤与继发性恶性骨肿瘤、骨转移性肿瘤组之间的差异也有统计学意义 (P<0.05)。结论 血清ICTP是反映骨肿瘤骨代谢的一个灵敏而简便的检测指标,并对良恶性骨肿瘤的诊断及鉴别诊断具有重要的临床意义。     

Effect of the menopause and hormone replacement therapy on the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen

We investigated the effect of the menopause and postmenopausal hormone replacement therapy (HRT) on the serum concentration of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), a potential new biochemical marker of bone resorption. A group of 44 healthy postmenopausal women, aged 45–54 years, had about 19% higher serum ICTP than did a group of 42 healthy premenopausal women aged 35–50 years (3.6±0.8 µg/l v 3.0±0.7 µg/l (mean ±SD);p<0.01), although there was a large overlap in the values. The 44 postmenopausal women also participated in a longitudinal clinical study, in which 20 received HRT and 24 received a placebo. Compared with the placebo group, those who received HRT had a significant (p<0.05) decrease in ICTP of about 12% at the end of 1 year of treatment, but again there was considerable overlap in the values. The menopause-and HRT-induced changes in ICTP were less than those seen in serum osteocalcin, serum total alkaline phosphatase, and fasting urinary excretion of hydroxyproline, calcium, pyridinoline and deoxypyridinoline. We conclude that the menopause increases and HRT decreases ICTP, although these changes are less pronounced than those seen in other biochemical markers of bone turnover.     

Paget's disease of bone affecting a single vertebra: Clinical,radiologic, and histopathologic correlations

Summary We report a 67-year-old man who presented with a 3-month history of progressively increasing pain in the lumbar spine. His past medical history was unremarkable, and physical examination disclosed local tenderness over the lower spine. No neurologic dysfunction was identified. Routine laboratory evaluation including alkaline phosphatase activity was normal. An X-ray film of the lumbar spine showed enlargement and increased density of L-5 vertebra. A wholebody bone scan revealed markedly increased uptake at the L-5 level. To further evaluate the nature of the disorder and the cause of his pain, a computed tomography (CT) scan was obtained. It disclosed multiple lucent areas with some sclerotic changes mainly affecting the vertebral body of L-5. No spinal stenosis was found. Subsequently, a bone biopsy of L-5 was performed that showed typical findings consistent with Paget's disease. The patient was treated with etidronate (200 mg b.i.d. for 6 months) followed by salmon calcitonin (50 IU 3 times/week s.c. for 6 months). The pain declined gradually in severity and the patient became symptom free after 12 months of treatment. A repeat X-ray film, obtained at that time, showed no significant change. However, a bone scan showed almost complete normalization. The present case illustrates that a high index of suspicion is required when only a single vertebra is affected by Paget's disease, especially, when alkaline phosphatase activity is normal. It may present with severe pain without evidence of neurologic dysfunction. CT scan may be a useful adjunct in establishing the diagnosis and elucidating the cause of pain.     

子宫内膜癌术后激素替代治疗对肿瘤预后的影响——一项小样本的配对研究

目的探讨子宫内膜癌术后激素替代治疗（HRT）对肿瘤预后的影响。方法收集1983年1月至2005年12月期间,北京协和医院收治的年龄小于50岁、手术绝经的子宫内膜癌患者76例,按照患者的年龄段、接受治疗年限,以1：2匹配研究组和对照组。共收集到术后行HRT的患者17例,设为研究组。匹配未接受HRT的患者34例,设为对照组。对上述51例患者的临床资料进行回顾性分析和统计学检验。结果研究组1例复发（5．9％）,对照组4例复发（11．8％）,两组间差异无统计学意义（P=0．654）。病例组无瘤缓解期（64．00±33．20）月,对照组（49．38±36．97）月,两组间差异无统计学意义（P=0．346）。多因素Cox回归模型分析,HRT不是患者术后复发的独立危险因素（P=0．338）。结论对于Ⅰ期子宫内膜癌患者术后行HRT未增加肿瘤的复发率。     

The effect of the menopause and hormone replacement therapy on serum carboxyterminal propeptide of type I collagen

We investigated the effect of the menopause and postmenopausal hormone replacement therapy on the serum concentration of carboxyterminal propeptide of type I procollagen (PICP), which is a biochemical marker of type I collagen synthesis. A group of 124 healthy postmenopausal women, aged 45–53 years, had about 20% higher serum PICP than did a group of 40 healthy premenopausal women aged 35–52 years (114±35 µg/1 vs. 95±26 µg/l (mean ± SD);p=0.002). The 124 postmenopausal women were also participating in a double-masked longitudinal study with two placebo groups and four different hormone replacement therapy groups. The four hormone regimens resulted in similar responses in serum PICP. Compared with placebo, 1 year of treatment with any of the four hormone replacement therapies significantly decreased serum PICP to premenopausal levels. We conclude that the formation of type I collagen is increased shortly after the menopause and that hormone replacement therapy reverses this increase.     

Significance of serum CrossLaps as a predictor of changes in bone mineral density during estrogen replacement therapy; comparison with serum carboxyterminal telopeptide of type I collagen and urinary deoxypyridinoline

The newly developed Elecsys -CrossLaps/serum assay measures C-terminal telopeptide of type I collagen and has thus been proposed as a reliable serum marker for bone resorption. We investigated its usefulness for monitoring the therapeutic effect of estrogen replacement therapy on bone turnover and bone mineral density (BMD) in patients with postmenopausal osteoporosis. Serum -CTx decreased by 43.2% ± 9.2% (mean ± SD), and 55.1% ± 7.0% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy (ERT), which was significantly greater than the respective value of urinary excretion of deoxypyridinoline (DPD) (27.8% ± 4.1%, 34.1% ± 4.9%, respectively) or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) assay (14.5% ± 4.1%, 13.1% ± 5.0%, respectively). The percent reduction in serum -CTx at 1, 3, and 6 months after initiation of ERT was significantly correlated in a negative manner with the percent increase in spinal BMD at 6 months. Further, ROC analysis to determine the significance of the percent change in bone resorption markers after 3 months of ERT in predicting the gain in spine BMD after 6 months suggested that serum -CTx and urinary DPD might provide a more discriminating indicator than serum ICTP. In conclusion, the findings suggest that the Elecsys -CrossLaps/serum assay provides a sensitive, and thus useful, tool for assessing bone resorption state in Japanese patients.     

Thirty Cases of Concurrent Paget's Disease and Primary Hyperparathyroidism: Sex Distribution, Histomorphometry, and Prediction of the Skeletal Response to Parathyroidectomy

Studies of the effect of parathyroidectomy (PTX) on bone turnover in patients with the combination of primary hyperparathyroidism (PHPT) and Paget's disease (PD) are largely limited to case reports. The etiology of the combination is disputed. We report 30 patients and their biochemical (n = 17) and histomorphometric (n = 4) responses to PTX in 18. All 18 patients except one had a post-PTX fall in plasma alkaline phosphatase (pAP). There was a significant positive correlation between the degree of post-PTX fall in pAP and both the preoperative plasma total corrected calcium (CaC) (P < 0.01) and serum ionized calcium (P < 0.05). For the patients with CaC levels >3.0 mmol/liter, the mean % fall in pAP was 68% of pretreatment (to 32%). For those with CaC levels ≥2.68 mmol/liter the fall in pAP was >18%. Of 12 literature cases treated by PTX and followed up, 11 had a postoperative fall in pAP (range 6–83%). Pretreatment bone biopsies (n = 6) could not be distinguished from uncomplicated PD. No significant histomorphometric changes were documented postoperatively in the four patients studied; however, % fibrotic surfaces declined in each of the four. Of the 18 patients, only one had radiologic subperiosteal erosions preoperatively; none had clinical tetany postoperatively—thus distinguishing this combination of diseases from severe PHPT bone disease—a situation easily biochemically confused with this combination. The sex distribution of 2.75:1 F/M in this series resembles reported ratios in pure PHPT of 2.37:1, unlike the ratios found in pure PD (0.49–1.01:1). The prevalence of PHPT in PD is 2.2–6.0% (mean 4.4%) in 1836 patients. In our series, 73% of patients with both diseases were females >60 years of age. In population studies >60 years, PHPT was present in 3% of women and 1% of men. Hypercalcemia in PD is frequently attributed to immobilization. As part of this study, we examined 184 patients referred with PD for the existence of, and cause of hypercalcemia. Of this group, 21 were hypercalcemic, 19 (90%) of whom had PHPT; none had immobilization hypercalcemia. In patients with both disorders, the indications for PTX should include the potential post-PTX improvement in pagetic biochemistry and symptoms. The sex distribution (resembling pure PHPT) and the similar prevalence of PHPT in Paget's, and in the elderly population, support the likelihood, in most cases, that these two common diseases are associated by chance. Received: 20 November 1998 / Accepted: 23 April 1999     

Clinical Observations with a New Specific Assay for Bone Alkaline Phosphatase: A Cross-Sectional Study in Osteoporotic and Pagetic Subjects and a Longitudinal Evaluation of the Response to Ovariectomy,Estrogens, and Bisphosphonates

The purpose of this study was to examine the serum levels of bone alkaline phosphatase (BALP) measured with a new assay in normal and in osteoporotic women, and to evaluate prospectively its responsiveness to changes of bone metabolism. The following groups of subjects were studied: (1) 95 healthy women (44–75 years) (22 pre- and 73 postmenopausal) and 35 osteoporotic women [vertebral bone mineral density (BMD) more than 2.5 SD below the normal adult mean]; (2) 10 women (44–50 years) ovariectomized (OVX) for benign uterine diseases, examined before and 12 months after surgery; (3) 16 OVX women (36–54 years), examined before and after 12 months of transdermal estrogen replacement therapy (50 μg/day); (4) 12 previously untreated pagetic patients (4 women and 8 men, 50–80 years), examined before and 3 months after the I.V. administration of clodronate (600 mg) or alendronate (5 mg) for 2 consecutive days. The median BALP value was 11.6 U/liter (25–75th percentiles: 10.5–12.7; range 7.7–19.3) in healthy premenopausal (PreMP) women and significantly higher (median: 16.8 U/liter; 25–75th percentile: 13.8–21.8; P < 0.01) in postmenopausal (PostMP) women. There was a clear age-related increase in normal subjects (r = 0.43; P < 0.001). In the osteoporotic group, BALP levels, as well as other biochemical parameters of bone turnover, were not significantly different from those of normal women when adjusted for age. In OVX women, BALP levels showed a marked increase 12 months after surgery (median: 113%; 25–75th percentile: 87–139%), significantly higher than the increase of total ALP (median: 43%; 25–75th percentile: 25–66%; P < 0.001), and similar to the increases of serum osteocalcin and urinary hydroxyproline. Transdermal estrogen treatment prevented the BALP increase, even if no reduction was observed; total ALP showed a similar behavior. The basal levels of BALP were significantly elevated in pagetic patients (median: 91 U/liter; range 18–610 U/liter) and correlated to the scintigraphic extent of the disease (r = 0.76; P < 0.01). Three months after the I.V. administration of bisphosphonates, the decrease of BALP was more marked than that of total ALP (median: −54% versus −41%; P < 0.05). In conclusion, these results suggest that BALP measurement with this immunoassay may be clinically useful, and more sensitive than total ALP, in the assessment of bone turnover during changes of the estrogen status as well as in monitoring the effects of treatments that modify the metabolic activity of the skeleton. Received: 25 January 1996 / Accepted: 3 May 1996     

Oncological validation of bone turnover markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) in patients with prostate cancer and bone metastases

BackgroundBone formation markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) were reported to be increased in patients with prostate cancer (PC) and bone metastases. The objective of the presented study was to investigate the utility of serum 1CTP and P1NP values in the diagnosis of bone metastases and in predicting oncological outcome in patients with PC.MethodsIn total, serum samples of 186 patients were included retrospectively including 53 (28.50%) benign prostatic hyperplasia (BPH) patients and 133 (71.50%) PC-patients. The group of patients with PC consisted of 58 patients with non-metastatic PC (cM0) (43.61%) and 70 (52.63%) patients with bone metastases (cM1b). Serum 1CTP and P1NP were measured by radioimmunoassay (RIA). Results were compared to clinical variables including oncologic follow-up data by univariate and multivariate analyses.ResultsMedian 1CTP concentrations were significantly higher in patients with PC compared to the BPH group [5.08 (range, 1.73–158.00) vs. 4.00 (range, 2.18–34.19) µg/L, P=0.019]. However, no significant difference of P1NP levels could be shown for these groups. With median values of 6.04 (1.73–158.00) and 3.91 µg/L (2.04–34.51) for 1CTP and 48.60 (9.12–1,074.37) and 33.90 (8.72–149.30) for P1NP both markers were altered in cM1b patients compared to cM0 patients (P=0.001 each). Furthermore, cancer-specific survival (CSS) and overall survival (OS) were significantly shorter in cM1b patients with higher 1CTP concentrations (P=0.037 and P=0.019, respectively), whereas no associations of P1NP and outcomes were observed.ConclusionsThe present study confirms that increased levels of 1CTP and P1NP concentrations are associated with presence of metastatic disease in the bone. Moreover, these markers are able to predict clinical course in PC patients with bone metastases. The potential use of these markers for treatment selection in advanced PC remains to be determined.     

Respiratory symptoms and dysphagia in patients with gastroesophageal reflux disease: a comparison of medical and surgical therapy

 Background: Gastroesophageal reflux disease (GERD) is a common condition and may frequently lead to dysphagia and respiratory symptoms. The aim of this study was to investigate the effects of medical and surgical therapy to control these symptoms. Methods: Eighty GERD patients with either dysphagia or respiratory symptoms were studied by means of a detailed symptom questionnaire, upper gastrointestinal endoscopy, esophageal manometry, 24-h esophageal pH monitoring and a barium esophagogram. All patients had been receiving medical therapy with proton-pump inhibitors and cisapride for 6 months. After withdrawal of medical therapy and relapse of GERD, 62 patients decided to undergo anti-reflux surgery (laparoscopic Nissen fundoplication in 19 and laparoscopic partial posterior fundoplication in 43 patients). Symptoms were assessed prior to treatment, at 6 months following medical therapy and 6 months after surgery. Results: Heartburn and esophagitis were effectively treated by medical and surgical therapy. Dysphagia was improved in all patients following surgery but only in 27% of patients following medical therapy. Improvement of respiratory symptoms was found in 86% of patients following surgery but only in 14% following medical therapy. Improvement of regurgitation was registered only following surgical therapy. Conclusions: Since medical treatment is likely to fail in GERD patients with complex symptoms such as dysphagia, regurgitation and respiratory symptoms, the need for surgery arises in these patients and may be the only successful treatment in the long term. Received: 5 March 1999 Accepted: 7 July 1999     

Effect of early risedronate treatment on bone mineral density and bone turnover markers after liver transplantation: a prospective single‐center study

The aim of this study was to investigate the effect of risedronate (RIS) on bone loss and bone turnover markers after liver transplantation (LT). Patients with osteopenia or osteoporosis within the first month after LT were randomized to receive RIS 35 mg/week plus calcium 1000 mg/day and vitamin D₃ 800 IU/day (n = 45) or calcium and vitamin D₃ at same dosages (n = 44). Primary endpoint was change in bone mineral density (BMD) 6 and 12 months after LT. Secondary endpoints included changes in serum β‐CrossLaps (β‐CTX) and procollagen type 1 amino‐terminal peptide (P1NP) and fracture rate. Spine X‐rays were obtained at baseline and after 12 months. There was no significant difference in BMD changes between both treatment groups at any sites; either at 6 or 12 months. Spine BMD increased in both groups at 12 months vs. baseline (P = 0.001). RIS patients had a significant increase in intertrochanteric BMD at 12 months (P < 0.05 vs. baseline). Serum β‐CTX decreased in both groups (P < 0.01), with significant differences between groups at 3 months. No significant difference in vertebral fracture incidence was found. After 12 months, BMD improved at lumbar spine and did not change at hip in both groups. Significant differences between both groups were not found. Other factors (calcium and vitamin D replacement, early prednisone withdrawal) seem to have also positive effects in BMD.     

Effect of surgical stress on endogenous morphine and cytokine levels in the plasma after laparoscopoic or open cholecystectomy

Background: Endogenous morphine in the brain leads to various biological responses after surgery. The aim of this study was to determine whether morphine levels in the plasma would be enhanced by open laparotomy rather than by laparoscopic procedures. Methods: We compared 19 patients who underwent laparoscopic cholecystectomy with five patients who underwent resection of the gallbladder by open laparotomy. Morphine levels in the plasma were measured by an electrochemical detection system. Results: Postoperative endogenous morphine levels were higher with open laparotomy than with the laparoscopic technique (three h after surgery: open, 200 ± 52.6 fmol/ml vs laparoscopy, 17.6 ± 3.7, p < 0.01). This morphine elevation accounted for higher levels of cytokine, greater pain scores, and longer duration of fasting in open laparotomized patients than in laparoscopic cholecystectomy patients. Stress hormone levels in the plasma were also higher with open laparotomy than with laparoscopy. Conclusion: Morphine synthesis was enhanced by open laparotomy, resulting in greater biological response postoperatively than that seen with laparoscopic cholecystectomy. Received: 21 October 1998/Accepted: 3 April 1999     

Effects of skeletal loading on bone mass and compensation mechanism in bone: a new insight into the "mechanostat" theory

 We have suggested that: (i) osteocalcin carboxylation is related to bone material properties (bone quality), and (ii) impairment of bone material properties could be compensated by bone mass increase. The aim of the present prospective study was to investigate whether the effects of skeletal loading on bone mass were associated with the compensation mechanism between bone mass and bone material properties. The subjects were 56 healthy female volunteers aged around 50 years. They were classified into pre- and postmenopausal groups, and each group was then subdivided into a no-exercise (control) and a vertical jumping exercise group. Bone mineral density (BMD) was measured at baseline and after the 6-month study period. Urinary γ-carboxyglutamate (Gla), a possible parameter of osteocalcin carboxylation, was also measured at baseline. Among the premenopausal women, hip BMD in the exercise group increased significantly in comparison to the control value. Among the postmenopausal women, however, there was no significant difference in the BMD change between the control and the exercise group. In addition, the baseline urinary Gla level showed an inverse correlation with the change in whole body BMD in the premenopausal exercise group. These results suggest that: (i) estrogen plays a certain role in the high-impact exercise-induced bone gain, and (ii) the effects of skeletal loading on bone mass are involved in the compensation mechanism, i.e., bone gain due to high-impact exercise becomes greater in accordance with the degree of deterioration in bone material properties. Our concept of the compensation mechanism could provide a new insight into the understanding of the skeleton's adaptability to load-bearing. Received: April 16, 2001 / Accepted: February 8, 2002     

Paget’s disease of bone: benefits of neridronate as a first treatment and in cases of relapse after clodronate

This study assessed the efficacy of 200 mg of aminohexane bisphosphonate (neridronate) administered by intravenous infusion in a single dose or in two separate doses on consecutive days in 32 patients (16 males and 16 females, average age 66 years) affected by active Paget’s disease of bone. Fifteen patients had never been treated with any antiresorptive agent and 17 had had unsatisfactory results from a prior clodronate treatment. All of the latter patients had failed to enter a remission stage (i.e., normalization of bone turnover was not reported at any time during treatment) and had had a full relapse within 6 months after clodronate infusion. In the present study bone-specific alkaline phosphatase (bAp), deoxypyridinoline (dPyr), and N- and C-terminal polypeptide of collagen type 1 (Ntx, Ctx) were determined before neridronate administration and at 1, 3, 6, and 12 months thereafter. Basal values of bAp were 51.7 ± 2.3 μg/L, range 31.7–92.5 (normal range 6.2–23.6). No statistical differences in markers of bone turnover were evident in the basal state between new pagetic patients (bAp = 55.1 ± 4.1) and those suffering a relapse after clodronate (bAp = 48.8 ± 2.6). Neridronate induced an average percent change from baseline in excess bAp of 68.0 ± 4.3 and in excess dPyr, Ntx, and Ctx of 68.1 ± 11, 60.6 ± 8.5, and 86.7 ± 7.8, respectively. Markers of bone resorption declined more slowly in patients treated previously with clodronate, although the average change in percent decrement from baseline in excess bAp as well as in excess of bone resorption markers was not different from that registered in untreated pagetic patients. Response to treatment, defined as a percent decrement from baseline in excess bAp of 50% or more at any time during the 12-month follow-up, was observed in 27 patients (84.4%). Remission (a drop in bAp to within normal range) was achieved in 21 patients (65.6%) and was maintained in 12 at 12-month follow-up, with no significant differences between either 1- or 2-day infusions, or between new pagetic patients and those relapsing after clodronate. In 15 of 21 patients requiring analgesics to alleviate bone pain, pain was reduced or completely alleviated in 8. A slight, short-lived acute phase reaction (fever and/or arthromyalgia) occurred in 6 patients. To summarize, 200 mg of intravenous neridronate, in one or two doses, significantly reduced the biochemical indices of disease activity in the majority of patients, showing a normalization of bAp in more than 60%. We conclude that neridronate can be used safely in the treatment of patients with Paget’s disease of bone either as a first bisphosphonate treatment or as retreatment for patients relapsing after clodronate.     

Effect of surgical versus medical therapy on estimated cardiovascular event risk among adolescents with type 2 diabetes and severe obesity

BackgroundCardiovascular disease (CVD) remains the leading cause of mortality in type 2 diabetes (T2D). Better interventions are needed to mitigate the high lifetime risk for CVD in youth T2D.ObjectiveTo compare 30-year risk for CVD events in 2 cohorts of adolescents with T2D and severe obesity undergoing medical or surgical treatment of T2D.SettingLongitudinal multicenter studies at University hospitals.MethodsA secondary analysis of data collected from the participants with T2D enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n = 30) and participants of similar age and racial distribution from the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY, n = 63) studies was performed. Teen-LABS participants underwent metabolic bariatric surgery (MBS). TODAY participants were randomized to metformin alone or in combination with rosiglitazone or intensive lifestyle intervention, with insulin therapy given for glycemic progression. A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome, assessed at baseline (preoperatively for Teen-LABS), 1 year, and 5 years of follow-up.ResultsParticipants with T2D from Teen-LABS (n = 30; mean ± SD age = 16.9 ± 1.3 yr; 70% female; 60% white; body mass index (BMI) = 54.4 ± 9.5 kg/m²) and TODAY (n = 63; 15.3 ± 1.3 yr; 56% female; 71% white; BMI 40.5 ± 4.9 kg/m²) were compared. The likelihood of CVD events was higher in Teen-LABS versus TODAY at baseline (17.66 [1.59] versus 12.11 [.79]%, adjusted P = .002). One year after MBS, event risk was significantly lower in Teen-LABS versus TODAY (6.79 [1.33] versus 13.64 [0.96]%, adjusted P < .0001), and sustained at 5 years follow-up (adjusted P < .0001).ConclusionDespite higher pretreatment risk for CVD events, treatment with MBS resulted in a reduction in estimated CVD event risks, whereas medical therapy associated with an increase in risk among adolescents with T2D and severe obesity.     

目标导向液体治疗对缺血型烟雾病患者脑血管重建术后谵妄的影响

目的探讨目标导向液体治疗对缺血型烟雾病患者脑血管重建术后谵妄(POD)的影响。方法择期行颞浅动脉-大脑中动脉分支吻合术的缺血型烟雾病患者40例,男24例,女16例,年龄18～59岁,BMI 18.5～24.0 kg/m~2,ASAⅡ或Ⅲ级,Suzuki分期≥3,MMSE评分24分。采用随机数字表法将其分为两组(n=20):常规补液组(R组)和目标导向液体治疗组(G组)。R组采用常规4-2-1补液原则,维持CVP 5～10 cmH_2O;G组采用目标导向液体治疗,维持每搏量变异度(SVV)10%。两组维持MAP波动幅度在基础值20%以内,MAP下降幅度超过基础值20%以上时,静脉注射麻黄碱6～10 mg或输注去甲肾上腺素0.01～0.03μg·kg~(-1)·min~(-1)。记录麻醉诱导前即刻(T_0)、血管阻断前10 min(T_1)、阻断后10 min(T_2)、血管开放后10 min(T_3)时的局部脑氧饱和度(rSO_2)、MAP、HR、BIS值、鼻咽温。于T_1—T_3时采集动脉血样1 ml,行血气分析,并测定Hct和PaCO_2。于术后3 d,采用CAM量表评估患者POD的发生情况。结果两组不同时点MAP、HR、鼻咽温、BIS值、Hct和PaCO_2差异无统计学意义;与T_0时比较,T_1—T_3时G组患者两侧rSO_2明显升高,T_3时R组患侧rSO_2明显升高(P0.05);与R组比较,T_1—T_3时G组患者两侧rSO_2明显升高(P0.05)。与R组比较,G组患者补液量明显减少,POD发生率明显降低(P0.05)。结论目标导向液体治疗可降低缺血型烟雾病患者脑血管重建术后POD的发生率,其机制可能与改善rSO_2有关。     

重骨颗粒对强直性脊柱炎患者疾病活动及骨代谢的影响

目的 观察重骨颗粒对强直性脊柱炎(ankylosing spondylitis, AS)患者疾病活动及骨代谢的影响。方法 将84例AS患者随机分成对照组和观察组,每组42例。对照组予以基础治疗,口服柳氮磺吡啶片联合塞来昔布胶囊,观察组在对照组的基础上加重骨颗粒口服,疗程均为12周。观察治疗前后巴氏AS疾病活动度指数(BASDAI)、AS疾病活动度评分(ASDAS)、巴氏AS功能指数(BASFI)和中医症状评分的变化,检测治疗前后C反应蛋白(C-reactive protein, CRP)、红细胞沉降率(erythrocyte sedimentation rate, ESR)、抑炎因子[白介素10(IL-10)]、促炎因子[白介素1β(IL-1β)、白介素17(IL-17)]、骨代谢指标[骨特异性碱性磷酸酶(BALP)、血清β胶原降解产物(β-CTX)、I型前胶原氨基末端肽(PINP)]水平。结果 两组均无脱落病例,治疗后观察组ASAS20达标率83.33%,显著优于对照组的64.29%(χ²=3.941,P<0.05);ASAS50达标率为71.43%,显著...     

Effect of essential trace metal on bone metabolism in the femoral-metaphyseal tissues of rats with skeletal unloading: Comparison with zinc-chelating dipeptide

The effect of essential trace metals on bone metabolism was investigated in the femoral-metaphyseal tissues obtained from skeletal-unloaded rats. Skeletal unloading was designed by using the model of hindlimb suspension in rats; the animals were fed for 4 days with the unloading. Femoral-metaphyseal tissues were cultured for 24 hours in a medium containing either vehicle (control), nickel, manganese, cobalt, copper, zinc, or zinc-chelating dipeptide (ß-alanyl-L-histidinato zinc; AHZ) in the concentration range of 10^-6 to 1(T^-4 M. Bone biochemical components (alkaline phosphatase activity, glucose consumption, and DNA content) were significantly decreased by skeletal unloading. The presence of zinc sulfate or AHZ (10~5 and 10^-4 M) caused a significant increase of alkaline phosphatase activity in the bone tissues from unloaded rats. This effect was not seen by nickel, manganese, cobalt and copper (10^-6 to 10⁴ M). The culture medium glucose was clearly consumed by the bone tissues. This consumption was inhibited by nickel, manganese, or copper (10^-5 and 10^-4 M), while cobalt, zinc, and AHZ had no effect. DNA content in the bone tissues from unloaded rats was significantly increased by all metal compounds (10^-5 M). The effect of AHZ on bone components was greater than zinc sulfate. The AHZ (10^-5 M)-increased alkaline phosphatase activity in the bone tissues from unloaded rats was clearly blocked by the presence of cycloheximide (10^-6 M), staurosporine (10^-T7 M), dibucaine (10^-4 M), or okadaic acid (10⁷ M). The present study demonstrates that, of various essential trace metals, zinc compounds have an unique anabolic effect on bone metabolism in the femoral-metaphyseal tissues of rats with skeletal unloading. Zinc-chelating dipeptide may stimulate bone protein synthesis through the mechanism that is involved in protein kinases.     

The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized,double-blind,placebo-controlled trial

We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 g transdermal 17-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D₃. L₁–L₄ spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.     

Effect of type I collagen on the adhesion, proliferation, and osteoblastic gene expression of bone marrow-derived mesenchymal stem cells

tificially synthesizedpolymericproductssuchaspolylactide (PLA ) ,polyglycolide (PGA ) ,andtheircopolymersarefrequently usedtissueengineeringmatrixsubstitutivematerials .Unfortunately ,theirapplicationisseriouslyrestrictedfortheirpoorhydrophilicproperty ,weakcelladsorptionforces ,anddifficultyininteractionwithcells .1,2 ThisstudyintendstoevaluatethecapacityofcollagenIinpromotingadhesion ,proliferation ,anddifferentiationofMSCs ,tolayanexperimentalbasisforbonytissueengineering .METHODSPrep…