Tumor necrosis factor alpha suppresses osteogenic differentiation of MSCs by inhibiting semaphorin 3B via Wnt/β-catenin signaling in estrogen-deficiency induced osteoporosis

The proinflammatory cytokines, especially tumor necrosis factor alpha (TNF-α), have been shown to inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and bone formation in estrogen-deficiency-induced osteoporosis, but the mechanisms of TNF-α impaired bone formation remain poorly understood. Semaphorins have been shown to regulate cell growth, cell migration, and cell differentiation in a variety of tissues, including bone tissue. Here, we identified a novel mechanism whereby TNF-α, suppressing Semaphorin3B expression contributes to estrogen-deficiency-induced osteoporosis. In this study, we found that TNF-α could decrease Semaphorin3B expression in osteogenic differentiation of MSCs. Overexpression of Semaphorin3B in MSCs attenuated the inhibitory effects of TNF-α on MSCs proliferation and osteoblastic differentiation. Mechanistically, activation of the Wnt/β-catenin signaling markedly rescued TNF-α-inhibited Semaphorin3B expression, suggesting that Wnt/β-catenin signaling was involved in the regulation of Semaphorin3B expression by TNF-α. Taken together, our results revealed a novel function for Semaphorin3B and suggested that suppressed Semaphorin3B may contribute to impaired bone formation by elevated TNF-α in estrogen-deficiency-induced osteoporosis. This study may indicate a therapeutic target gene of Semaphorin3B for osteoporosis.     

Preoperative neutrophil-to-lymphocyte ratio is a more valuable prognostic factor than platelet-to-lymphocyte ratio for nonmetastatic rectal cancer

Several combinations of inflammatory factors, including neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been reported to be prognostic factors in various malignant tumors, including colorectal cancer (CRC). The aim of this study was to evaluate the prognostic value of NLR and PLR for patients with rectal cancer (RC) who underwent curative surgery. Data from patients who underwent curative resection for RC were retrospectively reviewed. The cutoff for NLR and PLR was defined as 2.3 and 144 by receiver operating characteristic (ROC) curve. Overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier method. Multivariable Cox regression model was used to evaluate the independent prognostic significance of variables. A total of 140 patients were eligible in the study. High NLR (> 2.3) and high PLR (> 144) both predicted lower OS and DFS according to Kaplan-Meier method. But in the multivariable Cox regression model, only the high NLR retained significance for reduced OS and DFS. According to Chi-square test, patients with higher NLR had larger tumor size and higher pN-stage. While PLR was only associated with the pN-stage. High preoperative NLR was shown to be a negative independent prognostic factor in patients undergoing resection for nonmetastatic RC. It may be helpful as a factor to guide the postoperative therapies.     

Safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density: a meta-analysis

Purpose: The aim of this meta-analysis was to assess the safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density (BMD). Methods: Safety of denosumab was compared with placebo or bisphosphonates. A systematic literature search without language restriction was conducted up to January, 2014. The RevMan 5.1 software was used for statistical analysis. Results: A total of 11 English literatures were eventually identified. The pooled data in the overall analysis revealed that there was no significant difference when compared denosumab with placebo or bisphosphonates in any adverse events (AAE) (RR=0.99, 95% CI=0.98-1.01, p=0.29), serious adverse event (SAE) (RR=1.05, 95% CI=0.98-1.13, p=0.18), neoplasm/cancer (RR=1.14, 95% CI=0.95-1.37, p=0.16) and deaths (RR=0.77, 95% CI=0.57-1.04, p=0.09). However, significant differences were found when compared denosumab with placebo or bisphosphonates in SAE related to infection (RR=1.23, 95% CI=1.00-1.52, p=0.05) and non-vertebral fracture (RR=0.86, 95% CI=0.74-1.00, p=0.05). Subgroup analysis was performed by the type of drugs which was used in the control group. The results of subgroup analysis did not demonstrate the differences between denosumab and bisphosphonates in SAE related to infection (RR=1.13, 95% CI=0.63-2.03) and non-vertebral fracture (RR=1.31, 95% CI=0.87-1.98). Conclusions: Compared to placebo, denosumab treatment significantly decreased the risk of non-vertebral fracture but increased the risk of SAE related to infection in the postmenopausal women with osteoporosis or low BMD. However, no difference between the safety of denosumab and bisphosphonates was found.     

足跟再造术长期疗效观察

目的 研究应用组织移植一期重建全足跟及足跟大部缺损的方法及远期功能效果。方法 用小腿外侧复合瓣逆行带血管移植一期再造足跟,即用对折的腓骨代替跟骨,小腿外侧皮瓣修复足跟部皮肤缺损,吻合腓肠神经外侧支与近侧皮神经重建足跟感觉功能,携带部分肌肉充填缺损并恢复足跟部饱满外形。结果 4例全足跟缺损,8例部分足跟缺损修复全部成功。经过2－13年随访（平均5年2个月）,再造足跟不仅功能恢复良好,其组织结构也发生了适应性变化,移植腓骨逐渐“跟骨化”,皮肤受力处出现胼胝,足跟部皮肤两点辨别觉达到0．8－3.0cm,所有病例均参加体力劳动,按综合功能评价标准优11例,良1例。结论 用小腱外侧复合瓣一期移植再造足跟不仅足跟部各种组织都可以得到修复,而且经过术后长期适应和功能锻炼,骨骼皮肤等组织结构可以改变,功能越来越满意。     

Bryan cervical disc prostheses: preservation of function over time

Preserving the function of cervical disc prostheses, even over the short term, is a matter of concern among surgeons. Our case series highlights our results and protocol for increasing the probability of continued device function. Twenty-five consecutive patients with a mean (±SEM) age of 44.3 ± 8.3 years underwent 29 cervical total disc arthroplasties for disc herniations. Three patients underwent primary bilevel arthroplasty, and one patient underwent a second arthroplasty for another herniation 2 years after the first. Prosthesis ranges of motion were measured using dynamic plain X-ray studies and compared to the ranges of motion of adjacent segments. At follow-up, all prostheses were in the correct location and without subsidence. All displayed firm secondary stability. One segment had fused. Twenty-eight of 29 devices were mobile an average of 9.5° ± 4.7° (range 3° to 20°) (for all 29 devices the average movement angle was 9.2° ± 5°; range 0° to 20°), 25 upper adjacent segments were mobile an average of 10.9° ± 4.5° (range 2° to 20°) (excluding the fused prosthesis: 11° ± 4.6°) and 15 lower adjacent segments were mobile an average of 9.8° ± 6° (range 1° to 21°). With our protocol, 28 of 29 cervical disc prostheses in 25 consecutive patients were mobile after an average of 22.3 ± 9.4 months. Prosthesis motion was physiological and very similar to that of the healthy adjacent segments. Long-term studies including larger numbers of patients are required to validate our initial observations.     

The CYP1B1 Leu432Val polymorphism and risk of urinary system cancers

The cytochrome P450 1B1 (CYP1B1) gene plays a key role in the metabolism of various carcinogens. The CYP1B1 Leu432Val polymorphism leads to leucine to valine substitution at codon 432. A lot of studies have shown that the CYP1B1 Leu432Val polymorphism was associated with urinary system cancers, especially prostate cancer. However, the results were still inconclusive. In this meta-analysis, by searching online databases and references of related reviews, we identified 17 eligible studies to assess the relationship between CYP1B1 Leu432Val polymorphism and urinary system cancers, including 7,783 cancer cases and 7,238 controls. By pooling all eligible studies, we found that the CYP1B1 Leu432Val polymorphism was not associated with overall urinary system cancers. However, in subgroup analyses, we found that the variant 432Val allele significantly increased the risk of prostate cancer (Val vs. Leu, odds ratio (OR)?=?1.064, 95 % confidence interval (CI) 0.981–1.154; P _{heterogeneity}?=?0.002), while no association was found for bladder cancer (Val vs. Leu, OR?=?0.942, 95 % CI 0.853–1.041; P _{heterogeneity}?=?0.504). No evidence of publication bias was found (Begg’s test, P?=?0.053; Egger’s test, P?=?0.073). In conclusion, based on 17 eligible studies, we found that the CYP1B1 Leu432Val polymorphism was associated with an increased risk of prostate cancer, while no association of bladder cancer was observed.     

Successful management of a childhood osteosarcoma with epiphysiolysis and distraction osteogenesis

In an 11-year-old boy with osteosarcoma in the proximal tibia (type iii), 2 cycles of dia chemotherapy (cisplatin, ifosfamide, doxorubicin) were administered preoperatively while epiphysiolysis was performed. Clinical response was determined to be complete by radiography and histopathology. Marginal excision was then performed with preservation of the proximal tibial epiphysis. Metaphyseal reconstruction was performed using distraction osteogenesis. Six cycles of dia chemotherapy were administered postoperatively. Twenty months later, the patient had developed no complications and experienced full bone healing, with no limb discrepancy.In selected adolescent patients with osteosarcoma, in whom the tumour is in full contact with the epiphysis, epiphyseal preservation by epiphysiolysis and reconstruction by distraction osteogenesis can provide an excellent outcome, resulting in a stable reconstruction that functionally restores the native limb.     

邻近逆行穿支带蒂双皮瓣修复足部贯通伤

摘 要:［目的］探讨以邻近逆行带蒂双皮瓣修复足部贯通伤的治疗方法及临床疗效。［方法］2010年1月至2014年7月,收治并获得随访的9例足部贯通伤患者,伤足均有不同程度的两侧软组织缺损,早期彻底清创、止血,大量液体冲洗下负压封闭引流覆盖创面,择期以邻近逆行带蒂腓肠神经营养血管皮瓣和内踝上皮瓣一次性修复两侧皮肤软组织缺损。［结果］术后2例皮瓣边缘坏死,分别经换药和植皮后成活;1例外侧皮瓣创口长时间渗出,经换药引流,4周后愈合。余患者皮瓣均顺利成活,供区创面Ⅰ期愈合。9例均获随访,患者对其外形、色泽、厚度可接受。［结论］邻近穿支带蒂双皮瓣是修复足部贯通伤的有效方法,围手术期处理使污染创面变成相对清洁创面是皮瓣成功的基础条件,合理选择、设计皮瓣,深筋膜充分填塞创腔是治疗成功的关键。     

Early hypothermia as risk factor in severely burned patients: A retrospective outcome study

IntroductionBurn trauma-related hypothermia is a frequent observation but risk factors and impact on patient related outcome are ambiguously reported. It is expected that hypothermia is associated with increased mortality and reduced overall outcome in severely burned patients, but available evidence is limited.MethodsThis retrospective single-center-study reviewed preclinical service protocols and medical records of patients sustaining a burn with a total body surface area (TBSA) ≥15% from 2008 to 2012. General patient and burn specific characteristics, outcome parameters as well as body temperature at admission measured via urine catheter or nasal temperature probe were recorded and statistically analyzed comparing normothermic (≥36 °C), mild hypothermic (<36 °C) and severely hypothermic (<34.5 °C) patients. Chi-square test was performed to demonstrate impact of hypothermia on primary outcome parameters and to reveal risk factors for developing hypothermia. To assess independent influences on mortality, a multivariate logistic regression analysis was performed.ResultsOut of 300 patients matching inclusion criteria, a sufficient record of temperature was found in 144 patients (48%). Out of 141 eligible patients with an average burn extent (SD) of 33.38% (24.5%) TBSA, 31.9% (n = 45) suffered from severe hypothermia (<34.5 °C) and 28.4% (n = 40) showed mild hypothermia. Total burn extent, presence of full thickness burns, presence of inhalation injury, preclinical mechanical ventilation and administration of sedative drugs were risk factors for developing hypothermia. Patients’ age, total burn extent and presence of full thickness burns could be identified as independent factor for mortality. Although a trend towards an independent positive influence of normothermia at admission on mortality was seen, it was not statistically significant.ConclusionIncidental hypothermia of burned patients is associated with an increased mortality and needs to be addressed by emergency health care providers and immediately at the burn center. Especially patients with extensive burns, full-thickness burns, inhalation injury or patients undergoing preclinical intubation are at risk for hypothermia and benefit from any measures for temperature preserving.     

非扩髓带锁髓内钉固定联合皮瓣修复治疗ⅢB型胫骨开放性骨折

目的探讨一期治疗ⅢB型胫骨开放性骨折的方法。方法自1999年2月～2002年2月收治16例ⅢB型胫骨开放性骨折患者,年龄19～47岁,平均27岁。皮肤软组织缺损面积为4.5cm×3cm～14cm×6cm。术前预防性使用抗生素,进行彻底清创,用非扩髓带锁髓内钉固定骨折,皮瓣或肌皮瓣转移(移植)覆盖创面。对4例伴骨缺损的患者采用自体髂骨进行植骨。结果随访6～14个月,平均9个月。所有皮瓣均成活,未出现深部感染。14例骨折在6个月内愈合,有2例在术后10个月内愈合。按Johner-Wruch标准判定功能恢复结果,优14例,良2例。结论非扩髓带锁髓内钉固定联合皮瓣修复治疗ⅢB型胫骨开放性骨折效果较好。