Effects of low intensity vibration on bone and muscle in rats with spinal cord injury

Summary

Spinal cord injury (SCI) causes rapid and marked bone loss. The present study demonstrates that low-intensity vibration (LIV) improves selected biomarkers of bone turnover and gene expression and reduces osteoclastogenesis, suggesting that LIV may be expected to benefit to bone mass, resorption, and formation after SCI.

Introduction

Sublesional bone is rapidly and extensively lost following spinal cord injury (SCI). Low-intensity vibration (LIV) has been suggested to reduce loss of bone in children with disabilities and osteoporotic women, but its efficacy in SCI-related bone loss has not been tested. The purpose of this study was to characterize effects of LIV on bone and bone cells in an animal model of SCI.

Methods

The effects of LIV initiated 28 days after SCI and provided for 15 min twice daily 5 days each week for 35 days were examined in female rats with moderate severity contusion injury of the mid-thoracic spinal cord.

Results

Bone mineral density (BMD) of the distal femur and proximal tibia declined by 5 % and was not altered by LIV. Serum osteocalcin was reduced after SCI by 20 % and was increased by LIV to a level similar to that of control animals. The osteoclastogenic potential of bone marrow precursors was increased after SCI by twofold and associated with 30 % elevation in serum CTX. LIV reduced the osteoclastogenic potential of marrow precursors by 70 % but did not alter serum CTX. LIV completely reversed the twofold elevation in messenger RNA (mRNA) levels for SOST and the 40 % reduction in Runx2 mRNA in bone marrow stromal cells resulting from SCI.

Conclusion

The findings demonstrate an ability of LIV to improve selected biomarkers of bone turnover and gene expression and to reduce osteoclastogenesis. The study indicates a possibility that LIV initiated earlier after SCI and/or continued for a longer duration would increase bone mass.     

超声实时组织弹性成像诊断颈动脉易损斑块

目的探讨超声实时组织弹性成像(RTE)技术对颈动脉易损斑块的诊断价值。方法选取缺血性脑血管病患者60例,对颈动脉斑块进行超声弹性成像;采用Itoh 5分法对斑块RTE图像进行评分,并与颈动脉内膜切除术(CEA)术后病理学检查进行对照分析。结果超声弹性图彩色编码显示斑块脂质坏死核心为绿色,纤维为蓝色,钙化为蓝白色,出血/血栓为绿色、红绿色相间、蓝绿色相间。60例中,纤维斑块12例,粥样斑块24例,斑块内出血/血栓9例,复杂斑块15例。弹性成像诊断易损斑块的敏感度、特异度、准确率分别为93.75%(45/48)、83.33%(10/12)、91.67%(55/60),阳性预测值、阴性预测值分别为95.74%(45/47)、76.92%(10/13),阳性似然比、阴性似然比分别为5.62、0.075。结论超声弹性成像技术对颈动脉易损斑块有较好的诊断价值。     

The effect of renal function on surgical outcomes of intracapsular hip fractures with osteosynthesis

Background

Chronic kidney disease (CKD) affects many physiologic systems, including bone quality, nutrition, and cardiovascular condition. Femoral neck fractures in patients on dialysis are associated with frequent complications and a high risk of mortality. However, the effect of CKD on clinical outcomes of patients with hip fractures treated with osteosynthesis remains unclear.

Methods

One hundred and thirty patients with 130 femoral neck fractures treated with internal fixation were divided into two groups and the data were then analyzed. Group 1 consisted of 98 patients (98 hip fractures) with normal renal function (estimated glomerular filtration rate, or eGFR, ≥60 ml/min/1.73 m²). Group 2 was composed of 32 patients (32 hip fractures) with CKD (eGFR <60 ml/min/1.73 m²) without dialysis. Clinical outcomes as well as early and late complications were recorded for each group. Survivorship analysis was performed, and the mortality and complication rates for the groups were then compared.

Results

In Group 1, 32 complications (32.6 %) occurred in 98 hips, including 5 cases of nonunion and 16 cases of osteonecrosis. In Group 2, 24 complications (75 %) developed in 32 hips; these included 8 cases of nonunion and 3 cases of osteonecrosis. The mean duration of follow-up was 32 months. The overall mortality rate was 11.5 %. No difference was noted in early, late, or overall mortality rate between two groups. Patient with CKD had a higher nonunion rate (OR = 5.9, P = 0.023). Meanwhile, CKD and displaced fracture pattern were independent predictors for revision surgery (OR = 3.0, P = 0.032; OR = 6.9, P = 0.001, respectively).

Conclusions

Osteosynthesis is a safe and effective treatment for femoral neck fractures; however, patients with femoral neck fracture and CKD have a higher risk of nonunion and subsequent surgical revision.

Level of relevance

Prognostic studies, Level III.     

Significance of mTOR Signaling and Its Inhibitor Against Cancer Stem-Like Cells in Colorectal Cancer

Purpose

To determine the role of the mammalian target of rapamycin (mTOR) signaling in sustaining cancer stem-like cells and its clinical values in colorectal cancer (CRC).

Methods

mTOR expression in CRC patients was analyzed by immunohistochemistry and survival analysis was used to confirm the clinical value of mTOR. Colorectal cell lines were treated by mTOR inhibitors rapamycin and PP242, and sphere formation assay and aldehyde dehydrogenase (ALDH) assay were utilized to determine the impact of mTOR inhibition in CRC stem-like cells, combined or not combined with chemotherapeutic drug (fluorouracil and oxaliplatin).

Results

mTOR expression was associated with outcomes of CRC patients and predicted poor prognosis in stage II CRC patients. mTOR signaling was activated in stem-like colorectal cancer cells, and mTOR inhibitors (rapamycin and PP242) decreased the capacity of sphere formation as well as ALDH activity. Furthermore, mTOR inhibitors also were demonstrated to suppress the stimulation of stem-like cells by chemotherapy.

Conclusions

mTOR shared predictive significance in stage II CRC patients’ outcomes and played a vital role in the maintenance of colorectal cancer stem-like cells. mTOR inhibitors might hold the potential to become a therapeutic target against CRC stem cells.     

选择性三野淋巴结清扫术治疗胸段食管鳞癌的临床研究

目的分析行选择性三野淋巴结清扫术对胸段食管鳞癌患者的预后影响。 方法2009年6月至2012年9月,四川省肿瘤医院对127例胸段食管癌患者根据肿瘤的位置、外侵程度、术前颈部超声检查结果,进行选择性三野淋巴结清扫。全组共127例患者,其中上段49例;中段67例;下段11例;Ⅰ期2例,Ⅱ期26例,Ⅲ期99例。 结果127例患者共清扫淋巴结4963枚,平均每例清扫淋巴结39.3枚;手术时间(325.6±9.3)min,出血量(316.0±18.7)ml。术后76例患者发生并发症,发生率为59.8%(76/127)病死率为1.6%(2/127)。选择性三野淋巴结清扫术后喉返神经旁淋巴结转移率40.2%(51/127);颈部淋巴结转移率55.9%(71/127),其中,胸中下段食管鳞癌颈部淋巴结转移与喉返神经转移显著相关(χ²＝0.005,P＝0.006)。全组中位生存时间(35.0±1.9)个月,3年生存率51.8%。其中Ⅱ期中位生存时间(42.1±3.4)个月,3年生存率74.5%;Ⅲ期生存时间(32.3±2.0)个月,3年生存率44.8%,两组间比较差异有统计学意义(χ²＝3.940,P＝0.047)。颈部淋巴结阳性患者的中位生存时间(26.2±2.1)个月,3年生存率34.9%;阴性患者中位生存时间(41.5±2.3)个月,3年生存率67.6%,差异有统计学意义(χ²＝15.283,P<0.001)。 结论选择性三野淋巴结清扫术是一种安全可行、可提高颈部淋巴结清扫率,同时又能筛选出潜在获益患者、延长生存的手术方式。     

DNA Methylation Profiling Identifies EYA4 Gene as a Prognostic Molecular Marker in Hepatocellular Carcinoma

Background

DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values.

Materials and Methods

DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene.

Results

Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P < 0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P < 0.050).

Conclusions

EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.     

Preoperative Aspartate Aminotransferase to Platelet Ratio is an Independent Prognostic Factor for Hepatitis B-Induced Hepatocellular Carcinoma After Hepatic Resection

Background

There is conflicting evidence concerning platelet status and hepatocellular carcinoma (HCC) prognosis. We evaluated the prognostic value of platelet-based indices, including platelet count, platelet/lymphocyte ratio (PLR), and aspartate aminotransferase to platelet ratio index (APRI) in HCC after hepatic resection.

Methods

We retrospectively reviewed 332 patients with HCC treated with hepatectomy between 2006 and 2009. Preoperative platelet count, as well as demographic, clinical, and pathologic data, were analyzed.

Results

Both disease-free survival (DFS) and overall survival (OS) were significantly improved for patients with low platelet count, PLR, and APRI compared to patients with elevated values. On multivariate analysis, APRI, tumor size ≥5 cm, noncapsulation, and multiple tumors were all associated with both poor DFS and OS. The 1-, 3-, and 5-year DFS rates were 52, 36, and 32 % for patients with APRI <0.62 and were 35, 22, and 19 % for patients with APRI ≥0.62. Correspondingly, the 1-, 3-, and 5-year OS rates were 77, 51, and 42, and 63, 35, and 29 % for both groups. Both DFS and OS of patients with APRI <0.62 were significantly better compared to patients with an elevated APRI (P = 0.009 and 0.002, respectively). Patients with elevated APRI tended to have cirrhosis, hepatitis B virus (HBV) infection, surgical margin <1 cm, and noncapsulated tumors.

Conclusions

Elevated platelets based inflammatory indices, especially APRI, was associated with adverse characteristic features and poor prognosis in HCC, especially for patients with HBV infection or cirrhosis. Antiplatelet treatment may represent a potential therapy for HBV-induced HCC recurrence.     

The role of rosiglitazone in the proliferation of vascular smooth muscle cells after experimental subarachnoid hemorrhage

Background

Recent evidence has demonstrated that rosiglitazone can attenuate cerebral vasospasm following subarachnoid hemorrhage (SAH). Some studies have shown that rosiglitazone can suppress inflammation and immune responses after SAH. However, the precise molecular mechanisms by which cerebral vasospasm is attenuated is not clear.

Methods

In this study, SAH was created using a “double hemorrhage” injection rat model. Rats were randomly divided into three groups and treated with saline (control group), untreated (SAH group), or treated with rosiglitazone. Using immunocytochemistry, hematoxylin and eosin (HE) staining, and measurement of the basilar artery, we investigated the formation of pathologic changes in the basilar artery, measured the expression of caveolin-1 and proliferating cell nuclear antigen (PCNA), and investigated the role of rosiglitazone in vascular smooth muscle cell (VSMC) proliferation in the basilar artery after SAH.

Results

In this study, we observed significant pathologic changes in the basilar artery after experimental SAH. The level of vasospasm gradually increased with time during the 1st week, peaked on day 7, and almost recovered on day 14. After rosiglitazone treatment, the level of vasospasm was significantly attenuated in comparison with the SAH group. Immunocytochemistry staining showed that caveolin-1 expression was significantly increased in the rosiglitazone group, compared with the SAH group. Inversely, the expression of PCNA showed a notable decrease after rosiglitazone treatment.

Conclusions

The results indicate that rosiglitazone can attenuate cerebral vasospasm following SAH. Up-regulation of caveolin-1 by rosiglitazone may be a new molecular mechanism for this response, which is to inhibit proliferation of VSMCs after SAH, and this study may provide a novel insight to prevent delayed cerebral vasospasm (DCVS).     

新型腰椎经皮椎弓根螺钉植入定位方法及其对放射暴露剂量的影响

 目的 探讨新型腰椎微创定位方法在定位时间、次数及放射暴露剂量方面的优势。方法 2010年5 月至2013年2 月收治腰椎间盘突出症合并腰椎不稳及胸腰椎骨折121例,随机分为两组：68例采用传统定位方法植入经皮椎弓根螺钉,单节段病变41例、双节段病变27例;53例采用自行研制的腰椎微创定位系统,单节段病变34例、双节段病变19例。两组患者性别、年龄、病程、手术节段的差异无统计学意义。结果 传统定位方法组、微创定位方法组术前定位时间分别为（8.26±3.44） min、（3.51±1.82） min,平均定位次数分别为3.57次、1.22次,准确率分别为60.8%及96.2%。两组单节段病变患者植入双枚经皮椎弓根螺钉,术中定位时间分别为（15.12±4.69） min、（5.51±1.32） min,定位次数分别为6.47次、2.45次;双节段病变患者植入三枚经皮椎弓根螺钉,术中定位时间分别为（24.91±7.43） min、（8.84±2.32） min,定位次数分别为11.72次、3.69次。传统定位方法组手术人员颈部、胸部及手腕部检测出的放射暴露剂量分别为（3.09±0.24） Gy、（4.23±0.71） Gy、（5.17±0.62） Gy,微创定位方法组分别为（1.38±0.47） Gy、（2.69±0.33） Gy、（3.21±1.05） Gy。两组定位时间、定位次数及放射暴露剂量的差异有统计学意义。结论 腰椎微创定位系统及定位方法能够简化手术操作,具有定位准确性高、定位时间短、透视次数少、医护人员及患者接受X线射线暴露量低的优点。     

人股骨头坏死微观结构及成骨、破骨细胞活性的区域性分布特征

 目的 比较人股骨头坏死标本不同区域的骨微观结构及成、破骨细胞活性。方法 收集2011年3月至2013年5月行全髋关节置换的非创伤性股骨头坏死患者术后的股骨头标本10例（Ficat Ⅳ期）,男6例,女4例;年龄40～57岁,平均47.7岁。Micro-CT扫描后,根据影像学识别骨质密度不同,将每个标本分为软骨下骨区、坏死区、硬化区、健康区,通过病理学检测、纳米压痕、实时荧光定量PCR、免疫组化染色等方法对不同区域的骨微观结构、微观力学性能及成骨、破骨细胞活性进行比较。结果 Micro-CT结果显示,股骨头坏死标本软骨下骨区及坏死区的骨小梁连续性破坏;硬化区的骨小梁数目增多,间隙变窄;正常区域骨小梁结构完整,厚度分布均匀。软骨下骨区、坏死区、硬化区和健康区骨小梁的弹性模量分别为（13.808±4.22） GPa、（13.999±3.816） GPa、（17.266±3.533） GPa和（11.927±1.743） GPa;硬度分别为（0.425±0.173） GPa、（0.331±0.173） GPa、（0.661±0.208） GPa和（0.423±0.088） GPa。抗酒石酸酸性磷酸酶（Trap）染色结果显示,软骨下骨区和坏死区可见Trap染色阳性细胞,硬化区及健康区未见Trap染色阳性细胞。免疫组化染色结果显示,骨形成相关因子Runx2和BMP2在硬化区及健康区表达高于其他区域;骨吸收相关因子RANK和RANKL在软骨下骨区及坏死区表达高于其他区域。结论 股骨头坏死塌陷过程中,骨微观结构发生明显改变,而坏死区骨小梁微观力学强度较健康区无显著降低。股骨头坏死标本中软骨下骨区及坏死区破骨细胞活性增强,硬化区成骨细胞活性增强。