High-repetition cyclic loading is a risk factor for a lumbar disorder

Epidemiological data suggest that prolonged exposure to cyclic lumbar flexion elicits a chronic neuromuscular disorder and disability in workers. This study provides a physiological and biomechanical assessment of various repetitions of cyclic lumbar flexion sessions as a risk factor for development of an acute neuromuscular disorder. An in vivo feline model was subjected to 10 minutes of cyclic (0.25-HZ) loading, followed by a 10-minute rest period, repeated three times in one experimental group, six times in a second group, and nine times in the third group, followed by rest for 7 hours. Displacement of the lumbar viscoelastic tissue and reflex electromyographic (EMG) activity from the lumbar multifidus muscle were monitored. Creep developed and accumulated during each load/rest period and partially recovered during the subsequent rest. Loading periods were characterized by a decrease in reflex EMG activity with superimposed spasms. In the 7-hour recovery period, initial hyperexcitability was present in all groups, whereas only the six- and nine-repetition groups displayed significant delayed hyperexcitability, indicating the presence of acute inflammation. The mathematical model developed fit the data reasonably well, as the R2 values were generally near 0.90. It was concluded that the resulting delayed muscular hyperexcitability constitutes an acute neuromuscular disorder associated with exposure to many repetitions of cyclic lumbar flexion. The acute disorder can become chronic if not allowed sufficient rest to resolve itself. Workers engaged in cyclic lumbar flexion (e.g., loading/unloading, assembly workers) should avoid long-term exposure in order to prevent the development of a chronic neuromuscular condition known as cumulative trauma disorder.     

高亲和力IgE-he受体介导IgE合至郎格罕细胞

正常人表皮郎格罕细胞(LC)能特异性结合IgiJ,这种结合能被针对高亲和力IgE-Fc受体(FcERI)单克隆抗体(mAb)15-1完全阻断.然而,抗低亲和力IgE-Fc受体(FcsRII)mAb MHM、抗II型IgG-Fc受体(FcγRII)mAb IV3或乳精则不能阻断IgE结合至LC.这些观察结果提示IgE结合至LC是通过FcεRI,而不是FceRII,FcyRII或IgE结合蛋白(eBP)所介导.免疫标记研究进一步显示抗FcεRI mAb能特异性标记LC表面本研究首次证明表皮LC具有FcεRI.     

Static load magnitude is a risk factor in the development of cumulative low back disorder

Occupations requiring frequent periods of static lumbar flexion are known epidemiologically to be risk factors for the development of cumulative low back disorder. The impact of the load magnitude sustained during a series of short static lumbar flexions followed by an equally long rest period on the development of a cumulative low back disorder was addressed in an in vivo feline model. Static loads of 20, 40, and 60 N were applied over 10 min of flexion followed by 10-min rest sessions that were repeated six times (for a total of 2 h) while monitoring lumbar viscoelastic creep (laxity) and reflex electromyographic (EMG) activity from the multifidus muscles. Creep and EMG were also monitored over 7 h of rest following the six flexion-rest sessions. It was found that the creep developed in the 10-min flexion periods did not recover completely during the following 10 min of rest, giving rise to a large cumulative creep at the end of the work-rest session. Muscle activity demonstrated spasms during the static flexion periods as well as initial and delayed hyperexcitability during the 7-h rest period. Loads of 20 and 40 N did not result in delayed hyperexcitability, whereas loads of 60 N resulted in delayed hyperexcitability. Statistical analysis demonstrated that increased load significantly intensified the magnitude of the hyperexcitabilities (P < 0.05). Thus, repeated periods of static lumbar flexion were found to result in a transient neuromuscular disorder with an intensity directly related to the load magnitude, which should be considered a compounding risk factor.     

表皮郎格罕细胞表达高亲和力IgE-Fc受体

为了进一步证实抗Ｆ　ＲＩｍＡｂ特异性地结合至郎格罕细胞（ＬＣ）表面，我们用免疫金标记技术进行了免疫电镜检查。发现５ｎｍ金颗粒不连续性地分布于ＬＣ，而非其它表皮细胞表面，从而证明ＬＣ是抗Ｆｃ　ＲＩ反应性表皮细胞。最后，为了了解ＬＣ的Ｆｃ　ＲＩ基因表达与否，进行了ＰＣＲ试验。结果显示在富集ＬＣ而非去除ＬＣ的表皮细胞悬液中存在Ｆｃ　ＲＩａ、　和　链的转录物。总之，本研究提供了直接证据证明正常人表皮ＬＣ表达Ｆ　ＲＩ。     

Cytochemical and Ultrastructural Studies of the Langerhans' Cells

Abstract: In the guinea pig, experimental allergic contact dermatitis (ACD) And primary irritant contact dermatitis (PICD) were induced with different concentrations of dinitrochlorobenzene (DNCB). The epidermal Langerhans' cells (LCs) were observed sequentially by both adenosine triphosphatase (ATPase) and electron microscopy. Light microscopically, in ACD, the density and dendritic processes of LC decreased markedly within 12 h after antigen challenge. Almost no recognization LCs could be seen within 2 to 5 days. Later, LCs began to repopulale in the epidermis. Within 14 days, the density and shape of the LCs returned to normal. On the contrary, LCs changed more rapidly in PICD. The dendritic processes of LC decreased within 2 h and cell density decreased dramatically within 6 h after DNCB application. LCs also repopulated more rapidly in the epidermis. Electron microscopically, in ACD, we observed that lymphocyte-like cells apposed to LCs; LCs were activated and damaged; however, in PICD, we found neither the apposition of lymphocyte-like cells to LCs, nor the activation of LCs. LCs play an important role in the convalescence phase as well as in the early and later phases of contact allergic reaction.     

Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China

AIM: To determine whether the positive status of human epidermal growth receptor 2(HER2) can be regarded as an effective prognostic factor for patients with gastric cancer(GC) undergoing R0 resection.METHODS: A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical(IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-nodemetastasis(TNM) stage, with additional adjustment for potential prognostic factors.RESULTS: Among 1562 patients, 548(positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender(P = 0.004), minority(P 0.001), tumor location(P = 0.001), pathological grade(P 0.001), TNM stage(P 0.001) and adjuvant radiotherapy(74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival(HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival(HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged 60 years or with early TNM stages(Ⅰ and Ⅱ). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION: The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.     

核苷酸切除修复系统基因遗传多态与晚期非小细胞肺癌患者铂类药物敏感性关系

背景与目的:肿瘤细胞对铂类药物的化疗敏感性与个体的DNA损伤修复能力关系密切,本研究探讨核苷酸切除修复系统(nucleotideexcisionrepair,NER)的重要成员XPC、XPD和ERCC1基因的遗传多态与晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)患者对铂类药物敏感性的关系。方法:对接受含铂类药物化疗的200例晚期NSCLC患者进行临床疗效评价。以聚合酶链-扩增片段长度多态性(PCR-AFLP)和限制性片段长度多态性(RFLP)的方法检测XPC-PAT、XPDLys751Gln(rs1052559)和ERCC1C8092A(rs1052559)多态的基因型,比较不同基因型与化疗敏感性的关系。结果:结合疗效情况,XPC-PAT遗传多态各基因型在化疗有效组(CR PR)和无效组(SD PD)中的分布频率差异有显著性(!2检验,P=0.023),携带XPCLL基因型个体的化疗敏感性是XPCSS基因型携带者的3.04倍(95%CI为1.25～7.41,P=0.015)。没有发现XPDLys751Gln和ERCC1C8092A多态与化疗敏感性的相关性。但联合分析后发现,核苷酸切除修复系统的这三个遗传多态在晚期NSCLC患者对铂类药物敏感性中存在一定的联合作用(趋势检验,P=0.021)。结论:核苷酸切除修复系统中XPC-PAT、XPDLys751Gln和ERCC1C8092A遗传多态可能与NSCLC患者对铂类药物敏感性相关。     

Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients

Overexpression of human epidermal growth factor receptor-2(HER2) in metastatic breast cancer(MBC) is associated with poor prognosis.This single-arm open-label trial(EGF109491;NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC.The primary endpoint was clinical benefit rate(CBR).Secondary endpoints included progression-free survival(PFS),time to response(TTR),duration of response(DoR),centr...     

Neuromuscular dysfunction elicited by cyclic lumbar flexion

An attempt was made to develop an in vivo model that could explain the neurophysiological and biomechanical processes active in the development of the idiopathic low back disorder common in workers who perform repetitive lifting tasks in industry. Passive cyclic flexion of the feline lumbar spine at 0.1 HZ for 20 min resulted in creep of the supraspinous ligament and other lumbar viscoelastic tissues as well as spasms superimposed on a decreasing electromyogram (EMG) elicited reflexly from the multifidus muscles. Rest for 7 h did not allow full recovery of the viscoelastic creep; the multifidus EMG gradually increased with initial and delayed hyperexcitability. Increasing the peak load of the cyclic flexion resulted in larger creep in the passive tissues and required a longer time for recovery of reflex EMG activity and longer delayed hyperexcitability, but development of spasms and hyperexcitability was unaffected. It is conceivable that damage to the viscoelastic tissues elicits an inflammatory process that in turn triggers a transient neuromuscular disorder. The present findings provide a biomechanical and neurophysiological explanation for a common idiopathic low back disorder as well as for the development of a cumulative trauma disorder often seen in workers engaged in repetitive lumbar flexion.