ALDH1 and tumor infiltrating lymphocytes as predictors for neoadjuvant chemotherapy response in breast cancer

Many studies have reported that Aldehyde dehydrogenase 1 (ALDH1) and tumor-infiltrating lymphocytes (TIL) are related to breast cancer prognosis. However, the clinical significance of ALDH1 and tumor-infiltrating immune cells in breast cancer has not been fully investigated in patients who received neoadjuvant chemotherapy (NAC). We studied the significance of the expression of ALDH1 and the population of TIL for predicting the prognosis and chemotherapeutic response of patients with breast cancer who had received NAC. Forty patients who underwent NAC were enrolled in this study. ALDH1 and TIL (T cells and tumor associated macrophages) were evaluated before and after NAC. The influences of ALDH1 expression status and TIL populations on both prognosis and chemotherapeutic response were evaluated. ALDH1 positivity was related to estrogen receptor (p?=?0.026) and progesterone receptor negativity (p?=?0.025). Positive change of ALDH1 after NAC tended to be associated with a poor NAC response (p?=?0.078). Patients with more CD8+ T cells before NAC and fewer CD68 (+) macrophages after NAC tended to have better OS, respectively (p?=?0.086, p?=?0.096). The chemotherapeutic response and prognosis of patients with breast cancer who received NAC are thought to be determined by the tumor microenvironment. Further research with more patients and a longer study period is needed.     

T4N (+)Ⅲ期食管胸中下段癌3DRT长期生存分析

目的 观察T₄N (+)Ⅲ期食管胸中下段癌IMRT长期生存情况及不良反应。方法 2004-2010年间300例T₄N (+)Ⅲ期食管中下段癌患者采用3DCRT 202例、IMRT 98例,常规分割照射剂量60 Gy。比较两种不同治疗方式的长期生存情况及不良反应。Kaplan Meier法计算生存率并Logrank法检验。结果 5、7年样本量分别为239、120例。3DCRT和IMRT组1、3、5、7年LC率分别为64.4%、40.6%、38.3%、34.2%和68.3%、55.3%、51.9%、51.9%(P=0.048),OS率分别为54.5%、19.8%、14.7%、10.9%和63.3%、34.7%、24.4%、20.3%(P=0.013)。分层分析显示年龄>65岁、放疗前食管造影长度>8.0 cm、CT最大横径>4.6 cm、GTV>60 cm³、邻近组织或器官受累、非手术 N₂期、未行化疗者,IMRT组OS率高于3DCRT组(P=0.022、0.003、0.022、0.034、0.016、0.044、0.047)。IMRT组GTVD_min、GTVD₁₀₀高于3DCRT组(P=0.000、0.000),脊髓D_max低于3DCRT组(P=0.000)。IMRT组急性放射性食管炎发生率明显高于3DCRT组,以轻度(1-2级)食管炎为著(P=0.000)。3DCRT组死于肿瘤局部因素的比率明显高于IMRT组(P=0.039)。结论 局部晚期食管胸中下段癌IMRT安全有效,LC率明显提高,正常组织保护良好,长期生存获益显著。基于回顾分析结果还有待前瞻性随机对照研究的证实。     

Invasive cutaneous squamous cell carcinoma incidence in US health care workers

Little data on cutaneous squamous cell carcinoma (SCC) epidemiology within the United States are currently available. Prior studies have focused on populations outside of the United States or been limited to regions within the US. In this study, prospective data were collected via biennial questionnaires from a total of 261,609 participants, which included women in the Nurses’ Health Study (NHS, 1976–2008) and Nurses’ Health Study II (NHS II, 1989–2009), and men in the Health Professionals Follow-Up Study (HPFS, 1986–2008). History of physician-diagnosed invasive SCC was confirmed by pathology record review. Over the entire follow-up period for each cohort, there were 1,265 invasive SCC cases per 100,000 persons in the NHS cohort, 389 cases per 100,000 persons in NHS II, and 2,154 cases per 100,000 persons in HPFS. An 18-year follow-up of participants in these cohorts revealed increasing invasive SCC incidence rates over time, with rates for men being consistently higher than those for women. In women, a larger proportion of invasive SCC lesions occurred on the lower extremities as compared to men (21 % in NHS vs. 6 % in HPFS, p < 0.0001; 14 % in NHS II vs. 6 % in HPFS, p < 0.0001), while in men, a larger proportion occurred on the head/neck (43 % in NHS vs. 60 % in HPFS, p < 0.0001; 48 % in NHS II vs. 60 % in HPFS, p < 0.0001). In summary, invasive SCC incidence rates among US men have been greater than those for women with distinct sites of common occurrence between men and women.     

Fate of mandibular canals displaced by enlarged cystic lesions: does the inferior alveolar neurovascular bundle relocate to its original position?

Our aim was to identify the positional changes of the inferior alveolar neurovascular bundle and evaluate the relocation of the displaced mandibular canal after enucleation of a cyst. Seventy patients (72 sites) who had had cysts enucleated were divided into three groups based on the degree of encroachment of the cystic lesion into the mandibular canal and whether a bone graft had been inserted after the cyst had been enucleated. The mean (range) of patients’ ages was 45 (18–75) years, and there were 29 male and 41 female patients. Group A comprised cysts with encroachment on the mandibular canal that were enucleated without a bone graft; Group B consisted of cysts with no encroachment of the mandibular canal, but were enucleated without a bone graft; and Group C comprised cysts with encroachment of the mandibular canal that were enucleated with a bone graft. The displacement of the mandibular canal was identified from analysis of computed tomographic (CT) images. Changes in the position of the mandibular canal were measured on panoramic radiographs. The mandibular canal was repositioned superiorly by a mean (SD) of 2.4 (1.65) mm after enucleation of the cyst, which was significant in Group A (p < 0.001), but not in Groups B and C. These results indicate that the displaced inferior alveolar neurovascular bundles that were not surrounded by bony canal tended to relocate towards a supposedly normal position, and after enucleation of the cyst the mandibular canal was remodelled in this new location. This tendency to relocate was blocked by bone grafting. Bone grafts are therefore recommended in cases where enough bony height is required for future insertion of implants.     

基于数据挖掘分析林慧娟教授诊治心系疾病的中药配伍研究＊

目的 收集并整理林慧娟教授多年诊治心系疾病临床处方资料，对林教授辨证诊治心系疾病的常用中药配伍规律进行深入分析与研究，总结其在治疗心系疾病方面的临床经验，为挖掘和继承名老中医学术经验提供借鉴与参考。方法 收集林慧娟教授于2011年1月-2019年6月在山东中医药大学附属医院门诊系统中的处方数据，筛选后保留10942个处方数据。采用频数分析、点式互信息、关联规则等数据挖掘分析方法对林教授临床处方数据资料进行药物配伍分析。总结林慧娟教授在诊治心系疾病的用药规律。结果 林教授在诊治心系疾病中，以高血压病、冠心病及心律失常患者较多，发现林教授共使用中药397味，并对中药频次进行排序，获得17对主要配伍药对，与林教授临床诊治心系疾病的经验高度吻合。结论 点式互信息、关联规则等数据挖掘分析方法可分析林慧娟教授治疗心系疾病得学术经验，为名中医传承研究提供服务。     

Factors affecting the osteolysis around the components after posterior-stabilized total knee replacement arthroplasty

Knee Surgery, Sports Traumatology, Arthroscopy - The purpose of the present study was to evaluate factors that affect the occurrence of osteolysis through clinical and radiological comparison...     

Identification and Validation of Six Autophagy-related Long Non-coding RNAs as Prognostic Signature in Colorectal Cancer

Colorectal cancer (CRC) is a commonly occurring tumour with poor prognosis. Autophagy-related long non-coding RNAs (lncRNAs) have received much attention as biomarkers for cancer prognosis and diagnosis. However, few studies have focused on their prognostic predictive value specifically in CRC. This research aimed to construct a robust autophagy-related lncRNA prognostic signature for CRC. Autophagy-related lncRNAs from The Cancer Genome Atlas database were screened using univariate Cox, LASSO, and multivariate Cox regression analyses, and the resulting key lncRNAs were used to establish a prognostic risk score model. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression of several lncRNAs in cancer tissues from CRC patients and in normal tissues adjacent to the cancer tissues. A prognostic signature comprising lncRNAs {"type":"entrez-nucleotide","attrs":{"text":"AC125603.2","term_id":"21630347","term_text":"AC125603.2"}}AC125603.2, LINC00909, {"type":"entrez-nucleotide","attrs":{"text":"AC016876.1","term_id":"6539320","term_text":"AC016876.1"}}AC016876.1, MIR210HG, AC009237.14, and LINC01063 was identified in patients with CRC. A graphical nomogram based on the autophagy-related lncRNA signature was developed to predict CRC patients'' 1-, 3-, and 5-year survival. Overall survival in patients with low risk scores was significantly better than in those with high risk scores (P < 0.0001); a similar result was obtained in an internal validation sample. The nomogram was shown to be suitable for clinical use and gave correct predictions. The 1- and 3-year values of the area under the receiver operating characteristic curve were 0.797 and 0.771 in the model sample, and 0.656 and 0.642 in the internal validation sample, respectively. The C-index values for the verification samples and training samples were 0.756 (95% CI = 0.668-0.762) and 0.715 (95% CI = 0.683-0.829), respectively. Gene set enrichment analysis showed that the six autophagy-related lncRNAs were greatly enriched in CRC-related signalling pathways, including p53 and VEGF signalling. The qRT-PCR results showed that the expression of lncRNAs in CRC was higher than that in adjacent tissues, consistent with the expression trends of lncRNAs in the CRC data set. In summary, we established a signature of six autophagy-related lncRNAs that could effectively guide clinical prediction of prognosis in patients with CRC. This lncRNA signature has significant clinical implications for improving the prediction of outcomes and, with further prospective validation, could be used to guide tailored therapy for CRC patients.     

Loss of GRB2 associated binding protein 1 in arteriosclerosis obliterans promotes host autophagy

Background:Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.