Clinical characteristics and prognosis of triple-negative breast cancer

Objective： We investigated the clinical characteristics, and the prognostic factors of triple-negative breast cancer. Methods： 130 triple-negative breast cancer patients were reviewed on clinical characteristics and prognosis. All cases were lack of expression of estrogen receptor, progesterone receptor, and HER2/neu determined by immunohistochemistry. Results： 17.1% of all breast cancer patients （774 cases） were triple-negative breast cancer, and 68.9% of triple-negative breast cancer patients （91 cases） were premenopausal. 53.8% of patients （71 cases） had the tumors with T2 size, and 39.4% of them （52 patients） had lymph node metastasis. The rate of relapse in patients with lymph node metastasis was obviously higher than that in patients without lymph node metastasis （P = 0.001）. The median time of follow-up was 63 months. 33 cases relapsed and 20 patients died. 23 patients had at least two organs metastasis. The 5-year disease-free and overall survival rates were 73.8% and 85.7%. Conclusion： Triple-negative breast cancer patients commonly have high rate of multiple distant metastasis in 2-3 years after treatment. The status of lymph node is the most important prognostic factor. The triple-negative breast caner patients with lymph node metastasis have poor prognosis.

Formation process of extension knee joint contracture following external immobilization in rats

BACKGROUND Current research lacks a model of knee extension contracture in rats.AIM To elucidate the formation process of knee extension contracture.METHODS We developed a rat model using an aluminum external fixator.Sixty male Sprague-Dawley rats with mature bones were divided into the control group(n=6)and groups that had the left knee immobilized with an aluminum external fixator for 1,2,and 3 d,and 1,2,3,4,6,and 8 wk(n=6 in each group).The passive extension range of motion,histology,and expression of fibrosis-related proteins were compared between the control group and the immobilization groups.RESULTS Myogenic contracture progressed very quickly during the initial 2 wk of immobilization.After 2 wk,the contracture gradually changed from myogenic to arthrogenic.The arthrogenic contracture progressed slowly during the 1^(st) week,rapidly progressed until the 3^(rd) week,and then showed a steady progression until the 4^(rd) week.Histological analyses confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time.Correspondingly,the level of transforming growth factor beta 1(TGF-β1)and phosphorylated mothers against decapentaplegic homolog 2(p-Smad2)in the anterior joint capsule also increased with the immobilization time.Over time,the cross-sectional area of muscle fibers gradually decreased,while the amount of intermuscular collagen and TGF-β1,p-Smad2,and p-Smad3 was increased.Unexpectedly,the amount of intermuscular collagen and TGF-β1,p-Smad2,and p-Smad3 was decreased during the late stage of immobilization(6-8 wk).The myogenic contracture was stabilized after 2 wk of immobilization,whereas the arthrogenic contracture was stabilized after 3 wk of immobilization and completely stable in 4 wk.CONCLUSION This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches.

孤立性肺结节的循证医学影像处理

孤立性肺结节（solitary pulmonary nodule,SPN）定义为被肺实质包绕的直径≤3 cm的圆形/类圆形不透明影。大多数吸烟者的薄层CT扫描均可以发现SPN,其中大部分直径〈7 mm。在过去,如偶然发现此类结节临床采用2年以上随访,包括3,6,12,18,24个月的CT随访。该方案使随访者接受的辐射量增加。结节形态特性,如形状、边缘特征、空洞、位置等难以准确鉴别良恶性结节。当首次检查中的SPN不能定性时,应评估包括患者年龄和吸烟史等危险因素。Fleischner学会2005年指南指明所有4 mm或更小的结节中至少99%为良性;当结节直径为5-9 mm时,最佳策略是随访。随访检查的时间点依据结节大小（4-6,6-8 cm）和患者病史而不一,特别是是否存在恶性肿瘤低危/高危因素。直径〉8 mm的非钙化结节高度提示恶性肿瘤,此时应考虑额外检查如造影剂增强CT,正电子发射断层扫描（positron emission tomography,PET）,经皮肺穿刺活检,胸腔镜切除术或电视辅助胸腔镜切除术。

关于Del Chiaro及同事应用磁共振做胰腺癌筛查的报道

胰腺癌是一种致命的疾病，其发病率和病死率几乎一样。在西方国家5年存活率为4%，是所有癌症类型中最低的[1]。在中国胰腺癌为恶性肿瘤死亡原因的第六位，总累积5年存活率为1%~3%[2-3]。中国胰腺癌患病危险因素类似于西方国家[2-3]。通过影像学偶然发现的胰腺癌生存期似乎有所增加[4-6]。最近基因测序证据[7-8]表明，胰腺癌从基因癌变开始到转移期胰腺癌需要15年时间。20世纪90年代之前，胰腺癌可以是一种遗传性疾病这点没有被广泛认识，而现在知道在某些基因异常的个体，如BRCA2、p16、遗传性非息肉性大肠癌、家族性胰腺炎和Peutz-Jeghers综合征的个人都较易患胰腺癌[9-14]。然而胰腺癌只有10%的患者有已知的危险因素，其他90%的癌症目前未有已知的风险因素[4-12]。

Effect and safety of mark-guided vs standard peroral endoscopic myotomy: A retrospective case control study

BACKGROUND Peroral endoscopic myotomy(POEM)is a promising therapeutic modality for esophageal achalasia worldwide.However,clinical failure and adverse events of POEM have still been concerned.AIM To compare the efficacy and safety of a novel mark-guided POEM with standard POEM.METHODS A total of 133 patients with esophageal achalasia who underwent POEM from May 2013 to May 2019 were enrolled in this retrospective study.Of the 133 patients,there were 64 patients in the mark-guided POEM group and 69 patients in the standard POEM group.The clinical success,procedural duration and adverse events were compared between the two groups at 3 mo,12 mo and 24 mo postoperatively.RESULTS Characteristic baseline was similar in the mark-guided POEM group and standard POEM group.The clinical success was comparable between the two groups,ranging from 92%to 98%,at 3 mo,12 mo and 24 mo postoperatively(all P>0.5).Eckart score,Gastroesophageal Reflux Disease Questionnaire score and SF-36 score were not different between the two groups after treatment(all P>0.05).No severe adverse events occurred in the two groups.However,markguided POEM required shorter procedural duration,and less use of proton pump inhibitors and lower incidence of reflux symptoms than the standard POEM(all P<0.001).CONCLUSION Mark-guided POEM and standard POEM were both effective and safe for the treatment of esophageal achalasia.However,the mark-guided POEM was characterized by shorter procedural duration,less use of proton pump inhibitors and lower incidence of reflux symptoms.

On pancreatic cancer screening by magnetic resonance imaging with the recent evidence by Del Chiaro and colleagues

Pancreatic cancer is a lethal disease because incidence and mortality rates are nearly identical.The 5-year survival rate in Western countries is 4%,the lowest among all types of cancer（1）.In China,pancreatic cancer is the sixth leading cause of death from malignant disease,with an overall cumulative 5-year survival rate of 1%to 3%（2,3）.

孤立性肺结节的循证医学影像处理

孤立性肺结节（SPN）定义为被肺实质包绕的直径≤3 cm的圆形/类圆形不透明影。大多数吸烟者的薄层CT扫描均可以发现SPN,其中大部分直径小于7 mm。在过去,如偶然发现此类结节临床采用2年以上随访,包括3个月、6个月、12个月、18个月、24个月的CT随访。该方案使随访者接受的辐射量增加。结节形态特性,如形状、边缘特征、空洞、位置等难以准确鉴别良恶性结节。当首次检查中的SPN不能定性时,应评估包括患者年龄和吸烟史等危险因素。Fleischner学会2005年指南指明所有4 mm或更小的结节中至少99%为良性;当结节直径为5~9 mm时,最佳策略是随访。随访检查的时间点依据结节大小（4~6 mm或6~8 mm）和患者病史而不一,特别是是否存在恶性肿瘤低危/高危因素。直径〉8 mm的非钙化结节高度提示恶性肿瘤,此时应考虑额外检查如造影剂增强CT,正电子发射断层扫描（PET）,经皮肺穿刺活检,胸腔镜切除术或电视辅助胸腔镜切除术。

Protein tyrosine kinase inhibitor resistance in malignant tumors:molecular mechanisms and future perspective

Protein tyrosine kinases(PTKs)are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways.Their basal function is essential for maintaining normal cell growth and differentiation.However,aberrant activation of PTKs caused by various factors can deviate cell function from the expected trajectory to an abnormal growth state,leading to carcinogenesis.Inhibiting the aberrant PTK function could inhibit tumor growth.Therefore,tyrosine kinase inhibitors(TKIs),target-specific inhibitors of PTKs,have been used in treating malignant tumors and play a significant role in targeted therapy of cancer.Currently,drug resistance is the main reason for limiting TKIs efficacy of cancer.The increasing studies indicated that tumor microenvironment,cell death resistance,tumor metabolism,epigenetic modification and abnormal metabolism of TKIs were deeply involved in tumor development and TKI resistance,besides the abnormal activation of PTK-related signaling pathways involved in gene mutations.Accordingly,it is of great significance to study the underlying mechanisms of TKIs resistance and find solutions to reverse TKIs resistance for improving TKIs efficacy of cancer.Herein,we reviewed the drug resistance mechanisms of TKIs and the potential approaches to overcome TKI resistance,aiming to provide a theoretical basis for improving the efficacy of TKIs.

GNL-Scorer: a generalized model for predicting CRISPR on-target activity by machine learning and featurization

CRISPR/Cas9 is an adaptive immunity system in bacteria and most archaea(Koonin and Makarova,2009;Horvath and Barrangou,2010).The CRISPR/Cas9 gene editing system is comprised of two key components,a small guide RNA(gRNA)and a Cas9 endonuclease(Deltcheva etal.,2011;Jineketal.,2012).