The functional mechanism of the long non-coding RNAs (lncRNA) GAPLINC in triple-negative breast cancer (TNBC) remains poorly understood. The present study aimed to explore GAPLINC in TNBC and its contribution to regulating tumor progression through the microRNA (miRNA)-331-3p/ insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1) axis. Tumor tissue samples and adjacent normal tissue samples were collected from 150 TNBC patients, and TNBC-related cell lines were cultured. mRNA expression was determined using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Functional parameters were assessed through the following experimental methods: the cell counting kit-8 (CCK-8) assay was employed to evaluate proliferation capacity, the Transwell was conducted to assess migration and invasion, and the dual-luciferase assay was performed to confirm the targeted binding relationships. GAPLINC was significantly upregulated in TNBC tissues and cell lines (P < 0.001), and its expression was closely correlated with poor clinical prognosis. Similarly, miR-331-3p was markedly downregulated in TNBC samples (P < 0.001), while IGF2BP1 expression was significantly overexpressed (P < 0.001). Silencing GAPLINC effectively suppressed proliferation, migration, and invasion, accompanied by a notable upregulation miR-331-3p expression (P < 0.001). Importantly, inhibition of miR-331-3p partially reversed the suppressive effects induced by GAPLINC knockdown. Furthermore, miR-331-3p targeted IGF2BP1. Additional knockdown of IGF2BP1 counteracted this reversal effect, thereby effectively abrogating the tumor-promoting function of GAPLINC. This study identified GAPLINC as a crucial oncogenic lncRNA in TNBC. It promoted tumor progression by competitively binding to miR-331-3p, thereby derepressing its target IGF2BP1. These findings not only elucidated a new GAPLINC/miR-331-3p/IGF2BP1 regulatory axis, but also highlighted that GAPLINC may be a potential prognostic biomarker for triple-negative breast cancer.

Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy (NAC) for breast cancer (BC) at present. However, 30

BACKGROUND:Triple-negative breast cancer (TNBC), which is so called because of the lack of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) receptors on the cancer cells, accounts for 10%-15% of all breast cancers. The heterogeneity of the tumor microenvironment is high. However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood. METHODS:We analyzed single-cell RNA sequencing data from five HER2 positive, 12 ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry. RESULTS:Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2-integrin-aLb2 complex, and then release interleukin 1 beta (IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth. CONCLUSION:Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.

Background: Brain metastasis (BM) represents one of the most common advanced disease states in breast cancer (BC), especially in human epidermal growth factor receptor 2 (HER2)-positive BC, and is associated with poor survival outcomes. Methods: In this study, in- depth analysis of the microarray data from the GSE43837 dataset with 19 BM samples of HER2-positive BC patients and 19 HER2-positive nonmetastatic primary BC samples was conducted. The differentially expressed genes (DEGs) between BM and primary BC samples were identified and function enrichment analysis of the DEGs was conducted to identify potential biological functions. The hub genes were identified by constructing the protein-protein interaction (PPI) network using STRING and Cytoscape. UALCAN and Kaplan-Meier plotter online tools were used to verify the clinical roles of the hub DEGs in HER2-positive BC with BM (BCBM). Results: A total of 1,056 DEGs including 767 downregulated and 289 upregulated genes were identified by comparing the microarray data of the HER2-positive BM and primary BC samples. Functional enrichment analysis demonstrated that the DEGs were mainly enriched in pathways related to extracellular matrix (ECM) organization, cell adhesion, and collagen fibril organization. PPI network analysis identified 14 hub genes. Among these, CD44, COL1A2, MMP14, POSTN, and SOX9 were associated with the survival outcomes of HER2-positive patients. Conclusions: In summary, 5 BM-specific hub genes were identified in the study; those are potential prognostic biomarkers and therapeutic targets for HER2- positive BCBM patients. However, further investigations are necessary to unravel the mechanisms by which these 5 hub genes regulate BM in HER2-positive BC.

目的 探寻乳腺癌远处转移及其影响因素,为转移性乳腺癌治疗提供理论依据.方法 回顾性分析2015年1月至2017年12月在首都医科大学附属北京天坛医院乳腺科进行手术的204例乳腺癌患者远处转移情况及其影响因素.结果 25例乳腺癌患者发生远处转移(12.3％).乳腺癌远处转移与肿瘤大小、有无腋窝淋巴结转移及有无脉管癌栓相关(P<0.05),进一步研究分析远处转移与腋窝淋巴结转移个数相关(P<0.05).但与年龄、是否绝经、乳腺癌卵巢癌家族史、肿瘤分级、雌激素受体、孕激素受体、人类表皮生长因子受体2、三阴性乳腺癌无关(P>0.05).结论 肿瘤大小、腋窝淋巴结转移及脉管癌栓与乳腺癌远处转移密切相关.

目的 探讨乳腺癌和/或卵巢癌(breast and/or ovarian cancer,BCOC)家族史与乳腺浸润性导管癌临床病理学特征的关系.方法 纳入2019年1月至2020年12月首都医科大学附属北京天坛医院收治的237例女性乳腺浸润性导管癌患者,分析BCOC家族史与其他临床病理参数的关系.结果 在237例患者中,76例(32.1%)有肿瘤家族史,其中32例(13.5%)有BCOC家族史.患者年龄越小,有BCOC家族史的比例越高(P=0.039).有BCOC家族史的患者发病年龄[(47.1±9.2)岁]低于无家族史者[(52.6±9.5)岁],三阴性乳腺癌的比例(21.9%)高于无家族史者(9.8%),差异有显著性(P＜0.05),但BCOC家族史与乳腺癌患者的肿瘤大小、组织学分级、TNM分期、腋窝淋巴结转移、ER、PR、HER2、是否双侧乳腺癌无关(P＞0.05).结论 BCOC家族史与乳腺癌的发生密切相关,密切关注有家族史的女性可为乳腺癌的筛查、早期诊断和治疗提供有力的理论支持.

目的 比较耳后注射和全身应用糖皮质激素治疗突发性聋的效果.方法 收集2018年1月至2020年12月阜阳市第六人民医院177例突发性聋患者病历资料,其中50例低频下降型突发性聋和43例中高频下降型突发性聋用甲泼尼龙琥珀酸钠行耳后注射、46例低频下降型突发性聋和38例中高频下降型突发性聋行静脉滴注地塞米松磷酸钠,比较两种治疗方法的效果.结果 低频下降型突发性聋患者用甲泼尼龙琥珀酸钠耳后注射后有效率为88％,用地塞米松磷酸钠静脉滴注有效率为67.3％,差异有统计学意义(P<0.05);中高频下降型突发性聋用甲泼尼龙琥珀酸钠耳后注射有效率为76.7％,用地塞米松磷酸钠静脉滴注治疗有效率为60.5％,差异无统计学意义(P>0.05).结论 针对低频下降型突发性聋患者,耳后注射甲泼尼龙琥珀酸钠优于全身静脉滴注地塞米松磷酸钠;针对中高频下降型突发性聋患者,两种给药方法疗效差异无统计学意义.

下肢不等长(leg length discrepancy,LLD), 是指双下肢长度不相等,分为结构性不等长和功能性不等长 [1-4].结构性不等长是指下肢存在骨性长度差异 [4,5],根据长度差异及引起不等长的原因可以采用手术或补高鞋、足部矫形器等保守方法.功能性不等长是由下肢关节的生物力学功能差异引起的 [3,4],如单侧足部过度旋前 [5]、骨盆倾斜、软组织挛缩等,其治疗方法也要根据原因合理选择足部矫形器、功能锻炼或手法治疗.LLD会引起脊柱、骨盆、膝关节、踝关节的姿势和步态改变 [6],增加行走时肌肉的能量消耗 [7].当LLD>5 mm时,会出现步态不对称 [8].

Background and purpose: In the 8th edition of the TNM staging of gastric cancer, extranodal invasion is listed as one of the independent disease registration variables. The positive patients have a higher disease-related mortality and recurrence rate, which is closely related to the poor prognosis. This study explored the relationship between extracapsular lymph node involvement (EC-LNI) and clinicopathological features of gastric cancer, and analyzed its impact on the survival prognosis of gastric cancer patients. Methods: A retrospective study of 2 386 patients with gastric cancer who underwent radical surgery from Jan. 1, 2012 to Jan. 1, 2015 in the Department of External Medicine of the Fourth Hospital of Hebei Medical University was analyzed. The relationship between EC-LNI and clinicopathological characteristics and its effect on the survival of gastric cancer patients were analyzed. Results: Among the 2 386 gastric cancer patients, 333 (13.96%) were EC-LNI (+), and 2 053 (86.04%) were EC-LNI (-). Univariate analysis showed that tumor diameter, histological type, Borrmann classification, depth of invasion pT stage, tumor pTNM stage, Lauren classification, vascular tumor thrombus, nerve invasion, Ki-67 positive ratio and the expressions of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate (CA)19 -9 and CA72-4] were related to the status of EC-LNI (both P<0.05). The results of multivariate analysis showed that the tumor diameter (P=0.010), histological type (P=0.016), tumor infiltration depth pT staging (P=0.011), tumor pTNM staging (P=0.003), Borrmann type (P=0.032) and vascular tumor thrombus (P=0.022) were all independent risk factors for EC-LNI. Complete follow-up data were received from 2 273 (95.26%) of the 2 386 gastric cancer patients. The 5-year overall survival (OS) rate of the group was 49.32%, and the 5-year disease-free survival (DFS) rate was 44.61%. Among them, the EC-LNI (+) 5-year OS rate was 27.86%, the 5-year DFS rate was 25.39%, and the EC-LNI (-) 5-year OS and DFS rates were 52.87% and 47.79%, respectively. There were statistically significant differences in the 5-year OS rates and DFS rates between the two groups of patients (both P<0.001). Univariate analysis showed that the number of EC-LNI (P=0.000) was related to the prognosis of gastric cancer patients, and mean age, lesion location, tumor diameter, histological type, Borrmann classification, tumor invasion depth pT stage, lymph node metastasis pN stage, tumor pTNM stage, Lauren classification, presence or absence of vascular tumor thrombus, positive rate of Ki-67 and postoperative chemotherapy were also related to prognosis (all P<0.05). Multivariate analysis showed that tumor histology type (P=0.013), depth of invasion pT stage (P=0.020), lymph node metastasis pN stage (P=0.019), tumor pTNM stage (P=0.001), presence or absence of vascular tumor thrombus (P=0.031) and the number of EC-LNI (P=0.001) were independent risk factors that affected the prognosis of patients, and postoperative adjuvant chemotherapy (P=0.003) was a protective factor for patient’s prognosis. Conclusion: EC-LNI is closely related to the tumor stage and prognosis of patients with gastric cancer. The presence or absence of EC-LNI and the number of EC-LNI are risk factors that affect the prognosis of gastric cancer patients.

目的:观察小剂量泼尼松联合手术治疗肉芽肿性乳腺炎的临床疗效及安全性.方法:90例肉芽肿性乳腺炎患者随机均分为试验组和对照组.试验组口服泼尼松0.4 mg·kg-1·d-1,起始剂量治疗4周,第5周起每周减2.5 mg·d-1,减量至5 mg·d-1,维持2周后停药.对照组45例,口服泼尼松0.75 mg·kg-1·d-1,起始剂量治疗4周,第5周起每周减5 mg·d-1,减量至5mg·d-1,维持2周后停药.两组均在激素治疗6-8周后手术,进行完整病灶清除术,若疗程中肿块缩小明显,直径＜2cm即可采取手术治疗.计量数据行t检验;计数资料行卡方检验.结果:两组手术情况比较结果显示,试验组和观察组在药物治疗有效率、手术切除腺体量、术中出血量、术后满意度、术后痊愈时间方面基本相同,无统计学差异(P＞ 0.05);并发症率比较无统计学差异(P＞0.05);试验组不良反应发生率明显低于观察组,两者比较有统计学差异(P＜0.05).结论:小剂量泼尼松联合手术治疗肉芽肿性乳腺炎效果满意,安全性好.

PurposeThe ataxia telangiectasia-mutated (ATM) gene is a moderate susceptibility gene for breast cancer. However, little is known about the breast cancer phenotypes associated with ATM mutation. We therefore investigated the spectrum and clinical characteristics of ATM germline mutations in Chinese breast cancer patients.MethodsA multi-gene panel was performed to screen for ATM germline mutations in 7657 BRCA1/2-negative breast cancer patients. All deleterious mutations were validated by independent polymerase chain reaction (PCR)-Sanger sequencing.ResultsA total of 31 pathogenic mutations in the ATM gene across 30 carriers were identified, and the ATM mutation rate was 0.4% (30/7,657) in this cohort. The majority of the mutations (90.3%, 28/31) were nonsense or frameshift mutations. Of the total ATM mutations, 61.3% (19/31) were novel mutations and 13 recurrent mutations were found. ATM mutations carriers were significantly more likely to have a family history of breast and/or ovarian cancer (26.7% in carriers vs. 8.6% in non-carriers, p<0.001), as well as a family history of any cancer (60.0% in carriers vs. 31.5% in non-carriers, p=0.001). In addition, ATM mutations carriers were significantly more likely to have oestrogen receptor (ER)-positive (p=0.011), progesterone receptor (PR)-positive (p=0.040), and lymph node-positive breast cancer (p=0.034).ConclusionsThe prevalence of the ATM mutation is approximately 0.4% in Chinese BRCA1/2-negative breast cancer. ATM mutation carriers are significantly more likely to have a family history of cancer and to develop ER- and/or PR-positive breast cancer or lymph node-positive breast cancer.

Musashi 2 (MSI2), a marker of stem and progenitor cells, has been identified as an oncogene. Various investigations have revealed that MSI2 is differently expressed in several types of blood cancer and solid cancers. However, its expression and biological functions in gastric cancer (GC) remain unclear. In the present study, MSI2 mRNA and protein expression were assessed in GC tissue samples. The associations between MSI2 mRNA expression and the clinicopathological characteristics of patients with GC were analyzed, and the effect of MSI2 on the prognosis of patients with GC was verified. The biological functions of MSI2 in GC cells were assessed using gain-of-function assays in vitro. The results revealed that MSI2 was overexpressed in the majority of GC tissue samples, although this difference was not significant. MSI2 mRNA expression levels were associated with invasion depth, tumor-node-metastasis stage, degree of differentiation and tumor size (P<0.05), but were not associated with sex, age, tumor location or human epidermal growth factor receptor 2 expression. Increased MSI2 expression resulted in a poorer prognosis in patients with GC (chi(2)=4.221; P=0.040). In vitro assays revealed that MSI2 promoted MKN-28 cell proliferation, migration and invasion, and promoted tube formation in HUVECs. Although no significance of MSI2 expression was found, its oncogenic functions in the GC cell line indicated that MSI2 may be a potential oncogene that may serve as a biomarker for GC diagnosis and prognosis with verification from a larger sample and more GC cell lines.

Lymphatic metastasis is a primary cause of gastric cancer-related death, yet factors governing tumor cell lymphatic metastasis have not been fully elucidated. Little is known about the contributions of long noncoding RNAs (lncRNAs) to lymphatic metastasis in gastric cancer. Differentially expressional lncRNAs between metastatic lymph node tissues and normal lymph node tissues were identified and validated by microarray and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Our results found that the expression level of C21orF96 was over-expressed in positive lymph node tissues and gastric cancer tissues. We evaluated the altered expressions of C21orF96 in gastric cancer tissues comparing to adjacent normal specimens, and their association with clinicopathological factors. We showed that the expression levels of C21orF96 were associated with gross appearance, lymphatic metastasis and distal metastasis. The effect of C21orF96 was assessed by over-expressing the lncRNA. We also found that C21orF96 promoted the tubular formation, migration and invasion. Together, our results suggest that C21orF96 is an oncogenic lncRNA that promotes tumor progression and plays a pivotal role in the development of gastric cancer.

目的 探寻胃癌组织中Musashi2 (MSI2)表达水平及与其临床病理学特征的关系.方法 应用实时定量PCR方法检测67例胃癌患者MSI2 mRNA在肿瘤和癌旁组织中的表达水平,用Western blot法验证其高表达者MSI2蛋白表达水平;分析其表达水平和胃癌临床病理学特征的关系,并分析比较MSI2 mRNA高表达者(胃癌组织与相应癌旁组织中MSI2 mRNA表达水平之比≥2倍)和MSI2 mRNA低表达者(胃癌组织与相应癌旁组织中MSI2 mRNA表达水平之比＜2倍)的预后情况.结果 MSI2 mRNA在胃癌组织和癌旁组织间的表达水平差异无统计学意义(P＞0.05).MSI2 mRNA表达水平与肿瘤浸润深度(P=0.017)、TNM分期(P=0.028)、分化程度(P=0.020)及肿瘤大小(P=0.030)相关,与患者的性别、年龄及肿瘤部位无关(P＞0.05).MSI2 mRNA高表达者的总体生存率明显低于低表达者(x2=4.221,P=0.040).结论 MSI2表达水平与胃癌的侵袭、分期和分化程度相关,高表达者预后较差.MSI2可能作为未来胃癌治疗的新的分子靶点.

The contribution of long noncoding RNAs (lncRNAs) to metastasis of gastric cancer remains largely unknown. We used microarray analysis to identify lncRNAs differentially expressed between normal gastric tissues and gastric cancer tissues and validated these differences in quantitative real-time (qRT)-PCR experiments. The expression levels of lncRNA olfactory receptor, family 3, subfamily A, member 4 (OR3A4) were significantly associated with lymphatic metastasis, the depth of cancer invasion, and distal metastasis in 130 paired gastric cancer tissues. The effects of OR3A4 were assessed by overexpressing and silencing OR3A4 in gastric cancer cells. OR3A4 promoted cancer cell growth, angiogenesis, metastasis, and tumorigenesis in vitro and in vivo. Global microarray analysis combined with RT-PCR, RNA immunoprecipitation, and RNA pull-down analyses after OR3A4 transfection demonstrated that OR3A4 influenced biologic functions in gastric cancer cells via regulating the activation of PDLIM2, MACC1, NTN4, and GNB2L1. Our results reveal OR3A4 as an oncogenic lncRNA that promotes tumor progression, Therefore, lncRNAs might function as key regulatory hubs in gastric cancer progression.

Gastric cancer is the second leading cause of cancer-related deaths. Metastasis, which is an important element of gastric cancer, leads to a high mortality rate and to a poor prognosis. Gastric cancer metastasis has a complex progression that involves multiple biological processes. The comprehensive mechanisms of metastasis remain unclear, though traditional regulation modulates the molecular functions associated with metastasis. Long non-coding RNAs (lncRNAs) have a role in different gene regulatory pathways by epigenetic modification and by transcriptional and post-transcription regulation. lncRNAs participate in various diseases, including Alzheimer's disease, cardiovascular disease, and cancer. The altered expressions of certain lncRNAs are linked to gastric cancer metastasis and invasion, as with tumor suppressor genes or oncogenes. Studies have partly elucidated the roles of lncRNAs as biomarkers and in therapies, as well as their gene regulatory mechanisms. However, comprehensive knowledge regarding the functional mechanisms of gene regulation in metastatic gastric cancer remains scarce. To provide a theoretical basis for therapeutic intervention in metastatic gastric cancer, we reviewed the functions of lncRNAs and their regulatory roles in gastric cancer metastasis.

Gastric cancer (GC) is a major threat to human health, and its prognosis is poor due to the lack of appropriate biomarkers. LncRNAs are a group of non-protein-coding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. LncRNAs play essential roles in GC initiation and development in the same way as oncogenes or tumour suppressor genes. Recent investigations have revealed that lncRNAs are often aberrantly expressed in GC; are involved in cell proliferation, apoptosis, migration and invasion; and correlate with the malignant phenotype of GC. LncRNAs, especially the lncRNAs present in the blood and gastric juice, show potential value as biomarkers for the diagnosis of GC or for determining disease prognosis. However, there are still many challenges to be faced before lncRNAs can be used in clinical applications. In this review, we summarise lncRNAs as the potential biomarkers for GC and the current challenges associated with the clinical application.

目的 总结目前长链非编码RNA (long noncoding RNA,lncRNA)在胃癌转移中的作用及研究进展.方法 通过Web of Knowledge、Pubmed等数据库检索并下载有关lncRNAs和胃癌转移相关文献,对lncRNAs参与胃癌转移相关文献进行分析.结果 近年来lncRNAs作为研究热点,越来越受到研究者的重视,它们能够在染色质、转录和转录后水平参与基因调节.lncRNAs在胃癌中异常表达,并通过调节胃癌血管生成、细胞间连接和细胞外基质调节胃癌转移.结论 lncRNAs作为胃癌转移的重要调节因素,可以作为胃癌治疗的分子靶点,为深入研究如何防治胃癌的转移提供了一种有效的科学思路.

Objective To analyze and verify the expression profiles of long non-coding RNAs (lncRNAs) in gastric cancer (GC) metastatic lymphonodus.Methods Microarray analysis was performed in 3 GC positive lymphonodus and 1 normal lymph node with Agilent Array platform to measure the expression levels of lncRNAs and mRNAs and to investigate the expression differences of lncRNAs in GC metastatic lymphonodus and normal lymphonodus, and hierarchical clustering used to screen out the differently expressed lncRNAs.15 up-regulated lncRNAs and 15 down-regulated lncRNAs were randomly chosen and RT-PCR was used to verify the expression differences.Results Comparing with normal lymphonodus, 353 lncRNAs and 547 mRNAs are up-regulated, but 464 lncRNAs and 562 mRNAs are down-regulated in GC metastatic lymphanodus as 6 times or more variation was found.The expressions of lncRNA OR3A4, LOC84740, FCGR1C and C21orf 96 were increased in GC metastatic lymphonodus, but lncRNA MSTO2P, LOC344595, TUG1, TYW3 and KRT8P10 decreased.Conclusions LncRNAs are aberrantly expressed in GC metastatic lymphonodus.

目的 探讨足跟垫配合封闭治疗跟痛症的临床疗效.方法 以足跟垫配合封闭治疗80例跟痛症患者,并与只采用封闭治疗跟痛症的对照组80例进行疗效比较.结果 治疗组有效率96.2%,对照组有效率77.5%,有统计学意义(p<0.05),治疗组优于对照组.结论 足跟垫配合封闭治疗跟痛症疗效确切,是一种值得推广的方法.