Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis.

BACKGROUND: Emerging studies have demonstrated that circular RNAs (circRNAs) are key regulators for tumorigenesis in cancers, including papillary thyroid carcinoma (PTC). In this study, we aimed to explore the effects of circ_LDLR on PTC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the levels of circ_LDLR, miR-195-5p and lipase H (LIPH). RNase R digestion assay and Actinomycin D assay were utilized to analyze the characteristics of circ_LDLR. Colony formation assay and 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay were conducted to evaluate cell proliferation. Western blot assay was used for the determination of protein levels. Flow cytometry analysis was applied to determine cell apoptosis. Transwell assay was performed to determine cell migration and invasion. Dual-luciferase reporter assay was used to verify the associations among circ_LDLR, miR-195-5p and LIPH. The murine xenograft model was constructed to explore the roles of circ_LDLR in vivo. RESULTS: Compared to normal tissues and cells, circ_LDLR was upregulated in PTC tissues and cells. Silencing of circ_LDLR suppressed PTC cell colony formation, proliferation, migration and invasion and promoted apoptosis in vitro and hampered tumor growth in vivo. For mechanism investigation, circ_LDLR could regulate LIPH expression via sponging miR-195-5p. Moreover, miR-195-5p inhibition restored the effects of circ_LDLR knockdown on the malignant behaviors of PTC cells. MiR-195-5p overexpression inhibited PTC cell colony formation, proliferation, migration and invasion and facilitated apoptosis by targeting LIPH. CONCLUSION: Circ_LDLR knockdown decelerated PTC progression by regulating miR-195-5p/LIPH axis, which might provide a novel therapeutic target for PTC.

Analysis of factors related to N2- or N3-stage breast cancer associated with 1-2 positive sentinel lymph nodes in Chinese patients.

BACKGROUND: This study aims to determine the incidence of N2- or N3-stage disease in a cohort of patients with T1-T2 invasive breast cancer and one or two positive sentinel lymph nodes (SLNs), and identify the risk factors for N2/3 disease in this cohort. METHODS: The present study involved 298 patients with T1-T2 tumors who underwent SLN biopsy and were found to have one or two metastatic SLNs. The proportion of patients with N2/3 disease was calculated in the whole cohort, and in the T1 and T2 subgroups. Furthermore, univariate and multivariate analyses were used to identify the risk factors for N2/3 disease in the cohort. RESULTS: The final N stage, as determined by the postoperative pathological examination, was N1 for 250 (83.9%) patients, and N2 or N3 for 48 (16.1%) patients (11.41% had clinical N2 disease, while 4.70% had clinical N3 disease). Among the 156 patients with T1 tumors, 17 (10.9%) patients had N2/3 disease, while for the 142 patients with T2 tumors, 31 (21.8%) patients had N2/3 disease. T2 stage, lymphovascular invasion, and the number of positive SLNs were independent predictors of N2/3 disease in the cohort (P<0.05). CONCLUSIONS: N2/3 lymph node metastasis occurs in patients with T1-T2 breast cancer, and one or two positive SLNs, particularly in patients with T2 tumors. The rate of N2/3 disease is not negligible. T2 stage, lymphovascular invasion, and the number of positive SLNs were independent predictors of N2/3 disease in the present patient population.

Comparison of 21-gene assay and St.Gallen International Expert Consensus in the treatment decision for patients with early invasive breast cancers.

This study aimed to evaluate the impacts of 21-gene recurrence score (RS) and St. Gallen International Expert Consensus on treatment decision and prognosis of patients with invasive breast cancer. We retrospectively analyzed the therapy protocol and outcome of 134 cases based on age, body mass index (BMI), menopause, pathological types, tumor-node-metastasis (TNM) stages, percentage of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), Ki-67, molecular subtype, and tumor biomarkers. RS was calculated based on 21-gene assay following traditional (old RS cutoff) and updated (new RS cutoff) National Comprehensive Cancer Network (NCCN) guideline. In addition, we also compared treatment protocol of NCCN guidelines with St. Gallen International Expert Consensus. The results showed that BMI, PR, Ki-67, and molecular subtype are critical for the evaluation of risk factors. Based on the new cutoff, low, middle, and high RS were 18%, 66%, and 16%, respectively. In contrast, based on the old cutoff, low, middle, and high RS were 60%, 29%, and 11%, respectively. The agreement rate of NCCN guidelines and St. Gallen International Expert Consensus for adjuvant treatment was 50. However, there is minimal agreement (0.151, 0.071) in kappa coefficient of old and new cutoff. This study revealed that the combination of NCCN guidelines and St. Gallen International Expert Consensus might improve the benefits of adjuvant treatment in patients with early invasive breast cancer.

Distinct Diagnostic and Prognostic Values of Kinesin Family Member Genes Expression in Patients with Breast Cancer.

BACKGROUND This study investigated the diagnostic and prognostic values of kinesin superfamily proteins (KIFs) in breast cancer (BC) patients. MATERIAL AND METHODS All data were obtained from the Cancer Genome Atlas. DESeq was run to test for differentially expressed KIF genes. Patients were divided into high- and low-expression groups according to the median expression values of each KIF genes. Survival data were calculated using the Cox proportional hazard model. Comprehensive survival analysis was performed to evaluate the prognostic value of the prognostic signature. Gene set enrichment analysis (GSEA) was conducted to identify associated gene ontology and KEGG pathways. RESULTS Bioinformatics analysis showed that all KIF genes were significantly enriched during DNA replication and the cell cycle, and co-expressed with each other. Thirteen KIF genes were differentially expressed in cancer and adjacent tissues, and high levels of KIF15, KIF20A, KIF23, KIF2C and KIF4A genes were significantly correlated with poor overall survival (OS). GSEA showed that BC patients with high expression of KIF15, KIF20A, KIF23, KIF2C and KIF4A were enriched in the cell cycle process, P53 regulation pathway and mismatch repair. Combinations of low expression of KIF15, KIF20A, KIF23, KIF2C and KIF4A were more highly correlated with favorable OS. Nomograms showed that the KIF4A risk score provided the maximum number of risk points (range 0-100), whereas other genes made a lower contribution. CONCLUSIONS We conclude that 13 KIF genes are differentially expressed in BC tumor tissues, and KIF15, KIF20A, KIF23, KIF2C and KIF4A are associated with prognostic factors in BC.

Clinicopathological classification and traditional prognostic indicators of breast cancer.

Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. The objective of this study is to evaluate the value of molecular subtypes in breast cancer management according to a retrospective analysis of breast carcinoma molecular subtypes, histopathological grade, and TNM stage. A retrospective study of 475 paraffin-embedded tissues of breast cancer samples from the First Affiliated Hospital of Guangxi Medical University was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The differences of molecular subtypes of breast cancers in regard to TNM staging and pathological grade were analyzed using χ(2) tests. Values of P<0.05 were considered statistically significant. The frequency of luminal A, luminal B, HER2-positive luminal B, triple negative and non-luminal HER2-positive subtypes were: 35.5%, 22.5%, 13.1%, 15.2% and 13.7%, respectively. Among the five subtypes of breast cancer, the distribution of pathological grades showed a significant difference (P<0.001). There were significant differences in the distribution of TNM staging among the five subtypes of breast cancer (P<0.001). In addition to traditional prognostic indicators such as TNM staging and pathological grade, molecular subtype may aid clinical practice and research into breast cancer. Different molecular subtypes will lead to different prognosis and therapeutic option. Molecular subtyping is essential for breast cancer management.

Presence of PDGFRA and DOG1 mutations in gastrointestinal stromal tumors among Chinese population.

Approximately 15% of gastrointestinal stromal tumors (GIST) do not express KIT mutations and of these about 5 to 7% harbor mutations in PDGFRA. DOG1 was specifically expressed in GISTs. These cases require special attention for PDGFRA and DOG1 mutational status. Hundred cases of GIST were diagnosed between August 2007 and October 2012 at the First Affiliated Hospital of Guangxi Medical University. DNA from tumor tissues and normal adjacent tissues was isolated and amplified for the 22 exons of PDGFRA and 26 exons of DOG1. Each PCR product was sequenced. Amino acid sequences were inferred from DNA and aligned to GenBank reference sequences to determine the position and type of mutations. Overall, 16.0% of the samples had a mutation in PDGFRA, and GISTs with mutations in the DOG1 gene were not found. Of the mutations detected, they were in PDGFRA exon 18 (8 cases, 8%), PDGFRA exon 12 (5 cases, 5%), PDGFRA exon 14 (1 cases, 1.0%), PDGFRA exon 11 (1 cases, 1.0%), and PDGFRA exon 8 (1 cases, 1.0%). Of these, Y392S, L521P and T632K mutant occurred in PDGFRA exon 8, exon 11 and exon 14, respectively. The mutation of PDGFRA has been considered as another causative genetic event as PDGFRA mutations were found in most GISTs lacking a KIT mutation. PDGFRA mutations occurred preferentially in exon 18 and exon 12. Mutations occurring in PDGFRA exon 8 (Y392S), exon 11 (L521P) and exon 14 (T632K) also were first identified. The over-expression of DOG1 was not related to DOG1 gene mutation.

Abdominal drainage versus no drainage post-gastrectomy for gastric cancer.

BACKGROUND: Gastrectomy remains the primary therapeutic method for resectable gastric cancer. Thought of as an important measure to reduce post-operative complications and mortality, abdominal drainage has been used widely after gastrectomy for gastric cancer in previous decades. The benefits of abdominal drainage have been questioned by researchers in recent years. OBJECTIVES: The objectives of this review were to assess the benefits and harms of routine abdominal drainage post-gastrectomy for gastric cancer. SEARCH METHODS: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 11); MEDLINE (via PubMed) (1950 to November 2014); EMBASE (1980 to November 2014); and the Chinese National Knowledge Infrastructure (CNKI) Database (1979 to November 2014). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing an abdominal drain versus no drain in patients who had undergone gastrectomy (not considering the scale of gastrectomy and the extent of lymphadenectomy); irrespective of language, publication status, and the type of drain. We excluded RCTs comparing one drain with another. DATA COLLECTION AND ANALYSIS: We adhered to the standard methodological procedures of The Cochrane Collaboration. From each included trial, we extracted the data on the methodological quality and characteristics of the participants, mortality (30-day mortality), re-operations, post-operative complications (pneumonia, wound infection, intra-abdominal abscess, anastomotic leak, drain-related complications), operation time, length of post-operative hospital stay, and initiation of a soft diet. For dichotomous data, we calculated the risk ratio (RR) and 95% confidence interval (CI). For continuous data, we calculated mean difference (MD) and 95% CI. We tested heterogeneity using the Chi(2) test. We used a fixed-effect model for data analysis with RevMan software, but we used a random-effects model if the P value of the Chi(2) test was less than 0.1. MAIN RESULTS: We included four RCTs involving 438 patients (220 patients in the drain group and 218 in the no-drain group). There was no evidence of a difference between the two groups in mortality (RR 1.73, 95% CI 0.38 to 7.84); re-operations (RR 2.49, 95% CI 0.71 to 8.74); post-operative complications (pneumonia: RR 1.18, 95% CI 0.55 to 2.54; wound infection: RR 1.23, 95% CI 0.47 to 3.23; intra-abdominal abscess: RR 1.27, 95% CI 0.29 to 5.51; anastomotic leak: RR 0.93, 95% CI 0.06 to 14.47); or initiation of soft diet (MD 0.15 days, 95% CI -0.07 to 0.37). However, the addition of a drain prolonged the operation time (MD 9.07 min, 95% CI 2.56 to 15.57) and post-operative hospital stay (MD 0.69 day, 95% CI 0.18 to 1.21) and led to drain-related complications. Additionally, we should note that 30-day mortality and re-operations are very rare events and, as a result, very large numbers of patients would be required to make any sensible conclusions about whether the two groups were similar. The overall quality of the evidence according to the GRADE approach was 'very low' for mortality and re-operations, and 'low' for post-operative complications, operation time, and post-operative length of stay. AUTHORS' CONCLUSIONS: We found no convincing evidence to support routine drain use after gastrectomy for gastric cancer.

Clinico-pathological characteristics and prognostic factors of gastrointestinal stromal tumors among a Chinese population.

Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the digestive tract. GISTs include a group of heterogeneous tumors with different morphology, biologic behavior, and genetic characteristics, so their epidemiology, clinico-pathological features and prognosis is distinct in different countries. The objective of this study is to analyze clinico-pathological characteristics and prognostic factors of GISTs among Chinese population. We investigated 112 GIST patients were diagnosed between July 2008 and January 2013 at the First Affiliated Hospital of Guangxi Medical University. Histologic evaluation and immunohistochemistry analysis was performed on paraffin-embedded tissue from the 112 GISTs. Overall survival analysis was carried out using the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed according to Cox's proportional hazards model. Three and 5-year OS rates were 71.4 and 58.6% respectively. Univariate analysis showed that the following factors were significant in predicting OS: tumor site, tumor size, metastasis, resection margin status, cell type, invasion of adjacent organ, invasion of smooth muscle, mitotic rate, P53 and adjuvant therapy with imatinib (P<0.05). Multivariate analysis showed that tumor size, metastasis, resection margin status, mitotic rate, P53 and adjuvant therapy with imatinib were independent prognostic factors associated with OS. This may aid in the prediction of clinical evolution and guide treatments in patients with GIST in China.

Abdominal drainage versus no drainage post gastrectomy for gastric cancer.

BACKGROUND: Gastrectomy remains the primary therapeutic method for resectable gastric cancer. Thought of as an important measure to reduce post-operative complications and mortality, abdominal drainage was used widely after gastrectomy for gastric cancer in previous decades. The benefits of abdominal drainage have been questioned by researchers in recent years. OBJECTIVES: The objectives of this review were to access the benefits and harms of routine abdominal drainage post gastrectomy for gastric cancer. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Central/CCTR) in The Cochrane Library (2010, Issue 10), including the Specialised Registers of the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group; MEDLINE (via Pubmed, 1950 to October, 2010); EMBASE (1980 to October, 2010); and the Chinese National Knowledge Infrastructure (CNKI) Database (1979 to October, 2010). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing abdominal drain versus no drain in patients who had undergone gastrectomy (not considering the scale of gastrectomy and the extent of lymphadenectomy; irrespective of language, publication status, and the type of drain). We excluded RCTs comparing one drain with another. DATA COLLECTION AND ANALYSIS: From each trial, we extracted the data on the methodological quality and characteristics of the included studies, mortality (30-day mortality), re-operations, post-operative complications (pneumonia, wound infection, intra-abdominal abscess, anastomotic leak, drain-related complications), operation time, length of post-operative hospital stay and initiation of soft diet. For dichotomous data, we calculated the risk ratio (RR) and 95% confidence intervals (CI). For continuous data, we calculated mean differences (MD) and 95% CI. We tested heterogeneity using the Chi(2) test. We used a fixed-effect model for data analysis with RevMan software but we used a random-effects model if the P value of the Chi(2) test was less than 0.1. MAIN RESULTS: We included four RCTs involving 438 patients (220 patients in the drain group and 218 in the no-drain group).There was no evidence of a difference between the two groups in mortality (RR 1.73, 95% CI 0.38 to 7.84); re-operations (RR 2.49, 95% CI 0.71 to 8.74); post-operative complications (pneumonia: RR 1.18, 95% CI 0.55 to 2.54; wound infection: RR 1.23, 95% CI 0.47 to 3.23; intra-abdominal abscess: RR 1.27, 95% CI 0.29 to 5.51; anastomotic leak: RR 0.93, 95% CI 0.06 to 14.47); and initiation of soft diet (MD 0.15 day, 95% CI -0.07 to 0.37). However, the addition of a drain prolonged the operation time (MD 9.07 min, 95% CI 2.56 to 15.57) and post-operative hospital stay (MD 0.69 day, 95% CI 0.18 to 1.21) and lead to drain-related complications. Additionally, we should note that 30-day mortality and re-operations are very rare events and, as a result, very large numbers of patients would be required to make any sensible conclusions about whether the two groups were similar. The overall quality of the evidence according to the GRADE approach was "Very Low" for mortality and re-operations, and "Low" for post-operative complications, operation time, and post-operative length of stay. AUTHORS' CONCLUSIONS: We found no convincing evidence to support routine drain use after gastrectomy for gastric cancer.

Bilateral coronoid hyperplasia (Jacob disease on right and elongation on left): report of a case and literature review.

A case is reported of bilateral coronoid hyperplasia. The literature is reviewed concerning this condition's etiology, pathogenesis, clinical characteristics, diagnosis, and treatment. Jacob disease and coronoid elongation are both clinical features of coronoid hyperplasia. It is usually accompanied by restricted opening. The etiology and pathogenesis of coronoid hyperplasia are unclear. The condition can be diagnosed by panoramic radiographs and with 3-dimensional reconstructions from computerized tomography image data sets. Hyperplasia of the coronoid processes can be treated using an intraoral approach for coronoidectomy and dynamic laser physiotherapy after surgery. Although hyperplasia of the coronoid processes is uncommon in clinic, it can be found through careful examination and proper radiographic study. A 39-year-old female patient was referred for coronoid hyperplasia (Jacob disease on right and elongation on left). The histologic diagnosis for the right condylar condition was osteochondroma.

Scapular rotation in swimmers with and without impingement syndrome: practice effects.

PURPOSE: The purpose of this study was to examine the effects of a normal swim practice on the scapular kinematics of swimmers with impingement syndrome and healthy swimmers. METHODS: Twenty swimmers with no known shoulder pathology and 20 swimmers with shoulder impingement syndrome participated in this study. Shoulder strength measurements were made with a hand-held dynamometer. Static scapular upward rotation was measured with an inclinometer with the arm at rest, and at 45, 90, and 135 degrees of humeral elevation. Measurements were made pre- and postswim training. RESULTS: There were no differences in baseline measurements of kinematics between the two groups. After swimming, both groups experienced muscle fatigue as indicated by a significant reduction in force generation. Although swimming practice resulted in no significant differences in scapular kinematics for the healthy swimmers, there were significant decreases in scapular upward rotation in subjects with shoulder impingement. CONCLUSIONS: Abnormal scapular kinematics in swimmers with impingement syndrome may only be observed after an intense swim practice. The examination of swimmers immediately after swimming may provide more information regarding impingement syndrome than a typical clinical exam.