tsRNA: A Promising Biomarker in Breast Cancer.

tRNA-derived small RNAs (tsRNAs) are a novel class of non-coding small RNAs, generated from specific cleavage sites of tRNA or pre-tRNA. tsRNAs can directly participate in RNA silencing, transcription, translation, and other processes. Their dysregulation is closely related to the occurrence and development of various cancers. Breast cancer is one of the most common and fastest-growing malignant tumors in humans. tsRNAs have been found to be dysregulated in breast cancer, serving as a new target for exploring the pathogenesis of breast cancer. They are also considered new tumor markers, providing a basis for diagnosis and treatment. This article reviews the generation, classification, mechanism of action, function of tsRNAs, and their biological effects and related mechanisms in breast cancer, in the hope of providing a new direction for the diagnosis and treatment of breast cancer.

Efficacy and safety of total parathyroidectomy with autotransplantation vs. subtotal parathyroidectomy for secondary hyperparathyroidism: A retrospective study.

Background: No consensus has been reached on the best surgical approach for secondary hyperparathyroidism (SHPT). We evaluated the short-term and long-term efficacy and safety of total parathyroidectomy with autotransplantation (TPTX + AT) and subtotal parathyroidectomy (SPTX). Methods: We retrospectively analyzed the data of 140 patients undergoing TPTX + AT and 64 undergoing SPTX between 2010 and 2021 in Second Affiliated Hospital of Soochow University, and carried out follow-up. We compared the differences in symptoms, serological examinations, complications and mortality between the two methods, and explored the independent risk factors of secondary hyperparathyroidism recurrence. Results: In short time after surgery, serum intact parathyroid hormone and calcium level was lower in TPTX + AT group than that in SPTX group (both P < 0.05). Severe hypocalcemia was more common in TPTX group (P = 0.003). The recurrent rate was 17.1% for TPTX + AT and 34.4% for SPTX (P = 0.006). There was no statistical difference in all-cause mortality, cardiovascular events, cardiovascular mortality between the two methods. Higher preoperative serum phosphorus level (HR: 1.929 95% CI 1.045-3.563, P = 0.011) and the SPTX surgical method (HR: 2.309, 95% CI 1.276-4.176, P = 0.006) were found to be independent risk factors for SHPT recurrence. Conclusions: Compared with SPTX, TPTX + AT is more effective in reducing the recurrent risk of SHPT without increasing the risk of all-cause mortality and cardiovascular events.

Reprogramming of human peripheral blood mononuclear cells into induced mesenchymal stromal cells using non-integrating vectors.

Mesenchymal stromal cells (MSCs) have great value in cell therapies. The MSC therapies have many challenges due to its inconsistent potency and limited quantity. Here, we report a strategy to generate induced MSCs (iMSCs) by directly reprogramming human peripheral blood mononuclear cells (PBMCs) with OCT4, SOX9, MYC, KLF4, and BCL-XL using a nonintegrating episomal vector system. While OCT4 was not required to reprogram PBMCs into iMSCs, omission of OCT4 significantly impaired iMSC functionality. The omission of OCT4 resulted in significantly downregulating MSC lineage specific and mesoderm-regulating genes, including SRPX, COL5A1, SOX4, SALL4, TWIST1. When reprogramming PBMCs in the absence of OCT4, 67 genes were significantly hypermethylated with reduced transcriptional expression. These data indicate that transient expression of OCT4 may serve as a universal reprogramming factor by increasing chromatin accessibility and promoting demethylation. Our findings represent an approach to produce functional MSCs, and aid in identifying putative function associated MSC markers.

Superior Fidelity and Distinct Editing Outcomes of SaCas9 Compared to SpCas9 in Genome Editing.

A series of the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9) systems have been engineered for genome editing. The most widely used Cas9 is SpCas9 from Streptococcus pyogenes and SaCas9 from Staphylococcus aureus. However, a comparison of their detailed gene editing outcomes is still lacking. By characterizing the editing outcomes of 11 sites in human induced pluripotent stem cells (iPSCs) and K562 cells, we found that SaCas9 could edit the genome with greater efficiency than SpCas9. We also compared the spacer lengths of single-guide RNA (sgRNA, 18-21 nt for SpCas9 and 19-23 nt for SaCas9) and found that the optimal spacer lengths were 20 nt and 21 nt for SpCas9 and SaCas9, respectively. However, the optimal spacer size for a particular guide RNA ranged from 18-21 nt or 21-22 nt for SpCas9 and SaCas9, respectively. Furthermore, SpCas9 exhibited a more substantial bias than SaCas9 for nonhomologous end-joining (NHEJ) +1 insertion at the fourth nucleotide upstream of the protospacer adjacent motif (PAM), characteristic of a staggered cut. Accordingly, editing with SaCas9 led to higher knock-in efficiencies of NHEJ-mediated double-stranded oligodeoxynucleotide (dsODN) insertion or adeno-associated virus serotype 6 (AAV6) donor-mediated homology-directed repair (HDR). Finally, GUIDE-seq analysis revealed that SaCas9 exhibited significantly reduced off-target effects compared with SpCas9. Our work indicates the superior performance of SaCas9 to SpCas9 in transgene integration-based therapeutic gene editing and the necessity to identify the optimal spacer length to achieve desired editing results.

Effective control of large deletions after double-strand breaks by homology-directed repair and dsODN insertion.

BACKGROUND: After repairing double-strand breaks (DSBs) caused by CRISPR-Cas9 cleavage, genomic damage, such as large deletions, may have pathogenic consequences. RESULTS: We show that large deletions are ubiquitous but are dependent on editing sites and cell types. Human primary T cells display more significant deletions than hematopoietic stem and progenitor cells (HSPCs), whereas we observe low levels in induced pluripotent stem cells (iPSCs). We find that the homology-directed repair (HDR) with single-stranded oligodeoxynucleotides (ssODNs) carrying short homology reduces the deletion damage by almost half, while adeno-associated virus (AAV) donors with long homology reduce large deletions by approximately 80%. In the absence of HDR, the insertion of a short double-stranded ODN by NHEJ reduces deletion indexes by about 60%. CONCLUSIONS: Timely bridging of broken ends by HDR and NHEJ vastly decreases the unintended consequences of dsDNA cleavage. These strategies can be harnessed in gene editing applications to attenuate unintended outcomes.

lncRNA NEAT1 facilitates the progression of colorectal cancer via the KDM5A/Cul4A and Wnt signaling pathway.

Colorectal cancer (CRC) is a major cause of cancer­related mortality. The aberrant expression of long non­coding RNAs (lncRNAs) is implicated in the pathogenesis of CRC. The present study investigated the role of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in CRC. lncRNA NEAT1 expression was detected in CRC tissues and cell lines. HCT116 cells were transfected with si­NEAT1, and the malignant behavior of the cells was detected. The binding associations between NEAT1 and E2F1, as well as between E2F1 and KDM5A were verified. si­NEAT1­transfected cells were also transfected with si­KDM5A. H3K4me3 methylation and cullin 4A (Cul4A) expression in HCT116 cells were detected. The si­NEAT1­transfected cells were also transfected with pc­Cul4A. Proteins related to the Wnt pathway were detected. A xenograft model of CRC using nude mice was established and the mice were injected with si­NEAT1­transfected HCT116 cells. lncRNA NEAT1 was found to be upregulated in CRC tissues and cells. NEAT1 silencing inhibited the malignant behaviors of the HCT116 cells. lncRNA NEAT1 inhibited KDM5A expression by binding to E2F1. The downregulation of KDM5A reversed the inhibitory effects of NEAT1 silencing on the malignant behavior of the cells. KDM5A inhibited Cul4A expression via the demethylation of H3K4me3. The overexpression of Cul4A promoted the malignant behavior of the si­NEAT1­transfected HCT116 cells. lncRNA NEAT1 activated the Wnt pathway via KDM5A/Cul4A. In vivo experiments confirmed the role of NEAT1 in CRC. On the whole, the present study demonstrates that lncRNA NEAT1 facilitates the progression of CRC via the KDM5A/Cul4A/Wnt axis.

Dynamics and competition of CRISPR-Cas9 ribonucleoproteins and AAV donor-mediated NHEJ, MMEJ and HDR editing.

Investigations of CRISPR gene knockout editing profiles have contributed to enhanced precision of editing outcomes. However, for homology-directed repair (HDR) in particular, the editing dynamics and patterns in clinically relevant cells, such as human iPSCs and primary T cells, are poorly understood. Here, we explore the editing dynamics and DNA repair profiles after the delivery of Cas9-guide RNA ribonucleoprotein (RNP) with or without the adeno-associated virus serotype 6 (AAV6) as HDR donors in four cell types. We show that editing profiles have distinct differences among cell lines. We also reveal the kinetics of HDR mediated by the AAV6 donor template. Quantification of T50 (time to reach half of the maximum editing frequency) indicates that short indels (especially +A/T) occur faster than longer (>2 bp) deletions, while the kinetics of HDR falls between NHEJ (non-homologous end-joining) and MMEJ (microhomology-mediated end-joining). As such, AAV6-mediated HDR effectively outcompetes the longer MMEJ-mediated deletions but not NHEJ-mediated indels. Notably, a combination of small molecular compounds M3814 and Trichostatin A (TSA), which potently inhibits predominant NHEJ repairs, leads to a 3-fold increase in HDR efficiency.

[Effects of electroacupuncture on proangiogenesis process and protein turnover in a mouse model of sarcopenia].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on proangiogenesis process and protein turn-over in a mouse model of sarcopenia, so as to explore its potential molecular mechanism anti-aging. METHODS: Fourteen 30-week-old male SAMP8 mice were randomly divided into a model group (n=7) and an EA group (n=7). Seven anti-rapidly aging SAMR1 mice of the same age were used as the control group (n=7). EA (1 mA, 4 Hz) was applied to bilateral "Zusanli"(ST36) and "Yanglingquan"(GB34) for 20 minutes each time once a day, 6 times a week for 4 weeks. The exhausted running platform was used to test the sports function. Gastrocnemius muscle mass and relative ratio of gastrocnemius muscle mass to body mass were measured. HE staining and transmission electron microscope were used to observe the morphology, and the cross-sectional area of gastrocnemius muscle was calculated. Relative protein expressions of protein kinase B (AKT) , phosphorylated (p) -AKT, mammalian target of rapamycin (mTOR) , p-mTOR, p70 ribosomal protein S6 kinase (p70S6K) , p-p70S6K,hypoxia inducible factor-1α (HIF-1α) and relative mRNA expressions of HIF-1α, vascular endothelial growth factor A (VEGF-A) , muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) were detected by Western blot and real-time fluorescence quantitative PCR, seperatively. RESULTS: Compared with the control group, the running time and distance, body mass and gastrocnemius mass, and the ratio of gastrocnemius mass to body mass decreased(P<0.01, P<0.05), cross-sectional area of gastrocnemius, related protein expression of p-AKT,p-mTOR, p-p70S6K and HIF-1α, mRNA expression of HIF-1α and VEGF-A decreased (P<0.01), while mRNA expression of MuRF1 and MAFbx increased (P<0.01) in the model group. Following EA intervention, the running time and distance, body mass and gastrocnemius mass and the ratio of gastrocnemius mass to body mass increased (P<0.05), cross-sectional area of gastrocnemius, related protein expression of p-AKT,p-mTOR, p-p70S6K and HIF-1α, mRNA expression of HIF-1α and VEGF-A were significantly up-regulated (P<0.01), mRNA expression of MuRF1 and MAFbx down-regulated (P<0.01, P<0.05) in the EA group compared with the model group. CONCLUSION: EA may delay the aging muscle atrophy in mice by regulating the gastrocnemius muscle's proangiogenesis process and protein turnover.

Breast Reconstruction with Silicone Prosthesis Immediately Following Polyacrylamide Gel Removal.

OBJECTIVE: To determine the feasibility and efficacy of breast reconstruction with silicone prosthesis immediately following polyacrylamide gel removal. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Breast and Thyroid Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China, from November 2013 to May 2017. METHODOLOGY: Twenty-seven patients with serious complications resulting from polyacrylamide gel (PAAG) injection were operated in our hospital. Using an inframammary fold incision, the PAAG and surrounding tissues were completely removed. All patients were received mastopexy and immediate breast reconstruction. RESULTS: Of all patients, 26 reported relief of preoperative complications, without obvious postoperative complications. Only one patient developed recurring infections after surgery and removed the prostheses. CONCLUSION: After removal of PAAG, mastopexy followed by immediate breast reconstruction allows the patient to obtain a satisfactory appearance without serious complications. The key to successful breast reconstruction with prostheses first lies with the complete excision of PAAG and surrounding tissues.

[Effect of Electroacupuncture on Synovial M 1/M 2 Macrophage Polarization in Rats with Acute Gouty Arthritis].

OBJECTIVE: To explore the effect of electroacupuncture (EA) on the expression of synovial AMP-activated protein kinase (AMPK) protein α， arginase-1 mRNA, nitric oxide synthase 2 (NOS 2) mRNA, NOD-like receptor protein 3 (NLRP 3) mRNA, and interleukin-1 ß (IL-1 ß) mRNA in acute gouty arthritis (AGA) rats, so as to explore its mechanisms underlying improvement of AGA via M 1/M 2 macrophage polarization. METHODS: Male Wistar rats were randomly divided into normal control, model, medication (colchicine) and EA groups (n＝15 rats in each group). The AGA model was established by injection of sodium urate crystal (MSU) suspension (0.2 mL) into the articular cavity of the left knee. The rats of the normal control group received articular injection of normal saline (0.2 mL) of the left knee, and those of the medication group were treated by gavage of the colchicine (0.3 mg•kg－1•d－1) once daily for 7 days. EA (2 Hz/10 Hz, 1.0 mA) was applied to "Zusanli"(ST 36) and "Sanyinjiao" (SP 6) of the left hind limb for 10 min, once daily for 7 days. The inflammatory conditions of the synovial membrane tissue of the left knee joint were observed by H．E. staining. The expression levels of phosphorylated AMPKα (p-AMPKα) protein, and arginase-1 (a maker of M 2 macrophages) mRNA, NOS 2 (a maker of M 1 macrophages) mRNA, NLRP 3 mRNA, and IL-1 ß mRNA in the knee joint synovial tissue were detected by Western blot and quantitative real-time PCR, respectively. RESULTS: Compared with the normal group, the inflammatory cell infiltration of the synovial tissue was more severe, the expression of p-AMPKα protein was significantly decreased (P<0.01), and the expression levels of arginase-1, NOS 2, IL-1 ß and NLRP 3 mRNAs were considerably increased in the model group (P<0.01). The expression levels of p-AMPKα protein and arginase-1 mRNA were significantly up-regulated, and those of NOS 2, IL-1 ß and NLRP 3 mRNAs obviously down-regulated in both EA and medication groups relevant to the model group (P<0.01, P<0.05), suggesting an increase of M 2 macrophage and a decrease of M 1 macrophage activity after EA. No significant differences were found between the EA and medication groups in up-regulating p-AMPKα expression and in down-regulating NOS 2, IL-1 ß and NLRP 3 mRNA expression (P>0.05), except higher up-regulation of arginase-1 mRNA in the medication group (P<0.05)．. CONCLUSION: EA intervention can up-regulate the expression of arginase-1 mRNA and p-AMPKα protein, and down-regulate the expression of NOS 2, IL-1 ß and NLRP 3 mRNAs in synovial tissues in AGA rats, which may contribute to its anti-inflammatory effect by promoting conversion of macrophages from M 1 pro-inflammatory phenotype to M 2 anti-inflammatory phenotype.

Circulating HER-2 mRNA in the peripheral blood as a potential diagnostic and prognostic biomarker in females with breast cancer.

Breast cancer is a prevalent malignant cancer worldwide, and a lack of defined biomarkers for early prognostication contributes to its high associated mortality rate, especially in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. In the present study, HER-2 mRNA levels in patients were detected prior to surgery and during neoadjuvant chemotherapy to explore its potential diagnostic and prognostic value. Blood samples were collected from 70 patients with breast cancer, including 50 HER-2-negative and 20 HER-2-positive patients, prior to and following surgery (postoperative, n=13; neoadjuvant chemotherapy, n=5); the control group included 35 samples from healthy individuals. The relative mRNA level of HER-2 in blood was determined by one-step reverse transcription-quantitative polymerase chain reaction. HER-2 expression curves of measurements taken during neoadjuvant chemotherapy were compared with the tumor size. A significant difference in the blood HER-2 mRNA level was observed between healthy women and patients with breast cancer (P<0.0001). A cutoff value of 1.512 was established for the circulating HER-2 level in healthy subjects based on the upper 95% confidence interval value of samples from the control group. The level of HER-2 mRNA in blood was associated with the HER-2 status, Ki-67 expression, and lymphovascular invasion in primary tumor tissue samples; however, there was no association with the lymph node status, tumor stage, tumor grade, tumor size, patient age, estrogen or progesterone receptor status of the primary tumor. HER-2 mRNA levels were associated with the response rate, as determined by primary tumor size, in patients who received neoadjuvant chemotherapy. In conclusion, baseline and early changes in peripheral blood HER-2 mRNA indicated that HER-2 mRNA may be a potential diagnostic biomarker for breast cancer and a prognostic marker for predicting the efficacy of neoadjuvant therapy.

MiR-539 inhibits proliferation and migration of triple-negative breast cancer cells by down-regulating LAMA4 expression.

BACKGROUND: Recent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcinogenesis. However, its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Furthermore, we also identified the potential miRNA directly targeting LAMA4. METHODS: Western blot, Real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) were used to detect the expression of LAMA4 in TNBC. The effects of LAMA4 on TNBC cell proliferation, migration and invasion were also explored in vitro. The potential miRNA that targets LAMA4 was determined by dual luciferase reporter assay and verified by qPCR and western blot analysis. RESULTS: Our study showed LAMA4 mRNA (p = 0.001) and protein (p = 0.005) expression in TNBC tissue samples were elevated compared with adjacent normal tissue samples, and LAMA4 was mainly expressed in the cytoplasm of breast carcinoma cells. Knockdown of LAMA4 inhibited TNBC cell proliferation, migration and invasion in vitro. Moreover, further study revealed that LAMA4 was a putative target of miR-539, and miR-539 negatively regulated LAMA4 expression by directly targeting its 3'-UTR. CONCLUSIONS: Our study suggested that miR-539 suppressed the expression of LAMA4. LAMA4 plays an important role in tumor progression and may be an important target in treatment of TNBC.

ATP citrate lyase is increased in human breast cancer, depletion of which promotes apoptosis.

Breast cancer is a malignant tumor that is harmful to women's health around the world. Investigating the biological mechanism is, therefore, of pivotal importance to improve patients' prognoses. Compared to non-neoplastic tissues, enhanced glucose and lipid metabolism is one of the most common properties of malignant breast cancer. Adenosine triphosphate (ATP) citrate lyase is a key enzyme linking aerobic glycolysis and fatty acid synthesis and is of high biological and prognostic significance in breast cancer. In our clinical study, fresh clinical tissues were used to analyze ATP citrate lyase expression by western blotting, and paraffin archived samples from 62 breast cancer patients were used to analyze ATP citrate lyase expression by immunohistochemistry. In the cellular study, following small interfering RNA-mediated inhibition of ATP citrate lyase in MCF-7 cells, cell viability and apoptosis were measured using the Cell Counting Kit-8 and flow cytometry, respectively. Breast cancer tissues showed strong expression of ATP citrate lyase, whereas adjacent normal tissues showed weak expression. Silencing of endogenous ATP citrate lyase expression by small interfering RNA in MCF-7 cells suppressed cell viability and increased cell apoptosis. Collectively, our study revealed that expression of ATP citrate lyase was significantly increased in breast cancer tissue compared with normal tissue. In addition, we found that depletion of ATP citrate lyase suppressed tumor growth, which suggests that ATP citrate lyase-related inhibitors might be potential therapeutic approaches for breast cancer.

Role of Magnetic Resonance Imaging in Detection of Pathologic Complete Remission in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: A Meta-analysis.

Pathologic complete remission after neoadjuvant chemotherapy has a role in guiding the management of breast cancer. The present meta-analysis examined the accuracy of contrast-enhanced magnetic resonance imaging (CE-MRI) and diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting the response to neoadjuvant chemotherapy and compared CE-MRI with ultrasonography, mammography, and positron emission tomography/computed tomography (PET/CT). Medical subject heading terms and related keywords were searched to generate a compilation of eligible studies. The pooled sensitivity, specificity, diagnostic odds ratio, area under summary receiver operating characteristic curve (AUC), and Youden index (Q* index) were used to estimate the diagnostic efficacy of CE-MRI, DW-MRI, ultrasonography, mammography, and PET/CT. A total of 54 studies of CE-MRI and 8 studies of DW-MRI were included. The overall AUC and the Q* index values for CE-MRI and DW-MRI were 0.88 and 0.94 and 0.80 and 0.85, respectively. According to the summary receiver operating characteristic curves, CE-MRI resulted in a higher AUC value and Q* index compared with ultrasonography and mammography but had values similar to those of DW-MRI and PET/CT. CE-MRI accurately assessed pathologic complete remission in specificity, and PET/CT and DW-MRI accurately assessed pathologic complete remission in sensitivity. The present meta-analysis indicates that CE-MRI has high specificity and DW-MRI has high sensitivity in predicting pathologic complete remission after neoadjuvant chemotherapy. CE-MRI is more accurate than ultrasonography or mammography. Additionally, PET/CT is valuable for predicting pathologic complete remission. CE-MRI, combined with PET/CT or DW-MRI, might allow for a more precise assessment of pathologic complete remission.

Ligustrazine induces apoptosis of breast cancer cells in vitro and in vivo.

INTRODUCTION: Ligustrazine, the active ingredient present in Umbelliferae plant roots used in Chinese medicine, plays a vital role in reversing multidrug resistance in tumors. This study aims to investigate its anticancer activity and underlying mechanisms in human breast cancer cells in vitro and in vivo. MATERIALS AND METHODS: Human breast cancer cell line MDA-MB-231 was incubated with different concentrations of ligustrazine. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; and cell apoptosis and cell cycle were assessed by flow cytometry. Subcutaneous MDA-MB-231 xenograft tumors were established in nude BALB/c mice. Ligustrazine was intraperitoneally administered. The tumor growth was monitored. RESULTS: In vitro, ligustrazine inhibited cell survival in a dose-and time-dependent manner, and induced apoptosis, as indicated by a dramatic increase in sub-G0/G1 cells. The in vivo results were consistent with the in vitro ones: Administration of ligustrazine substantially inhibited tumor growth, which also indicated that ligustrazine inhibited proliferation of MDA-MB-231 cells in vitro. CONCLUSIONS: Ligustrazine causes apoptotic death and tumor regression in human breast cancer cells in vitro and in vivo models.

Laparoscopic permanent sigmoid stoma creation through the extraperitoneal route versus transperitoneal route. A meta-analysis of stoma-related complications.

OBJECTIVES: To compare laparoscopic extraperitoneal colostomy with transperitoneal colostomy for construction of a permanent stoma by measuring the incidence of parastomal hernia, and other postoperative complications related to colostomy. METHODS: The meta-analysis was carried out in the General Surgery Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China in 2014. A literature search of Medline, EMBASE, Cochrane database, and the Chinese Biomedical Literature Database (CBM) from the years 1990 to 2014 was performed. The literature searches were carried out using medical subject headings and free-text words: extraperitoneal colostomy, transperitoneal colostomy, laparoscopic extraperitoneal colostomy, rectal cancer,  laparoscopic abdominoperineal resection, parastomal hernia, permanent stoma, and colostomy-related complications. Two different reviewers carried out the search and evaluated studies independently. RESULTS: One randomized controlled trial and 6 retrospective studies were included. A total of 378 patients (209 extraperitoneal colostomy and 169 transperitoneal colostomy) were identified. Our analysis showed that there was a significantly lower rate of parastomal hernia (odds ratio 0.10; 95% confidence interval 0.03-0.29, p<0.0001) in the extraperitoneal colostomy group. However, the other stoma-related complications were not significantly different between the 2 groups. CONCLUSION: Colostomy construction via the extraperitoneal route using a laparoscopic approach can largely reduce the incidence of parastomal hernia. Laparoscopic permanent sigmoid stoma creation through the extraperitoneal route should be the first choice after laparoscopic abdominoperineal resection. 

Increased activity of CHK enhances the radioresistance of MCF-7 breast cancer stem cells.

The resistance of breast cancer to radiotherapy remains a major obstacle to successful cancer management. Radiotherapy may result in DNA damage and activate breast cancer stem cells. DNA damage may lead to activation of the checkpoint kinase (CHK) signaling pathway, of which debromohymenialdisine (DBH) is a specific inhibitor. Radiotherapy also increases the expression of phosphorylated CHK1/2 (pCHK1/2) in the breast cancer cell line, MCF-7, in vitro in a dose-dependent manner. DBH is a relatively stable effective inhibitor that significantly reduces pCHK1/2 expression and MCF-7 proliferation. Low-dose radiotherapy combined with DBH resulted in a higher MCF-7 inhibition rate compared with high-dose radiation alone. This result indicates that the inhibition of the CHK1/2 signal pathway may significantly reduce DNA damage within radiated cells. Radiotherapy may also regulate the proportion of CD44+/CD24- MCF-7 cancer stem cells in a dose- and time-dependent manner. However, the stem cell proportion of MCF-7 cells was significantly reduced by treatment with DBH. The inhibition is relatively stable and time dependent. Significant reductions were observed after 3 days of culture (P<0.01). The results of the present study indicate that the DBH-induced downregulation of CHK may provide a novel method of enhancing the effect of radiotherapy and reducing stem cell survival in the MCF-7 cell line.

Endoscopic subcutaneous mastectomy: A novel and effective treatment for gynecomastia.

The aim of this study was to evaluate the procedure for and efficacy of endoscopic subcutaneous mastectomy for gynecomastia. Endoscopic subcutaneous mastectomy was performed on 100 benign, palpable breast enlargements in 58 male patients who were followed-up for 15-63 months. The surgery was conducted with the insufflation of CO2 subdermally. No cases were converted to open surgery. The unilateral surgery time was 70-90 min. The mean volume of the resected tissue was 200 ml. All procedures were completed successfully, with satisfactory clinical effects and ideal esthetic results postoperatively. There were three cases (3%) of papillary epidermal partial necrosis; following removal of the dressing during the hospital stay, normal nipple sensation returned. Endoscopic subcutaneous mastectomy had good clinical effects and ideal cosmetic results and is an appropriate approach for gynecomastia.

Expression and clinical significance of activating transcription factor 3 in human breast cancer.

OBJECTIVE(S): Breast cancer is the most common type of cancer among women worldwide. This study investigated the expression and clinical significance of activating transcription factor 3 (ATF3) in human breast cancer and its relationship with the clinical outcome of breast cancer. Materials and Methods : ATF3 expressions were detected in 114 primary breast cancer tissues and 114 adjacent normal tissues using immunohistochemistry (IHC) assay. Categorical variables were statistically compared by chi-square or Fisher's exact test. Survival curves were evaluated using the Kaplan-Meier method and comparisons of survival rates were tested using a Log-rank test. Results : IHC analysis showed that the positive expression of ATF3 protein was detected in breast cancer tissue with a positive ratio of 76.3%, and the positive ATF3 expression in adjacent normal breast tissue was 13.2%, which is lower than that in breast cancer tissue samples (P<0.01). Furthermore, ATF3 expression showed significant correlation with TNM stage, invasion, lymph node metastasis and number of metastatic lymph nodes (P=0.038, P=0.029, P=0.026, and P=0.039 respectively), and did not correlate with patients' age and tumor size (P>0.05). A significant difference in overall survival rate was found between the patients with positive expression of ATF3 protein and those with negative expression (P=0.041). Conclusion : Increased ATF3 expression participate in the tumorigenesis, invasion and metastasis of breast cancer, and ATF3 may be useful as a new prognostic indicator for breast cancer patients.