The Scar-Hidden Surgery on Gynecomastia: Experiences from a Single-Institutional Large Case Series.

BACKGROUND: To summarize the experiences on the mastoscopic subcutaneous mastectomy for gynecomastia by "nine-step method" based on the "5S" goal and standardize this operation. PATIENTS AND METHODS: Between January 1, 2002, and October 31, 2021, a total of 2035 breasts of 1082 male patients with gynecomastia, of which 129 patients with one side, were underwent mastoscopic subcutaneous mastectomy. The follow-up endpoint was 3 months after surgery. RESULTS: All patients were successfully completed the operation, and none of them was transferred to open operation. The operation time for unilateral breast was 12-28 min, and the average time was 17.7 ± 6.2 min. The amount of bleeding during unilateral operation was very small, about 5-10 ml. The total drainage volume was 5-50 ml after the operation, and the drainage tube was removed in 3-5 days. The epidermal necrosis occurred in 0.3% nipple. 0.2% chest wall had a little ecchymosis in the supero-medial region of the breast. All patients had the normal feeling of nipples and areola, the smoothing and symmetrical chest wall, and the natural contour. There was no recurrence during the follow-up period. CONCLUSIONS: The mastoscopic subcutaneous mastectomy for gynecomastia by "nine-step method" based on the "5S" goal has a short operation time, few surgical complications and good esthetics. It achieves the "5S" goals on the complete removal of glandular tissue (sweeping), small and scar-hidden incision are small (scarless), good symmetry of bilateral chest wall (symmetry), normal chest shape (shape), and smoothing chest wall (smoothing). LEVEL OF EVIDENCE III: The journal asks authors to assign a level of evidence to each article. For a complete description of Evidence-Based Medicine ratings, see the Table of Contents or the online Instructions for Authors at www.springer.com/00266 .

Novel immune-related genes in the tumor microenvironment with prognostic value in breast cancer.

BACKGROUND: Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical. METHODS: The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas (TCGA) were employed to comprehensively evaluate the TME. Then, TME characteristics were assessed, overlapping genes of the top 3 Gene Ontology (GO) terms and upregulated differentially expressed genes (DEGs) were analyzed. Finally, through combined analyses of overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network, novel immune related genes with good prognosis were screened and validated in both TCGA and GEO database. RESULTS: Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on GO functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. The top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1. CONCLUSIONS: High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.

Identification of key candidate genes and pathways in anaplastic thyroid cancer by bioinformatics analysis.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a refractory and poor prognosis tumor Present study aimed to investigate the underlying biological functions and pathways involved in the development of ATC and to identify potential hub genes and candidate biomarkers of ATC. MATERIALS AND METHODS: Bioinformatics analyses were performed to identify the differentially expressed genes (DEGs) between ATC tissue samples and adjacent normal tissue samples. Protein-protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape software and divided into sub-networks using the Molecular Complex Detection (MCODE) plug-in. DEGs in each module was analyzed by enrichment analysis of the KEGG Orthology Based Annotation System (KOBAS) web software version 3.0. Eventually, the hub genes from bioinformatics analysis were verified by qRT-PCR assay in different ATC cell lines. RESULTS: Thirty hub genes were selected and three modules were built by the Cytoscape software from the PPI network. Seven genes (CDK1, CCNB2, BUB1B, CDC20, RRM2, CHEK1 and CDC45) were screened from thirty hub genes. Enrichment analysis showed that these hub genes were primarily accumulated in 'cell cycle', 'p53 signaling pathway', 'viral carcinogenesis', 'pyrimidine metabolism' and 'ubiquitin mediated proteolysis'. The results of qRT-PCR indicated that seven hub genes were unregulated in three ATC cell lines compared with normal thyroid gland cell. CONCLUSIONS: These findings suggest that CDK1, CCNB2, BUB1B, CDC20, RRM2, CHEK1 and CDC45 may serve as novel diagnosis biomarkers and potential therapeutic target for ATC.

MicroRNA-214-3p Targeting Ctnnb1 Promotes 3T3-L1 Preadipocyte Differentiation by Interfering with the Wnt/ß-Catenin Signaling Pathway.

Differentiation from preadipocytes into mature adipocytes is a complex biological process in which miRNAs play an important role. Previous studies showed that miR-214-3p facilitates adipocyte differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. The detailed function and molecular mechanism of miR-214-3p in adipocyte development is unclear. In this study, the 3T3-L1 cell line was used to analyze the function of miR-214-3p in vitro. Using 5-Ethynyl-2'-deoxyuridine (EdU) staining and the CCK-8 assay, we observed that transfection with the miR-214-3p agomir visibly promoted proliferation of 3T3-L1 preadipocytes by up-regulating the expression of cell cycle-related genes. Interestingly, overexpression of miR-214-3p promoted 3T3-L1 preadipocyte differentiation and up-regulated the expression of key genes for lipogenesis: PPARγ, FABP4, and Adiponectin. Conversely, inhibition of miR-214-3p repressed 3T3-L1 preadipocyte proliferation and differentiation, and down-regulated the expression of cell cycle-related genes and adipogenic markers. Furthermore, we proved that miR-214-3p regulates 3T3-L1 preadipocyte differentiation by directly targeting the 3'-untranslated regions (3'UTR) of Ctnnb1, which is an important transcriptional regulatory factor of the Wnt/ß-Catenin pathway. Taken together, the data indicate that miR-214-3p may positively regulate preadipocyte proliferation and enhance differentiation through the Wnt/ß-Catenin signaling pathway.

Matrine reversed multidrug resistance of breast cancer MCF-7/ADR cells through PI3K/AKT signaling pathway.

Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, and has been used clinically for breast cancer with marked therapeutic efficacy in China. However, the mechanism has not been well known. Thus, the present study was to explore whether Matrine reverses multidrug resistance for breast cancer cells through the regulation of PI3K/AKT signaling pathway. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the inhibitory action; Annexin V to detect apoptosis; fluorospectrophotometry to examine intracellular adriamycin (ADR) accumulation; and Western blot to label the proteins of P-glycoprotein (P-gp), MRP1, PTEN, p-AKT, Bcl-2, Bax, and Caspase-3. Matrine (0-2.5 mg/mL) inhibited MCF-7/ADR cell growth and induced apoptosis (P < 0.01). A total of 0.2 mg/mL Matrine could increase the intracellular concentration of ADR; the accumulation in MCF-7/ADR cells increased 3.56 times. Compared with control group, 0.6, 1.2 mg/mL Matrine reduced protein expressions of P-gp, MRP1, p-AKT, Bcl-2, but increased PTEN, Bax, and cleaved caspase-3 gradually, and unchanged caspase-3. Matrine was more likely to reduce the expression of P-gp, MRP1, and p-AKT at the same inhibition radio of Matrine, (0.6 mg/mL) and MK2206 (0.05 µmol/L). Matrine inhibited MCF-7/ADR cell growth, induced apoptosis, and reversed multidrug resistance for breast cancer cells through the regulation of downstream apoptosis factors of PI3K/AKT signaling pathway by decreasing cell phosphorylation of AKT level.

Intracellular Delivery of Therapeutic Protein via Ultrathin Layered Double Hydroxide Nanosheets.

The therapeutic application of biofunctional proteins relies on their intracellular delivery, which is hindered by poor cellular uptake and transport from endosomes to cytoplasm. Herein, we constructed a two-dimensional (2D) ultrathin layered double hydroxide (LDH) nanosheet for the intracellular delivery of a cell-impermeable protein, gelonin, towards efficient and specific cancer treatment. The LDH nanosheet was synthesized via a facile method without using exfoliation agents and showed a high loading capacity of proteins (up to 182%). Using 2D and 3D 4T1 breast cancer cell models, LDH-gelonin demonstrated significantly higher cellular uptake efficiency, favorable endosome escape ability, and deep tumor penetration performance, leading to a higher anticancer efficiency, in comparison to free gelonin. This work provides a promising strategy and a generalized nanoplatform to efficiently deliver biofunctional proteins to unlock their therapeutic potential for cancer treatment.

A study on the antibacterial property and biocompatibility of ramie fiber.

Ramie fiber (RF) has excellent tensile strength and breathability, making it a promising material for biomedical applications. However, few studies on the antibacterial properties and biocompatibility of RF have been reported. This study aimed to investigate the antibacterial property and biocompatibility of RF with bacteria and fibroblasts. The results showed that the antibacterial activity of RF was better than that of natural cotton fiber (NCF) and close to that of medical cotton fiber (MCF) for bothStaphylococcus aureus(S. aureus) andEscherichia coli(E.coli), and RF was more antibacterial againstS. aureusthanE.coli. The RF, MCF and NCF promoted the proliferation and spread of mouse fibroblast (L929) cells. The results indicated that RF has excellent antibacterial properties and biocompatibility, making it a potential biomaterial for biomedical applications.

The response of bioactive titanium surfaces with different structure to UVC-irradiation to eliminate the negative effect on biological properties during aging time.

The biological aging of titanium implants affects the service lifetime negatively in clinical applications, and Ultraviolet (UV) irradiation is an applicable method to overcome the biological aging. This study investigated the changes in surface characteristics and biological properties of bioactive titanium surfaces with different structure and topography after Ultraviolet C (UVC) irradiation. The bioactive titanium surfaces were prepared by anodizing (AO), sandblasting and acid-etching (SLA), acid-alkali etching (AA), alkali-heat etching (AH) methods. Samples were stored at dark for 7 weeks to simulate biological aging process and then irradiated by UVC for 2 h. The results showed that the hydroxyl groups (Ti-OH) on surfaces, which are crucial to enhance the biological properties, were easier to be generated on AO surfaces by UVC-irradiation, owing to a mixture of anatase and rutile on surfaces. UVC-irradiation had the strongest effect on AO surfaces to enhance the bioactivity in bone-like apatite deposition and better biocompatibility in mesenchymal stem cells (MSCs) attachment and proliferation. Therefore, titanium surfaces with a mixture phase of anatase and rutile have the potential to effectively utilize the benefits of UVC-irradiation to overcome the negative effects of the biological aging and have a promising clinical application prospect.

17-Year Follow-up of Comparing Mastoscopic and Conventional Axillary Dissection in Breast Cancer: A Multicenter, Randomized Controlled Trial.

INTRODUCTION: Longer follow-up was necessary to determine the exact value of mastoscopic axillary lymph node dissection (MALND). METHODS: From January 1, 2003, to December 31, 2005, 1027 patients with breast cancer were randomly assigned to two groups: MALND and CALND (conventional axillary lymph node dissection); 996 eligible patients were enrolled. RESULTS: The final cohort of 996 patients was followed for an average of 198 months. Events other than death differed significantly between the two cohorts (p = 0.0311; 46.3% in MALND and 53.2% in CALND, respectively). The sum of events other than death and deaths from other causes was much higher in the CALND (59.6%) than MALND (53.4%) group (p = 0.0494). The 17-year disease-free survival DFS rates were 36.7% for the MALND and 33.6% for the CALND group, respectively. There was a significant difference between the groups (p = 0.0306). Overall survival (OS) rates were 53.2% after MALND and 46.0% after CALND (p = 0.0119). MALND patients had much less axillary pain (p = 0.0000), numbness or paresthesia (p = 0.0000), arm mobility (p = 0.0000) and arm swelling on the operated side (p = 0.0000). Aesthetic appearance of the axilla was much better in the MALND than CALND group (p = 0.0000) at an average follow-up of 17 years. CONCLUSIONS: The use of MALND in breast cancer surgery not only decreases the relapse and arm complications but also improves long-term survival of patients. Therefore, MALND should be one of the preferred approaches for breast cancer surgery when ALND is needed. TRIAL REGISTRATION INFORMATION: The comparison of long-term outcomes of mastoscopic and conventional axillary lymph node dissection in breast cancer: a multicenter randomized control trial. ChiCTR-TRC-11001477, CHiCTR. First registration 08/14/2011.

PDRG1 gene silencing contributes to inhibit the growth and induce apoptosis of gastric cancer cells.

OBJECTIVE: This paper aims to provide some experimental basis for unveiling the role of PDRG1 (P53 And DNA Damage-Regulated Gene 1) gene silencing in the growth and development of gastric cancer. METHODS: PDRG1 levels in gastric cancer tissues and cell lines were measured by Western blotting. Then, gastric cancer BGC-823 cells, divided into Control, PDRG1 siRNA, NC siRNA and PDRG1 siRNA + KU55933 (ATM inhibitor) groups, were used to conduct a series of in vitro experiments including MTT, Flow cytometry, Wound-healing and Transwell assays. Expression of PDRG1 and ATM/p53 pathway-related proteins were determined by Western blot. Eventually, experiment in vivo was carried out to verify the control of PDRG1 on gastric cancer cells after establishing the tumor xenograft model in nude mice. RESULTS: PDRG1 was significantly elevated in gastric cancer tissues and was associated with lower cell differentiation degree, more severe lymph node metastasis and higher tumor stage of gastric cancer patients. The growth of BGC-823 cells were significantly retarded and the cell apoptosis was increased in the PDRG1 siRNA group; besides, cell cycle was arrested in G2/M phase, and the expressions of p-ATM, p53, p21, p-cdc2 and cleaved caspase-3 were up-regulated with the reduced PDRG1. However, KU55933 could reverse the anti-tumor effect of PDRG1 siRNA on BGC-823 cells. The in-vivo experiment confirmed PDRG1 siRNA can inhibit tumor xenograft growth in nude mice. CONCLUSION: Specific PDRG1 gene silencing may inhibit the growth and metastasis of gastric cancer cells through the activation of ATM/p53 pathway.

A Novel lnc-RNA, Named lnc-ORA, Is Identified by RNA-Seq Analysis, and Its Knockdown Inhibits Adipogenesis by Regulating the PI3K/AKT/mTOR Signaling Pathway.

Obesity is closely associated with numerous adipogenic regulatory factors, including coding and non-coding genes. Long noncoding RNAs (lncRNAs) play a major role in adipogenesis. However, differential expression profiles of lncRNAs in inguinal white adipose tissue (iWAT) between wild-type (WT) and ob/ob mice, as well as their roles in adipogenesis, are not well understood. Here, a total of 2809 lncRNAs were detected in the iWAT of WT and ob/ob mice by RNA-Sequencing (RNA-Seq), including 248 novel lncRNAs. Of them, 46 lncRNAs were expressed differentially in WT and ob/ob mice and were enriched in adipogenesis signaling pathways as determined by KEGG enrichment analysis, including the PI3K/AKT/mTOR and cytokine-cytokine receptor interaction signaling pathways. Furthermore, we focused on one novel lncRNA, which we named lnc-ORA (obesity-related lncRNA), which had a seven-fold higher expression in ob/ob mice than in WT mice. Knockdown of lnc-ORA inhibited preadipocyte proliferation by decreasing the mRNA and protein expression levels of cell cycle markers. Interestingly, lnc-ORA knockdown inhibited adipocyte differentiation by regulating the PI3K/AKT/mTOR signaling pathway. In summary, these findings contribute to a better understanding of adipogenesis in relation to lncRNAs and provide novel potential therapeutic targets for obesity-related metabolic diseases.

Bifenthrin Induces Fat Deposition by Improving Fatty Acid Uptake and Inhibiting Lipolysis in Mice.

Chemical residues in the environment are considered to be important factors that cause obesity. Bifenthrin is one of the pyrethroid pesticides and is widely used worldwide. However, its effect on adipose tissue is ill-defined. Here, we administered bifenthrin/corn oil to adult C57BL/6 mice by gavage. After 6 weeks, the bifenthrin treatment significantly increased their body weight (P = 0.015) and fat mass (P < 0.001). Then we identified 246 differently expressed proteins by proteomic analysis, and they were highly involved in fatty acid uptake and lipid metabolism processes. Interestingly, protein hormone-sensitive lipase and adipose triacylglyceride lipase were downregulated while lipoprotein lipase is upregulated after bifenthrin treatment. Similar effects in 3T3-L1 cells treated with bifenthrin validated the in vivo results. Thus, this study suggests that long-term exposure to low-dose bifenthrin induces fat deposition in mice by improving fatty acid uptake and inhibiting lipolysis, and it may cause obesity in humans.

Evaluation of ε-polylysine as antimicrobial alternative for liquid-stored boar semen.

ε-polylysine (ε-PL) has potent antibacterial effects and is often used in the food industry. However, no studies have clarified the antibacterial effects of ε-PL during storage of boar semen. In this study, boar semen samples were diluted with BTS buffer supplemented with different concentrations (0, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28 g/L) of ε-PL and different combinations of ε-PL plus gentamicin during liquid storage at 17 °C for 5 days. Bacterial concentrations, bacterial community compositions, sperm quality parameters, and in vitro fertilization (IVF) were evaluated in order to analyze the antibacterial effects of these parameters during boar semen preservation. The results indicated that the optimum concentration of ε-PL was 0.16 g/L, which significantly improved sperm quality parameters, including sperm motility, plasma membrane integrity, mitochondrial membrane potential, and acrosome integrity, and changed bacterial proliferation and composition (P < 0.05). Moreover, compared with the control group, IVF parameters in the treatment groups also significantly improved (P < 0.05), although there were no significant differences among treatment groups. Interestingly, the antibacterial effect of 0.16 g/L ε-PL in combination with 0.125 g/L gentamycin was similar to that of 0.25 g/L gentamicin alone. In conclusion, our results showed that 0.16 g/L ε-PL is promising for the replacement of gentamicin to improve sperm quality parameters, sperm capacitation, and IVF by reducing bacterial concentrations and disrupting bacterial community composition.

Mechanism of the enhancing effects of miR-93 on resistance of breast cancer MCF-7 cells to adriamycin.

This study aimed to investigate the effects of miR-93 on resistance of breast cancer MCF-7 cells to adriamycin, and to explore the possible mechanism. Expression of miR-93 in breast cancer cell lines MCF-7 and MCF-7/ADM was detected by reverse transcription-quantitative PCR (RT-qPCR). miR-93 mimics and inhibitors were transfected into MCF-7/ADM and MCF-7 cells, and MTT assay was used to detect the resistance of cells to adriamycin after transfection. Western blot analysis was used to detect the expression of anti-apoptotic protein Bcl-2 and multidrug resistance gene MDR1 related P-gp protein in MCF-7/ADM and MCF-7 cells before and after the transfection of miR-93 mimics. Expression level of miR-93 in MCF-7/ADM cells was decreased, and was 40% of that in MCF-7 cells (0.39±0.04, p<0.05). Before transfection, IC50 value of MCF-7 cells to adriamycin (11.02±0.95) was lower than that of MCF-7/ADM cells (21.29±1.83, p<0.05). IC50 value of MCF-7/ADR cells at 72 h after transfection with miR-93 mimics (13.55±0.86) was lower than that of the negative control group (24.67±1.51, p<0.05). IC50 value of MCF-7 cells 72 h after transfection with miR-93 inhibitor (19.88±1.28) was higher than that of negative control group (11.02±0.95, p<0.05). Expression levels of Bcl-2 and P-gp proteins in MCF-7/ADM cells were 1.63±0.24 and 1.76±0.22 times that of MCF-7 cells, respectively (p<0.05). At 72 h after transfection of miR-93 mimics, expression levels of Bcl-2 and P-gp proteins in MCF-7/ADM cells were 0.27±0.06 and 0.39±0.05, respectively, compared with the negative control group (p<0.05). At 72 h after transfection with miR-93 inhibitor, expression levels of Bcl-2 and P-gp protein in MCF-7 cells were 1.48±0.10 and 1.56±0.11 times of the negative control group, respectively (p<0.05). miR-93 can increase the apoptosis of MCF-7/ADM cells and their resistance to adriamycin by inhibiting the expression of Bcl-2 and P-gp proteins.

Eighty-six cases of laparoscopic vaginoplasty using an ileal segment.

BACKGROUND: The surgical management of the absence of the vagina is a complex problem and constitutes a significant technical challenge. As the laparoscopy has been an important tool for the treatment of uterovaginal anomalies, we evaluated the feasibility of laparoscopic vaginoplasty using an ileal segment retrospectively. METHODS: Totally 86 patients who underwent laparoscopic vaginoplasty using an ileal segment in Beijing Anzhen Hospital during February 2004 to July 2007 were enrolled in this study. Of the 86 patients, 70 (81.4%) underwent primary operations and 16 (18.6%) secondary operations. Nineteen (22.1%) patients underwent total laparoscopic vaginoplasty and 67 (77.9%) patients underwent laparoscope-assisted vaginoplasty. The operation time, cost of hospitalization, and hospital duration were compared between the two laparoscopic groups. The Student's t test and the Mann-Whitney test were used to examine the differences. RESULTS: All the surgeries were successfully completed with no any intraoperative complication. There were three major surgical complications in the postoperative period: one case of intra-abdominal hemorrhage, one case of meatal stenosis, and one case of intestinal obstruction. The mean follow-up period of this series was 18 months. Seventy-eight patients were satisfied with their sexual lives after the surgeries except 5 women complaining of vaginal stenosis and 3 with no sexual partner during the follow-up. Significant differences were obtained between total laparoscopic and laparoscope-assisted vaginoplasty groups, such as the operation time, cost of hospitalization, and hospital duration (P < 0.01). There were no significant differences in sexual function between the two groups. CONCLUSIONS: The laparoscopic vaginoplasty using an ileal segment is satisfactory for cosmetic, functional, and anatomic results. Vaginoplasty with an ileal segment, performed by either total laparoscopic or laparoscope-assisted techniques, has a high success rate for a functional vagina.