Deciphering programmed cell death mechanisms in osteosarcoma for prognostic modeling.

Osteosarcoma (OS), known for its high recurrence and metastasis rates, poses a significant challenge in oncology. Our research investigates the role of programmed cell death (PCD) genes in OS and develops a prognostic model using advanced bioinformatics. We analyzed single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify subpopulations, distinguish malignant from non-malignant cells, assess cell cycle phases, and map PCD gene distribution. Additionally, we applied consistency clustering to bulk sequencing data from GEO and TARGET (Therapeutically Applicable Research to Generate Effective Treatments) databases, facilitating survival analysis across clusters with the Kaplan-Meier method. We calculated PCD scores for each cluster using the Single-sample Gene Set Enrichment Analysis (ssGSEA), which enabled a detailed examination of PCD-related gene expression and pathway scores. Our study also explored drug sensitivity differences and conducted comprehensive immune cell infiltration analyses using various algorithms. We identified differentially expressed genes, leading to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses that provided insights into relevant biological processes and pathways. The prognostic model, based on five pivotal genes (BAMBI, TMCC2, NOX4, DKK1, and CBS), was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and validated in the TARGET-OS and GSE16091 datasets, showing significant predictive accuracy. This research enhances our understanding of PCD in OS and supports the development of effective treatments.

Establishment and validation of a nomogram to predict postoperative anemia after total hip arthroplasty.

BACKGROUND: Anemia is a common complication of total hip arthroplasty (THA). In this study, we evaluated the preoperative risk factors for postoperative anemia after THA and developed a nomogram model based on related preoperative and intraoperative factors. METHODS: From January 2020 to May 2023, 927 THA patients at the same medical center were randomly assigned to either the training or validation cohort. The correlation between preoperative and intraoperative risk factors and postoperative anemia after THA was evaluated using univariate and multivariate logistic regression analysis. A nomogram was developed using these predictive variables. The effectiveness and validation for the clinical application of this nomogram were evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: Through univariate and multivariate logistic regression analysis, 7 independent predictive factors were identified in the training cohort: Lower body mass index (BMI), extended operation time, greater intraoperative bleeding, lower preoperative hemoglobin level, abnormally high preoperative serum amyloid A (SAA) level, history of cerebrovascular disease, and history of osteoporosis. The C-index of the model was 0.871, while the AUC indices for the training and validation cohorts were 84.4% and 87.1%, respectively. In addition, the calibration curves of both cohorts showed excellent consistency between the observed and predicted probabilities. The DCA curves of the training and validation cohorts were high, indicating the high clinical applicability of the model. CONCLUSIONS: Lower BMI, extended operation time, increased intraoperative bleeding, reduced preoperative hemoglobin level, elevated preoperative SAA level, history of cerebrovascular disease, and history of osteoporosis were seven independent preoperative risk factors associated with postoperative anemia after THA. The nomogram developed could aid in predicting postoperative anemia, facilitating advanced preparation, and enhancing blood management. Furthermore, the nomogram could assist clinicians in identifying patients most at risk for postoperative anemia.

Early clinical efficacy analysis of enhanced recovery following surgery combined with interscalene brachial plexus block for arthroscopic rotator cuff repair.

To explore the early clinical value of enhanced recovery after surgery (ERAS) with interscalene brachial plexus block (ISB) for arthroscopic rotator cuff repair (ARCR). We enrolled 240 patients who underwent arthroscopic rotator cuff repair, randomly divided into 3 groups (n = 80 each). Groups A, B, and C underwent only surgery, surgery + ERAS, and ISB + surgery + ERAS, respectively. We analyzed the clinical data and postoperative indicators for the 3 patient groups. Group comparisons of clinical data and postoperative indicators revealed no significant differences in clinical characteristics (P > .05). Group C showed superior Visual Analog Scale scores at 0-6 and 6-24 hours postoperatively (P < .05), and the shortest length of hospital stay (LOS) (P < .05). At 6 weeks and 3 months postoperatively, Constant-Murley shoulder score and University of California-Los Angeles scores were better in Groups B and C than in Group A (P < .05). Joint swelling was more common in Group A than in Groups B and C (P < .05) but with no significant difference in the incidence of postoperative stiffness (P > .05). ERAS can relieve postoperative pain, shorten LOS, and help restore shoulder joint mobility, thereby reducing postoperative swelling. ISB + ERAS optimized pain control and allowed a shorter LOS, but had similar effects on early functional recovery and complications.

Patient satisfaction after nipple-sparing mastectomy with intraoperative radiotherapy and breast reconstruction for breast cancer.

INTRODUCTION: The use of nipple-sparing mastectomy (NSM) combined with breast reconstruction is increasing in breast cancer surgeries despite its controversial safety profile. To reduce the recurrence rate of tumors in the nipple-areola complex (NAC), we used intraoperative radiotherapy (IORT). The purpose of this study was to explore patients' feedback on this novel treatment strategy. PATIENTS AND METHODS: From January 2014 to May 2018, eligible patients with breast cancer were enrolled in this study and separated into 2 groups. Patients in the NSM group underwent IORT to the NAC flap, and patients in the skin-sparing mastectomy (SSM) group underwent SSM and breast reconstruction. The postoperative satisfaction was collected and assessed using the Breast-Q reconstruction questionnaire and a standardized questionnaire; this was compared between the 2 groups. RESULTS: There were 46 patients (52 NSMs) in the NSM group and 20 patients (22 SSMs) in the SSM group. The breast-Q scores were higher in the NSM group than the SSM group, with trends for a 'higher satisfaction with breasts' (67.39 ± 20.59 vs. 55.00 ± 19.33; p = 0.026) and 'higher sexual well-being' (61.74 ± 22.24 vs. 49.50 ± 20.12; p = 0.039). All the patients recognized the importance of nipple preservation. Thirty-seven women (80.40%) were satisfied or very satisfied with the appearance and shape of the NAC in the NSM group, while 38/46 women (82.60%) were very unsatisfied or unsatisfied with the sensitivity of the nipples. CONCLUSIONS: The Breast-Q scores showed great satisfaction with breasts and sexual well-being in the NSM group. However, more effort should be made in improving postoperative NAC sensitivity.

Host-guest complexation of cyclophosphamide by carboxylatopillar[6]arene for increasing stability and enhancing its curative effect on breast carcinoma.

Advanced chemotherapy strategies are in urgent demand for improving antitumor efficacy on breast carcinoma. Herein, a drug delivery system comprised of host-guest complex between carboxylated pillar[6]arene (CP6A) and cyclophosphamide (CTX) has been designed with view to overcoming several drawbacks associated with this antitumor agent. NMR and fluorescence titration served to confirm the complexation of CTX/CP6A. Baring CP6A did not affect cell viability as inferred from comparison studies carried out in human normal mammary epithelial cells and breast adenocarcinoma cells. Stability experiment proved that complexation of CTX by CP6A could increase the inherent stability of CTX in phosphate buffer (pH = 7.4) at 37 °C in a statistically significant way. In vivo research confirmed that CTX/CP6A was not only able to promote antitumor efficacy but also reduce CTX-related systemic toxicity on breast adenocarcinoma cells derived subcutaneous tumor xenograft mouse models. This drug delivery system could also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for more patients.

Meta-Analysis of Knee Joint Function Recovery after Anterior Cruciate Ligament Reconstruction by Accelerated Rehabilitation Surgery.

Objective: This investigation was undertaken to systematically assess the impact of increasingly rapid recovery treatment on the functional status of the knee following anterior cruciate ligament restructuring. Methods: Computer search from the establishment of the database to March 2022 in China Knowledge Network Database (CNKI), PubMed, EMBASE, ScienceDirect, CochraneLibrary, China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM). The control group was given only traditional rehabilitation training, and the observation group was treated with perioperative accelerated rehabilitation surgery intervention randomized controlled trial (RCT). Data for all included studies were extracted by two independent researchers, and the risk of bias for the quality of each included study was assessed by the Cochrane Handbook 5.1.0 criteria. Meta-analysis of the collected data by using RevMan5.4 statistical software. Results: A total of 593 articles were retrieved from the computer database and 8 RCT articles with a total of 636 samples were finally included for meta-analysis. According to the Jadad scale, the RCT score of 8 articles was ≥4 points. Meta-analysis was performed on the postoperative VAS scores of the ERAS group and the traditional rehabilitation group, and the heterogeneity test showed Chi2 = 288.60, df = 5, P < 0.00001, and I 2 = 99%. There was a statistically significant difference in the postoperative VAS scale between the intervention and the traditional rehabilitation model (P < 0.05). Eight articles reported the effect of accelerated rehabilitation surgery on the recovery of knee joint motion after ACL rehabilitation. After meta-analysis, the heterogeneity test showed Chi2 = 314.98, df = 7, P < 0.00001, and I 2 = 98%, and it can be concluded from the analysis that, compared with the traditional rehabilitation model, the enhanced rehabilitation surgery has an effect on the joint function after anterior cruciate ligament reconstruction. The improvement effect was more significant, and the difference was statistically significant (P < 0.05). Four articles reported the effect of enhanced recovery after surgery intervention on the range of motion of the knee joint of patients, the heterogeneity test showed Chi2 = 117.52, df = 2, P < 0.00001, and I 2 = 98%, through analysis, and compared with the traditional rehabilitation model and the enhanced recovery. The effect of surgery on the range of motion of the knee joint after ACL reconstruction was more significant, and the difference was statistically significant (P < 0.05). The effect of enhanced recovery after surgery and traditional rehabilitation mode on the incidence of postoperative adverse reactions in patients undergoing ACL reoperation was analyzed. The results of heterogeneity test showed that Chi2 = 1.59, df = 2, P=0.66 > 0.05, and I 2 = 98%, and the analysis showed that, compared with the traditional rehabilitation mode, enhanced rehabilitation surgery can significantly reduce the risk of adverse reactions after anterior cruciate ligament reconstruction (P < 0.05). An inverted funnel plot was used to analyze publication bias in studies with quality of life as an outcome measure. The results showed that Egger's test P=0.0005 < 0.001 suggesting that there may be a certain degree of publication bias. Conclusion: The existing research evidence shows that accelerating the reconstruction of anterior cruciate ligament can effectively promote the recovery of knee joint function, reduce the pain of patients, and reduce postoperative complications. However, more research is needed to further verify this.

GABPB1-AS1 Promotes the Development of Osteosarcoma by Targeting SP1 and Activating the Wnt/ß-Catenin Pathway.

In this study, the role of GABPB1-AS1 in osteosarcoma (OS) was analyzed. The expression of GABPB1-AS1 in different OS cell lines U2OS, HOS, MG63, and hFOB1.19 was detected. SiRNA GABPB1-AS1 was transfected with U2OS and HOS cell lines. The effects of GABPB1-AS1 silencing on proliferation, clonal formation, and migration of U2OS and HOS were detected by CCK-8 method, plate cloning method, and Transwell chamber. Western blot analysis was used to detect the protein levels of SP1, Wnt, ß-catenin, c-Myc, and SOX2 in osteosarcoma cells. The binding relationship between GABPB1-AS1 and miR-199a-3p in OS cells was detected by a dual-luciferase reporter gene assay. Results showed that GABPB1-AS1 was higher in OS cells than that in hFOB1.19. Silencing GABPB1-AS1 inhibited the proliferation, clonal formation, migration, and epithelial-mesenchymal transformation of U2OS and HOS. There was a binding relationship between GABPB1-AS1 and miR-199a-3p in OS cells. GABPB1-AS1 mediated osteosarcoma cells via the SP1/Wnt/ß-catenin signaling pathway. This study suggested that GABPB1-AS1 plays a carcinogenic role in OS through the SP1/Wnt/ß-catenin signaling pathway through competitive binding and inhibition of miR-199a-3p.

α-Mangostin protects lipopolysaccharide-stimulated nucleus pulposus cells against NLRP3 inflammasome-mediated apoptosis via the NF-κB pathway.

Intervertebral disc degeneration (IDD) is a common and chronic inflammatory disorder. α-Mangostin exhibits a novel biological function against inflammation in various inflammatory diseases. Here, we aimed to explore the role of α-mangostin in IDD using an in vitro cell model. Human nucleus pulposus cells (NPCs) were exposed to lipopolysaccharide (LPS) to induce inflammatory injury. Cell viability of NPCs was determined by CCK-8 assay. ELISA was performed to examine the production of interleukin (IL)-1ß and IL-18. Apoptotic cell death in NPCs was detected by TUNEL staining. The expression levels of apoptotic-associated proteins were detected by western blotting. Nuclear factor-kappa B (NF-κB) activation was examined by determining the expression levels of p-p65, p65, and nuclear p65. Results showed that treatment with α-mangostin improved the viability of LPS-treated NPCs. α-Mangostin treatment also inhibited the LPS-induced increase in expression levels of NLRP3, ASC and pro-caspase-1, as well as the production of IL-1ß and IL-18 in NPCs. Moreover, treatment with α-mangostin or NLRP3 inhibitor (MCC950) significantly decreased apoptotic cell death in NPCs, as compared with treatment with LPS. In addition, the expression levels of cleaved caspase-3 and Bax were decreased, while Bcl-2 expression was increased in α-mangostin- or MCC950-treated NPCs. Treatment with α-mangostin also suppressed LPS-induced increase of p-p65/p65 and nuclear p65 levels. Moreover, inhibition of NF-κB by PDTC aggravated the inhibitory effects of α-mangostin on NLRP3 inflammasome activation and apoptosis in LPS-induced NPCs. These findings suggested that α-mangostin exerted a protective effect on NLRP3 inflammasome-mediated apoptosis in LPS-induced NPCs through regulating NF-κB signaling.

Aldehyde dehydrogenase 2 alleviates monosodium iodoacetate-induced oxidative stress, inflammation and apoptosis in chondrocytes via inhibiting aquaporin 4 expression.

BACKGROUND: Knee osteoarthritis (KOA) is a common cause of disability among the elderly. We aimed to explore the effects of aldehyde dehydrogenase (ALDH) 2 on the progression of KOA and identifying the potential mechanisms. METHODS: First, ALDH2 expression in knee joint effusion of patients with KOA and the levels of oxidative stress-related markers were determined. After ALDH2 overexpression in monosodium iodoacetate (MIA)-treated SW1353 cells, cell viability was tested with CCK-8 assay. Subsequently, oxidative stress and inflammation-associated factors were measured. Meanwhile, cell apoptosis was assessed with TUNEL staining and expression of apoptosis-related proteins was detected by western blotting. To analyze the mechanism of ALDH2 in KOA, aquaporin 4 (AQP4) expression was determined using western blotting following ALDH2-upregulation. Subsequently, AQP4 was overexpressed to evaluate the changing of oxidative stress, inflammation and apoptosis in SW1353 cells exposed to MIA with ALDH2 overexpression. RESULTS: Results indicated that knee joint effusion with higher ALDH2 expression displayed lower oxidative stress. In addition, significantly upregulated ALDH2 expression was observed in MIA-treated SW1353 cells. ALDH2 overexpression oxidative stress, inflammation and apoptosis in SW1353 cells exposed to MIA. Moreover, MIA-triggered elevated expression of AQP4, which was reduced by ALDH2 overexpression. By contrast, AQP4-upregulation abrogated the inhibitory effects of ALDH2 on oxidative stress, inflammation and apoptosis in MIA-induced SW1353 cells. CONCLUSIONS: ALDH2 inactivates the expression of AQP4, by which mechanism the MIA-induced oxidative stress, inflammation and apoptosis injuries were alleviated, which provides a novel insight for understanding the mechanism of KOA and a promising target for the treatment of this disease.

[Comparative study between 3D guide plate assisted and free-hand insertion of anterior cervical transpedicular screw].

OBJECTIVE: To compare accuracy of anterior cervical pedicle screws between assist of rapid prototyping 3D guide plate and free-hand insertion, and evaluate the safety of two methods. METHODS: Eight adult cervical cadaver specimens after formaldehyde immersion, including 4 males and 4 females, aged 32 to 65(40.3±5.6) years old. After X-ray examination to exclude bone damage and deformity, 4 of them (3D guide plate group) randomly selected were for CT scan to obtain DICOM format data, and the data was imported into Mimics software for model, designed the ideal entry point and nail path for anterior cervicaltranspedicular screw (ATPS). After obtaining the personalized guide plate of the nail channel, it was exported as STL data, and the individual guide plate was printed by rapid prototyping and 3D printing technology. In turn, with the assistance of 3D guide plates, one-to-one personalized ATPS screws were placed on the four lower cervical cadaver specimens. Another 4 (free-hand group) lower cervical cadaver specimens were implanted with ATPS screws using free-hand technique. All specimens were performed CT thin-layer scanning and three-dimensional reconstruction after operation. The Tomasino method was used to evaluate the safety of the screws on the CT cross-sectional and sagittal images, to determine whether there was a cortical puncture of the lower and inner edges of the pedicle. According to the CT rating results, gradeⅠandⅡwere safe, and grade Ⅲ- Ⅴ were dangerous.And the accuracy of screws was recorded and analyzed between two groups. RESULTS: Two screws were inserted in each segment from C3 to C7 in 8 adult cadavers. A total of 80 screws were inserted, 40 in the 3D guide plate group, and 40 in the free-hand group. The Tomasino screw rating method was used to evaluate the safety of screw, 21 screws were gradeⅠ, 14 screws were gradeⅡ, 3 screws were grade Ⅲ, 1 screw was grade Ⅳ, 2 screws were grade Ⅴ in 3D guide plate group, while 14 screws were gradeⅠ, 8 screws were gradeⅡ, 8 screws were grade Ⅲ, 6 screws were grade Ⅳ, 2 screws were grade Ⅴ in free-hand group. The safety rate of 3D guide plate group was 87.5%, and 55.0% of the free hand group (χ2=8.7, P=0.003). CONCLUSION: The 3D printing rapid prototyping guide plate assisted insertion of the anterior cervical pedicle screw can significantly improve the accuracy and safety, and provide a theoretical basis for further clinical application.

Construction of an immune-related genes nomogram for the preoperative prediction of axillary lymph node metastasis in triple-negative breast cancer.

Immune system disorder is associated with metastasis of triple-negative breast cancers (TNBCs). A robust, individualized immune-related genes (IRGs)-based classifier was aimed to develop and validate in our study to precisely estimate the axillary lymph node (ALN) status preoperatively in patients with early-stage TNBC. We first analyzed RNA sequencing profiles in TNBC patients from The Cancer Genome Atlas database by using bioinformatics approaches, and screened 23 differentially expressed IRGs. A 9-gene panel was generated with an area under the curve (AUC) of 0.77 [95% confidence interval (95% CI), 0.68-0.87]. We detected the 9 ALN-status-related IRGs in the training set (n = 133) and developed a reduced and optimized five-IRGs signature, which effectively distinguished TNBC patients with ALN metastasis (AUC, 0.80; 95% CI, 0.65-0.86), and was superior to preoperative ultrasound-based ALN status (AUC, 0.73; 95% CI, 0.53-0.93). Predictive efficiency (AUC, 0.77; 95% CI 0.61-0.93) of this five-IRGs signature was validated in the validation set (n = 81). Furthermore, IRGs nomogram incorporated IRGs signature with US-based ALN status showed higher ALN status prediction efficacy than US-based ALN status and five-IRGs signature alone in both training and validation sets. IRGs nomogram may aid in identifying patients who can be exempted from axillary surgery.Novelty and impact: An immune-related genes (IRGs) nomogram was first developed and externally validated in our study, which incorporated the IRGs signature with ultrasound (US)-based axillary lymph nodes (ALN) status. IRGs nomogram is superior to IRGs signature alone for preoperative estimation of ALN metastasis in patients with triple-negative breast cancer (TNBC). It is a favourable biomarker for preoperatively predicting ALN metastasis risk and may aid in clinical decision-making in early-stage TNBCs.

Aberrant Expression of miR-100 in Plasma of Patients with Osteoporosis and its Potential Diagnostic Value.

BACKGROUND: Osteoporosis is one of the most commonly diagnosed age-related bone diseases worldwide, and it is also one of the leading causes of fracture. MicroRNAs (miRNAs) are critical molecular regulators that are involved in the bone re-modelling processes, and the circulating miRNAs were stable in the peripheral blood. Thus, to detect the level of miRNAs in plasma of osteoporotic patients may be an efficient, repeatable, and inexpensive method for the early diagnosis and evaluation of the therapeutic efficacy of osteoporosis. The aim of the present study was to investigate the potential diagnostic value of miR-100 in plasma of patients with osteoporosis. METHODS: A total of 120 osteoporotic patients were recruited and 120 healthy individuals were also included as the control group. The plasma of the participants was collected and the RNAs were extracted. The expressions of miR-100 in different clinical samples were examined using the RT-qPCR method. Furthermore, receiver operating characteristics curve (ROC) was drawn to determine the diagnostic value of miR-100 for osteoporosis. Next, the correlation between the plasma levels of miR-100 and T-scores of the patients were evaluated and, finally, the correlation between the plasma level of miR-100 and the expression levels of 25OH-D2 and 25OH-D3 were analyzed. RESULTS: miR-100 was significantly increased in plasma of patients with osteoporosis in comparison with healthy individuals; moreover, results of ROC analysis indicated that plasma level of miR-100 is a sensitive biomarker that could distinguish osteoporosis patients from healthy controls (AUC, 0.8916, 95% confidence interval (CI), 0.8468 to 0.9364). Furthermore, miR-100 was found to be negatively correlated with both vBMD (r = -0.3117, p = 0.0005) and Lumbar Spine L2-L4 T-score in patients with osteoporosis (r = -0.2929, p = 0.012). Finally, the plasma level of miR-100 was negatively correlated with the levels of 25OH-D2 (r = -0.3002, p = 0.0008) and 25OH-D3 (r = -0.3105, p = 0.0006) of the osteoporotic patients. CONCLUSIONS: miR-100 was abnormally increased in the plasma of osteoporotic patients, suggesting that circulating miR-100 could serve as potential biomarker for the diagnosis and treatment osteoporosis.

Correction to: IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma.

[This corrects the article DOI: 10.1186/s13578-019-0310-2.].

IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma.

BACKGROUND: Thyroid cancer is the most common malignant endocrine tumor and is classified into papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) and anaplastic thyroid cancer (ATC), which have substantially different characteristics. Insulin-like growth factor binding protein 7 (IGFBP7) has recently been recognized as a tumor suppressor in many cancer types. However, the expression pattern of IGFBP7 and its biological function in various types of thyroid carcinoma remain poorly understood. RESULTS: We found that the protein levels of IGFBP7 in FTC and ATC tissues were significantly lower or even absent compared with those in normal thyroid, benign thyroid adenoma and classical PTC tissues. Moreover, overexpression of IGFBP7 in two undifferentiated ATC cell lines, ARO and FRO, and one differentiated FTC cell line, WRO, significantly inhibited cell proliferation in vitro. In vivo experiments revealed that ectopic IGFBP7 expression markedly suppressed growth of tumor xenografts derived from these thyroid cancer cell lines, while IGFBP7 silencing accelerated tumor growth. At the mechanistic level, overexpression of IGFBP7 dramatically suppressed phosphorylation-mediated activation and kinase activity of AKT, causing an upregulation of cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p21Cip1 and induction of G1/S cell cycle arrest, while silencing IGFBP7 exerted the opposite effects. CONCLUSIONS: IGFBP7 expression is decreased or even absent in FTC and ATC. Acting as a cell cycle repressor, IGFBP7 plays an important tumor-suppressive role in human thyroid cancer, especially in FTC and ATC subtypes and may represent a promising biomarker and therapeutic target for human thyroid cancer treatment.

Artificial intelligence detection of distal radius fractures: a comparison between the convolutional neural network and professional assessments.

Background and purpose - Artificial intelligence has rapidly become a powerful method in image analysis with the use of convolutional neural networks (CNNs). We assessed the ability of a CNN, with a fast object detection algorithm previously identifying the regions of interest, to detect distal radius fractures (DRFs) on anterior-posterior (AP) wrist radiographs. Patients and methods - 2,340 AP wrist radiographs from 2,340 patients were enrolled in this study. We trained the CNN to analyze wrist radiographs in the dataset. Feasibility of the object detection algorithm was evaluated by intersection of the union (IOU). The diagnostic performance of the network was measured by area under the receiver operating characteristics curve (AUC), accuracy, sensitivity, specificity, and Youden Index; the results were compared with those of medical professional groups. Results - The object detection model achieved a high average IOU, and none of the IOUs had a value less than 0.5. The AUC of the CNN for this test was 0.96. The network had better performance in distinguishing images with DRFs from normal images compared with a group of radiologists in terms of the accuracy, sensitivity, specificity, and Youden Index. The network presented a similar diagnostic performance to that of the orthopedists in terms of these variables. Interpretation - The network exhibited a diagnostic ability similar to that of the orthopedists and a performance superior to that of the radiologists in distinguishing AP wrist radiographs with DRFs from normal images under limited conditions. Further studies are required to determine the feasibility of applying our method as an auxiliary in clinical practice under extended conditions.

Intrabeam Radiation Inhibits Proliferation, Migration, and Invasiveness and Promotes Apoptosis of MCF-7 Breast Cancer Cells.

Intraoperative radiotherapy differs from the more commonly used external beam radiation with respect to fractionation, radiation energy, dose rate, and target volume, which may influence the irradiated cells in a complex manner. However, experimental studies of intraoperative radiotherapy are limited. Intrabeam is a frequently used intraoperative radiotherapy device; we evaluated its effects on the proliferation, apoptosis, migration, and invasion of MCF-7 human breast cancer cells. We performed colony formation assays for cells irradiated with single radiation doses of 0 to 16 Gy. Other cells were irradiated with single radiation doses of 0 to 6 Gy and then continued to be cultured. We measured cell-cycle distributions and apoptosis rates 24 hours later, using flow cytometry, and performed wound-healing assays, Transwell tests, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling staining 4 weeks later. Colony formation assays showed no positive colonies from cells irradiated with doses of ≥6 Gy. In flow cytometry, the experimental groups had higher late-apoptosis/necrosis rates ( P < .01) and higher percentages of cells arrested in G1 phase ( P < .01). Experimental groups also had much lower scratch-repair rates in the wound healing assay ( P < .001) and higher apoptosis rates in the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling assay ( P < .05). In Transwell tests, the 4 Gy and 6 Gy groups had fewer invading cells than the control group ( P < .05). Single-dose irradiation of 6 Gy with the Intrabeam device can effectively inhibit proliferation, migration, and invasiveness and promote apoptosis in MCF-7 cells with long-lasting effects.

Oncologic outcomes and radiation safety of nipple-sparing mastectomy with intraoperative radiotherapy for breast cancer.

BACKGROUND: Nipple-sparing mastectomy combined with breast reconstruction helps to optimize the contour of the breast after mastectomy. However, the indications for nipple-sparing mastectomy are still controversial. Local radiation to the nipple-areola complex may play some roles in improving the oncological safety of this procedure. METHODS: From January 2014 to December 2017, 41 consecutive patients who underwent nipple-sparing mastectomy combined with Intrabeam intraoperative radiotherapy to the nipple-areola complex flap and breast reconstruction were enrolled in this prospective study. The prescribed radiation dose at the surface of the spherical applicator was 16 Gy. RESULTS: In eight cases, carcinomas were in the central portion of the breast. Partial necrosis of the nipple-areola complex occurred in three cases. Over 90% of patients reported "no or poor sensation" of the nipple-areola complex postoperatively. With a median follow-up time of 26 months, no recurrences or metastases were identified; however, breast-cancer mortality occurred in one patient. Pathologic evaluation of paraffin-embedded sections showed ductal carcinoma in situ in the remaining tissues deep to the nipple-areola complex flap in two patients. Although no further treatment was administered to the nipple-areola complexes postoperatively, no recurrences or metastases were identified 20 months and 24 months later, respectively. Optical microscopy and transmission electron microscopy revealed changes in some normal tissues immediately after Intrabeam intraoperative radiotherapy. Karyopyknosis were observed in gland tissues, and the collagenous fibers became sparse and arranged chaotically. As assessed by thermoluminescence, radiation doses at different sites in the nipple-areola complex flap varied considerably and were about 10 Gy at the areola surface. No Intrabeam intraoperative radiotherapy-related acute or chronic radiation injuries of the lung, heart or bone marrow were identified. CONCLUSIONS: Our findings indicate that Intrabeam intraoperative radiotherapy during nipple-sparing mastectomy combined with breast reconstruction is safe and feasible. TRIAL REGISTRATION: The current study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (registering order 201750). All participants gave their written informed consent.

miR-145-5p Suppresses Breast Cancer Progression by Inhibiting SOX2.

BACKGROUND: In this study, we aimed to investigate the expression and clinical significance of miR-145-5p and its tumor-suppressive effect in breast cancer patients. METHODS: We used luciferase reporter assay, real-time quantitative reverse transcription polymerase chain reaction and Western blot to identify sex-determining region Y-box2 (SOX2) as the target gene of miR-145-5p. Their expression levels in breast cancer tissues (n = 122) were detected by real-time quantitative polymerase chain reaction. We also applied 3-(4,5-dimethyl- 2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry to reveal the effect of miR-145-5p on proliferation in breast cancer. RESULTS: miR-145-5p expression is downregulated in breast cancer tissues and negatively correlated with SOX2 expression. Decreased miR-145-5p expression was significantly associated with larger tumor size, distal metastasis, higher Ki67 expression level, and shorter overall survival. miR-145-5p inhibits breast cancer cell proliferation via targeting SOX2, and multivariate regression showed that both miR-145-5p and SOX2 were unfavorable prognostic factors. CONCLUSIONS: miR-145-5p played a suppressive role in the proliferation of breast cancer cells by targeting SOX2, and miR-145-5p is a putative biomarker for risk assessment in patients with breast cancer.

Diagnostic and prognostic value of serum MACC1 in breast cancer patients.

Metastasis-associated in colon cancer-1 (MACC1) promotes colorectal cancer progression and predicts prognosis. The aim of our study was to determine the diagnostic and prognostic value of preoperative serum MACC1 levels in breast cancer patients. Serum MACC1 levels were measured in 378 breast cancer patients, 120 patients with benign breast disease, and 40 healthy volunteers using an ELISA. Serum MACC1 levels were higher in breast cancer patients than patients with benign disease or healthy volunteers. Increased serum MACC1 was associated with breast cancer TNM stage (P < 0.001), tumor size (P < 0.001), lymph node metastasis (P < 0.001), and Ki-67 status (P = 0.014). Serum MACC1 measurement successfully discriminated breast cancer patients from normal and healthy controls (AUC = 0.785, 95% CI: 0.746-0.825) with an optimal cut-off value of 38.35 pg/ml (sensitivity = 0.725, specificity = 0.696). Moreover, serum MACC1 exhibited significant prognostic value in breast cancer (AUC = 0.757, 95% CI: 0.700-0.814), and high MACC1 was associated with poor disease-free survival (HR 5.63, 95% CI: 3.51-9.04; P < 0.001). Our findings demonstrated that circulating MACC1 could serve as a reliable diagnostic and prognostic biomarker for breast cancer.

Prophylactic Effect of Lamivudine for Chemotherapy-Induced Hepatitis B Reactivation in Breast Cancer: A Meta-Analysis.

BACKGROUND: Three strategies using lamivudine have been proposed to prevent chemotherapy-induced HBV (hepatitis B virus) reactivation in the clinical setting. The purpose of this meta-analysis is to evaluate the efficacy of the early preemptive strategy, deferred preemptive strategy and therapeutic strategy in patients with HBsAg-positive breast cancer during chemotherapy. METHODS: Clinical studies published from database inception until Nov 1, 2014, were included for analysis. The primary outcomes were overall survival, rate of chemotherapy disruption and virological and clinical reactivation. The secondary outcomes were the rates of HBV-related chemotherapy disruption, HBV-related mortality, YMDD mutations and withdrawal hepatitis. RESULTS: Four hundred and thirty patients in four studies that compared the early preemptive strategy with a therapeutic strategy were included. Application of early preemptive lamivudine was superior in reducing HBV recurrence (pooled OR: 0.12, 95% CI, 0.04 to 0.31, P< 0.0001), the incidence of HBV-related hepatitis (pooled OR: 0.13, 95% CI, 0.04 to 0.37, P< 0.0001) and the rate of chemotherapy disruption (pooled OR: 0.37, 95% CI, 0.23 to 0.60, P< 0.0001). In these two groups, no significant difference was found in overall mortality (P = 0.32), YMDD mutant rate (P = 0.13) or incidence of withdrawal hepatitis (P = 0.38). Of the two studies that compared the efficacy of an early and a deferred preemptive strategy, one showed that an early preemptive strategy significantly reduced the incidence of hepatitis (P = 0.046), whereas the other showed no significant difference (P = 0.7). CONCLUSIONS: An early preemptive strategy is superior to a therapeutic strategy in decreasing the incidence of HBV reactivation, incidence of HBV-related hepatitis and rate of chemotherapy disruption in patients with breast cancer. A deferred preemptive strategy might be an alternative approach to controlling viral replication.