Bioinformatics analysis and experimental verification of TIGD1 in non-small cell lung cancer.

Introduction: Non-small cell lung cancer (NSCLC) is a prevalent respiratory system tumor. Triggered transposable element derivative 1 (TIGD1) exhibits significant overexpression in various tumor cells and tissues, suggesting its involvement in cancer progression. Methods: Clinical data and gene expression profiles of lung adenocarcinoma were collected from TCGA, UCSC XENA, and GEO databases. Computational techniques and empirical studies were employed to analyze the role of TIGD1 in NSCLC. Cellular experiments were conducted using the H1299 cell line, including RNA interference, cell viability assays, quantitative PCR, wound-healing assays, western blotting, and plate clone formation assays. Results: Bioinformatics analysis revealed TIGD1's potential as a biomarker for diagnosing and predicting lung cancer. It also indicated promise as a target for immune-related therapy and targeted drug therapy. Cellular studies confirmed TIGD1's involvement in cancer cell proliferation, invasion, and migration. Furthermore, an association between TIGD1 and the PI3K/AKT signaling pathway was suggested. Discussion: The findings suggest that TIGD1 plays a vital role in NSCLC progression, making it a potential diagnostic biomarker and therapeutic target. The association with the PI3K/AKT signaling pathway provides insights into the underlying molecular mechanisms. Integrating computational analysis with empirical studies enhances our understanding of TIGD1's significance in NSCLC and opens avenues for further research into targeted therapies.

Upregulation of HLA-II related to LAG-3+CD4+ T cell infiltration is associated with patient outcome in human glioblastoma.

Glioblastoma (GBM) is the most common malignant diffuse glioma of the brain. Although immunotherapy with immune checkpoint inhibitors (ICIs), such as programmed cell death protein (PD)-1/PD ligand-1 inhibitors, has revolutionized the treatment of several cancers, the clinical benefit in GBM patients has been limited. Lymphocyte-activation gene 3 (LAG-3) binding to human leukocyte antigen-II (HLA-II) plays an essential role in triggering CD4+ T cell exhaustion and could interfere with the efficiency of anti-PD-1 treatment; however, the value of LAG-3-HLA-II interactions in ICI immunotherapy for GBM patients has not yet been analyzed. Therefore, we aimed to investigate the expression and regulation of HLA-II in human GBM samples and the correlation with LAG-3+CD4+ T cell infiltration. Human leukocyte antigen-II was highly expressed in GBM and correlated with increased LAG-3+CD4+ T cell infiltration in the stroma. Additionally, HLA-IIHighLAG-3High was associated with worse patient survival. Increased interleukin-10 (IL-10) expression was observed in GBM, which was correlated with high levels of HLA-II and LAG-3+ T cell infiltration in stroma. HLA-IIHighIL-10High GBM associated with LAG-3+ T cells infiltration synergistically showed shorter overall survival in patients. Combined anti-LAG-3 and anti-IL-10 treatment inhibited tumor growth in a mouse brain GL261 tumor model. In vitro, CD68+ macrophages upregulated HLA-II expression in GBM cells through tumor necrosis factor-α (TNF-α). Blocking TNF-α-dependent inflammation inhibited tumor growth in a mouse GBM model. In summary, T cell-tumor cell interactions, such as LAG-3-HLA-II, could confer an immunosuppressive environment in human GBM, leading to poor prognosis in patients. Therefore, targeting the LAG-3-HLA-II interaction could be beneficial in ICI immunotherapy to improve the clinical outcome of GBM patients.

Effect of laparoscopic sleeve gastrectomy on male reproductive function in chinese men with obesity: A prospective cohort study.

BACKGROUND: Obesity is a widely recognized global public health issue, and bariatric surgery has emerged as an effective intervention for alleviating obesity associated health complications. However, the impact of bariatric surgery on male reproductive function remains inconclusive in the literature. The current understanding of the impact of laparoscopic sleeve gastrectomy on male reproductive function remains ambiguous, despite its status as the most commonly performed bariatric surgery. This prospective cohort study aimed to investigate the impact of laparoscopic sleeve gastrectomy on erectile function and semen quality. PATIENTS AND METHODS: A total of thirty-four obese patients were enrolled in this study and underwent laparoscopic sleeve gastrectomy (LSG). Prior to the operation and at 3, 6, and 12 months postoperation, all participants were required to complete the International Index of Erectile Function-5 (IIEF-5) questionnaire and undergo a nocturnal erectile function test and semen quality analysis. RESULTS: Within 12 months postoperation, body mass index, blood lipids, and insulin resistance showed significant improvement. The IIEF-5 score increased significantly (18.88±5.97 vs. 23.78±3.19, P < 0.05), and the frequency and duration of erections significantly improved compared to baseline. Sperm concentration, total motility, survival rate, and sperm morphology parameters exhibited a significant decline at 3 months but demonstrated a significant improvement at 6 and 12 months post-operation. At 12 months, sperm concentration was shown to be correlated with changes in zinc (r = 0.25, P = 0.033) as well as changes in testosterone (r = 0.43, P = 0.013). CONCLUSIONS: LSG has beneficial effects on erectile function, despite a transient decline in semen quality at 3 months postoperatively, followed by a significant improvement at 12 months.

ITGB4 upregulation is associated with progression of lower grade glioma.

Gliomas originating in the neuroepithelium account for about 80% of brain malignancies and are the most common cancer of the central nervous system. Clinical management of gliomas remains challenging despite significant advances in comprehensive therapies, including radiotherapy, chemotherapy, and surgery. The ITGB4 (Integrin subunit beta 4) gene encodes a receptor for laminins and its upregulation in tumor tissues is associated with poor prognosis. However, its role in glioma is not well understood. First, we performed a pan cancer analysis of ITGB4 expression in The Cancer Genome Atlas (TCGA) dataset. Survival analysis was done on Chinese Glioma Genome Atlas (CGGA) and TCGA. Immunohistochemistry was then used to validate the expression and role of ITGB4 in glioma. We finally analyzed the possible mechanism by immune infiltration and single-cell sequencing analysis. Here, we found that ITGB4 is upregulated in glioma and accurately predicts the prognosis of lower grade glioma (LGG). Univariate and multivariate Cox regression analyses showed that ITGB4 is a risk factor for LGG. Immunohistochemical analysis confirmed that ITGB4 accurately predicts LGG prognosis. Non-negative matrix factorization (NMF) cluster analysis showed that ITGB4 was closely related to immune related genes. Immune cell infiltration and single cell sequencing analyses indicated that ITGB4 may be closely related to the microenvironment of gliomas, especially tumor-associated fibroblasts. ITGB4 is a promising diagnostic and therapeutic factor in LGG patients.

Insulin resistance levels predicted metabolic improvement and weight loss after metabolic surgery in Chinese patients with type 2 diabetes.

BACKGROUND: The causes for failure of metabolic improvement and inadequate weight loss after metabolic surgery (MS) in Chinese patients with type 2 diabetes (T2D) have not been fully elucidated. The effect of insulin resistance (IR) on the outcome of T2D, hypertension, hyperlipidemia, and obesity after MS in Chinese patients with T2D and a body mass index (BMI) of 25-32.5 kg/m2 warrants further study. OBJECTIVES: Patients with T2D and a BMI of 25-32.5 kg/m2 who underwent MS between July 2019 and June 2021 were included. SETTING: University hospital, China. METHODS: IR levels were evaluated with the glucose disposal rate (GDR). Improvement of T2D, hypertension, and hyperlipidemia was assessed with the composite triple endpoint (CTEP), and weight loss was assessed with the percent of total weight loss (%TWL). Partial correlation analysis, binary logistic regression analysis, multiple linear regression analysis, receiver operating characteristic curve (ROC) analysis, and subgroup analysis were used to analyze the relationship between the CTEP, %TWL at 1 year postoperative, and GDR preoperative. RESULTS: This study analyzed the data of 51 patients with T2D and a BMI of 25-32.5 kg/m2 (30 men and 21 women) with a mean preoperative GDR of 3.72 ± 1.48 mg/kg/min. Partial correlation coefficients between CTEP, %TWL, and GDR were .303 (P = .041) and .449 (P = .001), respectively. The preoperative GDR was significantly positively correlated with CTEP (OR = 1.610, P = .024) and %TWL (ß = 1.38, P = .003). The preoperative GDR predicted cutoff values of 4.36 and 5.35 mg/kg/min for CTEP attainment and %TWL ≥ 20%, respectively. CONCLUSION: IR levels predicted metabolic improvement and weight loss 1 year after MS in Chinese patients with T2D and a BMI of 25-32.5 kg/m2.

Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer.

The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.

Clinical factors associated with remission of obese acanthosis nigricans after laparoscopic sleeve gastrectomy: a prospective cohort study.

BACKGROUND: Acanthosis nigricans (AN) involves skin hyperpigmentation in body folds and creases. Obesity-associated AN (OB_AN) is the most common type of AN. The skin condition of obese patients with AN can be improved through bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG), after weight loss. However, the contributing factors to the remission of AN after surgery are still not fully determined. The authors aimed to assess the metabolic and pathological factors associated with remission of AN following LSG in obese individuals. METHODS: The study included 319 obese patients who underwent LSG at our hospital. The subjects were divided into obesity (OB) only (OB, n =178) or OB with AN (OB_AN, n =141) groups. The basic clinical and metabolic indices and the dermatological features via reflectance confocal microscopy and histology were collected from patients prior to and after LSG. RESULTS: OB_AN patients had higher fasting plasma glucose, homeostatic model assessment for insulin resistance, and testosterone levels than OB patients. LSG could significantly improve the biochemical and histopathological features of OB_AN patients. The remissive rate of OB_AN patients was about 86.5% (122 out of 141) after surgery. The remission of OB_AN skin lesions was positively correlated with testosterone levels ( P <0.01). In addition, there was a significant positive correlation between changes in AN scores and epidermal thickness and skin pigmentation scores after surgery ( P <0.01). CONCLUSION: The remissive rate of OB_AN after LSG is associated with improved testosterone levels and reduced epidermal thickness and skin pigmentation levels.

CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS: CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.

Sex-Specific Changes in Body Composition Following Metabolic and Bariatric Surgery Are Associated with the Remission of Metabolic Syndrome.

PURPOSE: Metabolic and bariatric surgery (MBS) is the most effective treatment for metabolic syndrome (MetS). However, the mechanism of MetS remission after MBS remains unclear. We aimed to explore the relationship between sex differences, body composition, and the remission of MetS after MBS. MATERIALS AND METHODS: Cross-sectional study of 80 patients with obesity and MetS who underwent MBS with case-control design. The International Diabetes Federation criteria were used to define MetS. Body composition was measured using dual-energy X-ray absorptiometry before and 1 year after the operation. In addition to calculating changes in MetS and its prevalence, we performed a multiple logistic regression to determine predictors of MetS remission. RESULTS: There were significant differences in body composition between males and females after MBS. Both males and females had significant improvements in the overall prevalence of MetS, decreasing from 100 to 21.74% (P <0.001) and from 100 to 35.29% (P <0.001), respectively. A higher percentage of visceral adipose tissue (VAT) reduction tends to be associated with a higher chance of MetS remission in men. In females, the MetS nonremission subgroup had a higher %Trunk lean body mass (LBM), and %Android LBM reduction than the remission subgroup, but the multiple logistic regression analysis result was not statistically significant. CONCLUSION: After MBS, reduced VAT might be related to MetS reversibility in males, while reduced LBM may result in MetS nonremission in females.

Effect of laparoscopic sleeve gastrectomy on mobilization of site-specific body adipose depots: a prospective cohort study.

BACKGROUND: Effect of bariatric surgery on mobilization of site-specific body adipose depots is not well investigated. Herein, the authors conducted a prospective cohort study to assess whether bariatric surgery can differentially affect specific fat storage pools and to further investigate correlations between site-specific fat mobilization and clinical outcomes. MATERIALS AND METHODS: In this single-centre prospective cohort study, 49 participants underwent laparoscopic sleeve gastrectomy (LSG) from 24 May 2022 to 20 October 2022 and underwent MRI to estimate subcutaneous fat area, visceral fat area (VFA), hepatic and pancreatic proton density fat fraction (PDFF) at baseline and 3 months after surgery. The protocol for this study was registered on clinicaltrials.gov. RESULTS: Among 49 patients who met all inclusion criteria, the median [interquartile range (IQR)] age was 31.0 (23.0-37.0) years, the median (IQR) BMI was 38.1 (33.7-42.2) kg/m 2 and 36.7% were male. Median (IQR) percentage hepatic PDFF loss was the greatest after bariatric surgery at 68.8% (47.3-79.7%), followed by percentage pancreatic PDFF loss at 51.2% (37.0-62.1%), percentage VFA loss at 36.0% (30.0-42.4%), and percentage subcutaneous fat area loss at 22.7% (17.2-32.4%) ( P <0.001). By calculating Pearson correlation coefficient and partial correlation coefficient, the positive correlations were confirmed between change in VFA and change in glycated haemoglobin ( r =0.394, P =0.028; partial r =0.428, P =0.042) and between change in hepatic PDFF and change in homoeostatic model assessment of insulin resistance ( r =0.385, P =0.025; partial r =0.403, P =0.046). CONCLUSIONS: LSG preferentially mobilized hepatic fat, followed by pancreatic fat and visceral adipose tissue, while subcutaneous adipose tissue was mobilized to the least extent. Reduction in visceral adipose tissue and hepatic fat is independently associated with the improvement of glucose metabolism after LSG.

Effects of Sleeve Gastrectomy on Patients with Obesity and Polycystic Ovary Syndrome: a Meta-analysis.

PURPOSE: This study aimed to evaluate the efficacy of sleeve gastrectomy (SG) on patients with obesity and polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies published prior to December 2, 2022. Meta-analysis was performed on menstrual irregularity, total testosterone, sex hormone-binding globulin (SHBG), anti-Mullerian hormone (AMH), glucolipid metabolism indicators, and body mass index (BMI) following SG. RESULTS: Six studies and 218 patients were included in the meta-analysis. Following SG, menstrual irregularity significantly decreased (odds ratio [OR] 0.03; 95% confidence intervals [CIs], 0.00-0.24; P=0.001). Additionally, SG can lower total testosterone levels (MD -0.73; 95% CIs -0.86-0.60; P< 0.0001), as well as BMI (MD -11.59; 95% CIs -13.10-10.08; P<0.0001). A significant increase was observed in the levels of SHBG and high-density lipoprotein (HDL) after SG. In addition to reducing fasting blood glucose, insulin, triglycerides (TG), and low-density lipoprotein levels, SG significantly reduced low-density lipoprotein levels as well. CONCLUSIONS: Following SG, we firstly demonstrated significant improvements in menstrual irregularity, testosterone and SHGB levels, glycolipid metabolism indicators, and BMI. Therefore, SG may be considered as a new option for the clinical treatment of patients with obesity and PCOS.

Is prior bariatric surgery associated with poor COVID-19 outcomes? A systematic review and meta-analysis of case-control studies.

Background: Obesity is an independent risk factor for severe coronavirus disease 2019 (COVID-19), but there is little evidence on whether prior bariatric surgery benefits the outcomes of patients with COVID-19. We aimed to summarize this relationship by conducting a systematic review and meta-analysis of current case-control studies. Methods: We searched several electronic databases for case-control studies conducted between January 2020 and March 2022. We compared the rates of mortality, mechanical ventilation, intensive care unit (ICU) admission, dialysis, hospitalization, and length of hospital stay between COVID-19 patients with and without a history of bariatric surgery. Results: We included six studies with 137 903 patients; 5270 (3.8%) had prior bariatric surgery, while 132 633 (96.2%) did not. COVID-19 patients with a history of bariatric surgery had significantly lower mortality (odds ratio (OR) = 0.42; 95% confidence interval (CI) = 0.23-0.74), ICU admission (OR = 0.48; 95% CI = 0.36-0.65), and mechanical ventilation rates than those with a history of non-bariatric surgery (OR = 0.51; 95% CI = 0.35-0.75). Conclusions: Prior bariatric surgery was associated with a reduced risk of mortality and reduced severity of COVID-19 in patients with obesity compared to those with no prior bariatric surgery. Further large-sample prospective studies are needed to support these results. Registration: CRD42022323745.

NPAS2 promotes aerobic glycolysis and tumor growth in prostate cancer through HIF-1A signaling.

BACKGROUND: Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. METHODS: Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. RESULTS: Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. CONCLUSION: NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

Basic performance of domestic surgical robot and the safety and effectiveness of integrated energy equipment. / å›½äº§æ‰‹æœ¯æœºå™¨äººåŸºæœ¬æ€§èƒ½å’Œæ•´åˆèƒ½é‡è®¾å¤‡çš„å®‰å ¨æ€§åŠæœ‰æ•ˆæ€§.

OBJECTIVES: Surgical robot system has broken the limitation of traditional surgery and shown excellent performance in surgery, and has been widely used in minimally invasive treatment in most areas of surgery. This study aims to verify the basic performance of the domestic surgical robot system and the safety and effectiveness of the integrated bipolar electrocoagulation and ultrasonic knife. METHODS: The basic performance of the domestic surgical robot system was evaluated by completing the square knot and surgical knot, vertical and horizontal perforation and right ring perforation and suture, as well as picking up beans. Compared with laparoscopy, the safety and effectiveness of the domestic surgical robot after integrated interconnection bipolar electrocoagulation and ultrasonic scalpel were evaluated by detecting the vascular closure performance and the degree of histopathological damage in animals. RESULTS: Compared with freehand knotting, domestic robot knotting speed and circumference were slightly worse, but better than laparoscopic knotting. There was no statistical significance in the tension difference of the surgical knots among the 3 methods (P>0.05), but the tension of the square knots made by the freehand and the domestic surgical robot was greater than that of the laparoscopy (P<0.05). The space required for both the left and right forceps heads of knots was smaller than that of laparoscopy (P<0.001), which successfully completed the 4 quadrant suture tasks, and the time of picking up beans was significantly less than that of laparoscopy (P<0.05). There was no significant difference in the temperature of the liver tissue after the bipolar electrocoagulation between the interconnected domestic surgical robot and the laparoscopy (P>0.05), and the acute thermal injury was observed under the light microscope. The temperature of the liver tissue treated by the domestic robotic ultrasound knife was higher than that of the laparoscopic ultrasound knife (P<0.05). CONCLUSIONS: Domestic surgical robots are obviously superior to laparoscopy in suturing, knotting, and moving objects, and domestic surgical robots' interconnect bipolar electrocoagulation and ultrasonic knife have achieved success in animal experiments, and hemostasis is considered to be safe and effective.

Disease-specific mortality and major adverse cardiovascular events after bariatric surgery: a meta-analysis of age, sex, and BMI-matched cohort studies.

BACKGROUND: Obesity is associated with a significant predisposition towards cardiovascular events and acts as an important risk factor for mortality. Herein, we conducted a comprehensive meta-analysis to estimate the protective effect of bariatric surgery on disease-specific mortality and major adverse cardiovascular events (MACEs) in patients with severe obesity. METHODS: PubMed and Embase were searched from inception to 4 June 2022. Eligible studies were age, sex, and BMI-matched cohort studies. The protocol for this meta-analysis was registered on PROSPERO (ID: CRD42022337319). RESULTS: Forty matched cohort studies were identified. Bariatric surgery was associated with a lower risk of disease-specific mortality including cancer mortality [hazard ratio with 95% confidence interval: 0.46 (0.37-0.58)], cardiovascular mortality [0.38 (0.29-0.50)], and diabetes mortality [0.25 (0.11-0.57)]. Bariatric surgery was associated with a lower incidence of MACEs [0.58 (0.51-0.66)] and its components including all-cause mortality [0.52 (0.47-0.58)], atrial fibrillation [0.79 (0.68-0.92)], heart failure [0.52 (0.42-0.65)], myocardial infarction [0.55 (0.41-0.74)], and stroke [0.75 (0.63-0.89)]. According to subgroup analysis on all-cause mortality, patients with severe obesity and type 2 diabetes benefited more from bariatric surgery than those with severe obesity only (heterogeneity between groups: P =0.001), while different surgical approaches brought similar benefits (heterogeneity between groups: P =0.87). CONCLUSIONS: This meta-analysis of 40 matched cohort studies supports that bariatric surgery reduces disease-specific mortality and incidence of both MACEs and its components in patients with severe obesity compared with nonsurgical subjects. Bariatric surgery deserves a more aggressive consideration in the management of severe obesity.

Ribosomal protein L22-like1 promotes prostate cancer progression by activating PI3K/Akt/mTOR signalling pathway.

Prostate cancer (PCa) is one of the most common malignancies in men. Ribosomal protein L22-like1 (RPL22L1), a component of the ribosomal 60 S subunit, is associated with cancer progression, but the role and potential mechanism of RPL22L1 in PCa remain unclear. The aim of this study was to investigate the role of RPL22L1 in PCa progression and the mechanisms involved. Bioinformatics and immunohistochemistry analysis showed that the expression of RPL22L1 was significantly higher in PCa tissues than in normal prostate tissues. The cell function analysis revealed that RPL22L1 significantly promoted the proliferation, migration and invasion of PCa cells. The data of xenograft tumour assay suggested that the low expression of RPL22L1 inhibited the growth and invasion of PCa cells in vivo. Mechanistically, the results of Western blot proved that RPL22L1 activated PI3K/Akt/mTOR pathway in PCa cells. Additionally, LY294002, an inhibitor of PI3K/Akt pathway, was used to block this pathway. The results showed that LY294002 remarkably abrogated the oncogenic effect of RPL22L1 on PCa cell proliferation and invasion. Taken together, our study demonstrated that RPL22L1 is a key gene in PCa progression and promotes PCa cell proliferation and invasion via PI3K/Akt/mTOR pathway, thus potentially providing a new target for PCa therapy.

Clavien-Dindo classification and risk prediction model of complications after robot-assisted radical hysterectomy for cervical cancer.

Although significant progress has been made with surgical methods, the incidence of complications after minimally invasive surgery in patients with cervical cancer remains high. Established as a standardized system, Clavien-Dindo classification (CDC) has been applied in a variety of surgical fields. This study is designed to evaluate the complications after robot-assisted radical hysterectomy (RRH) for cervical cancer using CDC and further establish a prediction model. This is a study on the development of prediction model based on retrospective data. Patients with cervical cancer who received RRH treatment in our hospital from January 2016 to April 2019 were invited to participate in the study. The demographic data, laboratory and imaging examination results and postoperative complications were collected, and the logistic regression model was applied to analyze the risk factors possibly related to complications to establish a prediction model. 753 patients received RRH. The overall incidence of complications was 32.7%, most of which were grade I and grade II (accounting for 30.6%). The results of multivariate analysis showed that the preoperative neoadjuvant chemotherapy (OR = 1.693, 95%CI: 1.210-2.370, P = 0.002), preoperative ALT (OR = 1.028, 95%CI: 1.017-1.039, P < 0.001), preoperative urea nitrogen (OR = 0.868, 95%CI: 0.773-0.974, P = 0.016), preoperative total bilirubin (OR = 0.958, 95%CI: 0.925-0.993, P = 0.0.018), and preoperative albumin (OR = 0.937, 95%CI: 0.898-0.979, P = 0.003) were related to the occurrence of postoperative complications. The area under the curve (AUC) of receiver-operating characteristic (ROC) in the prediction model of RRH postoperative complications established based on these five factors was 0.827 with 95% CI of 0.794-0.860. In patients undergoing robot-assisted radical hysterectomy for cervical cancer, preoperative ALT level, urea nitrogen level, total bilirubin level, albumin level, and neoadjuvant chemotherapy were significantly related to the occurrence of postoperative complications. The regression prediction model established on this basis showed good prediction performance with certain clinical promotion and reference value.

Gibberellin derivative GA-13315 overcomes multidrug resistance in breast cancer by up-regulating BMP6 expression.

Chemoresistance represents a major obstacle in breast cancer treatment. Bone morphogenetic protein 6 (BMP6) was reported to participate in the occurrence and development of various tumors. In the present study, the results of transcriptome sequencing, qRT-PCR and western blot analysis revealed that BMP6 was down-regulated in multidrug resistant MCF-7/Adr breast cancer cells and BMP6 overexpression sensitized MCF-7/Adr cells to chemotherapeutic drugs, indicating that BMP6 downregulation was involved in the mechanisms of multidrug resistance (MDR) of MCF-7/Adr breast cancer cells. GA-13315 (GA5) is a new tetracyclic diterpenoid selected from a series of gibberellin derivatives. Here, we found that GA5 exhibited more potent anti-tumor activity in multidrug resistant MCF-7/Adr breast cancer cells and xenografts, indicating that GA5 could overcome MDR. Mechanistically, GA5 increased BMP6 expression, and BPM6 knockdown partially reversed the inhibitory effect of GA5 on cell proliferation. Furthermore, we found that ERK phosphorylation and P-gp expression were increased in MCF-7/Adr cells when compared with MCF-7 cells. Either overexpression of BMP6 or treatment the cells with GA5 significantly decreased ERK phosphorylation and P-gp expression, indicating that GA5 reversed MDR of MCF-7/Adr cells by upregulating BMP6, thereby inhibiting the activation of ERK signaling pathway and reducing P-gp expression. Collectively, our present study demonstrated that the MDR of MCF-7/Adr cells was closely related to the low expression of BMP6, and revealed the molecular mechanisms by which GA5 overcame MDR in breast cancer, providing evidence in supporting the development of GA5 to be a promising agent for overcoming MDR in clinical cancer therapy in the future.

A Model for Predicting Clinical Prognosis in Patients with WHO Grade 2 Glioma.

Objectives: Although patients with grade 2 glioma have a relatively better prognosis and longer survival than those with high-grade glioma, there are still a number of patients with disappointing outcomes. In order to accurately predict the prognosis of patients, relevant risk factors were included in the analysis to establish a clinical prediction model so as to provide a basis for clinically individualized treatment. Methods: A retrospective study was conducted in patients diagnosed with grade 2 glioma. Data including clinical features, pathological type, molecular classification, neuroimaging examination, treatment, and survival were collected. The data sets were randomly assigned, with 80% of the data used for model building and 20% for validation. Cox proportional hazard regression analysis was used to construct the model using important risk factors and present it in the form of a nomogram. The nomogram was evaluated a using C-index and calibration chart. Results: A total of 160 patients were enrolled in this analysis, including 128 in the training group and 32 in the validation group. In the training group, eight important risk factors including preoperative KPS, the first presenting symptom, the extent of resection, the gross tumor size, 1p19q, IDH, radiotherapy, and chemotherapy were identified to construct the model. The C-index of the training group and the validation group was 0.832 and 0.801, respectively, indicating that the model had good prediction ability. The calibration charts of the two groups were drawn respectively, which showed that the calibration line and the standard line had a good consistency, which suggested that the model-predicted risk had a good consistency with the actual risk. Conclusions: Based on the data of our center, a nomogram prediction model with eight variables has been established as an off-the-rack tool and verified its accuracy, which can guide clinical work and provide consultation for patients.