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The 1092 bp F3H gene from Trapa bispinosa Roxb., which was named TbF3H, was cloned and it encodes 363 amino acids. Bioinformatic and phylogenetic tree analyses revealed the high homology of TbF3H with flavanone 3-hydroxylase from other plants. A functional analysis showed that TbF3H of Trapa bispinosa Roxb. encoded a functional flavanone 3-hydroxylase; it catalyzed the formation of dihydrokaempferol (DHK) from naringenin in S. cerevisiae . The promoter strengths were compared by fluorescence microscopy and flow cytometry detection of the fluorescence intensity of the reporter genes initiated by each constitutive promoter (FITC), and DHK production reached 216.7 mg/L by the promoter adjustment strategy and the optimization of fermentation conditions. The results presented in this study will contribute to elucidating DHK biosynthesis in Trapa bispinosa Roxb.

Background: We conducted a meta-analysis and trial sequential analysis (TSA) to compare the therapeutic efficacy and adverse events (AEs) between the following treatment strategies for patients with hepatocellular carcinoma (HCC): TACE plus tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) (TACE + T + I) versus TACE plus TKIs (TACE + T)., Methods: We systematically searched PubMed, the Web of Science, the Cochrane Library, and Embase for studies comparing TACE + T + I and TACE + T for the treatment of BCLC intermediate- or advanced-stage HCC. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and AEs were included as outcomes. We used a fixed- or random-effects model based on the results of a heterogeneity evaluation and performed a meta-analysis using Review Manager 5.3 and Stata 16.0. We then carried out the TSA., Results: Five studies examining a total of 425 patients were included in this study. Our meta-analysis revealed that, compared to TACE + T, TACE + T + I significantly improved the ORR (risk ratio [RR] = 1.53, 95% confidence interval [CI] = 1.27-1.85, p < 0.01) and extended both the median PFS (mean difference [MD] = 4.51 months, 95% CI = 2.16-6.87, p < 0.01) and median OS (MD = 5.75 months, 95% CI = 4.03-7.48, p < 0.01). These results were tested to be true by the TSA without requiring a larger information size. Among AEs, hypertension tended to occur more often in patients treated with TACE + T + I than in those treated with TACE + T (RR = 1.58, 95% CI = 1.05-2.40, p < 0.05). However, the TSA suggested that additional cases are necessary to confirm this difference. Regarding the other AEs, no significant differences were detected between the two groups., Conclusion: TACE + T + I showed better effects on the ORR, PFS, and OS than TACE + T as a treatment for BCLC stages B and C HCC, without an obvious increase in the AEs. Based on these findings, well-designed, large RCTs are suggested., (© 2023. Asian Pacific Association for the Study of the Liver.)

The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Immunohistochemistry and multiplex immunofluorescence staining were used to further validate it. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming. The findings indicate that in imatinib-resistant TME, tumor cells with activated immune and cytokine-mediated immune responses interacted with a higher proportion of Treg cells via the TIGIT-NECTIN2 axis. Future immunotherapeutic strategies targeting Treg may provide new directions for the treatment of imatinib-resistant patients. In addition, IDO1+ dendritic cells (DC) were highly enriched in imatinib-resistant TME, interacting with various myeloid cells via the BTLA-TNFRSF14 axis, while the interaction was not significant in imatinib-sensitive TME. Our study highlights the transcriptional heterogeneity and distinct immunosuppressive microenvironment of advanced GIST, which provides novel therapeutic strategies and innovative immunotherapeutic agents for imatinib resistance., (© 2024. The Author(s).)

Background: Although minimally invasive surgery (MIS) for gastric patients has gained popularity in recent decades, reports on the comparison of short and long clinical outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer patients with BMI≥30 kg/m 2 are still limited., Methods: A total of 226 obese gastric cancer patients who underwent either RG (n = 81) or LG (n = 145) were enrolled in this study between October 2014 and September 2022. Propensity score matching (PSM) (1:1) was performed to reduce confounding bias. Short-term and long-term outcomes were compared between the RG and LG groups., Results: The clinicopathological characteristics of 156 patients in the RG group (n = 79) and LG group (n = 79) were well balanced after PSM. Compared with the LG group, the RG group had a significantly shorter operation time, less estimated blood loss, more harvested lymph nodes, a faster postoperative recovery course, reduced surgical morbidity, and a shorter postoperative hospital stay. The long-term outcomes were comparable between the two groups., Conclusions: RG is a safe and feasible approach for gastric cancer with a BMI≥30 kg/m 2 and has better short-term clinical outcomes than LG. However, RG is similar to LG in terms of long-term prognosis., (© 2023 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients., Methods: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC., Results: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ 2  = 10.622, p = 0.001; χ 2  = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ 2  = 8.063, p = 0.005; χ 2  = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044)., Conclusions: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes., (© 2023 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: We aimed to construct and validate a deep learning (DL) radiomics nomogram using baseline and restage enhanced computed tomography (CT) images and clinical characteristics to predict the response of metastatic lymph nodes to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC)., Methods: We prospectively enrolled 112 patients with LAGC who received NACT from January 2021 to August 2022. After applying the inclusion and exclusion criteria, 98 patients were randomized 7:3 to the training cohort (n = 68) and validation cohort (n = 30). We established and compared three radiomics signatures based on three phases of CT images before and after NACT, namely radiomics-baseline, radiomics-delta, and radiomics-restage. Then, we developed a clinical model, DL model, and a nomogram to predict the response of LAGC after NACT. We evaluated the predictive accuracy and clinical validity of each model using the receiver operating characteristic curve and decision curve analysis, respectively., Results: The radiomics-delta signature was the best predictor among the three radiomics signatures. So, we developed and validated a DL delta radiomics nomogram (DLDRN). In the validation cohort, the DLDRN produced an area under the receiver operating curve of 0.94 (95% confidence interval, 0.82-0.96) and demonstrated adequate differentiation of good response to NACT. Furthermore, the DLDRN significantly outperformed the clinical model and DL model (p < 0.001). The clinical utility of the DLDRN was confirmed through decision curve analysis., Conclusions: In patients with LAGC, the DLDRN effectively predicted a therapeutic response in metastatic lymph nodes, which could provide valuable information for individualized treatment., (© 2023. Society of Surgical Oncology.)

Objective: To investigate the association of fat and lean mass in specific regions with all-cause and cardiovascular-related mortality., Design: Population based cohort study., Setting: US National Health and Nutrition Examination Survey (2003-2006 and 2011-2018)., Participants: 22 652 US adults aged 20 years or older., Exposures: Fat and lean mass in specific regions obtained from the whole-body dual-energy X-ray absorptiometry., Main Outcome Measures: All-cause and cardiovascular-related mortality., Results: During a median of 83 months of follow-up, 1432 deaths were identified. Associations between body composition metrics and mortality risks were evident above specific thresholds. For all-cause mortality, Android fat mass showed elevated HRs above 2.46 kg (HR: 1.17, 95% CI 1.02 to 1.34), while Android lean mass (ALM) had similar trends above 2.75 kg (HR: 1.17, 95% CI 1.03 to 1.33), and Android total mass above 5.75 kg (HR: 1.08, 95% CI 1.01 to 1.16). Conversely, lower HRs were observed below certain thresholds: Gynoid fat mass (GFM) below 3.71 kg (HR: 0.72, 95% CI 0.56 to 0.93), Gynoid lean mass below 6.44 kg (HR: 0.77, 95% CI 0.64 to 0.92), and Gynoid total mass below 11.78 kg (HR: 0.76, 95% CI 0.70 to 0.84). Notably, below 0.722 kg, the HR of visceral adipose tissue mass (VATM) was 1.25 (95% CI 1.04 to 1.48) for all-cause mortality, and above 3.18 kg, the HR of total abdominal fat mass was 2.41 (95% CI 1.15 to 5.05). Cardiovascular-related mortality exhibited associations as well, particularly for Android fat mass (AFM) above 1.78 kg (HR: 1.22, 95% CI 1.01 to 1.47) and below 7.16 kg (HR: 0.50, 95% CI 0.36 to 0.69). HRs varied for Gynoid total mass below and above 10.98 kg (HRs: 0.70, 95% CI 0.54 to 0.93, and 1.12, 95% CI 1.02 to 1.23). Android per cent fat, subcutaneous fat mass (SFM), AFM/GFM, and VATM/SFM were not statistically associated with all-cause mortality. Android per cent fat, Gynoid per cent fat, AFM/GFM, and VATM/SFM were not statistically associated with cardiovascular-related mortality. Conicity index showed that the ALM/GLM had the highest performance for all-cause and cardiovascular-related mortality with AUCs of 0.785, and 0.746, respectively., Conclusions: The relationship between fat or lean mass and all-cause mortality varies by region. Fat mass was positively correlated with cardiovascular mortality, regardless of the region in which they located. ALM/GLM might be a better predictor of all-cause and cardiovascular-related mortality than other body components or body mass index., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Gastric cancer (GC) diagnosed in the elderly population has become a serious public health problem worldwide. Given the combined effects of frailty and the consequences of cancer treatment, older individuals with GC are more likely than young patients to suffer from postoperative complications and poor clinical outcomes. Nutrition, functional capacity and psychological state-based multimodal prehabilitation, which is dominated by Enhanced Recovery After Surgery (ERAS) pathway management, has been shown to reduce postoperative complications, promote functional recovery and decrease hospitalisation time in certain malignancies. However, no previous studies have investigated the clinical application of multimodal prehabilitation in frail older patients with GC., Methods and Analysis: The study is a prospective, multicentre randomised controlled trial in which a total of 368 participants who meet the inclusion criteria will be randomised into either a prehabilitation group or an ERAS group. The prehabilitation group will receive multimodal prehabilitation combined with ERAS at least 2 weeks before the gastrectomy is performed, including physical and respiratory training, nutritional support, and therapy and psychosocial treatment. The ERAS group patients will be treated according to the ERAS pathway. All interventions will be supervised by family members. The primary outcome measures are the incidence and severity of postoperative complications. Secondary outcomes include survival, functional capacity and other short-term postoperative outcomes. Overall, the multimodal prehabilitation protocol may improve functional capacity, reduce the surgical stress response and concomitant systemic inflammation, and potentially modulate the tumour microenvironment to improve short-term and long-term clinical outcomes and patients' quality of life., Ethics and Dissemination: All procedures and participating centres of this study were approved by their respective ethics committees (QYFYKYLL 916111920). The final study results will be published separately in peer-reviewed journals., Trial Registration Number: NCT05352802., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Some studies have demonstrated the short-term recovery course for patients who underwent laparoscopic gastrectomy according to preoperative computed tomography angiography (CTA) assessment. However, reports of the long-term oncological outcomes are still limited., Methods: The data of 988 consecutive patients who underwent laparoscopic or robotic radical gastrectomy between January 2014 and September 2018 were analyzed retrospectively at our center, and propensity score matching was used to eliminate bias. Study cohorts were divided into the CTA group (n = 498) and the non-CTA group (n = 490) depending on whether preoperative CTA was available. The primary and secondary endpoints were the 3-year overall survival (OS) and disease-free survival (DFS) rates and the intraoperative course and short-term outcomes, respectively., Results: 431 patients were included in each group after PSM. Compared with the non-CTA group, the CTA group had more harvested lymph nodes and less operative time, blood loss, intraoperative vascular injury and total cost, especially in the subgroup analysis with BMI ≥ 25 kg/m 2 patients. There was no difference in the 3 year OS and DFS between the CTA group and the non-CTA group. When further stratified by BMI < 25 or ≥ 25 kg/m 2 , the 3-year OS and DFS were significantly higher in the CTA group than in the non-CTA group in terms of BMI ≥ 25 kg/m 2 ., Conclusions: Laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making has the possibility of improving short-term outcomes. However, there is no difference in the long-term prognosis, except for a subgroup of patients with BMI ≥ 25 kg/m 2 ., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study was performed to evaluate the safety and efficacy of laparoscopic gastrectomy (LG) in patients with locally advanced gastric cancer (LAGC) who received neoadjuvant chemotherapy (NACT)., Methods: We retrospectively analyzed patients who underwent gastrectomy for LAGC (cT2-4aN+M0) after NACT from January 2015 to December 2019. The patients were divided into a LG group and an open gastrectomy (OG) group. The short- and long-term outcomes in both groups were examined following propensity score matching., Results: We retrospectively reviewed 288 patients with LAGC who underwent gastrectomy following NACT. Of these 288 patients, 218 were enrolled; after 1:1 propensity score matching, each group comprised 81 patients. The LG group had significantly lower estimated blood loss than the OG group [80 (50-110) vs. 280 (210-320) mL, P < 0.001) but a longer operation time [205 (186.5-222.5) vs. 182 (170-190) min, P < 0.001], a lower postoperative complication rate (24.7% vs. 42.0%, P = 0.002), and a shorter postoperative hospitalization period [8 (7-10) vs. 10 (8-11.5) days, P = 0.001]. Subgroup analysis revealed that patients who underwent laparoscopic distal gastrectomy had a lower rate of postoperative complications than patients in the OG group (18.8% vs. 38.6%, P = 0.034); however, such a pattern was not seen in patients who underwent total gastrectomy (32.3% vs. 45.9%, P = 0.251). The 3-year matched cohort analysis showed no significant difference in overall survival or recurrence-free survival (log-rank P = 0.816 and P = 0.726, respectively) (71.3% and 65.0% in OG vs. 69.1% and 61.7% in LG, respectively)., Conclusion: In the short term, LG following NACT is safer and more effective than OG. However, the long-term results are comparable., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Studies on robotic total gastrectomy (RTG) are currently limited. This study aimed to compare the intraoperative performance as well as short- and long-term outcomes of RTG and laparoscopic total gastrectomy (LTG)., Methods: A total of 969 patients underwent robotic (n = 161) or laparoscopic (n = 636) total gastrectomy between October 2014 and October 2021. The two groups of patients were matched 1:3 using the propensity score matching (PSM) method. The intraoperative performance as well as short- and long-term outcomes of the robotic (n = 147) and the laparoscopic (n = 371) groups were compared., Results: After matching, the estimated intraoperative blood loss was lower (80.51 ± 68.77 vs. 89.89 ± 66.12, p = 0.008), and the total number of lymph node dissections was higher (34.74 ± 12.44 vs. 29.83 ± 12.22, p < 0.001) in the RTG group compared with the LTG group. More lymph node dissections at the upper edge of the pancreas were performed in the RTG group than in the LTG (12.59 ± 4.18 vs. 10.33 ± 4.58, p = 0.001). Additionally, postoperative recovery indicators and laboratory data were greater in the RTG group than those in the LTG group, while postoperative complications were comparable between the two groups (19.0% vs. 18.9%, p = 0.962). For overweight or obese patients with body mass indexes (BMIs) ≥25, certain clinical outcomes of the RTG remained advantageous, and no significant differences in three-year overall survival (OS) or relapse-free survival (RFS) were observed., Conclusions: Robotic total gastrectomy demonstrated better intraoperative performance, could improve the short-term clinical outcomes of patients, and was more conducive to patient recovery. However, the long-term efficacies of the two approaches were similar. Robotic surgical systems may reduce surgical stress responses in patients, allowing them to receive postoperative chemotherapy sooner., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To evaluate the multiple factors influencing the survival of elderly patients with locally advanced gastric cancer (LAGC) and develop and validate the novel nomograms for predicting the survival., Methods: The clinical features of patients treated between 2000 and 2018 were collected and collated from the Surveillance, Epidemiology, and End Results (SEER) database and three medical centres in China, and the patients were randomly divided into a training cohort (3494), internal validation cohort (1497) and external validation cohort (841). Univariate and multivariate analyses of the prognostic values were performed to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS), and two nomogram models were developed. Harrell's concordance index (C-index) and calibration curves were employed to assess discrimination and calibration. Decision curve analysis (DCA) and receiver-operating characteristic (ROC) curves were utilized to investigate the clinical usefulness., Results: In the SEER database, the 5-year OS of the patients was 31.08%, while the 5-year CSS of the patients was 44.09%. Furthermore, in the external validation set, the 5-year OS of the patients was 49.58%, and the 5-year CSS of these patients was 53.51%. After statistical analysis, nine independent prognostic factors of OS and CSS were identified, including age, race, tumour size, differentiation, TNM stage, gastrectomy type, lymph node metastasis (LNM), lymph node ratio (LNR) and chemotherapy. The C-index (approximately 0.7) and calibration curve (close to the optimal calibration line) indicated satisfactory discrimination and calibration of the nomogram. DCA and ROC curves showed that the developed nomogram was superior to TNM stage., Conclusion: The novel validated nomogram could accurately predict the prognosis of individual elderly patients with LAGC and guide the selection of clinical treatment measures., (© 2023. The Author(s).)

Purpose: Accurate preoperative diagnosis of parotid tumor is essential for the formulation of optimal individualized surgical plans. The study aims to investigate the diagnostic performance of radiomics nomogram based on contrast-enhanced computed tomography (CT) images in the differentiation of the two most common benign parotid gland tumors., Methods: One hundred and ten patients with parotid gland tumors including 76 with pleomorphic adenoma (PA) and 34 with adenolymphoma (AL) confirmed by histopathology were included in this study. Radiomics features were extracted from contrast-enhanced CT images of venous phase. A radiomics model was established and a radiomics score (Rad-score) was calculated. Clinical factors including clinical data and CT features were assessed to build a clinical factor model. Finally, a nomogram incorporating the Rad-score and independent clinical factors was constructed. Receiver operator characteristics (ROC) curve was generated and the area under the ROC curve (AUC) was calculated to quantify the discriminative performance of each model on both the training and validation cohorts. Decision curve analysis (DCA) was conducted to evaluate the clinical usefulness of each model., Results: The radiomics model showed good discrimination in the training cohort [AUC, 0.89; 95% confidence interval (CI), 0.80-0.98] and validation cohort (AUC, 0.89; 95% CI, 0.77-1.00). The radiomics nomogram showed excellent discrimination in the training cohort (AUC, 0.98; 95% CI, 0.96-1.00) and validation cohort (AUC, 0.95; 95% CI, 0.88-1.00) and displayed better discrimination efficacy compared with the clinical factor model (AUC, 0.93; 95% CI, 0.88-0.99) in the training cohort (p < 0.05). The DCA demonstrated that the combined radiomics nomogram provided superior clinical usefulness than clinical factor model and radiomics model., Conclusions: The CT-based radiomics nomogram combining Rad-score and clinical factors exhibits excellent predictive capability for differentiating parotid PA from AL, which might hold promise in assisting radiologists and clinicians in the exact differential diagnosis and formulation of appropriate treatment strategy., (© 2022 American Association of Physicists in Medicine.)

The preferred treatment for lung cancer is surgical resection, but a large number of patients are not suitable for surgical resection in clinic. CT-guided cryoablation and immunotherapy can play an important role in patients with advanced lung cancer who are ineligible for surgery. CT-guided cryoablation has been widely used in the clinical treatment of lung tumors due to its advantages of less trauma, fewer complications, significant efficacy and rapid recovery. Cryoablation can not only cause tumor necrosis and apoptosis, but also promote the release of tumor-derived autoantigens into the blood circulation, and stimulate the host immune system to produce a good anti-tumor immune effect against primary and metastatic tumors. Since the study of immune checkpoint inhibitors has proved that lung cancer can be an immunotherapeutic response disease, the relationship between cryoablation and immunotherapy of lung cancer has been paid more attention. Therefore, we reviewed the literature on cryoablation for lung cancer, as well as the research progress of cryoablation combined with immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Qi, Jiang, Shang, Xu and Shao.)

Background: Neuro-oncological ventral antigen 1 (NOVA1) is a neuron-specific RNA-binding protein which regulates alternative splicing in the developing nervous system. Recent research has found that NOVA1 plays a significant role in carcinogenesis. In this paper, we examine the role of NOVA1 in non-small cell lung cancer (NSCLC) and its underlying molecular mechanisms., Methods: The expression of NOVA1 in NSCLC was detected by immunohistochemistry and correlations between NOVA1 expression and clinicopathological factors were analyzed by chi-square tests. Kaplan-Meier survival analysis and the Cox regression model were used to evaluate the predictive effect of prognostic factors. Western blotting, Cell Counting Kit-8, colony formation, apoptosis, migration and invasion assays were used to detect the effects of silencing (si)NOVA1 RNA on Wnt/β-catenin signaling and biological behavior in NSCLC cell lines., Results: Our study showed that expression of NOVA1 was up-regulated and significantly correlated with poor differentiation (p = 0.020), advanced TNM stage (P = 0.001), T stage (P = 0.001) and lymph node metastasis (P = 0.000) as well as the expression of β-catenin (P = 0.012) in NSCLC. The down-regulation of NSCLC by siRNA significantly inhibited proliferation, migration and invasion and promoted apoptosis in NSCLC cells. Expression of Wnt signaling molecules, including β-catenin, activated β-catenin, cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-7, was also significantly reduced by siNOVA1. The inhibition of Wnt/β-catenin signaling in A549 and H1299 cells by siNOVA1 was reversed after treatment with a β-catenin expression plasmid., Conclusion: The present study suggests that NOVA1 may serve as a potential prognosis biomarker in NSCLC. High NOVA1 expression was associated with poor survival rate. Finally, in vitro experiments verified that NOVA1 promotes NSCLC cell proliferation and invasion by regulating Wnt/β-catenin signaling., (© 2022. The Author(s).)

Objectives: Surgery can significantly improve the prognosis of patients with gastric cancer. However, some patients are at a later stage at diagnosis and need to receive neoadjuvant chemotherapy (NACT). Previous studies have shown that NACT may lead to more postoperative complications. Probiotics have the potential to reduce postoperative complications and infections, but no similar clinical trials have been conducted in patients with gastric cancer receiving NACT. The aim of this study was to investigate the effect of probiotics on postoperative infections and other short-term outcomes in patients with gastric cancer receiving NACT., Methods: This was a randomized, double-blind, controlled trial. All patients who underwent minimally invasive surgery after NACT were included and randomized into a probiotic group (PG; n = 33) or a control group (CG; n = 33). Postoperative infectious complications, recovery of gastrointestinal function, postoperative hospital stay, medical costs, time to initiate adjuvant chemotherapy, 30-d readmission and mortality, and common laboratory inflammatory indexes were observed., Results: PG patients had significantly fewer postoperative infections (P = 0.027). Time to first flatus and bowel movement was quicker (P = 0.001 and P < 0.001, respectively) and inflammatory indexes were lower in the PG patients. Postoperative hospital length of stay was shorter in the PG than in the CG (P = 0.001). Due to fewer postoperative infections and faster recovery, adjuvant chemotherapy was initiated earlier in PG patients (P < 0.001)., Conclusions: Perioperative probiotic supplements can reduce postoperative infection, improve short-term clinical outcomes, and reduce the level of common inflammatory indicators in patients with gastric cancer receiving NACT. Patients in the PG started adjuvant chemotherapy earlier than CG patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Mitogen-inducible gene 6 (Mig-6) is a tumor suppressor gene that plays an important role in many types of cancers by interacting with EGFR. However, its molecular mechanism in hepatocellular carcinoma (HCC) and its relationship with miRNAs need to be elucidated. Therefore, this study aimed to explore whether Mig-6 could promote apoptosis and the inhibition of autophagy via its downstream miRNA in HCC cell lines. We used two cell lines, HepG2 and HLE, to establish Mig-6 overexpression and knockdown experiments, as well as miR-193a mimic and inhibitor experiments. The miRNA microarray profiling was also used to verify Mig-6-regulated miRNA. We found that Mig-6 induced apoptosis and reduced autophagy of HCC cell lines. miR-193a-3p is a Mig-6-regulated miRNA in the Mig-6-overexpression model. It affected the apoptosis and autophagy of HCC cells, at least partly by regulating the expression of TGF-β2. Additionally, the relationship between Mig-6 and transforming growth factor TGF-β2 was explored in depth for the first time. These findings revealed an important role of Mig-6 in the apoptosis and autophagy of HCC cells by regulating miR-193a-3p, providing a novel insight into the therapeutic target in HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Research on short-term outcomes and oncology results after robotic gastrectomy (RG) is still limited, especially from a single surgical team. The purpose of this study was to compare the short-term and long-term outcomes of robotic and laparoscopic gastrectomy (LG)., Methods: Between October 2014 and September 2019, 1686 consecutive patients who underwent MIS gastrectomy were enrolled. The patients were divided into RG and LG groups according to surgical type. Groups were matched at a 1:1 ratio using propensity scores based on the following variables: age, sex, ASA score, primary tumor location, histologic type, pathological stage, and neoadjuvant chemotherapy. The primary outcomes were 3-year overall survival (OS) and relapse-free survival (RFS). The secondary outcomes were postoperative short-term outcomes., Results: Demographic and baseline characteristics were similar between the two groups after matching. Compared to the LG group, the RG group had a significantly higher retrieved lymph node (LN) number (32.15 vs 30.82, P = 0.040), more retrieved supra-pancreatic LNs (12.45 vs 11.61, P = 0.028), lower estimated blood loss (73.67 vs 98.08 ml, P < 0.001), but longer operation time (205.18 vs 185.27 min, P < 0.001) and higher hospitalization costs ($13,607 vs $10,928, P < 0.001) in the matched cohort. In the subgroup analysis, we observed that compared with LG, patients with advanced gastric cancer benefitted more from RG surgery. The matched cohort analysis demonstrated no statistically significant differences for 3-year OS or RFS (log-rank, P = 0.648 and P = 0.951, respectively): 80.3% and 77.0% in LG vs. 81.2% and 76.6% in RG, respectively., Conclusion: RG has certain technical advantages over LG, especially in patients with advanced gastric cancer. However, RG does not improve long-term oncology outcomes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objective: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after LDG., Summary of Background Data: Currently, the ERAS program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer., Methods: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery, and laboratory outcomes were compared between the ERAS and conventional groups., Results: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the 2 groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P < 0.001; 8.85 vs 7.27 days, P < 0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P < 0.001; 3.09 vs 1.13 days, P < 0.001; 2.85 vs 1.38 days, P < 0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day 3 were significantly lower and the hemoglobin levels on postoperative day 5 were significantly higher in the ERAS group than in the conventional group., Conclusion: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Gastric cancer, which is the fifth most common malignancy and the third most common cause of cancer-related death, is particularly predominant in East Asian countries, such as China, Japan and Korea. It is a serious global health issue that causes a heavy financial burden for the government and family. To our knowledge, there are few reports of multicentre randomized controlled trials on the utilization of CT angiography (CTA) for patients who are histologically diagnosed with gastric cancer before surgery. Therefore, we planned this RCT to verify whether the utilization of CTA can change the short- and long-term clinical outcomes., Method: The GISSG 20-01 study is a multicentre, prospective, open-label clinical study that emphasises the application of CTA for patients who will undergo laparoscopic gastrectomy to prove its clinical findings. A total of 382 patients who meet the inclusion criteria will be recruited for the study and randomly divided into two groups in a 1:1 ratio: the CTA group (n = 191) and the non-CTA group (n = 191). Both groups will undergo upper abdomen enhanced CT, and the CTA group will also receive CT angiography. The primary endpoint of this trial is the volume of blood loss. The second primary endpoints are the number of retrieved lymph nodes, postoperative recovery course, hospitalization costs, length of hospitalization days, postoperative complications, 3-year OS and 3-year DFS., Discussion: It is anticipated that the results of this trial will provide high-level evidence and have clinical value for the application of CTA in laparoscopic gastrectomy., Trial Registration: ClinicalTrials.gov , NCT04636099. Registered November 19, 2020., (© 2021. The Author(s).)

Discovering novel biomarkers that easily accessed is a key step towards the personalized medicine approach for gastric cancer patients. Integrin-β6 (ITGB6) is a subtype of integrin that is exclusively expressed on the surface of epithelial cells and is up-regulated in various tumors. In the present study, a retrospective cohort with 135 gastric cancer patients and a prospective cohort with 34 gastric cancer patients were constructed, ITGB6 expression were detected in both the serum specimens and the tissue specimens. Detailed clinicopathological parameters as well as patients' survival were recorded. A nomogram including ITGB6 expression was also constructed and validated to predict the prognosis of gastric cancer patients. Results showed that serum ITGB6 expression was obviously increased and associated with tumor stage in gastric cancer patients, serum ITGB6 expression was relatively high in patients with liver metastasis. High ITGB6 expression indicated a poor prognosis, and nomogram including serum ITGB6 expression could predict the prognosis of gastric cancer patients effectively. Moreover, serum ITGB6 expression was associated with ITGB6 expression in tumor tissues. Furthermore, combined serum ITGB6 and CEA levels contributed to the risk stratification and prognostic prediction for gastric cancer patients. In addition, the serum expression of ITGB6 decreased significantly after radical surgery, and a new rise in serum ITGB6 expression indicated tumor recurrence or progression. The present study identified a novel serum biomarker for the risk stratification, prognostic prediction and surveillance of gastric cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Sun, Xu, Yang, Liu, Tian, Cao and Zhou.)

Chitosan (CTS) is a deacetylated derivative of chitin that is involved in adaptive response to abiotic stresses. However, the regulatory role of CTS in heat tolerance is still not fully understood in plants, especially in grass species. The aim of this study was to investigate whether the CTS could reduce heat-induced senescence and damage to creeping bentgrass associated with alterations in antioxidant defense, chlorophyll (Chl) metabolism, and the heat shock pathway. Plants were pretreated exogenously with or without CTS (0.1 g L -1 ) before being exposed to normal (23/18 °C) or high-temperature (38/33 °C) conditions for 15 days. Heat stress induced detrimental effects, including declines in leaf relative water content and photochemical efficiency, but significantly increased reactive oxygen species (ROS) accumulation, membrane lipid peroxidation, and Chl loss in leaves. The exogenous application of CTS significantly alleviated heat-induced damage in creeping bentgrass leaves by ameliorating water balance, ROS scavenging, the maintenance of Chl metabolism, and photosynthesis. Compared to untreated plants under heat stress, CTS-treated creeping bentgrass exhibited a significantly higher transcription level of genes involved in Chl biosynthesis ( As PBGD and As CHLH ), as well as a lower expression level of Chl degradation-related gene ( As PPH ) and senescence-associated genes ( AsSAG12 , AsSAG39 , Asl20 , and Ash36 ), thus reducing leaf senescence and enhancing photosynthetic performance under heat stress. In addition, the foliar application of CTS significantly improved antioxidant enzyme activities (SOD, CAT, POD, and APX), thereby effectively reducing heat-induced oxidative damage. Furthermore, heat tolerance regulated by the CTS in creeping bentgrass was also associated with the heat shock pathway, since As HSFA-6a and As HSP82 were significantly up-regulated by the CTS during heat stress. The potential mechanisms of CTS-regulated thermotolerance associated with other metabolic pathways still need to be further studied in grass species.

Background: Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a newly discovered negative immune regulator. Studies have shown that TIPE2 causes significant malignant biological effects and is differentially expressed in various malignant tumors. However, the expression and roles of TIPE2 in pancreatic ductal adenocarcinoma (PDAC) are largely unknown. Materials and Methods: The expression of TIPE2 in PDAC tissues was assessed by immunohistochemistry, qPCR and western blot analysis and related clinicopathological parameters including survival time were analyzed. After overexpression of TIPE2, cell proliferation and apoptosis analysis were conducted, and the associated underlying molecular mechanism was also explored. Results: In the present study, TIPE2 was upregulated in early PDAC tissues, and TIPE2 expression decreased as the tumor progressed ( P <0.001). TIPE2 expression was negatively associated with tumor size, TNM stage and metastasis of lymph nodes. Furthermore, as an independent risk factor, TIPE2 could be used to predict the survival of patients with PDAC ( P =0.035). TIPE2 overexpression significantly suppressed the viability, proliferation and induced apoptosis of PDAC cells by inhibiting survivin and increasing the activity of caspase3/7. Conclusions: For the first time, this study demonstrated that TIPE2 is an independent prognostic factor in PDAC. TIPE2 inhibited the proliferation and induced apoptosis via regulating survivin/caspase3/7 signaling pathway. These results indicated that TIPE2 is a potential biomarker for predicting the prognosis of PDAC patients and plays a pivotal role in the progression of PDAC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: To investigate the efficacy of radiomics in diagnosing patients with coronavirus disease (COVID-19) and other types of viral pneumonia with clinical symptoms and CT signs similar to those of COVID-19., Methods: Between 18 January 2020 and 20 May 2020, 110 SARS-CoV-2 positive and 108 SARS-CoV-2 negative patients were retrospectively recruited from three hospitals based on the inclusion criteria. Manual segmentation of pneumonia lesions on CT scans was performed by four radiologists. The latest version of Pyradiomics was used for feature extraction. Four classifiers (linear classifier, k-nearest neighbour, least absolute shrinkage and selection operator [LASSO], and random forest) were used to differentiate SARS-CoV-2 positive and SARS-CoV-2 negative patients. Comparison of the performance of the classifiers and radiologists was evaluated by ROC curve and Kappa score., Results: We manually segmented 16,053 CT slices, comprising 32,625 pneumonia lesions, from the CT scans of all patients. Using Pyradiomics, 120 radiomic features were extracted from each image. The key radiomic features screened by different classifiers varied and lead to significant differences in classification accuracy. The LASSO achieved the best performance (sensitivity: 72.2%, specificity: 75.1%, and AUC: 0.81) on the external validation dataset and attained excellent agreement (Kappa score: 0.89) with radiologists (average sensitivity: 75.6%, specificity: 78.2%, and AUC: 0.81). All classifiers indicated that "Original&#95;Firstorder&#95;RootMeanSquared" and "Original&#95;Firstorder&#95;Uniformity" were significant features for this task., Conclusions: We identified radiomic features that were significantly associated with the classification of COVID-19 pneumonia using multiple classifiers. The quantifiable interpretation of the differences in features between the two groups extends our understanding of CT imaging characteristics of COVID-19 pneumonia., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

BACKGROUND Enhanced Recovery After Surgery (ERAS) programs can optimize clinical outcomes and have been widely used across multiple specialties, but a personalized prediction model involving ERAS for the prognosis of gastric cancer is lacking. MATERIAL AND METHODS We retrospectively collected clinical data on 725 gastric cancer patients within ERAS who underwent curative gastric resection in the Affiliated Hospital of Qingdao University from 2007 to 2014. Kaplan-Meier method, log-rank test, and Cox proportional risk model were used to determine the independent prognostic factors of patients. The accuracy of model was evaluated by C-index, calibration curve, and Decision Curve Analysis (DCA), and the receiver operator characteristic (ROC) curve was used to compare the nomogram model with the predictive value of TNM staging system. RESULTS The 5-year overall survival (OS) of 725 patients within ERAS was 72.5%. Age at diagnosis, T stage, N stage, and postoperative complications were determined to be independent factors affecting the prognosis of patients within ERAS, and nomogram model was constructed. The C-index of the training group was 0.809 and that of the verification group was 0.804; the calibration curves and DCA of the 2 groups showed good accuracy. Through verification, we found that, compared with the TNM staging assessment method, the nomogram model was more accurate in predicting the prognosis of gastric cancer. CONCLUSIONS This study identified factors affecting the prognosis of patients with gastric cancer, and we constructed the first prognostic nomogram model in ERAS mode to facilitate postoperative personalized prognostic evaluation.

Aim: The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions., Methods and Results: In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20-0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19-1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31-2.37; P = 0.772)., Conclusion: For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting., Study Registration: http://www.clinicaltrials.com; Identifier: NCT02284750., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: The incidence of gastric cancer in East Asia is much higher than the international average. Therefore, improving the prognosis of patients and establishing effective clinical pathways are important topics for the prevention and treatment of gastric cancer. At present, the enhanced recovery after surgery (ERAS) pathway is widely used in the field of gastric surgery. Many randomized controlled trial (RCT) studies have proven that the ERAS regimen can improve the short-term clinical outcomes of patients with gastric cancer. However, a prospective study on the effect of the ERAS pathway on the prognosis of patients with gastric cancer has not yet been reported. This trial aims to confirm whether the ERAS pathway can improve the disease-free survival and overall survival of patients undergoing laparoscopic-assisted radical resection for distal gastric cancer., Methods/design: This study is a prospective, multicentre RCT. This experiment will consist of two groups - an experimental group and a control group - randomly divided in a 1:1 ratio. The perioperative period of the experimental group will be managed according to the ERAS pathway and that of the control group will be managed according to the traditional management mode. An estimated 400 patients will be enrolled. The main endpoint for comparison is the 3-year overall survival and disease-free survival between the two groups., Discussion: The results of this RCT should clarify whether the ERAS pathway is superior to traditional treatment on inflammatory indexes, short-term clinical outcome and survival for laparoscopic-assisted radical resection of distal gastric cancer. It is hoped that our data will provide evidence that the ERAS pathway improves survival in patients with gastric cancer., Trial Registration: Chinese Clinical Trial Registry, CHiCTR1900022438. Registered on 11 April 2019.

Background: With the increasing number of cancer treatments, the emergence of multidisciplinary teams (MDTs) provides patients with personalized treatment options. In recent years, artificial intelligence (AI) has developed rapidly in the medical field. There has been a gradual tendency to replace traditional diagnosis and treatment with AI. IBM Watson for Oncology (WFO) has been proven to be useful for decision-making in breast cancer and lung cancer, but to date, research on gastric cancer is limited., Objective: This study compared the concordance of WFO with MDT and investigated the impact on patient prognosis., Methods: This study retrospectively analyzed eligible patients (N=235) with gastric cancer who were evaluated by an MDT, received corresponding recommended treatment, and underwent follow-up. Thereafter, physicians inputted the information of all patients into WFO manually, and the results were compared with the treatment programs recommended by the MDT. If the MDT treatment program was classified as "recommended" or "considered" by WFO, we considered the results concordant. All patients were divided into a concordant group and a nonconcordant group according to whether the WFO and MDT treatment programs were concordant. The prognoses of the two groups were analyzed., Results: The overall concordance of WFO and the MDT was 54.5% (128/235) in this study. The subgroup analysis found that concordance was less likely in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors than in patients with HER2-negative tumors (P=.02). Age, Eastern Cooperative Oncology Group performance status, differentiation type, and clinical stage were not found to affect concordance. Among all patients, the survival time was significantly better in concordant patients than in nonconcordant patients (P<.001). Multivariate analysis revealed that concordance was an independent prognostic factor of overall survival in patients with gastric cancer (hazard ratio 0.312 [95% CI 0.187-0.521])., Conclusions: The treatment recommendations made by WFO and the MDT were mostly concordant in gastric cancer patients. If the WFO options are updated to include local treatment programs, the concordance will greatly improve. The HER2 status of patients with gastric cancer had a strong effect on the likelihood of concordance. Generally, survival was better in concordant patients than in nonconcordant patients., (©Yulong Tian, Xiaodong Liu, Zixuan Wang, Shougen Cao, Zimin Liu, Qinglian Ji, Zequn Li, Yuqi Sun, Xin Zhou, Daosheng Wang, Yanbing Zhou. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 20.02.2020.)

The characterization of high recurrence rate of HCC after TAE provides insights into persistent issues surrounding the role of adjunct therapies administered with TAE. As a regulator of the HER family, Mig-6 is down-regulated in HCC and predicts the prognosis of HCC. In this study, we found up-regulation the expression of Mig-6 enhances autophagy in HCC cells. This function of Mig-6 is related to the activation of the JNK pathway. Next AAV-9 encoding Mitogen inducible gene 6 (Mig-6) was delivered into VX2 liver transplant tumor of rabbits by using hepatic artery catheter. Wild-type AAV is not associated with any human or animal disease and has very low immunogenicity. There are over 100 different AAV serotypes that vary in the amino acid sequence of their capsid protein. We also describe a novel combination therapy coupling AAV-Mig-6 and TAE in a rabbit model resulted in a growth rate decrease in tumor compared with TAE alone. Furthermore, we show that the changes of LC3b and p62, as well as the p-JNK were consistent with changes in vitro experiments. These results suggest that Mig-6 efficiently inhibits tumor progression in vivo . Our findings suggest that Mig-6 induced autophagy inhibition may become a necessary target for adjunct therapy in TAE., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: Animal models are required to explore the mechanisms of and therapy for proximal descending thoracic aortic aneurysm (TAA). This study aimed to establish a reproducible swine model of proximal descending TAA that can further explain the occurrence and progression of proximal descending TAA., Methods: Eighteen Chinese Wuzhishan miniature pigs (30.32 ± 1.34 kg) were randomized into the elastase group (n = 12) and the control group (n = 6). The elastase group received intra-adventitial injections of elastase (5 mL, 20 mg/mL), and the control group received injections of physiologic saline solution. A 4-cm descending thoracic aortic segment proximal to the left subclavian artery was isolated. The distance between the left subclavian artery and the injection starting point of the descending thoracic aorta was 0.5 cm. Elastic protease was circumferentially injected intra-adventitially into the isolated segment of the aortic wall in the elastase group by a handmade bent syringe. The length of the elastic protease injection was 2 cm. An average of 12 injection points were distributed in this 2-cm aortic segment. Each injection point used about 0.4 mL of elastic protease. The distance between two injection points was about 1.5 cm. All animals underwent digital subtraction angiography preoperatively and 3 weeks after operation. Three weeks after TAA induction, aortas were harvested for biochemical and histologic measurements., Results: All animals in the elastase group developed TAAs. No aneurysms were observed in the control group. The distance between the left subclavian artery and the TAA was 8.00 ± 4.19 mm. Preoperative and postoperative aortic diameters of the elastase group were 15.42 ± 0.43 mm and 24.53 ± 1.41 mm, respectively (P < .0001). Preoperative and postoperative aortic diameters of the control group were 15.31 ± 0.33 mm and 15.57 ± 0.40 mm, respectively (P = .5211). The changes of aortic structure and composition included reduction of smooth muscle cells and degradation of elastic fibers. Levels of matrix metalloproteinases 2 and 9 were increased in TAA tissue., Conclusions: This study established a reproducible large animal model of proximal descending TAA. This model has the same biochemical characteristics as human aneurysms in the aspects of aortic expansion, aortic middle-level degeneration, and changes in the levels of matrix metalloproteinases and provides a platform for further study., (Copyright © 2017. Published by Elsevier Inc.)

Increasing study has suggested that microRNAs (miRNAs) are pivotal regulators in regulating hypoxia-induced injury. miR-142-5p has been suggested as a critical regulator for cellular survival. However, the role of miR-142-5p in regulating hypoxia-induced injury remains unknown. In this study, we aimed to investigate the mechanistic roles of miR-142-5p in regulating cell survival during hypoxia treatment using H9C2 cardiomyoblasts and primary cardiomyocytes. We showed that miR-142-5p expression level was significantly repressed by hypoxia treatment. Overexpression of miR-142-5p during hypoxia induced extensive cell injury and apoptosis whereas suppression of miR-142-5p significantly promoted cell viability and attenuated cell apoptosis with hypoxia treatment. Sirtuin7 (SIRT7) was identified as a direct target gene of miR-142-5p by bioinformatics analysis and dual-luciferase reporter assays. Overexpression of miR-142-5p significantly decreased SIRT7 expression, while suppression of miR-142-5p increased SIRT7 expression. Furthermore, overexpression of SIRT7 protected H9C2 cardiomyoblasts and primary cardiomyocytes against hypoxia-induced injury and apoptosis. The silencing of SIRT7 markedly abrogated the protective effect induced by miR-142-5p suppression. Taken together, these results suggest that downregulation of miR-142-5p alleviates hypoxia-induced injury through upregulation of SIRT7. Our study suggests miR-142-5p/SIRT7 as potential therapeutic targets for ischemic heart disease., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The ablation of Mig-6 has been shown to induce tumor formation in various tissues. However, the relationships between Mig-6 expression, clinical pathological factors, and prognosis have not been clarified in hepatocellular carcinoma (HCC), and the mechanism by which Mig-6 regulates the proliferation of HCC cells has not been reported. In this study, we investigated the clinical significance of the loss of Mig-6 expression in HCC and the mechanism underlying the inhibition of cell proliferation by Mig-6. The down-regulation of Mig-6 correlated significantly with large tumors, a more advanced BCLC stage, and a more advanced TNM stage, and low Mig-6 expression predicted significantly reduced survival. Low Mig-6 expression and high Cyclin D1 expression were independent predictors for survival. The overexpression of Mig-6 led to significant G 1 arrest and growth inhibition in HCC cells, possibly through the inhibition P-ERK and Cyclin D1. These results indicate that Mig-6 expression is low in HCC, which predicts a poor prognosis. Mig-6 may regulate cell proliferation and the cell cycle through the P-ERK/Cyclin D1 pathway., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a standard treatment option for the management of portal hypertension in liver cirrhosis. Since the introduction of covered stents, shunt patency has been greatly improved. However, it remains uncertain about whether covered stents could improve survival. A meta-analysis of randomized controlled trials has been performed to compare the outcomes of covered versus bare stents for TIPS., Methods: PubMed, EMBASE, and Cochrane Library databases were searched to identify the relevant randomized controlled trials. Overall survival, shunt patency, and hepatic encephalopathy were the major endpoints. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was calculated. Cochrane risk of bias tool was employed., Results: Overall, 119 papers were identified. Among them, four randomized controlled trials were eligible. Viatorr covered stents alone, Fluency covered stents alone, and Viatorr plus Fluency covered stents were employed in one, two, and one randomized controlled trials, respectively. Risk of bias was relatively low. Meta-analyses demonstrated that the covered-stents group had significantly higher probabilities of overall survival (HR = 0.67, 95% CI = 0.50-0.90, p  = 0.008) and shunt patency (HR = 0.42, 95% CI = 0.29-0.62, p  < 0.0001) than the bare-stents group. Additionally, the covered-stents group might have a lower risk of hepatic encephalopathy than the bare-stents group (HR = 0.70, 95% CI = 0.49-1.00, p  = 0.05). The heterogeneity among studies was not statistically significant in the meta-analyses., Conclusions: Compared with bare stents, covered stents for TIPS may improve the overall survival. In the era of covered stents, the indications for TIPS may be further expanded., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In the era of bare stents, transjugular intrahepatic portosystemic shunt (TIPS) is the second-line choice of therapy for the prevention of variceal rebleeding in liver cirrhosis. In the era of covered stents, the role of TIPS should be re-evaluated., Aim: The aim of the study was to compare the outcomes of covered TIPS versus the traditional first-line therapy (i.e, drug plus endoscopic therapy) for the prevention of variceal rebleeding in liver cirrhosis., Methods: All relevant randomized controlled trials were searched via the PubMed, EMBASE, and Cochrane Library databases. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) and P values were calculated for the cumulative risk and overall risk, respectively. Heterogeneity among studies was also calculated., Results: Three of 111 retrieved papers were eligible. Among them, the proportion of patients who were switched from drug plus endoscopic therapy to TIPS was 16% to 25%. The risk of bias was relatively low in all included randomized controlled trials. Meta-analyses demonstrated that the covered TIPS group had a similar overall survival (HR = 0.84, 95% CI = 0.55-1.28, P = 0.41; OR = 1.00, 95% CI = 0.59-1.69, P = 0.99), a significantly lower risk of variceal rebleeding (HR = 0.30, 95% CI = 0.18-0.48, P < 0.00001; OR = 0.24, 95% CI = 0.12-0.46, P < 0.0001), and a similar risk of hepatic encephalopathy (HR = 1.35, 95% CI = 0.72-2.53, P = 0.36; OR = 1.28, 95% CI = 0.54-3.04, P = 0.57). In most of meta-analyses, the heterogeneity among studies was not statistically significant., Conclusions: Compared with drug plus endoscopic therapy, covered TIPS had a significant benefit of preventing from variceal rebleeding, but did not increase the overall survival or risk of hepatic encephalopathy., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Rheumatic heart disease (RHD) is a serious cardiovascular disorder worldwide. Several articles have reported the effect of angiotensin I-converting enzyme gene insertion/deletion (ACE I/D) polymorphism in RHD risk. However, the results still remain inconsistent. The objective of the present study was to assess more precise estimations of the relationship between ACE I/D variant and RHD susceptibility. Relevant case-control studies published between January 2000 and 2016 were searched in the electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of the effect. A total of nine articles were retrieved, including 1333 RHD patients and 1212 healthy controls. Overall, our result did not detect a significant association between ACE I/D polymorphism and RHD risk under each genetic model (P > 0.05). Subgroup analysis by ethnicity showed no positive relationship in Asians as well (P > 0.05). With respect to the severity of RHD, our result found that the frequency differences between mitral valve lesion (MVL), combined valve lesion (CVL) and healthy controls were not significantly different. Furthermore, no significant association was found between female, male RHD patients and the controls regarding to the ACE I/D polymorphism. In conclusion, our result indicated that ACE I/D polymorphism might not be a risk factor for RHD progression based on the existing research results. Additional well-designed studies with larger samples are still needed to confirm these findings., (© 2016 The Author(s).)

Objective: To evaluate the effects of different treatments on the prognosis of patients with synchronous colorectal liver metastasis(CLM)., Methods: Clinicopathological data of 121 patients with synchronous CLM in The First Affiliated Hospital of Xinjiang Medical University between January 2010 and December 2014 were retrospectively analyzed. According to the metastatic lesions, patients were divided into simple operation group(22 patients, receiving operation only), simple chemotherapy group(43 patients, receiving chemotherapy only), and combination group(56 patients, receiving chemotherapy based on operation). The prognosis of patients in three groups was investigated. Univariate and multivariate analyses were performed through the long-rank test and Cox model to evaluate the related factors affecting prognosis., Results: The median survival time was 10(3-39) months in simple operation group, 7(3-36) months in simple chemotherapy group, and 18 (4-66) months in combination group. The differences among groups were all statistically significant (all P<0.05). Extent of lymph node metastasis, number of liver metastatic lesion, size of liver metastatic lesion, resection edge extent of liver metastatic lesion, and treatment method were independent factors of synchronous CLM(all P<0.05)., Conclusion: Combination therapy of a variety of treatment can prolong the survival of patients with synchronous CLM.