Revealing the Mechanisms of Qilongtian Capsules in the Treatment of Chronic Obstructive Pulmonary Disease Based on Integrated Network Pharmacology, Molecular Docking, and In Vivo Experiments.

The Qilongtian capsule (QLT) is a Chinese patent medicine that has been approved for the treatment of chronic obstructive pulmonary disease (COPD). However, the precise pharmacodynamic material basis and molecular mechanism have not been well illustrated. In this study, we identified the effect of QLT on COPD through a cigarette smoke extract (CSE)/lipopolysaccharide (LPS) induced COPD mice model. The absorption of blood components in QLT were identified using ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was used to predict the potential targets and therapeutic mechanisms of QLT, which were further validated using in vivo experiments and molecular docking. Pharmacodynamic studies revealed that QLT could ameliorate pulmonary function and pulmonary pathology, reduce collagen fiber accumulation, and attenuate inflammatory responses in mice with CSE/LPS induced COPD. A total of 21 components of QLT absorbed in the blood were detected. Network pharmacology analysis indicated that TNF, IL-6, EGFR, and AKT1 may be the core targets, mainly involving the MAPK signaling pathway. Besides, Sachaloside II, Ginsenoside Rh1, Ginsenoside F1, Rosiridin, and Ginsenoside Rf were the key compounds. Molecular docking results showed that the key components could spontaneously bind to EGFR and MAPK to form a relatively stable conformation. In vivo experiments revealed that QLT could suppress the activation of the EGFR/MAPK signaling pathway, thereby improving lung injury in mice with COPD. Overall, these findings provide evidence for the treatment of COPD with QLT.

Transcatheter Arterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND/AIMS: In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. RESULTS: The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. CONCLUSION: In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

The association between patella alignment and morphology and knee osteoarthritis.

OBJECTIVE: This study aims to quantitatively assess the relationship between the patella alignment and morphology and knee osteoarthritis (KOA), as well as the kinematics and kinetics of the knee, using gait analysis. METHODS: Eighty age-matched patients with KOA and control subjects were evaluated. Incident radiographic osteoarthritis (iROA) was identified using a Kellgren-Lawrence (KL) grade of ≥ 2. The modified Insall-Salvati ratio (Mod-ISR), patellar tilt angle (PTA), and patella index (PI) were utilized to evaluate the sagittal and transverse alignment of the patella and its morphology, respectively. Regression analyses were conducted to explore associations between patellar measurements and KOA, iROA, kinematics, and kinetics. RESULTS: Significant differences were observed between the control and KOA groups in terms of KL grade, patella alta, abduction angle, and reaction force to the ground (P < 0.05, respectively). Following adjustment for covariates, a significant positive association was found between patella alta and KOA (OR = 0.307, 95%CI: 0.103 to 0.918, P = 0.035). Additionally, a significant negative association was observed between PTA and abduction angle (B = -0.376, 95%CI: -0.751 to -0.002; P = 0.049). The PI exhibited a statistically significant association with log-transformed vertical ground reaction force (B = 0.002, 95%CI: 0.001 to 0.003, P = 0.002). Furthermore, adjustment for covariates did not reveal any significant correlations with other indicators (P > 0.05, respectively). CONCLUSION: This study provides further evidence that proper alignment and morphology of the patella might be associated with maintaining normal biomechanical function. In addition, intervention measures targeting relevant patellar parameters, such as Mod-ISR, PTA, and PI, may positively impact KOA treatment outcomes.

Transcatheter Arterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

Prognostic value of cardiopulmonary exercise test in patients with acute myocardial infarction after percutaneous coronary intervention.

To determine the independent risk factors of cardiopulmonary exercise test (CPET) parameters related to adverse prognostic events within 5 years in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and establish a prediction model for the occurrence of adverse events within 5 years to provide a reference for cardiac rehabilitation training. From August 2015 to December 2021, patients who underwent PCI for AMI and completed CPET within 1-2 weeks after surgery before discharge from the Department of Cardiovascular Medicine of Zhengzhou Central Hospital Affiliated to Zhengzhou University, Henan Provincial Hospital of Traditional Chinese Medicine, and Anyang District Hospital were selected as participants. Univariate and multivariate analyses were used to screen for independent risk factors associated with 5-year adverse events. Feature importance was interpreted using SHapley Additive exPlanations (SHAP), and a logistic regression model was established for prediction. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the prediction model. Calibration was assessed by the Hosmer-Lemeshow test and the calibration curve. In total, 375 patients met the inclusion criteria. Based on whether adverse events occurred during the 5-year follow-up period, the patients were divided into two groups: the event group (n = 53) and the non-event group (n = 322). Peak oxygen uptake (peakVO2), carbon dioxide ventilation equivalent slope (VE/VCO2slop), and peak end-tidal carbon dioxide partial pressure (PETCO2) were three independent risk factors for re-acute myocardial infarction (re-AMI), heart failure (HF), and even death after PCI for AMI (P < 0.05). The SHAP plots demonstrated that the significant contributors to model performance were related to peakVO2, VE/VCO2slop, and PETCO2. The risk of adverse events was significantly reduced when the peakVO2 was ≥ 20 mL/kg/min and the VE/VCO2slop was < 33. The ROC curves of the three models were drawn, including the no-event and event groups, re-AMI group, and HF group, which performed well, with AUC of 0.894, 0.760, and 0.883, respectively. The Hosmer-Lemeshow test showed that the three models were a good fit (P > 0.05). The calibration curve of the three models was close to the ideal diagonal lines. CPET parameters can predict the prognosis of adverse events within 5 years after PCI in patients with AMI and provide a theoretical basis for cardiac rehabilitation training.

Comparison of totally robotic and totally laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.

MEG3 in hematologic malignancies: from the role of disease biomarker to therapeutic target.

Maternally expressed gene 3 ( MEG3 ) is a noncoding RNA that is known as a tumor suppressor in solid cancers. Recently, a line of studies has emphasized its potential role in hematological malignancies in terms of tumorigenesis, metastasis, and drug resistance. Similar to solid cancers, MEG3 can regulate various cancer hallmarks via sponging miRNA, transcriptional, or posttranslational regulation mechanisms, but may regulate different key elements. In contrast with solid cancers, in some subtypes of leukemia, MEG3 has been found to be upregulated and oncogenic. In this review, we systematically describe the role and underlying mechanisms of MEG3 in multiple types of hematological malignancies. Particularly, we highlight the role of MEG3 in drug resistance and as a novel therapeutic target.

Pan-cancer single-cell landscape of drug-metabolizing enzyme genes.

OBJECTIVE: Varied expression of drug-metabolizing enzymes (DME) genes dictates the intensity and duration of drug response in cancer treatment. This study aimed to investigate the transcriptional profile of DMEs in tumor microenvironment (TME) at single-cell level and their impact on individual responses to anticancer therapy. METHODS: Over 1.3 million cells from 481 normal/tumor samples across 9 solid cancer types were integrated to profile changes in the expression of DME genes. A ridge regression model based on the PRISM database was constructed to predict the influence of DME gene expression on drug sensitivity. RESULTS: Distinct expression patterns of DME genes were revealed at single-cell resolution across different cancer types. Several DME genes were highly enriched in epithelial cells (e.g. GPX2, TST and CYP3A5 ) or different TME components (e.g. CYP4F3 in monocytes). Particularly, GPX2 and TST were differentially expressed in epithelial cells from tumor samples compared to those from normal samples. Utilizing the PRISM database, we found that elevated expression of GPX2, CYP3A5 and reduced expression of TST was linked to enhanced sensitivity of particular chemo-drugs (e.g. gemcitabine, daunorubicin, dasatinib, vincristine, paclitaxel and oxaliplatin). CONCLUSION: Our findings underscore the varied expression pattern of DME genes in cancer cells and TME components, highlighting their potential as biomarkers for selecting appropriate chemotherapy agents.

Corrigendum: Radiomic machine learning and external validation based on 3.0T mpMRI for prediction of intraductal carcinoma of prostate with different proportion.

[This corrects the article DOI: 10.3389/fonc.2022.934291.].

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Tumor-infiltrating mast cells stimulate ICOS+ regulatory T cells through an IL-33 and IL-2 axis to promote gastric cancer progression.

INTRODUCTION: In solid tumors, regulatory T cell (Treg) and mast cell perform different roles depending on the microenvironment. Nevertheless, mast cell and Treg-mediated interactions in gastric cancer (GC) are unclear, as are their regulation, function, and clinical significance. OBJECTIVE: The present study demonstrated the mechanism of tumor-infiltrating mast cells stimulating ICOS+ regulatory T cells via the IL-33/IL-2 axis to promote the growth of gastric cancer. METHODS: Analyses of 98 patients with GC were conducted to examine mast cell counts, ICOS+ Tregs, and the levels of IL-33 or IL-2. Isolated ICOS+ Treg and CD8+ T cell were stimulated, cultured and tested for their functional abilities in vitro and in vivo. RESULTS: GC patients exhibited a significantly more production of IL-33 in tumors. Mast cell stimulated by tumor-derived IL-33 exhibited a prolonged lifespan through IL-33 mediated inhibition of apoptosis. Moreover, mast cells stimulated by tumor-derived IL-33 secreted IL-2, which induced Treg expansion. These inducible Tregs displayed an activated immunosuppressive phenotype with positive expression for the inducible T cell co-stimulator (ICOS). In vitro, IL-2 from IL to 33-stimulated mast cells induced increased numbers of ICOS+ Tregs with increased immunosuppressive activity against proliferation and effector function of CD8+ T cell. In vivo, ICOS+ Tregs were treated with anti-IL-2 neutralizing antibody followed by co-injection with CD8+ T cells in GC mouse model, which showed an increased CD8+ T cell infiltration and effector molecules production, meanwhile tumor growth and progression were inhibited. Besides, reduction in GC patient survival was associated with tumor-derived ICOS+ Tregs. CONCLUSION: Our results highlight a crosstalk between GC-infiltrating mast cells and ICOS+ Tregs and provide a novel mechanism describing ICOS+ Treg expansion and induction by an IL-33/mast cell/IL-2 signaling axis in GC, and also provide functional evidence that the modulation of this immunosuppressive pathway can attenuate GC-mediated immune tolerance.

[Mechanism of Qilongtian Capsules in treatment of acute lung injury based on network pharmacology prediction and experimental validation].

This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1ß, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1ß, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.

Long-term oncologic and surgical outcomes of robotic and laparoscopic gastrectomy for Siewert II/III esophagogastric junction carcinoma: A propensity score-matched retrospective cohort study.

BACKGROUND: This study aimed to investigate the short-term surgical and long-term survival outcomes after robotic gastrectomy (RG) or laparoscopic gastrectomy (LG) for patients with Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). METHODS: We retrospectively analyzed 84 and 312 patients with Siewert type II/III AEG who underwent RG or LG between January 2005 and September 2016 in our center. We performed a 1:2 matched propensity score matching (PSM) analysis between the RG and LG group for clinical features to reduce confounding bias. Additionally, the long- and short-term outcomes between the RG and LG group were compared. RESULTS: The clinicopathological characteristics of 246 patients (RG group: n = 82; LG group: n = 164) were well balanced after PSM. Patients in the RG group showed less estimated blood loss, less time to first flatus, less time to first ambulation, less drainage tube removed time, and retrieved more lymph nodes than the LG group. The overall complication rate was comparable between the RG and LG groups. The 5-year overall survival (OS) was 44.4% in the RG group and 43.7% in the LG group (p = 0.898). The 5-year disease-free survival (DFS) was 43.2% in the RG group and 43.2% in the LG group (p = 0.990). The RG and LG groups exhibited a similar recurrence rate and pattern within 5 years after surgery. CONCLUSION: Robotic gastrectomy could be a feasible and safe option for patients with Siewert II/III AEG in terms of surgical and oncologic outcomes.

Robotic Gastrectomy Versus Laparoscopic Gastrectomy for Gastric Cancer: A Multicenter Cohort Study of 5402 Patients in China.

OBJECTIVE: A large-scale multicenter retrospective cohort study was conducted to compare the short- and long-term outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. SUMMARY OF BACKGROUND DATA: RG is being increasingly used worldwide, but data from large-scale multicenter studies on the short- and long-term oncologic outcomes of RG versus LG are limited. The potential benefits of RG compared with LG for gastric cancer remain controversial. METHODS: Data from eligible patients who underwent RG or LG for gastric cancer of 11 experienced surgeons from 7 centers in China between March 2010 and October 2019 were collected. The RG group was matched 1:1 with the LG group by using propensity score matching. The primary outcome was postoperative complications. RESULTS: After propensity score matching, a well-balanced cohort of 3552 patients was included for further analysis. The occurrence of overall complications (12.6% vs 15.2%, P = 0.023) was lower in the RG group than in the LG group. RG was associated with less blood loss (126.8 vs 142.5 mL, P < 0.001) and more retrieved lymph nodes in total (32.5 vs 30.7, P < 0.001) and in suprapancreatic areas (13.3 vs 11.6, P < 0.001).The long-term oncological outcomes were comparable between the two groups. CONCLUSIONS: The results of this multicenter study demonstrate that RG is a safe and effective treatment for gastric cancer when performed by experienced surgeons, although longer operation time and higher costs are still concerns about RG. This study provides evidence suggesting that RG may represent an alternative surgical treatment to LG.

Surgical and oncological outcomes of distal gastrectomy compared to total gastrectomy for middle-third gastric cancer: A systematic review and meta-analysis.

Distal gastrectomy (DG) and total gastrectomy (TG) are the most common types of radical surgery for patients with middle-third gastric cancer (MTGC). However, the indications and benefits of the two procedures still remain controversial. The present meta-analysis aimed to compare the surgical and oncological outcomes of DG and TG in the treatment of MTGC. A rigorous literature review was performed in the databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Chinese BioMedical Literature to retrieve studies published up to February 2022. The Newcastle-Ottawa Scale was used to assess the quality of included studies and a meta-analysis was performed using RevMan 5.3 software. A total of 12 retrospective studies performing comparisons of DG and TG were included in the present meta-analysis. For patients who underwent DG, a lower rate of overall post-operative complications, anastomosis leakage and intro-abdominal infection was determined. No significant difference was observed between DG and TG in the 5-year overall survival when the proximal resection margin ranged from 3 to 5 cm. Although DG was associated with a higher 5-year overall survival rate when compared to TG, there was no significant difference in the stratified analyses by TNM stage. In conclusion, the prognosis of MTGC did not depend on the extent of gastrectomy. With lower complications and acceptable oncological outcomes, DG was a safe and feasible surgical procedure for MTGC when a negative proximal margin was confirmed.

Efficacy and Safety of Minimally Invasive Surgery Versus Open Laparotomy for Interval Debulking Surgery of Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: A Systematic Review and A Meta-Analysis.

Objective: The selection of minimally invasive surgery (MIS) or open laparotomy for ovarian cancer (OC) after neoadjuvant chemotherapy still remains controversial. This study aimed to assess the efficacy and safety of MIS versus open laparotomy following neoadjuvant chemotherapy for advanced OC, so as to provide another option to select optimal surgical procedures for patients with OC. Methods: Relevant literature studies about the risks of progression or mortality between women receiving MIS and open laparotomy for interval debulking surgery (IDS) were searched in the online databases, including PubMed, Embase, and the Cochrane Library with the following keywords: "ovarian neoplasms", "minimally invasive surgical procedures", "laparotomy", and "neoadjuvant therapy". Eligible studies were screened out for further meta-analysis. Results: Six eligible literature studies, with 643 patients in the MIS group and 2,885 patients in the open laparotomy group, were included in this meta-analysis. No significant differences were detected in the overall survival (OS) of patients with OC who were treated with MIS or open laparotomy [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.59-1.23; heterogeneity: P = 0.051, I2 = 57.6%]. However, the progression-free survival (PFS) was significantly higher in patients with OC treated with MIS than those treated with laparotomy (HR = 0.73; 95% CI = 0.57 to 0.92; heterogeneity: P = 0.276, I2 = 22.4%). The completeness of debulking removal (R0 rate) in the open laparotomy group was not statistically higher compared with the control group (RR = 1.07; 95% CI = 0.93 to 1.23; heterogeneity: P = 0.098, I2 = 52.3%), and no significant differences in residual disease of ≤1 cm (R1) (RR = 1.08; 95% CI = 0.91 to 1.28; heterogeneity: P = 0.330, I2 = 12.6%) and postoperative complications were found between the two groups (RR = 0.72; 95% CI = 0.34 to 1.54; heterogeneity: P = 0.055, I2 = 60.6%). Furthermore, the length of stays in hospital was significantly shorter in patients with OC treated with MIS than those treated with open laparotomy (Standard Mean Difference (SMD) = -1.21; 95% CI = -1.78 to -0.64; heterogeneity: P < 0.001, I2 = 92.7%]. Conclusions: For IDS after NACT in patients with advanced OC, complete cytoreductive surgery with MIS is another feasible and effective choice. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298519, identifier CRD42022298519.

Radiomic Machine Learning and External Validation Based on 3.0 T mpMRI for Prediction of Intraductal Carcinoma of Prostate With Different Proportion.

Purpose: To assess the association of radiomics features based on multiparametric MRI (mpMRI) with the proportion of intraductal carcinoma of prostate (IDC-P) and validate the predictive models. Materials and Methods: We retrospectively included pre-treatment MR images of prostate cancer (PCa) with IDC components of high proportion (≥10%, hpIDC-P), low proportion (<10%, lpIDC-P), and pure acinar adenocarcinoma (PAC) from our institution for training and internal validation and cooperated cohort for external validation. Normalized images of T2WI, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) map, and dynamic contrast enhanced (DCE) sequences were used for radiomics modeling. The clinical model was built based on serum total prostate specific antigen (tPSA) and Gleason score (GS), and the integrated model was the combination of Rad-score and clinicopathological data. The discrimination ability was assessed by area under the receiver operating characteristic curve (ROC-AUC) in the internal and external validation sets and compared by DeLong test. Results: Overall, 97 patients with hpIDC-P, 87 lpIDC-P, and 78 PAC were included for training and internal validation, and 11, 16, and 19 patients for external validation. The integrated model for predicting hpIDC-P got the best ROC-AUC of 0.88 (95%CI = 0.83-0.93) in internal and 0.86 (95%CI = 0.72-1.0) in external validation, which both outperformed clinical models (AUC=0.78, 95% CI = 0.72-0.85, AUC=0.69, 95% CI = 0.5-0.85, respectively) based solely on GS, and the radiomics model (AUC=0.85, 95% CI = 0.79-0.91) was slightly inferior to the integrated model and better than the clinical model in internal dataset. The integrated model for predicting lpIDC-P outperformed both radiomics and clinical models in the internal dataset, while slightly inferior to the integrated model for predicting hpIDC-P. Conclusions: Radiomics signature improved differentiation of both hpIDC-P and lpIDC-P versus PAC when compared with the clinical model based on Gleason score, and was validated in an external cohort.

PLXDC2 enhances invadopodium formation to promote invasion and metastasis of gastric cancer cells via interacting with PTP1B.

Plexin-domain containing 2 (PLXDC2) has been reported as an oncoprotein in several human malignancies. However, its expression and roles in gastric cancer remain largely unclear. In this study, we found that PLXDC2 was highly expressed in gastric cancer tissues, and the expression levels were positively correlated with clinicopathological features, but negatively with the patients' outcome. Cox regression analysis identified PLXDC2 as an independent prognostic indicator for the patients. Knockdown of PLXDC2 markedly suppressed the in vitro invasion and in vivo metastasis of gastric cancer cells, while overexpression of PLXDC2 resulted in opposite effects. Mechanistically, PLXDC2 enhanced the level of phosphorylated Cortactin (p-Cortactin) by physically interacting with protein tyrosine phosphatase 1B (PTP1B), an important dephosphorylase, to prevent its dephosphorylating of p-Cortactin, thereby promoting the formation of invadopodia. Collectively, our results indicate that PLXDC2 contributes to the invasion and metastasis of gastric cancer by inhibiting PTP1B to facilitate the invadopodium formation, and may serve as a potential prognostic biomarker and a therapeutic target for this disease.

A comparative study on perioperative outcomes between robotic versus laparoscopic D2 total gastrectomy.

OBJECTIVE: Robotic surgery has been increasingly used worldwide owing to its advanced features. However, the significant benefits of robotic total gastrectomy (RTG) over laparoscopic total gastrectomy (LTG) have yet to be demonstrated. We conducted a prospective cohort study to compare the safety and efficacy of robotic and laparoscopic total gastrectomy (LTG) with D2 lymphadenectomy for AGC. METHODS: Between March 26, 2018 and July 30, 2021, 155 patients between 18 and 80 years of age with locally advanced gastric cancer (cT2-4a, N0/+, M0) were enrolled. The perioperative outcomes within 30 days after surgery were compared between the RTG (n = 69) and LTG (n = 73) groups on a per-protocol (PP) basis. Postoperative complications were evaluated according to the Clavien-Dindo classification. RESULTS: The overall postoperative morbidity rate was 21.74% in the RTG group and 28.77% in the LTG group with no significant difference (P = 0.44), RTG was associated with a lower incidence of pneumonia (4.35% vs. 15.07%, P = 0.047). No mortality was observed in either group. There was no significant difference in the total operative time (284.48 vs. 271.73 min, P = 0.171), but RTG was associated with a lower estimated volume of blood loss (110 vs. 150 ml, P < 0.001) and more total retrieved lymph nodes (LNs) (41.36 vs 35.1, P = 0.019), more extraperigastric LNs (14.91 vs. 12.19, P = 0.024) and more LNs in the suprapancreatic areas (14.68 vs. 11.82, P = 0.017). The laboratory data (amylase, inflammatory, Albumin and T lymphocyte levels) of the RTG group were better than those of the LTG group. CONCLUSION: According to the results of this prospective cohort study, for patients with locally advanced gastric cancer, Robotic surgery has advantages over laparoscopic surgery for radical total gastrectomy with D2 lymphadenectomy performed by well-trained doctors.

Comparison of the Postoperative Complications Between Robotic Total and Distal Gastrectomies for Gastric Cancer Using Clavien-Dindo Classification: A Propensity Score-matched Retrospective Cohort Study of 726 Patients.

BACKGROUND: This study was designed to compare the postoperative complications after Robotic total gastrectomy (RTG) and robotic distal gastrectomy (RDG) and to systematically evaluate the safety and feasibility of RTG for the treatment of gastric cancer (GC). METHODS: Patients with GC who underwent RTG or RDG for curative intent between March 2010 and August 2019 were analyzed. We used propensity score matching (PSM) to reduce selection bias. The morbidity and mortality within 30 days after surgery between the RTG and the RDG groups were compared. RESULTS: According to Clavien-Dindo (C-D) classification, the morbidity and mortality of the RTG group were comparable to those of the RDG group. Subgroup analyses showed no significant difference between the RTG and RDG groups in all stratified parameters (all P > .05). Multivariate analysis revealed that age ≥70 years (P = .002) and surgeons' experience ≤25 cases (P = .013) were independent risk factors for overall complication. Surgeons' experience ≤25 cases (P = .010) was identified as an independent risk factor for severe complication. CONCLUSION: RTG is a safe and feasible surgical procedure for the treatment of GC with acceptable morbidity and mortality. More complications were observed for RTG, indicating that RTG is more invasive than RDG.