Trocar puncture with modified sump drainage for duodenal stump fistula after radical gastrectomy for gastric cancer: A retrospective controlled study.

Duodenal stump fistula (DSF) is a serious complication of radical gastrectomy for gastric cancer. Herein, we illustrated an innovative choice for treating duodenal stump fistulas by placing a modified sump drainage through trocar puncture into the DSF-related abscess (DSF-abscess) cavity. We retrospectively analyzed 974 consecutive patients who underwent gastrectomy for gastric cancer between 2011 and 2021. Of these patients, 34 who developed postoperative duodenal stump fistulas postoperatively were enrolled into our study, and their clinical data were retrospectively assessed. From January 2011 to December 2017, 15 patients received conventional treatments (percutaneous catheter drainage, PCD group) known as the traditional percutaneous method, and 19 patients from January 2018 to December 2021 received new treatments (Troca's SD group) consisting of conventional therapies and placement of a modified sump drainage through trocar puncture into DSF-abscess cavity. The demographics, clinical characteristics and treatment outcomes were compared between two groups. Compared with the PCD group, the rates of postoperative complications, duodenostomy creation, subsequent surgery, fistula healing rates of the DSF, and length of postoperative hospital stay were significantly decreased in the Troca SD group. However, there was no significant difference in the abscess recurrence rate and mortality rates. Trocar puncture with a modified sump drainage is an safe, effective, and technically feasible treatment for duodenal stump fistula after radical gastrectomy for gastric cancer. This novel technique should be further investigated using large-scale RCT research.

Risk-factor model for postpartum hemorrhage after cesarean delivery: a retrospective study based on 3498 patients.

This study aimed to investigate the risk factors of patients with postpartum hemorrhage (PPH) after cesarean delivery (CD) and to develop a risk-factor model for PPH after CD. Patients were selected from seven affiliated medical institutions of Chongqing Medical University from January 1st, 2015, to January 1st, 2020. Continuous and categorical variables were obtained from the hospital's electronic medical record systems. Independent risk factors were identified by univariate analysis, least absolute shrinkage and selection operator and logistic regression. Furthermore, logistic, extreme gradient boosting, random forest, classification and regression trees, as well as an artificial neural network, were used to build the risk-factor model. A total of 701 PPH cases after CD and 2797 cases of CD without PPH met the inclusion criteria. Univariate analysis screened 28 differential indices. Multi-variable analysis screened 10 risk factors, including placenta previa, gestational age, prothrombin time, thrombin time, fibrinogen, anemia before delivery, placenta accreta, uterine atony, placental abruption and pregnancy with uterine fibroids. Areas under the curve by random forest for the training and test sets were 0.957 and 0.893, respectively. The F1 scores in the random forest training and test sets were 0.708. In conclusion, the risk factors for PPH after CD were identified, and a relatively stable risk-factor model was built.

[Screening biomarkers for hypertensive heart disease: Analysis based on data from 7 medical institutions].

Objective: To screen the influencing factors of hypertensive heart disease (HHD), establish the predictive model of HHD, and provide early warning for the occurrence of HHD. Methods: Select the patients diagnosed as hypertensive heart disease or hypertensionfrom January 1, 2016 to December 31, 2019, in the medical data science academy of a medical school. Influencing factors were screened through single factor and multi-factor analysis, and R software was used to construct the logistics model, random forest (RF) model and extreme gradient boosting (XGBoost) model. Results: Univariate analysis screened 60 difference indicators, and multifactor analysis screened 18 difference indicators (P<0.05). The area under the curve (AUC) of Logistics model, RF model and XGBoost model are 0.979, 0.983 and 0.990, respectively. Conclusion: The results of the three HHD prediction models established in this paper are stable, and the XGBoost prediction model has a good diagnostic effect on the occurrence of HHD.

Lentivirus-Mediated Overexpression of SIVA-1 Reverses Cisplatin Resistance in Gastric Cancer in vitro.

SIVA-1 plays a critical role in the induction of apoptosis in a number of different cell lines and participates in the mechanism of cisplatin (DDP)-mediated antitumor effects. However, the involvement of SIVA-1 in cisplatin resistance in gastric carcinoma has not been revealed. To explore the effect of SIVA-1 on DDP resistance, a recombinant pGV358-GFP-SIVA-1 lentiviral vector was constructed and transfected into human cisplatin-resistant MKN45/DDP gastric cancer cells. Subsequently, stable SIVA-1 overexpression was established in MKN45/DDP cells, which resulted in increased DDP sensitivity in MKN45/DDP cells in vitro. Flow cytometry demonstrated that SIVA-1 overexpression increased the percentage of apoptotic cells compared to that in the control. The colony formation assay clearly revealed that cell growth and proliferation were significantly suppressed following SIVA-1 overexpression. In addition, overexpression of SIVA-1 inhibited the migratory and invasive potential of MKN45/DDP cells in vitro. Western blot analysis indicated that SIVA-1 increased the expression levels of p53, p73, and p14ARF, whereas it reduced Bcl-2, MDM2, and Bcl-xL expression. In short, SIVA-1 upregulated the protein expression of p53, p73, and p14ARF and decreased that of Bcl-2, MDM2, and Bcl-xL in vitro and subsequently reversed cisplatin resistance in gastric cancer cells, suggesting that SIVA-1 serves as a valuable potential target for attenuating chemotherapy resistance.

Surgical-related risk factors associated with anastomotic leakage after resection for rectal cancer: a meta-analysis.

OBJECTIVES: Anastomotic leakage (AL) after anterior resection always leads to longer hospital stays, decreased quality of life and even increased mortality. Despite extensive research, no consensus on the world well-concerned surgical-related risk factors exists. We therefore conducted a meta-analysis of the available published literature to identify the effects of surgical-related risk factors for AL after anterior resection for rectal cancer, hoping to provide more information and improved guidance for clinical workers managing patients with rectal cancer who are at a high risk for AL. METHODS: In this study, the relevant articles were systematically searched from EMBASE, MEDLINE, PubMed, WangFang (Database of Chinese Ministry of Science & Technology), Chinese National Knowledge Infrastructure Database and China Biological Medicine Database. The pooled odds ratio (OR) with 95% confidence interval (95% CI) were calculated. Meta-analysis was performed using of RevMan 5.3 software. RESULTS: A total of 26 studies met the inclusion criteria and comprised 34238 cases. Analysis of these 26 studies showed that no defunctioning stoma was highly correlated with AL (pooled OR = 1.28, 95%CI: 1.05-1.57, P = 0.01, random effect), and intraoperative blood transfusion was significantly associated with AL (pooled OR = 1.64, 95%CI: 1.34-2.02, P = 0.02, random effect). However, the AL was not associated with type of anastomosis, type of surgery, technique of anastomosis, level of inferior mesenteric artery ligation, operation time and splenic flexure mobilization. CONCLUSIONS: Depend on this meta-analysis, no defunctioning stoma and intraoperative blood transfusion are the major surgical-related risk factors for AL after resection for rectal cancer. Because of the inherent limitations of the research, future prospective randomized controlled trials will need to confirm this conclusion.

Plasma disturbance of phospholipid metabolism in major depressive disorder by integration of proteomics and metabolomics.

INTRODUCTION: Major depressive disorder (MDD) is a highly prevalent mental disorder affecting millions of people worldwide. However, a clear causative etiology of MDD remains unknown. In this study, we aimed to identify critical protein alterations in plasma from patients with MDD and integrate our proteomics and previous metabolomics data to reveal significantly perturbed pathways in MDD. An isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomics approach was conducted to compare plasma protein expression between patients with depression and healthy controls (CON). METHODS: For integrative analysis, Ingenuity Pathway Analysis software was used to analyze proteomics and metabolomics data and identify potential relationships among the differential proteins and metabolites. RESULTS: A total of 74 proteins were significantly changed in patients with depression compared with those in healthy CON. Bioinformatics analysis of differential proteins revealed significant alterations in lipid transport and metabolic function, including apolipoproteins (APOE, APOC4 and APOA5), and the serine protease inhibitor. According to canonical pathway analysis, the top five statistically significant pathways were related to lipid transport, inflammation and immunity. CONCLUSION: Causal network analysis by integrating differential proteins and metabolites suggested that the disturbance of phospholipid metabolism might promote the inflammation in the central nervous system.

COX-2/PGE2 Axis Regulates HIF2α Activity to Promote Hepatocellular Carcinoma Hypoxic Response and Reduce the Sensitivity of Sorafenib Treatment.

Purpose: Hypoxia-inducible factor-2α (HIF2α) is regarded as a preferential target for individualized hepatocellular carcinoma (HCC) treatment and sorafenib resistance. Our study aimed to identify the regulatory mechanisms of HIF2α activity under hypoxic conditions. We sought to determine whether the COX-2/PGE2 axis is involved in the regulatory mechanisms of HIF2α activity and of sorafenib resistance in hypoxic HCC cells.Experimental Design: The cell viability, migration, and invasion abilities were measured to analyze the effects of HIF2α on hypoxic HCC cells. Both in vitro and in vivo HCC models were used to determine whether the COX-2/PGE2 axis is a driver of HIF2α level and activity, which then reduces the sensitivity of sorafenib treatment in hypoxic HCC cells.Results: Under hypoxic conditions, the COX-2/PGE2 axis effectively stabilized HIF2α and increased its level and activity via decreasing von Hippel-Lindau protein (p-VHL) level, and also enhanced HIF2α activity by promoting HIF2α nuclear translocation via MAPK pathway. The activation of HIF2α then led to the enhanced activation of VEGF, cyclin D1, and TGFα/EGFR pathway to mediate HCC development and reduce the sensitivity of sorafenib. More importantly, COX-2-specific inhibitors synergistically enhanced the antitumor activity of sorafenib treatment.Conclusions: Our data obtained demonstrate that the COX/PGE2 axis acts as a regulator of HIF2α expression and activity to promote HCC development and reduce sorafenib sensitivity by constitutively activating the TGFα/EGFR pathway. This study highlights the potential of COX-2-specific inhibitors for HCC treatment and particularly for enhancing the response to sorafenib treatment. Clin Cancer Res; 24(13); 3204-16. ©2018 AACR.

Sex differences in gut microbiota in patients with major depressive disorder.

OBJECTIVE: Our previous studies found that disturbances in gut microbiota might have a causative role in the onset of major depressive disorder (MDD). The aim of this study was to investigate whether there were sex differences in gut microbiota in patients with MDD. PATIENTS AND METHODS: First-episode drug-naïve MDD patients and healthy controls were included. 16S rRNA gene sequences extracted from the fecal samples of the included subjects were analyzed. Principal-coordinate analysis and partial least squares-discriminant analysis were used to assess whether there were sex-specific gut microbiota. A random forest algorithm was used to identify the differential operational taxonomic units. Linear discriminant-analysis effect size was further used to identify the dominant sex-specific phylotypes responsible for the differences between MDD patients and healthy controls. RESULTS: In total, 57 and 74 differential operational taxonomic units responsible for separating female and male MDD patients from their healthy counterparts were identified. Compared with their healthy counterparts, increased Actinobacteria and decreased Bacteroidetes levels were found in female and male MDD patients, respectively. The most differentially abundant bacterial taxa in female and male MDD patients belonged to phyla Actinobacteria and Bacteroidia, respectively. Meanwhile, female and male MDD patients had different dominant phylotypes. CONCLUSION: These results demonstrated that there were sex differences in gut microbiota in patients with MDD. The suitability of Actinobacteria and Bacteroidia as the sex-specific biomarkers for diagnosing MDD should be further explored.

MicroRNA­34a attenuates the proliferation, invasion and metastasis of gastric cancer cells via downregulation of MET.

Proliferation, invasion and metastasis are key features of gastric cancer, contributing to high mortality rates in patients with gastric cancer worldwide. As a direct target of p53, the functions of microRNA (miR)­34a are important, but controversial, in the progression of gastric cancer. In the present study, the clinical importance of miR­34a in GC specimens (n=40) were investigated and were confirmed in an independent cohort from The Cancer Genome Atlas (TCGA; n=352). The prognostic value of miR­34a was analyzed using a Kaplan­Meier survival curve in the TCGA cohort, in combination with complete follow­up data (n=157). The level of miR­34a was detected in the human gastric cancer cell line and normal gastric epithelial cell line. The effect of miR­34a on proliferation and invasion were evaluated using Cell Counting Kit 8, colony formation and cell invasion assays. The molecular basis of miR­34a was determined by bioinformatics prediction. The correlation between miR­34a and MET was assessed using reverse transcription­quantitative polymerase chain reaction and western blot analyses. The results indicated that miR­34a was downregulated in the gastric cancer tissues, compared with the normal gastric tissues (P<0.01). miR­34a was negatively correlated with the depth of invasion and lymph node metastasis of gastric cancer (P<0.01). In the TCGA cohort, the levels of miR­34a were lower in T3 and T4 tumor stages, compared with the level in the T1 stage, and low levels of miR­34a predicted significantly longer survival rates in patients with GC (P<0.05). miR­34a also attenuated the proliferation ability, and inhibited the colony formation and cell invasion abilities of the cells (P<0.01). A negative correlation was observed between miR­34a and MET in gastric cancer (P<0.01; r=­0.9526), and >60% of cases exhibited consistent expression of miR­34a and MET in gastric cancer (P<0.01). In conclusion, miR­34a was associated with the clinicopathological features of gastric cancer and was a valuable predictor of patient prognosis. miR­34a acted as a tumor suppressor to inhibit gastric cancer proliferation and invasion via the downregulation of MET.

Selective tropism of liver stem cells to hepatocellular carcinoma in vivo.

AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC. METHODS: WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein (EGFP). An animal model of HCC in Wistar rats was established by implanting HCC cells (CBRH7919) combined with an immunosuppressive drug. EGFP labeled liver stem cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stem cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stem cells within the tumor tissue were observed and analyzed. RESULTS: Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue. CONCLUSION: Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.

[Tropism of adult liver stem cells toward hepatocellular carcinoma cells in vitro].

OBJECTIVE: To explore the biological behavior of adult liver stem cells in a co-cultured system of them with hepatocellular carcinoma (HCC) cells without direct contact between the two kinds of cells. METHODS: WB-F344, a kind of rat adult liver stem cell, and rat embryonic fibroblasts (REF) from a primary culture were engineered to express enhanced green fluorescent protein (EGFP) by recombinant adenoviral-mediated methods. Two kinds of cells marked with EGFP were established, namely WB-EGFP and REF-EGFP. After the HCC cells grew to 40%-60% confluence in the culture dish with a 10-mm cell-free area, a similar number of WB-EGFP and REF-EGFP were placed in the blank areas respectively. Then, we constantly studied the movement behavior of WB-EGFP in the co-culture system with HCC cells. RESULTS: The results showed that WB-EGFP cells migrated to the area of HCC cells slowly. Their appearance was found not only when WB-EGFP cells were seeded into the cell-free area at the center of the dish, but also when seeded into the blank area at the extreme edge of the plate. This trait was not observed in the co-cultured system of REF-EGFP and HCC cells, and most REF-EGFP were still localized in their initial area after 72 hours of incubation. CONCLUSIONS: The results mean that adult liver stem cells have a biological behavior of selective tropism toward HCC cells in vitro, and suggest a possibility of using migratory liver stem cells as a delivery vehicle for gene therapy for HCC.