Percutaneous Ventricular Restoration Prevents Left Ventricular Remodeling Post Myocardial Infarction: One-Year Evaluation of the Heartech First-in-man Study.

BACKGROUND: This is first-in-man investigation of an implantable Heartech left ventricular partitioning device (LVPD) therapy for chronic heart failure (HF) after a myocardial infarction. METHODS AND RESULTS: Initially, 16 patients were chosen from 3 cardiac centers within China. All patients were treated with percutaneous ventricular restoration involving the Heartech LVPD implantation. Major adverse cardiovascular and cerebrovascular events were documented. Functional status, echocardiograph evaluation, European five-dimensional health scale, 6-minute walk test before the procedure and at postoperative follow-ups were recorded. We demonstrated successful implantation and device function with a success rate of 93.75%. One patient suffered a fatal myocardial infarction within the 12 ± 1 month follow-up. However, other patients did not report any major adverse cardiovascular and cerebrovascular events at their 12 ± 1 month follow-ups. After the operation, the average left ventricular end-systolic volume index decreased dramatically (66.00 mL/m2, interquartile range [IQR] 63.00-89.00 mL/m2 vs 48.00 mL/m2, IQR 32.25-68.25 mL/m2, P = .001), along with the left ventricular end-diastolic volume index (105.00 mL/m2, IQR 90.00-130.00 mL/m2 vs 76.50 mL/m2, IQR 57.75-120.25 mL/m2, P = .002). The left ventricular ejection fraction (35.00%, IQR 27.00-38.00% vs 42.50%, IQR 34.75-50.25%, P = .003), 6-minute walk test (383.13 ± 108.70 m vs 491.17 ± 118.44 m, P = .01), and European five-dimensional health scale (65.93 ± 11.25 vs 82.50 ± 5.44, P < .001), in turn, improved significantly. CONCLUSIONS: In our study, the Heartech LVPD was demonstrated as both safe and effective in reducing LV volume, enhancing LV function after implantation. These results remain constant at least till the 12 month follow-up. (Trial Registration: NCT02938637.).

Effect of complete reduction of hernia sac and transection of hernia sac during laparoscopic indirect inguinal hernia repair on seroma.

INTRODUCTION: This study investigated the effect of complete reduction and transection of the hernia sac during laparoscopic indirect inguinal hernia repair on seroma. METHODS: Retrospective analysis was performed on 1763 cases undergoing laparoscopic indirect inguinal hernia repair in three centers from January 2017 to September 2019, among them, 311 patients with transection of hernia sac and 1452 patients with reduction of hernia sac, the data of the two groups were tested by t-test. Logistic univariate analysis was performed on 233 cases of postoperative seroma, and variables p < 0.05 in univariate analysis were included for multivariate analysis. Then, the transection group and the reduction group were matched with 1:1 propensity score matching, and the caliper value was set at 0.05. Finally, 274 patients matched in each group were analyzed by univariate analysis again to evaluate whether the transection of hernia sac had an impact on postoperative seroma. RESULTS: The results of univariate analysis of 233 patients with postoperative seroma showed that: ASA-3 p = 0.031, classification-L3 p < 0.001, surgery-TEP p < 0.001, transect group p = 0.005. The results of multivariate analysis show that: ASA-3 p < 0.001, classification-L3 p < 0.001, surgery-TEP p < 0.001, transect group p = 0.020. The results of univariate analysis after propensity score matching showed that transection of the hernia sac is significant for postoperative seroma (p < 0.001). CONCLUSION: Transection of the hernia sac during laparoscopic indirect inguinal hernia repair can significantly lead to postoperative seroma.

Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion.

BACKGROUND: The role of circular RNAs (circRNAs) in the occurrence and development of gastric cancer (GC) has recently attracted increasing interest. The following study investigates the role of a newly discovered hsa_circ_0008434, which has been confirmed to be highly expressed in GC tissues, in regulating GC biological behaviour. METHODS: High-throughput RNA sequencing was used to identify differentially expressed genes between normal gastric tissues and GC tissues; actinomycin D and RNase R assays were used to determine the stability and loop structure of hsa_circ_0008434; and the miRanda database was used to predict the target genes of hsa_circ_0008434. The role of hsa_circ_0008434 in cell proliferation, migration, and invasion was examined using CCK-8, wound healing, Transwell and colony formation assays. The regulatory relationships among hsa_circ_0008434, microRNA-6838 (miR-6838), and ubiquitin-specific peptidase 9X (USP9X) were determined by dual-luciferase activity assays. The expression of hsa_circ_0008434 and miR-6838 was measured by qPCR; the expression of USP9X was detected by immunohistochemistry and Western blotting. The effects of hsa_circ_0008434 on in vivo tumour growth were assessed in xenograft models. RESULTS: We found that hsa_circ_0008434 was one of the most upregulated circRNAs in GC tissue versus normal tissue. Further in vitro testing indicated that by acting as a miRNA sponge for miR-6838-5p, hsa_circ_0008434 promotes the expression of USP9X and further increases the proliferation, migration, and invasion of GC cells. In addition, animal studies indicated that hsa_circ_0008434 could promote tumour growth in vivo. CONCLUSIONS: Hsa_circ_0008434 may promote GC proliferation, invasion and migration by regulating the expression of miR-6838 and USP9X.

Subxiphoid top-down endoscopic totally preperitoneal approach (eTPA) for midline ventral hernia repair.

PURPOSE: Midline abdominal wall hernia repair is among the most common surgical interventions performed worldwide. However, the optimal surgical technique remains controversial. To overcome the disadvantages of both open and transabdominal procedures, we developed a totally endoscopic preperitoneal approach (eTPA) with placement of a large mesh. METHODS: From December 2019 to October 2020, 20 consecutive patients with small to medium-sized midline ventral hernias underwent repair using a completely preperitoneal subxiphoid top-down approach. The preperitoneal space was entered directly below the xiphoid, and careful endoscopic development of the plane between the peritoneum and posterior sheath of the rectus fascia was then performed behind the linea alba. The hernia sac and its contents were identified and reduced. The hernia defect was closed with sutures, and a mesh with an adequate high defect: mesh ratio was placed in the newly created preperitoneal space. RESULTS: Twenty patients were enrolled in this study, including 14 with primary umbilical hernias, 4 with primary epigastric hernias, and 2 with recurrent umbilical hernias. 15 patients suffered from a mild concomitant diastasis recti. All operations were successfully completed without conversion to open repair. The mean operative time was 105.3 min (range, 60-220 min). Postoperative pain was mild, and the mean visual analog scale score for pain was 1.8 on the first postoperative day. The average postoperative hospital stay was 1.8 days (range, 1-4 days). One patient developed a minor postoperative seroma, but it had no adverse impact on the final outcome. No patients developed recurrence during the 3- to 10-month follow-up period. CONCLUSIONS: The subxiphoid top-down totally endoscopic preperitoneal approach (eTPA) technique is feasible and effective. It may become a valuable alternative for the treatment of primary small- (defect size < 2 cm) and medium-sized (2-4 cm) midline ventral hernias, particularly in presence of a concomitant diastasis recti.

Population-based analysis on predictors for lymph node metastasis in T1 colon cancer.

BACKGROUND: In this study, we aimed to identify independent predictive factors for lymph node metastasis (LNM) in T1 colon cancer. METHODS: Data of 8056 eligible patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2004-2012. We performed logistic regression analysis to identify predictive factors for LNM. Both unadjusted and adjusted Cox regression analyses were used to determine the association between LNM and patient survival. Finally, we used competing risks analysis and the cumulative incidence function (CIF) to further confirm the prognostic role of LNM in cancer-specific survival (CSS). RESULTS: The overall risk of LNM in patients with T1 colon cancer was 12.0% (N = 967). Adjusted logistic regression models revealed that mucinous carcinoma [odds ratio (OR) = 2.26, P < 0.001], moderately differentiated (OR 1.74, P < 0.001), poorly differentiated (OR 5.16, P < 0.001), and undifferentiated carcinoma (OR 3.01, P = 0.003); older age (OR 0.66, P < 0.001 for age 65-79 years, OR 0.44, P < 0.001 for age over 80 years); and carcinoma located in the ascending colon (OR 0.77, P = 0.018) and sigmoid colon (OR 1.24, P = 0.014) were independent predictive factors for LNM. Adjusted Cox regression analysis showed that positive lymph node involvement was significantly associated with CSS [hazard ratio (HR) = 3.02, P < 0.001], which was further robustly confirmed using a competing risks model and the CIF. CONCLUSIONS: This population-based study showed that mucinous carcinoma, tumor grade, age, and primary tumor location were independent predictive factors for LNM in T1 colon cancer. The risk of LNM should be carefully evaluated in patients with T1 colon cancer, before clinical management.

First-in-man study of Heartech® percutaneous left ventricular partitioning device for treatment of heart failure postmyocardial infarction.

OBJECTIVE: This first-in-man (FIM) study aimed to determine the safety and efficacy of the Heartech® left ventricular partitioning device (LVPD) in patients with chronic heart failure (HF) postmyocardial infarction. METHODS: Sixteen patients were enrolled from three cardiac intervention centers in China. All patients underwent percutaneous ventricular restoration (PVR) procedures with implantation of the Heartech® LVPD. Safety and immediate success rates were recorded. Major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause mortality, myocardial infarction, stroke, emergent or selective surgery or interventional therapy, renal failure requiring hemodialysis, and major bleeding were recorded. Efficacy features included functional status, echocardiographic characteristics, life quality characteristics including peak oxygen consumption of cardiopulmonary exercise testing (CPET), European five-dimensional health scale (EQ-5D), 6-min walk test (6MWT) at baseline and during follow-up (NCT02938637). RESULTS: The device success rate was 93.75% (15 successes in 16 patients) with 100% safety. During follow-up of 36 ± 4.5 days, no MACCEs were found. The left ventricular end-systolic volume index decreased significantly (LVESVi, 72.47 ± 22.77 mL/m2 vs. 50.13 ± 13.36 mL/m2 , p < .001) as did left ventricular end diastolic volume index (LVEDVi, 106.27 ± 28.01 mL/m2 vs. 83.20 ± 16.87 mL/m2 , p = .001). Left ventricular ejection fraction (LVEF, 32.47 ± 6.98% vs. 40.41 ± 6.15, p < .001), 6MWT (383.13 ± 108.70 vs. 453.47 ± 88.24, p < 0.001) and EQ-5D (65.93 ± 11.25 vs. 78.67 ± 8.35, p < .001) improved significantly. CONCLUSIONS: Heartech® LVPD appeared to be safe and effective for treatment of HF postmyocardial infarction.

Autophagy Facilitates Metadherin-Induced Chemotherapy Resistance Through the AMPK/ATG5 Pathway in Gastric Cancer.

BACKGROUND/AIMS: Metadherin (MTDH) is overexpressed in some malignancies and enhances drug resistance; however, its role in gastric cancer (GC) and the underlying mechanisms remain largely unexplored. Here, we explore the mechanism by which MTDH induces drug resistance in GC. METHODS: We analysed the level of MTDH in GC and adjacent normal gastric mucosal tissues by real-time quantitative PCR (q-PCR). We also analysed the level of autophagy by western blot analysis, confocal microscopy, and transmission electron microscopy after MTDH knockdown and overexpression, and examined fluorouracil (5-FU) resistance by Cell Counting Kit-8 at the same time. Finally, GC patient-derived xenograft tumours were used to demonstrate 5-FU resistance. An AMPK pathway inhibitor was applied to determine the molecular mechanisms of autophagy. RESULTS: MTDH expression was significantly increased in the GC specimens compared with that in the adjacent normal gastric mucosal tissues. Further study showed a positive correlation between the expression level of MTDH and 5-FU resistance. MTDH overexpression in MKN45 cells increased the levels of P-glycoprotein (P-gp) and promoted 5-FU resistance, while inhibition of MTDH showed the opposite result. The simultaneous inhibition of autophagy and overexpression of MTDH decreased the levels of P-gp and inhibited 5-FU resistance. Moreover, MTDH induced AMPK phosphorylation, regulated ATG5 expression, and finally influenced autophagy, suggesting that MTDH may activate autophagy via the AMPK/ATG5 signalling pathway. Our findings reveal a unique mechanism by which MTDH promotes GC chemoresistance and show that MTDH is a potential target for improved chemotherapeutic sensitivity and GC patient survival. CONCLUSIONS: MTDH-stimulated cancer resistance to 5-FU may be mediated through autophagy activated by the AMPK/ATG5 pathway in GC.

Evidence of Apis cerana Sacbrood virus Infection in Apis mellifera.

Sacbrood virus(SBV) is one of the most destructive viruses in the Asian honeybee Apis cerana but is much less destructive in Apis mellifera In previous studies, SBV isolates infecting A. cerana(AcSBV) and SBV isolates infecting A. mellifera(AmSBV) were identified as different serotypes, suggesting a species barrier in SBV infection. In order to investigate this species isolation, we examined the presence of SBV infection in 318A. mellifera colonies and 64A. cerana colonies, and we identified the genotypes of SBV isolates. We also performed artificial infection experiments under both laboratory and field conditions. The results showed that 38A. mellifera colonies and 37A. cerana colonies were positive for SBV infection. Phylogenetic analysis based on RNA-dependent RNA polymerase (RdRp) gene sequences indicated that A. cerana isolates and most A. mellifera isolates formed two distinct clades but two strains isolated fromA. mellifera were clustered with theA. cerana isolates. In the artificial-infection experiments, AcSBV negative-strand RNA could be detected in both adult bees and larvae ofA. mellifera, although there were no obvious signs of the disease, demonstrating the replication of AcSBV inA. mellifera Our results suggest that AcSBV is able to infectA. melliferacolonies with low prevalence (0.63% in this study) and pathogenicity. This work will help explain the different susceptibilities ofA. cerana and A. melliferato sacbrood disease and is potentially useful for guiding beekeeping practices.

Bone marrow-derived mesenchymal stem cells increase drug resistance in CD133-expressing gastric cancer cells by regulating the PI3K/AKT pathway.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited to primary tumours to compose the tumour microenvironment. In various cancers, CD133-positive cells have been shown to possess cancer stem cell properties that confer chemoresistance. This study aimed to investigate the role of BM-MSCs in the anti-tumour drug resistance of CD133-expressing gastric cancer cells and explore the underlying mechanisms that governing this role. We found that CD133+ gastric cancer cells displayed more resistance to chemotherapeutics than CD133- cells. In addition, BM-MSCs increased the anti-apoptotic abilities and chemoresistance of CD133+ cells via upregulation of Bcl-2 and downregulation of BAX. Mechanistically, BM-MSCs triggered activation of the PI3K/Akt signalling cascade in CD133+ cells. Blocking the PI3K/Akt pathway inhibited the promotion of chemoresistance. Furthermore, BM-MSCs enhanced the drug resistance of CD133-overexpressing cells in vitro and in vivo, but not that of CD133-knockdown cells, which demonstrated the contribution of CD133 to this process. In conclusion, we demonstrated that BM-MSCs increased the anti-apoptotic abilities and drug resistance of CD133-expressing cells via activation of the PI3K/Akt pathway following Bcl-2 upregulation and BAX downregulation, in which CD133 played a significant role. Targeting this route may help improve the efficacy of chemotherapy in gastric cancer.

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function.

BACKGROUND: Cell therapy, such as hepatocyte transplantation (HTx), is promising for the treatment of metabolic liver diseases or as a bridge to orthotopic liver transplantation in patients with fulminant liver failure. However, one of the limitations of this therapy is the shortage of donors. The present study aims to investigate whether the two-layer method (TLM) of cold preservation with oxygenation improves the viability and activity of hepatocytes from rat donation after cardiac death (DCD) donors compared with results obtained with the University of Wisconsin (UW) solution. Moreover, we evaluated the hepatocyte function after culture or transplantation into the spleen. MATERIALS AND METHODS: We used male Sprague-Dawley rats for this study. The DCD model was induced by phrenotomy after injecting heparin. We assigned rats based on warm ischemia times of 15 and 30 min to groups S and L, respectively. Each group (n = 5) was then subdivided as follows: (1) group S: not preserved (S/N), preserved by TLM for 3 h (S/TLM3) and 12 h (S/TLM12), and in the UW solution for 3 h (S/UW3) and 12 h (S/UW12), and (2) group L: not preserved (L/N), preserved by TLM for 3 h (L/TLM3) and 12 h (L/TLM12), and in the UW solution for 3 h (L/UW3) and 12 h (L/UW12). The cell viability and function of isolated DCD hepatocytes were analyzed for culture or HTx into the spleen. RESULTS: The viability and ATP levels of DCD hepatocytes significantly improved after TLM compared with the values after preservation in cold UW solution in group S/N (p < 0.059). The levels of albumin production and urea synthesis by hepatocytes after culture were significantly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12 (p < 0.05), respectively. Further, serum albumin levels after HTx were also markedly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12. The morphological features revealed that cultured and transplanted hepatocytes remained clearly viable and maintained an expression for specific hepatic function, such as the production of albumin and glycogen. CONCLUSION: This novel method of oxygenated cold preservation of DCD livers can expand the hepatocyte donor pool for HTx and establish a wider application of this developing technique.

Case Report of snare-assisted coaxiality optimized technique during valve deployment in patient with pure aortic regurgitation.

In high-risk patients with pure native aortic regurgitation (PNAR), transcatheter aortic valve replacement (TAVR) remains an off-label intervention. Due to anatomical variations in the aortic root and technical challenges unique to PNAR, the transfemoral approach (TF-TAVR) requires continued accumulation of experience and technological refinement. In this context, we successfully and safely performed a snare-assisted TF-TAVR procedure for a patient with PNAR, characterized by significant aortic angulation. We introduced an innovative technique termed "snare-assisted coaxiality optimized technique" (SACOT) during valve deployment. SACOT played a crucial role in optimizing valve positioning, enhancing coaxiality, and achieving the ideal implantation depth for PNAR. Post-procedure assessments demonstrated stability and the absence of paravalvular regurgitation (PVR).

Internal Ring Defect Closure Technique in Laparoscopic Mesh Hernioplasty for Indirect Inguinal Hernia.

PURPOSE: The best way to reduce seroma formation after laparoscopic indirect hernia repair is debated. We noticed that internal ring defect closure in laparoscopic mesh hernioplasty could provide promising outcomes with an effect on diminishing seroma formation. We introduce our closure technique and report our experience. METHODS: This prospective study was conducted from May 2019 to May 2021. Patients with European Hernia Society classification L3 indirect or scrotal hernia were recruited and underwent laparoscopic transabdominal patch plasty (TAPP). Hernia defect closure was performed before mesh deployment. The primary outcomes were seroma formation, postoperative pain, and hernia recurrence. Perioperative data and postoperative complications were also recorded. RESULTS: Consecutive 77 patients with 89 indirect hernias (including 51 scrotal hernias) were recruited in two regional tertiary hospitals. All operations were successful without open conversion. The mean size of the hernia defect was 3.7 ± 0.5 cm (range, 2.5-5.0 cm). The mean operative time for each hernia repair (peritoneum to peritoneum) was 48.3 ± 10.8 min (range, 33-72 min), and the mean time required for internal ring closure was 6.7 ± 2.2 min (range, 4-10 min). Intraoperative bleeding was minimal. The mean visual analog scale pain score at rest on the first postoperative day was 2.2 (range, 1-4). The average postoperative length of hospital stay was 18 h (range, 14-46 h). During a mean follow-up period of 9.4 months (range, 3-23 months), no hernia recurrence or chronic pain were noted. Seroma formation was detected on six sides of unilateral hernias (6.7%) on postoperative day 7, with a mean volume of 45.8 ml (range, 24-80 ml). All seromas were mild and resolved spontaneously within 3 months, with no need for evacuation or other treatment and without major impact on the final outcome. CONCLUSIONS: Defect closure in laparoscopic mesh hernioplasty for large indirect hernias is safe and feasible and can significantly reduce postoperative seroma formation and relative complications. This approach is recommended in large indirect or scrotal hernia repair.

Quantitative Data-Independent Acquisition Mass Spectrometry Proteomics and Weighted Correlation Network Analysis of Plasma Samples for the Discovery of Chronic Kidney Disease-Specific Atherosclerosis Risk Factors.

Chronic kidney disease (CKD) accelerates atherosclerosis. The mechanism of CKD-related atherosclerosis is complex, and CKD-specific risk factors may contribute to this process in addition to traditional risk factors such as hypertension, diabetes, and hypercholesterolemia. In the present study, to discover CKD-specific atherosclerosis risk factors, a total of 62 patients with different stages of kidney function were enrolled. All patients underwent coronary angiographies and the severity of coronary atherosclerosis was defined by the SYNTAX score. Patients were divided into different groups according to their kidney function levels and coronary atherosclerosis severity. Data-independent acquisition mass spectrometry was used to identify differentially expressed proteins (DEPs) in the plasma samples, and weighted correlation network analysis (WGCNA) was employed to identify significant protein modules and hub proteins related to CKD-specific atherosclerosis. The results showed that 10 DEPs associated with atherosclerosis were found in the comparative groups with modest and severe CKD. Through WGCNA, 1768 proteins were identified and 8 protein modules were established. Enrichment analyses of protein modules revealed functional clusters mainly associated with inflammation and the complement and coagulation cascade as atherosclerosis developed under CKD conditions. The results may help to better understand the mechanisms of CKD-related atherosclerosis and guide future research on developing treatments for CKD-related atherosclerosis.

Study on lymph node metastasis correlated to lymphangiogenesis, lymphatic vessel invasion, and lymph node micrometastasis in gastric cancer.

BACKGROUND: This study aimed to evaluate the clinical significance of lymphangiogenesis, lymph vessel invasion (LVI), and lymph node (LN) micrometastasis (LNMM) in patients with gastric cancer. METHODS: The influences of the expression levels of LVI, lymph vessel density (LVD) by D2-40 immunohistochemical (IHC) staining (n=68), LNMM (including CK 20 and CK pan immunostainings, n=51) on the clinicopathologic profiles and the prognosis were analyzed. RESULTS: The higher positive rate of LVI-IHC was related to deeper invasion (P=0.044), later TNM stage (P=0.003), and more extensive LN metastasis (LNM, P=0.000). The level of LVD was significantly associated with venous invasion (P=0.037), later TNM stage (P=0.020), positive LVI-HE (P=0.040), positive LVI-IHC status (P=0.001), and severer LNM (P=0.001). Better prognosis in LVI negative group than LVI positive group has been identified. The survival rate of the group with LVD≥15/field was significantly lower than that in the group with LVD≤14/field (P=0.032). Invasion depth, N stage, LNM, blood vessel invasion, or LVI was respectively an independent prognostic factor to 3-y survival rate. The incidence of patients with LNM and metastasized LNs increased respectively from 74.5% (38/51) by HE staining to 88.2% (45/51) by CK immunostaining and from 32.0% (253/791) to 41.5% (328/791) (P=0.001). The increment of LNMM was correlated to larger tumor diameter (P=0.001), deeper invasion (P=0.018), LNM (P=0.001) and later TNM stage (P=0.012), positive LVI (P=0.04). Meanwhile, the evaluation on LNMM revealed the migration of LN stage (N(0)→N(1) in seven patients, N(1)→N(2) in six patients, and N(2)→N(3) in one patient), and TNM stage (I(b)→II in four patients, II→III(a) in 4 patients, III(a)→III(b) in 3 patients, and III(b)→IV in one patient). Survival analysis demonstrated that better prognosis in patients without LNM and/or LNMM. CONCLUSION: Our immunohistochemical analyses using antibodies of D2-40 and CK, including both CK 20 and CK pan, detected a higher incidence of LVIs and LNMs in gastric cancer specimens. This study shows close correlations among lymphangiogenesis related factors, such as LVI, LVD, and LNMM, and patients' prognosis after surgery. Therefore, immunohistochemical evaluations of these factors could be used for the accurate determination of tumor aggressiveness.

[Experimental study on liver injury induced by intraperitoneal hypertension under mechanical ventilation].

OBJECTIVE: To investigate the effects of mechanical ventilation on liver cytological and enzymatic indexes in abdominal compartment syndrome (ACS) by establishing a porcine model of abdominal hypertension. METHODS: Six healthy adult pigs were selected. After general anesthesia, they were intubated and given ventilator assisted breathing. The breathing mode was volume controlled ventilation (VCV), tidal volume (VT) 10 mL/kg, respiratory rate (RR) 16 time/min, fraction of inspiration oxygen (FiO2) 0.40, positive end expiratory pressure (PEEP) 5 cmH2O (1 cmH2O = 0.098 kPa). Intraperitoneal pressure was simulated by injecting normal saline into the pressurized water sac, and the pressure was measured once every 50 mL of normal saline. 5 mL of blood was collected from ear vein every 1 hour before and 4 hours after operation for liver enzyme examination. 4 hours after operation, the animals were sacrificed and the liver was collected to observe pathological changes under light microscope. RESULTS: Six pigs were successfully modeled. The RR and heart rate (HR) of the animals remained stable. No one suffered from barotrauma or death during the experiment. There was a positive correlation between abdominal pressure and abdominal volume increase (r2 = 0.839 6, P = 0.003 7). There were no significant differences in the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and cholinesterase (ChE) preoperative and 1, 2, 3, 4 hours after operation. As time went on, aspartate aminotransferase (AST) increased first and then decreased, and increased significantly at 1 hour after operation (U/L: 46.84±8.57 vs. 23.35±5.14, P < 0.05), and decreased significantly 2, 3, 4 hours after operation (U/L: 16.33±3.58, 14.54±3.35, 15.44±3.21 vs. 23.35±5.14, all P < 0.05). The level of γ-glutamyltranspeptidase (GGT) increased and then decreased, but there was significant difference only at 1 hour after operation, compared with baseline (U/L: 101.20±17.79 vs. 51.34±9.13, P < 0.05). Under the light microscope, there were dilation and congestion of interlobular vein, dilation of interlobular bile duct, hyperplasia of small bile duct, hyperplasia of connective tissue in portal area, infiltration of a large number of acute and chronic inflammatory cells, swelling of hepatocytes, light staining of cytoplasm, balloon like transformation of some cells, and punctate necrosis. CONCLUSIONS: Abdominal hypertension under mechanical ventilation can cause obvious enzyme changes and cytological damage of liver.

Prognostic and Predictive Value of m6A "Eraser" Related Gene Signature in Gastric Cancer.

BACKGROUND: N6-methyladenosine (m6A) RNA modification plays a critical role in gastric cancer (GC). However, the relationship between the m6A "eraser", FTO, and ALKBH5, and the prognosis of GC still remains unclear. This study aimed to evaluate the effect of FTO and ALKBH5 on the prognosis of patients and their potential roles in GC. MATERIALS AND METHODS: A total of 738 GC samples with clinical information obtained from two independent datasets were included and divided into training set and testing set. Differential expression analysis of the m6A "eraser" related genes was performed. The LASSO Cox regression model was constructed to analyze the m6A "eraser" related risk genes. The univariate and multivariate Cox regression model were employed to identify the independent prognostic factors. Kaplan-Meier method was used for survival analysis. A nomogram model was then carried out to predict the prognosis of GC patients. Additionally, GO and KEGG analyses were conducted to identify the potential role of the m6A "eraser" related genes in GC. The relative proportion of 22 different genotypes in immune infiltrating cells was calculated by CIBERSORT algorithm. RESULTS: In total, nine m6A "eraser" related risk genes and risk scores were obtained and calculated. Patients in high-risk group demonstrated significantly worse prognosis than those in low-risk group. Age, stage, and risk score were considered as independent prognostic factors. The nomogram model constructed accurately predicted the 3-year and 5-year overall survival (OS) of patients. Furthermore, m6A "eraser" might play a functional role in GC. The expression of m6A "eraser" leads to changes in tumor immune microenvironment. CONCLUSIONS: FTO and ALKBH5 showed association with the prognosis of GC. The m6A "eraser" related genes, which is considered as a reliable prognostic and predictive tool, assists in predicting the OS in GC patients.

Histone Methyltransferase SETD1A Induces Epithelial-Mesenchymal Transition to Promote Invasion and Metastasis Through Epigenetic Reprogramming of Snail in Gastric Cancer.

Aberrant epigenetic modification induces oncogene expression and promotes cancer development. The histone lysine methyltransferase SETD1A, which specifically methylates histone 3 lysine 4 (H3K4), is involved in tumor growth and metastasis, and its ectopic expression has been detected in aggressive malignancies. Our previous study reported that SETD1A promotes gastric cancer (GC) proliferation and tumorigenesis. However, the function and molecular mechanisms of SETD1A in GC metastasis remain to be elucidated. In this study, we found that overexpression of SETD1A promoted GC migration and invasion, whereas knockdown of SETD1A suppressed GC migration and invasion in vitro. Moreover, knockdown of SETD1A suppressed GC epithelial-mesenchymal transition (EMT) by increasing the expression of epithelial marker E-cadherin and decreasing the expression of mesenchymal markers, including N-cadherin, Fibronectin, Vimentin, and α-smooth muscle actin (α-SMA). Mechanistically, knockdown of SETD1A reduced the EMT key transcriptional factor snail expression. SETD1A was recruited to the promoter of snail, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on the snail promoter. Furthermore, SETD1A could be a coactivator of snail to induce EMT gene expression. Rescue of snail restored SETD1A knockdown-induced GC migration and invasion inhibition. In addition, knockdown of SETD1A suppressed GC metastasis in vivo. In summary, our data revealed that SETD1A mediated the EMT process and induced metastasis through epigenetic reprogramming of snail.

Involvement of Th17 and Th1 effector responses in patients with Hepatitis B.

BACKGROUND: Local production of cytokines within the liver may play a pivotal role in the regulation of pathophysiological processes during inflammation. CD4+ T cells are regarded as the most prolific cytokine producers. The purpose of this study was to quantify intrahepatic expression of Th1, Th2, Th17, and Treg-associated cytokines or transcription factors in patients with acute hepatitis B or chronic hepatitis B (CHB) and to analyze their relative roles in the promotion and regulation of hepatitis B virus (HBV)-associated liver diseases. METHODS: Distribution and expression of IL-17, IFN-gamma, IL-4, Foxp3, and other cytokines in liver tissues were detected by immunohistochemistry and real-time quantitative PCR. Patients with hepatitis B were compared with patients with chronic hepatitis C, primary biliary cirrhosis, alcoholic liver cirrhosis, and healthy controls. RESULTS: The frequencies of intrahepatic IL-17 and IFN-gamma-producing cells in patients with HBV-associated liver dysfunction were much higher than that of IL-4 and Foxp3-positive cells. The level of the IL-17/IFN-gamma-positive cell ratio of patients with Child-Pugh class C (1.57+/-0.09) was much higher than that of patients with Child-Pugh class B (1.00+/-.02) or A (0.93+/-0.05). There are more IL-17-producing cells than IFN-gamma-producing cells accumulating in the liver with severe hepatocellular damage. Liver IL-17-producing cell infiltration was positively associated with the grade of liver inflammation in CHB and positively correlated to intrahepatic IL-8 expression (r=0.801, p<0.01) or neutrophil infiltration (r=0.917, p<0.01). CONCLUSIONS: These results suggest that the balance of effector CD4+ Th responses (Th17 and Th1 responses) and regulatory response is an important element of immune regulation. Inappropriate, excessive, and non-specific Th17 and Th1 effector responses may be involved in the pathogenesis of HBV-associated liver inflammation and hepatocellular damage. Th17 response, especially, may exacerbate the inflammatory processes leading to liver failure. IL-17-mediating liver neutrophil recruitment via induction of IL-8 may be one potential mechanism of liver injury in patients with hepatitis B. An improved understanding of the factors that influence the differentiation and function of these cell types in vivo will be of great importance to the future development of immune therapies in HBV-associated liver disease.

Giant right atrial diverticulum in an adult.

We describe a 32-year-old man with chest pain and a giant right atrial diverticulum who underwent surgical resection. Examination of resected atrial tissue showed extreme wall thinning, central aneurysmal formation, and focal endocardial fibrosis consistent with idiopathic dilatation of the right atrium. It is unclear what the best treatment of right atrial diverticulum are, nor are the risks of thromboembolism, arrhythmia, and rupture of the diverticulum clearly defined, either for patients as a whole or for symptomatic or asymptomatic subgroups. However, to reduce the risk of sudden death we recommend surgical resection of large diverticula.

Over expression of METRN predicts poor clinical prognosis in colorectal cancer.

BACKGROUND: The role of meteorin (METRN) in colorectal cancer has not been reported previously. We aimed to explore the relationship between METRN and colorectal cancer (CRC) prognosis. METHODS: Data were retrieved from the Gene Expression Omnibus database. Gene expression values were log2 transformed and normalized by quantile normalization. Missing values were imputed with the R impute package. Differentially expressed genes were analyzed using the R limma package. METRN expression was compared between normal and CRC tissues and among different stages and subtypes of CRC. We assessed the relationship between METRN and KRAS/BRAF mutations in CRC. Five-year overall (OS), disease-free (DFS), and disease-specific survival (DSS) rates were determined by Kaplan-Meier analysis and analyzed by log-rank test. RESULTS: METRN was expressed at a higher level in CRC (p = .0011) than in normal tissues, especially in advanced stages (p = .0343). METRN expression levels were higher in the MSI (dMMR) subtype (p < .001) and usually with BRAF mutations (p < .0001). METRN overexpression was associated with poor prognosis and low OS (p = .01014), DFS (p = .0146), and DSS (p < .0001) rates. CONCLUSION: METRN overexpression is a predictive factor for poor prognosis in patients with CRC.