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.

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.

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.

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.).

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.

[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.

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.

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.

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 interacts with HIF1α to enhance glycolysis and promote cancer progression in gastric cancer.

Growing tumors alter their metabolic profiles to support the increased cell proliferation. SETD1A, a histone lysine methyltransferase which specifically methylates H3K4, plays important roles in both normal cell and cancer cell functions. However, the function of SETD1A in gastric cancer (GC) progression and its role in GC metabolic reprogramming are still largely unknown. In the current study, we discovered that the expression of SETD1A was higher in GC tumor specimens compared to surrounding nontumor tissues. Upregulation of SETD1A increased GC cell proliferation, whereas downregulation of SETD1A inhibited GC cell proliferation. Furthermore, knockdown of SETD1A reduced glucose uptake and production of lactate and suppressed glycolysis by decreasing the expression of glycolytic genes, including GLUT1, HK2, PFK2, PKM2, LDHA, and MCT4. Mechanistically, SETD1A interacted with HIF1α to strengthen its transactivation, indicating that SETD1A promotes glycolysis through coactivation of HIF1α. SETD1A and HIF1α were recruited to the promoter of HK2 and PFK2, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on HK2 and PFK2 promoter and reduced HIF1α recruitment necessary to promote transcription of glycolytic genes. Inhibition of HIF1α decelerated SETD1A-enhanced GC cell growth. In additional, there was a linear correlation between SETD1A and several key glycolytic genes in human GC specimens obtained from TCGA dataset. Thus, our results demonstrated that SETD1A interacted with HIF1α to promote glycolysis and accelerate GC progression, implicating that SETD1A may be a potential molecular target for GC treatment.

Reduction of Hip2 suppresses gastric cancer cell proliferation, migration, invasion and tumorigenesis.

BACKGROUND: Hip2, a ubiquitin-conjugating enzyme, has been shown to modulate the stability of cyclin B1, a cell cycle regulator. However, the function of Hip2 in gastric cancer (GC) remains largely elusive. METHODS: The expression of Hip2 in GC cell lines was analyzed by RT-qPCR, Western Blotting and Immunohistochemical Staining. shRNA was utilized to knock down the expression of Hip2. Cell growth, cell cycle, migration, invasion and tumorigenesis were performed by CCK-8, BrdU staining, flow cytometry, wound healing, transwell migration and invasion, and xenograft assay, respectively. RESULTS: Hip2 was highly expressed in GC cell lines and patients. High level of Hip2 indicated poor prognosis. Knockdown of Hip2 suppressed cell growth, lead to G2/M phase arrest, and reduced cell migration and invasion in vitro. Furthermore, downregulation of Hip2 inhibited tumorigenesis in vivo. CONCLUSIONS: Elevated expression of HIP2 in GC patients suggested poor prognosis. Reduction of Hip2 suppressed GC progression, indicating that Hip2 may be a potential target for the management of GC.

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.

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.

[Experimental study on the pathological changes in lung of abdominal compartment syndrome model rabbits].

OBJECTIVE: To investigate the secondary pathological changes in lung of abdominal compartment syndrome (ACS). METHODS: Twenty-five healthy adult clean New Zealand rabbits were randomly divided into control group (n = 5) and experimental group (n = 20) according to the random number table method. The experimental group was subdivided into two subgroups according to the observation time: 24 hours and 48 hours, with 10 rabbits in each subgroup. A high pressure liquid animal model of abdominal cavity was reproduced by water bag superposition pressurization. In the control group, the pressurized water bag did not inject liquid, and intra-abdominal pressure (IAP) was maintained at 0; while in the experimental group, pressurized water infusion was performed, and IAP was maintained at 25 mmHg (1 mmHg = 0.133 kPa). The rabbits in the control group were sacrificed at 48 hours, those in the experimental group were sacrificed at 24 hours and 48 hours respectively, and the lungs were harvested completely. The pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining. RESULTS: In the control group, the activity of the rabbits was decreased, the food intake was decreased, and all the 5 animals survived; in the experimental group, the activity was decreased significantly, little food intake or not, the urine output was decreased significantly, and 1 rabbit died at 22, 27 and 37 hours respectively, and 17 survived. Light microscopy showed that there were terminal bronchioles and a large number of alveoli in the lung tissue of the control group, and small vessels dilated in the interstitium. In the experimental group, alveolar epithelial hyperplasia, alveolar septum of different sizes, alveolar fusion, alveolar septal bleeding, interstitial heart failure cells with phagocytosis of hemosiderin, bronchiolectasis, a large number of inflammatory cell infiltration near the bronchi, thrombosis in the blood vessels were found at 24 hours. A large number of erythrocyte and cellulose-like exudates were seen in the lumen of terminal bronchioles, alveolar dilatation and fusion were aggravated, and old hemorrhage in the lumen of the alveoli was observed, hemosiderosis containing hemosiderin was observed at 48 hours. CONCLUSIONS: ACS could cause severe lung injury and aggravate as time goes on.

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.

Interaction between CD133 and PI3K-p85 promotes chemoresistance in gastric cancer cells.

Chemoresistance in gastric cancer is the leading cause of tumor recurrence and poses a substantial therapeutic challenge. The stem cell biomarker CD133 has been implicated in drug resistance of tumor-initiating cells in a number of cancers including gastric cancer. Therefore, we investigated the molecular mechanism of CD133-associated multidrug resistance in gastric cancer cells. Using CD133 overexpressing and knockdown gastric cancer cell lines, we demonstrated that loss of CD133 significantly increased the growth inhibition of chemotherapeutic agents; whereas, overexpression significantly reduced growth inhibition. Furthermore, CD133 knockdown significantly reduced the enzymatic activity of phosphatidylinositol-3 kinase (PI3K) and the expression of P-glycoprotein (P-gp), B-cell lymphoma 2 (BCL2), and phosphorylated-protein kinase B (p-AKT), but elevated the expression of BCL2 associated X (BAX). Conversely, overexpression of CD133 significantly increased PI3K enzymatic activity, expression of P-gp, BCL2, and p-AKT, and decreased BAX expression. The PI3K/AKT inhibitor LY294002 mirrored the effects of loss of CD133; whereas, the PI3K/AKT activator epidermal growth factor reproduced the effects of CD133 overexpression. To identify the interaction between CD133 and PI3K, we used site-directed mutagenesis to mutate individual tyrosine residues of CD133. We found that binding between CD133 and p85, the regulatory subunit of PI3K, was significantly reduced when tyrosine 852 was mutated. In summary, we have demonstrated that CD133 activates the PI3K/AKT signal transduction pathway through direct interaction with PI3K-p85, resulting in multidrug resistance of gastric cancer cells. These results suggest that the interaction between CD133 and PI3K-p85 may offer a novel therapeutic target in multidrug resistant gastric cancer.

Large Wolffian adnexal tumor of the ovary: A case report and literature review.

Female Wolffian adnexal tumor (WAT) is a rare neoplasm arising from the remnants of the mesonephric duct and <100 cases have been reported globally. The present case report describes a 73-year-old female patient with WAT in the left ovary which, to the best of our knowledge, is the largest benign WAT tumor to be reported. In addition, the present case report reviewed previous studies on the clinical characteristics and therapy for WAT and the surgery methods for female WAT of ovary were summarized. WATs are typically benign; however, a number factors may increase the risk of malignancy.

Multicystic peritoneal mesothelioma: A short review.

Multicystic peritoneal mesothelioma (MCPM) is a rare neoplasm, predominantly affecting female patients during their reproductive years. The lesion is usually distributed diffusely in the abdomen and pelvis, but the peritoneum of the pelvic organs is the most common site. MCPM is composed of fluid-filled translucent cysts, connected by varying amounts of fibrous tissue, and lined by a layer of mesothelial cells. Because of the rarity of this disease, the pathogenesis and natural history of MCPM remain poorly understood and continuously debated. Some authors consider it to be a reactive process for its association with prior surgery or abdominal inflammation. But its high rate of local-regional recurrence, as well as its malignant potential, suggests a neoplastic etiology. Preoperative diagnosis is often very difficult. Imaging methods, such as ultrasound, computed tomography, and magnetic resonance imaging, are of little value for an accurate diagnosis of MCPM. The definitive diagnosis relies on histologic examination of target lesions combined with immunohistochemical stains. There is no consensus on the clinical management of MCPM, although surgical removal remains the first-line treatment of choice. But no standards have been reached concerning which surgical options-traditional debulking surgery or more aggressive one-should be chosen. Alternative therapeutic approaches include hand-off treatment, hormonal supplementation, laser vaporization, and sclerotherapy, and they all come with uncertain results. Moreover, the lesions show no response to adjuvant chemotherapy and radiotherapy. This article aimed to focus on those controversial problems in pathogenesis, natural history, diagnosis, and treatment strategies to help medical workers to better understand this rare disease.