Spontaneous isolated gastric intramural hematoma combined with spontaneous superior mesenteric artery intermural hematoma: a rare case.

BACKGROUND: Gastric intramural hematoma is a rare disease. Here we report a case of spontaneous isolated gastric intramural hematoma combined with spontaneous superior mesenteric artery intermural hematoma. CASE PRESENTATION: A 75-years-old man was admitted to our department with complaints of abdominal pain. He underwent a whole abdominal computed tomography (CT) scan in the emergency department, which showed extensive thickening of the gastric wall in the gastric body and sinus region with enlarged surrounding lymph nodes, localized thickening of the intestinal wall in the transverse colon, localized indistinct demarcation between the stomach and transverse colon, and a small amount of fluid accumulation in the abdominal cavity. Immediately afterwards, he was admitted to our department, and then we arranged a computed tomography with intravenously administered contrast agent showed a spontaneous isolated gastric intramural hematoma combined with spontaneous superior mesenteric artery intermural hematoma. Therefore, we treated him with anticoagulation and conservative observation. During his stay in the hospital, he was given low-molecular heparin by subcutaneous injection for anticoagulation therapy, and after discharge, he was given oral anticoagulation therapy with rivaroxaban. At the follow-up of more than 4 months, most of the intramural hematoma was absorbed and became significantly smaller, and the intermural hematoma of the superior mesenteric artery was basically absorbed, which also confirmed that the intramural mass was an intramural hematoma. CONCLUSION: A gastric intramural hematoma should be considered, when an intra-abdominal mass was found to be attached to the gastric wall. Proper recognition of gastric intramural hematoma can reduce the misdiagnosis rate of confusion with gastric cancer.

Key Roles of p53 Signaling Pathway-Related Factors GADD45B and SERPINE1 in the Occurrence and Development of Gastric Cancer.

p53 can function as an independent and unfavorable prognosis biomarker in cancer patients. We tried to identify the key factors of the p53 signaling pathway involved in gastric cancer (GC) occurrence and development based on the genotype-tissue expression (GTEx) and the Cancer Genome Atlas (TCGA) screening. We downloaded gene expression data and clinical data of GC included in the GTEx and TCGA databases, followed by differential analysis. Then, the key factors in the p53 signaling pathway were identified, followed by an analysis of the correlation between key factors and the prognosis of GC patients. Human GC cell lines were selected for in vitro cell experiments to verify the effects of key prognostic factors on the proliferation, migration, invasion, and apoptosis of GC cells. We found 4,944 significantly differentially expressed genes (DEGs), of which 2,465 were upregulated and 2,479 downregulated in GC. Then, 27 DEGs were found to be involved in the p53 signaling pathway. GADD45B and SERPINE1 genes were prognostic high-risk genes. The regression coefficients of GADD45B and SERPINE1 were positive. GADD45B was poorly expressed, while SERPINE1 was highly expressed in GC tissues, highlighting their prognostic role in GC. The in vitro cell experiments confirmed that overexpression of GADD45B or silencing of SERPINE1 could inhibit the proliferation, migration, and invasion and augment the apoptosis of GC cells. Collectively, the p53 signaling pathway-related factors GADD45B and SERPINE1 may be key genes that participate in the development of GC.

Hpgd affects the progression of hypoxic pulmonary hypertension by regulating vascular remodeling.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a syndrome of abnormally elevated pulmonary artery pressure, and it is mostly caused by vasoconstriction and remodeling of the pulmonary artery induced by long-term chronic hypoxia. There is a high incidence of HPH, a short survival time of the patients, but currently no effective treatments. METHODS: In this study, HPH-related single cell sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data were downloaded from the public database of Gene Expression Omnibus (GEO) for bioinformatics analysis in order to find out genes with important regulatory roles in the development of HPH. 523 key genes were identified through cell subpopulation identification and trajectory analysis of the downloaded scRNA-seq data, and 41 key genes were identified through weighted correlation network analysis (WGCNA) of the bulk RNA-seq data. Three key genes: Hpgd, Npr3 and Fbln2 were identified by taking intersection of the key genes obtained above, and Hpgd was finally selected for subsequent verification. The human pulmonary artery endothelial cells (hPAECs) were treated with hypoxia for different periods of time, and it was found that the expression of Hpgd decreased in hypoxia-treated hPAECs in a time-dependent manner. In order to further confirm whether Hpgd affects the occurrence and development of HPH, Hpgd was overexpressed in hPAECs. RESULTS: Hpgd was confirmed to regulate the proliferation activity, apoptosis level, adhesiveness and angiogenesis ability of hypoxia-treated hPAECs through multiple experiments. CONCLUSIONS: Downregulation of Hpgd can improve the proliferation activity, reduce apoptosis, and enhance adhesion and angiogenesis in endothelial cells (ECs), thus promoting the occurrence and development of HPH.

TIMP-2 as a predictive biomarker in 5-Fu-resistant colorectal cancer.

PURPOSE: This study aims to evaluate the value of tissue inhibitors of MMPs-2 (TIMP-2) to indicate 5-Fluorouracil (5-Fu) resistance status in colorectal cancer. METHODS: The 5-Fu resistance of colorectal cancer cell lines was detected using Cell-Counting Kit-8 (CCK-8) and calculated using IC50. Enzyme-linked immunosorbent assay (ELISA) and real time-quantitative polymerase chain reaction (RT-qPCR) were used to detect TIMP-2 expression level in the culture supernatant and serum. Twenty-two colorectal cancer patients' TIMP-2 levels and clinical characteristics were analyzed before and after chemotherapy. Additionally, the patient-derived xenograft (PDX) model of 5-Fu resistance was used to evaluate the feasibility of TIMP-2 as a predictive biomarker of 5-Fu resistance. RESULTS: Our experimental results display that TIMP-2 expression is elevated in colorectal cancer drug-resistant cell lines, and its expression level is closely related to 5-Fu resistance. Moreover, TIMP-2 in colorectal cancer patient serum undergoing 5-Fu-based chemotherapy could indicate their drug resistance status, and its efficacy is higher than CEA and CA19-9. Finally, PDX model animal experiments reveal that TIMP-2 can detect 5-Fu resistance in colorectal cancer earlier than tumor volume. CONCLUSION: TIMP-2 is a good indicator of 5-Fu resistance in colorectal cancer. Monitoring the serum TIMP-2 level can help the clinician identify 5-Fu resistance in colorectal cancer patients earlier during chemotherapy.

Helicobacter pylori is associated with weakened pulmonary function and reduced incidence of allergic conditions in patients with chronic cough.

The present study aimed to investigate the potential association between Helicobacter pylori (a H. pylori) positive state and chronic cough. A clinical observational study with systematic analysis was performed, including 278 patients with complaints of chronic cough and 148 healthy controls. a H. pylori positive state was present in 61.2% of the patients in the chronic cough group and 68.9% in the chronic refractory cough group, as opposed to 43.9% in the control group. There was a significant improvement in 65.5% of the patients with chronic refractory cough following successful a H. pylori eradication therapy. In addition, patients with chronic cough exposed to a H. pylori exhibited decreased pulmonary function with a decrease in forced expiratory volume in 1 sec by 84 ml, a decrease in the forced vital capacity by 53 ml and a decrease in maximal vital capacity by 46 ml. The difference was even more obvious in the chronic refractory cough group. The allergy status differed significantly according to age between a H. pylori-positive and -negative cases in the cough variant asthma and allergic cough groups. Among patients aged <40 years, a H. pylori-positive cases had a lower prevalence of atopy and lower total serum immunoglobin E levels compared with a H. pylori-negative cases. However, there was no significant association between a H. pylori status and C-reactive protein levels, erythrocyte sedimentation rate or eosinophil count in the peripheral blood. In conclusion, the present study demonstrated that a H. pylori infection may be a factor associated with chronic cough and it may be associated with a decline in pulmonary function and reduced incidence of allergic conditions. Thus, a H. pylori may represent a target for the treatment of chronic cough.

Long-Chain Non-Coding RNA Metastasis-Related Lung Adenocarcinoma Transcript 1 (MALAT1) Promotes the Proliferation and Migration of Human Pulmonary Artery Smooth Muscle Cells (hPASMCs) by Regulating the MicroRNA-503 (miR-503)/Toll-Like Receptor 4 (TLR4) Signal Axis.

BACKGROUND To study the role of the long-chain noncoding RNA (lncRNA) metastasis-related lung adenocarcinoma transcript 1 (MALAT1), microRNA-503 (miR-503), Toll-like receptor 4 (TLR4) signal axis in the pathogenesis of pulmonary arterial hypertension (PAH). MATERIAL AND METHODS Total RNA was extracted from the plasma of 45 PAH patients and 45 healthy subjects, and the expression of lncRNA MALAT1 and miR-503 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of lncRNA MALAT1 and miR-503 on Toll-like receptor 4 (TLR4) and the proliferation, migration, and apoptosis of human pulmonary artery smooth muscle cells (hPASMCs) were tested following in vitro transfection of hPASMCs. RESULTS lncRNA MALAT1 was highly expressed in the plasma of PAH patients and in hypoxia-induced hPASMCs. Silencing lncRNA MALAT1 inhibited the proliferation and migration of hPASMC cells while promoting their apoptosis. MiR-503 is underexpressed in plasma and hPASMCs of patients with PAH. TLR4 was a target gene of miR-503 and was highly expressed in peripheral blood mononuclear cells (PBMCs) of PAH patients. lncRNA MALAT1 was a "molecular sponge" of miR-503, regulating the expression of TLR4 and the proliferation, migration, and apoptosis of hPASMCs through miR-503. CONCLUSIONS lncRNA MALAT1 promotes the proliferation and migration of hPASMCs and inhibits their apoptosis by inhibiting the miR-503/TLR4 signal axis.

Development of NKG2D-based chimeric antigen receptor-T cells for gastric cancer treatment.

Gastric cancer is the third leading cause of cancer-related mortalities worldwide and mostly incurable. It remains an urgent need for novel strategies in the management of patients with advanced gastric cancer. Chimeric antigen receptor (CAR) T therapy has shown unprecedented clinical success in hematological malignancies and potential utility is going on various solid tumors like gastric cancer. In this study, a broad expression of NKG2D ligands was observed in gastric cancer cell lines, making them suitable targets for gastric cancer therapy. T cells were engineered with an NKG2D-based second-generation CAR and the resulting NKG2D-CAR-T cells showed significantly increased cytolytic activity against gastric cancer compared to untransduced T cells. In vivo, these cells can significantly suppressed the growth of established gastric cancer xenografts. Besides, cisplatin was shown to upregulate NKG2D ligand expression in gastric cancer cells and enhance the susceptibility to NKG2D-CAR-T-cell-mediated cytotoxicity. In conclusion, NKG2D-based CAR-T cells have potent in vivo and in vitro anti-tumor activities against gastric cancer and could be a new paradigm for patients with gastric cancer, either used alone or combined with chemotherapy.

Short- and long-term outcomes after conversion of laparoscopic total gastrectomy for gastric cancer: a single-center study.

PURPOSE: Conversion of laparoscopic surgery for colorectal cancer has been fully studied. However, no study has investigated conversion of laparoscopic total gastrectomy for gastric cancer. We evaluated the effect of conversion to open total gastrectomy on short- and long-term outcomes among patients who underwent laparoscopic total gastrectomy for gastric cancer and identified factors predictive of survival. METHODS: A prospective database of consecutive laparoscopic total gastrectomies for gastric cancer was reviewed. Patients who required conversion (converted group) were compared with those who had completed laparoscopic total gastrectomy (completed group). Kaplan-Meier method was used to compare and analyze survival. Univariate and multivariate analyses were performed to identify predictors of poor survival. RESULTS: The conversion rate was 17.4%, and the most common reason for conversion was a locally advanced tumor. Conversion was associated with significantly longer operative time and greater blood loss. No differences were observed in terms of postoperative morbidity or mortality between the converted and completed patients. The converted group had significantly worse 5-year overall survival (OS) and disease-free survival (DFS). Univariate analysis showed that conversion to open total gastrectomy, pathological (p) T4 disease, and pathological N2-N3 disease were significant risk factors for OS and DFS. In multivariate analysis, pT4 cancer was the only independent predictor of DFS and OS. CONCLUSION: Conversion to open total gastrectomy per se was not associated with worse short-term outcomes or worse long-term survival.

[Impact of the extent of gastric resection on the prognosis of patients with middle one-third gastric cancer].

OBJECTIVE: To investigate the impact of the extent of gastric resection on the prognosis of patients with middle one-third gastric cancer. METHODS: From January 1998 to December 2005, 222 patients with middle one-third gastric cancer underwent D2 radical resection in the Affiliated Union Hospital, Fujian Medical University. Among them, 66 underwent distal gastrectomy (DG group), while 156 underwent total gastrectomy (TG group). The 5-year survival rates were compared between two groups. The prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: The 5-year survival rates of DG group and TG group were 63.9% and 49.8% respectively, with significant difference (P<0.05). Nevertheless, compared to DG group, the tumors in TG group had bigger size, later TNM stage, and higher proportion of locating lesser curvature of stomach (all P<0.01). Multivariate analysis revealed that invasion depth, lymph node metastasis and TNM classification were independent prognostic factors (all P<0.05), but the extent of gastric resection was not (P>0.05). CONCLUSION: If curative resection can be performed, the long-term prognosis of patients with middle one-third gastric cancer is not affected by the extent of gastric resection, and distal gastrectomy is feasible.