Staged laparoscopic management of locally advanced gastric cancer with outlet obstruction.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer with outlet obstruction is poor. Gastrectomy with curative intent is often initially impossible or difficult. OBJECTIVE: We report our experience of curative distal gastrectomy after laparoscopic gastrojejunostomy and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy to examine the feasibility and safety of this modified strategy for locally advanced gastric cancer with outlet obstruction, initially deemed unresectable. METHODS: Between October 2017 and June 2019, 15 patients diagnosed with locally advanced gastric cancer with outlet obstruction sequentially underwent gastrojejunostomy, received four cycles of FLOT chemotherapy, and underwent laparoscopic distal gastrectomy with curative intent (R0 resection + D2 lymphadenectomy). Clinical data were retrospectively collected and analyzed. RESULTS: R0 resection was possible in 12/15 patients, laparoscopically in 11, and one conversion to laparotomy was necessary. There was no perioperative mortality in the 12 patients. Pathologic evaluation of the resected specimens revealed that complete tumor grade regression 1a (TRG1a), TRG1b, TRG2, and TRG3 occurred in 3, 2, 4, and 3 patients, respectively. CONCLUSION: This case series showed that curative surgical resection was feasible as a staged approach for patients with locally advanced gastric cancer with outlet obstruction, after initial staged gastrojejunostomy and chemotherapy.

[Clinical significance of minimal residual disease in B-lineage acute lymphoblastic leukemia pediatric patients with different fusion gene backgrounds].

OBJECTIVE: To study the clinical significance of minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (B-ALL) pediatric patients with different fusion gene backgrounds. METHODS: A retrospective analysis was performed on the medical data of 441 B-ALL children who were treated from January 2008 to April 2015. Among the 441 children, 336 had negative fusion gene, 79 had positive ETV6-RUNX1 fusion gene, and 26 had positive E2A-PBX1 fusion gene. Flow cytometry was used to detect MRD, and the influence of MRD on day 15 (TP1), day 33 (TP2), and week 12 (TP3) of induction therapy on prognosis was analyzed. RESULTS: In patients with negative fusion gene, the positive MRD group had significantly lower overall survival (OS) rate and event-free survival (EFS) rate (P < 0.05) and significantly higher recurrence rate and mortality rate at TP1, TP2, and TP3, compared with the negative MRD group (P < 0.05). In patients with positive ETV6-RUNX1, the positive MRD group had significantly lower OS and EFS rates (P < 0.05) and significantly higher recurrence rate and mortality rate (P < 0.05) than the negative MRD group only at TP1. In patients with positive E2A-PBX1, there were no significant differences in the OS rate, recurrence rate, and mortality rate between the positive and negative MRD groups at TP1, TP2, and TP3 (P > 0.05). CONCLUSIONS: MRD has the most definite prognostic significance in pediatric B-ALL patients with negative fusion gene, while it has unsatisfactory prognostic significance in those with positive ETV6-RUNX1 or positive E2A-PBX1.

[CD20 is not a poor prognostic factor for childhood B-lineage acute lymphoblastic leukemia with high white blood cell count].

OBJECTIVE: To study the significance of CD20 combined with white blood cell (WBC) count at diagnosis in the prognosis assessment in children with B-lineage acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed on the medical data of 821 B-ALL children who were treated with CCLG-ALL2008 regimen from April 2008 to April 2015. Their survival status was followed up. RESULTS: Among the 821 children, 547 (66.6%) were negative, while 274 (33.4%) were positive for CD20 expression. Among 694 children with WBC<50×109/L (lower WBC count), the 5-year EFS rates were 65.9%±3.2% and 77.3%±2.0% for CD20 positive and negative patients respectively (P=0.001); the 5-year OS rates were 78.3%±2.9% and 87.5%±1.6% for CD20 positive and negative patients respectively (P=0.005); CD20 positive expression was an independent risk factor for EFS (HR=1.634, P=0.001) and OS (HR=1.761, P=0.005). Among 127 children with WBC>50×109/L (higher WBC count), the 5-year EFS rates was 64.3%±7.7% and 53.7%±5.5% for CD20 positive and negative patients respectively (P=0.135); the 5-year OS rate was 81.4%±6.4% and 58.6%±5.6% for CD20 positive and negative patients respectively (P=0.022); CD20 positive expression was an independent protective factor for OS (HR=0.367, P=0.016). CONCLUSIONS: In children with B-ALL who are treated with CCLG-ALL2008 regimen, those with CD20 positive expression in lower WBC count at diagnosis have a poor prognosis; however, those with CD20 positive expression in higher WBC count at diagnosis have a better long-time survival.

Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis.

Background: Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear. Methods: Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed. Results: MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04). Conclusions: This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion.

BACKGROUND: Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity. Therefore, we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion, thus contributing to the prevention and cure of prediabetes. AIM: To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT. METHODS: We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression. Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay, and the protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) was determined using western blot. Further, mRNA expression of forkhead box protein O1, phosphoenolpyruvate carboxykinase, and glucose-6 phosphatase was detected via quantitative polymerase chain reaction, and the correlation between the expression of proteins was analyzed via bioinformatics. RESULTS: In mice with IGT and VEGFB knockout, glucagon secretion increased, and the protein expression of PI3K/AKT decreased dramatically. Further, in mice with VEGFB overexpression, glucagon levels declined, with the activation of the PI3K/AKT signaling pathway. CONCLUSION: VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

DNA barcoding of Chinese snakes reveals hidden diversity and conservation needs.

DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbour distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species-delimitation methods (ABGD, sGMYC, and sPTP) recover 320 operational taxonomic units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty-eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most probably caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes.

Efficacy of neoadjuvant CapeOX/mFOLFOX6 without radiation for patients with baseline resectable mid-low locally advanced rectal cancer.

OBJECTIVES: Chemotherapy without radiation therapy for locally advanced rectal cancer (LARC) has attracted increasing attention, but the optimal schema remains controversial. In this study, we aimed to assess the efficacy and toxicity of neoadjuvant chemotherapy (nCT) of two regimens for patients with mid-low baseline resectable LARC. METHODS: A retrospective study was performed in 131 patients with baseline resectable LARC in a single center between April 2016 and August 2020. All patients received four cycles of neoadjuvant CapeOX or mFOLFOX6 before surgery. Clinical characteristics, pathological response, and survival status were then assessed. RESULTS: After a 1:1 propensity score matching, 96 patients were enrolled, including 48 receiving CapeOX and 48 receiving mFOLFOX6. The objective regression rates were 50.00% and 58.33%, and the pathological complete response rates were 6.25% and 8.33%, respectively, in the CapeOX and mFOLFOX6 groups. Patients who received mFOLFOX6 had a better tumor regression grade (TRG) than those who received CapeOX (P = 0.005). Patients in both groups had similar survival outcomes. CONCLUSIONS: The nCT has shown promising tumor response and survival outcomes, which can be a treatment option for baseline resectable LARC. For the two regimens, mFOLFOX6 provided better TRG than CapeOX, although no differences were observed in disease-free survival and OS.

[The influences of different vegetation ecosystems on heavy metals in soil in semi-arid region].

The ecological environment of semi-arid regions in China is fragile, and the situation of protecting environment is grim. So it is urgent to strengthen environment protection and ecological construction in semi-arid region. Four different vegetation ecosystems were selected in semi-arid region with Wuchuan County in Inner Mongolia as a case study: the bushes, the trees, the alfalfa land, and artificially mixed sowing grassland. The soil was sampled and carried to laboratory for analysis of the content of lead, cadmium and chromium in the soil in May and September (the start of the growing season and the end of the growing season). It was showed that among the four different ecosystems, the lead and cadmium contents in the soil were significantly different in variability, while the chromium is not significant. And the changing rate trend of the content of lead and cadmium is consistent: the contents of the both elements in May are higher than in September obviously. The degree of the order of the content change is also very close. The biggest of the change scope is from the bushes and artificially mixed sowing grassland, followed by the alfalfa land, and finally the trees. Therefore, it is more favorable to plant shrubs and grass for absorbing heavy metals in the soil in the common local vegetation eco-system.

Elevated lymphocyte specific protein 1 expression is involved in the regulation of leukocyte migration and immunosuppressive microenvironment in glioblastoma.

Immune cell infiltration mediates therapeutic response to immune therapies. The investigation on the genes regulating leukocyte migration may help us to understand the mechanisms regulating immune cell infiltration in tumor microenvironment. Here, we collected the data from Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) to analyze the expression of leukocyte migration related genes in glioblastoma (GBM). Lymphocyte specific protein 1 (LSP1) was identified as the only gene in this family which not only has an elevated expression, but also serve as an independent predictive factor for progressive malignancy in glioma. We further confirmed these results in clinical glioma samples by quantitative PCR, immunofluorescence, immunohistochemistry, and western blot. Moreover, LSP1 expression was closely related to the response to radio- and chemotherapy in GBM, and positively correlated with immunosuppressive cell populations, including M2 macrophages, neutrophil, and regulatory T cell. Additionally, elevated LSP-1 expression enhanced the expression of immunosuppression related genes like programmed cell death 1 (PD1) and leukocyte associated immunoglobulin like receptor 1 (LAIR1) in macrophages. LSP1 also promoted the migration of macrophages. Together, our study suggests a novel role of LSP1 contributing to immunosuppressive microenvironment in GBM and serving as a potential therapeutic target for it.

Integrin Beta 5 Is a Prognostic Biomarker and Potential Therapeutic Target in Glioblastoma.

Background: Glioblastoma (GBM) is the most lethal cancer of the central nervous system. Integrin beta 5 (ITGB5) is thought to be involved in intercellular signal transduction and regulation of tumor initiation and progression. However, the function of ITGB5 in GBM is not known. Methods: To address this question, we evaluated the expression level of ITGB5 in clinical specimens by immunohistochemistry and western blotting, as well as the association between ITGB5 expression and GBM patient survival using data from Chinese Glioma Genome Atlas and The Cancer Genome Atlas. The biological function of ITGB5 in GBM was investigated by Gene Ontology, gene set enrichment, and in vitro loss-of-function experiments using glioma cells. Results: Among integrin family members, ITGB5 showed the greatest difference in expression between low-grade glioma and GBM. Elevated ITGB5 expression was highly correlated with glioma progression and a mesenchymal subtype and poor survival in GBM patients. ITGB5 was found to be associated with regulation of the immune response and angiogenesis in GBM, and was required for migration and invasion of glioma cells and tube formation by endothelial cells. Conclusions: These data indicate that ITGB5 can serve as a predictive biomarker for GBM patient survival and is a potential therapeutic target in GBM treatment.