Shapirothyssen4756

Background Acute graft-versus-host disease (aGVHD) is a medical complication which may result in significant morbidity and mortality after transplantation. The aim of this study investigated the therapeutic effect and underlying mechanism of 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in the treatment of aGVHD. Method An aGVHD model was built by transferring splenocytes of B6 mice into B6D2F1 mice. 1α,25(OH)2D3 was added to evaluate the protective function to aGVHD; the phenotype and cytokine expression profile of spleen cells from the aGVHD model were determined using flow cytometry 2 weeks after the model is established. Result Administration of 1α,25(OH)2D3 significantly slowed aGVHD progression and improved survival of B6D2F1 recipients of grafted B6 splenocytes. 1α,25(OH)2D3 treatment also resulted in an increased number of CD4+Foxp3+ regulatory T cells (Tregs) but decreased the number of CD4+IL-4+ cells. In vitro analysis demonstrated that 1α,25(OH)2D3 directly increased forkhead box P3 (Foxp3) and IL-10 expression and enhanced the function of induced Tregs (iTregs). Conclusions This analysis indicated that the effect of 1α,25(OH)2D3 is mediated in part by improving the number of Tregs. 1α,25(OH)2D3 administration thus represents a viable approach for treating aGVHD. 2019 Annals of Translational Medicine. All rights reserved.Background Anastomosis leakage after esophagectomy is a major threat which leads to many subsequent complications even mortality. But current diagnosis and treatment methods are inefficient. This retrospective study aims to evaluate the utilization of endoscope-assisted mediastinal drainage therapy in treatment for anastomosis leakage after esophagectomy. Methods Between January 2014 and June 2018, 51 patients were confirmed anastomosis leakage using gastroscopy. Of them, 23 patients were treated with endoscope-assisted mediastinal drainage therapy (drainage group); and the other 28 patients received endoscope-assisted biomedical fibrin glue occlusion (occlusion group). Short-term clinical outcomes were examined. Factors related to length of postoperative hospitalization (LPH) was analyzed. Results Endoscope provided highly accurate information on the condition of anastomosis leakage. And there was no evidence that early endoscopy could cause damage to the anastomosis or gastric conduit. One patient from drainage group and two from occlusion group discharged against medical advice. Other 48 patients were completely cured without reoperation or mortality. The median LPH was 32 days in drainage group (range from 17 to 80 days) and 81 days in occlusion group (range from 32 to 190 days), respectively (P less then 0.05). Linear regression indicated statistically significant correlation between LPH and length from diagnosis to drainage or occlusion (R=0.688, P less then 0.001). Conclusions Endoscope-assisted mediastinal drainage therapy is a satisfactory treatment for anastomosis leakage. Early diagnosis and treatment may facilitate the recovery of anastomosis leakage and reduce LPH. 2019 Annals of Translational Medicine. All rights reserved.Background The possibility of using a bone-tendon quadriceps tendon graft and platelet rich plasma (PRP) injection to enhance healing capability, to solve the defect created by stump retraction in chronic Achilles tendon ruptures was studied in a series of 8 patients. Methods A series of 8 patients studied prospectively and followed for more than 24 months is presented. Results were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) score, and evaluating pain, level of activity, footwear restrictions, and satisfaction. Statistical analysis was done by the sign test for matched pairs and Wilcoxon signed-rank test. Alpha error was set at 0.05. Results Preoperatively, patients showed an average AOFAS score of 77.25 (range, 67-88). After surgery, AOFAS score showed a marked improvement in all the cases, with an average of 95.6 (range, 87-100). Improvement in AOFAS score results was statistically significant, both for sign test for matched pairs (P=0.008) and for Wilcoxon signed-rank test (P=0.012). All of the patients were satisfied with the results of the procedure, and would undergo it again. Conclusions Autologous quadriceps tendon graft (in bone-tendon configuration) has proved as a simple technique that offers good results to patients with tissue defects in the Achilles tendon. 2019 Annals of Translational Medicine. All rights reserved.Background The present study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) in gastric adenocarcinoma. Methods We performed integrated analysis to determine DEGs and DEmiRNAs of gastric adenocarcinoma based on the GEO database. A DEmiRNA-target interaction network was established. GO and KEGG pathway enrichment analyses were utilized. Then, MKN45 cells were transfected with shRNA-RAB23 to knock down the expression of RAB23. CCK-8, transwell and flow cytometry assays were utilized to measure the capacities for cell proliferation, migration and apoptosis, and the apoptosis-related gene and protein levels were measured by using polymerase chain reaction (PCR) and Western blot, respectively. Colocalization analysis of Snc1 with the vesicular protein VAMP3 and the endoplasmic reticulum protein Calnexin was performed to assess the influence of RAB23 on vesicle transport. Finally, we performed metabolomic analysis by using gas chromatography mass spectrometry (GC-MS). Results We performed MMIA of gastric adenocarcinoma based on two miRNA datasets and two mRNA datasets. A total of 4,586 DEmRNAs and 30 DEmiRNAs were obtained. The DEmRNAs of gastric adenocarcinoma were significantly enriched in PI3K/Akt signaling. We identified three interactions, hsa-miR-23a-3p-PTPN4, hsa-miR-20b-5p (hsa-miR-130a-3p)-TNFRSF10B, and hsa-miR-130a-3p (hsa-miR-363-3p)-RAB23, that may be related to the pathogenesis of gastric adenocarcinoma. The growth of MKN45 cells was inhibited by RAB23 knockdown via shRNA-RAB23 transfection. Metabolic analysis of three groups revealed a number of significantly altered metabolites, including glycerol, niacinamide, and nonadecanoic acid methylester. Conclusions RAB23 might be a target gene of hsa-miR-130a-3p and hsa-miR-363-3p. In gastric adenocarcinoma cells, knockdown of RAB23 inhibited cell proliferation, migration, and invasion and increased apoptosis by downregulating the PI3K/Akt pathway. 2019 Annals of Translational Medicine. All rights reserved.Background Anatomical location is considered in diagnostic and therapeutic approaches of cholangiocarcinoma (CCA). However, disparities and its extents in proportion of surgical candidates, prognostic factors, prognostic genetic networks, susceptibility for lymph node dissection, and disease stage at diagnosis remain to be confirmed. Methods A total of 11,710 patients with cholangiocarcinoma from Surveillance, Epidemiology, and End Results Cancer Registries (SEER) and 45 CCA patients with paired tumor and normal specimens from The Cancer Genome Atlas were studied. Kaplan-Meier estimation, Cox proportional hazards regression, Pearson's correlation, comparison between anatomical location (distal, intrahepatic, and perihilar)-dependent CCAs, differential expressive gene stratification, potential interactive gene identification, and confirmation on pathways of the prognostic networks were carried out. Results Survival outcomes were most favorable in the distal type, followed by perihilar and intrahepatic types, but postsurgical prognosis was slightly higher in intrahepatic type compared to perihilar type. Distant historic stage at diagnosis was noticed in intrahepatic type. Significant prognostic factors and their hazards ratios were dependent to the anatomical location. In addition, lymph node dissection provided significant survival benefits in perihilar type only. Furthermore, prognosis-predictive genes, as well as potential processes and pathways, were significantly among the anatomical location-dependent types that the genes barely overlapped. Conclusions There are disparities in almost all aspects among distal, intrahepatic, and perihilar CCAs. Anatomical location needs to be considered in treatment, prognostic estimation, identifying targets, and developing therapeutic approaches for CCA. 2019 Annals of Translational Medicine. All rights reserved.Background To analyze oncologic outcomes and reconstruction quality in locally advanced stage breast cancer after performing immediate autologous breast reconstruction (IABR). Methods From 2007 to 2014, data of patients aged ≤70 years old with stage II-III breast cancer who received total mastectomy (TM) were extracted from medical records. Exclusion criteria were previous contralateral breast cancer, follow-up loss before adjuvant therapy completion, and artificial reconstruction. Patients were divided into two groups (I) TM alone, and (II) TM + IABR. Overall survival (OS) and loco-regional recurrence free survival (LRRFS) were calculated. Times of minor revision, abnormal image findings in breast, and change of breast height were observed. Results Sixty-one of 188 patients received IABR after TM. Stage IIIB-C was the most important prognostic factor for OS (P less then 0.001) and LRRFS (P less then 0.001). For stage II, five-year TM and TM + IABR OS rates were 96.8% and 100% (P=0.324), respectively. For stage IIIB-C, five-year TM and TM + IABR OS rates were 57.6% and 62.5% (P=0.544), respectively. For stage II, five-year TM and TM + IABR LRRFS were 98.1% and 95.7% (P=0.998), respectively. For stage IIIB-C, five-year TM and TM + IABR LRRFS were 70.8% and 62.5% (P=0.378), respectively. Two major complications were observed after IABR. Minor revisions, abnormal image findings, and change of breast height were common without showing significant relation with adjuvant radiotherapy or tumor stage. Conclusions IABR showed feasible oncologic outcomes in 5-year follow-up. Adjuvant radiotherapy had little effect on quality of reconstruction. However, IABR in advanced stage should be cautiously applied considering expected survival and minor problems after IABR. 2019 Annals of Translational Medicine. All rights reserved.Background Assess the respiratory-related parameters associated with subsequent severe acute kidney injury in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). Methods Retrospective cohort, analyzing a large public database-Multiparameter Intelligent Monitoring in Intensive Care-III. Adult patients with at least 48 h of mechanical ventilation (MV), under volume controlled ventilation and an oxygenation index less than 300 mmHg were included. Results A total of 1,142 patients had complete data and were included in the final analyses. According to a causal directed acyclic graph (DAG) that included respiratory system compliance (Crs), tidal volume (Vt), driving pressure (ΔP), plateau pressure (PPlat), PEEP, PaO2 and PaCO2 as possible exposures related to severe AKI, only Crs and PEEP levels had significant causal association with severe acute kidney injury (AKI) (OR 0.90, 95% CI 0.84-0.94 for each 5-mL/cmH2O reduction in Crs; OR, 1.05 95% CI 1.03-1.10 for each 1-cmH2O increase of PEEP).