Identification and validation of hub genes in drug induced acute kidney injury basing on integrated transcriptomic analysis.

Background: Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers. Methods: Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin's were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models' hub gene expression was verified in vivo and in vitro using PCR and western blot. To investigate the hub gene's potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples. Results: 95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model in vivo and in vitro. External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI. Conclusion: The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI.

Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis.

This study aimed to determine the role of long noncoding RNA (lncRNA) WT1 antisense RNA (WT1-AS) in the occurrence and progression of preeclampsia (PE) and to determine the underlying molecular mechanisms. The associations between WT1-AS and microRNA (miR)-186-5p, and miR-186-5p and cell adhesion molecule 2 (CADM2) were predicted using StarBase software and verified via dual-luciferase assays. To explore the role of the human chorionic trophoblast line HTR-8/SVneo, gene (WT1-AS/miR-186-5p) gain/loss of function experiments were performed. Qualitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to evaluate transfection efficiency. Cell proliferation, apoptosis, cell migration, and invasion were assessed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and transwell analysis, respectively. Moreover, CADM2 protein expression was measured by western blotting. The results indicated that overexpression of WT1-AS inhibited cell viability, migration, and invasion, and induced apoptosis in HTR-8/SVneo cells. We observed that miR-186a-5p directly targeted WT1-AS, and miR-186a-5p knockdown reversed the effects of WT1-AS knockdown in HTR-8/SVneo cells. Binding sites were found between miR-186-5p and CADM2, and CADM2-overexpression reversed the influence of miR-186-5p mimic on HTR-8/SVneo cells. In summary, our findings demonstrated that lncRNA WT1-AS participates in PE by regulating the proliferation and invasion of placental trophoblasts, through the miR-186-5p/CADM2 axis.

Symptom clusters in patients with colorectal cancer after colostomy: a longitudinal study in Shanghai.

OBJECTIVE: Research is lacking regarding the experiences of patients after colostomy, which is needed so as to take necessary specific actions. In this study, we aimed to describe the trajectory of symptom clusters experienced by patients after colostomy over time. METHODS: This was a longitudinal observational study using data from 149 patients with colorectal cancer after colostomy. We investigated symptoms and symptom clusters at 2 weeks, 1 month, 3 months, 6 months, and 1 year after colostomy. RESULTS: Four main symptom clusters were identified, including a psychological symptom cluster, digestive and urinary symptom cluster, lack of energy symptom cluster, and pain symptom cluster in patients after colostomy in the first year after surgery. We further explored the symptom trajectory. CONCLUSIONS: We explored symptom clusters and the trajectory of symptom resolution in patients after colostomy during the first year after surgery. Four stages were proposed to describe the different statuses of symptom clusters experienced by patients. Our findings may provide insight into how to improve symptom management and postoperative quality of life for patients after colostomy.

Effective Predictor of Colorectal Cancer Survival Based on Exclusive Expression Pattern Among Different Immune Cell Infiltration.

Tumor-infiltrating immune/inflammatory cells, the important components of the tumor microenvironment (TME), remarkably affect the progression of human cancers. To understand the actual conditions within the TME of colorectal cancer (CRC), the interrelationship among tumor-infiltrating neutrophils, M2 macrophages, and regulatory T-cells (Tregs) was systematically analyzed. The infiltration conditions of CD66b+ neutrophils, CD163+ M2 macrophages, and FOXP3+ Tregs in tissue microarrays including 1021 cases of CRC were determined by immunohistochemical analysis. The prediction power of these immune cells for CRC prognosis was evaluated by subgroup analysis of the CRC cohort. Results revealed the existence pattern of infiltrating neutrophils, and Tregs/M2 macrophages fulfilled a "X-low implies Y-high" Boolean relationship, indicative of a mutually exclusive correlation between neutrophils and M2 macrophages, and between neutrophils and Tregs in the TME of CRC. What's more, the tumor-infiltrating M2 macrophages and Tregs were associated with adverse prognostic factors, whereas neutrophils were corelated with favorable factors. The high infiltration of neutrophils predicted longer survival and better chemotherapeutic response. Nonetheless, high infiltration of M2 macrophages and Tregs predicted poor prognosis. The combination of these tumor-infiltrating immune cells can serve as an effective predictor for the survival of CRC and for the chemotherapeutic outcomes of stage II-III patients. .

The clinical significance of sCD14-ST for blood biomarker in neonatal hematosepsis: A diagnostic accuracy study.

Hematosepsis is a systemic inflammatory response syndrome (SIRS) with suspected or confirmed infection, which is the most common infectious disease in clinical neonatal intensive care unit. As the rapid development of neonatal hematosepsis caused by various basic diseases, the mortality rate is high, and there are some sequelae.We report the lasted study to date with 96 cases from Fujian Longyan First Hospital between 2013 and 2015. The aim of our study is to explore the value of soluble cluster of differentiation 14 subtype (sCD14-ST) in whole blood for differential diagnosis of neonatal hematosepsis at an early stage, and used in evaluation of the severity about sepsis combined with acute physiology and chronic health evaluation II (APACHE-II) score, procalcitonin (PCT), C reactive protein (CRP), and leukocyte (WBC).In our cohort, all cases met the diagnostic criteria for hematosepsis specific for newborns. We selected 42 neonates with hematosepsis, 54 neonates with nonhematosepsis, 44 noninfectious SIRS neonates, and 53 healthy neonatal controls. Which were determined the sCD14-ST, PCT, CRP, and WBC of all samples before treatment. Then assign the APACHE-II score for the all samples before and after treatment.The study shows, sCD14-ST levels were significantly higher in hematosepsis than nonhematosepsis group (t = -2.112, P = .041). Meanwhile, sCD14-ST levels were significantly higher in neonatal hematosepsis than in noninfectious SIRS group and controls (χ = 57.812, 68.944, P < .01). However, sCD14-ST in hematosepsis group was positively correlated with APACHE-II score (R-value = 0.415, P < .01). During treatment, the sCD14-ST level was decreased obviously along with APACHE-II score, PCT, CRP, and WBC (χ = 35.019, 78.399, 52.363, 25.912, 7.252, all P values <.01). The area under the curve (AUC) of sCD14-ST was 0.942. The differences in ROC of sCD14-ST compared with PCT, CRP, and WBC were statistically significant (Z = -6.034, -4.474, -5.722, all P values <.01). The sensitivity and specificity of sCD14-ST were 95.2% and 84.9%, respectively.sCD14-ST could be a blood biomarker for early identification and disease valuation in newborns hematosepsis infection; and its diagnostic value is superior to other laboratory indexes.

[Comparison of oncologic clearance and long-term outcomes of laparoscopic surgery versus open surgery in radical resection of rectal cancer].

OBJECTIVE: To compare the oncologic clearance and long-term outcomes between laparoscopic surgery and open surgery in radical resection of rectal cancer. METHODS: Clinicopathological and follow-up data of 1184 cases with rectal cancer undergoing radical resection from July 2005 to December 2011 were analyzed retrospectively. According to the surgical method, cases were divided into laparoscopy group (104 cases) and open group(1080 cases). Demographics, number of harvested lymph nodes, distance between distal margin and tumor, incidence of anastomotic complications, disease-free survival (DFS) and overall survival(OS) were compared between the two groups. RESULTS: There were no significant differences in the number of harvested lymph nodes (15.5 vs. 14.4, P>0.05), length of distal margin (2.5 cm vs. 2.1 cm, P>0.05) and incidence of anastomotic complications (1.9% vs. 1.9%, P>0.05) between the two groups. And there were no significant differences in DFS and OS between the two groups (both P>0.05). The 3-year and 5-year DFS in laparoscopy group were 79.0% and 69.3%, and were 78.0% and 72.5% in open group. The 3-year and 5-year OS in laparoscopy group were 93.5% and 81.2%, which were 87.6% and 80.7% in open group. There were no significant differences in DFS and OS after stratification by TNM stage. CONCLUSION: The oncologic clearance and long-term outcomes after laparoscopic surgery are comparable with open surgery in radical resection of rectal cancer.