Cyr61 Mediates Angiotensin II-Induced Podocyte Apoptosis via the Upregulation of TXNIP.

Purpose: It is well documented that angiotensin II (Ang II) elevation promotes apoptosis of podocytes in vivo and vitro, but the potential mechanism is still oscular. The current study is aimed at probing into the assignment of cysteine-rich protein 61 (Cyr61) in Ang II-induced podocyte apoptosis. Methods: Podocytes were treated with Ang II (10-6 mol/L) for 48 hours to establish an injury model in vitro. Western blot assays were detected the expression of Cyr61, Cyt-c, Bax, and Bcl-2. Gene microarray was used to analyze the expression of mRNAs after treatment with Ang II. CRISPR/Cas9 technology was used to knock down Cyr61 and overexpress TXNIP gene, respectively. Results: The expression of Cyr61, TXNIP, Cyt-c, and Bax in podocytes treated with Ang II were upregulated, but the expression and apoptotic rates of Bcl-2 in podocytes were inhibited. The level of the above factors was not significantly different after the knockdown of Cyr61 with Ang II in podocytes. In Ang II group, when knocked down Cyr61, the expressed level of TXNIP, Cyt-c, and Bax was diminished after Ang II treatment; interestingly Bcl-2 expression and podocyte apoptotic rate were reduced. Under the stimulation of Ang II, the expression of Cyt-c and Bax were growing, whereas Bcl-2 was reduced, and the apoptotic rates were higher in the TXNIP overexpression group. Cyt-c and Bax were put on, whereas that of Bcl-2 was to be cut down when the Cyr61 was knockdown, and the apoptotic rates were gained in the TXNIP overexpression+Cyr61 knockdown group. Conclusions: The results of the study extrapolate that Cyr61 plays a dominant role in Ang II-induced podocyte apoptosis. Additionally, Cyr61 may mediate the Ang II-induced podocyte apoptosis by promoting the expression of TNXIP.

Bioinformatics analysis identifies diagnostic biomarkers and their correlation with immune infiltration in diabetic nephropathy.

Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Currently, microalbuminuria is mainly used as a diagnostic indicator of DN, but there are still limitations and lack of immune-related diagnostic markers. In this study, we aimed to explore diagnostic biomarkers associated with immune infiltration of DN. Methods: Immune-related differentially expressed genes (DEGs) were derived from those at the intersection of the ImmPort database and DEGs identified from 3 datasets, which were based on the Gene Expression Omnibus (GEO). Functional enrichment analyses were performed; a protein-protein interaction (PPI) network was constructed; and hub genes were identified by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). After screening the key genes using least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), a prediction model for DN was constructed. The predictive performance of the model was quantified by receiver-operating characteristic curve, decision curve analysis, and nomogram. Next, infiltration of 22 types of immune cells in DN kidney tissue was evaluated using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). Expression of diagnostic markers was analyzed in DN and control patient groups to determine the genes with the maximum diagnostic potential. Finally, we explored the correlation between diagnostic markers and immune cells. Results: Overall, 191 immune-related DEGs were identified, that primarily positively regulated with cell adhesion, T cell activation, leukocyte proliferation and migration, urogenital system development, lymphocyte differentiation and proliferation, and mononuclear cell proliferation. Gene sets were related to the PI3K-Akt, MAPK, Rap1, and WNT signaling pathways. Finally, CCL19, CD1C, and IL33 were identified as diagnostic markers of DN and recognized in the 3 datasets [area under the curve (AUC) =0.921]. Immune cell infiltration analysis demonstrated that CCL19 was positively correlated with macrophages M1 (R=0.47, P<0.001) and macrophages M2 (R=0.75, P<0.001). CD1C was positively correlated with macrophages M1 (R=0.47, P<0.05), macrophages M2 (R=0.75, P<0.01), and monocytes (R=0.42, P<0.01). IL33 was positively correlated with macrophages M1 (R=0.45, P<0.05), macrophages M2 (R=0.74, P<0.01), and monocytes (R=0.41, P<0.01). Conclusions: Our results provide evidence that CCL19, CD1C, and IL33, which are associated with immune infiltration, are the potential diagnostic biomarkers for DN candidates.

Dynamic activity of NF-kappaB in multiple trauma patients and protective effects of ulinastain / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the dynamic activity of NF-kappaB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain.</p><p><b>METHODS</b>From January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment), ulinastain group (25 cases of multiple injury with ulinastain treatment), and mild injury group (20 cases) for basic control. The inclusion criteria for mild injury group were AIS-2005 less than or equal to 3, single wound, previously healthy inhospital patients without the history of surgical intervention. In addition to routine treatment, patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and subsequently injected at the interval of every 8 hours for 7 days. NF-kappaB activity in monocytes and the level of TNF-alpha,IL-1, IL-6 in serum on admission (day 0), day 1, 2, 3, 4, and 7 were measured. Data were compared and analyzed between different groups.</p><p><b>RESULTS</b>NF-kappaB activity in monocytes and TNF-alpha,IL-1 and IL-6 of these patients reached peak levels at 24 hour after trauma, with gradual decrease to normal at 72 hour after trauma. NF-kappaB activity and levels of TNF-alpha,IL-1 and IL-6 were lower in ulinastain group than control one, without any significant difference between the two groups. The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d+/-3.1 d and 10 d+/-3.5 d in ulinastain group and control group respectively, and showed a significant difference.</p><p><b>CONCLUSIONS</b>NF-kappaB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma. Ulinastain may shorten the duration of systemic inflammatory response syndrome and multiple organ dysfunction syndrome, but does not show the ability to decrease the activity of NF-kappaB .</p>

Comparison of severe trauma care effect before and after advanced trauma life support training / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the emergency care effect of in-hospital severe trauma patients with the injury severity score (ISS) larger than or equal to 16 after medical staff received advanced trauma life support (ATLS) training.</p><p><b>METHODS</b>ATLS training was implemented by lectures, scenarios, field practices, and examinations. The clinical effect of in-hospital severe trauma care was compared 2 years before and after ATLS training.</p><p><b>RESULTS</b>During 2 years (from January 1, 2004, to December 31, 2005) before ATLS training, 438 cases of severe trauma were admitted and treated emergently in our department. Among them, ISS score was 28.6+/-7.8 on average, and 87 cases died with the mortality of 19.9%. The duration in emergency department and from admission to operation were 69.5 min+/-11.5 min and 89.6 min+/-9.3 min respectively. Two years (from January 1, 2007, to December 31, 2008) after ATLS training, 382 cases of severe trauma were admitted and treated. The ISS was 25.3+/-6.1 on average and 62 cases died with the mortality of 15.1%. The duration in emergency department and from admission to operation were 47.8 min+/-10.7 min and 61.5 min+/-9.9 min respectively. The ISS score showed no significant difference between the two groups (P > 0.05), but the mortality, the duration in emergency department and from admission to operation were markedly decreased after ATLS training and showed significant difference between the two groups (P <0.05).</p><p><b>CONCLUSION</b>ATLS course training can improve the emergency care effect of in-hospital severe trauma patients, and should be put into practice as soon as possible in China.</p>

First aid strategy for severe traumatic patients in hospital / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the emergency management principles of severe trauma in hospital (injury severity score larger than or equal to 16).</p><p><b>METHODS</b>We used "ATP principle" to manage severe traumatic patients. The ATP principle is composed of: 1) attending surgeons offering initial management (A); 2) teamwork commencement immediately after patients admitted to hospital (T); 3) parallel principle, ie, emergency resuscitation, evaluation and laboratory test performed simultaneously (P). Clinical effects before and after applying ATP principle were retrospectively analyzed and compared.</p><p><b>RESULTS</b>During January 1, 2002 to December 31, 2003, 338 patients were treated without applying ATP principle, in which ISS was 25.9+/-6.4, 152 cases died with the mortality being 39.2%, and the time stayed in emergency department and the time to operation room after admission were (102.8+/-16.7) min, (140.3+/-20.6) min, respectively. During January 1, 2004 to December 31, 2005, 438 patients were treated based on ATP principle, in which ISS was 28.6+/-7.8, 87 cases died with the mortality being 19.9%, and the time in emergency department and the time to operation room after admission were (69.5+/-11.5) min, (89.6+/-9.3) min, respectively. ISS showed no significant difference between the two groups (P larger than 0.05) but the mortality, the time stayed in emergency department and the time to operation room after admission were greatly reduced and showed significant difference between the two groups (P less than 0.05).</p><p><b>CONCLUSIONS</b>Applying ATP principle to treat severe traumatic patients can shorten emergency treatment time in hospital and decrease mortality.</p>