IR Group Research Articles

Mismatch Repair Status is an Effective Prognostic Factor for Early-Stage Endometrial Carcinoma

This study is to evaluate the impact of mismatch repair (MMR) status on prognosis among patients with stage I to II (FIGO 2009) endometrial carcinoma (EC) treated with hysterectomy and adjuvant RT. Between Oct. 2017 and Dec. 2020, patients with stage I to II (FIGO 2009) EC who had undergone hysterectomy followed by adjuvant RT in our institution were retrospectively reviewed. Clinical characteristics were compared between patients with proficient and deficient mismatch repair (pMMR and dMMR) using Pearson Chi-Square test for categorical variables. Kaplan-Meier method and log-rank test were used to compared overall survival (OS), disease-free survival (DFS), local-regional recurrence free survival (LRFS) and distant metastasis free survival (DMFS). Statistically significant difference was set as p<0.05. Totally 276 stage I to II EC patients with known MMR status were included in this study. Among them, 211 patients were classified as pMMR while 65 patients were classified as dMMR. When compared to pMMR, patients with dMMR were more likely to have grade 3 and non-endometrioid type(37.8% vs. 20.8%, p = 0.014), lympho-vascular invasion (36.7% vs. 16.3%, p = 0.000), young age (<60) (28.6% vs. 17.2%, p = 0.027), HIR to HR classification(30.9% vs. 16.1%, p = 0.004). Of all the 276 patients, the median follow-up time was 31 months. Two-year DMFS was superior for pMMR compared to dMMR patients (96.3% vs. 95.0%, p = 0.048). Two-year DFS tended to be better for pMMR than dMMR patients with survival curves not crossed over each other (93.0% vs. 86.8%, p = 0.074). Two-year OS (98.9% vs. 98.4%, p = 0.716) and LRFS (96.3% vs. 95.0%, p = 0.815) were not different between pMMR/dMMR patients. For HIR to HR group, we reached the similar conclusion while for LR to IR group, survival statistics were not different between pMMR/dMMR patients. As to failure pattern, dMMR were more likely to have distant failure while local and regional failure were not different between the two groups. For stage I to II EC, patients with dMMR have poorer DMFS and DFS compared to pMMR patients especially in HIR to HR risk classification. The combination of MMR status and other clinical and pathological factors may establish a new prognostic model and form a new risk stratification system.

Evaluation of the Effects of Radiation Therapy on Muscle Contractibility and Skin Healing: An Experimental Study of the Cancer Treatment Implications.

Radiotherapy can affect healthy cells, resulting in side effects. This study aimed to assess the impact of radiotherapy on soft tissue in surgical wounds in rats. The animals were divided into four groups: control (S) group without irradiation, immediate irradiation (S-IIr) group receiving irradiation right after surgery, late irradiation (S-LIr) group receiving irradiation four weeks after surgery, and early irradiation (Ir-S) group receiving irradiation before surgery. The irradiated groups underwent two fractional stages of 15 Gy. Muscle contractibility (EMG) was evaluated at two different time points, and after 2 and 7 weeks, the animals were euthanized for histological analysis of the muscles and skin. There was no significant difference between the EMG1 and EMG2 values of the S and S-LIr groups, but both S-IIr and Ir-S groups exhibited a statistically significant difference. The S group demonstrated a larger diameter of muscle fiber compared to other groups, showing a significant difference. In terms of skin analysis, the S-IIr group had the least inflammatory infiltrate and the highest amount of red fibers, differing significantly from the other groups. Regardless of the duration, radiotherapy was found to have effects on the surrounding soft tissues, as concluded by this study.

Rhabdomyosarcoma of the genitourinary system in girls - the role of magnetic resonance imagining in diagnosis, treatment monitoring, and follow-up.

Rhabdomyosarcoma of the genitourinary system in girls is a rare neoplasm, especially in non-dedicated centers. Our work aimed to sum up and present genitourinary rhabdomyosarcomas in girls from the radiological point of view. We retrospectively reviewed all girls with genitourinary RMS who underwent treatment at the Institute of Mother and Child in Warsaw between 2009 and 2022. We evaluated the demographic, clinical, and pathological patient data and imaging studies. During the study period, ten patients presented with genitourinary RMS and underwent magnetic resonance imaging (MRI). The median age at the time of diagnosis was 2.8 years, six patients were younger than three years, and four patients were older than ten years. The most common clinical symptoms were tumor fragments protruding from the vagina/falling out of the vagina and vaginal bleeding or discharge, and the most common original location was the vagina. One hundred percent of patients had the embryonal subtype of RMS, and 100% of cases where molecular tests for PAX3/FOXO1 fusion gen status were performed had negative status. At presentation, the median tumor volume was 114 cm³. Eight patients (80%) were classified as clinical group III according to the IRS Group, and most patients (70%) were in a standard-risk group. All patients received multimodal treatment, including surgery and chemotherapy; 60% received radiotherapy. Neoadjuvant chemotherapy was the primary treatment for all our patients. In six patients (60%) with a measurable tumor mass after a biopsy, a gradual tumor volume reduction was observed after induction chemotherapy (approximately ten weeks of treatment) - all of which had a partial response (PR). All our patients (100%) responded completely to treatment. MRI was performed at every stage of diagnosis and treatment as well as during follow-up. It allowed for staging, monitoring of chemotherapy, and guided surgery.

Effect of Gallic Acid Treatment on Hepatic Tissue in Ischemia-Reperfusion

Aim: Hepatic IR occurs in many clinical conditions such as liver injury, liver hemorrhage and shock, surgical resection, and transplantation. In our study, it is aimed to investigate whether gallic acid (GA) can be used for hepatoprotective purposes, histopathologically.&#x0D; Study Desıgn: 24 Wistar albino male rats were divided into 3 groups (n:8). Surgical procedures were done under general anesthesia. A 4 cm midline abdominal incision were opened to observe hepatoduodenal ligament. The portal vein and hepatic artery was closed with a rubber band and silk suture, and ischemia was performed for 60 minutes. The suture was opened and hepatic reperfusion was performed for 6 hours. 50 mg/kg Gallic Acid was administered to the rats in this group by intraperitoneal route once a day for 14 days.&#x0D; Results: Normal histology of lvier was observed with regular vena centralis, endothelial cells, hepatocytes and sinusoid. In IR group, blood vessels were dilated and congested with cell infiltrations. Hepatocytes were degenerated with irregular sinusoides and hyperplasic Kupfer cells. IR+GA group, mononuclear cell infiltration continued with thickening of the basement membrane of the vessels. Vacuolated hepatocyte was observed. GA treatment alleviasted the pathologies occurred due to IR injury.&#x0D; Conclusion: It was thought that the cellular damage in the inflammation signal, which started as a result of the cessation of blood flow after ischemia-reperfusion injury, affects the classical lobule of the liver especially around the vena, and may cause necrotic changes by increasing cell apoptosis due to functional nutritional deficiency.&#x0D; Keywords: liver, ischemia, reperfusion, gallic acid, histology

Sex Hormone Binding Globulin is an Independent Predictor for Insulin Resistance in Male Patients with Newly Diagnosed Type2 Diabetes Mellitus.

This study explored the correlation between sex hormones, sex hormone binding globulin (SHBG), and insulin resistance in male patients with newly diagnosed type2 diabetes mellitus (T2DM). A total of 48 male patients with newly diagnosed T2DM were enrolled in this study between March 2022 and December 2022. Clinical characteristics, sex hormones, and SHBG levels were collected. All enrolled subjects received intensive hypoglycemic treatment with insulin pump for 1week to achieve glycemic control, then the steady-state glucose infusion rate (GIR), an indicator of insulin sensitivity, was determined by the hyperinsulinemic-euglycemic clamp. Correlation analysis and multivariate logistic regression analysis were performed to explore the association of clinical characteristics, sex hormones, and SHBG with insulin sensitivity. The optimal cutoff value to predict insulin resistance was calculated using receiver operating characteristic (ROC) curve. According to the GIR cut-point value of 5.700mg/(kgmin), there were 40 patients with insulin resistance (IR group) and 8 patients without (non-IR group). The IR group exhibited lower testosterone and SHBG levels than the non-IR group (all p < 0.050). Correlation analysis showed that insulin sensitivity was positively associated with testosterone and SHBG, while negatively associated with body mass index, fasting blood glucose, alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, and apolipoproteinB (all p < 0.050). Multivariate logistic regression analysis demonstrated that SHBG is an independent predictor for insulin resistance (p = 0.029). Further ROC curve analysis revealed that the optimal cutoff value of SHBG to predict insulin resistance is 17.200nmol/L, with the corresponding area under the curve (AUC) and its 95% confidence interval (CI) being 0.813 and 0.691-0.934. SHBG is an independent predictor for insulin resistance in male patients with newly diagnosed T2DM. KY20220314-01.

Proanthocyanidin Alleviates Liver Ischemia/Reperfusion Injury by Suppressing Autophagy and Apoptosis via the PPARα/PGC1α Signaling Pathway.

Hepatic ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon in clinical practice, which usually occurs in liver transplantation, liver resection, severe trauma, and hemorrhagic shock. Proanthocyanidin (PC), exerted from various plants with antioxidant, antitumor, and antiaging activity, were administrated in our study to investigate the underlying mechanism of its protective function on IRI. Two doses of PC (50 mg/kg, 100 mg/kg) were given to BALB/c mice by intragastric administration for 7 days before partial (70%) warm IR surgery. Serum and liver tissues were collected 2, 8, and 24 h after reperfusion for relevant experiments. The results of transaminase and hematoxylin and eosin staining indicated that PC pretreatment significantly alleviated IRI in mice. Serum total superoxide dismutase increased and malondialdehyde decreased in PC pretreatment groups. Enzyme-linked immunosorbent assays, western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry showed that inflammation, apoptosis, and autophagy in PC preprocessing groups were significantly inhibited and were dose-dependent. The protein, mRNA expression, and immunohistochemical staining results of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in the PC pretreatment groups were significantly upregulated compared with the IR group in a dose-dependent manner. PC pretreatment suppressed inflammation, apoptosis, and autophagy via the PPAR-α signaling pathway to protect against IRI of the liver in mice.

Maresin1 inhibits the NF-κB/caspase-3/GSDME signaling pathway to alleviate hepatic ischemia-reperfusion injury

Objective: To investigate the role of Maresin1 (MaR1) in hepatic ischemia-reperfusion injury (HIRI). Methods: The HIRI model was established and randomly divided into a sham operation group (Sham group), an ischemia-reperfusion group (IR group), and a MaR1 ischemia-reperfusion group (MaR1+IR group). MaR1 80ng was intravenously injected into each mouse's tail veins 0.5h before anesthesia. The left and middle hepatic lobe arteries and portal veins were opened and clamped. The blood supply was restored after 1h of ischemia. After 6h of reperfusion, the mice were sacrificed to collect blood and liver tissue samples. The Sham's group abdominal wall was only opened and closed. RAW267.4 macrophages were administered with MaR1 50ng/ml 0.5h before hypoxia, followed by hypoxia for 8h and reoxygenation for 2h, and were divided into the control group, the hypoxia-reoxygenation group (HR group), the MaR1 hypoxia-reoxygenation group (MaR1 + HR group), the Z-DEVD-FMK hypoxia-reoxygenation group (HR+Z group), the MaR1 + Z-DEVD-FMK hypoxia-reoxygenation group (MaR1 + HR + Z group), and the Con group without any treatment. Cells and the supernatant above them were collected. One-way analysis of variance was used for inter-group comparisons, and the LSD-t test was used for pairwise comparisons. Results: Compared with the Sham group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β, and IL-18 in the IR group were significantly higher (P < 0.05), with remarkable pathological changes, while the level in the MaR1 + IR group was lower than before (P < 0.05), and the pathological changes were alleviated. Compared with the Con group, the HR group had higher levels of IL-1β and IL-18 (P < 0.05), while the MaR1 + HR group had lower levels of IL-1β and IL-18 (P < 0.05). Western blot showed that the expressions of caspase-3, GSDME, and GSDME-N were significantly higher in the HR group and IR group than in the other groups; however, the expression was lower following MaR1 pretreatment. The Z-DEVD-FMK exploration mechanism was inhibited by the expression of caspase-3 in HIRI when using MaR1. Compared with the HR group, the IL-1β and IL-18 levels and the expressions of caspase-3, GSDME, and GSDME-N in the HR + Z group were decreased (P < 0.05), while the expression of nuclear factor κB was increased, but following MaR1 pretreatment, nuclear factor κB was decreased. There was no significant difference in the results between the MaR1 + H/R group and the MaR1 + H/R + Z group (P > 0.05). Conclusion: MaR1 alleviates HIRI by inhibiting NF-κB activation and caspase-3/GSDME-mediated inflammatory responses.

#6315 CHARACTERIZATION OF BRAIN DAMAGE AFTER ACUTE KIDNEY INJURY

Abstract Background and Aims Acute kidney injury (AKI) is a very common condition in inpatients. Severe AKI is frequently associated with by neurological disorders such as confusion, the mechanisms of which are poorly understood. We have shown in several animal models that chronic kidney disease is associated with impaired cognitive performance such as memory and increased permeability of the blood-brain barrier (BBB), related to the accumulation of uremic toxin indoxyl sulfate. The goal of these experiments was to highlight the influence of AKI on cerebral impairment in mice, particularly the BBB permeability, and to describe the mechanisms involved. Method We performed an AKI in C57/Bl6 WT mice, by unilateral nephrectomy and transient ischemia-reperfusion of the remaining kidney for 20 minutes (RIRI20 group) and compared them to two other groups: control mice and mice with unilateral ischemia-reperfusion without nephrectomy (IR20). Modified neurological severity score (mNSS) was performed daily. BBB permeability was assessed by quantification of the Evans Blue leakage in the brain and by cerebral 68Ga-DTPA TEP/CT imaging. Cerebral immuno-histochemistry was performed to evaluate the neuro-inflammatory processes. Results Glomerular filtration rate at Day 1 was lower in AKI group compared to the control group 0.21 ± 0.26 vs. 0.94 ± 0.13 mL/min/100g b.w (p&amp;lt;0.0001) and IR group: 0.75 ± 0.17 mL/min/100g b.w (p = 0.0007). Mice with AKI displayed a neurological impairment at day 1 and day 2 post-AKI, compared to control mice and IR20 mice, with mainly an impairment of the balance. Mean mNSS score at Day 1 was 2.6 ± 4.5 in AKI group, and 0.0 ±-0.0 in both the control and IR groups (p = 0.002). BBB permeability at Day 2 was higher in the AKI group than in the control group (p = 0.10) and the IR group (p = 0.0006) by Evans blue staining. Cerebral TEP imaging found similar results with increased BBB permeability in AKI mice to compared to control mice at D1 and D2 (p = 0.004 and p = 0.009, respectively). On immunohistochemistry, brains of mice after AKI displayed more astrocytosis and microglial activation compared to brains of control mice. Conclusion AKI in mice is specifically associated with early neurological damage, unlike renal ischemia-reperfusion alone, related to a BBB disruption in the first two days after AKI. AKI appears to induce astrocytosis and altered microglial phenotype, potentially due to increased neuroinflammatory processes following BBB disruption.

Antibacterial and antioxidant activities of curcumin/Zn metal complex with its chemical characterization and spectroscopic studies

Curcumin is an active component of the rhizome turmeric. Curcumin/zinc (Cur/Zn) complex was synthesized and characterized using the elemental analysis, the molar conductance, FT-IR, UV–Vis,1HNMR, scanning (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). The molar conductance value is very low, referring to the absence of Cl− ions inside or outside chelate sphere confirming non electrolytic nature. Based on IR and electronic spectra curcumin CO group in enol form chelated to Zn (II) ion. The surface morphology of curcumin chelate with Zn showed elevated in particle size and irregular grains shaped with elongated morphology. Transmission electron microscopy revealed that the curcumin chelate with Zn has spherical black spots like shape with particle size range from (33–97 nm). The antioxidant activities of curcumin and Cur/Zn complex were assessed. Results showed that the Cur/Zn complex showed potent antioxidant activities than curcumin. For antibacterial activity, Curcumin/Zn showed inhibitory effect against both (+ve and –ve) gram bacteria (Bacillus subtilis and Escherichia coli) at very low concentration. Cur/Zn recorded antibacterial and inhibition activity at 0.009 against E. coli and at 0.625 against B. subtilis. Cur/Zn complex showed higher capacity in scavenging the ABTS radical, FARAP capacity and metal chelating activity than curcumin itself and it showed more scavenging and inhibition activity for DPPH. The synthesized complex of Cur/Zn showed potent antioxidant and antibacterial activities than curcumin itself and it may benefit in treatment of aging and degenerative diseases with elevated and excessive production of free radicals.

Erb‐(IL10)2 ameliorates radiation‐induced skin injury through eliminate oxygen free radicals

AbstractObjectiveRadiation‐induced skin injury (RISI) remains a serious concern during radiotherapy. IL‐10 is considered as an immune suppressive cytokine by inhibiting the secretion of the proinflammatory cytokines in cells. The aim of this study was to evaluate the protective role of Erb (IL10) 2 against ionizing radiation.MethodsWe fused Interleukin 10 (IL‐10) dimer onto an anti‐epidermal growth factor receptor antibody Cetuximab (Erbitux) to form a new bispecific protein Erb‐(IL10)2. The protective effect and biological activity of Erb‐(IL10)2 was measured in model of RISI.ResultsUnder the condition of 20 Gy irradiation, surviving cells in the IR group decreased significantly compared with the non‐IR group (p = 0.0021). The survival rates of HaCaT (p = 0.0038) and WS1 (p = 0.0003) cells were significantly increased after IL‐10 treatment. The apoptosis rates of HaCaT (p = 0.0048) and WS1 (p = 0.0074) cells in the IL‐10 group were significantly lower compared to the NC group. Under 20 Gy irradiation conditions, IL‐10 fusion protein reduced the level of reactive oxygen in HaCaT (p = 0.0046) and WS1 (p&lt;0.0001) cells compared to the control group. Relatively normal granular mitochondrial morphology was observed in the IL‐10 group after 20 Gy X‐ray irradiation compared with the NC group. Ater 35 Gy electron radiation, the levels of reactive oxygen species in the skin tissue of C57/B6 mice injected with IL‐10 fusion protein were significantly lower than those in the PBS group (p = 0.001). Compared with the PBS group and the other IL‐10 groups, the group treated with 0.2 mg/kg IL‐10 showed a significant decrease in MDA level (p = 0.0024). Compared with the PBS group, the thickness of the stratum corneum in groups treated with 0.05, 0.1 and 0.2 mg/kg IL‐10 decreased, and the skin appendages were well‐preserved. In the group treated with 0.2 mg/kg IL‐10, the skin tissue structure was still relatively intact, and the masson staining area was smaller than that of the PBS group.ConclusionIL‐10 plays a role in inhibiting radioactive fibrosis in radioactive skin injury. IL‐10 has a protective effect on skin cell damage after ionizing radiation irradiation both in vitro and in vivo. Moreover, IL‐10 plays a role in inhibiting radioactive fibrosis in radioactive skin injury.

Expression of VEGF in Fallopian tubes in Ovarian Ischemia-Reperfusion

Aim: Our aim was to investigate expression level of VEGF in tuba uterine in ovarian ischemia-reperfusion (I/R) by immunohistochemical techniques. Material and Methods: 30 Sprague Dawley female rats were categorized into three groups. Sham group: The abdomen was opened and closed without any treatment. Ischemia (I) group: 1-hour ischemia was allowed to create ischemic injury. Ischemia-reperfusion (I/R) group: 1-hour ischemia and then 3-hour reperfusion was allowed to create I/R injury. Results: MDA and MPO levels were increased after ischemia and IR while GSH content was decreased. Histological scores of follicular degeneration, inflammation, hemorrhage were high in I and IR groups. Normal histology of tuba uterine was observed in sham group. In I and IR group, degenerated cilia, desquamative epithelial cells impaired basement membrane leukocytes infiltration, apoptotic nuclei, vascular dilatation, thrombosis and inflammation and adenoma were observed. VEGF expression was mainly in sham group. In I and IR group, endothelial cells, adenoma structures, vessels, macrophage and inflammatory leukocyte cells and fibroblast cells showed positive VEGF expression. Conclusion: IR damage affected inflammation and angiogenesis, changes in implantation.

SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury.

We previously showed that SerpinA3K is present in urine from rats and humans with acute kidney injury (AKI) and chronic kidney disease (CKD). However, the specific role of SerpinA3K during renal pathophysiology is unknown. To begin to understand the role of SerpinA3K on AKI, SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing ischemia/reperfusion (I/R) and compared to wild type (WT) mice. Four groups were studied: WT+S, WT+IR, KOSA3+S, and KOSA3+IR. As expected, I/R increased serum creatinine and BUN, with a GFR reduction in both genotypes; however, renal dysfunction was ameliorated in the KOSA3+IR group. Interestingly, the increase in UH2O2 induced by I/R was not equally seen in the KOSA3+IR group, an effect that was associated with the preservation of antioxidant enzymes' mRNA levels. Additionally, FOXO3 expression was initially greater in the KOSA3 than in the WT group. Moreover, the increase in BAX protein level and the decrease in Hif1a and Vegfa induced by I/R were not observed in the KOSA3+IR group, suggesting that these animals have better cellular responses to hypoxic injury. Our findings suggest that SerpinA3K is involved in the renal oxidant response, HIF1α/VEGF pathway, and cell apoptosis.

Impact of race and ethnicity on presentation and outcomes of patients treated on rhabdomyosarcoma clinical trials: A report from the Children's Oncology Group.

Racial and ethnic disparities have been demonstrated in pediatric and adult cancers. However, there is no consensus on whether such disparities exist in the presentation, treatment, and outcome of patients with rhabdomyosarcoma (RMS). Patient information from the seven most recent RMS clinical trials was obtained from the Children's Oncology Group (COG). Chi-squared analyses were used to compare patient, tumor, and treatment characteristics across racial and ethnic groups. Pairwise analyses comparing Non-Hispanic Black (NHB) versus Non-Hispanic White (NHW) racial groups and Hispanic versus NHW ethnic groups were conducted for significant characteristics. Kaplan-Meier method and Wilcoxon signed-rank tests were performed to analyze outcomes. In the overall cohort (n = 2157), patients'self-identified race/ethnicity was: 0.4% American Indian/Alaska Native, 2.6% Asian, 12.6% Hispanic, 0.2% Native American/other Pacific Islander, 12.8% NHB, 61.9% NHW, and 9.6% unknown. Six characteristics differed by race/ethnicity: age, histology, IRS group, invasiveness, metastatic disease, and FOXO1 fusion partner. Five were significant in pairwise comparisons: NHB patients were more likely to present at age ≥ 10 years and with invasive tumors than NHW patients; Hispanic patients were more likely to present with alveolar histology, metastatic disease, and IRS group IV disease than NHW patients. No differences were found in event free or overall survival of the entire cohort, in risk group-based subset analyses, or among patients with high-risk characteristics significant on pairwise analysis. While NHB and Hispanic patients enrolled in COG trials presented with higher risk features than NHW patients, there were no outcome differences by racial or ethnic group.

Effect of insulin resistance on CAC scores in cancer survivors

BackgroundMany ca. survivors exhibit signs of IR, an important risk factor for the development of CAD. CAC scans offer a risk assessment of CV disease before cardiac damage has occurred. We investigated how IR affects CAC scores in cancer survivors.ObjectivesThe aim of this study was to show that CAC scores differ significantly between insulin-sensitive- and -resistant cancer survivors.MethodsWe enrolled 90 cancer survivors of a large community hospital from March 2021 to January 2022 into this pilot study. Patients were subdivided into three groups: insulin-sensitive (IS), insulin-resistant/prediabetic and insulin-resistant/diabetic. All patients received a CAC scan.Results70% of asymptomatic survivors overall and 81% of asymptomatic IR patients show CAD on CAC scans. 17 CAC scans in the IS group, 6 CAC scans in the IR/prediabetic group and 5 CAC scans in the IR/diabetic group showed an Agatston score of 0. The p-value between the three groups was statistically significant (p = 0.005) whereas the IR/prediabetic- and the IR/diabetic group did not differ statistically from each other. The mean MESA 10-year CHD risk with CAC was 7.8. There was a highly significant difference between the 3 groups (p < 0.001). The two IR groups did not differ statistically (p = 0.076).ConclusionsSurvivors with IR including prediabetes have less frequent zero CAC scores than insulin-sensitive survivors. Our study also showed that IR including prediabetes significantly increases the MESA 10-yr. CHD Risk with CAC in cancer survivors. This trial highlights the importance of screening survivors for IR and draws attention to the association of IR to CAC not only in diabetes but also in prediabetes. The high fraction of asymptomatic survivors with CAD is concerning and calls for further investigation. CAC scans are an inexpensive and efficient way of screening asymptomatic cancer survivors for CAD.

THE MYOKINE IRISIN INHIBITS TENOCYTE INFLAMMATION IN VITRO

The purpose of this study was to evaluate the beneficial effects of r-Irisin (IR) on human primary tenocytes (hTCs) in vitro. Indeed, Irisin is secreted from muscles in response to exercise and mediates many beneficial effects on tissues and organs.Tissue samples (n=3) were analyzed by histology and immunohistochemistry for αVβ5 receptor. hTCs isolated, culture expanded were treated with: 1) RPMI medium as control; 2) IR at different concentrations; 3) IL-1β; 4) pre-treated with IL-1β for 24 h and then co-treated with IR; 5) pre-treated with IR for 24 h and then co-treated with IL-1β. We evaluated: cell metabolic activity (MTT); cell proliferation (trypan blue staining and PicoGreen); nitrite concentration (Griess). The analysis were performed in triplicate for each donor and each experiment was repeated at least three times. Data were expressed as mean ± S.D. One-way ANOVA analysis was used to compare the groups under exam.We found the presence of the αVβ5 receptor on hTCs plasma membrane supporting the potential interaction with irisin. Cell proliferation was significantly increased with IR at 5, 10 and 25 ng/mL. IR 25 ng/mL after IL1β pre-treatment was able to counteract the increase of nitrite production (p &lt; 0.001) compared to the inflamed hTCs (p &lt; 0.01; p &lt; 0.0001), as well as IR at 10 and 25 ng/ml showed a protective role from oxidative damage. We observed a significant increase in cell metabolic viability in culture under IR at 5 and 25 ng/mL (p &lt; 0.001; p &lt; 0.05) in the pre-treated IR groups, whereas IR showed anti-inflammatory effects at the highest concentration of r-Irisin (p &lt; 0.05).This is the first study reporting the capability of irisin to attenuate tendinopathy in vitro by acting on acute inflamed tenocytes. Our results confirmed and highlighted the potential cross-talk mechanism between muscle and tendon.

Clinical, biological, and outcome features of P2RY8-CRLF2 and CRLF2 over-expression in pediatric B-cell precursor acute lymphoblastic leukemia according to the CCLG-ALL 2008 and 2018 protocol.

CRLF2 alterations are associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This study aimed to explore the clinical, biological, and outcome features of pediatric BCP-ALL with CRLF2 abnormalities. This study enrolled 630 childhood BCP-ALLs treated on CCLG-ALL 2008 or 2018 protocol. P2RY8-CRLF2 was determined by Sanger sequencing and CRLF2 expression was evaluated by qRT-PCR. The correlation between clinical, biological features and outcomes with P2RY8-CRLF2 or CRLF2 over-expression were analyzed. P2RY8-CRLF2 and CRLF2 over-expression were found in 3.33% and 5.71% respectively. P2RY8-CRLF2 was associated with male, higher frequency of CD7 expression, high WBC and MRD before consolidation. CRLF2 over-expression showed ETV6-RUNX1- , higher frequency of CD22, CD34, CD66c, CD86 expression, hyperdiploidy and high MRD at early treatment. The lower overall survival (OS) was found in patients with P2RY8-CRLF2 and confined only in IR group. Furthermore, adverse event-free survival and OS of P2RY8-CRLF2 were discovered comparing to those without known fusions or treated on CCLG-ALL 2008 protocol. However, P2RY8-CRLF2 was not confirmed as independent prognostic factors and no prognostic impact of CRLF2 over-expression was found. These findings indicate P2RY8-CRLF2 identifies a subset of patients with specific features and adverse outcomes that could be improved by risk-directed treatment.

Point-of-care salivary oxidative and renal functional markers to assess kidney function in reperfusion-induced acute kidney injury in male rats.

Saliva is one of the most promising body fluids in the research of new biomarker for various diseases diagnosis. However, serial sampling in this condition is very dangerous and pose iatrogenic anemia with blood loss. This study was done to evaluate the cost-effectiveness of point-of-care salivary tests and identify the validity of salivary markers. Rats were randomly assigned to four experimental groups: (1) control (2) IR-3h (3) IR-6h (4) IR-24h. Both renal pedicles were occluded for 55min and then were declamped to allow reperfusion for 3, 6 and 24h in IR groups. After reperfusion, all rats received pilocarpine 1mg/kg to collect saliva. Plasma samples were also collected. Renal parameters including Cr, uric acid, and urea, malondialdehyde (MDA) levels, Bax/Bcl2 ratio, nitrite/nitrate ratio, corticosterone levels and oxidant/antioxidant ratio were measured in both plasma and salivary samples. There were significant increased level of renal function parameters, MDA levels, Bax/Bcl2 ratio, nitrite/nitrate ratio and corticosterone in both saliva and plasma. The comparison of above parameters in both saliva and plasma showed significant correlation. This study demonstrated that concentrations of indices specifically renal functional parameters increase in saliva in the IR-induced kidney injury in male rats and result indicate the potential of saliva as a tool to monitoring AKI. Measurement of salivary parameters may can become reliable diagnostic tests for patients with AKI.

Momordica charantia reduced ovarian ischemia - reperfusion injury by suppressing APAF-1 expression.

We investigate the effect of Momordica charantia (MC) against ovarian ischemia-reperfusion injury (IRI). Forty-eight Sprague Dawley female rats were divided into 6 groups. 3 hours ischemia/3 hours reperfusion was conducted. Before and/or after IR, 600 mg/kg MC were introduced to rats via an orogastric tube. At the end of the experiment, total serum antioxidant/oxidant status (TAS/TOS) and Anti-Mullerian Hormone (AMH) level were measured. Ovarian histopathology and APAF-1 expression level were analyzed. TAS and AMH levels were the lowest, while TOS level and OSI were the highest in the IR group. TAS and AMH levels were higher, and TOS levels and OSI were lower in MC-treated groups compared to IR group. Follicular degeneration, granulosa and stromal cell degeneration, mononuclear cell infiltration and vascular congestion and dilatation were observed in the IR group. Ovarian histopathology was improved in groups that received MC extract. APAF-1 immune activity was intense in IR and MC+IR groups while decreased in the groups treated with MC extract after IRI. MC treatment downregulated APAF-1 protein after IRI. MC extract restored negative biochemical and histochemical changes caused by IRI due to its antioxidant properties and supported cell survival by suppressing APAF-1 expression.

Impact of Optimizing Critical Care Resources in Pediatric Surgery Patients

Background: Prediction scores could help to timely identify patients at risk. More intense care monitoring outside the pediatric intensive care unit (PICU) could improve outcomes. These concepts of critical care without borders could be implemented shortly with local resources and improve patient safety. Predict more, do less in PICUs, and more in the ward. The aim of this work was to evaluate the impact of prediction scores for identification of postoperative high risk surgical patients and their need for pediatric intensive care unit admission.&#x0D; Methods: This prospective study was carried out on 40 pediatric patients. The studied patients were divided into three groups. LR Group: 14 cases with ASA = 1, 2 PEWS ≤ 2, pSOFA ≤ 7, LqSOFA &lt; 2. IR Group: 10 cases with PEWS = 3, 4 pSOFA = 8 -11 HiR Group: 16 cases with ASA = 3 -5, PEWS ≥ 5, pSOFA ≥ 12, LqSOFA ≥ 2. American Society of Anaesthesiologists (ASA) scoring was obtained from each patient preop. The Pediatric Early Warning (PEWS) Scoring was obtained from each patient immediately postop. The Pediatric Sequential Organ Failure Assessment (pSOFA) Scoring was obtained from patients admitted to PICU on day 1 and day 7. Liverpool quick Sequential Organ Failure Assessment (LqSOFA) scoring was obtained from all patients on admission.&#x0D; Results: Regarding prognostic performance of different scores to predict mortality. For ASA score: it was statistically significant with AUC = .882, cut off values &gt; 3, sensitivity = 75%, specificity = 88.89%, PPV = 42.9% and NPV = 97%. -For PEW score: it was statistically significant with AUC = .892, cut off values &gt; 5, sensitivity = 79%, specificity = 80.56%, PPV =30% and NPV = 96.7%. -For pSOFA score: it was statistically significant with AUC = .931, cut off values &gt; 14, sensitivity = 85%, specificity = 86.11%, PPV =37.5%, and NPV = 96.9%. All ASA, PEW, and pSOFA were statistically significant as univariate but none was significant as multivariate.&#x0D; Conclusions: ASA score, pSOFA score and PEWS score were significant predictor to length of stay (&gt;21 days). ASA score, PEW score and pSOFA score were significant as predictor to mortality. ASA score and PEWS score were highly significant as to predict PICU Admission postop. PEWS score was highly significant as to predict PICU Admission postop. ASA, PEWs, and pSOFA were predictors for LOS for more than 21 days, predictors of mortality and predictors for PICU admission Postop. Decreased platelets and increased WBCs, urea, creatinine, AST, and RBG were significant with HiR. LqSOFA is a simple variable bedside tool for identifying septic patients at high risk for poor outcomes.

Immune checkpoints expression patterns in early-stage triple-negative breast cancer predict prognosis and remodel the tumor immune microenvironment.

Currently, targeting immune checkpoint molecules holds great promise for triple-negative breast cancer (TNBC). However, the expression landscape of immune checkpoint genes (ICGs) in TNBC remains largely unknown. Herein, we systematically investigated the ICGs expression patterns in 422 TNBC samples. We evaluated the ICGs molecular typing based on the ICGs expression profile and explored the associations between ICGs molecular subtypes and tumor immune characteristics, clinical significance, and response to immune checkpoint inhibitors (ICIs). Two ICGs clusters and two ICGs-related gene clusters were determined, which were involved in different survival outcomes, biological roles and infiltration levels of immune cells. We established a quantification system ICGs riskscore (named IRS) to assess the ICGs expression patterns for individuals. TNBC patients with lower IRS were characterized by increased immune cell infiltration, favorable clinical outcomes and high sensitivity to ICIs therapy. We also developed a nomogram model combining clinicopathological variables to predict overall survival in TNBC. Genomic feature analysis revealed that high IRS group presented an increased tumor mutation burden compared with the low IRS group. Collectively, dissecting the ICGs expression patterns not only provides a new insight into TNBC subtypes but also deepens the understanding of ICGs in the tumor immune microenvironment.