The predictive value of the Kampala Trauma Score (KTS) in the outcome of multi-traumatic patients compared to the estimated Injury Severity Score (eISS).

PURPOSE: The classification of trauma patients in emergency settings is a constant challenge for physicians. However, the Injury Severity Score (ISS) is widely used in developed countries, it may be difficult to perform it in low- and middle-income countries (LMIC). As a result, the ISS was calculated using an estimated methodology that has been described and validated in a high-income country previously. In addition, a simple scoring tool called the Kampala Trauma Score (KTS) was developed recently. The aim of this study was to compare the diagnostic accuracy of KTS and estimated ISS (eISS) in order to achieve a valid and efficient scoring system in our resource-limited setting. METHODS: We conducted a cross-sectional study between December 2020 and March 2021 among the multi-trauma patients who presented at the emergency department of Imam Reza hospital, Tabriz, Iran. After obtaining informed consent, all data including age, sex, mechanism of injury, GCS, KTS, eISS, final outcome (including death, morbidity, or discharge), and length of hospital stay were collected and entered into SPSS version 27.0 and analyzed. RESULTS: 381 multi-trauma patients participated in the study. The area under the curve for prediction of mortality (AUC) for KTS was 0.923 (95%CI: 0.888-0.958) and for eISS was 0.910 (95% CI: 0.877-0.944). For the mortality, comparing the AUCs by the Delong test, the difference between areas was not statistically significant (p value = 0.356). The diagnostic odds ratio (DOR) for the prediction of mortality KTS and eISS were 28.27 and 32.00, respectively. CONCLUSION: In our study population, the KTS has similar accuracy in predicting the mortality of multi-trauma patients compared to the eISS.

Wortmannin Inhibits Cell Growth and Induces Apoptosis in Colorectal Cancer Cells by Suppressing the PI3K/AKT Pathway.

BACKGROUND: Colorectal cancer (CRC) remains a significant contributor to mortality, often exacerbated by metastasis and chemoresistance. Novel therapeutic strategies are imperative to enhance current treatments. The dysregulation of the PI3K/Akt signaling pathway is implicated in CRC progression. This study investigates the therapeutic potential of Wortmannin, combined with 5-fluorouracil (5-FU), to target the PI3K/Akt pathway in CRC. METHODS: Anti-migratory and antiproliferative effects were assessed through wound healing and MTT assays. Apoptosis and cell cycle alterations were evaluated using Annexin V/Propidium Iodide Apoptosis Assay. Wortmannin's impact on the oxidant/antioxidant equilibrium was examined via ROS, SOD, CAT, MDA, and T-SH levels. Downstream target genes of the PI3K/AKT pathway were analyzed at mRNA and protein levels using RTPCR and western blot, respectively. RESULTS: Wortmannin demonstrated a significant inhibitory effect on cell proliferation, modulating survivin, cyclinD1, PI3K, and p-Akt. The PI3K inhibitor attenuated migratory activity, inducing E-cadherin expression. Combined Wortmannin with 5-FU induced apoptosis, increasing cells in sub-G1 via elevated ROS levels. CONCLUSION: This study underscores Wortmannin's potential in inhibiting CRC cell growth and migration through PI3K/Akt pathway modulation. It also highlights its candidacy for further investigation as a promising therapeutic option in colorectal cancer treatment.

Interplay between LncRNA/miRNA and TGF-ß Signaling in the Tumorigenesis of Gynecological Cancer.

Gynecologic cancers are among the most common malignancies with aggressive features and poor prognosis. Tumorigenesis in gynecologic cancers is a complicated process that is influenced by multiple factors, including genetic mutations that activate various oncogenic signaling pathways, including the TGF-ß pathway. Aberrant activation of TGF-ß signaling is correlated with tumor recurrence and metastasis. It has been shown that non-coding RNAs (ncRNAs) have crucial effects on cancer cell proliferation, migration, and metastasis. Upregulation of various ncRNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs), has been reported in several tumors, like cervical, ovarian, and endometrial cancers, but their cellular mechanisms remain to be investigated. Thus, recognizing the role of ncRNAs in regulating the TGF-ß pathway may provide novel strategies for better treatment of cancer patients. The present study summarizes recent findings on the role of ncRNAs in regulating the TGF-ß signaling involved in tumor progression and metastasis in gynecologic cancers.

Regulatory role of miRNAs on Wnt/ß-catenin signaling in tumorigenesis of glioblastoma.

Glioblastoma (GBM) is one of the most aggressive tumors in the brain with high mortality worldwide. Despite recent advances in therapeutic strategies, the survival rate remains low in patients with GBM. The pathogenesis of GBM is a very complicated process involving various genetic mutations affecting several oncogenic signaling pathways like Wnt/ß-catenin axis. Overactivation of the Wnt/ß-catenin signaling pathway is associated with decreased survival and poor prognosis in patients with GBM. MicroRNAs (miRNAs) were shown to play important roles in the regulation of cell proliferation, differentiation, apoptosis, and tumorigenesis by modulating the expression of their target genes. Aberrant expression of miRNAs were reported in various human malignancies including GBM, breast, colorectal, liver, and prostate cancers, but little is known about their cellular mechanisms. Therefore, recognition of the expression profile and regulatory effects of miRNAs on the Wnt/ß-catenin pathway may offer a novel approach for the classification, diagnosis, prognosis, and treatment of patients with GBM. This review summarizes previous data on the modulatory role of miRNAs on the Wnt/ß-catenin pathway implicated in tumorigenesis of GBM.

Vactosertib potently improves anti-tumor properties of 5-FU for colon cancer.

BACKGROUND: Several studies have shown that the TGF-ß signaling pathway plays a critical role in colorectal cancer (CRC) pathogenesis. The aim of the current study is to investigate the therapeutic potential of Vactosertib (EW-7197), a selective inhibitor of TGF-ß receptor type I, either alone or in combination with the standard first-line chemotherapeutic treatment, 5-Fluorouracil (5-FU), in CRC progression in both cellular and animal models. METHODS: Real-Time PCR, Zymography, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) tissue staining, and Flow cytometry techniques were applied to determine the anti-tumor properties of this novel TGF-ß inhibitor in in vitro (CT-26 cell line) and in vivo (inbred BALB/C mice) samples. RESULTS: Our findings showed that Vactosertib decreased cell proliferation and induced spheroid shrinkage. Moreover, this inhibitor suppressed the cell cycle and its administration either alone or in combination with 5-FU induced apoptosis by regulating the expression of p53 and BAX proteins. It also improved 5-FU anti-cancer effects by decreasing the tumor volume and weight, increasing tumor necrosis, and regulating tumor fibrosis and inflammation in an animal model. Vactosertib also enhanced the inhibitory effect of 5-FU on invasive behavior of CRC cells by upregulating the expression of E-cadherin and inhibiting MMP-9 enzymatic activity. CONCLUSION: This study demonstrating the potent anti-tumor effects of Vactosertib against CRC progression. Our results clearly suggest that this inhibitor could be a promising agent reducing CRC tumor progression when administered either alone or in combination with standard treatment in CRC patients.

The recent insight in the release of anticancer drug loaded into PLGA microspheres.

Cancer is a series of diseases leading to a high rate of death worldwide. Microspheres display specific characteristics that make them appropriate for a variety of biomedical purposes such as cancer therapy. Newly, microspheres have the potentials to be used as controlled drug release carriers. Recently, PLGA-based microspheres have attracted exceptional attention relating to effective drug delivery systems (DDS) because of their distinctive properties for a simple preparation, biodegradability, and high capability of drug loading which might be increased drug delivery. In this line, the mechanisms of controlled drug release and parameters that influence the release features of loaded agents from PLGA-based microspheres should be mentioned. The current review is focused on the new development of the release features of anticancer drugs, which are loaded into PLGA-based microspheres. Consequently, future perspective and challenges of anticancer drug release from PLGA-based microspheres are mentioned concisely.

Dual targeting of TGF-ß and PD-L1 inhibits tumor growth in TGF-ß/PD-L1-driven colorectal carcinoma.

Immunosuppressive factors within the tumor microenvironment (TME), such as Transforming growth factor beta (TGF-ß), constitute a crucial hindrance to immunotherapeutic approaches in colorectal cancer (CRC). Furthermore, immune checkpoint factors (e.g., programmed death-ligand 1 [PD-L1]) inhibit T-cell proliferation and activation. To cope with the inhibitory effect of immune checkpoints, the therapeutic value of dual targeting PD-L1 and TGF-ß pathways via M7824 plus 5-FU in CRC has been evaluated. Integrative-systems biology approaches and RNAseq were used to assess the differential level of genes associated with 88 metastatic-CRC patients. The level of PD-L1 and TGF-ß was evaluated in a validation cohort. The anti-proliferative, migratory, and apoptotic effects of PD-L1/TGF-ß inhibitor, M7824, were assessed by MTT, wound-healing assay, and flow cytometry. Anti-tumor activity was assessed in a xenograft model, followed by biochemical studies and histological staining, and gene/protein expression analyses by RT-PCR and ELISA/IHC. The result of differentially expressed genes (DEGs) analysis showed 1268 upregulated and 1074 downregulated genes in CRC patients. Among the highest scoring genes and dysregulated pathways associated with CRC, PD-L1, and TGF-ß were identified and further validated in 92 CRC patients. Targeting of PD-L1-TGF-ß inhibited cell growth and migration, associated with modulation of CyclinD1 and MMP9. Furthermore, M7824 inhibited tumor growth via targeting TGF-ß and PD-L1 pathways, resulting in modulation of inflammatory response and fibrosis via TNF-α/IL6/CD4-8 and COL1A1/1A2, respectively. In conclusion, our data illustrated that co-targeting PD-L1 and TGF-ß pathways increased the effect of Fluorouracil (5-FU) and reduced the tumor growth in PD-L1/TGF-ß expressing tumors, providing a new therapeutic option in the treatment of CRC.

Fenugreek Seed Extract Regulates Human Umbilical Vein Endothelial Cell Angiogenesis and Proliferation via the PI3K/Akt/Cyclin D1 Pathway.

The significance of angiogenesis in tumour progression has been widely documented. Hence, the identification of anti-angiogenic agents with fewer common side effects would be valuable in cancer therapy. In this study, we evaluated the anti-angiogenic and anti-proliferative effects of a hydro-alcoholic extract of fenugreek seed (HAEF) on human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cells were treated with various concentrations of HAEF and the half-maximal inhibitory concentration (IC50) value was estimated by using the MTT assay. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase enzyme (MMP-2 and MMP-9) gene expression profiles were evaluated by using quantitative RT-PCR (qRT-PCR). Moreover, MMP activities and PI3K, Akt and cyclin D1 protein expression levels were evaluated by gel zymography and Western blotting, respectively. HAEF reduced HUVEC viability, with an IC50 value of 200 µg/ml. The qRT-PCR results demonstrated that treatment with HAEF markedly reduced MMP-2/MMP-9, VEGF and bFGF gene expression, as compared to the control group. We also found that MMP-2/MMP-9 enzyme activity and PI3K/Akt/cyclin D1 protein expression were notably decreased in cells treated with HAEF. Our results suggest that HAEF can potentially inhibit angiogenesis, and also affect cellular proliferation by targeting the PI3K/Akt/cyclin D1 pathway. Thus, fenugreek seed extract merits further investigation as a source of compounds with anti-cancer properties.

The Interplay between Noncoding RNAs and p21 Signaling in Gastrointestinal Cancer: From Tumorigenesis to Metastasis.

Non-coding RNAs (ncRNAs) are emerging as important regulators in various pathological conditions, including human cancers. NcRNAs exert potentially crucial effects on cell cycle progression, proliferation, and invasion in cancer cells by targeting various cell cycle-related proteins at transcriptional and post-transcriptional levels. As one of the key cell cycle regulatory proteins, p21 is involved in various processes, including the cellular response to DNA damage, cell growth, invasion, metastasis, apoptosis, and senescence. P21 has been shown to have either a tumor-suppressive or oncogenic effect depending on the cellular localization and posttranslational modifications. P21 exerts a significant regulatory effect on both G1/S and G2/M checkpoints by regulating the function of cyclin-dependent kinase enzymes (CDKs) or interacting with proliferating cell nuclear antigen (PCNA). P21 has an important effect on the cellular response to DNA damage by separating DNA replication enzymes from PCNA and inhibiting DNA synthesis resulting in G1 phase arrest. Furthermore, p21 has been shown to negatively regulate the G2/M checkpoint through the inactivation of cyclin-CDK complexes. In response to any cell damage caused by genotoxic agents, p21 exerts its regulatory effects by nuclear preservation of cyclin B1-CDK1 and preventing their activation. Notably, several ncRNAs, including lncRNAs and miRNAs, have been shown to be involved in tumor initiation and progression through the regulation of the p21 signaling axis. In this review, we discuss the miRNA/lncRNA-dependent mechanisms that regulate p21 and their effects on gastrointestinal tumorigenesis. A better understanding of the regulatory effects of ncRNAs on the p21 signaling may help to discover novel therapeutic targets in gastrointestinal cancer.

Non-hospital healthcare center's preparedness assessment toolbar for providing basic emergency care: a sequential exploratory mixed-method study.

BACKGROUND: Basic emergency management in urban and rural areas is a critical challenge, which can affect the pre-hospital mortality rate. Therefore, Non-hospital Healthcare Center (NHHC) must be prepared to manage such emergency cases that may occur in the geographic area where these centers act. The main aim of the study was to develop and validate an toolbar for NHHCs' preparedness to provide initial emergency care. METHODS: This study was designed based on a sequential exploratory mixed- method in two phases, in each of which there are three steps. In the phase I, the literature systematic review and qualitative methods (Focus Group Discussions (FGDs) and Semi-Structured Interviews (SSIs)) were applied to identify the domains and items. In the phase II, content validity, feasibility, and reliability of the toolbar were performed. Content validity was assessed using a modified Kappa coefficient based on clarity and relevance criteria. Feasibility of the toolbar was randomly assessed through its implementation in 10 centers in Tabriz. Reliability was randomly assessed in a pilot on 30 centers. Reliability was assessed by measuring internal consistency, test-retest reliability, and inter-rater agreement. The main statistical methods for assessing reliability include Cronbach's alpha, Intra-class Correlation Coefficient, and Kendal's Tau-b. All the statistical analyses were performed using Stata 14. RESULTS: In the phase I, primary version of the toolbar containing 134 items related to assessing the preparedness of NHHCs was generated. In the phase II, item reduction was applied and the final version of the toolbar was developed containing 126 items, respectively. These items were classified in 9 domains which include: "Environmental Infrastructures of Centers", "Protocols, Guidelines and Policies", "Medical Supplies and Equipment", "Emergency Medicines", "Human Resources", "Clinical Interventions", "Maintenance of equipment", "Medicine Storage Capability", and "Management Process". The toolbar had acceptable validity and reliability. CONCLUSIONS: This study provided a standard and valid toolbar that can be used to assess the preparedness of NHHCs to deliver initial emergency care.

The protective effect of curcumin on thrombin-induced hyper-permeability.

Objective: Thrombin is a proinflammatory and pro-coagulant agent which is upregulated in several human diseases. Thrombin has a critical role in promoting cell proliferation and microvascular leakage in malignant cells, resulting in cancer growth and progression. Here, we explored the potential therapeutic value of curcumin on permeability induced by thrombin in mice. Materials and Methods: To assess the activity of curcumin on thrombin-induced vascular permeability mice model, C57BL / 6 mice were randomly divided into four groups: (1) control (2) Thrombin (3) Thrombin + Curcumin and (4) Thrombin + Metformin. Thirty minutes after treatment, Evans blue was injected intravenously through the tail vein to mice. Then, animals were sacrificed and the dye was extracted from the skin tissue by incubation with formamide. Heatmap and correlation map were generated and protein-protein interaction network of the hub genes was drawn by Cytoscape software. Results: Hub DEG expression rate showed that Heat shock protein a1 (Hspa1) family (comprised of HSPa1a, b, and HSPa5), caspase 3, and minichromosome maintenance complex component 2 were overexpressed after treatment with curcumin. Functional modules of curcumin enriched through Enrich gene biological process and revealed positive association of gene expression of apoptosis process with the therapy. Curcumin was also found to reduce leucocyte migration in murine tissues. Additionally, treatment with curcumin resulted in downregulation of heat shock proteins and proinflammatory cytokines such as monocyte chemotactic protein 1, interleukin-6 and chemokine (C-X-C motif) ligand 3. Conclusion: Curcumin inhibited the proinflammatory cytokines and inflammatory HSPs in endothelial cells and reduced thrombin-induced barrier destabilization in vivo.

The recent advancement in the PLGA-based thermo-sensitive hydrogel for smart drug delivery.

To date, hydrogels have opened new prospects for potential applications for drug delivery. The thermo-sensitive hydrogels have the great potential to provide more effective and controllable release of therapeutic/bioactive agents in response to changes in temperature. PLGA is a safe FDA-approved copolymer with good biocompatibility and biodegradability. Recently, PLGA-based formulation have attracted a lot of interest for thermo-sensitive hydrogels. Thermo-sensitive PLGA-based hydrogels provide the delivery system with good spatial and temporal control, and have been widely applied in drug delivery. This review is focused on the recent progression of the thermo-sensitive and biodegradable PLGA-based hydrogels that have been reported for smart drug delivery to the different organs. Eventually, future perspectives and challenges of thermo-sensitive PLGA-based hydrogels are discussed briefly.

SARS-CoV-2 infection might be a predictor of mortality in intracerebral hemorrhage.

BACKGROUND: SARS-CoV-2 infection may be associated with uncommon complications such as intracerebral hemorrhage (ICH), with a high mortality rate. We compared a series of hospitalized ICH cases infected with SARS-CoV-2 with a non-SARS-CoV-2 infected control group and evaluated if the SARS-CoV-2 infection is a predictor of mortality in ICH patients. METHODS: In a multinational retrospective study, 63 cases of ICH in SARS-CoV-2 infected patients admitted to 13 tertiary centers from the beginning of the pandemic were collected. We compared the clinical and radiological characteristics and in-hospital mortality of these patients with a control group of non-SARS-CoV-2 infected ICH patients of a previous cohort from the country where the majority of cases were recruited. RESULTS: Among 63 ICH patients with SARS-CoV-2 infection, 23 (36.5%) were women. Compared to the non-SARS-CoV-2 infected control group, in SARS-CoV-2 infected patients, ICH occurred at a younger age (61.4 ± 18.1 years versus 66.8 ± 16.2 years, P = 0.044). These patients had higher median ICH scores ([3 (IQR 2-4)] versus [2 (IQR 1-3)], P = 0.025), a more frequent history of diabetes (34% versus 16%, P = 0.007), and lower platelet counts (177.8 ± 77.8 × 109/L versus 240.5 ± 79.3 × 109/L, P < 0.001). The in-hospital mortality was not significantly different between cases and controls (65% versus 62%, P = 0.658) in univariate analysis; however, SARS-CoV-2 infection was significantly associated with in-hospital mortality (aOR = 4.3, 95% CI: 1.28-14.52) in multivariable analysis adjusting for potential confounders. CONCLUSION: Infection with SARS-CoV-2 may be associated with increased odds of in-hospital mortality in ICH patients.

Interplay between lncRNA/miRNA and Wnt/ß-catenin signaling in brain cancer tumorigenesis.

Brain cancers are among the most aggressive malignancies with high mortality and morbidity worldwide. The pathogenesis of brain cancers is a very complicated process involving various genetic mutations affecting several oncogenic signaling pathways like Wnt/ß-catenin axis. Uncontrolled activation of this oncogenic signaling is associated with decreased survival rate and poor prognosis in cancer patients. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were shown to play important roles in regulating cell proliferation, differentiation, and apoptosis by regulating the expression of their target genes. Aberrant expression of these non-coding RNAs (ncRNAs) was reported in many human cancers, including glioblastoma, medulloblastoma, meningioma, and pituitary adenoma. Multiple lncRNAs were shown to participate in brain tumor pathogenesis by targeting Wnt signaling regulatory miRNAs. SNHG7/miR-5095, PCAT6/miR-139-3p, SNHG6/miR-944, SNHG1/ miR-556-5p, SNHG17/ miR-506-3p, LINC00702/miR-4652-3p, DLGAP1-AS1/miR-515-5p, HOTAIR/miR-1, HOTAIR/miR-206, CRNDE/miR-29c-3p, AGAP2-AS1/ miR-15a/b-5p, CLRN1-AS1/miR-217, MEG3/miR-23b-3p, and GAS5/miR-27a-5p are identified lncRNA/miRNA pairs that are involved in this process. Therefore, recognition of the expression profile and regulatory role of ncRNAs on the Wnt signaling may offer a novel approach to the diagnosis, prognosis, and treatment of human cancers. This review summarizes previous data on the modulatory role of lncRNAs/miRNAs on the Wnt/ß-catenin pathway implicated in tumor growth, EMT, metastasis, and chemoresistance in brain cancers.

Prevalence and Risk Factors of Anemia in the MASHAD Cohort Study.

BACKGROUND: Anemia is a serious public health problem which may be associated with cardiovascular diseases (CVDs) and brain damage. This survey aims to determine the prevalence of anemia and its association with demographic and biochemical factors and metabolic syndrome in a human sample derived from the MASHAD cohort study. METHODS: This survey was conducted on a sub-sample of 9847 individuals aged 35 to 65 as part of the MASHAD cohort study. Demographic characteristics and biochemical and anthropometrics indices were recorded. Data were analyzed using SPSS version 20. RESULTS: Anemia was seen in 11.5% of the population. Anemia was significantly more prevalent in younger subject (P<0.001), females (P<0.001) and those with elevated body mass index (BMI) (P<0.001). Mean high-density lipoprotein (HDL) was higher in anemic participant (P=0.032). The incidence of anemia was significantly lower in smokers (P<0.001) and also participant with hypertension (HTN) (P<0.001), diabetes mellitus (DM) (P<0.001) and metabolic syndrome (MetS) (P<0.001). Mean FBG (P<0.001), TG (P<0.001), total cholesterol (P<0.001), LDL (P<0.001) and uric acid (P<0.001) were significantly lower in anemic subjects. Cholesterol, MetS, low-density lipoprotein (LDL), BMI, uric acid, diabetes mellitus and also TG remained significantly different after multivariate analysis between anemic and healthy participants. CONCLUSION: The studied population had a lower prevalence of anemia compared to the previous WHO report for Iranians. Iron deficiency is recognized as the most important cause of anemia in Iran; however, further investigations will be need to confirm this pattern. We demonstrated that anemia is adversely associated with MetS and DM.

The interplay between non-coding RNAs and Wnt/ß-catenin signaling pathway in urinary tract cancers: from tumorigenesis to metastasis.

Non-coding RNAs (ncRNAs) are emerging as important regulators in various pathological conditions including tumorigenesis, metastasis, and drug resistance in human cancers. Oncogenic or tumor suppressor ncRNAs exert prominent effects on cell proliferation, migration and invasion in cancer cells through modulating various signaling pathways including Wnt/ß-catenin. Upregulation of the oncogenic Wnt/ß-catenin pathway was reported to be implicated in multiple human cancers including breast, liver, colorectal, and urothelial cancers. Therefore, identifying interactions between ncRNAs and canonical Wnt signaling components may represent novel therapeutic targets for better treatment and management of cancer. In this review, we summarized the recent findings about miRNA/lncRNA-dependent mechanisms that regulate Wnt/ß-catenin signaling involved in tumorigenesis and metastasis of urinary tract cancers.

Clinical and Laboratory Predictors of COVID-19-Related In-hospital Mortality; a Cross-sectional Study of 1000 Cases.

Introduction: Identifying patients at risk for mortality and using appropriate treatment for each patient based on their situation could be an effective strategy in improving their outcome. This study aimed to evaluated the predictors of COVID-19 in-hospital mortality. Methods: This descriptive cross-sectional study was conducted on all adult COVID-19 patients who were managed in Imam-Reza and Sina Hospitals, Tabriz, Iran, from November 2020 until December 2021. The demographic, clinical, and laboratory characteristics of patients were evaluated and predictors of in-hospital mortality were identified using logistic regression model. Results: 1000 patients with the mean age of 56.34 ± 18.00 years were studied (65.7% male). There were significant associations between COVID-19 in-hospital mortality and hospitalization above five days (p = 0.001), white blood cell count (WBC) > 4000 Cells*103/mL (p < 0.01), aspartate aminotransferase (AST) above 40 IU/L (p = 0.001), alanine transaminase (ALT) above 40 IU/L (p = 0.001), creatinine above 1.4 mg/dL (p = 0.007), urea above 100 mg/dL (p = 0.024), and SaO2 below 80% (p = 0.001). Hospital stay above five days (OR: 3.473; 95%CI: 1.272 - 9.479; p = 0.15), AST above 40 IU/L (OR: 0.269, 95%CI: 0.179 - 0.402; p = 0.001), creatinine above 1.4 mg/dL (OR: 0.529; 95%CI: 0.344 - 0.813; p = 0.004), urea above 100 mg/dL (OR: 0.327, 95%CI: 0.189 - 0.567; p = 0.001), and SaO2 below 80% (OR: 8.754, 95%CI: 5.413 - 14.156; p = 0.001) were among the independent predictors of COVID-19 in-hospital mortality. Conclusion: The mortality rate of patients with COVID-19 in our study was 29.9%. Hospitalization of more than five days, AST above 40 IU/L, creatinine above 1.4 mg/dL, urea above 100 mg/dL and SaO2 < 80% were independent risk factors of in-hospital mortality among patients with COVID-19.

Inhibition of the Wnt/b-catenin pathway using PNU-74654 reduces tumor growth in in vitro and in vivo models of colorectal cancer.

BACKGROUND: Colorectal-cancer (CRC) is amongst the most lethal-cancers, mainly due to its metastatic spread and drug chemoresistance. Hence there is a need for new approaches to either increase the efficacy of current therapy or introduce new therapies that have greater efficacy. There is increasing evidence that dysregulation of WNT-signaling-pathway plays an essential role in the development and prognosis of CRC. Here we have investigated the therapeutic potential of targeting the WNT/b-catenin pathway using a novel Wnt/b-catenin inhibitor, PNU-74654, in combination with 5-FU in CRC. METHODS: The anti-proliferative-effect of PNU-74654 was evaluated in two-/three-dimensional cell models. The activity of agents on cell growth, migration, invasion, cell cycle and apoptosis was evaluated by MTT, wound healing assay, invasion, FACS, and annexin V staining, respectively. The oxidant/antioxidant levels were also assessed by determining the level of MDA, SOD, as well as using the DCFH-DA assay. We used a xenograft model of CRC to investigate PNU-74654 activity alone and in combination with 5-FU follow by histological staining and biochemical and gene expression analyses by RT-PCR and western blot. RESULTS: PNU-74654 inhibited cell-growth and synergistically affected the anti-tumor properties of 5-FU via modulation of Cyclin D1 and survivin. This agent inhibited the migration/invasion of colorectal cancer cells via perturbation of E-cadherin. Furthermore, PNU-74654 inhibited the tumor growth, which was more pronounced using the PNU-74654 plus 5-FU combination via induction of reactive oxygen species, down-regulation of SOD and modulation of MCP-1, P53, TNF-α. CONCLUSIONS: Our finding demonstrated that PNU-74654 can target Wnt-pathway, interfere with cell-proliferation, induced-cell death, reduced-migration and interact with 5-FU, supporting further investigations on this therapeutic-approach for colorectal cancer.

Prognostic Value of Platelet to Lymphocyte Ratio in Sepsis: A Systematic Review and Meta-analysis.

The goal of this study was to conduct a systematic review of the literature on the relationship between peripheral blood platelet to lymphocyte ratio (PLR) and mortality in sepsis and to integrate the findings in a meta-analysis. An electronic search of three main databases was performed: PubMed, Embase, and Scopus on 19 December 2021. Finally, 16 studies comprising 2403 septic patients, including 1249 survivors and 1154 nonsurvivors, were included in this meta-analysis. We found that PLR levels were significantly higher in nonsurvivors than in survivors (random effect model: SMD = 0.72, 95% CI; 0.35-1.10, p < 0.001). However, significant heterogeneity was observed across the studies (I 2 = 94.1%, p < 0.01). So, we used random effect model in our meta-analysis. In the subgroup analysis, according to mortality time, patients deceased during one month after sepsis had elevated levels of PLR compared to survivors (SMD = 1.03, 95% CI = 0.15-1.92, p = 0.22). However, in-hospital mortality was not associated with PLR level (SMD = 0.41, 95% CI = -0.18-0.99, p = 0.175). Our findings support PLR to be a promising biomarker that can be readily integrated into clinical settings to aid in the prediction and prevention of sepsis mortality.

Designing and conducting initial application of a performance assessment model for in-hospital trauma care.

BACKGROUND: Trauma is a major cause of death worldwide, especially in Low and Middle-Income Countries (LMIC). The increase in health care costs and the differences in the quality of provided services indicates the need for trauma care evaluation. This study was done to develop and use a performance assessment model for in-hospital trauma care focusing on traffic injures. METHODS: This multi-method study was conducted in three main phases of determining indicators, model development, and model application. Trauma care performance indicators were extracted through literature review and confirmed using a two-round Delphi survey and experts' perspectives. Two focus group discussions and 16 semi-structured interviews were conducted to design the prototype. In the next step, components and the final form of the model were confirmed following pre-determined factors, including importance and necessity, simplicity, clarity, and relevance. Finally, the model was tested by applying it in a trauma center. RESULTS: A total of 50 trauma care indicators were approved after reviewing the literature and obtaining the experts' views. The final model consisted of six components of assessment level, teams, methods, scheduling, frequency, and data source. The model application revealed problems of a selected trauma center in terms of information recording, patient deposition, some clinical services, waiting time for deposit, recording medical errors and complications, patient follow-up, and patient satisfaction. CONCLUSION: Performance assessment with an appropriate model can identify deficiencies and failures of services provided in trauma centers. Understanding the current situation is one of the main requirements for designing any quality improvement programs.