MicroRNA-155 acts as a potential prognostic and diagnostic factor in patients with ankylosing spondylitis by modulating SOCS3.

BACKGROUND: Ankylosing spondylitis (AS) is a progressive inflammatory disease. Our primary objective was to explore the role of miR-155 and its targeted factors in AS pathogenesis. METHODS AND RESULTS: PBMCs were isolated from 30 AS patients and 30 healthy individuals using the Ficoll-hypaque isolation approach. The expression of miR-155 and its associated targets, including Suppressor Of Cytokine Signaling 3 (SOCS3), STAT3, and IL-21, were determined using qT-qPCR. Then, PBMCs were cultured, and the effect of miR-155, SOCS3 siRNA (to suppress its expression), pEFSOCS3 (enforced expression), and their combination were investigated by qRT-PCR and western blotting. We also treated the cultured PBMCs with Brefeldin A, a potent inhibitor of cytokine secretion, to determine its effect on IL-21 expression and secretion. In addition, the association between miR-155 and patients' clinicopathological features was examined. The results showed that miR-155, IL-21, and STAT3 were increased in patients with AS, while SOCS3 had decreasing expression trend. It was also determined that miR-155 alleviates SOCS3 expression and increases IL-21 and STAT3 expression; it had a prominent effect when combined with SOCS3 siRNA. Besides, we showed that simultaneous transfection of miR-155 and pEFSOCS3 had no significant effect on IL-21 and STAT3 expression, revealing that miR-155 could alleviate the enforced expression of SOCS3. It was also proven that Brefledine A led to IL-21 up-regulation or accumulation while relieving its secretion. Also, a significant correlation between miR-155 and pathological features of AS patients was found. CONCLUSION: miR-155 acts as a potential prognostic and diagnostic biomarker. Its up-regulation leads to the down-regulation of SOCS3 and increased expression of IL-21 and STAT3 as characteristic of TH-17 lymphocytes, leading to worsening inflammatory conditions in patients with AS.

TRIM8: a double-edged sword in glioblastoma with the power to heal or hurt.

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor and one of the most lethal central nervous system tumors in adults. Despite significant breakthroughs in standard treatment, only about 5% of patients survive 5 years or longer. Therefore, much effort has been put into the search for identifying new glioma-associated genes. Tripartite motif-containing (TRIM) family proteins are essential regulators of carcinogenesis. TRIM8, a member of the TRIM superfamily, is abnormally expressed in high-grade gliomas and is associated with poor clinical prognosis in patients with glioma. Recent research has shown that TRIM8 is a molecule of duality (MoD) that can function as both an oncogene and a tumor suppressor gene, making it a "double-edged sword" in glioblastoma development. This characteristic is due to its role in selectively regulating three major cellular signaling pathways: the TP53/p53-mediated tumor suppression pathway, NFKB/NF-κB, and the JAK-STAT pathway essential for stem cell property support in glioma stem cells. In this review, TRIM8 is analyzed in detail in the context of GBM and its involvement in essential signaling and stem cell-related pathways. We also discuss the basic biological activities of TRIM8 in macroautophagy/autophagy, regulation of bipolar spindle formation and chromosomal stability, and regulation of chemoresistance, and as a trigger of inflammation.

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.

In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.

Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): a rapidly evolving strategy.

Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy has become a game-changing therapeutic approach revolutionizing the treatment setting of human malignancies, such as renal cell carcinoma (RCC). Despite the remarkable clinical activity of anti-PD-1 or anti-PD-L1 monoclonal antibodies, only a small portion of patients exhibit a positive response to PD-1/PD-L1 blockade therapy, and the primary or acquired resistance might ultimately favor cancer development in patients with clinical responses. In light of this, recent reports have signified that the addition of other therapeutic modalities to PD-1/PD-L1 blockade therapy might improve clinical responses in advanced RCC patients. Until, combination therapy with PD-1/PD-L1 blockade therapy plus cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitor (ipilimumab) or various vascular endothelial growth factor receptors (VEGFRs) inhibitors axitinib, such as axitinib and cabozantinib, has been approved by the United States Food and Drug Administration (FDA) as first-line treatment for metastatic RCC. In the present review, we have focused on the therapeutic benefits of the PD-1/PD-L1 blockade therapy as a single agent or in combination with other conventional or innovative targeted therapies in RCC patients. We also offer a glimpse into the well-determined prognostic factor associated with the clinical response of RCC patients to PD-1/PD-L1 blockade therapy.

A comprehensive review about the utilization of immune checkpoint inhibitors and combination therapy in hepatocellular carcinoma: an updated review.

A pharmacological class known as immune checkpoint inhibitors (ICIs) has been developed as a potential treatment option for various malignancies, including HCC. In HCC, ICIs have demonstrated clinically significant advantages as monotherapy or combination therapy. ICIs that target programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1), as well as cytotoxic T lymphocyte antigen 4 (CTLA-4), have made significant advances in cancer treatment. In hepatocellular carcinoma (HCC), several ICIs are being tested in clinical trials, and the area is quickly developing. As immunotherapy-related adverse events (irAEs) linked with ICI therapy expands and gain worldwide access, up-to-date management guidelines become crucial to the safety profile of ICIs. This review aims to describe the evidence for ICIs in treating HCC, emphasizing the use of combination ICIs.

Umbilical cord mesenchymal stem cells and breast cancer: a good therapeutic candidate or not? A minireview.

Breast cancer (BC), as the most common cancer among women, affects a great number of subjects around the world. This heterogenic disease is divided into several types and subtypes, and each subtype has various phenotypes and genotypes. Against BC, several options have been proposed, such as surgery, radiotherapy, and chemotherapeutic agents. However, these approaches may have detrimental effects on health and life quality of patients. Hence, harnessing a therapeutic tool with high effectiveness and low side effects is required. Recently, mesenchymal stem cells (MSCs) have created a new window to treat various disorders, like cancer, and among these, umbilical cord (UC)-derived MSCs have acquired much interest due to their advantages. Therefore, in this narrative review, the influences of UC-derived MSCs on BC were reviewed and summarized with a focus on the molecular mechanisms involved in its pathogenesis and treatment.

Microbiota-Pain Association; Recent Discoveries and Research Progress.

The relationship between gut microbiota and pain, such as visceral pain, headaches (migraine), itching, prosthetic joint infection (PJI), chronic abdominal pain (CAP), joint pain, etc., has received increasing attention. Several parts of the evidence suggest that microbiota is one of the most important pain modulators and they can regulate pain in the central and peripheral nervous systems. Any alteration in microbiota by diet or antibiotics mediation may characterize a novel therapeutic strategy for pain management. The present study includes the most up-to-date and influential scientific findings on the association of microbiota with pain, despite the fact that the underlying mechanism is not identified in most cases. According to recent research, identifying the molecular mechanisms of the microbiota-pain pathway can have a unique perspective in treating many diseases, even though there is a long way to reach the ideal point. This study will stress the influence of microbiota on the common diseases that can stimulate the pain with a focus on underlying mechanisms.

Quercetin and Osteoarthritis: A Mechanistic Review on the Present Documents.

BACKGROUND: Osteoarthritis (OA), as one of the chronic debilitating conditions, affects 15% of people globally and is linked with serious problems, such as cardiovascular diseases, metabolic syndrome, and autoimmune inflammatory disorders. The current therapeutic options for this disease include nonsteroidal anti-inflammatory drugs, surgery, gene therapy, intrasynovial gel injection, and warm needle penetration. However, these approaches may be accompanied by considerable side effects, high costs, and some limitations for patients. Thus, using an alternative way is needed. SUMMARY: Presently, natural compounds based-therapies, like flavonoids, have acquired much attention in the current era. One of the compounds belonging to the flavonoid family is quercetin, and its therapeutic effects on disorders related to joints and cartilage have been addressed in vivo and in vitro studies. KEY MESSAGES: In this review, we summarized evidence indicating its curative capacity against OA with a mechanistic insight.

SARS-CoV-2 effects on sperm parameters: a meta-analysis study.

AIM: The rapid outbreak of the coronavirus disease 2019 (COVID-19) pandemic posed challenges across different medical fields, especially reproductive health, and gave rise to concerns regarding the effects of SARS-CoV-2 on male infertility, owing to the fact that the male reproductive system indicated to be extremely vulnerable to SARS-CoV-2 infection. Only a small number of studies have investigated the effects of SARS-CoV-2 on male reproduction, but the results are not consistent. So, we performed this meta-analysis to draw a clearer picture and evaluate the impacts of COVID-19 on male reproductive system. METHOD: We searched Embase, Web of Science, PubMed, and Google Scholar databases to identify the potentially relevant studies. Standardized mean difference (SMD) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity testing, sensitivity analysis, and publication bias testing were also performed. RESULTS: A total of twelve studies including 7 case control investigations and 5 retrospective cohort studies were found relevant and chosen for our research. Our result showed that different sperm parameters including semen volume [SMD = - 0.27 (- 0.46, - 1.48) (p = 0.00)], sperm concentration [SMD = - 0.41 (- 0.67, - 0.15) (p = 0.002)], sperm count [SMD = - 0.30 (- 0.44, - 0.17) (p = 0.00)], sperm motility [SMD = - 0.66 (- 0.98, - 0.33) (p = 0.00)], and progressive motility [SMD = - 0.35 (- 0.61, - 0.08) (p = 0.01)] were negatively influenced by SARS-CoV-2 infection. However, sperm concentration (p = 0.07) and progressive motility (p = 0.61) were not found to be significantly associated with SARS-CoV-2 infection in case control studies. No publication bias was detected. CONCLUSION: The present study revealed the vulnerability of semen quality to SARS-CoV-2 infection. Our data showed a strong association of different sperm parameters with SARS-CoV-2 infection. The results suggested that SARS-CoV-2 infection in patients may negatively influence their fertility potential in a short-term period, but more studies are needed to decide about the long-term effects.

Resveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis of randomized controlled trials.

We perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify the effect of resveratrol supplementation on endothelial function. A comprehensive search was performed in electronic databases including PubMed, Scopus, Web of Science, and Cochrane Library up to February 2021 with no limitation in time and language. A meta-analysis of eligible studies was performed using a random-effects model to estimate the pooled effect size of flow-mediated dilation (FMD), intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). In total, 21 arms from 17 studies were included. The meta-analysis results showed that resveratrol significantly change the concentrations of FMD (WMD: 1.43%; 95% CI: 0.98 to 1.88, p < .001) and ICAM-1 (WMD: -7.09 ng/ml, 95% CI: -7.45 to -6.73, p < .001). However, VCAM-1, fibrinogen, and PAI-1 did not change significantly after resveratrol supplementation. In conclusion, the results of this study suggest that resveratrol supplementation can improve endothelial function which could be important, especially in patients with cardiovascular diseases.

Critical role of the long non-coding RNAs (lncRNAs) in radiotherapy (RT)-resistance of gastrointestinal (GI) cancer: Is there a way to defeat this resistance?

Radiotherapy (RT) is a frequently used treatment for cervical cancer, effectively decreasing the likelihood of the disease returning in the same area and extending the lifespan of individuals with cervical cancer. Nevertheless, the primary reason for treatment failure in cancer patients is the cancer cells' resistance to radiation therapy (RT). Long non-coding RNAs (LncRNAs) are a subset of RNA molecules that do not code for proteins and are longer than 200 nucleotides. They have a significant impact on the regulation of gastrointestinal (GI) cancers biological processes. Recent research has shown that lncRNAs have a significant impact in controlling the responsiveness of GI cancer to radiation. This review provides a concise overview of the composition and operation of lncRNAs as well as the intricate molecular process behind radiosensitivity in GI cancer. Additionally, it compiles a comprehensive list of lncRNAs that are linked to radiosensitivity in such cancers. Furthermore, it delves into the potential practical implementation of these lncRNAs in modulating radiosensitivity in GI cancer.

Lymphopenia associated with survivin and its downstream pathway in COVID-19 serving as a potential route in COVID-19 pathogenesis.

PURPOSE: Starting in 2019, coronavirus disease 2019 (COVID-19) caused an epidemic that was growing rapidly and has harmed millions of people globally. It has been demonstrated that survivin regulates lymphocyte survival, a main route involved in COVID-19 pathogenesis. Survivin belongs to the inhibitor of apoptosis protein (IAP) family, and its primary functions comprise regulating mitosis and inhibiting apoptosis. Since lower survivin expression has been shown to increase the sensitivity of lymphocytes to apoptotic induction, we looked into the function of survivin and its corresponding pathways in COVID-19 pathogenesis. MATERIALS AND METHODS: The expression of survivin, X-linked inhibitor of apoptosis protein (XIAP), caspases 3, 7, 9, and poly (ADP-ribose) polymerase (PARP) was evaluated at both mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) derived from healthy donors and patients with severe and moderate COVID-19 by qRT-PCR and Western blotting, respectively. Then, we enforced apoptosis to COVID-19 patient-derived lymphocytes, and the percent was assessed by flow cytometry. RESULTS: Survivin and XIAP were less expressed in PBMCs derived from COVID-19 patients as apoptosis inhibitors than PARP, cleaved-PARP, caspase 9, and cleaved caspases 3 and 7, according to the results of real-time PCR and Western blot analysis. Additionally, according to the flow cytometry results, the down-regulation of survivin served as a potential factor in the lymphocyte depletion observed in patients with COVID-19. CONCLUSION: The role of survivin and its related pathway was first discovered in the development of COVID-19 and may serve as a potential prognostic and therapeutic target.

The therapeutic effects of mesenchymal stem cell (MSCs) exosomes in covid-19 disease; Focusing on dexamethasone therapy.

The study of diseases, specifically their aetiologies, their step-by-step progressions (pathogenesis), and their impact on normal structure and function, is the focus of pathology, a branch of science and medicine. In therapeutic fields, it is critical to decrease significantly elevated levels of proinflammatory cytokines. The immunomodulatory drugs such as dexamethasone have been used in several of inflammatory diseases such as Covid-19. The use of dexamethasone alone or in combination with other drugs or method such as mesenchymal stem cell (MSC) is one of the most up-to-date discussions about Covid-19. In this review, we first examined the effects of dexamethasone as monotherapy on inflammatory cytokines and then examined studies that used combination therapy of dexamethasone and other drugs such as Baricitinib, Tofacitinib and tocilizumab. Also, therapeutic aspects of MSCs are examined in this review.

Targeting programmed cell death protein 1 (PD-1) for treatment of non-small-cell lung carcinoma (NSCLC); the recent advances.

The immune system uses various immune checkpoint axes to adjust responses, support homeostasis, and deter self-reactivity and autoimmunity. Nevertheless, non-small-cell lung carcinoma (NSCLC) can use protective mechanisms to facilitate immune evasion, which leads to potentiated cancer survival and proliferation. In this light, many blocking anti-bodies have been developed to negatively regulate checkpoint molecules, in particular, programmed cell death protein 1 (PD-1) / PD-ligand 1 (L1), and bypass these immune suppressive mechanisms. Meanwhile, anti-PD-1 anti-bodies such as nivolumab, pembrolizumab, cemiplimab, and sintilimab have shown excellent competence in successfully inspiring immune responses versus NSCLC. Accordingly, the United States Food and Drug Administration (FDA) has recently approved nivolumab (alone or in combination with ipilimumab) and pembrolizumab (alone or in combination with chemotherapy) as first-line treatment for advanced NSCLC patients. However, PD-1 blockade monotherapy remains inefficient in more than 60% of NSCLC patients, and many patients don't respond or acquire resistance to this modality. Also, toxicities related to anti-PD-1 anti-body have been progressively identified in clinical trials and oncology practice. Herein, we will outline the clinical benefits of PD-1 blockade therapy alone or in combination with other treatments (e.g., chemotherapy, radiotherapy, anti-angiogenic therapy) in NSCLC patients. Moreover, we will take a glimpse into the recently identified predictive biomarkers to determine patients most likely to suffer serious adverse events to decrease untoward toxicity risk and diminish treatment costs.

Recent advances in pre-conditioned mesenchymal stem/stromal cell (MSCs) therapy in organ failure; a comprehensive review of preclinical studies.

Mesenchymal stem/stromal cells (MSCs)-based therapy brings the reassuring capability to regenerative medicine through their self-renewal and multilineage potency. Also, they secret a diversity of mediators, which are complicated in moderation of deregulated immune responses, and yielding angiogenesis in vivo. Nonetheless, MSCs may lose biological performance after procurement and prolonged expansion in vitro. Also, following transplantation and migration to target tissue, they encounter a harsh milieu accompanied by death signals because of the lack of proper tensegrity structure between the cells and matrix. Accordingly, pre-conditioning of MSCs is strongly suggested to upgrade their performances in vivo, leading to more favored transplantation efficacy in regenerative medicine. Indeed, MSCs ex vivo pre-conditioning by hypoxia, inflammatory stimulus, or other factors/conditions may stimulate their survival, proliferation, migration, exosome secretion, and pro-angiogenic and anti-inflammatory characteristics in vivo. In this review, we deliver an overview of the pre-conditioning methods that are considered a strategy for improving the therapeutic efficacy of MSCs in organ failures, in particular, renal, heart, lung, and liver.

Evaluating Diagnostic Efficiency of Thyroid Imaging Reporting and Data Systems proposed by the American College of Radiology in Surgically Resected Thyroid Nodules.

AIM: Thyroid nodules are one of the most common clinical findings, with a prevalence of 68% in adults. Thyroid cancer is the fifth most common cancer in women. INTRODUCTION: The purpose of this study is to evaluate the diagnostic efficacy of Thyroid Imaging Reporting and Data Systems proposed by the American College of Radiology (ACR-TIRADS) for the diagnosis of malignancy in surgically resected thyroid nodules. METHODS: In this retrospective study, patients who underwent thyroid nodules resected surgically from 2018-2020 were included. Before resection, an ultrasound was performed for TIRADS scores, and after resection histopathology, thyroid mass was obtained. The outcomes of the two systems were statistically compared. RESULTS: The mean age of the 146 included patients was 47.6 ± 14.08 years, of which 109 (74.7%) were female. Based on TIRADS, 47 patients (32.2%) were in TI-RADS TR3, 36 patients (24.7%) were in TIRADS TR2, 34 (23.3%) in TIRADS 4, 24 (16.4%) in TIRADS TR5 and 5 patients (3.4%) were in TIRADS TR1. The overall sensitivity was 79.9% when ACR-TIRADS TR4 was set as a diagnostic cutoff value. Considering the total of TIRADS TR4 and TIRADS TR5 as predictors of thyroid malignancy, the sensitivity was 74.5% and the specificity was 76.8%. The positive and negative predictive value was 60.3% and 76.8%. CONCLUSION: ACR-TIRADS 4 and 5 can be considered good predictors of malignancy in thyroid nodules. More studies, including larger samples, are required to obtain a better conclusion.

Estimating Methods of the Undetected Infections in the COVID-19 Outbreak: A Systematic Review.

INTRODUCTION: The accurate number of COVID-19 cases is essential knowledge to control an epidemic. Currently, one of the most important obstacles in estimating the exact number of COVID-19 patients is the absence of typical clinical symptoms in a large number of people, called asymptomatic infections. In this systematic review, we included and evaluated the studies mainly focusing on the prediction of undetected COVID-19 incidence and mortality rates as well as the reproduction numbers, utilizing various mathematical models. METHODS: This systematic review aims to investigate the estimating methods of undetected infections in the COVID-19 outbreak. Databases of PubMed, Web of Science, Scopus, Cochrane, and Embase, were searched for a combination of keywords. Applying the inclusion/exclusion criteria, all retrieved English literature by April 7, 2022, were reviewed for data extraction through a two-step screening process; first, titles/abstracts, and then full-text. This study is consistent with the PRISMA checklist. RESULTS: In this study, 61 documents were retrieved using a systematic search strategy. After an initial review of retrieved articles, 6 articles were excluded and the remaining 55 articles met the inclusion criteria and were included in the final review. Most of the studies used mathematical models to estimate the number of underreported asymptomatic infected cases, assessing incidence and prevalence rates more precisely. The spread of COVID-19 has been investigated using various mathematical models. The output statistics were compared with official statistics obtained from different countries. Although the number of reported patients was lower than the estimated numbers, it appeared that the mathematical calculations could be a useful measure to predict pandemics and proper planning. CONCLUSION: In conclusion, our study demonstrates the effectiveness of mathematical models in unraveling the true burden of the COVID-19 pandemic in terms of more precise, and accurate infection and mortality rates, and reproduction numbers, thus, statistical mathematical modeling could be an effective tool for measuring the detrimental global burden of pandemic infections. Additionally, they could be a really useful method for future pandemics and would assist the healthcare and public health systems with more accurate and valid information.

Point-Of-Care Ultrasonography for Identification of Skin and Soft Tissue Abscess in Adult and Pediatric Patients; a Systematic Review and Meta-Analysis.

Introduction: Differentiating the soft tissue abscess from other types of skin and soft tissue infections (SSTIs) poses a particular challenge because they have similar physical evaluation findings, but each disease has a different course, outcome, and treatment. This meta-analysis aimed to investigate the diagnostic accuracy of point-of-care ultrasonography for diagnosis of soft tissue abscess in the emergency departments. Methods: A comprehensive literature search of MEDLINE, Scopus, Web of Science, Embase, and Google Scholar, from inception to January 2023, was conducted to identify relevant studies investigating the diagnostic performance of point-of-care ultrasonography for identification of abscess. Methodological quality of the included studies was assessed using a revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Results: The pooled estimates of diagnostic parameters of ultrasonography for diagnosis of abscess were as follows: sensitivity, 0.93 (95% CI: 0.92-0.94); specificity, 0.87 (95% CI: 0.85-0.89), and the area under the summary receiver-operating characteristic (SROC), 0.95. The pooled sensitivity, specificity, and area under the SROC of studies in adult patients were 0.98 (95% CI: 0.92-1), 0.92 (95% CI: 0.86-0.95), and 0.99, respectively. The pooled sensitivity, specificity, and area under the SROC of studies in pediatric patients were 0.9 (95% CI: 0.87-0.92), 0.78 (95% CI: 0.73-0.82), and 0.91, respectively. Conclusion: Our meta-analysis demonstrated that the point-of-care ultrasonography has excellent diagnostic value for the abscess in the emergency department. Furthermore, we found that the diagnostic performance of point-of-care ultrasonography for diagnosis of abscess was higher for adult cases than for pediatric patients.

Diagnostic Accuracy of Ultrasonography for Identification of Elbow Fractures in Children; a Systematic Review and Meta-analysis.

Introduction: In spite of the results of previous studies regarding the benefits of ultrasonography for diagnosis of elbow fractures in children, the exact accuracy of this imaging modality is still under debate. Therefore, in this diagnostic systematic review and meta-analysis, we aimed to investigate the accuracy of ultrasonography in this regard. Methods: Two independent reviewers performed systematic search in Web of Science, Embase, PubMed, Cochrane, and Scopus for studies published from inception of these databases to May 2023. Quality assessment of the included studies was performed using Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Meta-Disc software version 1.4 and Stata statistical software package version 17.0 were used for statistical analysis. Results: A total of 648 studies with 1000 patients were included in the meta-analysis. The pooled sensitivity and specificity were 0.95 (95% CI: 0.93-0.97) and 0.87 (95% CI: 0.84-0.90), respectively. Pooled positive likelihood ratio (PLR) was 6.71 (95% CI: 3.86-11.67), negative likelihood ratio (NLR) was 0.09 (95% CI: 0.03-0.22), and pooled diagnostic odds ratio (DOR) of ultrasonography in detection of elbow fracture in children was 89.85 (95% CI: 31.56-255.8). The area under the summary receiver operating characteristic (ROC) curve for accuracy of ultrasonography in this regard was 0.93. Egger's and Begg's analyses showed that there is no significant publication bias (P=0.11 and P=0.29, respectively). Conclusion: Our meta-analysis revealed that ultrasonography is a relatively promising diagnostic imaging modality for identification of elbow fractures in children. However, clinicians employing ultrasonography for diagnosis of elbow fractures should be aware that studies included in this meta-analysis had limitations regarding methodological quality and are subject to risk of bias. Future high-quality studies with standardization of ultrasonography examination protocol are required to thoroughly validate ultrasonography for elbow fractures.

The Application of Sensitive Nano-Confined Nanoparticle System Using siRNA Targeting Extracellular Signal-Regulated Kinase (ERK)/Mitogen-Activated Protein Kinase (MAPK) Pathway in Gastrointestinal Cancer.

In this study we tried to develop a Sensitive Nano-Confined Nanoparticles (S-NCN) system using siRNA against Programmed death-ligand 1 (PDL-1) and Polo Like Kinase 1 (Plk1) to treat gastrointestinal cancer. In this regard, we first synthesized the corresponding materials, prepared the S-NCN system, and verified its functionality. Subsequently, we demonstrated in vitro that S-NCN delivery of siPlk1 could effectively downregulate the expression of Plk1 gene in GC1436 cells and lead to significant apoptosis of tumor cells. Xenografted gastrointestinal cancer model mice were used to evaluate the in vivo efficacy of the nanoparticle. We have demonstrated that the developed S-NCN system can efficiently bind siRNA and deliver it into target tumor cells, solving the main obstacle of siRNA delivery in vivo and effectively silencing target genes with a very potential delivery option.