Synthesis of metformin-derived fluorescent quantum dots: uptake, cytotoxicity, and inhibition in human breast cancer cells through autophagy pathway.

BACKGROUND: Breast cancer remains a challenge for physicians. Metformin, an antidiabetic drug, show promising anticancer properties against cancers. An emerging quantum dot (QD) material improves therapeutic agents' anticancer and imaging properties. QD are nano-sized particles with extreme application in nanotechnology captured by cells and accumulated inside cells, suggesting bioimaging and effective anticancer outcomes. In this study, a simple one-pot hydrothermal method was used to synthesize fluorescent metformin-derived carbon dots (M-CDs) and then investigated the cytotoxic effects and imaging features on two human breast cancer cell lines including, MCF-7 and MDA-MB-231 cells. RESULTS: Results showed that M-CDs profoundly decreased the viability of both cancer cells. IC50 values showed that M-CDs were more cytotoxic than metformin either 24-48 h post-treatment. Cancer cells uptake M-CDs successfully, which causes morphological changes in cells and increased levels of intracellular ROS. The number of Oil Red O-positive cells and the expression of caspase-3 protein were increased in M-CDs treated cells. Authophagic factors including, AMPK, mTOR, and P62 were down-regulated, while p-AMPK, Becline-1, LC3 I, and LC3 II were up-regulated in M-CDs treated cells. Finally, M-CDs caused a decrease in the wound healing rate of cells. CONCLUSIONS: For the first, M-CDs were synthesized by simple one-pot hydrothermal treatment without further purification. M-CDs inhibited both breast cancer cells through modulating autophagy signalling.

Evaluation the -174G>C Genetic Polymorphism of Interleukin-6 in Iranian Patients with Chronic Lymphocytic Leukemia.

Background & Objective: Interleukin-6 (IL-6) is involved in inflammation and has a significant role in chronic lymphocytic leukemia (CLL) progression. Accordingly, IL-6 level may increase in CLL-affected patients compared to healthy individuals. The -174G>C single nucleotide polymorphism (SNP) in IL-6 promoter region has been related to differences in IL-6 transcription. Therefore, we investigated the possible association of IL-6 polymorphism with CLL. Methods: We examined the -174G>C SNP in IL-6 gene and studied its possible relationship with CLL in affected patients and in healthy controls using Amplification Refractory Mutation System- polymerase chain reaction genotyping method. IL-6 plasma level was measured in both studied groups. Results: According to the results, IL-6 mean plasma concentration was increased significantly in the CLL patients compared to the controls. However, 174G>C genotype of the IL-6 gene was not associated with CLL. Furthermore, there were no significant differences in the distribution of allele and genotype frequencies between the CLL-affected patients and the controls (P>0.05). Conclusion: Our study showed that -174G>C SNP in promotor of IL-6 gene could not be considered a risk factor for CLL. Larger prospective studies should be performed to confirm our results.

Laboratory methods: A concise review and update for COVID-19 diagnosis.

Since late December 2019, coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spread across the globe. The early, safe, sensitive, and accurate diagnosis of viral infection is required to decrease and control contagious infection and improve public health surveillance. The diagnosis generally is made by detecting SARS-CoV-2-related agents, including a range of nucleic acid detection-based, immunoassay-based, radiographic-based, and biosensor-based methods. This review presents the progress of various detection tools for diagnosing COVID-19 and addresses the advantages and restrictions of each detection method. Given that diagnosis of a contagious various like SARS-COV-2 can improve patient survival rates and break the transmission chain, there is no surprise that significant efforts should be made to reduce the limitations of tests that lead to false-negative results and to develop a substantial test for COVID-19 diagnosis.

Nitrogen and copper-doped saffron-based carbon dots: Synthesis, characterization, and cytotoxic effects on human colorectal cancer cells.

AIM: Doped carbon dots (CDs) have attracted tremendous attention in cancer therapy. We aimed to synthesize copper, nitrogen-doped carbon dots (Cu, N-CDs) from saffron and investigated their effects on HCT-116 and HT-29 colorectal cancer (CRC) cells. MAIN METHODS: CDs were synthesized by hydrothermal method and characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX), Fourier transform infrared (FT-IR) spectroscopy, ultraviolet-visible (UV-Vis) absorption spectroscopy, and fluorescence spectroscopy. HCT-116 and HT-29 cells were incubated with saffron, N-CDs, and Cu, N-CDs for 24 and 48 h for cell viability. Cellular uptake and intracellular reactive oxygen species (ROS) were evaluated by immunofluorescence microscopy. Oil Red O staining was used to monitor lipid accumulation. Apoptosis was evaluated using acridine orange/propidium iodide (AO/PI) staining and quantitative real-time polymerase chain reaction (Q-PCR) assay. The expression of miRNA-182 and miRNA-21 was measured by Q-PCR, while the generation of nitric oxide (NO) and lysyl oxidase (LOX) activity was calculated by colorimetric methods. KEY FINDINGS: CDs were successfully prepared and characterized. Cell viability decreased in the treated cells dose- and time-dependently. HCT-116 and HT-29 cells uptook Cu, N-CDs with a high level of ROS generation. The Oil Red O staining showed lipid accumulation. Concomitant with an up-regulation of apoptotic genes (p < 0.05), AO/PI staining showed increased apoptosis in the treated cells. In comparison to control cells, NO generation, and miRNA-182 and miRNA-21 expression significantly changed in the Cu, N-CDs treated cells (p < 0.05). SIGNIFICANCE: The results indicated that Cu, N-CDs could inhibit CRC cells through the induction of ROS generation and apoptosis.

Association of angiotensin-converting enzyme gene variations with coronary artery disease in the Iranian population.

BACKGROUND: The purpose of this study was to identify the angiotensin-converting enzyme (ACE) gene (I/D) variations in CAD patients and healthy controls in an Iranian population (West Azerbaijan province of Iran). METHOD: This cross-sectional study included 95 CAD patients and 203 healthy controls. ACE I/D polymorphisms were assessed using PCR, and their frequency was determined. RESULTS: There were 298 people, 95 CAD patients, and 203 controls, with an average age of 50.96±3.45 and 51.14±10.20. We discovered that the frequency of the D allele was significantly higher in CAD patients than in controls (P = 0.0009). In contrast, the frequency of the I allele was significantly higher in controls than in CAD patients (P = 0.0009). The D allele carriers genotypes (DD + ID) were more frequent in the CAD patients than in the control group (P = 0.008). The ACE II genotype-state carriers were more common in the control group than in CAD patients (P = 0.008). However, in the case of the ACE ID genotype, no significant differences were not found in the tested groups (P = 0.47). CONCLUSIONS: These findings suggest that individuals with the ACE DD genotype are predisposed to CAD, whereas individuals with the ACE II genotype state are protected.

Bile acid-based advanced drug delivery systems, bilosomes and micelles as novel carriers for therapeutics.

Diabetes mellitus affects almost half a billion patients worldwide and results from either destruction of ß-cells responsible for insulin secretion or increased tissue resistance to insulin stimulation and the reduction of glycemic control. Novel drug delivery systems can improve treatment efficacy in diabetic patients. The low aqueous solubility of most oral antidiabetic drugs decreases drug bioavailability; therefore, there is a demand for the use of novel methods to overcome this issue. The application of bile acids mixed micelles and bilosomes can provide an enhancement in drug efficacy. Bile acids are amphiphilic steroidal molecules that contain a saturated tetracyclic hydrocarbon cyclopentanoperhydrophenanthrene ring, and consist of three 6-membered rings and a 5-membered ring, a short aliphatic side chain, and a tough steroid nucleus. This review offers a comprehensive and informative data focusing on the great potential of bile acid, their salts, and their derivatives for the development of new antidiabetic drug delivery system.

Plant-derived extracellular vesicles: a novel nanomedicine approach with advantages and challenges.

BACKGROUND: Many eukaryote cells produce membrane-enclosed extracellular vesicles (EVs) to establish cell-to-cell communication. Plant-derived EVs (P-EVs) contain proteins, RNAs, lipids, and other metabolites that can be isolated from the juice, the flesh, and roots of many species. METHODS: In the present review study, we studied numerous articles over the past two decades published on the role of P-EVs in plant physiology as well as on the application of these vesicles in different diseases. RESULTS: Different types of EVs have been identified in plants that have multiple functions including reorganization of cell structure, development, facilitating crosstalk between plants and fungi, plant immunity, defense against pathogens. Purified from several edible species, these EVs are more biocompatible, biodegradable, and extremely available from many plants, making them useful for cell-free therapy. Emerging evidence of clinical and preclinical studies suggest that P-EVs have numerous benefits over conventional synthetic carriers, opening novel frontiers for the novel drug-delivery system. Exciting new opportunities, including designing drug-loaded P-EVs to improve the drug-delivery systems, are already being examined, however clinical translation of P-EVs-based therapies faces challenges. CONCLUSION: P-EVs hold great promise for clinical application in the treatment of different diseases. In addition, despite enthusiastic results, further scrutiny should focus on unravelling the detailed mechanism behind P-EVs biogenesis and trafficking as well as their therapeutic applications. Video Abstract.

Tumor Cells-derived exosomal CircRNAs: Novel cancer drivers, molecular mechanisms, and clinical opportunities.

Recently, circular RNAs (circRNAs) have appealed to a growing interest due to their abundant expression and potential functions in cancer development. The most biological function of circRNAs may include acting as a sponge for miRNAs and proteins in different physio/pathological conditions. CircRNAs promote cancer progression by regulating several procedures such as growth, invasion, metastasis, angiogenesis, and drug resistance. Emerging evidence has shown that circRNAs frequently have tumor-specific expression, proposing these molecules serve as diagnostic and prognostic cancer biomarkers. Furthermore, circRNAs may be used as a potential target for the treatment of cancers as they can sponge oncogenic miRNAs and proteins. Exosomes, a subtype of extracellular vesicles mediate intercellular communication, contain circRNAs and deliver them to target cells inducing cancer development through different signaling pathways. Exosomal circRNAs may serve as a diagnostic and prognostic biomarker for cancers. Targeting exosomes may represent novel approaches for the treatment of cancers through using them as cell-free therapy and drug-delivery system and inhibiting their biogenesis and distribution. However, research on circRNAs biology is advancing and some concerns such as technical issues in the characterization and analysis of circRNAs along with biological understanding gaps necessary to be considered to transfer this undeveloped field to the vanguard of clinical studies. In this review, we discuss the existing information on the formation of circRNA and its roles in the tumor as a biomarker and treatment target. Furthermore, we describe tumor-derived exosomes enclosed circRNAs and their possible roles in cancer development and their potential as biomarkers and therapeutic approaches.

Signaling Pathways Involved in 5-FU Drug Resistance in Cancer.

Anti-metabolite drugs prevent the synthesis of essential cell growth compounds. 5-fluorouracil is used as an anti-metabolic drug in various cancers in the first stage of treatment. Unfortunately, in some cancers, 5-fluorouracil has low effectiveness because of its drug resistance. Studies have shown that drug resistance to 5-fluorouracil is due to the activation of specific signaling pathways and increased expressions of enzymes involved in drug metabolites. However, when 5-fluorouracil is used in combination with other drugs, the sensitivity of cancer cells to 5-fluorouracil increases, and the effect of drug resistance is reversed. This study discusses how the function of 5-fluorouracil in JAK/STAT, Wnt, Notch, NF-κB, and hedgehogs in some cancers.

MicroRNAs and drug resistance in colorectal cancer with special focus on 5-fluorouracil.

Colorectal cancer is globally one of the most common cancers in all age groups. The current chemotherapy combinations for colorectal cancer treatment include 5-fluorouracil-based regimens; however, drug resistance remains one of the main reasons for chemotherapy failure and disease recurrence. Many studies have determined colorectal cancer chemoresistance mechanisms such as drug efflux, cell cycle arrest, DNA damage repair, apoptosis, autophagy, vital enzymes, epigenetic, epithelial-mesenchymal transition, stem cells, and immune system suppression. Several microRNAs affect drug resistance by regulating the drug resistance-related target genes in colorectal cancer. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with colorectal cancer. This work reviews and discuss the role of selected microRNAs in 5-fluorouracil resistance and their molecular mechanisms in colorectal cancer.

Potential therapeutic options for COVID-19: an update on current evidence.

SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.

MicroRNAs as therapeutic targets in breast cancer metastasis.

Breast cancer is a complex disease with multiple risk factors involved in its pathogenesis. Among these factors, microRNAs are considered for playing a fundamental role in the development and progression of malignant breast tumors. In recent years, various studies have demonstrated that several microRNAs exhibit increased or decreased expression in metastatic breast cancer, acting as indicators of metastatic potential in body fluids and tissue samples. The identification of these microRNA expression patterns could prove instrumental for the development of novel therapeutic molecules that either mimic or inhibit microRNA action. Additionally, an efficient delivery system mediated by viral vectors, nonviral carriers, or scaffold biomaterials is a prerequisite for implementing microRNA-based therapies; therefore, this review attempts to highlight essential microRNA molecules involved in the metastatic process of breast cancer and discuss recent advances in microRNA-based therapeutic approaches with potential future applications to the treatment sequence of breast cancer.

Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.

Deciphering the molecular downstream consequences of severe acute respiratory syndrome coronavirus (SARS-CoV)- 2 infection is important for a greater understanding of the disease and treatment planning. Furthermore, greater understanding of the underlying mechanisms of diagnostic and therapeutic strategies can help in the development of vaccines and drugs against COVID-19. At present, the molecular mechanisms of SARS-CoV-2 in the host cells are not sufficiently comprehended. Some of the mechanisms are proposed considering the existing similarities between SARS-CoV-2 and the other members of the ß-CoVs, and others are explained based on studies advanced in the structure and function of SARS-CoV-2. In this review, we endeavored to map the possible mechanisms of the host response following SARS-CoV-2 infection and surveyed current research conducted by in vitro, in vivo and human observations, as well as existing suggestions. We addressed the specific signaling events that can cause cytokine storm and demonstrated three forms of cell death signaling following virus infection, including apoptosis, pyroptosis, and necroptosis. Given the elicited signaling pathways, we introduced possible pathway-based therapeutic targets; ADAM17 was especially highlighted as one of the most important elements of several signaling pathways involved in the immunopathogenesis of COVID-19. We also provided the possible drug candidates against these targets. Moreover, the cytokine-cytokine receptor interaction pathway was found as one of the important cross-talk pathways through a pathway-pathway interaction analysis for SARS-CoV-2 infection.

Performance of capecitabine in novel combination therapies in colorectal cancer.

Colorectal cancer is one of the most common cancers throughout the world, and no definitive cure has ever been found. Perhaps a new insight into the effectiveness of chemotherapy drugs could help better treat patients. Targeted therapies have significantly improved the median overall survival of colorectal cancer patients. One of the standard chemotherapy regimens used for colorectal cancer is capecitabine, which is important in monotherapy and combination therapies. Capecitabine, with other chemotherapeutic agents (irinotecan, oxaliplatin, perifosine, 17-allylamino-17-demethoxygeldanamycin, aspirin, celecoxib, statins, quinacrine, inositol hexaphosphate and inositol, cystine/theanine, curcumin, and isorhamnetin), and biological ones (antibodies) plays an important role in the inhibition of some signaling pathways, increasing survival, reducing tumor growth and side effects of capecitabine. However, some drugs, such as proton pump inhibitors, are negatively related to capecitabine; therefore, the purpose of this work is to review and discuss the performance of capecitabine combination therapies in colorectal cancer.

Beneficial effects of memantine on ischemia/reperfusion injury following torsion/detorsion induced testicular damage in rats: Improvement in histological and biochemical parameters.

INTRODUCTION: Testicular torsion is a common urologic emergency and one of the causes of infertility in males. Hence, prompt diagnosis and treatment are important to prevent testicular damages. It has been reported that memantine, a drug for Alzheimer's disease has anti-oxidative role against cerebral ischemic stroke and cardiac ischemia reperfusion. OBJECTIVE: In this experimental study, the effects of memantine on a testicular torsion injury in adolescent rat testis after ischemia/reperfusion (I/R) were evaluated. STUDY DESIGN: Thirty-six adolescent rats were divided into three groups with 12 rats per group including sham-operated, T/D (torsion/detorsion) + vehicle, and T/D + memantine (10 mg/kg). Testicular torsion was induced for 2 h by rotating right testis 7200 in the clockwise direction. In treated group 30 min before detorsion, a single intraperitoneal dose of memantine was administered. After 4 h of reperfusion, orchiectomy was conducted and Histopathological and biochemical evaluations of testicular tissue samples were performed. RESULTS: The malondialdehyde level in the T/D group was significantly greater than in the sham operated group. Moreover, the testicular malondialdehyde values in the T/D + memantine group were significantly lower than in the T/D group. Also, significant decreases occurred in catalase and superoxide dismutase activities in the T/D group compared with sham operated group. These values were significantly greater in the memantine group than in the T/D group. Furthermore, after induction of T/D, histopathological evaluations also revealed severe testicular damages which were improved by memantine administration. DISCUSSION: Memantine prevented increases in oxidative stress markers and reductions of antioxidants during I/R injury in the current study. Subsequently the histologic injury was reduced in rats treated with memantine. The antioxidant characteristics of memantine and its protective effects have been shown in our study. CONCLUSION: These results suggest that administration of memantine before detorsion prevents I/R cellular damage in testicular torsion. This drug probably acts through reduction of reactive oxygen species and support antioxidant enzyme systems.

Topiramate: A novel protective agent against ischemia reperfusion-induced oxidative injury after testicular torsion/detorsion.

Testicular torsion is a common urologic emergency and one of the causes of genital injury in males. Hence, early diagnosis and treatment are necessary to prevent testicular damage and infertility. It has been proved that topiramate (TPM) a medication used to treat epilepsy and prevent migraines has anti-inflammatory and anti-oxidative effects. Therefore, this study was designed to determine the influence of TPM on ischemia/reperfusion injury following testicular torsion/detorsion (T/D). Thirty-six male Wistar rats were divided into three groups (n = 12 for each group) including sham operated, T/D + vehicle, T/D + TPM(100 mg/kg, 30 min before detorsion). Testicular torsion was induced for 1 h by rotating right testis 7200 in the clockwise direction. After 5 h of reperfusion the testis was removed and histological changes and biochemical markers such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and levels of malondialdehyde (MDA) and reduced glutathione (GSH) were evaluated. MDA level significantly increased and GSH level significantly decreased after T/D compared to the sham group (p < 0.001). Moreover, after inducing testicular T/D, GPx, CAT and SOD activity were decreased, whereas administration of TPM significantly increased GSH level and GPx, CAT and SOD activities and decreased MDA level in testis tissue as compared to T/D group. After induction of T/D, histopathological evaluations also revealed severe testicular damages which were improved by TPM administration. Our results indicate that TPM had an ameliorating impact on ischemia/reperfusion injury in the rat model of testicular T/D. This protective effect was most likely induced by anti-oxidative properties of this drug.

Neurological effects of long-term exposure to low doses of pesticides mixtures in male rats: Biochemical, histological, and neurobehavioral evaluations.

Humans are usually exposed to multiple pesticides in real life, but little is known as yet about the safety of low-dose pesticides mixtures. This study was conducted to evaluate the effects of long-term exposure to very low doses of pesticide mixtures on biochemical, histological, and neurobehavioral alterations in the rat model. For 90 days, four groups of male Wistar rats were given a mixture of five pesticides (in drinking water) in doses of 0, 0.25, 1 and 5 times the legally permitted levels (mg/kg body weight/day). After three-month exposure, the neurobehavioral effects of pesticide mixtures were evaluated by the Morris water maze, elevated plus maze and the open field tests. Then the biochemical and histopathological alterations in the hippocampus of studied animals were evaluated. Results showed that long-term exposure to a combination of five pesticides affected the nervous system in dose-dependent manner. As expected, nearly all of the parameters determined in this study were adversely changed in the high dose group. Exposure to medium dose (permitted level of pesticides mixture) was also able to induce oxidative stress and impaired memory and learning ability, although not all parameters were significantly changed in this group. It means that pesticides may behave differently when mixed. Interestingly, the administration of low doses of these chemicals induced an adaptive response by stimulating the redox system. In conclusion, it seems that the prolonged exposure to pesticide mixtures may cause adverse neurobehavioral effects, even at permitted levels.

Transcriptional activity of tumor necrosis factor-alpha gene in peripheral blood mononuclear cells in patients with coronary slow flow.

BACKGROUND: Coronary slow flow (CSF), an angiographic phenomenon that is characterized by a delayed coronary blood flow in the absence of obstructive coronary artery stenosis, is known as a disorder of the coronary microcirculation. Inflammation has an important role in the vascular hemostasis and endothelial dysfunction especially regarding monocyte adhesion and infiltration. Pro-inflammatory cytokines released by inflammatory cells result in endothelial cell dysfunction and cardiovascular diseases. It has been demonstrated that tumor necrosis factor-alpha (TNF-α) mainly influences the vascular homeostasis and endothelial dysfunction. In the present enquiry the transcriptional activity of TNF-α gene in peripheral blood mononuclear cells (PBMCs) of patients with CSF was compared with healthy controls in order to further survey the role of TNF-α in pathophysiology of CSF. METHODS: The study was carried out on 30 patients with CSF and 30 matched healthy controls. To analysis gene expression of TNF-α, total mRNA was isolated from PBMCs. The quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to compare the transcriptional activity of TNF-α gene between patients with CSF and controls. RESULTS: The mean ± standard error of mean of fold in CSF patients and controls were 0.20 ± 0.04 and 1.38 ± 0.27, respectively. The mRNA mean expressions of TNF-α (fold) were different in tested groups, which indicated a significant decrease in TNF-α in patients with CSF group (P = 0.0001). CONCLUSION: Expression of TNF-α was decreased in patients with CSF. Changes in TNF-α expression suggest a potential role for altered immune function in the pathophysiology of CSF.

Transcriptional Activity of Gene Encoding Subunits R1 and R2 of Interferon Gamma Receptor in Peripheral Blood Mononuclear Cells in Patients with Slow Coronary Flow.

BACKGROUND: Slow coronary flow (SCF) is a coronary artery disorder characterized with delayed opacification of epicardial coronary arteries without obstructive coronary disease. The pathophysiological mechanisms of SCF remain unclear. One of the possible mechanisms that may participate in the pathology of SCF is endothelial dysfunction related to the inflammatory process. Interferon gamma (IFN-γ) is an inflammatory cytokine that acts through its specific receptor composed of two subunits, IFN-γR1 and IFN-γR2. Transcriptional activity of the gene encoding these subunits influences IFN-γ activity. This study aimed to investigate the gene expression of IFN-γ receptor subunits in peripheral blood mononuclear cells (PBMC) from patients with SCF. METHODS: The study was performed with 30 patients (22 male/8 female) aged 35-76 (52.8±11.7 years) with SCF and 15 sex- (11 male/4 female), Body Max Index (BMI)- and age-matched (54.73±9.42 years) healthy subjects. Total mRNA was extracted from PBMC and was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The relative expression values (2-ΔΔCt) between control and case groups were determined and the Mann-Whitney U test was used for statistical analysis. RESULTS: There was a significant increase in the gene expression of IFN-γR1 in PBMC from SCF patients vs. controls (P< 0.0001); but the differences in IFN-γR2 gene expression were statistically insignificant between patient and control groups (P= 0.853). CONCLUSIONS: It can be concluded that IFN-γ gene expression may influence the function of microvasculature and thereby contribute to the pathophysiology of SCF.

Factors affecting complications according to the modified Clavien classification in complete supine percutaneous nephrolithotomy.

INTRODUCTION: An increase in percutaneous nephrolithotomy (PCNL) has been accompanied by an increase in complications. We identified the parameters affecting the severity of complications using the modified Clavien classification (MCC). METHODS: From 2008 to 2013, 330 patients underwent complete supine PCNL using subcostal access, one-shot dilation, rigid nephroscopy, and pneumatic lithotripsy. We assessed the impact of the following factors on complication severity based on the MCC: age, gender, body mass index, hypertension, diabetes, previous stone surgery and extracorporeal shock wave lithotripsy, preoperative hemoglobin, renal dysfunction (creatinine >1.4 mg/dL), preoperative urinary tract infection, anatomic upper urinary tract abnormality (AUUTA), significant (moderate-severe) hydronephrosis, stone-related parameters (opacity, number, burden, location, staghorn, complex stones), anesthesia type, kidney side, imaging and calyx for access, tract number, tubeless approach, operative time, postoperative hemoglobin, and hemoglobin drop and stone-free results. RESULTS: The complication rate was 19.7% (MCC: 0=80.3%, I=6.4%, II=11.2%, ≥III=2.1%). On univariate analyses, only the following factors affected MCC: gender, preoperative hemoglobin, AUUTA, significant hydronephrosis, imaging for access, calyx for access, tract number, postoperative hemoglobin, hemoglobin drop and stone-free result. Renal dysfunction was accompanied by higher complications, yet the results were not statistically significant. Multivariate logistic regression analysis demonstrated renal dysfunction, absence of significant hydronephrosis, AUUTA, multiple tracts, lower postoperative hemoglobin, and higher postoperative hemoglobin drop as the significant parameters which affected MCC and predicted higher grades. The paper's limitations include a low number of cases in the higher Clavien grades and some subgroups of variables, and not applying some techniques due to surgeon preference. INTERPRETATION: Many of the complete supine PCNL complications were in the lower Clavien grades and major complications were uncommon. Renal dysfunction, AUUTA, significant hydronephrosis, tract number, postoperative hemoglobin, and hemoglobin drop were the only factors affecting MCC.