Bosnian Journal of Basic Medical Sciences https://www.bjbms.org/ojs/index.php/bjbms <p>The BJBMS (Bosnian Journal of Basic Medical Sciences) is а premier venue for discoveries in basic and clinical biomedical science. The BJBMS was founded in 1998 and is published by the Association of Basic Medical Sciences, a nonprofit honor organization of physician-scientists.</p> <p>Broad readership and scope. The BJBMS reaches readers across a wide range of medical disciplines and sectors. The journal publishes basic and translational/clinical research submissions and reviews in all biomedical specialties, including Genetics and Molecular biology, Immunology, Microbiology, Pathology, Biochemistry, Pharmacology, Anatomy, Biomaterials, new and emerging research and diagnostic methods, new and emerging medical entities, and others.</p> Association of Basic Medical Sciences of FBIH en-US Bosnian Journal of Basic Medical Sciences 1512-8601 Development and validation a novel preoperative comprehensive prognostic score based on inflammatory and nutritional score, coagulation indicator and tumor marker in esophageal squamous cell carcinoma https://www.bjbms.org/ojs/index.php/bjbms/article/view/6350 <p><span style="font-weight: 400;">We herein propose a novel </span><span style="font-weight: 400;">integrative</span><span style="font-weight: 400;"> score based on </span><span style="font-weight: 400;">inflammatory and nutritional score, coagulation indicator and tumor marker</span><span style="font-weight: 400;">, named comprehensive prognostic score (CPS)</span><span style="font-weight: 400;">,</span><span style="font-weight: 400;"> to predict postoperative survival in resectable esophageal squamous cell carcinoma (ESCC). We also aimed to </span><span style="font-weight: 400;">establish and validate a nomogram based on CPS and other clinical features for individual survival prediction</span><span style="font-weight: 400;">. </span><span style="font-weight: 400;">A total of 490 </span><span style="font-weight: 400;">resectable ESCC patients were </span><span style="font-weight: 400;">randomly divided into either a training or validation cohort at a ratio of 7:3 for retrospective </span><span style="font-weight: 400;">analysis.</span> <span style="font-weight: 400;">The CPS, based on squamous cell carcinoma antigen (SCCA), C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR), and fibrinogen (FIB), was divided into two models to verify its prognostic value. </span><span style="font-weight: 400;">The predictive model of CPS-based nomogram was established and validated in two cohorts. </span><span style="font-weight: 400;">Patients with CPS low group in model 1 had better 5-year cancer-specific survival (CSS) than those in CPS high group (50.7% vs. 17.8%, P&lt;0.001). For model 2, the 5-year CSS for CPS 0, 1 and 2 were 75.0%, 38.9% and 13.3%, respectively (P&lt;0.001). CPS was confirmed as an independent prognostic score in both models. The CPS-based nomogram can accurately and effectively predict survival in resected ESCC. The CPS is a novel, simple, and effective predictor in resectable ESCC. Moreover, CPS has a potential independent prognostic value in predicting </span><span style="font-weight: 400;">postoperative survival</span><span style="font-weight: 400;">, </span><span style="font-weight: 400;">which </span><span style="font-weight: 400;">can accurately and effectively predict individual survival in resectable ESCC</span><span style="font-weight: 400;">.</span></p> Jifeng Feng Liang Wang Xun Yang Qixun Chen Copyright (c) 2021 Jifeng Feng, Liang Wang, Xun Yang, Qixun Chen https://creativecommons.org/licenses/by/4.0 2021-10-19 2021-10-19 21 5 10.17305/bjbms.2021.6350 CircFOXM1 promotes the proliferation, migration, invasion, and glutaminolysis of glioblastoma by regulating the miR-577/E2F5 axis https://www.bjbms.org/ojs/index.php/bjbms/article/view/6028 <p><span style="font-weight: 400;">Circular RNA (circRNA) is a key regulator of tumor progression. However, the role of circFOXM1 in glioblastoma (GBM) progression is unclear.</span></p> <p><span style="font-weight: 400;">The aim of this study was to investigate the role of circFOXM1 in GBM progression. The expression levels of circFOXM1, miR-577 and E2F transcription factor 5 (E2F5) were examined by</span> <span style="font-weight: 400;">real-time quantitative PCR. Cell counting kit 8 assay, EdU staining and transwell assay were used to detect cell proliferation, migration, and invasion. The levels of glutamine, glutamate and α-ketoglutarate were determined to evaluate the</span> <span style="font-weight: 400;">glutaminolysis ability of cells. Protein expression was tested by western blot analysis. Dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation assay were employed to verify the interaction between miR-577 and circFOXM1 or E2F5. Mice xenograft model for GBM was constructed to perform </span><em><span style="font-weight: 400;">in vivo</span></em><span style="font-weight: 400;"> experiments.</span></p> <p><span style="font-weight: 400;"> Our results showed that circFOXM1 was highly expressed in GBM tumor tissues and cells. Silencing of circFOXM1 inhibited GBM cell proliferation, migration, invasion, glutaminolysis, as well as tumor growth. MiR-577 could be sponged by circFOXM1, and its inhibitor could reverse the suppressive effect of circFOXM1 downregulation on GBM progression. E2F5 was a target of miR-577, and the effect of its knockdown on GBM progression was consistent with that of circFOXM1 silencing. CircFOXM1 positively regulated E2F5 expression, while miR-577 negatively regulated E2F5 expression. </span></p> <p><span style="font-weight: 400;">In conclusion, our data confirmed that circFOXM1 could serve as a sponge of miR-577 to enhance the progression of GBM by targeting E2F5, which revealed that circFOXM1 might be a biomarker for GBM treatment. </span></p> Xuhui Fan Meng Liu Li Fei Zhihui Huang Yufeng Yan Copyright (c) 2021 Xuhui Fan, Meng Liu, Li Fei, Zhihui Huang, Yufeng Yan https://creativecommons.org/licenses/by/4.0 2021-10-12 2021-10-12 21 5 10.17305/bjbms.2021.6028 Inflammatory cells in the ascending aortic aneurysm in patients with type 2 diabetes versus patients with hypertension https://www.bjbms.org/ojs/index.php/bjbms/article/view/6488 <p><span style="font-weight: 400;">Aortic aneurysms occur relatively frequently in the ascending thoracic aorta, but are rarely seen in patients with type 2 diabetes. Our aim was to evaluate inflammatory cell infiltration in the ascending aortic aneurysm wall in patients with diabetes without arterial hypertension (DM2 group, N=6) versus hypertensive non-diabetic patients (AH group, N=34). For histologic analysis, the sections were stained with hematoxylin-eosin and Movat pentachrome. The immunohistochemical staining was used to analyze the infiltration of pro-inflammatory (CD68) and anti-inflammatory macrophages (CD163), T helper (CD4) and T killer cells (CD8), and B (CD79a) and plasma cells (CD138) in all three layers of aneurysms of both groups. The statistical significance of the differences between groups was evaluated by ANOVA and the Welch test.</span></p> <p><span style="font-weight: 400;">In comparison to the AH group, the DM2 group developed less severe infiltration of pro-inflammatory macrophages (</span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">=0.004) and B cells (</span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">=0.025) in the tunica intima, and tunica media (</span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">=0.049, </span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">=0.007, respectively), and fewer plasma cells in the tunica media (</span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">=0.024) and tunica adventitia (</span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">=0.017). We found no significant differences in the number of T helper, T killer cells, and anti-inflammatory macrophages and in the amount of collagen and elastic fibers, ground substance, and smooth muscle cells in all three layers of the vessel wall. Except in tunica adventitia of DM2 group, there were more collagen fibers overall (</span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">=0.025).&nbsp;</span></p> <p><span style="font-weight: 400;">Thus, we conclude that the histological structure of the aneurysm in diabetics without hypertension is almost the same as in hypertensive patients without diabetes. Diabetics had significantly less inflammatory infiltration in all three layers of the vessel wall, and more collagen fibers in tunica adventitia.</span></p> Aleksandra Milutinović Ruda Zorc-Pleskovič Copyright (c) 2021 Aleksandra Milutinović, Ruda Zorc-Pleskovič https://creativecommons.org/licenses/by/4.0 2021-10-12 2021-10-12 21 5 10.17305/bjbms.2021.6488 Construction and validation of a preterm birth risk assessment model using fuzzy analytic hierarchy process https://www.bjbms.org/ojs/index.php/bjbms/article/view/6431 <p><span style="font-weight: 400;">Preterm births account for almost 1 million deaths globally. The objective of this study is to develop and evaluate a model that assists clinicians in assessing the risk of preterm birth, using fuzzy multicriteria analysis. The model allows experts to incorporate their intuition and judgment into the decision-making process and takes into consideration six (6) risk dimensions reflecting the socio-economic, behavioural and medical profile of pregnant women, thus adopting a holistic approach to risk assessment. Each risk dimension is further analysed and measured in terms of risk factors associated with it.&nbsp;</span><span style="font-weight: 400;">Data was collected from a selected group of 35 experts, each one with more than 20 years of obstetric experience. The model criteria were selected after a thorough literature analysis, so as to ensure a holistic approach to risk assessment. The criteria were reviewed by the experts and the model structure was finalised. The fuzzy analytic hierarchy method was applied to calculate the relative importance of each criterion and subsequent use of the model in assessing and ranking pregnant women by their preterm risk. The proposed model utilises fuzzy logic and multicriteria analysis. It addresses the multifactorial nature of decision making when assessing the preterm birth risk. It also incorporates the obstetricians’ intuitive judgement during risk assessment and it can be used to classify cases based upon their risk level. Additionally, it can be applied to evaluate the risk of individual cases in a personalised manner. The proposed model is compared and validated for its predictive value against judgments made by experts.&nbsp;</span></p> Stavroula Barbounaki Antigoni Sarantaki Copyright (c) 2021 Stavroula Barbounaki, Antigoni Sarantaki https://creativecommons.org/licenses/by/4.0 2021-10-04 2021-10-04 21 5 10.17305/bjbms.2021.6431 Prevalence, clinical features and prognosis of malignant solid tumors in infants: a 14-year study https://www.bjbms.org/ojs/index.php/bjbms/article/view/5121 <p>The onset of malignant solid tumors in infants is insidious and difficult to diagnose on time. The purpose of our study is to provide a theoretical basis for clinical diagnosis by retrospective analysis of the data in the past 14 years. Here, we retrospectively collected the clinical data of infants aged 0-12 months with malignant solid tumors in Beijing Tongren Hospital Affiliated to Capital Medical University from May 2005 to May 2019. The epidemiology, clinical characteristics, treatments and prognosis were statistically analyzed. A total of 496 infants (294 males and 202 females) with malignant solid tumors were analyzed. The main period of onset was 1-11 months. The most common tumor was retinoblastoma (RB, 51.8%), followed by hepatoblastoma (HB, 26.6%), neuroblastoma (NB, 10.5%), rhabdomyosarcoma (RMS, 3.4%), malignant renal tumors (3.2%), infantile fibrosarcoma (IFS, 1.6%), malignant teratoma (1.2%), Ewing’s sarcoma (ES, 0.8%), medulloblastoma (MB, 0.4%) and inflammatory myofibroblastic tumor (IMT, 0.4%). The median follow-up time was 32 months (range 2-162 months). The 1-year, 3-year, and 5-year overall survival of all patients were 97.3%, 89.2%, and 81.1%, respectively, and event-free survival was 94.7%, 84.8%, and 75.8%, respectively. In conclusion, as a special group, malignant solid tumors in infants are complex, heterogeneous, and relatively rare. The prognosis of RB, HB, NB, RMS, malignant renal tumors, IFS, malignant teratoma, ES, MB, and IMT, were excellent duo to timely diagnosis and rational treatment.</p> Tian Zhi Wei-Ling Zhang Yi Zhang Yi-Zhuo Wang Dong-Sheng Huang Copyright (c) 2020 Tian Zhi, Wei-Ling Zhang, Yi Zhang, Yi-Zhuo Wang, Dong-Sheng Huang https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 598 606 10.17305/bjbms.2020.5121 Trends of incidence and prognosis of upper tract urothelial carcinoma https://www.bjbms.org/ojs/index.php/bjbms/article/view/5345 <p>The purpose of this study was to investigate trends in the incidence of upper tract urothelial carcinoma (UTUC) in patients and to establish a reliable and practical nomogram based on significant clinical factors to predict the overall survival (OS) and cancer-specific survival (CSS) of UTUC patients. The Surveillance, Epidemiology, and End Results (SEER) database was used to extract data on UTUC patients between 1988 and 2015. Incidence was calculated using Joinpoint regression software, and trends were quantified by annual percentage change (APC). A nomogram was constructed using R software to predict the OS and CSS probabilities for individual patients. From 1988 to 2015, the incidence of UTUC showed a downward trend (1988: 1.57/100,000 to 2015: 1.51/100,000; APC=-0.1). After stratification according to sex, age and primary site, we found that the incidences of UTUC in males, patients 70+ years old and the renal pelvis were higher than those in females, patients &lt;70 years old and ureter cancer patients. In the training cohort, the nomogram established based on multivariate Cox regression results showed better OS and CSS accuracy (OS: C-index=0.701, AUC=0.736; CSS: C-index=0.729, and AUC=0.688) than SEER stage. In addition, the calibration curves showed good consistency between the predicted and actual 3-, 5- and 10-year OS and CSS rates of the nomogram. In the past 30 years, the incidence of UTUC has shown a general downward trend, and the prognostic nomogram we established can provide a personalized risk assessment for the survival of UTUC patients.&nbsp;</p> Jianping Wu Shuqiu Chen Xiaoli Wu Weipu Mao Yali Wang Bin Xu Donghui Zheng Ming Chen Copyright (c) 2020 Ming Chen, Jianping Wu, Shuqiu Chen, Xiaoli Wu, Weipu Mao, Yali Wang, Bin Xu, Donghui Zheng https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 607 619 10.17305/bjbms.2020.5345 Significance of chromogranin A and synaptophysin in medullary thyroid carcinoma https://www.bjbms.org/ojs/index.php/bjbms/article/view/5407 <p>Medullary thyroid carcinoma (MTC) is a relatively rare thyroid carcinoma of C-cell deviation and produces and secrete calcitonin (CT) and chromogranin A (CgA) into the blood. Thus, both CT and CgA are immunohistochemical and serum markers for MTCs. MTC occurs in both sporadic and inheritable cases and the hallmark of inheritable cases in multiple endocrine neoplasm 2 (NEN2) is MTC. MEN2 cases represent 30% of MTCs through germline RET protooncogene mutation and occur in younger ages involving bilateral thyroid lobes. Sporadic cases are 70% of cases of solitary tumor and occur in older ages. CgA and synaptophysin (SPY) are the two, most widely used and reliable immunohistochemical markers for neuroendocrine tumors including MTCs. This study aimed to detect different immunohistochemical staining patterns for CgA and SPY between non-symptomatic small, microscopic lesions and invading larger aggressive tumors in both MEA2 cases and sporadic cases. There was different CgA and SPY immunostaining in MEA2 cases where small tumors (≤ 0.3 cm) were lesser immunostained for CgA and SPY, despite strong staining for CT, compared to the larger (≥ 0.5cm) tumors, stronger immunostained for CgA. There was also different CgA and SPY immunohistochemical staining in sporadic cases between small lesion (≤ 0.5 cm) and larger tumors (≥ 1.0cm). One small sporadic tumor (0.5 x 0.3 cm) was strongly and weakly, patchy (about 10% of tumor tissue) stained for CgA and SPY, respectively, while larger sporadic tumors were diffusely, stronger stained for CgA and SPY. Therefore, stronger CgA and SPY immunostaining for larger tumors in both MEA2 and sporadic cases may be used as independent aggressive immunohistochemical markers for MTCs.</p> Tatsuo Tomita Copyright (c) 2020 Tatsuo Tomita https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 535 541 10.17305/bjbms.2020.5407 Development and validation of a SEER-based prognostic nomogram for cervical cancer patients below the age of 45 years https://www.bjbms.org/ojs/index.php/bjbms/article/view/5271 <p>In this study, we established a nomogram for the prognostic prediction of patients with early-onset cervical cancer (EOCC) for both overall survival (OS) and cancer-specific survival (CSS). The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 10,079 patients diagnosed with EOCC between 2004 and 2015; these cases were then randomly divided into training and validation sets. The independent prognostic factors were identified in a retrospective study of 7,055 patients from the training set. A prognostic nomogram was developed using R software according to the results of multivariable Cox regression analysis. Furthermore, the model was externally validated using the data from the remaining 3,024 patients diagnosed at different times and enrolled in the SEER database. For the training set, the C-indexes for OS and CSS prediction were determined to be 0.831 (95 % confidence interval [CI]: 0.815–0.847) and 0.855 (95 % CI: 0.839–0.871), respectively. Receiver operating characteristic (ROC) analysis has revealed that the nomograms were a superior predictor compared with TNM stage and SEER stage. The areas under the curve (AUC) of the nomogram for OS and CSS prediction in the ROC analysis were 0.855 (95 % CI: 0.847–0.864) and 0.782 (95 % CI: 0.760–0.804), respectively. In addition, calibration curves indicated a perfect agreement between the nomogram-predicted and the actual 1-, 3-, and 5-year OS and CSS rates in the validation cohort. Thus, in this study, we established and validated a prognostic nomogram that provides an accurate prediction for 3-, 5-, and 10-year OS and CSS of EOCC patients. This will be useful for clinicians in guiding counseling and clinical trial design for cervical cancer patients.</p> Qunlong Liu Wenxia Li Ming Xie Ming Yang Mei Xu Lei Yang Bing Sheng Yanna Peng Li Gao Copyright (c) 2020 Qunlong Liu, Wenxia Li, Ming Xie, Ming Yang, Mei Xu, Lei Yang, Bing Sheng, Yanna Peng, Li Gao https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 620 631 10.17305/bjbms.2020.5271 Expression of NEDD9 and connexin-43 in neoplastic and stromal cells of gastric adenocarcinoma https://www.bjbms.org/ojs/index.php/bjbms/article/view/5379 <p>Gastric cancer is related to high mortality rates and advanced disease stage at the time of diagnosis. Its carcinogenesis is extensively studied and is associated with genetic and epigenetic changes, changed the interaction between tumor and adjacent stromal cells, and changes in the microenvironment molecule status. Neural precursor cell-expressed developmentally down-regulated 9 (NEDD9) affects different signaling proteins and pathways, apoptosis, adhesion, cell migration, and invasiveness. Connexin-43 (Cx43) also assists in intercellular communications and has several channel-independent functions. Aberrant expression of those two gap junction proteins plays an essential role in metastatic processes. Our scope was to detect the expression of Cx43 and NEDD9 in epithelial and stromal gastric cancer compartments and its relation to tumor progression and lymph node metastases. Cancer tissue from 53 cases of node-negative and 55 cases of node-positive primary gastric carcinoma patients was analyzed for Cx43 and NEDD9 expression by immunohistochemical assay, and the results were correlated with the remaining clinical and pathological findings and survival. In our cohort of patients with lymph node metastases, we detected higher expression of epithelial Cx43 in the primary tumor and stromal Cx43 expression correlated with both epithelial NEDD9 (rho = 0.453) and stromal NEDD9 (rho = 0.484). Higher epithelial Cx43 and NEDD9 expression were associated with higher mortality (HR 1.54, 95% CI 1.01-2.37, <em>p</em> = 0.048). Epithelial Cx43 expression, both epithelial and stromal NEDD9 expression, T and N status were all independently associated with shorter survival. In summary, our findings suggest that increased expression of both epithelial and stromal NEDD9 and epithelial Cx43 could potentially be used as prognostic gastric cancer biomarkers.</p> Ivan Lerotić Petra Vuković Davor Hrabar Zvonimir Misir Ivan Kruljac Tajana Pavić Jelena Forgač Petra Ćaćić Monika Ulamec Copyright (c) 2021 Ivan Lerotić, Petra Vuković, Davor Hrabar, Zvonimir Misir, Ivan Kruljac, Tajana Pavić, Jelena Forgač, Petra Čačić, Monika Ulamec https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 542 548 10.17305/bjbms.2020.5379 Development and validation of nomograms for predicting survival of elderly patients with stage I small-cell lung cancer https://www.bjbms.org/ojs/index.php/bjbms/article/view/5420 <p>There is a lack of predictive models to determine the prognosis of elderly patients diagnosed with Stage I small-cell lung cancer (SCLC). The purpose of&nbsp;this&nbsp;study&nbsp;was to establish a useful nomogram to predict cancer-specific survival (CSS) in the elderly patient population. Based on the Surveillance, Epidemiology, and End Results registry database, patients aged ≥ 65 years with pathological AJCC (American Joint Committee on Cancer) Stage I SCLC from 2004 to 2014 were identified. The CSS was evaluated by the Kaplan-Meier method. Patients were randomly split into training and validation sets. In the training cohort, univariate analysis and multivariate analysis using the Cox regression identified risk factors that affected CSS, and the results were utilized to construct a nomogram for prediction of the 1-, 3-, and 5-year CSS rates of elderly patients with Stage I SCLC. The&nbsp;effectiveness of the nomogram was validated internally and externally by the bootstrap method. The clinical practicability and accuracy of the nomogram were evaluated by the concordance index (C-index), calibration curve, receiver operating characteristic curve, and decision curve analysis. In total, we extracted 1,623 elderly patients with Stage I SCLC. The median CSS was 34 months, and the 5-year CSS was 41%. Multivariate analysis revealed that histologic type, tumor size, age, and AJCC Stage were significant predictors of CSS. A nomogram was constructed according to the results of multivariate COX analysis. The C-indices of the nomogram for training and validation sets were 0.68 and 0.62, indicating that the nomogram demonstrated a favorable level of discrimination. The calibration curves exhibited satisfactory agreement between the actual observation and nomogram prediction. The net benefit of the nomogram was better than the AJCC TNM staging. A practical nomogram to predict the CSS of elderly patients with Stage I SCLC is constructed. The predictive tool is helpful for patient counseling and treatment decision-making.</p> Yaji Yang Shusen Sun Yuwei Wang Feng Xiong Yin Xiao Jing Huang Copyright (c) 2021 Yaji Yang, Shusen Sun, Yuwei Wang, Feng Xiong, Yin Xiao, Jing Huang https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 632 641 10.17305/bjbms.2020.5420 Sirtuin 1 rs7069102 polymorphism is associated with diabetic nephropathy in patients with type 2 diabetes mellitus https://www.bjbms.org/ojs/index.php/bjbms/article/view/5368 <p>The global prevalence for diabetes mellitus nearly doubled from 4.7% in 1980 to 8.5% in 2014. Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that is expressed in a variety of tissues. It modifies proteins that participate in DNA repair, stress, and inflammatory response. The aim of the study was to investigate the relationship between SIRT1 rs7069102 polymorphism and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). In our retrospective association study, we included 724 Slovene (Caucasian) patients who have had T2DM for at least 10 years. We classified the participants into two groups, the first group was comprised of 301 patients with DN, and the second (control) group was comprised of 423 patients without DN. We analyzed the rs7069102 polymorphism using StepOne real-time polymerase chain reaction (PCR) System and TaqMan SNP Genotyping Assay. We found a statistically significant difference in the distribution of rs7069102 genotypes and alleles between the two groups. We used logistic regression analysis and adjusted for systolic pressure, arterial hypertension (AH), duration of AH, triglycerides, the value of HbA1c, carotid disease, diabetic foot, and diabetic retinopathy. Furthermore, we discovered that patients with the CC genotype are significantly more likely to develop DN according to both the codominant (odds ratio [OR] = 1.94; 95% confidence interval [CI] = 1.09-3.45; <em>p</em> = 0.02) and recessive (OR = 2.39; 95% CI = 1.12-5.08; <em>p</em> = 0.02) models of inheritance. We found a significant association between the SIRT1 rs7069102 polymorphism and DN in T2DM. We speculate that SIRT1 rs7069102 might be an interesting marker of DN.</p> Jernej Letonja Matej Završnik Jana Makuc Maja Šeruga Ana Peterlin Ines Cilenšek Danijel Petrovič Copyright (c) 2021 Jernej Letonja, Matej Završnik, Jana Makuc, Maja Šeruga, Ana Peterlin, Ines Cilenšek, Danijel Petrovič https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 642 646 10.17305/bjbms.2020.5368 Extreme lateral interbody fusion (XLIF) in a consecutive series of 72 patients https://www.bjbms.org/ojs/index.php/bjbms/article/view/5261 <p>Extreme lateral interbody fusion (XLIF) has become the standard of minimally invasive lumbar segmental scoliosis treatment. Our objective is to determine the safety and efficacy of XLIF in spinal canal stenosis (SCS) and spondylodiscitis (SD). Patients treated with XLIF in our department between 2012 and 2018 were retrospectively analyzed. Patient records with clinical and radiographical parameters were evaluated. The patient cohort consists of 40 male and 32 female patients with a median age of 66.6 years. Forty-five patients had an SCS and 27 patients SD. The mean follow-up was 23 months. One level XLIF was performed in 49 patients, 2 levels in 15, 3 levels in 7 patients and 4 levels in 1 patient. All but one patient received an additional dorsal stabilization. The pain was present in all patients with a mean Visual Analogue Scale (VAS) score of 8.8 vs. postoperative VAS of 2.8 (<em>p</em>&lt;0.05). Preoperative neurological deficits were found in 44 patients. Only 6 patients had a neurological deterioration, 45 patients improved, and 21 patients remained unchanged. One patient experienced a perioperative complication.&nbsp; Non-fusion occurred in 8 cases. There were no outcome differences regarding pain and radiological outcome between patients with SCS and SD as well as between patients with one level vs. multilevel surgery. Baseline characteristics and the radiological outcome did not differ between the two groups. Patients with SD had a higher rate of worsening of neurological deficits following surgery, a higher rate of non-fusion, and a longer hospital stay. Patients with spinal canal stenosis SCS had a longer surgery time and more frequent adjacent segment disease.</p> Mirza Pojskic Benjamin Saβ Benjamin Völlger Christopher Nimsky Barbara Carl Copyright (c) 2021 Mirza Pojskic, Benjamin Saβ, Benjamin Völlger, Christopher Nimsky, Barbara Carl https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 587 597 10.17305/bjbms.2020.5261 SARS-CoV-2 infection: Understanding the immune system abnormalities to get an adequate diagnosis https://www.bjbms.org/ojs/index.php/bjbms/article/view/5400 <p>COVID-19 is the current pandemic caused by the novel coronavirus, SARS-CoV-2, that emerged from China at the end of December 2019. The scientific community is making extraordinary efforts to understand the virus structure and the pathophysiology and immunological processes activated in the host, in order to identify biomarkers, diagnostic tools, treatments, and vaccines to decrease COVID-19 incidence and mortality. Various abnormalities have been noted during SARS-CoV-2 infection both in lymphoid and myeloid cells. Such abnormalities may disturb the immune system function and cause a massive inflammatory response that impairs tissue function. This review discusses the close relationship between the immune system abnormalities and the broad spectrum of clinical manifestations, including fibrosis, in the context of COVID-19 disease. Moreover, we described the current strategies for COVID-19 diagnosis, and we provide a summary of the most useful clinical laboratory parameters to identify severe COVID-19 patients.</p> Karen Medina-Quero Omar Barreto-Rodriguez Voltaire Mendez-Rodriguez Anahí Sanchez-Moncivais Ivette Buendia-Roldan Leslie Chavez-Galan Copyright (c) 2021 Karen Medina-Quero, Omar Barreto-Rodriguez, Voltaire Mendez-Rodriguez, Anahí Sanchez-Moncivais, Ivette Buendia-Roldan, Leslie Chavez-Galan https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 503 514 10.17305/bjbms.2020.5400 Circ-RNF13, as an oncogene, regulates malignant progression of HBV-associated hepatocellular carcinoma cells and HBV infection through ceRNA pathway of circ-RNF13/miR-424-5p/TGIF2 https://www.bjbms.org/ojs/index.php/bjbms/article/view/5266 <p>Circular RNA RNF13 (circ-RNF13; ID: hsa_circ_0067717) is newly identified to be abnormally upregulated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. However, its role and mechanism remain to be further annotated. First of all, real-time quantitative PCR (RT-qPCR) was utilized to examine RNA expression, and circ-RNF13 was upregulated in HBV-infected human HCC tissues and HBV-expressing cells (Huh7-HBV and Hep3B-HBV), accompanied with TGFβ-induced factor homeobox 2 (TGIF2) upregulation and microRNA (miR)-424-5p downregulation. Loss-of-functional experiments were performed using MTS assay, colony formation assay, flow cytometry, enzyme-linked immunosorbent assay, transwell assay, and xenograft tumor model. As a result, blocking circ-RNF13 enhanced the apoptosis rate of Huh7-HBV and Hep3B-HBV cells, but inhibited cell proliferation, colony formation, migration, and invasion <em>in vitro</em>, along with suppressed tumor growth&nbsp;<em>in vivo</em>. Besides, RT-qPCR data showed that HBV DNA copies and levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were diminished by circ-RNF13 knockdown in Huh7-HBV and Hep3B-HBV cells. Mechanistically, circ-RNF13 and TGIF2 could directly interacting with miR-424-5p according to dual-luciferase reporter assay, suggesting that circ-RNF13 and TGIF2 served as competing endogenous RNAs (ceRNAs) for miR-424-5p. Functionally, overexpressing miR-424-5p mimicked and silencing miR-424-5p counteracted the effects of circ-RNF13 depletion in HBV-expressing HCC cells<em>&nbsp;in vitro</em>; TGIF2 restoration partially abrogated the role of miR-424-5p upregulation. In conclusion, circ-RNF13 might sponge miR-424-5p to suppress HBV-associated HCC cells malignant progression and HBV infection by regulating TGIF2, providing a novel insight into the occurrence and treatment of HBV-associated HCC.&nbsp;</p> Yan Chen Shuhua Li Yinbin Wei Zhihong Xu Xiongfei Wu Copyright (c) 2021 Yan Chen, Shuhua Li, Yinbin Wei, Zhihong Xu, Xiongfei Wu https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 555 568 10.17305/bjbms.2020.5266 Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense https://www.bjbms.org/ojs/index.php/bjbms/article/view/5543 <p>Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host. The virus can counteract type I interferon (IFN-I) production, attenuating IFN-I signaling pathway activation and disrupting antigen presentation. Simultaneously, SARS-CoV-2 infection can enhance apoptosis and the production of inflammatory mediators, which ultimately results in increased disease severity. SARS-CoV-2 produces an array of effector molecules, including nonstructural proteins (NSPs) and open-reading frames (ORFs) accessory proteins. We describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host’s signaling mediating immune evasion in the current review. In addition, the crucial role played by immunomodulation therapy to address immune evasion is discussed. Thus, the current review can provide new directions for the development of vaccines and specific therapies.</p> Abualgasim Elgaili Abdalla Jianping Xie Kashaf Junaid Sonia Younas Tilal Elsaman Khalid Omer Abdalla Abosalif Ayman Ali Mohammed Alameen Mahjoob Osman Mahjoob Mohammed Yagoub Mohammed Elamir Hasan Ejaz Copyright (c) 2021 Abualgasim Elgaili Abdalla , Jianping Xie, Kashaf Junaid, Sonia Younas, Tilal Elsaman, Khalid Omer Abdalla Abosalif, Ayman Ali Mohammed Alameen, Mahjoob Osman Mahjoob, Mohammed Yagoub Mohammed Elamir, Hasan Ejaz https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 515 527 10.17305/bjbms.2020.5543 Development and validation of a ferroptosis-related lncRNAs prognosis signature in colon cancer https://www.bjbms.org/ojs/index.php/bjbms/article/view/5617 <p>Ferroptosis is a form of iron-dependent programmed cell death. Regulation of ferroptosis in tumor cells is a novel treatment modality. The present study aimed to investigate ferroptosis-related long non-coding RNAs (lncRNAs) and construct a prognostic model for colon adenocarcinoma (COAD). RNA- sequencing data and ferroptosis-related genes were obtained from The Cancer Genome Atlas database and FerrDb database. COAD patients were randomly assigned to training- and validation groups. The Least Absolute Shrinkage and Selection Operator regression and Cox regression model were used to determine and develop a predictive model. The model was corroborated using the validation group and the entire group. In total, 259 ferroptosis-related genes and 905 ferroptosis-related LncRNAs were obtained. Cox model revealed and constructed seven ferroptosis-related LncRNAs signature (LINC01503, AC004687.1, AC010973.2, AP001189.3, ARRDC1-AS1, OIP5-AS1, and NCK1-DT). Patients were assigned into two groups according to the median risk score. Kaplan–Meier survival curves showed that overall survival between high- and low-risk groups was statistically significant (P&lt;0.01). Cox multivariate analysis seven ferroptosis-related LncRNAs signature was an independent risk factor for COAD outcomes (P&lt;0.05). The relationship between seven ferroptosis-related LncRNAs and clinicopathological features was also examined. The principal component analysis showed a difference between high- and low-risk groups intuitively. With the aid of gene set enrichment analysis, the underlying mechanisms of seven ferroptosis-related LncRNAs were uncovered, including the MAPK signaling pathway, mTOR signaling pathway, and glutathione metabolism pathway. Finally, we established and validated seven ferroptosis-related lncRNAs signature for COAD patients to predict survival. These results may provide meaningful targets for future study.</p> Hua-jun Cai Zhi-cheng Zhuang Yong Wu Yi-yi Zhang Xing Liu Jin-fu Zhuang Yuan-feng Yang Yuan Gao Bin Chen Guo-xian Guan Copyright (c) 2021 Hua-jun Cai, Zhi-cheng Zhuang, Yong Wu, Yi-yi Zhang, Xing Liu, Jin-fu Zhuang, Yuan-feng Yang, Yuan Gao, Bin Chen, Guo-xian Guan https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 569 576 10.17305/bjbms.2020.5617 The role of WDR76 protein in human diseases https://www.bjbms.org/ojs/index.php/bjbms/article/view/5506 <p>The WD40 repeat (WDR) domain is one of the most abundant protein interaction domains in the human proteome. More than 360 protein interaction domains have been annotated thus far. The WDR domains mediate interactions with peptide regions of important interaction partners in a variety of biological processes. Proteins with the WDR domain which typically contains a seven-bladed β propeller, are continuously being discovered. They represent a large class of proteins that are likely to play important roles. WD40 repeat domain-containing protein 76 (WDR76) is a member of WDR domain-containing proteins. Although it remains poorly understood, it is potentially involved in DNA damage repair, apoptosis, cell cycle progression, and gene expression regulation. Ongoing research on WDR76 is increasing the knowledge regarding its basic functions and role in different pathophysiological. The study of WDR76 is challenging due to the complexity of its interactions with its partners. In the present review, we summarized the current knowledge regarding WDR76, its physiological functions, the close relationship with human diseases, and potential opportunities for target therapy.</p> Jie Yang Fei Wang Baoan Chen Copyright (c) 2021 Jie Yang, Fei Wang, Baoan Chen https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 528 534 10.17305/bjbms.2020.5506 Quantitative detection of circulating MT-ND1 as a potential biomarker for colorectal cancer https://www.bjbms.org/ojs/index.php/bjbms/article/view/5576 <p>Liquid biopsy represents a diagnostic and monitoring tool and the circulating cell-free mitochondrial DNA (mtDNA) plays a vital role in tumor diagnosis and dynamic assessment. Colorectal cancer (CRC) is one of the most common fatal cancers worldwide. Mitochondrially encoded NADH dehydrogenase subunit 1 (MT-ND1) encodes the biggest subunit of respiratory complex I of mtDNA, and mutations in the MT-ND1 are common in CRC. We sought to determine if mutations in circulating MT-ND1 could be a potential biomarker for colorectal cancer. In this study, twenty-two CRC patients at Zhujiang Hospital were included. We mainly used droplet digital PCR to determine the mutation status of MT-ND1, combined with clinical data. In the experiment<em> in vivo</em>, cell-free mtDNA generally presented high concordance with tumor tissues. By quantitative PCR, the MT-ND1 content of plasma in CRC patients was significantly higher than that in healthy individuals (58.01 vs. 0.64, <em>p</em>=0.027). The detection of circulating MT-ND1 content and variants (m.3606 A&gt;G, m.3970 C&gt;T, m.4071 C&gt;T, m.4086 C&gt;T) in cfDNA showed a good correlation with predicted tumor response and progression to chemotherapy. In conclusion, the content and variants of circulating MT-ND1 may become a versatile tool for the diagnosis and monitoring of colorectal cancer.</p> Yichun Xu Jiajing Zhou Qing Yuan Jun Su Qian Li Xiaoliang Lu Liwen Zhang Zhai Cai Junsong Han Copyright (c) 2021 Yichun Xu, Jiajing Zhou, Qing Yuan, Jun Su, Qian Li, Xiaoliang Lu, Liwen Zhang, Zhai Cai, Junsong Han https://creativecommons.org/licenses/by/4.0 2021-10-01 2021-10-01 21 5 577 586 10.17305/bjbms.2021.5576 Application of microfluidic chips in anticancer drug screening https://www.bjbms.org/ojs/index.php/bjbms/article/view/6484 <p><span style="font-weight: 400;">With the continuous development of drug screening technology, new screening methodologies and technologies are constantly emerging, driving drug screening into rapid, efficient and high-throughput development. Microfluidics is a rising star in the development of innovative approaches in drug discovery. In this article, we summarize the recent years' progress of microfluidic chip technology in drug screening, including the developmental history, structural design, and applications in different aspects of microfluidic chips on drug screening. Herein, the existing microfluidic chip screening platforms are summarized from four aspects: chip structure design, sample injection and drive system, cell culture technology on a chip, and efficient remote detection technology. Furthermore, this review discusses the application and developmental prospects of using microfluidic chips in drug screening, particularly in screening natural product anticancer drugs based on chemical properties, pharmacological effects, and drug cytotoxicity.</span></p> Xin-yue Fan Zhuo-fen Deng Yan-yan Yan Valerii E. Orel Andrii Shypko Valerii B. Orel Donika Ivanova Christian Pilarsky Jing Tang Zhe-Sheng Chen Jian-ye Zhang Copyright (c) 2021 Xin-yue Fan, Zhuo-fen Deng, Yan-yan Yan, Valerii E. Orel, Andrii Shypko, Valerii B. Orel, Donika Ivanova, Christian Pilarsky, Jing Tang, Zhe-Sheng Chen, Jian-ye Zhang https://creativecommons.org/licenses/by/4.0 2021-09-30 2021-09-30 21 5 10.17305/bjbms.2021.6484 Quercetin ameliorates testosterone secretion disorder by inhibiting endoplasmic reticulum stress through the miR-1306-5p/HSD17B7 axis in diabetic rats https://www.bjbms.org/ojs/index.php/bjbms/article/view/6299 <p><span style="font-weight: 400;">Testicular damage and testosterone secretion disorder are associated with diabetes mellitus. Quercetin,&nbsp; a common flavonoid, has antioxidant, anti-cancer,&nbsp; and blood sugar lowering effects. Therefore, this study aims to investigate the effect of quercetin on the reproductive system of male rats with diabetes in vivo and in vitro and elucidate its mechanism. Streptozotocin (STZ)&nbsp; induction was used to establish a diabetes model in forty male Sprague Dawley (SD) rats, which were subsequently administered with 20 or 50 mg/kg of quercetin. Leydig cells of rat testes were treated by high glucose (HG) followed by 5 or 10 μM quercetin. Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose,and inhibited oxidative stress. RT-qPCR and Western blotting revealed that quercetin alleviated STZ-induced testicular damage and promoted testosterone synthesis. Both doses of quercetin reduced ROS and MDA levels, and increased SOD level in HG-treated cells. Both, in vivo and in vitro results confirmed that a high dose of quercetin was more effective. MiR-1306-5p was upregulated in testicular tissue of diabetic rats and HG-treated cells. 17β-hydroxysteroid dehydrogenase (HSD17B7) was a target of miR-1306-5p and HSD17B7 was downregulated in STZ-induced rat tissues and HG-treated cells. HSD17B7 overexpression reversed the increase of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (Grp78) protein levels as well as eIF2α phosphorylation level and promotion of cell apoptosis caused by miR-1306-5p overexpression. Moreover, overexpression of HSD17B7 activated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis in HG-treated cells. In conclusion, quercetin inhibits ER stress and improves testosterone secretion disorder through the miR-1306-5p/HSD17B7 axis in diabetic rats.</span></p> <p><br><br></p> Di Wang Yan Li Qian-qian Zhai Yun-feng Zhu Bei-yan Liu Yun Xu Copyright (c) 2021 Di Wang, Yan Li, Qian-qian Zhai, Yun-feng Zhu, Bei-yan Liu, Yun Xu https://creativecommons.org/licenses/by/4.0 2021-09-28 2021-09-28 21 5 10.17305/bjbms.2021.6299