Bosnian Journal of Basic Medical Sciences 2022-01-24T18:32:34+01:00 Faruk Skenderi Open Journal Systems <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> The Association between NOTCH3 expression and the clinical outcome in the urothelial bladder cancer patients 2022-01-24T18:32:34+01:00 Ana Ristic Petrovic Dragana Stokanović Slavica Stojnev Milena Potić Floranović Miljan Krstić Ivana Djordjević Aleksandar Skakić Ljubinka Janković Veličković <p class="normal" style="line-height: 200%;">Disrupted NOTCH activity is a driving event in urothelial bladder cancer (UBC). After activation by hypoxia, the NOTCH3 receptor participates in tumor cell proliferation, acquisition of the epithelial-mesenchymal transition phenotype, and angiogenesis. The aim was to analyze the association of NOTCH3 expression with histopathological and clinical parameters, and to determine its predictive impact on the clinical outcome in UBC patients. The present research included 614 UBC samples incorporated in paraffin tissue microarrays, evaluated by immunohistochemistry for NOTCH3 expression. The accrual period was four years, while the follow-up period was two years. The membranous expression was semi-quantified (0-3), and the mean degree was 1.81±0.94. Criteria for semi-quantification the NOTCH3 expression were the intensity of the staining and the percentage of positive cells. The samples with negative (0) and weak (1) NOTCH3 immunohistochemical (IHC) score were considered negative, while the samples that showed moderate (2) and strong (3) expression were considered positive. Higher degree of positivity was associated with higher risk of cancer-specific mortality (p&lt;0.001). Independent predictors for cancer-specific mortality were NOTCH3 expression and high stage (p&lt;0.001). NOTCH3 expression was not a statistically significant predictor of recurrence-free survival (p=0.816). This study indicated that NOTCH3 is a predictor of poor outcome, suggesting that the NOTCH3 could be potentially reliable IHC marker for selecting the UBC patients that would require more intensive follow-up, especially if they diagnosed in higher stage, with divergent differentiation in pathological report, and without recurrences which would lead them to more frequent medical assessments.</p> 2022-01-24T17:38:24+01:00 Copyright (c) 2022 Ana Ristic Petrovic, Dragana Stokanović, Slavica Stojnev, Milena Potić Floranović, Miljan Krstić, Ivana Djordjević, Aleksandar Skakić, Ljubinka Janković Veličković Whole-exome sequencing reveals rare genetic variations in ovarian granulosa cell tumor 2022-01-21T02:55:40+01:00 Seungyeon Kim Songmi Kim Seyoung Mun Yongsik Kwak Kwang-Sun Suh Song-Yi Choi Kyudong Han <p>Ovarian granulosa cell tumor (OGCT) is a rare ovarian tumor that accounts for about 2-5% of all ovarian tumors. Despite the low grade of ovarian tumors, high and late recurrences are common in OGCT patients. Even though this tumor usually occurs in adult women with high estrogen levels, the cause of OGCT is still unknown. To screen genetic variants associated with OGCT, we collected normal and matched-tumor formalin-fixed paraffin-embedded (FFPE) from 11 OGCT patients and performed whole-exome sequencing (WES) using Illumina NovaSeq 6000. A total of 1,067,219 single nucleotide polymorphisms (SNPs) and 162,155 insertions/deletions (indels) were identified from 11 pairs of samples. Of these, we identified 44 tumor-specific SNPs in 22 genes and four tumor-specific indels in one gene that were common to 11 patients. We used three cancer databases (TCGA, COSMIC, and ICGC) to investigate genes associated with ovarian cancers. Nine genes (<em>SEC22B</em>, <em>FEZ2</em>, <em>ANKRD36B</em>, <em>GYPA</em>, <em>MUC3A</em>, <em>PRSS3</em>, <em>NUTM2A</em>, <em>OR8U1</em>, and <em>KRTAP10-6) </em>associated with ovarian cancers were found in all three databases. In addition, we identified seven rare variants with MAF ≤ 0.05 in two genes (<em>PRSS3</em> and <em>MUC3A</em>). Of seven rare variants, five variants in <em>MUC3A</em> are potentially pathogenic. Furthermore, we conducted gene enrichment analysis of tumor-specific 417 genes in SNPs and 106 genes in indels using cytoscape and metascape. In GO analysis, these genes were highly enriched in “selective autophagy”, and “regulation of anoikis”. Taken together, we suggest that <em>MUC3A</em> is implicated in OGCT development, and <em>MUC3A</em> could be used as a potential biomarker for OGCT diagnosis.</p> 2022-01-17T21:15:25+01:00 Copyright (c) 2022 Seungyeon Kim, Songmi Kim, Seyoung Mun, Yongsik Kwak, Kwang-Sun Suh, Song-Yi Choi, Kyudong Han The hemoglobin, albumin, lymphocyte, and platelet (HALP) score as a prognostic marker for patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy: a retrospective study from two centers 2022-01-19T06:33:34+01:00 Xiaomin Gao Binwei Lin Qi Lin Tingyu Ye Tao Zhou Maolin Hu Honghui Zhu Feng Lu Wei Chen Peng Xia Fangyi Zhang Zhixian Yu <p>The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP&lt;28.67 group and HALP≥28.67 group. Kaplan-Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (<em>P</em>&lt;0.001) and progression-free survival (PFS) (<em>P</em>&lt;0.001). Multivariate analysis demonstrated that lower HALP score was an independent risk factor for OS (HR=1.54, 95%CI, 1.14-2.01, <em>P</em>=0.006) and PFS (HR=1.44, 95%CI, 1.07-1.93, <em>P</em>=0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without. In the subgroup analysis, the HALP score could also stratify patients with respect to survival under different pathologic T stages. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.</p> 2022-01-12T22:25:45+01:00 Copyright (c) 2022 Xiaomin Gao, Binwei Lin, Qi Lin, Tingyu Ye, Tao Zhou, Maolin Hu, Honghui Zhu, Feng Lu, Wei Chen, Peng Xia, Fangyi Zhang, Zhixian Yu TPRG1 contributes to inflammation and cell proliferation of cystitis glandularis through regulating NF-кB/COX2/PGE2 axis 2022-01-24T16:03:23+01:00 Tao Hong Songzhe Piao Liangxue Sun Yiran Tao Mang Ke <p>Cystitis glandularis is characterized by chronic inflammation and hyperproliferation of bladder mucosa, and contributes to progression of bladder adenocarcinoma. TPRG1 (Tumor Protein P63 Regulated 1) is related to cellular inflammatory response, and dysregulation of TPRG1 in tumor tissues is associated with tumor early recurrence. The effect of TPRG1 on cystitis glandularis was investigated in this study. Firstly, bladder specimen were isolated from patients with cystitis glandularis and <em>E. coli-</em>induced cystitis rat. Expression of TPRG1 was found to be up-regulated in the bladder specimen. Moreover, adeno-associated virus (AAV)-mediated silence of TPRG1 was delivered into rat, and data from hematoxylin and eosin (H and E) staining showed that injection with AAV-shTPRG1 ameliorated <em>E. coli-</em>induced histological changes in bladder tissues of rats, and suppressed the inflammatory response. Secondly, TPRG1 was also increased in primary cystitis glandularis cells. Knockdown of TPRG1 decreased cell proliferation of primary cystitis glandularis cells, and suppressed the migration. Thirdly, cyclooxygenase-2 (COX-2) was up-regulated in the bladder specimen isolated from patients with cystitis glandularis and <em>E. coli-</em>induced cystitis rat. Injection with AAV-shTPRG1 reduced protein expression of COX-2, p65 and prostaglandin E2 (PGE2) in the bladder specimen. Lastly, interference of COX-2 attenuated TPRG1 over-expression-induced increase of cell proliferation and migration in the primary cystitis glandularis cells. In conclusion, TPRG1 promoted inflammation and cell proliferation of cystitis glandularis through activation of NF-кB/COX2/PGE2 axis.</p> 2022-01-07T10:24:01+01:00 Copyright (c) 2022 Tao Hong, Songzhe Piao, Liangxue Sun, Yiran Tao, Mang Ke Impact of Smoking on the Incidence and Postoperative Complications of Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Cohort Studies 2022-01-15T13:05:18+01:00 Yuqi He Mohamed Omar Xiaoyuan Feng Claudia Neunaber Michael Jagodzinski <p>Osteoarthritis and rheumatoid arthritis are the most ubiquitous joint disorders which cause tremendous loss of life quality and impose an economic burden on society. At present, the treatment options for these two diseases comprise non-operative and surgical treatments, amongst those total knee arthroplasties (TKA). Various studies have recognized smoking as a significant risk factor for postoperative complications. Therefore, the purpose of this study was to examine the impact of smoking on the incidence and postoperative complications after a total knee arthroplasty by a systematic review and meta-analysis. The research was performed using PUBMED, Cochrane Library and EMBASE, extracting data from thirteen suitable studies and incorporating 2,109,482 patients. Cohort studies evaluating the impact of smoking on TKA with sufficient data were included for the study, and cohort studies without a proper control group and complete data were excluded. A fixed-effects or random-effects model was used to measure the pooled risk ratio (RR) or hazard ratio (HR) with 95% confidence interval (CI). Compared to non-smokers, smokers had a significantly lower incidence of TKA (p&lt;0.01). However, smokers had a higher incidence of total complications (p=0.01), surgical complications (p&lt;0.01), pneumonia (p&lt;0.01) and revision surgery (p=0.01). No significant difference in the risk of blood transfusion (p=0.42), deep vein thrombosis (p=0.31), pulmonary embolism (p=0.34), urinary tract infection (p=0.46) or mortality (p=0.39) was found between smokers and non-smokers. In conclusion, the study indicated that tobacco has two diametrically opposite effects on TKA patients: 1. Tobacco increases the incidence of surgical complications, pneumonia and revision after TKA; 2. It decreases the overall risk of being a candidate for TKA.</p> 2021-12-19T20:20:27+01:00 Copyright (c) 2021 Yuqi He, Mohamed Omar, Xiaoyuan Feng, Claudia Neunaber, Michael Jagodzinski MicroRNA-573 inhibits cell proliferation, migration and invasion and is downregulated by PICSAR in cutaneous squamous cell carcinoma 2022-01-18T13:41:05+01:00 Yanhua Wang Shengjian Tang Jianping Lv <p>The incidence of cutaneous squamous cell carcinoma (cSCC) has been increasing in recent years. Meanwhile, microRNAs (miRNAs) have been found to play vital roles in various cancers, including cSCC. This study aimed to investigate the expression of microRNA-573 (miR-573) in cSCC, its relationship with long non-coding RNA PICSAR and analyze its biological role. The relationship between PICSAR and miR-573 was confirmed by dual-luciferase reporter assay and Pearson’s correlation coefficient analysis. The levels of PICSAR and miR-573 were measured using quantitative Real-Time PCR. Cell Counting Kit-8 assay was used to evaluate the cSCC cell proliferation ability. The migration and invasion abilities of cSCC cells were evaluated by Transwell assay. PICSAR expression was increased and miR-573 was decreased in tumor tissues and cSCC cell lines. PICSAR and miR-573 can bind directly, and miR-573 expression was downregulated by PICSAR in cSCC. Overexpression of miR-573 significantly inhibited the proliferation, migration and invasion abilities of A431 and SCC13 cells. Additionally, miR-573 overexpression reversed the promotion effects of PICSAR overexpression on cSCC cell proliferation, migration and invasion abilities. In conclusion, our findings indicated that miR-573 expression was decreased in tumor tissues and cSCC cells and was downregulated by PICSAR in cSCC. Additionally, miR-573 overexpression inhibited cSCC cell proliferation, migration and invasion, and reversed the promotion effects of PICSAR overexpression on cSCC cell biological functions. Thus, miR-573 might function as a tumor suppressor and might be involved in the regulatory effects of PICSAR on tumorigenesis in cSCC.</p> 2021-12-15T01:41:17+01:00 Copyright (c) 2021 Yanhua Wang, Shengjian Tang, Jianping Lv LncRNA ADAMTS9-AS1 knockdown suppresses cell proliferation and migration in glioma via down-regulating Wnt/β-catenin signaling pathway 2022-01-15T13:27:34+01:00 Chunhui Zhou Hulin Zhao Shuiwei Wang Chao Dong Fan Yang Jianning Zhang <p>The long non‐coding RNA antisense 1 ADAMTS9-AS1 has been reported to serve as an oncogene or tumor suppressor in several tumors, including colorectal cancer and hepatocellular carcinoma. Nevertheless, the clinical significance and biological behaviors of ADAMTS9-AS1 in glioma still remain unclear. Therefore, the goal of this study was to evaluate the functional roles and potential mechanisms of ADAMTS9-AS1 in glioma cells. Using quantitative real-time PCR analysis, we found that ADAMTS9-AS1 was upregulated in glioma tissues and cells in comparison to corresponding controls. ADAMTS9-AS1 expression level was correlated to tumor size (p=0.005) and WHO grade (p=0.002). Kaplan-Meier analysis and Cox multivariate analysis showed that ADAMTS9-AS1 could serve as an independent prognostic factor affecting the overall survival of glioma patients. Functionally, depletion of ADAMTS9-AS1 significantly suppressed the proliferation, migration and invasion in glioma cell lines (U251 and U87), as shown via CCK-8 assay, Edu corporation assay, wound healing assay and transwell assay. Furthermore, we demonstrated that knockdown of ADAMTS9-AS1 suppressed Wnt1, β-catenin, c-myc and PCNA, while upregulating E-cadherin expression. In conclusion, our data revealed that ADAMTS9-AS1 confers oncogenic function in the progression of glioma, thus targeting ADAMTS9-AS1 might be a promising therapeutic strategy for this disease.</p> 2021-12-11T20:56:06+01:00 Copyright (c) 2021 Chunhui Zhou, Hulin Zhao, Shuiwei Wang, Chao Dong, Fan Yang, Jianning Zhang Three-dimensional telomere profiles in papillary thyroid cancer variants: a pilot study 2022-01-12T14:29:55+01:00 Aline Rangel-Pozzo Tinuccia Dettori Daniela Virginia Frau Federica Etzi John Gartner Garbor Fisher Roberta Vanni Sabine Mai Paola Caria <p>Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.</p> 2021-12-08T23:55:42+01:00 Copyright (c) 2021 Aline Rangel-Pozzo, Tinuccia Dettori, Daniela Virginia Frau, Federica Etzi, John Gartner, Garbor Fisher, Roberta Vanni, Sabine Mai, Paola Caria Predictive performance of CT for adverse outcomes among COVID-19 suspected patients: a two-center retrospective study 2021-10-29T10:25:52+02:00 Begümhan Baysal Mahmut Bilal Dogan Mutlu Gulbay Mine Sorkun Murathan Koksal Aliye Bastug Sumeyye Kazancioglu Bahadir Orkun Ozbay Sacit Icten Ferhat Arslan Yasemin Cag Hurrem Bodur Haluk Vahaboglu <p>The aim of the study was to compare the performance of various computed tomography (CT) reporting tools, including zonal CT visual score (ZCVS), the number of involved lobes, and Radiological Society of North America (RSNA) categorization in predicting adverse outcomes among patients hospitalized due to the lower respiratory symptoms during the coronavirus disease 2019 (COVID-19) pandemic. A total of 405 patients admitted with severe respiratory symptoms who underwent a chest CT were enrolled. The primary adverse outcome was intensive care unit (ICU) admission of patients. Predictive performances of reporting tools were compared using the area under the receiver operating characteristic curves (AUC ROC). Among the 405 patients, 39 (9.63%) required ICU support during their hospital stay. At least two or more observers reported a typical and indeterminate COVID-19 pneumonia CT pattern according to RSNA categorization in 70% (285/405) of patients. Among these, 63% (179/285) had a positive polymerase chain reaction (PCR test for the SARS-CoV-2 virus. The median number of lobes involved according to CT was higher in patients who required ICU support (median interquartile range [IQR], 5[3; 5] vs. 3[0; 5]). The median ZCVS score was higher among the patients that subsequently required ICU support (median [IQR], 4[0; 12] vs. 13[5.75; 24]). The bootstrap comparisons of AUC ROC showed significant differences between reporting tools, and the ZCVS was found to be superior (AUC ROC, 71-75%). The ZCVS score at the first admission showed a linear and significant association with adverse outcomes among patients with the lower respiratory tract symptoms during the COVID-19 pandemic.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Begümhan Baysal, Mahmut Bilal Dogan, Mutlu Gulbay, Mine Sorkun, Murathan Koksal, Aliye Bastug, Sumeyye Kazancioglu, Bahadir Orkun Ozbay, Sacit Icten, Ferhat Arslan, Yasemin Cag, Hurrem Bodur, Haluk Vahaboglu Efficacy of chemotherapeutics in classic and non-classic Kaposi sarcoma: A single-center retrospective real-world data 2021-10-29T10:27:36+02:00 Sibel Oyucu Orhan Ahmet Bilgehan Sahin Erdem Cubukcu Adem Deligonul Birol Ocak Bedrettin Orhan Turkkan Evrensel <p>Kaposi sarcoma is a rare disease and there is a gap in the literature about which chemotherapeutics should be applied, especially for the classical type. We aimed to present our institutional data on the demographic characteristics, treatment, and treatment efficacy in 16 Kaposi sarcoma (KS) patients treated with chemotherapy. We retrospectively analyzed the demographic and clinical characteristics, and the chemotherapeutic agents administered to the 16 KS patients diagnosed in our center and treated with chemotherapy, based on the medical records obtained. The median age, gender, type of KS, site of involvement, cytotoxic agents administered, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles of the patients were evaluated. The median age at disease onset was 61.07 years (range, 39.4–85.8 years). Among the patients, 1 had immunosuppression-related KS, 4 had AIDS-related KS, and 11 had classical KS. In the first-line cytotoxic therapy, 7 patients received pegylated-liposomal doxorubicin (PLD), 6 patients received paclitaxel, 2 patients received oral etoposide, and 1 patient received the adriamycin, bleomycin, and vincristine regimen. In the Kaplan–Meier analysis, the PFS was 39.9 months (95% CI, 7.7–72.0). In the first-line setting, a significant difference in terms of PFS was observed between the PLD- and paclitaxel-treated groups (not reached vs. 12.8 months, <em>p</em> = 0.033). The OS was 66.1 months (95% CI, 30.2–102.0). The ORR of the 16 patients was 43.8%, and their DCR was 81.3%. No grade 3 or 4 toxicity was observed. This retrospective study showed that PLD seems better than paclitaxel in terms of PFS and response rates and it has shown to have a good safety profile in KS patients.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Sibel Oyucu Orhan, Ahmet Bilgehan Sahin, Erdem Cubukcu, Adem Deligonul, Birol Ocak, Bedrettin Orhan, Turkkan Evrensel Clinicopathological characteristics and survival in lung signet ring cell carcinoma: a population-based study 2021-10-29T10:29:08+02:00 Yunting Cai Yan Xie Yanli Xiong Wei Guan Yu Pu Dong Wang Mingfang Xu Shenglan Meng <p>Lung signet-ring cell carcinoma (LSRCC) is a very rare type of lung cancer, the clinical characteristics, and prognosis of which remain to be clarified. In order to explore the clinicopathological and survival-related factors associated with LSRCC, we performed a large population-based cohort analysis of data included in the Surveillance, Epidemiology, and End Results (SEER) registry from 2001 to 2015. A total of 752 LSRCC and 7518 lung mucinous adenocarcinoma (LMAC) patients were incorporated into our analysis, with respective mean ages of 63.8 and 67.5 years at the time of diagnosis. LSRCC patients were significantly more likely than LMAC patients to have distant-stage disease (72.1% vs. 45.8%, <em>p </em>&lt; 0.0001), tumors of a high pathological grade (40.6% vs. 10.8%, <em>p </em>&lt; 0.0001), have undergone chemotherapy (62.1% vs. 39.9%, p&lt;0.0001), be male (52.7% vs. 48.5%, <em>p </em>= 0.03), and be &lt; 40 years old (3.3% vs. 1.3%, <em>p </em>= 0.022), whereas they were less likely to have undergone surgical treatment (52.4% vs. 77.0%, <em>p </em>&lt; 0.0001). LSRCC and LMAC patients exhibited median overall survival (OS) duration of 8 and 18 months (<em>p </em>&lt; 0.0001), respectively, although these differences were not significant after adjusting for confounding variables. Independent factors associated with a favorable patient prognosis included a primary site in the middle or lower lung lobe, underwent surgery, and underwent chemotherapy. However, age ≥80 years, higher grade, distant summary stage disease, and T4 stage disease were linked to poor prognosis. Patient age, tumor grade, primary tumor site, summary stage, T stage, surgery, and chemotherapy were all significantly associated with LSRCC patient prognosis.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Yunting Cai , Yan Xie , Yanli Xiong , Wei Guan , Yu Pu, Dong Wang, Mingfang Xu, Shenglan Meng Construction and verification of prognostic nomogram for early-onset esophageal cancer 2021-10-29T10:31:41+02:00 Xiaoxiao Liu Wei Guo Xiaobo Shi Yue Ke Yuxing Li Shupei Pan Yingying Jin Yuchen Wang Qinli Ruan Hongbing Ma <p>This study aimed to build up nomogram models to evaluate overall survival (OS) and cancer-specific survival (CSS) in early-onset esophageal cancer (EOEC). Patients diagnosed with esophageal cancer (EC) from 2004 to 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Clinicopathological characteristics of younger versus older patients were compared, and survival analysis was performed in both groups. Independent related factors influencing the prognosis of EOEC were identified by univariate and multivariate Cox analysis, which were incorporated to construct a nomogram. The predictive capability of the nomogram was estimated by the concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). A total of 534 younger and 17,243 older patients were available from the SEER database. Younger patients were randomly segmented into a training set (n = 266) and a validation set (n = 268). In terms of the training set, the C-index of the OS nomogram was 0.740 (95% CI: 0.707-0.773), and that of the CSS nomogram was 0.752 (95% CI: 0.719-0.785). In view of the validation set, the C-index of OS and CSS were 0.706 (95% CI: 0.671-0.741) and 0.723 (95% CI: 0.690-0.756), respectively. Calibration curves demonstrated the consistent degree of fit between actual and predicted values in nomogram models. From the perspective of DCA, the nomogram models were more beneficial than the tumor-node-metastasis (TNM) and the SEER stage for EOEC. In brief, the nomogram model can be considered as an individualized quantitative tool to predict the prognosis of EOEC patients to assist clinicians in making treatment decisions.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Xiaoxiao Liu, Wei Guo, Xiaobo Shi, Yue Ke, Yuxing Li; Shupei Pan, Yingying Jin, Yuchen Wang, Qinli Ruan; Hongbing Ma Effects of L-dopa on expression of prolactin and synaptotagmin IV in 17-beta-estradiol-induced prolactinomas of ovariectomized hemiparkinsonian rats 2021-11-19T19:16:04+01:00 Maja Zorovic Kaja Kolmančič Marko Živin <p>Parkinson’s disease (PD) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. Dopamine precursor levodopa (L-dopa) is used as the first-line treatment for PD. Evidence suggests neuroprotective effects of estrogens in PD. Since both 17b-estradiol (E2) and L-dopa act as regulators of prolactin (PRL) secretion from the pituitary gland, we investigated their effect on the expression of PRL in prolactinomas that developed in ovariectomized hemiparkinsonian rats treated with E2. We also investigated the effect of E2 and L-dopa on the expression of synaptotagmin IV (Syt IV), an immediate early gene whose product is abundant in the pituitary gland and was found to be highly co-expressed with PRL in lactotrophs (&gt;90%). The hemiparkinsonian rat model was obtained by unilateral lesioning of dopaminergic nigrostriatal neurons. Rats received silastic tubing implants with E2 and were treated with L-dopa. Enzyme-linked immunosorbent assay and immunohistochemistry were used to assess the serum concentrations of PRL and E2 and expression of PRL and Syt IV in the tissue of adenohypophysis, respectively. We found that high levels of serum E2 were associated with the upregulation of Syt IV and PRL in PRL-ir cells, while treatment with L-dopa decreased the size of prolactinomas and downregulated Syt IV but had no effect on PRL expression or serum concentrations.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Maja Zorovic, Kaja Kolmančič, Marko Živin Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis 2021-10-29T10:14:51+02:00 Archana A. Gupta Supriya Kheur Saranya Varadarajan Sameena Parveen Harisha Dewan Yaser Ali Alhazmi Thirumal A. Raj Luca Testarelli Shankargouda Patil <p>The objective of the present article was to qualitatively and quantitatively review the association between chronic mechanical irritation and oral squamous cell carcinoma (OSCC). PubMed, SCOPUS, and Web of Science databases were searched using the keyword combinations “chronic trauma and oral squamous cell carcinoma; chronic irritation and oral squamous cell carcinoma; chronic irritation and oral cancer; and chronic trauma and oral cancer.” Duplicates and irrelevant articles were excluded after the title and abstract screening. The full texts of the remaining articles were assessed using selection criteria. A total of 375 (PubMed-126; SCOPUS-152; WOS-97) articles were screened, and 343 duplicates and irrelevant articles were excluded from the study. Only 9 of the remaining 32 articles met the selection criteria and were included in the qualitative analysis. Buccal mucosa and tongue, being highly prone to chronic irritation through the dental prosthesis, were the common sites for OSCC. Edentulous subjects with ill-fitting dentures were at a high risk of developing chronic irritation associated-OSCC. According to the Joanna Briggs Institute of risk assessment, eight of the nine included studies had a low risk of bias. The quantitative analysis showed a significant association (<em>p </em>&lt; 0.00001) between the chronic oral mucosal irritation and OSCC with an overall risk ratio of 2.56 at a confidence interval of 1.96-3.35. Chronic oral mucosa irritation has a significant association with OSCC, and the nature of association could be that of a potential co-factor (dependent risk factor) rather than an independent risk factor.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Supriya Kheur, Saranya Varadarajan, Sameena Parveen, Harisha Dewan, Yaser Ali Alhazmi, Thirumal A. Raj , Luca Testaralli, Shankargouda Patil Integrated profiling identifies ITGB3BP as prognostic biomarker for hepatocellular carcinoma 2021-11-19T19:29:15+01:00 Qiuli Liang Chao Tan Feifei Xiao Fuqiang Yin Meiliang Liu Lei Lei Liuyu Wu Yu Yang Hui Juan Jennifer Tan Shun Liu Xiaoyun Zeng <p>Hepatocellular carcinoma (HCC) is a highly malignant tumor. In this study, we sought to identify a novel biomarker for HCC by analyzing transcriptome and clinical data. The R software was used to analyze the differentially expressed genes (DEGs) in the datasets GSE74656 and GSE84598 downloaded from the Gene Expression Omnibus database, followed by a functional annotation. A total of 138 shared DEGs were screened from two datasets. They were mainly enriched in the “Metabolic pathways” pathway (Padj = 8.21E-08) and involved in the carboxylic acid metabolic process (Padj = 0.0004). The top 10 hub genes were found by protein-protein interaction analysis and were upregulated in HCC tissues compared to normal tissues in The Cancer Genome Atlas database. Survival analysis distinguished 8 hub genes CENPE, SPDL1, Hyaluronan-mediated motility receptor, Rac GTPase activating protein 1, Thyroid hormone receptor interactor 13, cytoskeleton-associated protein (CKAP) 2, CKAP5, and Integrin subunit beta 3 binding protein (ITGB3BP) were considered as prognostic hub genes. Multivariate cox regression analysis indicated that all the prognostic hub genes were independent prognostic factors for HCC. Furthermore, the receiver operating characteristic curve revealed that the 8-hub genes model had better prediction performance for overall survival compared to the T stage (<em>p </em>= 0.008) and significantly improved the prediction value of the T stage (<em>p </em>= 0.002). The Human Protein Atlas showed that the protein expression of ITGB3BP was upregulated in HCC, so the expression of ITGB3BP was further verified in our cohort. The results showed that ITGB3BP was upregulated in HCC tissues and was significantly associated with lymph node metastasis.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Qiuli Liang, Chao Tan, Feifei Xiao, Fuqiang Yin, Meiliang Liu, Lei Lei, Liuyu Wu, Yu Yang, Hui Juan Jennifer Tan, Shun Liu, Xiaoyun Zeng The preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) score is a useful predictor in patients with resectable esophageal squamous cell carcinoma 2021-10-29T10:33:30+02:00 Ji-Feng Feng Liang Wang Xun Yang <p>The hemoglobin, albumin, lymphocyte and platelet (HALP) score has been confirmed as a prognostic factor in several types of cancers. The current study aimed to assess the prognostic value of preoperative HALP score, an inflammatory and nutritional based score, in predicting cancer-specific survival (CSS) in resectable patients undergoing curative resection for esophageal squamous cell carcinoma (ESCC). The clinical data of 355 consecutive patients with ESCC who underwent curative resection were retrospectively conducted and analyzed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value for preoperative HALP. The areas under the curve (AUC) for preoperative HALP and other variables were calculated and compared. Cox regression analyses and Kaplan–Meier methods were used to identify the factors associated with CSS. According to the ROC curve, the optimal cut-off value for preoperative HALP was 31.8. The 5-year CSS for preoperative HALP low (≤31.8) and high (&gt;31.8) was 15.1% and 47.5%, respectively (<em>p </em>&lt; 0.001). Preoperative HALP had reliable abilities to predict CSS in resectable ESCC patients in any stage or gender, according to the subgroup analysis based on the patients’ cancer stage and gender. Multivariate analyses confirmed that preoperative HALP was an independent prognostic score regarding CSS in patients with resectable ESCC (<em>p </em>&lt; 0.001). This study confirmed that the postoperative HALP score could be regarded as a potential independent prognostic factor for CSS in patients with resectable ESCC.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Ji-Feng Feng, Liang Wang, Xun Yang Analysis of the diagnostic and prognostic value of miR-9-5p in carotid artery stenosis 2021-11-19T19:30:22+01:00 Hongxin Liu Juan Zhou Wei Jiang Feng Wang <p>More and more evidence shows that microRNAs (miRNAs) play an important role in the diagnosis and prognosis of human diseases. In this study, we investigated the diagnostic value of miR-9-5p for asymptomatic carotid artery stenosis (CAS) and its predictive value for future cerebrovascular events within 5 years. A total of 88 asymptomatic CAS patients and 86 healthy individuals were recruited. The expression level of serum miR-9-5p was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic value of miR-9-5p in CAS was assessed by a receiving operator characteristic (ROC) curve. The predictive value of miR-9-5p for the occurrence of cerebrovascular events was evaluated by the Kaplan-Meier method. The serum level of miR-9-5p was significantly decreased in asymptomatic CAS patients. ROC curve had an AUC value of 0.910, with the sensitivity and specificity of 80.7% and 87.2% at the cut-off value of 0.72, respectively. A total of 25 patients had cerebrovascular events during the 5-year follow-up, including 3 strokes and 22 transient ischemic attacks<strong>&nbsp;</strong>(TIAs). Kaplan-Meier survival analysis revealed that the low expression level of miR-9-5p was an independent factor closely related to the occurrence of cerebrovascular events. Serum miR-9-5p could be used as a new biomarker for the diagnosis of CAS, and the low expression of miR-9-5p is associated with poor prognosis.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Hongxin Liu, Juan Zhou, Wei Jiang, Feng Wang Pharmacogenetics of new classes of antidiabetic drugs 2021-11-19T19:04:35+01:00 Selma Imamovic Kadric Aida Kulo Cesic Tanja Dujic <p>Type 2 diabetes (T2D) has a continuously rising prevalence worldwide. Pharmacogenetics has been recognized as a promising concept for pharmacological treatment of T2D, as antidiabetic drugs are not equally effective and safe for all patients, and the costs of diabetes treatment are increasing. The latest published guidelines on T2D treatment firmly endorse the use of newer antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-IVi), and glucagon-like peptide-1 receptor agonists (GLP-1RA), considering their satisfactory pharmacological effect and good safety profile. Furthermore, SGLT2i and GLP-1RA show protective effects in patients with established atherosclerotic cardiovascular disease and chronic kidney disease. However, there has been growing evidence that the effectiveness and safety of these drug classes could depend on genetic variability. Here, we summarized the results of the published studies on the pharmacogenetic biomarkers for the three drug classes. A number of genetic variations have been investigated so far. The explored candidate genes mostly encode drug targets, drug-metabolizing enzymes, and genes linked to T2D risk. Although many of the results are promising, it is still necessary to obtain more information from larger controlled studies to confirm their clinical significance. This approach may lead towards more personalized treatment for patients with T2D.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Selma Imamovic Kadric, Aida Kulo Cesic, Tanja Dujic Letter regarding “Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis” 2021-10-29T10:35:14+02:00 Jian Xie Lang Li <p>Dear Editor:</p> <p>We have read with a great interest the article by Gupta et al. [1] who performed a meta-analysis exploring the association between chronic mechanical irritation and oral squamous cell carcinoma. The conclusion of the meta-analysis is that chronic oral mucosa irritation has a significant association with oral squamous cell carcinoma, and the nature of association could be that of a potential co-factor (dependent risk factor) rather than an independent risk factor.</p> <p>Read more in <a href="">PDF.</a></p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Jian Xie, Lang Li Reply to the letter regarding “Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis” 2021-10-29T10:34:49+02:00 Archana A Gupta Supriya Kheur Saranya Varadarajan Sameena Parveen Harisha Dewan Yaser Ali Alhazmi A. Thirumal Raj Luca Testarelli Shankargouda Patil <p>Dear Editor,</p> <p>We thank Dr. Jian Xie for the valuable inputs on our paper titled ‘Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis [1].’ The first concern of Dr. Xie was that we had included two studies that were based on the same population. We re-examined these papers, one was published in 2010 [2] and the other in 2017 [3] by the same group of authors. Given the significant time difference between the two papers, we did not want to presume they were from the same sample population. There is no clear evidence that they are from the same sample population.</p> <p>Read more in <a href="">PDF</a>.</p> 2021-12-01T00:00:00+01:00 Copyright (c) 2021 Archana A Gupta, Supriya Kheur, Saranya Varadarajan, Sameena Parveen, Harisha Dewan, Yaser Ali Alhazmi, A. Thirumal Raj, Luca Testarelli, Shankargouda Patil