Bosnian Journal of Basic Medical Sciences 2021-06-12T16:35:17+02:00 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> Construction and validation of prognostic nomogram for metaplastic breast cancer 2021-06-10T17:41:10+02:00 Yongfeng Li Daobao Chen Haojun Xuan Mihnea P. Dragomir George A. Calin Xuli Meng Meng Chen Hongchuan Jin <p><span style="font-weight: 400;">In this study we aimed to develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with metaplastic breast cancer (MBC). Data of patients diagnosed with MBC from 1973 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors for OS and CSS of MBC patients. The obtained prognostic variables were combined to construct nomogram models for predicting OS and CSS in patients with MBC. Model performance was evaluated using concordance index (C-index) and calibration plots. Data from 1125 patients were collected and divided into a training (750) and a validation (375) cohort. The multivariate Cox model identified age, TNM stage, tumor size, and radiotherapy as independent covariates associated with OS and CSS. The nomogram constructed based on these covariates demonstrated excellent accuracy in estimating 3-, and 5-year OS and CSS, with a C-index of 0.769 (95% CI, 0.731-0.808) for OS and 0.761 (95% CI, 0.713-0.809) for CSS in the training cohort. In the validation cohort, the nomogram-predicted C-index was 0.738 (95%CI, 0.676-0.800) for OS and 0.747 (95%CI, 0.667-0.827) for CSS. All calibration curves exhibited good consistency between predicted and actual survival. The nomogram models established in this study may enhance the accuracy of prognosis prediction and therefore may improve individualized assessment of survival risks and enable constructive therapeutic suggestions. </span></p> 2021-06-10T00:00:00+02:00 Copyright (c) 2021 Yongfeng Li, Daobao Chen, Haojun Xuan, Mihnea P. Dragomir, George A. Calin, Xuli Meng, Meng Chen, Hongchuan Jin Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers 2021-06-05T17:39:02+02:00 Semir Vranic Zoran Gatalica <p>Antibody-drug conjugates (ADCs) represent a new class of highly potent antineoplastic drugs built by attaching a small molecule of an anticancer drug (payload) or another therapeutic agent to an antibody recognizing an epitope on the targeted cells. Trophoblast cell-surface antigen-2 (Trop-2) was originally described in trophoblasts and fetal tissues, but subsequently, its overexpression has been demonstrated in various solid malignancies. Sacituzumab govitecan, a conjugate of anti-Trop-2 antibody and SN-38 payload (an active metabolite of irinotecan), is the first in the class that has been clinically validated and approved by the Food and Drug Administration for the treatment of metastatic triple-negative breast (2020) and urothelial carcinomas (2021). In the current review, we summarize and critically appraise the most recent advances with Sacituzumab govitecan, emphasizing the predictive biomarker analysis.</p> 2021-06-04T23:50:22+02:00 Copyright (c) 2021 Semir Vranic, Zoran Gatalica Protocatechuic acid as an inhibitor of the JNK/CXCL1/CXCR2 pathway relieves neuropathic pain in CCI rats 2021-06-11T15:06:07+02:00 Hong-xia Chang Yue-feng Zhao <p><span style="font-weight: 400;">Emerging evidence has shown that protocatechuic acid (PCA) has antioxidant and anti-inflammatory effects. It can alleviate the injury of sciatic nerve, while the mechanism of its therapeutic effect on neuralgia remains unknown . In vivo, chromium bowel ligation was used to establish a chronic constriction injury (CCI) rat model to induce sciatic nerve pain, then two doses of PCA were used to treat CCI rats. In vitro, 10 ng/mL TNF-α was used to stimulate glial satellite cells derived from the dorsal root ganglia (DRG) L4-L6 of the sciatic nerve to simulate sciatic nerve pain. PCA relieved mechanical allodynia and thermal hyperalgesia in CCI rats. CCK-8 assay revealed that PCA inhibited the proliferation of glial satellite cells induced by TNF-α. Moreover, ELISA demonstrated that PCA could improve the inflammatory response of rats caused by CCI and cells induced by TNF-α. Next, RT-qPCR and Western blot assays testified that PCA blocked the c-Jun N-terminal kinase/the chemokine ligand 1/CXC chemokine receptor 2 (JNK/CXCL1/CXCR2) pathway by inhibiting CXCL1 levels in cells induced by TNF-α and DRG of CCI rats. In conclusion, PCA can alleviate neuropathic pain of CCI rats, improve oxidative stress by inhibiting the JNK/CXCL1/CXCR2 signaling pathway, which provides a new perspective for the treatment of neuropathic pain caused by CCI.</span></p> 2021-06-01T17:20:52+02:00 Copyright (c) 2021 Hong-xia Chang, Yue-feng Zhao The effect of VEGF rs35569394 in esophageal cancer and response to chemotherapy 2021-06-12T16:35:17+02:00 Zishan Wang Chenwei Li Xinjian Li Jianguang Shi Weijie Wu <p>The objective of this study was to investigate the possible association between the single nucleotide polymorphism (SNP), rs35569394, of the vascular endothelial growth factor gene (<em>VEGF</em>) and the risk of esophageal cancer (EC) in the Han Chinese population. A total of 290 EC subjects and 322 ethnically matched unrelated healthy controls free from the esophageal disease were studied. Genomic DNA was isolated from peripheral blood by salting out. Genotyping of <em>VEGF</em> rs35569394 polymorphism was carried out via polymerase chain reaction followed by agarose gel electrophoresis. The results showed that the distribution of genotypes was significantly different across the gender groups (<em>p</em>=0.032) and clinical stages (p=0.034). <em>VEGF</em> rs35569394 was associated with EC risk (<em>p</em>= 0.012, OR=1.34). A gender analysis break-down showed that rs35569394-D allele frequency was significantly higher in females than in the controls (<em>p</em>=0.0004, OR=1.81). Moreover, significant associations were also found in females under the dominant model (II versus ID+DD: χ2=8.18, <em>p</em>=0.003, OR=2.12) and the recessive model (II+ID versus DD: χ2=8.25, <em>p</em>=0.004, OR=2.39). Additionally, we found that the genotype, rs35569394-DD, was associated with a complete response + partial response to chemotherapy when compared with rs35569394-II (χ2=4.67, <em>p</em>=0.030, OR=0.47). In conclusion, our case-control study showed that the <em>VEGF</em> rs35569394 was significantly associated with the clinical stages and the increased risk of EC in Han Chinese females. In addition, the genotype rs35569394-DD showed a better response to chemotherapy.</p> <p><audio style="display: none;" controls="controls"></audio></p> <p><audio style="display: none;" controls="controls"></audio></p> 2021-06-01T00:00:00+02:00 Copyright (c) 2021 Zishan Wang, Chenwei Li, Xinjian Li, Jianguang Shi, Weijie Wu Uvulopalatopharyngoplasty and barbed reposition pharyngoplasty with and without hyoid suspension for obstructive sleep apnea hypopnea syndrome: A comparison of long-term functional results 2021-05-08T02:45:21+02:00 Antonio Minni Fabrizio Cialente Massimo Ralli Andrea Colizza Quirino Lai Angelo Placentino Melania Franco Valeria Rossetti Marco de Vincentiis <p>Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common condition; when conservative approaches are not effective, surgical techniques aimed at reducing the airway obstruction effect are used. This retrospective study aimed at comparing the functional outcomes in patients with OSAHS undergoing uvulopalatopharyngoplasty (UPPP) according to Fairbanks and barbed reposition pharyngoplasty (BRP) according to Mantovani, with or without hyoid suspension (HS). One-hundred twenty-two consecutive OSAHS patients who underwent surgical treatment were included in the study. Patients were divided into 4 groups; all patients underwent preoperative and postoperative polysomnography (PSG) with apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) evaluation, and Epworth Sleepiness Scale (ESS) evaluation. The results were analyzed according to the different surgical procedures in relation to the preoperative PSG and anthropometric data. A significant reduction was observed at 18-month follow-up for patients in BRP group for body mass index (<em>p</em> = 0.004), ESS (<em>p</em> &lt; 0.0001), ODI (<em>p</em> &lt; 0.0001), and AHI (<em>p</em> &lt; 0.0001). Risk factors for poor postoperative AHI reduction were evaluated; preoperative AHI was the strongest independent protective factor, while preoperative ODI was the strongest risk factor. The association of HS with UPPP or BRP showed significant results in terms of higher postoperative AHI reduction only when associated to UPPP (<em>p</em> &lt; 0.0001). This study showed that the BRP technique was more effective compared to UPPP for patients with OSAHS. The association of HS showed greater benefits in UPPP compared to BRP. Randomized prospective trials with longer follow-up are necessary to confirm our results and formulate a more accurate indication of the optimal therapeutic strategy.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Antonio Minni, Fabrizio Cialente, Massimo Ralli, Andrea Colizza, Quirino Lai, Angelo Placentino, Melania Franco, Valeria Rossetti, Marco de Vincentiis A three-dimensional computed tomography study to determine the ideal method for fluoroscopically-guided bone marrow aspiration from the iliac crest 2021-06-04T17:32:13+02:00 Ryan S. D'Souza Langping Li Shuai Leng Christine Hunt Luke Law Casey Muir Jason Eldrige Mohamad Bydon Meng Chi Shane Shapiro William D. Mauck Wenchun Qu <p>Bone marrow aspiration (BMA) through the iliac crest is potentially unsafe due to the vicinity of neurovascular structures in the greater sciatic notch. Our objective was to investigate the safety of a recently described BMA technique, specifically a trajectory from the posterior superior iliac spine (PSIS) to the anterior inferior iliac spine (AIIS). We conducted a chart review of 260 patients, analyzing three-dimensional reconstructed computed tomography images of the pelvis and sacrum to validate that this new approach offers a wide safety margin from the greater sciatic notch. Analysis of three-dimensional computed tomography scans demonstrated that the PSIS to AIIS trajectory never crossed the greater sciatic notch. The trajectory was noted to be at least one cm away from the greater sciatic notch in all measurements. The new trajectory entered the PSIS at 25.29 ± 4.34° (left side) and 24.93 ± 4.15° (right side) cephalad from the transverse plane, and 24.58 ± 4.99° (left side) and 24.56 ± 4.67° (right side) lateral from the mid-sagittal plane. The area of bone marrow encountered with the new approach was approximately 22.5 cm<sup>2</sup>. Utilizing the same CT scans, the trajectory from the traditional approach crossed the greater sciatic notch in all scans, highlighting the potential for violating the greater sciatic notch boundary and damaging important neurovascular structures. Statistically significant sex-related differences were identified in needle trajectory angles for both approaches. We conclude that based on this three-dimensional computed tomography study, a trajectory from the PSIS to the AIIS for BMA may offer a wide safety margin from the greater sciatic notch.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Ryan S. D'Souza, Langping Li, Shuai Leng, Christine Hunt, Luke Law, Casey Muir, Jason Eldrige, Mohamad Bydon, Meng Chi, Shane Shapiro, William D. Mauck, Wenchun Qu Clinical management of chronic mercury intoxication secondary to skin lightening products: A proposed algorithm 2021-06-04T17:00:35+02:00 Fitri Fareez Ramli <p>Mercury is a toxic substance that is commonly used in skin lightening products. Various effects on humans have been observed, which affect both users and non-users. Many studies reported delayed diagnosis and treatment, even after weeks of hospitalization. The possible reasons are non-specific clinical manifestation and lack of awareness and knowledge regarding chronic mercury intoxication secondary to skin lightening products. A thorough history of mercury exposure is crucial. Physical assessment and relevant supporting tests are indicated to establish a diagnosis. Blood and urine mercury levels are an essential examination for diagnosis and monitoring of the progress and response to treatment. The primary treatment is the discontinuation of the skin lightening products. Chelation therapy is not mandatory and is usually indicated for symptomatic patients. The prognosis depends on the duration of the product use, concentration of mercury in the skin product, and the severity of clinical presentation.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Fitri Fareez Ramli Lingual cyst with respiratory epithelium: The importance of differential diagnosis 2021-06-04T17:24:30+02:00 Fabrizio Cialente Giulia De Soccio Vincenzo Savastano Michele Grasso Michele Dello Spedale Venti Massimo Ralli Mara Riminucci Marco de Vincentiis Alessandro Corsi Antonio Minni <p>The lingual cyst with respiratory epithelium (LCRE) is a very rare congenital cyst of the tongue, floor of the mouth, pharynx, or hypopharynx with 21 cases reported in the literature [1,2]. Differential diagnosis is very important for patients presenting with lingual cysts, as this may impact treatment and follow-up. The LCRE should be included in the different diagnosis of a dermoid cyst [3], teratoid cyst [4], epidermoid cyst [5], thyroglossal duct cyst [6], lymphoepithelial cyst [7], and mucocele or ranula [8]. Each entity has a peculiar histologic presentation, although the clinical aspect may be very similar [1]. The dermoid cyst is lined by a keratinized squamous epithelium and contains skin appendages in the cyst. The epidermoid cyst is similar to the dermoid cyst but is characterized by non-keratinized squamous epithelium and has a lumen filled with keratin. The teratoid cyst contains derivatives of the endoderm, ectoderm, and/or mesoderm. The thyroglossal duct cyst is usually lined by columnar, stratified squamous epithelium, or an intermediate transition type of epithelium, with the mandatory presence of thyroid tissue in the cyst wall. The lymphoepithelial cyst is identified by the presence of lymphoid aggregates in the cyst wall. A mucous retention cyst, so-called mucocele or ranula, contains mucin and granulation tissue [1].</p> <p>Read the full text <a href=""><strong>[PDF]</strong></a></p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Fabrizio Cialente, Giulia De Soccio, Vincenzo Savastano, Michele Grasso, Michele Dello Spedale Venti, Massimo Ralli, Mara Riminucci, Marco de Vincentiis, Alessandro Corsi, Antonio Minni Surgical anatomy of microsurgical 3-level anterior cervical discectomy and fusion C4–C7 2021-06-04T16:52:38+02:00 Domagoj Gajski Alicia R. Dennis Kenan I. Arnautovic <p>Anterior cervical discectomy and fusion (ACDF) is one of the most common spinal procedures, frequently used for the treatment of cervical spine degenerative diseases. It was first described in 1958. Interestingly, to our knowledge, 3-level ACDF has not been previously published as a peer-reviewed video case with a detailed description of intraoperative microsurgical anatomy. In this video, we present the case of a 33-year-old male who presented with a combination of myelopathy (hyperreflexia and long tract signs in the upper and lower extremities) and bilateral radiculopathy of the upper extremities. He had been previously treated conservatively with physical therapy and pain management for 6 months without success. We performed 3-level microsurgical ACDF from C4 to C7. All 3 levels were decompressed, and bone allografts were placed to achieve intervertebral body fusion. A titanium plate was utilized from C4 to C7 for internal fixation. The patient was discharged home on the first postoperative day. His pain, numbness and tingling resolved, as well as his myelopathy. No perioperative complications were encountered. Herein we present the surgical anatomy of our operative technique including certain technical tips. Written consent was obtained directly from the patient.<br><br>VIDEO ANNOTATIONS<br>01:13 — opening the surgery site<br>02:29 — positioning of retractors<br>03:02 — start of 3-level discectomy<br>06:04 — allograft placement and fixation<br>08:20 — drain placement and closure</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Domagoj Gajski, Alicia R. Dennis, Kenan I. Arnautovic ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression 2021-05-08T02:32:14+02:00 Yange Wu Hongxia Liu Yufeng Gong Bo Zhang Wenxiu Chen <p>Breast cancer is one of the most prevalent malignancies in women worldwide. Although great advancements have been achieved in the diagnosis and treatment of breast cancer, the prognosis of patients with breast cancer is still poor due to distal recurrence and metastasis after surgery. This study aimed to assess the role of ankyrin repeat domain 22 (ANKRD22) in the progression of breast cancer and investigate the molecular mechanism. Using immunohistochemistry, we demonstrated that the expression level of ANKRD22 in human breast cancer tissues was significantly higher than that in normal breast tissues. <em>ANKRD22</em> knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells, as confirmed by BrdU, colony formation, transwell, and immunoblot assays. Immunoblot assays further indicated that ANKRD22 regulated the expression of nucleolar and spindle-associated protein 1 (NuSAP1) and then caused the activation of Wnt/β-catenin signaling pathway. Moreover, overexpression of <em>NUSAP1</em> reversed the inhibitory effects of <em>ANKRD22</em> knockdown on the proliferation, invasion, and EMT of breast cancer cells. In summary, this study demonstrated that ANKRD22 enhanced breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression, which might shed light on new therapeutic approaches for breast cancer.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Yange Wu, Hongxia Liu, Yufeng Gong, Bo Zhang, Wenxiu Chen LAPTM4B promotes the progression of nasopharyngeal cancer 2021-06-04T17:15:04+02:00 Qun Su Hongtao Luo Ming Zhang Liying Gao Fengju Zhao <p>Lysosomal protein transmembrane 4 beta (LAPTM4B) is a protein that contains four transmembrane domains. The impact of LAPTM4B on the malignancy of nasopharyngeal carcinoma (NPC) remains unclear. In the present study, we aimed to investigate the role of LAPTM4B in NPC. NPC tissue samples were used to evaluate the expression of LAPTM4B and its relationship with patient prognosis. Furthermore, we inhibited the expression of LAPTM4B in NPC cell lines and examined the effects of LAPTM4B on NPC cell proliferation, migration, and invasion. We found that LAPTM4B protein was mainly localized in the cytoplasm and intracellular membranes of NPC cells. LAPTM4B protein was upregulated in NPC tissues and cell lines. High LAPTM4B expression was closely related to pathological subtypes and disease stages in NPC patients. NPC patients with high LAPTM4B expression had a worse prognosis. <em>LAPTM4B</em> knockdown inhibited the proliferation, migration, and invasion ability of NPC cells. LAPTM4B plays a cancer-promoting role in the progression of NPC and may be a potential target for NPC therapy.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Qun Su, Hongtao Luo, Ming Zhang, Liying Gao, Fengju Zhao The effect and molecular mechanism of hypoxia on proliferation and apoptosis of CD133+ renal stem cells 2021-06-04T17:44:57+02:00 Hong Liu Cui Liu Yan Qu <p>Congenital hydronephrosis caused by ureteropelvic junction obstruction (UPJO) eventually leads to renal interstitial fibrosis and atrophy, after a series of pathophysiological problems. Renal repair after injury depends on renal stem cells. This study aimed to determine the expression of renal stem cell marker CD133 in children of different ages and the regulatory effect of stem cell microenvironment. Renal stem cells from children of different ages were identified and screened out by flow cytometry in the study. Children with hydronephrosis were divided into neonates, infants, preschool age, school age, and adolescents groups. A hypoxic cell model prepared with CoCl<sub>2</sub> was developed to detect the effect of hypoxia on the proliferation and apoptosis of renal stem cells. The effect and molecular mechanism of hypoxia-inducible factor 1-alpha (HIF-1α) on the proliferation and apoptosis of renal stem cells were also explored. Both hypoxia and HIF-1α significantly promoted the proliferation of renal stem cells and inhibited cell apoptosis. HIF-1α could bind to the promoter region of proliferating cell nuclear antigen (<em>PCNA</em>) and <em>PROM1 </em>(CD133) to mediate their transcription and expression. The content of CD133<sup>+</sup> renal stem cells was the highest in the neonatal group and it decreased with the increase of age. Taken together, this study clarified the effect of age on the content of human renal stem cells and determined the regulatory mechanism of hypoxia on renal stem cells. We expect our results to provide a research basis for the treatment and clinical application of renal stem cells.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Hong Liu, Cui Liu, Yan Qu Safety and effectiveness of new embolization microspheres SCBRM for intermediate-stage hepatocellular carcinoma: A feasibility study 2021-06-04T17:57:22+02:00 Yi-Sheng Liu Xi-Zhang Lin Chiung-Yu Chen Yen-Cheng Chiu Jui-Wen Kang Hung-Wen Tsai Hui-Yu Hung Chi-Ming Ho Ming-Ching Ou <p>Transarterial chemoembolization (TACE) is, currently, the recommended treatment for hepatocellular carcinoma (HCC). However, long-term chemoembolization triggers the inflammatory response and may lead to postembolization syndrome (PES). Although several types of degradable microspheres have been developed to reduce drug toxicity and PES incidence, the clinical outcomes remain unsatisfactory. Previously, we have developed a new type of spherical, calibrated, biodegradable, radiopaque microspheres (SCBRM) and demonstrated their safety and efficacy in a pig model. Thus, the goal of this feasibility study was to determine the clinical safety and efficacy of the new SCBRM in intermediate-stage HCC patients. In this study, 12 intermediate-stage HCC patients underwent TACE using SCBRM with a calibrated size of 100–250 μm. The disease control rates at 1 month and 3 months after TACE-SCBRM treatment were 100% and 75.0%, respectively. The objective response rates at 1 month and 3 months after treatment were 66.7% and 58.3%, respectively. Very few adverse events were observed with one patient developing nausea. One day after the treatment, alanine aminotransferase, alanine aminotransferase, and total bilirubin levels were slightly elevated in the patients, but all returned to baseline on day 7. The median and mean overall survival times were 33 months (interquartile range, 12.8–42.0) and 29.2 ± 14.3 months, respectively. The 1-year and 2-year survival rates were 91.7% and 58.3%, respectively. In conclusion, TACE with the new SCBRM microspheres is clinically safe and effective, and it represents a promising approach in the management of intermediate-stage HCC.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Yi-Sheng Liu, Xi-Zhang Lin, Chiung-Yu Chen, Yen-Cheng Chiu, Jui-Wen Kang, Hung-Wen Tsai, Hui-Yu Hung, Chi-Ming Ho, Ming-Ching Ou Postoperative respiratory depression after hysterectomy 2021-05-08T02:41:38+02:00 Mariana L. Laporta Michelle O. Kinney Darrell R. Schroeder Juraj Sprung Toby N. Weingarten <p>To investigate if sex-specific physiologic characteristics could impact postoperative respiratory depression risks in women, we studied incidence and risk factors associated with postoperative respiratory depression in a gynecologic surgical cohort. Only hysterectomies performed under general anesthesia from 2012 to 2017 were included to minimize interprocedural variability. Respiratory depression was defined as episodes of apnea, hypopnea, hypoxemia, pain-sedation mismatch, unplanned positive airway pressure device application, or naloxone administration in the post-anesthesia care unit. Multivariable logistic regression was used to explore the association with clinical characteristics. From 1,974 hysterectomies, 253 had postoperative respiratory depression, yielding an incidence of 128 (95% confidence interval, 114–144) per 1,000 surgeries. Risk factors associated with respiratory depression were older age (odds ratio 1.22 [95% confidence interval 1.02–1.46] per decade increase, <em>p </em>= 0.03), lower body weight (0.77 [0.62–0.94] per 10 kg/m<sup>2</sup>, <em>p</em> = 0.01), and higher intraoperative opioid dose (1.05 [1.01–1.09] per 10 mg oral morphine equivalents, <em>p</em> = 0.01); while sugammadex use was associated with a reduced risk (0.48 [0.30–0.75], <em>p</em> = 0.002). Respiratory depression was not associated with increased hospital stay, postoperative complications, or mortality. Postoperative respiratory depression risk in women increased with age, lower weight, and higher intraoperative opioids and decreased with sugammadex use; however, it was not associated with postoperative pulmonary complications.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Mariana L. Laporta, Michelle O. Kinney, Darrell R. Schroeder, Juraj Sprung, Toby N. Weingarten Dysbiosis of gut microbiota in inflammatory bowel disease: Current therapies and potential for microbiota-modulating therapeutic approaches 2021-05-08T02:28:33+02:00 Dikhnah Alshehri Omar Saadah Mahmoud Mosli Sherif Edris Rashad Alhindi Ahmed Bahieldin <p>There is a growing body of evidence reinforcing the unique connections between the host microbiome, health, and diseases. Due to the extreme importance of the symbiotic relationship between the intestinal microbiome and the host, it is not surprising that any alteration in the gut microbiota would result in various diseases, including inflammatory bowel disease (IBD), Crohn’s disease, (CD) and ulcerative colitis (UC). IBD is a chronic, relapsing-remitting condition that is associated with significant morbidity, mortality, compromised quality of life, and costly medical care. Dysbiosis is believed to exacerbate the progression of IBD. One of the currently used treatments for IBD are anti-tumor necrosis factor (TNF) drugs, representing a biologic therapy that is reported to have an impact on the gut microbiota composition. The efficacy of anti-TNF agents is hindered by the possibility of non-response, which occurs in 10-20% of treated patients, and secondary loss of response, which occurs in up to 30% of treated patients. This underscores the need for novel therapies and studies that evaluate the role of the gut microbiota in these conditions. The success of any therapeutic strategy for IBD depends on our understanding of the interactions that occur between the gut microbiota and the host. In this review, the health and disease IBD-associated microbiota patterns will be discussed, in addition to the effect of currently used therapies for IBD on the gut microbiota composition, as well as new therapeutic approaches that can be used to overcome the current treatment constraints.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Dikhnah Alshehri, Omar Saadah, Mahmoud Mosli, Sherif Edris, Rashad Alhindi, Ahmed Bahieldin Development and validation of prognostic nomogram for lung cancer patients below the age of 45 years 2021-05-08T02:44:06+02:00 Lili Dai Wei Wang Qi Liu Tongjia Xia Qikui Wang Qingqing Chen Ning Zhu Yu Cheng Ying Yan Jun Shu Kaixin Qu <p>This study aimed to establish a nomogram for the prognostic prediction of patients with early-onset lung cancer (EOLC) in both overall survival (OS) and cancer-specific survival (CSS). EOLC patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further divided into training and validation sets randomly. The prognostic nomogram for predicting 3-, 5- and 10-years OS and CSS was established based on the relative clinical variables determined by the multivariate Cox analysis results. Furthermore, the predictive performance of nomogram was assessed by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve. A total of 1,822 EOLC patients were selected and randomized into a training cohort (1,275, 70%) and a validation cohort (547, 30%). The nomograms were established based on the statistical results of Cox analysis. In training set, the C-indexes for OS and CSS prediction were 0.797 (95% confidence interval [CI]: 0.773-0.818) and 0.794 (95%CI:0.771-0.816). Significant agreement in the calibration curves was noticed in the nomogram models. The results of ROC and DCA indicated nomograms possessed better predict performance compared with TNM-stage and SEER-stage. And the area under the curve (AUC) of the nomogram for OS and CSS prediction in ROC analysis were 0.766 (95%CI:0.745-0.787) and 0.782 (95%CI:0.760-0.804) respectively. The prognostic nomogram provided an accurate prediction of 3-, 5-, and 10-year OS and CSS of EOLC patients which contributed clinicians to optimize individualized treatment plans.&nbsp;</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Kaixin Qu, Lili Dai, Wei Wang, Qi Liu, Tongjia Xia, Qikui Wang, Qingqing Chen, Ning Zhu, Yu Cheng, Ying Yan, Jun Shu Alectinib and lorlatinib function by modulating EMT-related proteins and MMPs in NSCLC metastasis 2021-05-08T02:39:12+02:00 Xu Feng En-Shi Xu <p>Most advanced non-small cell lung cancer (NSCLC) patients are accompanied by brain metastasis which is the major cause of increased mortality. The fusion rearrangement of anaplastic lymphoma kinase (ALK) gene is an important feature of brain metastasis in lung cancer. The novel ALK inhibitors alectinib and lorlatinib are shown to be effective against NSCLC brain metastasis, while their underlying mechanism of action is unclear. Epithelial–mesenchymal transition (EMT) proteins and matrix metalloproteinases (MMPs) play important roles in brain metastasis by regulating the blood-brain barrier (BBB). To reveal the molecular function of alectinib and lorlatinib, we explored their effects on the cellular levels of EMT markers: VIM and FN1 and the matrix metalloproteinases MMP-9 and MMP-7. The mRNA and protein levels of VIM, FN1, MMP-9, and MMP-7 were elevated in H3122 cells. However, upon alectinib and lorlatinib treatment, the levels were significantly reduced. Similar results were obtained when these experiments were performed either in a dose-dependent or time-dependent manner. Furthermore, alectinib and lorlatinib also inhibited the cell viability and migration of H3122 cells. Interestingly, in comparison to individual drugs, the combination of alectinib and lorlatinib was found to be substantially more effective. Overall, these results suggest that alectinib and lorlatinib possibly function through the downregulation of MMPs and EMT in NSCLC metastasis.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Xu Feng, En-Shi Xu Raloxifene inhibits the overexpression of TGF-β1 in cartilage and regulates the metabolism of subchondral bone in rats with osteoporotic osteoarthritis 2021-06-04T18:05:18+02:00 Shao-Hua Ping Fa-Ming Tian Hao Liu Qi Sun Li-Tao Shao Qiang-Qiang Lian Liu Zhang <p>Overexpression of transforming growth factor-beta 1 (TGF-β1) and subchondral bone remodelling play key roles in osteoarthritis (OA). Raloxifene (RAL) reduces the serum level of TGF-β1 in postmenopausal women. However, the effect of RAL on TGF-β1 expression in articular cartilage is still unclear. Therefore, we aimed to investigate the protective effect of RAL on osteoporotic osteoarthritis via affecting TGF-β1 expression in cartilage and the metabolism of subchondral bone. Osteoporotic osteoarthritis was induced by a combination of anterior cruciate transection (ACLT) and ovariectomy (OVX). Rats were divided into five groups (n = 12): The sham group, the ACLT group, the OVX group, the ACLT + OVX group, and the RAL group (ACLT + OVX + RAL, 6.25 mg/kg/day for 12 weeks). Assessment was performed by histomorphology, microcomputed tomography (micro-CT) scan, immunohistochemistry, and tartrate-resistant acid phosphatase (TRAP) staining. We found that severe cartilage degeneration was shown in the ACLT + OVX group. The histomorphological scores, the levels of TGF-β1, and its related catabolic enzymes and osteoclasts numbers in the ACLT + OVX group were higher than those in other groups (<em>p </em>&lt; 0.05). Furthermore, structure model index (SMI) and trabecular spacing (Tb.Sp) were decreased (<em>p </em>&lt; 0.05), while bone mineral density (BMD), bone volume fraction (BV/TV), and trabecular number (Tb.N) were increased by RAL compared with the ACLT + OVX group (<em>p </em>&lt; 0.05). Our findings demonstrated that RAL in clinical doses retards the development of osteoporotic osteoarthritis by inhibiting the overexpression of TGF-β1 in cartilage and regulating the metabolism of subchondral bone. These results provide support for RAL in the expansion of clinical indication for prevention and treatment in postmenopausal osteoarthritis.</p> 2021-06-01T00:00:00+02:00 Copyright (c) 2020 Shao-Hua Ping, Fa-Ming Tian, Hao Liu , Qi Sun, Li-Tao Shao, Qiang-Qiang Lian, Liu Zhang The prognostic significance of different proportion of signet-ring cells of colorectal carcinoma 2021-06-11T15:19:50+02:00 Wei Chen Huajun Cai Kui Chen Xing Liu Weizhong Jiang Shoufeng Li Yiyi Zhang Zhifen Chen Guoxian Guan <p><span style="font-weight: 400;">While the prognosis of patients with partial SRCC (PSRCC) has been rarely reported, colorectal signet-ring cell carcinoma (SRCC) has been associated with poor prognosis. The aim of this study was to analyze the prognosis of patients with different SRCC composition and establish a prediction model. A total of 91 patients with SRC component were included in the study. These patients were divided into two groups: SRCC group (SRC composition &gt; 50%; n=41) and partial SRCC (PSRCC) group (SRC composition ≤ 50%; n=50). COX regression model was used to identify independent prognostic factors for overall survival (OS). A predictive nomogram was established and compared with the 7th AJCC staging system. After a median follow-up of 16 months, no significant difference in OS was observed in either group. Preoperative carcinoembryonic antigen (CEA) level, pN stage, M stage, preoperative ileus, and adjuvant chemotherapy were independent prognostic risk factors for OS (<em>p</em>&lt;0.05). A nomogram for predicting the overall survival of colorectal SRCC was established with a C-index of 0.800, and it showed better performance than that of the 7th AJCC staging system (<em>p</em>&lt;0.001). In summary, the ratio of SRC component was not an independent prognostic factor of the OS. Those patients with less than 50% of SRC component should be given the same clinical attention. A predictive nomogram for survival based on five independent prognostic factors was developed and showed better performance than the 7th AJCC staging system. This resulted to be helpful for individualized prognosis prediction and risk assessment.</span></p> 2021-05-29T00:00:00+02:00 Copyright (c) 2021 Wei Chen, Huajun Cai, Kui Chen, Xing Liu, Weizhong Jiang, Shoufeng Li, Yiyi Zhang, Zhifen Chen, Guoxian Guan How are central foveal and choroidal thickness affected in patients with mild COVID-19 infection? 2021-06-07T20:26:17+02:00 Müge Fırat Sabiha Kobat <p>The aim of this study was to evaluate the effects of&nbsp; COVID-19 on central foveal and choroidal thicknesses. Thirty-two patients with a positive SARS-CoV-2 PCR test who received outpatient treatment within the previous two months and 32 healthy controls were included in the study. Patients requiring hospitalization due to COVID-19 as well as the patients who received either intensive care support and/or antiplatelet therapy, smokers, or patients with systemic or ocular diseases were excluded from the study. After full ophthalmological examination, central foveal and choroidal thicknesses were evaluated by using optical coherence tomography. Statistical analysis of the study data demonstrated no significant difference between the groups in terms of age or gender (<em>p</em>&gt;0.05). There was also no statistically significant difference between the groups in terms of central foveal thickness, central choroidal thickness, or nasal 500, nasal 1500, temporal 500, or temporal 500-micron distances (<em>p</em>&gt;0.05 for all parameters). Choroidal and retinal thicknesses were not affected in patients with recent mild COVID 19 without comorbidities.</p> 2021-05-21T16:26:56+02:00 Copyright (c) 2021 Müge Fırat