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Τρίτη 17 Νοεμβρίου 2020

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Exp Ther Med
2020 Dec;20(6):252. doi: 10.3892/etm.2020.9382. Epub 2020 Oct 23.
Clinical outcomes of MED and iLESSYS ® Delta for the treatment of lumbar central spinal stenosis and lateral recess stenosis: A comparison study
Boyu Wu 1, Chengjie Xiong 2, Linying Tan 1, Dongdong Zhao 3, Feng Xu 2, Hui Kang 2
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PMID: 33178350 PMCID: PMC7651884 DOI: 10.3892/etm.2020.9382
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Abstract
Microendoscopic discectomy (MED) is an established procedure used to treat lumbar central spinal stenosis (LCSS) and lateral recess stenosis (LRS). The Interlaminar Endoscopic Surgical System iLESSYS® Delta approach has been developed from the traditional interlaminar endoscopic technique for the treatment of LCSS and LRS. In the present study, MED was used as a reference to evaluate this newly developed approach. A total of 82 and 52 patients with radicular leg pain and/or neurogenic claudication symptoms were treated by spinal canal decompression using the MED or iLESSYS® Delta approach, respectively. The clinical outcomes of the patients were analyzed using the Modified MacNab's criteria, visual analogue scale (VAS) leg pain score, VAS back pain score and the Oswestry Disability Index (ODI) score. Finally, the effectiveness of the decompression was evaluated on a cross-sectional area of the dural sac (CSAD) at the disc level. The incision length in the iLESSYS® Delta group was significantly decreased compared with the MED group (P<0.05); however, the duration of the operation in the iLESSYS® Delta group was significantly longer compared with the MED group (P<0.05). The VAS score of the back and ODI score in the iLESSYS® Delta group were significantly decreased compared with the MED group at the 1-week follow-up (P<0.0125). The postoperative CSAD was also significantly increased in both groups compared with before the operation (P<0.05); however, there were no significant differences in the postoperative CSAD between the two groups. The good-to-excellent rates of the MED and iLESSYS® Delta approach were 89.0 and 90.4%, respectively, whereas the complication rates of the MED and iLESSYS® Delta system were 3.66 and 3.85% in the two groups, respectively. In conclusion, the iLESSYS® Delta approach was identified to be comparable with the MED approach for treating LCSS and LRS, demonstrating both precise and limited decompression. In addition, the iLESSYS� � Delta approach may reduce the short-term back pain and promote faster recovery compared with the MED.

Keywords: interlaminar endoscopic surgical system; lumbar central spinal stenosis; lumbar lateral recess stenosis; microendoscopic discectomy.

Copyright: © Wu et al.

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Review Exp Ther Med
2020 Dec;20(6):211. doi: 10.3892/etm.2020.9341. Epub 2020 Oct 14.
Mental health and immunity (Review)
Cristian Vasile 1
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PMID: 33149775 PMCID: PMC7604758 DOI: 10.3892/etm.2020.9341
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Abstract
The immune system consists of a complex biological and psychological network designed for fighting against infections and to protect the body from pathogen factors, including the internal ones. In the past, for a long time inflammation and infectious diseases were thought to be only the result of the genetic heritage and the biological functioning of the body, when the pathogenic factors acted within the body. Studies in recent decades stressed the importance of psychological balance and mental health on the body immunity. Psychoneuroimmunology studies indicated the thoughts and emotional patterns, and the psychological dynamics are strongly interrelated with the immune response. Moreover, the immunological mechanisms not only regulates the health of the person, but they are also an important part of the individual adaptive process in the environment. In various studies, the results of each treatment modality (drug interventions and psychosocial interventions) were observed and compa red in patients with mental health problems associated with immune reactions (inflammation). Psychosocial interventions suggest increased efficiency in reducing inflammation and improving immune system function.

Keywords: adaptation; immune system; mental health; psycho-neuroimmunology; psychological balance.

Copyright: © Vasile et al.

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Review Exp Ther Med
2020 Dec;20(6):234. doi: 10.3892/etm.2020.9364. Epub 2020 Oct 16.
Research and prospect of peptides for use in obesity treatment (Review)
Yao Gao 1, Xuewen Yuan 1, Ziyang Zhu 1, Dandan Wang 1, Qianqi Liu 1, Wei Gu 1
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PMID: 33149788 PMCID: PMC7604735 DOI: 10.3892/etm.2020.9364
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Abstract
Obesity and its related diseases, such as type 2 diabetes, hypertension and cardiovascular disease, are steadily increasing worldwide. Over the past few decades, numerous studies have focused on the differentiation and function of brown and beige fat, providing evidence for their therapeutic potential in treating obesity. However, no specific novel drug has been developed to treat obesity in this way. Peptides are a class of chemically active substances, which are linked together by amino acids using peptide bonds. They have specific physiological activities, including browning of white fat. As signal molecules regulated by the neuroendocrine system, the role of polypeptides, such as neuropeptide Y, brain-gut peptide and glucagon-like peptide in obesity and its related complications has been revealed. Notably, with the rapid development of peptidomics, peptide drugs have been widely used in the prevention and treatment of metabolic diseases, due to their short half-life, small appare nt distribution volume, low toxicity and low side effects. The present review summarizes the progress and the new trend of peptide research, which may provide novel targets for the prevention and treatment of obesity.

Keywords: metabolic diseases; obesity; peptides; peptidomics; treatment.

Copyright © 2020, Spandidos Publications.

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Exp Ther Med
2020 Dec;20(6):210. doi: 10.3892/etm.2020.9340. Epub 2020 Oct 14.
Predictive factors in early onset schizophrenia
Magdalena Budisteanu 1 2 3, Emanuela Andrei 1, Florentina Linca 1, Diana Stefania Hulea 4, Alexandra Catalina Velicu 4, Ilinca Mihailescu 1, Sorin Riga 1, Aurora Arghir 2, Sorina Mihaela Papuc 2, Carmen Adella Sirbu 5, Marian Mitrica 6, Any Docu-Axelerad 7 8, Minerva Claudia Ghinescu 5, Iuliana Dobrescu 1 4, Florina Rad 1 4
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PMID: 33149774 PMCID: PMC7604757 DOI: 10.3892/etm.2020.9340
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Abstract
Schizophrenia is a neurodevelopmental disorder, characterized by impairment in reasoning, affectivity and social relationships. Although the diagnosis of schizophrenia in children and adolescents has been challenged for many years, at present childhood-onset schizophrenia is considered and accepted as a clinical and biological continuum with the adult-onset disorder. The present study aimed to evaluate the influence of biological (psychiatric family history, perinatal factors), and socio-demographic factors (area of residence, gender) on the age at onset and severity of symptomatology in children and adolescent with schizophrenia. The data were collected from 2016 to 2019 and included 148 children and adolescents with schizophrenia. Data were analysed with statistical software (IBM SPSS 22, JASP and JAMOVI, Linear Regression Model, χ² tests, t-test, U-test). A positive familial history for psychiatric diseases was an important risk factor both for an early onset and for the severit y of symptoms. Urbanicity was another studied risk factor, 61% of patients being from urban areas; no statistically significant correlations between urbanicity and age at onset and severity of symptoms were identified. There was no statistically significant gender difference in terms of age at onset and severity of symptoms. Moreover, no statistically significant correlations were found between perinatal factors and age at onset and severity of symptoms. Positive psychiatric family history showed a statistically significant influence on age at onset and symptoms severity in children and adolescent schizophrenia; no statistical significant impact on the aforementioned schizophrenia aspects was observed for urbanicity, gender or perinatal factors.

Keywords: adolescents; biological factors; children; schizophrenia; socio-demographic factors.

Copyright © 2020, Spandidos Publications.

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Exp Ther Med
2020 Dec;20(6):255. doi: 10.3892/etm.2020.9385. Epub 2020 Oct 23.
MicroRNA-208a-3p promotes osteosarcoma progression via targeting PTEN
Yutuo Fu 1 2, Yan Wang 2, Ke Bi 2, Lei Yang 1, Yi Sun 3, Boyuan Li 2, Zhenzhong Liu 2, Fulin Zhang 2, Yuan Li 4, Chao Feng 4, Zhenggang Bi 1
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PMID: 33178353 PMCID: PMC7651880 DOI: 10.3892/etm.2020.9385
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Abstract
Osteosarcoma (OS) is a malignant bone tumor with a poor prognosis. Accumulated evidence has suggested that microRNAs (miRNAs/miRs) may function as either oncogenes or tumor suppressors, which are associated with tumorigenesis and the progression of different types of cancer. In the present study, the role of miR-208a-3p in OS was investigated. The expression levels of miR-208a-3p in OS tissues and cell lines were determined via reverse transcription-quantitative PCR (RT-qPCR). MTT and colony formation assays were performed to verify the proliferation rate of OS cells. In addition, the effects of miR-208a-3p on the migration and invasion of OS cells were revealed using wound-healing and Transwell assays, respectively. Furthermore, the association between miR-208a-3p and phosphatase and tensin homolog (PTEN) 3'-untranslated region was determined via luciferase reporter assays, western blot and RT-qPCR analysis. The results indicated that miR-208a-3p was upregulated in OS tissues and ce ll lines compared with adjacent normal tissues and human osteoblastic cells, respectively. miR-208a-3p overexpression promoted and miR-208a-3p knockdown inhibited OS cells proliferation and metastatic potential. Additionally, PTEN was validated as a direct target of miR-208a-3p and its expression was negatively associate with that of miR-208a-3p in OS cells. Taken together, these results may suggest that miR-208a-3p promoted OS cells proliferation and metastatic potential via targeting PTEN. Therefore, miR-208a-3p may be considered as a diagnostic biomarker for OS.

Keywords: invasion; microRNA-208a-3p; migration; osteosarcoma; phosphatase and tensin homolog; proliferation.

Copyright: © Fu et al.

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Exp Ther Med
2020 Dec;20(6):248. doi: 10.3892/etm.2020.9378. Epub 2020 Oct 22.
Application of interventional embolization in the treatment of iatrogenic pseudoaneurysms
Hao Xu 1, Cong Jing 1, Jie Zhou 2, Xuli Min 1, Jing Zhao 1, Lin Yang 1, Yongjun Ren 1
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PMID: 33178346 PMCID: PMC7651869 DOI: 10.3892/etm.2020.9378
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Abstract
The present study aimed to investigate the clinical effectiveness and safety of endovascular embolization for the treatment of pseudoaneurysm secondary to previous abdominal and pelvic surgery or radiological percutaneous abdominal procedure. A retrospective review was performed on all patients with abdominal and pelvic pseudoaneurysm confirmed by CT angiography or digital subtraction angiography and treated with endovascular embolization. Different techniques of embolization with coils were applied and the outcomes, including clinical effectiveness and safety, were assessed. A total of 31 patients with a total of 32 pseudoaneurysms were included in the present study. Of these pseudoaneurysms, 23 were from the main trunks and branches of the gastroduodenal artery, 5 were from the splenic artery, 2 were from the common hepatic artery, 1 was from the right hepatic artery and 1 was from the right internal iliac artery. There were no serious complications observed and there was no occurr ence of re-bleeding following embolization. The embolization of the pseudoaneurysms was successful in all patients. In conclusion, endovascular embolization is a safe and effective method for the treatment of secondary iatrogenic pseudoaneurysm in the abdomen and pelvis.

Keywords: abdominal surgery; embolization therapy; hemorrhage; iatrogenic disease; visceral artery pseudoaneurysm.

Copyright: © Xu et al.

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Exp Ther Med
2020 Dec;20(6):251. doi: 10.3892/etm.2020.9381. Epub 2020 Oct 23.
Biochanin A alleviates gingival inflammation and alveolar bone loss in rats with experimental periodontitis
Shengdan Zhang 1 2, Yulong Niu 3, Zhuo Yang 4, Yuwei Zhang 1 2, Qiang Guo 1, Yi Yang 3, Xuedong Zhou 1 5, Yi Ding 2, Chengcheng Liu 2
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PMID: 33178349 PMCID: PMC7654219 DOI: 10.3892/etm.2020.9381
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Biochanin A (BA) is an organic compound produced by Trifolium pretense and Arachis hypogaea with anti-inflammatory and antioxidative effects. The aim of the current study was to evaluate the effects of BA on gingival inflammation and alveolar bone destruction in rats with experimental periodontitis. Experimental rats (n=25) were distributed equally into five groups: i) Healthy control (control) group; ii) experimental periodontitis (ligation) group; and iii) and ligation plus low, medium and high dose of BA (12.5, 25 and 50 mg/kg/day, respectively) groups. A nylon ligature was inserted around rats' maxillary molars for 14 days to trigger the experimental periodontitis. BA was intravenous injected once daily for 4 weeks. After that, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and osteocalcin (OCN) levels were determined in gingival and/or serum samples using ELISA or reverse transcription-quantitative PCR. Alveolar bone volume was assesse d via hematoxylin and eosin staining and micro-computed tomography. Osteoclasts were identified by tartrate-resistant acid phosphatase staining, and the level of the nuclear factor erythroid-2 related factor 2 (Nrf2) was also detected by immunohistochemical staining. BA treatment groups showed alleviated alveolar bone resorption compared with the ligation group. Moreover, BA treatment significantly inhibited IL-1β, TNF-α, ROS levels, and reduced leukocyte acid phosphatase-positive cells, as well as increased OCN and Nrf2 levels compared with the ligation group. BA had beneficial effects on experimental periodontitis of rats. BA treatment inhibited inflammation, regulated unbalanced oxidative stress response and ameliorated the alveolar bone loss.

Keywords: biochanin A; bone loss; inflammation; periodontitis; reactive oxygen species.

Copyright: © Zhang et al.

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Exp Ther Med
2020 Dec;20(6):228. doi: 10.3892/etm.2020.9358. Epub 2020 Oct 15.
CD14 + monocytes and CD163 + macrophages correlate with the severity of liver fibrosis in patients with chronic hepatitis C
Su-Xian Zhao 1, Wen-Cong Li 1, Na Fu 1, Ling-Bo Kong 1, Qing-Shan Zhang 1, Fang Han 1, Wei-Guang Ren 1, Po Cui 1, Jing-Hua Du 1, Bao-Yu Wang 1, Yu-Guo Zhang 1, Rong-Qi Wang 1, Li Kong 1, Yue-Min Nan 1
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PMID: 33149783 PMCID: PMC7604741 DOI: 10.3892/etm.2020.9358
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Abstract
Hepatic fibrosis is a crucial pathological process involved in the development of chronic hepatitis C (CHC) and may progress to liver cirrhosis and hepatocellular carcinoma. Activated peripheral blood monocytes and intrahepatic macrophages further promote hepatic fibrogenesis by releasing proinflammatory and profibrogenic cytokines. The present study aimed to investigate the role of peripheral CD14+ monocytes and intrahepatic CD163+ macrophages in hepatitis C virus (HCV)-associated liver fibrosis and clarify whether serum soluble CD163 (sCD163) may serve as a fibrosis marker in patients with CHC. A total of 87 patients with CHC and 20 healthy controls were recruited. Serum sCD163 levels were measured by ELISA. Frequencies of peripheral CD14+ monocytes and inflammatory cytokines expressed by CD14+ monocytes were analyzed by flow cytometry. The degree of fibrosis in human liver biopsies was graded using the Metavir scoring system and patients were stratified into two groups based on th ose results (F<2 vs. F≥2). Hepatic expression of CD163 was examined by immunohistochemical staining. The diagnostic values of sCD163, aspartate aminotransferase to platelet ratio index (APRI), fibrosis 4 score (FIB-4) and the aspartate aminotransferase to alanine aminotransferase ratio (AAR) in significant fibrosis (F≥2) were evaluated and compared using receiver operating characteristic (ROC) curves. The results indicated that the serum sCD163 levels and the frequency of CD14+ monocytes were significantly higher in the patients than that in the controls and positively correlated with liver fibrosis. The level of serum sCD163 was consistent with hepatic CD163 expression in the liver sections from patients. The frequencies of interleukin (IL)-8- and tumor necrosis factor-α-expressing monocytes were increased and that of IL-10-expressing monocytes was decreased in the patients. The area under the ROC curve (AUROC) for sCD163, APRI, FIB-4 and AAR was 0.876, 0.785, 0.825 and 0.488, respectively, and the AUROC for sCD163 was significantly higher than those for APRI and AAR. In conclusion, sCD163 may serve as a novel marker for assessing the degree of liver fibrosis in HCV-infected patients.

Keywords: CD14; CD163; hepatitis C virus; liver fibrosis; soluble CD163.

Copyright: © Zhao et al.

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Exp Ther Med
2020 Dec;20(6):232. doi: 10.3892/etm.2020.9362. Epub 2020 Oct 16.
Predictive value of serum VEGF, IL-1 and TNF-α in the treatment of thromboangiitis obliterans by revascularization
Zheng-Fei Li 1, Xiao-Jun Shu 1, Wen-Hui Wang 1, Sheng-Ye Liu 1, Lei Dang 1, Yan-Qiang Shi 1, Yan-Wen Bai 1
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PMID: 33149786 PMCID: PMC7604734 DOI: 10.3892/etm.2020.9362
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Abstract
Effect of revascularization in the treatment of thromboangiitis obliterans (TAO) and the predictive value of serum vascular endothelial growth factor (VEGF), interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) of risk factors of amputation were investigated. From April 2012 to August 2015, a total of 117 patients with TAO admitted to the First Hospital of Lanzhou University were selected. Patients treated with revascularization combined with prostaglandin sodium and cilostazol were enrolled in group A (67 patients), and patients treated with sodium and cilostazol were enrolled in group B (50 patients). The clinical efficacy was evaluated by calculating the intermittent claudication distance and the ankle brachial index (ABI) of patients. The occurrence probability of nausea and vomiting, skin pruritus, abdominal pain, coagulation abnormalities and amputation were recorded. The concentration of serum VEGF, IL-1 and TNF-α were measured using enzyme-linked immunosorbent assay (E LISA). After treatment, the intermittent claudication distance, ABI and efficiency of group A was markedly higher than that of group B (P<0.05). After treatment, serum VEGF concentration in group A was clearly higher than that in group B (P<0.05), and IL-1 and TNF-α levels were much lower than those in group B (P<0.05). The amputation rate in group A was significantly lower than that in group B (P<0.05). Patients with amputation in both groups were enrolled in the study group (24 cases), and those without amputation were included in the control group (93 cases). The serum VEGF concentration in the study group before treatment was significantly lower than that in the control group (P<0.05), while IL-1 and TNF-α levels were significantly higher than those of the control group (P<0.05). In conclusion, pretreatment serum VEGF, IL-1 and TNF-α had a positive diagnostic value for poor prognosis of patients with amputation, and low concentration of VEGF and higher concentration of IL-1 a nd TNF-α are the risk factors for amputations in patients with TAO.

Keywords: clinical efficacy; prognosis; revascularization; thromboangiitis obliterans.

Copyright: © Li et al.

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Exp Ther Med
2020 Dec;20(6):245. doi: 10.3892/etm.2020.9375. Epub 2020 Oct 22.
Comparison of regulatory networks of E74-like factor 1 and cold-shock domain-containing E1 in breast cancer cell lines using ChIP datasets
Haibo Duan 1, Huafang He 2, Qian Hu 1, Yingxin Lin 1, Shuo Cao 1, Xiaoshan Lan 1, Litao Li 1, Danmei Pang 1
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PMID: 33178343 PMCID: PMC7651883 DOI: 10.3892/etm.2020.9375
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Abstract
In the present study, differences in the expression of target genes between chromatin immunoprecipitation sequencing (ChIP-seq) datasets of breast cancer MCF-7 cells treated with antibodies to E74-like factor 1 (ELF1) and cold-shock domain-containing E1 (CSDE1) were analyzed and gene regulatory networks were established. The datasets were downloaded from the Gene Expression Omnibus (GEO) database. ELF1-associated target genes and CSDE1-associated target genes were analyzed for functional prediction and protein-protein interaction (PPI) networks. The ELF1 ChIP-seq dataset contained 95 ELF1-associated target genes, while the CSDE1 ChIP-seq dataset contained 826 CSDE1-associated target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the ELF1- and CSDE1-associated target genes had different potential functions and signaling pathways. The ELF1-associated target genes were mainly enriched in the GO terms of molecular transducer activity, catalytic activity, cellular processes and response to sensitivity, and in the KEGG pathways of olfactory transduction, the chemokine signaling pathway, carbohydrate digestion and absorption, and starch and sucrose metabolism. The CSDE1-associated target genes were mainly enriched in the GO terms of binding, transcription regulator activity, cellular processes and metabolic processes, and in the KEGG pathways of ribosome, metabolic pathways, endocytosis, oxidative phosphorylation and transcriptional misregulation in cancer. PPI network analysis revealed that the ELF1 regulatory network primarily regulated chemokine-mediated malignant tumor cells, while the CSDE1 regulatory network mainly regulated ribosomes, metabolic pathways and oxidative phosphorylation. Reverse transcription-quantitative PCR indicated that ELF1 overexpression led to significant downregulation of C-X-C motif chemokine-8 and -6 expression levels in MCF-7 cells, while overexpression of CSDE1 significantly induced the mRNA expression of CSDE1-associated target genes, which included mitochondrial ribosomal protein L4, NADH: ubiquinone oxidoreductase subunit B7, small nuclear ribonucleoprotein polypeptide E, ribosomal protein S26 (RPS26), RPS11 and RPS6, in the MCF-7 cells. In breast cancer MCF-7 cells, the target genes and regulatory pathways of ELF1 and CSDE1 were different. Understanding these regulatory pathways may help to develop strategies for personalized breast cancer treatment.

Keywords: E74-like factor 1; Gene Expression Omnibus; breast cancer; chromatin immunoprecipitation; cold-shock domain-containing E1; transcription factor.

Copyright: © Duan et al.

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Exp Ther Med
2020 Dec;20(6):215. doi: 10.3892/etm.2020.9345. Epub 2020 Oct 15.
Tricalcium phosphate and hydroxyapatite treatment for benign cavitary bone lesions: A prospective clinical trial
Şerban Dragosloveanu 1 2, Christiana D M Dragosloveanu 3, Horia T Stanca 3, Dragoş C Cotor 2, Adrian C Andrei 2, Călin I Dragosloveanu 2, Cristian I Stoica 1 2
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PMID: 33149779 PMCID: PMC7604753 DOI: 10.3892/etm.2020.9345
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Abstract
Benign bone tumors are surgically treated by curettage and by filling the defect using bone grafts or bone substitutes, such as hydroxyapatite crystals and tricalcium phosphate. The tricalcium phosphate mixed with hydroxyapatite, although fragile, is a good alternative with good integration. Fifteen patients with benign bone lesions were randomized in two groups surgically treated by curettage and filling of the bone defect using allograft (7 cases) or a mixture of 35% tricalcium phosphate, with 60-85% pore volume, and 65% hydroxyapatite (8 cases). After the surgery, all patients were followed up every 3 weeks until 6 months, and then at 2 months interval until one year for the clinical and radiological assessment. The average age was 35.4 years (from 18 to 54) for the allograft group and 41 years (from 22 to 58) for the patients treated with bone substitute. Eight patients were male and seven female, with relatively equal distribution between both groups. The average bone defect was relatively equal: 14 cc (4-25 cc) for the allograft group and 15.1 cc (4-33 cc) for the ceramic group (P>0.1). During the follow-up, all the lesions gradually disappeared after 12 months, with a time of healing of 18.8 weeks (15-24 weeks) for the allograft group and 20.37 weeks (15-28) for the bone substitute group. There were no significant differences regarding the clinical status and the radiological assessment after 12 months. No patient required extra pain medication after 2 weeks. No complications have been recorded. The surgical treatment of small and medium sized lytic benign tumors has good results with both types of graft that were studied. Using tricalcium phosphate mixed with hydroxyapatite as bone substitute represents a good and low cost alternative, but it is a relatively fragile material with a slower time to integrate compared to the allograft.

Keywords: benign; bone cyst; bone substitute; ceramic; humans; prospective; tricalcium phosphate.

Copyright © 2020, Spandidos Publications.

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Exp Ther Med
2020 Dec;20(6):216. doi: 10.3892/etm.2020.9346. Epub 2020 Oct 15.
A new perspective towards failure of gamma nail systems
Şerban Dragosloveanu 1 2, Christiana D M Dragosloveanu 3, Horia T Stanca 3, Dragoş C Cotor 3, Călin I Dragosloveanu 3, Cristian I Stoica 1 2
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PMID: 33149780 PMCID: PMC7604752 DOI: 10.3892/etm.2020.9346
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Abstract
Uncommon causes of nail failures and surgical reinterventions were determined. The study included 23 osteoporotic patients, 13 of whom followed a fast recovery program with early walking (FWB group). The other 10 patients were not allowed full weight bearing until 6 weeks (NFWB group). The T-score was determined before surgery for all cases. A case with a nail breakage after a failed DCS implant fixed in another clinic was also analyzed. The nail was revised and the broken implant underwent a metallurgic and microscopic examination. The average T-score was 2.5 for the patients that followed the fast recovery program and 2.7 for the patients from non-full weight bearing. Four patients, 1 from the NFWB group and 3 from FWB group, presented a screw cut-out. It was found that the errors of the guiding instruments may create dents, scratches or micro-fractures on the titanium coating that lead to an early implant failure. Imperfect reduction leads to incorrect implant placement and a high incidence of failure. Damaging the titanium protective coating, in a low force, high cycles scenario can cause structural failure. Delays in fracture healing and material fatigue are the most common causes of nail failure and can lead to catastrophic complications.

Keywords: displaced implant; gamma nail system; internal fixation; nail failure; titanium fatigue; trochanteric fractures.

Copyright: © Dragosloveanu et al.

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Exp Ther Med
2020 Dec;20(6):231. doi: 10.3892/etm.2020.9361. Epub 2020 Oct 15.
HMGB-1/RAGE signaling inhibition by dioscin attenuates hippocampal neuron damage induced by oxygen-glucose deprivation/reperfusion
Aijun Liu 1 2, Wenqian Zhang 1 2, Shuwei Wang 1 2, Yuan Wang 1 2, Jun Hong 1 2
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PMID: 33149785 PMCID: PMC7604738 DOI: 10.3892/etm.2020.9361
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Cerebral ischemia is one of the most common clinical diseases characterized by high morbidity and mortality. Neurocyte apoptosis and a cascade of inflammatory signals following cerebral ischemia-reperfusion injury (IRI) may contribute to secondary brain damage, resulting in severe neurological damage. It has been reported that dioscin, a natural steroid saponin, exerts anti-inflammatory properties against different diseases. The present study aimed to investigate the role of dioscin in oxygen-glucose deprivation/reperfusion (OGD/R) induction in hippocampal cells in vitro and in vivo. For the in vitro study, hippocampal cells were collected from rat embryos of gestational age of E18. The oxygen-glucose deprivation model in primary hippocampal neurons was used to mimic cerebral IRI in vitro. To select the optimum dioscin concentration and acting time, cell viability was evaluated by a Cell Counting Kit-8 (CCK-8) assay. Neurons subjected to OGD/R were treated with dioscin and the inflam matory cytokines, high mobility group box chromosomal protein 1 (HMGB-1)/receptor for advanced glycation end products (RAGE) signaling molecules and apoptosis-associated genes were determined. The intracellular reactive oxygen species (ROS) generation was detected. Furthermore, the effects of dioscin on the antioxidant defense mechanisms were evaluated by measuring the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and the glutathione (GSH)/glutathione disulphide (GSSG) ratio. In addition, OGD/R-induced cells were transfected with pcDNA3.1-HMGB-1 and treated with dioscin, and the neuronal cell apoptosis rate was determined using a terminal deoxynucleotidyl transferase-mediated 2-deoxyuridine 5-triphosphate-biotin nick-end labeling (TUNEL) assay. The mRNA and protein expression levels of the inflammatory factors were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. For the in vivo investigation, the oxidation and anti-oxidation system in rat hippocampal tissue was evaluated by detecting the expression of the aforementioned oxidative stress-associated proteins, 3-NT as well as 8-oxo-deoxyguanosine (8-OHdG). In the hippocampal region, the apoptotic rate was determined using a TUNEL assay. The results demonstrated that dioscin at a dose of 400 ng/ml significantly reversed the increase in the expression levels of the inflammatory factors and attenuated those of apoptotic cytokines induced by OGD/R. Additionally, dioscin notably reversed the OGD/R-mediated activation of the HMGB-1/RAGE signaling pathway in vitro and in vivo. Cell treatment with dioscin significantly attenuated ROS production and increased the activity of antioxidant enzymes. Additionally, increasing the expression of HMGB-1 inhibited the protective effects of dioscin on cell apoptosis in the OGD/R-induced neurons. Furthermore, HMGB-1 overexpression reversed the antiapoptotic and anti-inflammatory effects of dioscin on neurons. The results of the present study indicated that dioscin exerted anti-inflammatory, antiapoptotic and antioxidant effects via the HMGB-1/RAGE signaling pathway. These results suggest a novel perspective of the protective effects of dioscin as a prospective remedial factor for IRI.

Keywords: apoptosis; dioscin; high mobility group box-1 protein; inflammation; oxygen-glucose deprivation.

Copyright: © Liu et al.

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Exp Ther Med
2020 Dec;20(6):240. doi: 10.3892/etm.2020.9370. Epub 2020 Oct 22.
Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL-22 expression to regulate the MAPK signaling pathway
Huijie Zhang 1, Meixv Chen 1, Ying Liu 1, Xiaomei Dong 1, Chan Zhang 1, Han Jiang 1, Xue Chen 1
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PMID: 33178338 PMCID: PMC7651781 DOI: 10.3892/etm.2020.9370
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Abstract
The objective of the present study was to observe the therapeutic effect of paroxetine combined with fluorouracil on mice with colorectal cancer (CRC) complicated with depression and to explore its mechanism of action. Using chronic mild stress and xenograft tumor methods to model CRC complicated with depression, 60 BALB/c mice were randomly divided into control, tumor model, tumor depression model, tumor depression antidepressant, tumor depression chemotherapy and tumor depression antidepressant plus chemotherapeutic drug groups. Changes in mouse sucrose preference and forced swimming tests were tracked. Changes in tumor volume and weight were compared, the tumor inhibition rate was calculated, Ki-67 expression in tumor tissues was detected using immunohistochemistry and IL-22 levels in peripheral blood were detected using ELISAs. Additionally, protein expression levels of IL-22, Bcl-2, Bax, caspase-3, p38, phosphorylated (p)-p38, ERK, p-ERK, JNK and p-JNK in tumor tissue were detec ted using western blotting. Following treatment with paroxetine and chemotherapy drugs, the sucrose preference index was increased, autonomic behavior dysfunction was alleviated and tumor growth was significantly inhibited. Furthermore, the expression levels of Ki-67 and apoptosis-related proteins, Bax and caspase-3, increased in tumor tissues, anti-apoptosis protein Bcl2 expression levels decreased significantly, IL-22 levels in the blood and tumor tissues were reduced and p-p38, p-ERK and p-JNK proteins were significantly reduced. It was concluded that paroxetine combined with chemotherapy drugs improved depressive behavior and promoted the survival state in a mouse model of CRC and depression, possibly through inhibiting IL-22 expression to regulate the activity of the MAPK signaling pathway.

Keywords: colorectal cancer; depression; mitogen-associated protein kinase signaling pathway; paroxetine.

Copyright: © Zhang et al.

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15
Exp Ther Med
2020 Dec;20(6):241. doi: 10.3892/etm.2020.9371. Epub 2020 Oct 22.
Lack of sphingomyelin synthase 2 reduces cerebral ischemia/reperfusion injury by inhibiting microglial inflammation in mice
Yu Yang 1, Fengxian Hu 1, Guifeng Yang 1, Qingmei Meng 1
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PMID: 33178339 PMCID: PMC7651782 DOI: 10.3892/etm.2020.9371
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Abstract
Recanalization of blood flow after ischemia can lead to ischemia/reperfusion injury, and inflammation plays an important role in the mechanisms behind cerebral ischemia/reperfusion injury. Sphingomyelin synthase 2 (SMS2) deficiency reduces inflammation; however, the effect and mechanism of action of SMS2 on the inflammatory response after cerebral ischemia/reperfusion injury are still unclear. Wild-type (WT) and SMS2 knockout C57BL/6 mice were used to establish a model of cerebral ischemia/reperfusion. The neurological deficit score was evaluated with Longa's method, and infarct volume was evaluated by magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining. Neurological deficit and infarct volume were used to evaluate the degree of cerebral ischemia/reperfusion injury in mice. Western blotting, reverse transcription-quantitative PCR and immunofluorescence were used to detect the expression profiles. The neurological deficit score of SMS2-/- mice was significantly lower than that of WT mice at 72 h after cerebral ischemia/reperfusion injury (P=0.027), but not significantly different at 24 h (P=0.064). Compared with WT mice at 24 and 72 h after cerebral ischemia/reperfusion, the infarct volume of SMS2-/- mice was decreased, the expression of pro-inflammatory cytokines galectin 3 and interleukin-1β were decreased, the activation of microglia was decreased, and the nuclear translocation of NF-κB p65 was decreased, but the expression of the anti-inflammatory factor arginase 1 was increased. Lack of SMS2 in mice can help to reduce the inflammatory reaction by inhibiting the activation of NF-κB signaling pathway, further attenuating cerebral ischemia/reperfusion injury in mice.

Keywords: cerebral ischemia reperfusion; inflammation; microglial; sphingomyelin synthase 2.

Copyright: © Yang et al.

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16
Review Exp Ther Med
2020 Dec;20(6):217. doi: 10.3892/etm.2020.9347. Epub 2020 Oct 15.
Vaccination in multiple sclerosis - Challenging practices (Review)
Carmen Adella Sirbu 1 2, Anca Alexandra Florea 2, Minerva Claudia Ghinescu 1, Any Docu-Axelerad 3, Anca Maria Sirbu 4, Ovidiu Gabriel Bratu 5 6, Florentina Ionita Radu 1 7
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PMID: 33149781 PMCID: PMC7604740 DOI: 10.3892/etm.2020.9347
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Abstract
Infections are an ever-present problem in the medical community, even more so for patients with multiple sclerosis (MS), for whom these infections have been linked to relapses and neurological disabilities. Even though it was believed that MS can be caused by an infection, research does not support this theory. MS is a chronic inflammatory disease considered to be autoimmune. Vaccination is proven to be one of the most effective means to prevent infections, but still it is surrounded by controversy in the general populations, as well as in the MS group. Vaccines are generally considered safe for MS patients. The exceptions from this, which turn into contraindications, are a medical history of allergic reactions to one of the vaccine components and immunosuppressed patients in the particular case of live vaccines. Given the presumed autoimmunity of the disease, some medication for MS is immunosuppressive and any live vaccine should be administered before starting treatment. Although t here is still confusion regarding this subject, the current guidelines have clearer recommendations about vaccinations in MS patients and especially in treated MS patients.

Keywords: disease modifying treatment; infection; multiple sclerosis; safety; vaccination.

Copyright © 2020, Spandidos Publications.

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17
Exp Ther Med
2020 Dec;20(6):243. doi: 10.3892/etm.2020.9373. Epub 2020 Oct 22.
Associations of BRAF V600E, clinical pathology and imaging factors with the recurrence rate of papillary thyroid microcarcinoma
Kun Huang 1, Ningning Gao 2, Donglin Bian 1, Qixi Zhai 1, Puxu Yang 1, Yunfei Zhang 1
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PMID: 33178341 PMCID: PMC7651867 DOI: 10.3892/etm.2020.9373
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Abstract
In the present study, the recurrence rate of papillary thyroid microcarcinoma (PTMC) was assessed by analyzing postoperative follow-up data of affected patients and its associations with BRAF V600E, clinical pathology and imaging factors were explored. A total of 506 patients with PTMC were selected who underwent surgery from January 2014 to March 2016. The maximal diameter of thyroid nodules was ≤1 cm and all patients who underwent BRAF V600E testing and evaluation for lymph node metastasis. Postoperatively, each patient was regularly followed up to detect recurrence. Categorical variables were comparatively analyzed using univariate Cox linear regression analysis to screen for protective and adverse factors influencing recurrence of PTMC. A stepwise Cox proportional hazards regression model analysis was performed to explore risk factors affecting recurrence. Among the 506 patients, 477 were followed up, 29 were lost to follow-up and 26 patients experienced recurrence. The 5-year recurrent rate of PTMC was 5.45%. The univariate Cox regression analysis indicated that PTMC recurrence was influenced by BRAF V600E, sex, multifocality, capsular invasion and lateral cervical lymph node metastasis (P<0.05), but not by age, tumor location on the thyroid, size, single central lymph node metastasis, distant metastasis and operative approach (P>0.05). The significant factors associated with recurrent PTMC were subjected to stepwise multivariate Cox proportional hazards regression model analysis and the results indicated that BRAF V600E, sex, multifocality and lateral cervical lymph node metastasis were independent factors influencing recurrence in patients with PTMC, with a statistically significant difference (P<0.05). In conclusion, BRAF V600E, sex, multifocality and lateral cervical lymph node metastasis are independent risk factors for recurrent PTMC.

Keywords: BRAF V600E; color Doppler ultrasonography; papillary thyroid microcarcinoma; recurrence rate.

Copyright © 2020, Spandidos Publications.

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18
Exp Ther Med
2020 Dec;20(6):242. doi: 10.3892/etm.2020.9372. Epub 2020 Oct 22.
MBD2 and EZH2 regulate the expression of SFRP1 without affecting its methylation status in a colorectal cancer cell line
Jun Yu 1 2, Yang Xie 1 2, Yuting Liu 1 2, Feng Wang 1 2, Mengying Li 1 2, Jian Qi 1 2
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PMID: 33178340 PMCID: PMC7651780 DOI: 10.3892/etm.2020.9372
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Abstract
Secreted frizzled-related protein 1 (SFRP1), which is an extracellular inhibitor involved in Wnt signalling, is downregulated by promoter hypermethylation in the early stages of colorectal tumorigenesis. Polycomb (PCG) and methyl-CpG-binding domain (MBD) proteins that serve a role in epigenetic gene regulation. The aim of the present study was to determine the role of PCG and MBD proteins in the regulation of SFRP1 gene expression in colorectal cancer (CRC), specifically in CRC cell lines and the human embryo intestinal mucosa cell line CCC-HIE-2. The methylation status of the SFRP1 gene promoter were analysed using methylation-specific PCR (MSP), whereas SFRP1 mRNA expression was analysed using reverse transcription-quantitative PCR. The association between PCG and MBD proteins and the SFRP1 gene was assessed, where associated proteins were screened by chromatin immunoprecipitation and their expression were subsequently knocked down using RNA interference to determine their role in the regulation of SFRP1 gene expression. The SFRP1 promoter was demonstrated to be hypermethylated in CRC cell lines and partially methylated in the non-cancerous cell line CCC-HIE-2. SFRP1 mRNA expression was significantly lower in CRC cell lines compared with that of CCC-HIE-2 cells. The expression of PCGs enhancer of zeste homolog 2 (EZH2) and BMI1, along with MBD2, was indicated to be upregulated with SFRP1 methylation in HCT116 and SW480 cells. The SFRP1 promoter region was enriched with EZH2 in CCC-HIE-2 cells and enriched with EZH2 and MBD2 in SW480 cells, whereas none of the proteins examined were indicated on the SFRP1 promoter in HCT116 cells. The expression of SFRP1 was reactivated by MBD2 small interfering (si)RNA but not by EZH2 siRNA in SW480 cells, but combined MBD2 and EZH2 knockdown effectively restored SFRP1 gene expression without affecting the methylation status of the SFRP1 promoter. In conclusion, data from the present study revealed that MBD2 and EZH2 regulate d SFRP1 expression without affecting the hypermethylation of SFRP1 in CRC cell lines. Instead, the regulation of SFRP1 expression may be through a distinct mechanism, which warrants further investigation.

Keywords: DNA methylation; colorectal cancer; enhancer of zeste homolog 2; methyl-CpG-binding domain protein 2; secreted frizzled related protein 1.

Copyright © 2020, Spandidos Publications.

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Exp Ther Med
2020 Dec;20(6):235. doi: 10.3892/etm.2020.9365. Epub 2020 Oct 16.
Rapid method for direct identification of positive blood cultures by MALDI-TOF MS
Yueling Wang 1, Yan Jin 1, Yuanyuan Bai 1, Zhen Song 1, Wenjun Chu 1, Mengqi Zhao 1, Yingying Hao 1 2, Zhiming Lu 1 2
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PMID: 33178337 PMCID: PMC7651779 DOI: 10.3892/etm.2020.9365
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Abstract
Application of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using positive blood cultures (BCs) is a revolution in identification of microorganisms in clinical microbiology laboratories. Although there are several commercial pretreatment protocols they are expensive. Here, we evaluated the performance of a locally produced Bioyong pre-treatment kit for the direct identification of microorganisms in positive BCs by MALDI-TOF MS method. The mocked positive BCs were performed using 200 Thermo aerobic blood culture bottles and 200 aerobic Scenker blood culture bottles. A total of 200 organisms were invovled, including 91 strains of Gram-positive bacteria, 97 strains of Gram-negative bacteria and 12 strains of Candida. The positive BCs were subcultured and identified by classical biochemical Vitek II testing as the gold standard of identification. The Bioyong pre-treatment kit could successfully identify microorganisms in 189 (94.5%) Thermo p ositive BCs and 189 (94.5%) Scenker positive blood cultures, respectively. In total, 94 (96.9%) Gram-negative bacteria, 86 (94.5%) Gram-positive bacteria and 9 (75.0%) candida isolated from Thermo positive BCs were correctly identified to species level and 95 (97.9%) Gram-negative bacteria, 86 (94.5%) Gram-positive bacteria and 8 (66.7%) candida isolated from Scenker positive BCs were correctly identified to species level. This method provides a rapid, accurate identification of bacteria and Candida within one hour in positive blood cultures. Routine application of this technique will improve the antimicrobial treatment within 24 h among the patients with bacteremia and candidemia.

Keywords: Bioyong® kit; MALDI-TOF MS; Vitek II; bacteremia; blood culture; candidemia.

Copyright © 2020, Spandidos Publications.

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Exp Ther Med
2020 Dec;20(6):233. doi: 10.3892/etm.2020.9363. Epub 2020 Oct 16.
Clinical study on repair of metacarpal bone defects using titanium alloy implantation and autologous bone grafting
Yue Zheng 1, Jinliang Wang 1, Bolun Chang 2, Li Zhang 1
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PMID: 33149787 PMCID: PMC7604737 DOI: 10.3892/etm.2020.9363
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Abstract
Due to various limitations in the use of autologous bone and allogeneic bone in the repair of bone defects, the use of synthetic bone graft substitute has become a hot topic in orthopedic surgery and repair medicine. A total of 53 patients treated for trauma-induced metacarpal bone defects were recruited. These patients were divided into the TiAl6V4 titanium alloy implantation group (group A) and the autologous bone graft group (group B). The symptoms of patients in the two groups were closely observed and followed up. The operation time, time to bone fusion, post-surgical pain [visual analog scale (VAS) scores], hand function recovery [total active flexion scale (TAFS) scores] and complications were compared between the two groups. Following surgery, none of the patients had necrosis of fingers or bone non-union. The recovery was rated as excellent and good in up to 91.6% of patients, indicating high clinical efficacy. Compared with the use of autologous bone grafting as the gold st andard (group B), there was no significant difference in the excellent and good recovery rate based on TAFS scores at 16 weeks after surgery (91.7 vs. 89.7%, P>0.05), and there was also no significant difference in the incidence of post-operative complications (33.3 vs. 41.3%, P>0.05). The operation time (82.08±6.64 min), time to bone fusion (7.75±1.73 weeks) and VAS scores at 3 days after surgery were all significantly lower in group A than in group B (P<0.05). The values of group B were 104.69±8.63 min, 9.17±2.78 weeks and [5(5, 6)], respectively. However, the hospitalization cost (22,657.8±1,595.4Ұ) was significantly higher than that in group B (14,808.2±2,291.3Ұ; P<0.05). In conclusion, the use of titanium alloy implantation may avoid new injury to the donor site, reduce the operation time and post-operative pain and accelerate bone fusion. Therefore, this method is worthy of popularization for defective bone reconstruction and recovery in the clinic.

Keywords: autologous bone grafting; clinical effect; metacarpal bone defects; titanium alloy implantation for metacarpal bone defects.

Copyright: © Zheng et al.

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