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1.
Orthop Surg ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39275890

RESUMO

OBJECTIVE: Severe limb amputation trauma often results in bone and soft tissue defects after debridement. Traditional replantation aims to save the limb by shortening the ischemic period and using autologous transplantation for repair, but it can lead to surgical trauma, donor site damage, and prolonged operation time. Due to contusion, pollution, and complex injury, there is no unified standard for replantation and fixation. Improper operation can easily lead to complications such as bone infection, nonunion, bone defect, and joint stiffness. This study introduces the Ilizarov technique into microsurgery to improve limb lengthening after reconstruction and standardizes the steps of replantation fixation for complex limb avulsion injuries, with a focus on clinical efficacy. METHODS: A retrospective analysis was performed on 51 patients with complex limb amputation who were treated in Zhengzhou Renji Hospital from June 2009 to March 2021. On the basis of microsurgical limb replantation, Ilizarov technology was introduced to innovate the internal and external combined stepwise fixation method for replantation. Patients' gender, age, height, weight, BMI, and other general information were collected. X-ray films were reviewed regularly to observe the surgical healing of fracture, that is, the degree of limb shortening. The lengthening time, carrying time after lengthening, follow-up time, Dahl classification, Paley fracture healing classification, and Chen Zhongwei's replantation function score were used to evaluate the recovery of the affected limb. RESULTS: A total of 51 patients were included in this group, including 36 male patients and 15 female patients. All the amputated wounds were single limb amputation. In this group of patients, the hind limbs were shortened by 2-12.5 cm (5.32 ± 2.24) after replantation. A total of 44 patients whose hind limbs were shortened by more than 2.5 cm were treated with two-stage Ilizarov lengthening for 1.5-5.5 months (3.19 ± 1.03). The carrying time was 3-7.5 months (4.25 ± 0.94), and the follow-up time was 1-7.8 years (3.76 ± 1.69). Among the 49 survived patients, the Dahl grade of external fixation was less than Grade 2 in 89.8%. The excellent and good rate of Paley fracture healing classification was 89.8%. The excellent and good rate of Chen Zhongwei's limb replantation function classification was 79.6%. CONCLUSION: Microsurgery combined with Ilizarov technique in the treatment of limb amputation injury, limb salvage reconstruction with internal and external combined step-by-step combined fixation, and one-stage shortening and two-stage limb lengthening can reduce the occurrence of osteomyelitis, bone defect and nonunion, expand the indications of limb replantation, improve the success rate of limb replantation, with satisfactory results, and facilitate the promotion of clinical techniques.

2.
PLoS Biol ; 22(8): e3002778, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39178313

RESUMO

The naked mole rat (NMR), Heterocephalus glaber, is known as the longest-lived rodent and is extraordinarily resistant to hypoxia and cancer. Here, both NMR embryonic fibroblasts (NEFs) and their mouse counterparts (MEFs) were subjected to anoxic conditions (0% O2, 5% CO2). A combination of comparative transcriptomics and proteomics was then employed to identify differentially expressed genes (DEGs). Notably, we observed distinct levels of histone H1.2 (encoded by HIST1H1C) accumulation between NEFs and MEFs. Subsequent mechanistic analyses showed that higher H1.2 expression in NEFs was associated with the lower expression of its inhibitor, PARP1. Additionally, we discovered that H1.2 can directly interact with HIF-1α PAS domains, thereby promoting the expression of HIF-1α through facilitating the dimerization with HIF-1ß. The overexpression of H1.2 was also found to trigger autophagy and to suppress the migration of cancer cells, as well as the formation of xenograft tumors, via the NRF2/P62 signaling pathway. Moreover, an engineered H1.2 knock-in mouse model exhibited significantly extended survival in hypoxic conditions (4% O2) and showed a reduced rate of tumor formation. Collectively, our results indicate a potential mechanistic link between H1.2 and the dual phenomena of anoxic adaptation and cancer resistance.


Assuntos
Histonas , Animais , Camundongos , Histonas/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Ratos-Toupeira/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteômica/métodos , Fibroblastos/metabolismo , Autofagia/genética , Adaptação Fisiológica/genética , Transcriptoma/genética , Hipóxia Celular/genética , Linhagem Celular Tumoral , Transdução de Sinais , Multiômica
3.
Front Oncol ; 14: 1360557, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38496755

RESUMO

Background: While hemangiomas are the most commonly occurring benign vascular tumors, their occurrence in the gastrointestinal system is rare. This case report presents a unique instance of small intestinal hemangioma in a pediatric patient. Case description: A 21-month-old girl was admitted to the hospital with a history of "recurrent blood in the stool for one year and anemia for five months." Upon evaluation at our facility, abdominal color ultrasound and enhanced CT scans revealed a protruding mass in the wall of the small intestine, leading to a preliminary diagnosis of small intestinal hemangioma. Subsequent single-site umbilical laparoscopic exploration identified a tumor measuring approximately 6cm×2.5cm×1.2cm on the jejunum wall. Consequently, segmental resection of the intestine was performed, and the postoperative pathological diagnosis confirmed cavernous hemangioma. Conclusion: Small intestinal hemangiomas, particularly in pediatric patients, are exceptionally rare and challenging to diagnose as the cause of gastrointestinal bleeding prior to surgery. Hence, small intestinal hemangiomas should be considered in such cases. Laparoscopic surgical resection emerges as the optimal approach for addressing small intestinal hemangiomas.

4.
Drug Resist Updat ; 73: 101060, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309140

RESUMO

Cancer lactate metabolic reprogramming induces an elevated level of extracellular lactate and H+, leading to an acidic immunosuppressive tumor microenvironment (TEM). High lactic acid level may affect the metabolic programs of various cells that comprise an antitumor immune response, therefore, restricting immune-mediated tumor destruction, and leading to therapeutic resistance and unsatisfactory prognosis. Here, we report a metal-phenolic coordination-based nanocomplex loaded with a natural polyphenol galloflavin, which inhibits the function of lactate dehydrogenase, reducing the production of lactic acid, and alleviating the acidic immunosuppressive TME. Besides, the co-entrapped natural polyphenol carnosic acid and the synthetic PEG-Ce6 polyphenol derivative (serving as a photosensitizer) could induce immunogenic cancer cell death upon laser irradiation, which further activates immune system and promotes immune cell recruitment and infiltration in tumor tissues. We demonstrated that this nanocomplex-based combinational therapy could reshape the TME and elicit immune responses in a murine breast cancer model, which provides a promising strategy to enhance the therapeutic efficiency of drug-resistant breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Animais , Camundongos , Feminino , Ácido Láctico , Polifenóis/farmacologia , Reprogramação Metabólica , Neoplasias/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Fenóis , Microambiente Tumoral
5.
ACS Appl Mater Interfaces ; 16(9): 11336-11348, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38407027

RESUMO

Articular cartilage injury is a common disease in clinical medicine. Because of its special physiological structure and lack of blood, lymph, and nerves, its ability to regenerate once damaged is very limited. In this study, we designed and synthesized a series of self- and coassembled cartilage-inducing functional peptide molecules and constructed a coassembled functional peptide hydrogel based on phenylboronic acid-o-dihydroxy "click chemistry" cross-linking to promote aggregation and signal transduction of mesenchymal stem cells (MSCs) in the early stage and differentiation toward cartilage, thereby promoting the repair of cartilage damage. Three functional peptide molecules were produced using solid-phase peptide synthesis technology, yielding a purity higher than 95%. DOPA-FEFEFEFEGHSNGLPL (DFP) and PBA-FKFKFKFKGHAVDI (BFP) were coassembled at near-neutral pH to form hydrogels (C Gels) based on phenylboronic acid-o-dihydroxy click chemistry cross-linking and effectively loaded transforming growth factor (TGF)-ß1 with a release period of up to 2 weeks. Furthermore, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) were cocultured with functional peptide hydrogels, and the results displayed that the coassembled functional peptide hydrogel group C Gels significantly promoted the proliferation of chondrocytes and MSCs. The chondrocyte markers collagen type I, collagen type II, and glycosaminoglycan (GAG) in the coassembled functional peptide hydrogel group were significantly higher than those in the control group, indicating that it can induce the differentiation of MSCs into cartilage. In vivo experiments demonstrated that the size and thickness of the new cartilage in the compound gel group were the most beneficial to cartilage regeneration. These results indicated that peptide hydrogels are a promising therapeutic option for cartilage regeneration.


Assuntos
Ácidos Borônicos , Cartilagem Articular , Hidrogéis , Hidrogéis/química , Cartilagem Articular/metabolismo , Condrócitos , Diferenciação Celular , Peptídeos/farmacologia , Peptídeos/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Condrogênese , Engenharia Tecidual/métodos
6.
Soft Matter ; 20(9): 2017-2023, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38334445

RESUMO

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.


Assuntos
Adesivos , Materiais Biocompatíveis , Animais , Materiais Biocompatíveis/farmacologia , Adesivos/química , Dopamina/química , Cartilagem , Condrócitos
7.
ESC Heart Fail ; 10(6): 3622-3636, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37798907

RESUMO

AIMS: Left ventricular remodelling subsequent to myocardial infarction (MI) constitutes a pivotal underlying cause of heart failure. Intervention with the nontoxic endogenous aryl hydrocarbon receptor (AHR) agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) in the acute phase of MI has been shown to ameliorate cardiac function, but its role in the chronic phase remains obscured. This study explores the beneficial role of ITE in delaying the progression of heart failure in the chronic phase of MI. METHODS AND RESULTS: MI rats established by ligating the left anterior descending coronary artery were treated with the indicated concentration of the AHR agonist ITE or vehicle alone. Echocardiography was performed to determine cardiac structure and function; myocardial morphology and fibrosis were observed by haematoxylin and eosin and Masson's trichrome staining; serum biochemical indices, BNP, and inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay; F4/80+ iNOS+ M1 macrophages and F4/80+ CD206+ M2 macrophages were detected by immunofluorescence; the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay was used to detect the apoptosis of cardiomyocytes; ultrastructural changes in myocardial tissue were observed by transmission electron microscopy; and Cyp1a1, Akt, P-Akt, p70S6K, P-p70S6K, Bcl-2, Bax, caspase-3, and cleaved caspase-3 protein levels were determined via Western blotting. We found that therapy with the AHR agonist ITE rescued cardiac remodelling and dysfunction in rats with MI and attenuated myocardial fibrosis, inflammation, and mitochondrial damage. Further studies confirmed that ITE dose-dependently improved myocardial cell apoptosis after MI, as demonstrated by reduced levels of the apoptosis-related proteins cleaved caspase-3 and Bax but increased expression levels of Bcl-2. These effects were attributed to ITE-induced activation of AHR receptors, leading to the down-regulation of Akt and p70S6K phosphorylation. CONCLUSIONS: The AHR agonist ITE alleviates cardiomyocyte apoptosis through the Akt/p70S6K signalling pathway, thereby rescuing left ventricular adverse remodelling and cardiac dysfunction after MI.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Ratos , Animais , Caspase 3 , Proteínas Quinases S6 Ribossômicas 70-kDa , Proteínas Proto-Oncogênicas c-akt , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/metabolismo , Remodelação Ventricular , Proteína X Associada a bcl-2 , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo
8.
Aging Cell ; 22(9): e13917, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37395176

RESUMO

The naked mole rat (Heterocephalus glaber), bats (e.g., genus Myotis), and elephants (family Elephantidae) are known as long-lived mammals and are assumed to be excellent cancer antagonists. However, whether there are common genetic changes underpinning cancer resistance in these long-lived species is yet to be fully established. Here, we newly generated a high-quality chromosome-level Asian elephant (Elephas maximus) genome and identified that the expanded gene families in elephants are involved in Ras-associated and base excision repair pathways. Moreover, we performed comparative genomic analyses of 12 mammals and examined genes with signatures of positive selection in elephants, naked mole rat, and greater horseshoe bat. Residues at positively selected sites of CDR2L and ALDH6A1 in these long-lived mammals enhanced the inhibition of tumor cell migration compared to those in short-lived relatives. Overall, our study provides a new genome resource and a preliminary survey of common genetic changes in long-lived mammals.


Assuntos
Elefantes , Neoplasias , Animais , Elefantes/genética , Mamíferos/genética , Neoplasias/genética , Genômica , Cromossomos , Ratos-Toupeira/genética
9.
Front Pediatr ; 11: 1205155, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342532

RESUMO

Small-intestinal duplication is a rare congenital developmental anomaly that is mainly single; multiple small-intestinal duplications are rare. Most malformations are located in the ileocecal region. The primary surgical treatment is complete resection of the malformations and adjacent intestinal ducts. However, the ileocecal junction plays an important role in children, and it is difficult to preserve it; multiple intestinal repairs increase the risk of postoperative intestinal fistula, which is a challenge for pediatric surgeons. Herein, we report a case of ileocecal preservation surgery for the treatment of multiple small intestinal duplication malformations near the ileocecal area. The child underwent laparoscopically assisted cyst excision and multiple intestinal repairs and had good postoperative recovery and follow-up.

10.
Sheng Wu Gong Cheng Xue Bao ; 39(4): 1462-1476, 2023 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-37154317

RESUMO

Antibiotics are playing an increasingly important role in clinical antibacterial applications. However, their abuse has also brought toxic and side effects, drug-resistant pathogens, decreased immunity and other problems. New antibacterial schemes in clinic are urgently needed. In recent years, nano-metals and their oxides have attracted wide attention due to their broad-spectrum antibacterial activity. Nano-silver, nano-copper, nano-zinc and their oxides are gradually applied in biomedical field. In this study, the classification and basic properties of nano-metallic materials such as conductivity, superplasticity, catalysis, and antibacterial activities were firstly introduced. Secondly, the common preparation techniques, including physical, chemical and biological methods, were summarized. Subsequently, four main antibacterial mechanisms, such as cell membrane, oxidative stress, DNA destruction and cell respiration reduction, were summarized. Finally, the effect of size, shape, concentration and surface chemical characteristics of nano-metals and their oxides on antibacterial effectiveness and the research status of biological safety such as cytotoxicity, genotoxicity and reproductive toxicity were reviewed. At present, although nano-metals and their oxides have been applied in medical antibacterial, cancer treatment and other clinical fields, some issues such as the development of green preparation technology, the understanding of antibacterial mechanism, the improvement of biosafety, and the expansion of application fields, require further exploration.


Assuntos
Nanopartículas Metálicas , Óxidos , Óxidos/farmacologia , Óxidos/química , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Zinco , Cobre
11.
J Funct Biomater ; 14(2)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36826912

RESUMO

Porous titanium interbody scaffolds are growing in popularity due to their appealing advantages for bone ingrowth. This study aimed to investigate the biomechanical effects of scaffold materials in both normal and osteoporotic lumbar spines using a finite element (FE) model. Four scaffold materials were compared: Ti6Al4V (Ti), PEEK, porous titanium of 65% porosity (P65), and porous titanium of 80% porosity (P80). In addition, the range of motion (ROM), endplate stress, scaffold stress, and pedicle screw stress were calculated and compared. The results showed that the ROM decreased by more than 96% after surgery, and the solid Ti scaffold provided the lowest ROM (1.2-3.4% of the intact case) at the surgical segment among all models. Compared to solid Ti, PEEK decreased the scaffold stress by 53-66 and the endplate stress by 0-33%, while porous Ti decreased the scaffold stress by 20-32% and the endplate stress by 0-32%. Further, compared with P65, P80 slightly increased the ROM (<0.03°) and pedicle screw stress (<4%) and decreased the endplate stress by 0-13% and scaffold stress by approximately 18%. Moreover, the osteoporotic lumbar spine provided higher ROMs, endplate stresses, scaffold stresses, and pedicle screw stresses in all motion modes. The porous Ti scaffolds may offer an alternative for lateral lumbar interbody fusion.

12.
Orthop Surg ; 14(9): 2339-2349, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35946442

RESUMO

OBJECTIVE: To investigate the biomechanics of transforaminal lumbar interbody fusion (TLIF) with interspinous process device (IPD) or pedicle screw fixation under both static and vibration conditions by the finite element (FE) method. METHOD: A validated FE model of the L1-5 lumbar spine was used in this study. This FE model derived from computed tomography images of a healthy female adult volunteer of appropriate age. Then the model was modified to simulate L3-4 TLIF. Four conditions were compared: (i) intact; (ii) TLIF combined with bilateral pedicle screw fixation (BPSF); (iii) TLIF combined with U-shaped IPD Coflex-F (CF); and (iv) TLIF combined with unilateral pedicle screw fixation (UPSF). The intact and surgical FE models were analyzed under static and vibration loading conditions respectively. For static loading conditions, four motion modes (flexion, extension, lateral bending, and axial rotation) were simulated. For vibration loading conditions, the dynamic responses of lumbar spine under sinusoidal vertical load were simulated. RESULT: Under static loading conditions, compared with intact case, BPSF decreased range of motion (ROM) by 92%, 95%, 89% and 92% in flexion, extension, lateral bending and axial rotation, respectively. While CF decreased ROM by 87%, 90%, 69% and 80%, and UPSF decreased ROM by 84%, 89%, 66% and 82%, respectively. Compared with CF, UPSF increased the endplate stress by 5%-8% in flexion, 7%-10% in extension, 2%-4% in lateral bending, and decreased the endplate stress by 16%-19% in axial rotation. Compared with CF, UPSF increased the cage stress by 9% in flexion, 10% in extension, and decreased the cage stress by 3% in lateral bending, and 13% in axial rotation. BPSF decreased the stress responses of endplates and cage compared with CF and UPSF. Compared BPSF, CF decreased the facet joint force (FJF) by 6%-13%, and UPSF decreased the FJF by 4%-12%. During vibration loading conditions, compared with BPSF, CF reduced maximum values of the FJF by 16%-32%, and vibration amplitudes by 22%-35%, while UPSF reduced maximum values by 20%-40%, and vibration amplitudes by 31%-45%. CONCLUSION: Compared with other surgical models, BPSF increased the stability of lumbar spine, and also showed advantages in cage stress and endplate stress. CF showed advantages in IDP and FJF especially during vertical vibration, which may lead to lower risk of adjacent segment degeneration. CF may be an effective alternative to pedicle screw fixation in TLIF procedures.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Adulto , Feminino , Humanos , Fenômenos Biomecânicos/fisiologia , Análise de Elementos Finitos , Vértebras Lombares/fisiologia , Vértebras Lombares/cirurgia , Amplitude de Movimento Articular , Fusão Vertebral/métodos , Vibração
13.
Front Genet ; 13: 802865, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265103

RESUMO

Background: The existence of maternal malignancy may cause false-positive results or failed tests of NIPT. Though recent studies have shown multiple chromosomal aneuploidies (MCA) are associated with malignancy, there is still no effective solution to identify maternal cancer patients from pregnant women with MCA results using NIPT. We aimed to develop a new method to effectively detect maternal cancer in pregnant women with MCA results using NIPT and a random forest classifier to identify the tissue origin of common maternal cancer types. Methods: For examination, 496 participants with MCA results via NIPT were enrolled from January 2016 to June 2019 at BGI. Cancer and non-cancer participants were confirmed through the clinical follow-up. The cohort comprising 42 maternal cancer cases and 294 non-cancer cases enrolled from January 2016 to December 2017 was utilized to develop a method named mean of the top five chromosome z scores (MTOP5Zscores). The remaining 160 participants enrolled from January 2018 to June 2019 were used to validate the performance of MTOP5Zscores. We established a random forest model to classify three common cancer types using normalized Pearson correlation coefficient (NPCC) values, z scores of 22 chromosomes, and seven plasma tumor markers (PTMs) as predictor variables. Results: 62 maternal cancer cases were confirmed with breast cancer, liver cancer, and lymphoma, the most common cancer types. MTOP5Zscores showed a sensitivity of 85% (95% confidence interval (CI), 62.11-96.79%) and specificity of 80% (95% CI, 72.41-88.28%) in the detection of maternal cancer among pregnant women with MCA results. The sensitivity of the classifier was 93.33, 66.67, and 50%, while specificity was 66.67, 90, and 97.06%, and positive predictive value (PPV) was 60.87, 72.73, and 80% for the prediction of breast cancer, liver cancer, and lymphoma, respectively. Conclusion: This study presents a solution to identify maternal cancer patients from pregnant women with MCA results using NIPT, indicating it as a value-added application of NIPT in the detection of maternal malignancies in addition to screening for fetal aneuploidies with no extra cost.

14.
Front Oncol ; 12: 1054976, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36686796

RESUMO

Introduction: It has been reported that GRB7 is closely related to a variety of human solid tumors, but its role in gastric cancer has not been reported yet. The purpose of this study was to investigate the expression level and intracellular effects of GRB7 in human gastric cancer. Methods: Real-time fluorescent quantitative PCR and Western blot were used to detect the expression of GRB7 in gastric cancer cell lines. The immunohistochemical staining and SPSS analysis verified the GRB7 protein expression. Stable gastric cancer cell lines, MTT experiments, clone formation experiments, cell cycle flow cytometry experiments, sphere formation experiments and lateral subpopulation cell sorting experiments were conducted to investigate the role of GRB7 in gastric cancer cells. Results: We found that the expression of GRB7 in gastric cancer cell lines was higher than that of the corresponding normal gastric epithelial cells, and correspondingly higher in gastric cancer tissues than its paired adjacent tissues. GRB7 protein was expressed more highly in cancer tissues than in adjacent tissues. GRB7 protein expression levels were positively correlated with the clinical stage of gastric cancer patients, and negatively correlated with the survival prognosis of patients. GSEA analysis of GRB7 mRNA levels in gastric cancer tissues and normal gastric epithelial tissues from public databases showed that GRB7 may affect cell proliferation and related processes of intracellular stem cells. GRB7 can promote the proliferation of gastric cancer cells and is positively related to the self-renewal ability of gastric cancer stem cells. Discussion: This study shows that GRB7 molecules highly expressed in gastric cancer tissues can promote the proliferation of gastric cancer cells and increase the proportion of gastric cancer stem cells, so it is expected to become a diagnostic molecule or potential therapeutic target for gastric cancer.

15.
Int J Numer Method Biomed Eng ; 37(8): e3498, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33998776

RESUMO

Lumbar spinal fusion may cause adjacent segment degeneration (ASD) in the long term. Recently, inserting an interspinous process device (IPD) proximal to the fusion has been proposed to prevent ASD. The aim of this study was to investigate the biomechanics of lumbar fusion with proximal IPD implantation (LFPI) under both static loads and whole body vibration (WBV). A previously validated finite element (FE) model of the L1-5 lumbar spine was modified to simulate L4-5 fusion. Three different IPDs (Coflex-F, Wallis and DIAM) were inserted at the L3-4 segment of the fusion model to construct the LFPI models. The intact and surgical FE models were analyzed under static loads and WBV, respectively. Under static loading conditions, LFPI decreased range of motion (ROM) and intradiscal pressure (IDP) at the transition segment L3-4 compared with the fusion case. At the segment (L2-3) adjacent to the transition level, LFPI induced higher motion and IDP than rigid fusion. Under WBV, vibration amplitudes of the L3-4 IDP and L4-5 facet joint force (FJF) decreased by more than 54.3% after surgery. The LFPI model with the DIAM system offered the most comparable biomechanics to the intact model under static loads, and decreased the dynamic responses of the L4-5 FJF under WBV. The LFPI model with the Wallis and Coflex-F systems could stabilize the transition segment, and decrease dynamic responses of the L3-4 IDP. The DIAM system may be more suitable in LFPI.


Assuntos
Fusão Vertebral , Articulação Zigapofisária , Fenômenos Biomecânicos , Análise de Elementos Finitos , Vértebras Lombares/cirurgia , Amplitude de Movimento Articular
16.
J Knee Surg ; 34(9): 952-961, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31968360

RESUMO

To improve the long-term outcomes of high tibial osteotomy (HTO) for gonarthritis, many cartilage repair procedures appeared, but their effects were controversial. To evaluate the efficacy of cartilage repair procedures during HTO for gonarthritis, we performed this update meta-analysis. We performed the system retrieval for clinical trials using various databases and then pooled the outcomes of the included studies. Fifteen studies were involved. The pooled results indicated that there were no significant differences in Kellgren and Lawrence (KL) scale (mean difference [MD] = 0.02, 95% confidence interval [CI] = -0.01 to 0.06, p = 0.24), the femorotibial angle (MD = 0.06, 95% CI = -0.04 to 0.16, p = 0.22), and magnetic resonance imaging (MRI) outcomes (MD = 12.53, 95% CI = -2.26 to 27.32, p = 0.10) of patients in experimental group than control. The subgroup analysis showed that the clinical outcomes of abrasion arthroplasty (AA) were worse than control group (standardized mean difference [SMD] -2.65, 95% CI = -3.67 to -1.63, p < 0.001), while mesenchymal stem cells (MSCs) injection improved the clinical outcomes (SMD = 2.37, 95% CI = 1.25-3.50, p < 0.001). There were significant differences between the two groups in arthroscopic (SMD = 1.38, 95% CI = 0.82-1.94, p < 0.001) and histologic results (relative risk [RR] = 1.77, 95% CI = 1.36-2.29, p < 0.001). The pain relief (MD = 0.17, 95% CI = -3.26 to 3.61, p = 0.92) and operative complications (RR = 1.42, 95% CI = 0.83-2.42; p = 0.19) of the two groups had no significant differences. Our analysis supports that concurrent cartilage repair procedures might improve arthroscopic and histologic outcomes, but they have no beneficial effect on clinical outcomes, radiograph, MRI, and pain relief. The concurrent procedures do not increase the risk of operative complication. Furthermore, MSC has some beneficial effects on clinical outcomes, while AA might play an opposite role.


Assuntos
Osteoartrite do Joelho , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Imageamento por Ressonância Magnética , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Osteotomia , Radiografia , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Resultado do Tratamento
17.
Genet Med ; 21(10): 2293-2302, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30976098

RESUMO

PURPOSE: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. METHODS: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. RESULTS: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. CONCLUSION: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies-positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.


Assuntos
Transtornos Cromossômicos/diagnóstico , Neoplasias/diagnóstico , Teste Pré-Natal não Invasivo/métodos , Adulto , Algoritmos , Aneuploidia , Biologia Computacional , Feminino , Testes Genéticos , Humanos , Idade Materna , Mães , Neoplasias/genética , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
World Neurosurg ; 116: 94-104, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29753897

RESUMO

OBJECTIVE: The aim of this study was to comprehensively compare the clinical and biomechanical efficiency of anterior cervical discectomy and fusion (ACDF) with anterior cervical disc replacement (ACDR) for treatment of multilevel cervical disc disease using a meta-analysis and systematical review. METHODS: A literature search was performed using PubMed, MEDLINE, EMBASE, and the Cochrane Library for articles published between January 1960 and December 2017. Both clinical and biomechanical parameters were analyzed. Statistical tests were conducted by Revman 5.3. Nineteen studies including 10 clinical studies and 9 biomechanical studies were filtered out. RESULTS: The pooled results for clinical efficiency showed that no significant difference was observed in blood loss (P = 0.09; mean difference [MD], 7.38; confidence interval [CI], -1.16 to 15.91), hospital stay (P = 0.33; MD, -0.25; CI, -0.76 to 0.26), Japanese Orthopaedic Association scores (P = 0.63; MD, -0.11; CI, -0.57 to 0.34), visual analog scale (P = 0.08; MD, -0.50; CI, -1.06 to 0.05), and Neck Disability Index (P = 0.33; MD, -0.55; CI, -1.65 to 0.56) between the 2 groups. Compared with ACDF, ACDR did show increased surgical time (P = 0.03; MD, 31.42; CI, 2.71-60.14). On the other hand, ACDR showed increased index range of motion (ROM) (P < 0.00001; MD, 13.83; CI, 9.28-18.39), lower rates of adjacent segment disease (ASD) (P = 0.001; odds ratio [OR], 0.27; CI, 0.13-0.59), complications (P = 0.006; OR, 0.62; CI, 0.45-0.87), and rate of subsequent surgery (P < 0.00001; OR, 0.25; CI, 0.14-0.44). As for biomechanical performance, ACDR maintained index ROM and avoided compensation in adjacent ROM and tissue pressure. CONCLUSIONS: Multilevel ACDR may be an effective and safe alternative to ACDF in terms of clinical and biomechanical performance. However, further multicenter and prospective studies should be conducted to obtain a stronger and more reliable conclusion.


Assuntos
Vértebras Cervicais/cirurgia , Discotomia/métodos , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Fusão Vertebral/métodos , Substituição Total de Disco/métodos , Fenômenos Biomecânicos/fisiologia , Discotomia/normas , Humanos , Degeneração do Disco Intervertebral/diagnóstico , Deslocamento do Disco Intervertebral/diagnóstico , Medição da Dor/métodos , Medição da Dor/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Fusão Vertebral/normas , Substituição Total de Disco/normas , Resultado do Tratamento
19.
World Neurosurg ; 114: e1302-e1309, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29627629

RESUMO

OBJECTIVE: To systematically investigate the effect of 3-level hybrid constructs on the cervical spine biomechanics based on a validated model of the C3-C7 segments. METHODS: Three hybrid constructs with 2 U-shaped dynamic cervical implants and 1 cage were simulated. The 3 constructs were 1) Cage-U-U (cage implanted at the C3-C4 level and U-shaped dynamic cervical implants implanted at the C4-C5 and C5-C6 levels), 2) U-Cage-U, and 3) U-U-Cage. Biomechanical parameters including moments, cervical motions, and stresses in the facet and implants were analyzed in flexion and extension. RESULTS: The flexion and extension motions at artificial cervical disc replacement levels increased for all hybrid constructs when compared with those of intact model. However, the maximum increase was 52% with U-U-Cage model. At the unoperated adjacent level, the maximum motion increase in extension was 23% with the U-U-Cage model. Also, the U-U-Cage and U-Cage-U model generated more than 40% increase in terms of flexion motion at the adjacent level. The facet stress at the adjacent level increased by 28%, 20%, and 39% with the Cage-U-U, U-Cage-U, and U-U-Cage models, respectively. The moments required to reach the same motion as the intact model were significantly increased. CONCLUSIONS: The study showed that the U-U-Cage model lead to more compensation in terms of motion and facet stress. Furthermore, the present results imply that when conducting the hybrid surgery, the segmental motions should be taken into account. Performing anterior cervical discectomy and fusion at the level whose motion is relatively small may decrease the compensation required at the adjacent level.


Assuntos
Vértebras Cervicais/cirurgia , Análise de Elementos Finitos , Imageamento Tridimensional/métodos , Fixadores Internos , Adulto , Vértebras Cervicais/anatomia & histologia , Vértebras Cervicais/diagnóstico por imagem , Análise de Elementos Finitos/tendências , Humanos , Imageamento Tridimensional/tendências , Fixadores Internos/tendências , Masculino , Próteses e Implantes/tendências , Amplitude de Movimento Articular/fisiologia , Fusão Vertebral/métodos , Substituição Total de Disco/métodos
20.
Spine (Phila Pa 1976) ; 43(6): 379-387, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28678112

RESUMO

STUDY DESIGN: Biomechanical analysis using a validated nonlinear finite element (FE) model. OBJECTIVE: The aim of this study was to combine the strategy of two-level hybrid surgery (HS) to explore how prostheses affect cervical biomechanics. SUMMARY OF BACKGROUND DATA: Few FE studies have explored differences in biomechanical behavior between combined and stand-alone structured prostheses with HS. No FE studies have considered whether the prosthesis type and hybrid strategy influence two-level HS. METHODS: Three prostheses-Prodisc-C, PCM, and DCI-were analyzed in flexion and extension during HS at C4-C6. There were two HS constructs: anterior cervical discectomy and fusion (ACDF) conducted at the C4-C5 levels and anterior cervical disc replacement (ACDR) conducted at C5-C6 levels (ACDF/ACDR); ACDR/ACDF. RESULTS: Flexion motion at adjacent levels was greater than that of intact spine. A maximum increase of 80% was observed with PCM in the ACDF/ACDR group. Extension motion at adjacent levels for both hybrid strategies with PCM, however, was similar to that of intact spine (<10% change), whereas it increased by 14% to 32% with DCI. The strain energy-storing capability with DCI tended to be similar to that of normal discs. Facet stress at the infra-adjacent level, however, significantly increased with DCI in both groups, whereas it increased with PCM and Prodisc-C only in the ACDR/ACDF group. All prostheses produced overloads on cartilage at the arthroplasty level. Prodisc-C and PCM cores showed stress above the yield stress of ultrahigh-molecular-weight polyethylene. CONCLUSION: Each prosthesis had advantages and disadvantages. In extension, DCI (vs. Prodisc-C and PCM) exhibited more compensation at adjacent levels in terms of motion, moments, and facet stress. The biomechanical performance of Prodisc-C was easily affected by the hybrid strategy. Thus, if only a combined-structure prosthesis is available for two-level HS (C4-C6 level), the hybrid strategy should be carefully evaluated and the ACDF/ACDR construct is recommended to avoid accelerating degeneration of adjacent segments. LEVEL OF EVIDENCE: 5.


Assuntos
Fenômenos Biomecânicos/fisiologia , Vértebras Cervicais/cirurgia , Degeneração do Disco Intervertebral/cirurgia , Implantação de Prótese , Humanos , Próteses e Implantes , Implantação de Prótese/métodos , Amplitude de Movimento Articular/fisiologia , Fusão Vertebral/métodos
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