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PURPOSE: The aims of this study had been to classify the superior angle of the scapula based on morphological features, and to investigate its correlation with the suprascapular notch. METHODS: 303 samples of Chinese dried scapular specimens were collected from the Department of anatomy, Southwest Medical University. According to the anatomical morphological characteristics of the superior angle of the scapula, the morphological classification was performed to explore its correlation with the suprascapular notch (SSN). RESULTS: The superior angle of the scapula was classified into three types (Hilly shape, Mountain Peak shape and Chimney shape). There were 143 cases of Hilly shape (47.20%), 144 cases of Mountain shape (47.52%), and 16 cases of Chimney shape (5.28%). The angle of Hilly shape (93.36° ± 7.76°) was significantly larger than the Mountain Peak shape (86.60° ± 6.61°) and the Chimney shape (86.22° ± 7.20°), and the difference was statistically significant (P < 0.05). The type I-III of Rengachary's classification to SSN was low risk of suprascapular nerve entrapment, while the type IV-VI was high risk of suprascapular nerve entrapment. Compared with the Mountain Peak shape and the Chimney shape, the Hilly shape corresponds to more types I-III of suprascapular notch but to fewer types IV-VI (P < 0.05). CONCLUSIONS: The superior angle of the scapula was divided into three types: Hilly shape (47.20%), Mountain Peak shape (47.52%) and Chimney shape (5.28%). The Mountain Peak shape might be more likely to result in inability of the levator muscle with acute or chronic overload mechanisms, and the risk of suprascapular nerve entrapment in Mountain peak shape was higher than that of Hilly shape. And, it might have a potential effect on neck pain.
Assuntos
Escápula/anatomia & histologia , Pontos de Referência Anatômicos , Cadáver , China , HumanosRESUMO
Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is the dominant hydrolase of 2',3'-cyclic GMP-AMP (cGAMP). Inhibition of ENPP1 contributes to increased cGAMP concentration and stimulator of interferon gene (STING) activation, with the potential to boost immune response against cancer. ENPP1 is a promising therapeutic target in tumor immunotherapy. To date, orally bioavailable ENPP1 inhibitors with highly potent activity under physiological conditions have been rarely reported. Herein, we report our effort in the design and synthesis of two different series of ENPP1 inhibitors, and in the identification of a highly potent ENPP1 inhibitor 27 (IC50 = 1.2 nM at pH 7.5), which significantly enhanced the cGAMP-mediated STING activity in THP-1 cells. Phosphonate compound 27 has good preclinical pharmacokinetic profiles with low plasma clearance rate in mouse, rat, and dog. It has been developed as bis-POM prodrug 36 which successfully improves the oral bioavailability of 27. In the Pan02 syngeneic mouse model of pancreatic cancer, orally administered 36 showed synergistic effect in combination with radiotherapy.
Assuntos
Antineoplásicos , Organofosfonatos , Diester Fosfórico Hidrolases , Pró-Fármacos , Pirofosfatases , Animais , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Pró-Fármacos/síntese química , Humanos , Organofosfonatos/química , Organofosfonatos/farmacologia , Organofosfonatos/síntese química , Organofosfonatos/farmacocinética , Diester Fosfórico Hidrolases/metabolismo , Administração Oral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Camundongos , Ratos , Cães , Pirofosfatases/antagonistas & inibidores , Pirofosfatases/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Descoberta de Drogas , Relação Dose-Resposta a Droga , Disponibilidade Biológica , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacocinética , Inibidores de Fosfodiesterase/farmacologia , Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/farmacocinética , Linhagem Celular Tumoral , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismoRESUMO
BACKGROUND: The identification and precise clavicle-coracoid drilling during coracoclavicular (CC) ligament reconstruction for acromioclavicular (AC) joint dislocation require a high level of experience and surgical skills. Furthermore, the improvement of flexible fixation, such as Endobutton techniques for CC ligament reconstructions is ongoing. We have developed a 3D printing technique navigation template for clavicle-coracoid drilling and a novel implant for the reconstruction. This study aimed to determine the efficiency of the navigation template for clavicle-coracoid drilling and to evaluate the biomechanical performance of the novel CC ligament reconstruction technique. METHODS: A total of 24 fresh-frozen human cadaveric shoulders were randomly assigned to 1 of 3 reconstruction groups or a control group: TightRope, Triple Endobutton, and the Adjustable Closed-Loop Double Endobutton technique. Computed tomography scans, navigation template designs, and 3D printing were performed for the shoulders. Then, AC joint dislocation was simulated in the reconstruction groups, and 3 CC ligament reconstruction techniques were operated via the 3D printing template separately. Furthermore, biomechanical protocols including the translation test (load from 5 to 70 N) and the load-to-failure test were performed to characterize the behaviors and strengths. One-way ANOVA test analyzed differences in displacement under the translation load and the load at failure. RESULTS: CC ligament reconstructions were performed successfully along with the 3D printing navigation template in the 3 reconstruction groups. During the translation test, no significant difference was found in displacements among the 4 groups. Meanwhile, the mean load of all reconstruction groups at failure (Adjustable Closed-Loop Double Endobutton, 722.1620 N; TightRope, 680.4020 N; Triple Endobutton, 868.5762 N) was significantly larger than the control group (564.6264 N, P<0.05). The Triple Endobutton group had the maximum load at failure (P<0.05), however, no significant difference was noticed between the other 2 reconstruction groups (P>0.05). CONCLUSIONS: The 3D printing navigation template may become helpful and reliable for AC joint dislocation surgery. Among the 3 CC ligament reconstruction techniques, the Triple Endobutton technique has the best strength in terms of biomechanics, while the biomechanical strength of the Adjustable Closed-Loop Double Endobutton technique is reliable in comparison with the TightRope technique.
RESUMO
BACKGROUND: The safety of cervical rotatory manipulation (CRM) is still controversial, especially in patients with carotid artery atherosclerosis (CAS). The study aimed to investigate the effects of CRM on carotid plaques in vulnerability. METHODS: 50 rabbits were randomly divided into four groups: model rabbits with CRM [CAS-CRM (n=15)]; model rabbits without CRM [CAS (n=15)]; normal rabbits with CRM [Normal-CRM (n=10)]; and Blank-control group (n=10). CAS disease models were induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. Then, CRM technique was performed in CAS-CRM and Normal-CRM groups for 3 weeks. In the end, determination of serum level of hs-CRP and Lp-PLA2, histological analysis under HE and Masson trichromic staining, and immunohistochemical analysis with CD34 and CD68 antibody were completed in order. RESULTS: Carotid stenosis rates on successful model rabbits ranged from 70% to 98%. The CAS-CRM group had an increased level of hs-CRP (P<0.05), in comparison with the CAS group, whereas effects were not significant between the Normal-CRM group and Blank-control group. In comparison with the CAS group, the positive expression of CD34 and CD68 in the CAS-CRM group increased significantly (P<0.05). CONCLUSION: CRM therapy may increase the vulnerability of carotid plaque in rabbits with severe CAS.
Assuntos
Oclusão com Balão/efeitos adversos , Proteína C-Reativa/genética , Doenças das Artérias Carótidas/cirurgia , Manipulação da Coluna/efeitos adversos , Placa Aterosclerótica/cirurgia , Animais , Antígenos CD34/genética , Proteína C-Reativa/metabolismo , Artérias Carótidas/metabolismo , Artérias Carótidas/fisiopatologia , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/fisiopatologia , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/fisiopatologia , Lesões das Artérias Carótidas/cirurgia , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Placa Aterosclerótica/sangue , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/fisiopatologia , CoelhosRESUMO
BACKGROUND: The variable of the suprascapular notch (SSN) is a common cause in suprascapular nerve (SN) entrapment. Hence, knowledge of SSN variations may be predictive valuable for the predisposition to compression of SN. The aim of this study was to propose the classification of SSN in Chinese population and took this complex morphology into account. MATERIAL AND METHODS: 308 human dry scapulae were analyzed thoroughly and systematically in this study. Morphological variations of the SSN were observed by visual inspection and the classification of SSN was determined by geometrical measurements. Then measurement results were averaged and recorded. RESULTS: Chinese dry scapulae were measured, we found seven types of SSN. Type â (â, 44.8%) was the most common, followed by type â ¡ (U, 41.9%) to â ¦ (double O, 0.6%). Right scapulae were larger in depth of SSN and thickness of A and C. Type â ¦ (double O) had the deepest SSN and type â (â) was widest among five types. For BC, type â (â) was shorter than type â ¢ (V). For thickness of A, type â ¦ (double O) was greater than type â (â). For thickness of C, type â (â) and type â ¡ (U) were shorter than type â ¢ (V). There were no significant differences in other measurements between types and sides of body. Seven types of SSN in Chinese population were defined in our study. CONCLUSION: These anatomical variations of the SSN may improve the diagnostic rate and success rate of the surgical for the suprascapular nerve entrapment.
Assuntos
Síndromes de Compressão Nervosa/fisiopatologia , Escápula/anatomia & histologia , Articulação do Ombro/anatomia & histologia , Povo Asiático , China , Feminino , Humanos , Masculino , Síndromes de Compressão Nervosa/genética , Escápula/inervação , Articulação do Ombro/inervaçãoRESUMO
Cardio-cerebrovascular disease is one of the three major causes of mortality in humans and constitutes a major socioeconomic burden. Carotid atherosclerosis (CAS) is a very common lesion of the arterial walls, which leads to narrowing of the arteries, in some cases occluding them entirely, increasing the risk of cardiovascular events. The aim of the present study was to evaluate a cynomolgus monkey model of carotid atherosclerosis (CAS) induced by puncturing and scratching combined with a high-fat diet. A total of 12 cynomolgus monkeys were randomly divided into four groups: A, puncturing and scratching carotid artery intimas + high-fat diet (n=3); B, puncturing and scratching carotid artery intimas + regular diet (n=3); C, high-fat diet only (n=3); and D, regular diet only (n=3). Blood was harvested at weeks 4, 6 and 8 and plasma lipid levels were assessed. At week 8, monkeys were sacrificed and carotid arteries were harvested for hematoxylin and eosin (H&E) staining to observe pathological changes. The results revealed that a high-fat diet led to increased plasma lipid levels and accelerated plaque formation. Carotid color Doppler ultrasonography was performed and, along with H&E staining, revealed plaque formation in group A. In summary, the results of the present study suggest that a cynomolgus monkey model of CAS model may be successfully constructed by puncturing and scratching of the carotid artery intimas in combination with a high-fat diet.