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1.
Cell ; 187(4): 861-881.e32, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38301646

RESUMO

Genomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection. However, cancer cells often evade these responses by overexpressing immune checkpoint regulators, such as PD-L1. Here, we identify the SNF2-family DNA translocase SMARCAL1 as a factor that favors tumor immune evasion by a dual mechanism involving both the suppression of innate immune signaling and the induction of PD-L1-mediated immune checkpoint responses. Mechanistically, SMARCAL1 limits endogenous DNA damage, thereby suppressing cGAS-STING-dependent signaling during cancer cell growth. Simultaneously, it cooperates with the AP-1 family member JUN to maintain chromatin accessibility at a PD-L1 transcriptional regulatory element, thereby promoting PD-L1 expression in cancer cells. SMARCAL1 loss hinders the ability of tumor cells to induce PD-L1 in response to genomic instability, enhances anti-tumor immune responses and sensitizes tumors to immune checkpoint blockade in a mouse melanoma model. Collectively, these studies uncover SMARCAL1 as a promising target for cancer immunotherapy.


Assuntos
Antígeno B7-H1 , DNA Helicases , Imunidade Inata , Melanoma , Evasão Tumoral , Animais , Camundongos , Antígeno B7-H1/metabolismo , Instabilidade Genômica , Melanoma/imunologia , Melanoma/metabolismo , DNA Helicases/metabolismo
2.
J Orthop Surg (Hong Kong) ; 31(2): 10225536231189783, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37458778

RESUMO

BACKGROUND: Checkrein deformity, is a rare claw toe dynamic deformity of the hallux or great toe. This study investigated the use of diagnostic ultrasound in positioning the accurate injury location causing checkrein deformity and its clinical significance for etiological diagnosis and selection of surgical methods. METHODS: This retrospective study included patients with confirmed checkrein deformities (according to typical symptoms) at the Department of Traumatic Orthopedics of Tianjin Hospital (Tianjin, China) from March 2017 to July 2021. RESULTS: A total of 11 patients (8 males and 3 females) with a mean age of 36.7 ± 16.8 (range 19-61) were included in this study. The injuries included six cases of tibia and fibula fracture, one case of single tibia fracture, and one case of single fibula fracture. Four patients were treated with steel plate internal fixation, three patients with intramedullary nailing, and one patient with external fixation. Three patients reported no history of any high-energy trauma or surgery. The ultrasound results showed that seven patients suffered from flexor hallucis longus (FHL) lesions, two patients suffered from flexor digitorum longus (FDL) lesions, and two patients suffered from FHL and FDL lesions. The patients underwent different surgeries tailored to their specific lesions. Toe flexion deformity was completely corrected after operation in all patients. The function of the toes was recovered to varying extent. CONCLUSION: The results of this study demonstrates that the checkrein deformities can be confirmed by ultrasound. It could be used to determine the adhesions before the operation, acting as guidance while establishing the surgical planning.


Assuntos
Hallux , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , , Dedos do Pé , Ultrassonografia
3.
Acta Radiol ; 64(4): 1608-1614, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36071627

RESUMO

BACKGROUND: Ultrasound (US) diagnostic techniques have the advantages of low cost, convenient operation, and high availability. PURPOSE: To explore the diagnostic accuracy of multiparametric US in evaluating signs of peripheral schwannoma. MATERIAL AND METHODS: This retrospective case-control study included patients with soft-tissue masses on the limbs (divided into the schwannoma and non-schwannoma groups) between January 2017 and November 2020. US features were compared between the two groups, and receiver operating characteristics analysis was used to evaluate the diagnostic efficacy of these features. RESULTS: A total of 165 patients were included in this study; of them, 63 (38.2%) were diagnosed with schwannoma. Regular morphology (95.2% vs. 39.2%), cystic degeneration (71.4% vs. 27.5%), target sign on elastography (82.5% vs. 0), and polar blood supply sign (87.3% vs. 14.7%) were more common in schwannomas than in non-schwannoma lesions (all P < 0.001). Combining the four signs for diagnosis of schwannomas, the sensitivity, specificity, and accuracy were 95.24%, 96.08%, and 95.76%, respectively, with an area under the curve (AUC) of 0.987 (95% confidence interval = 0.955-0.998). Entering and exiting nerve sign was observed in 87.3% of schwannomas and in 3.0% of non-schwannoma lesions (P < 0.001), while split-fat sign was similar between the two groups (9.5% vs. 2.0%; P = 0.068). CONCLUSION: Polar blood supply sign and target sign on elastography are specific US signs in peripheral schwannomas. The combination of two-dimensional imaging, color flow imaging, and elastography can achieve an excellent diagnostic accuracy in schwannomas.


Assuntos
Neurilemoma , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Imageamento por Ressonância Magnética/métodos , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Nervos Periféricos/patologia
4.
Orthop Surg ; 14(10): 2682-2691, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36076356

RESUMO

OBJECTIVE: Few studies have performed detailed ultrasound measurements of medial epicondyle-olecranon (MEO) ligament that cause the entrapment of ulnar nerve. This study aims to comprehensively evaluate dynamic ultrasonographic characteristics of MEO ligament and ulnar nerve for clinical diagnosis and accurate treatment of cubital tunnel syndrome (CuTS). METHODS: Thirty CuTS patients (CuTS group) and sixteen healthy volunteers (control group) who underwent ultrasound scanning from October 2016 to October 2020 were retrospectively collected, with 30 elbows in each group. Primary outcomes were thickness at six points, length and width of MEO ligament. Secondary outcomes were thickness of ulnar nerve under MEO ligament at seven parts and the cross-sectional area (CSA) of ulnar nerve at proximal end of MEO ligament (P0 mm ). The thickness of MEO ligament and ulnar nerve in different points of each group was compared by one-way ANOVA analysis with Bonferroni post hoc test, other outcomes were compared between two elbow positions or two groups using independent-samples t test. RESULTS: Thickness of MEO ligament in CuTS group at epicondyle end, midpoint in transverse view, olecranon end, proximal end, midpoint in axial view, and distal end was 0.67 ± 0.31, 0.37 ± 0.18, 0.89 ± 0.35, 0.39 ± 0.21, 0.51 ± 0.38, 0.36 ± 0.25 at elbow extension, 0.68 ± 0.34, 0.38 ± 0.27, 0.77 ± 0.39, 0.32 ± 0.20, 0.48 ± 0.22, 0.32 ± 0.12 (mm) at elbow flexion, respectively. Compared with control group, they were significantly thickened except for proximal end at elbow flexion. MEO ligament thickness at epicondyle end and olecranon end was significantly larger than midpoint in two groups. No significant difference was found in length and width of MEO ligament among different comparisons. Ulnar nerve thickness at 5 mm proximal to MEO ligament (P5 mm , 3.25 ± 0.66 mm) was significantly increased than midpoint of MEO ligament (Mid), distal end of MEO ligament (D0 mm ), 5 mm (D5 mm ), 10 mm (D10 mm ) distal to MEO ligament at extension in CuTS group. Compared with control group, ulnar nerve thickness at P5 mm in CuTS group was significantly increased at extension position, at D5 mm and D10 mm was significantly decreased at flexion position. CSA of ulnar nerve at extension position (14.44 ± 4.65 mm2 ) was significantly larger than flexion position (11.83 ± 3.66 mm2 ) in CuTS group, and CuTS group was significantly larger than control group at two positions. CONCLUSIONS: MEO ligament in CuTS patients was thickened, which compressed ulnar nerve and caused its proximal end swelling. Ultrasonic image of MEO ligament thickness was a significant indicator for CuTS and can guide surgeons in selecting the appropriate treatment.


Assuntos
Síndrome do Túnel Ulnar , Olécrano , Síndrome do Túnel Ulnar/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Nervo Ulnar/anatomia & histologia , Nervo Ulnar/diagnóstico por imagem , Nervo Ulnar/fisiologia , Ultrassom
5.
Orthop Surg ; 13(3): 840-846, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33749099

RESUMO

OBJECTIVE: To explore the effect of locating the ulnar nerve compression sites and guiding the small incision so as to decompress the ulnar nerve in situ on the elbow by high-frequency ultrasound before operation. METHODS: A retrospective analysis was conducted on 56 patients who underwent ultrasound-assisted in situ decompression for cubital tunnel syndrome from May 2018 to August 2019. The patients' average age was 51.13 ± 7.35 years, mean duration of symptoms was 6.51 ± 1.96 months, and mean postoperative follow-up was 6.07 ± 0.82 months. Nine patients had Dellon's stage mild, 39 had stage moderate, and eight had stage severe. Ultrasound and electromyography were completed in all patients before operation. The presence of ulnar nerve compressive lesion, the specific location, and the reason and extent of compression were determined by ultrasound. A small incision in situ surgery was given to decompress the ulnar nerve according to the pre-defined compressive sites. RESULTS: All patients underwent in situ decompression. The compression sites around the elbow were as follows: two in the arcade of Struthers, one in the medial intermuscular septum, four in the anconeus epitrochlearis muscle, five beside the cyst of the proximal flexor carpi ulnaris (FCU), and the remaining 44 cases were all from the compression between Osborne's ligament to the two heads of the FCU. The compression localizations diagnosed by ultrasound were confirmed by operations. Preoperative ultrasound confirmed no ulnar nerve subluxation in all cases. The postoperative outcomes were satisfactory. There was no recurrence or aggravation of symptoms in this group of patients according to the modified Bishop scoring system; results showed that 43 cases were excellent, 10 were good, and three were fair. CONCLUSIONS: High-frequency ultrasound can accurately and comprehensively evaluate the ulnar nerve compression and the surrounding tissues, thus providing significant guidance for the precise minimally invasive treatment of ulnar nerve compression.


Assuntos
Síndrome do Túnel Ulnar/cirurgia , Descompressão Cirúrgica/métodos , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
World J Gastroenterol ; 15(7): 888-91, 2009 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-19230055

RESUMO

Signet-ring cell carcinoma (SRCC) of ampulla of Vater is extremely uncommon, and less than 15 cases have been reported so far in literature. It mainly occurs in elderly people (median age 57 years). We report a rare case of SRCC of the ampulla of Vater in a 38-year-old woman who presented with a small tumor at the Vater, discovered by the contrast-enhanced ultrasound (CEUS). Histopathological examination showed prominent signet-ring features. We also describe the imaging features of SRCC of ampulla of Vater in CEUS.


Assuntos
Ampola Hepatopancreática/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Neoplasias do Ducto Colédoco/diagnóstico por imagem , Adulto , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Meios de Contraste , Duodeno/cirurgia , Feminino , Gastrectomia , Humanos , Excisão de Linfonodo , Pancreatectomia , Resultado do Tratamento , Ultrassonografia
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