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Objective: To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage â A lung adenocarcinoma patients. Methods: A retrospective analysis was conducted on 63 clinical stage â A lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis. Results: After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations (HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations (HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations (HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations (HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations (HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage â A lung adenocarcinoma patients. Conclusions: PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage â A lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.
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Adenocarcinoma de Pulmão , Receptores ErbB , Neoplasias Pulmonares , Mutação , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Proteína Supressora de Tumor p53 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Estudos Retrospectivos , Prognóstico , Receptores ErbB/genética , Proteína Supressora de Tumor p53/genética , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Caderinas/genética , Caderinas/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Sequenciamento do Exoma , Seguimentos , Masculino , Feminino , Pessoa de Meia-Idade , Proteínas de Ligação a DNA , Receptores de LDL , Fatores de TranscriçãoRESUMO
OBJECTIVE: To investigate the effect of type 2 dengue virus (DENV-2) infection on autophagy in human umbilical vein endothelial cells (HUVECs) and the mechanism mediating the inhibitory effect of baicalin against DENV-2 infection. METHODS: Cultured HUVECs with DENV-2 infection were treated with different concentrations of baicalin, and the changes in autophagy of the cells were detected using transmission electron microscopy. Lyso Tracker Red staining was used to examine pH changes in the lysosomes of the cells, and the expressions of ATG5, beclin-1, LC3, P62, STX17, SNAP29, VAMP8, and PI3K/AKT signaling pathway-related proteins were detected by Western blotting. DENV-2 replication in the cells were evaluated using RT-qPCR. The differentially expressed proteins in DENV-2-infected HUVECs were identified by proteomics screening. RESULTS: Treatment with baicalin did not significantly affect the viability of cultured HUVECs. Proteomic studies suggested that the PI3K-AKT pathway played an important role in mediating cell injury induced by DENV-2 infection. The results of RT-qPCR demonstrated that baicalin dose-dependently inhibited DENV-2 replication in HUVECs and produced the strongest inhibitory effect at the concentration of 50 µg/mL. Transmission electron microscopy, Lyso Tracker Red staining, RT-qPCR, and Western blotting all showed significant inhibitory effect of baicalin on DENV-2-induced autophagy in HUVECs. DENV-2 infection of HUVECs caused increased cellular expressions of LC3 and P62 proteins, which were significantly lowered by treatment with LY294002 (a PI3K inhibitor). CONCLUSION: Baicalin inhibits DENV-2 replication in HUVECs and suppresses DENV-2-induced cell autophagy by inhibiting the PI3K/AKT signaling pathway.
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Autofagia , Vírus da Dengue , Flavonoides , Células Endoteliais da Veia Umbilical Humana , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Vírus da Dengue/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Flavonoides/farmacologia , Replicação Viral/efeitos dos fármacos , Células CultivadasRESUMO
PURPOSE: At present, various treatment strategies are available for pituitary adenomas, including medications, surgery and radiation. The guidelines indicate that pharmacological treatments, such as bromocriptine (BRC) and cabergoline (CAB), are important treatments for prolactinomas, but drug resistance is an urgent problem that needs to be addressed. Therefore, exploring the mechanism of drug resistance in prolactinomas is beneficial for clinical treatment. METHODS: In our research, BRC-induced drug-resistant cells were established. Previous RNA sequencing data and an online database were used for preliminary screening of resistance-related genes. Cell survival was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assays and flow cytometry. Quantitative real-time polymerase chain reaction (qRTâPCR), western blotting, immunohistochemistry, immunofluorescence and Co-immunoprecipitation (Co-IP) were used to assess the molecular changes and regulation. The therapeutic efficacy of BRC and FGFR4 inhibitor fisogatinib (FISO) combination was evaluated in drug-resistant cells and xenograft tumors in nude mice. RESULTS: Consistent with the preliminary results of RNA sequencing and database screening, fibroblast growth factor 19 (FGF19) expression was elevated in drug-resistant cells and tumor samples. With FGF19 silencing, drug-resistant cells exhibited increased sensitivity to BRC and decreased intracellular phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels. After confirming that FGF19 binds to FGFR4 in prolactinoma cells, we found that FGF19/FGFR4 regulated prolactin (PRL) synthesis through the ERK1/2 and JNK signaling pathways. Regarding the effect of targeting FGF19/FGFR4 on BRC efficacy, FISO and BRC synergistically inhibited the growth of tumor cells, promoted apoptosis and reduced PRL levels. CONCLUSION: Overall, our study revealed FGF19/FGFR4 as a new mechanism involved in the drug resistance of prolactinomas, and combination therapy targeting the pathway could be helpful for the treatment of BRC-induced drug-resistant prolactinomas.
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OBJECTIVE: To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1ß levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. RESULTS: Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1ß, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. CONCLUSION: Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1ß/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.
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Artrite Experimental , Artrite Reumatoide , Medicamentos de Ervas Chinesas , Metaloproteinase 1 da Matriz , Ratos Sprague-Dawley , Membrana Sinovial , Fator de Necrose Tumoral alfa , Animais , Ratos , Artrite Reumatoide/tratamento farmacológico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 1 da Matriz/metabolismo , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Regulação para Baixo/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinases da Matriz/metabolismo , Tripterygium/química , Fator de Transcrição RelA/metabolismoRESUMO
Objective: To evaluate the clinical efficacy of posterior lumbar interbody fusion combined with Ponte osteotomy in the treatment of patients with degenerative scoliosis. Methods: The medical records and imaging data of degenerative scoliosis in department of orthopedics, Peking Union Medical College Hospital from 2013 to 2022 were retrospectively collected, and the shortest follow-up time was 1 year. A total of 38 patients were included, including 13 males and 25 females, aged 50-87(65.6±10.9) years old.The follow-up was12-119(43±20) months. Standing position full spine anteroposterior lateral X-ray examinations were performed on all patients preoperatively, postoperatively, and at latest follow-up. The length of hospital stay, complications, operation time, blood loss, instrumented segment, fusion segmen were recorded. The clinical scores and coronasagittal imaging indicators at three time points were compared. Results: The operation time was (274.5±70.5)min, and intraoperative blood loss was (619.2±93.5)ml. The coronal vertical axis was improved from (2.9±1.8)cm preoperatively to (1.2±1.0)cm postoperatively. The preoperative coronal Cobb angle was 16.6°±9.9° and the immediate postoperative correction was 6.4°±4.0°(t=-6.83, P<0.001). The difference was statistically significant (t=-6.12, P<0.001). The coronal Cobb Angle at the last follow-up was 5.7°±3.7°, and there was no significant orthopaedic loss at the last follow-up (t=-6.12, P<0.001).The sagittal vertical axis decreased from (5.6±3.9)cm preoperatively to (3.2±2.5) cm immediately after operation (t=-6.83,P<0.001), and was well maintained at the last follow-up[(2.7±1.8) cm,t=-7.77,P<0.001]. Lumbar lordosis increased from 21.8°±10.2° preoperatively to 35.8°±8.3° postoperatively(t=12.01, P<0.001)and 40.1°±8.6° at last follow-up(t=-10.21, P<0.001). Oswestry disability score (ODI score), visual analogue score (VAS) low back pain score and VAS leg pain score were also lower after surgery than before surgery (all P<0.05). Conclusion: Posterior lumbar interbody fusion combined with Ponte osteotomy can significantly improve the coronal and sagittal plane deformity and postoperative functional score in adult patients with degenerative scoliosis.
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Escoliose , Fusão Vertebral , Adulto , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Escoliose/cirurgia , Estudos Retrospectivos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Resultado do Tratamento , OsteotomiaRESUMO
Objective: To summarize the characteristics of multisystem deformities in patients with Klippel-Feil syndrome (KFS) combined with congenital scoliosis (CS). Methods: Within the framework of the "Deciphering Disorders Involving Scoliosis and Comorbidities (DISCO)" research collaboration, a retrospective analysis was conducted on patients diagnosed with KFS and CS at Peking Union Medical College Hospital between April 2005 and August 2022. Patient data, including imaging examinations and medical records, were collected to summarize the spinal and associated deformities. Results: A total of 82 KFS patients with concurrent CS were included, comprising 42 males and 40 females. The average age was (12.8±8.9) years. Among the KFS patients, there were 31 cases of Type â , 12 cases of Type â ¡, and 39 cases of Type â ¢. The most common location for the major curve of scoliosis was the mid-thoracic segment (42 cases, 51.2%). Hemivertebrae deformities were most frequently observed in the upper thoracic segment (31 cases, 60.8%). There were no statistically significant differences in age, gender, major curve Cobb angle, or region of hemivertebrae occurrence among the different types of KFS (all P>0.05). Apart from spinal vertebral deformities, intraspinal deformities had the highest comorbidity rate (33 cases, 40.2%). The subjects were divided into two groups based on the presence or absence of intraspinal deformity (absence as group G0, presence as group G1), there was a statistically significant difference in the main Cobb angle [M(Q1, Q3)] between the two groups, which was 45.0° (27.5°, 62.0°) and 60.0° (37.5°, 83.5°), respectively (P=0.044). Additionally, a portion of the patients had concurrent cardiovascular system abnormalities (13 cases, 15.9%), craniofacial-ocular-auricular abnormalities (8 cases, 9.8%), genitourinary system abnormalities (7 cases, 8.5%), and gastrointestinal abnormalities (2 cases, 2.4%). Conclusions: Patients with KFS combined with CS commonly present with a major curve of spinal deformity in the mid-thoracic segment and often have comorbidities involving multiple systems. When combined with intraspinal anomalies, the major curve exhibits a greater degree of curvature.
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Síndrome de Klippel-Feil , Escoliose , Masculino , Feminino , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Síndrome de Klippel-Feil/epidemiologia , Estudos Retrospectivos , Coluna Vertebral , Exame FísicoRESUMO
INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard approach for lung cancer staging. However, its diagnostic utility for other mediastinal diseases might be hampered by the limited tissue retrieved. Recent evidence suggests the novel sampling strategies of forceps biopsy and cryobiopsy as auxiliary techniques to EBUS-TBNA, considering their capacity for larger diagnostic samples. METHODS: This study determined the added value of forceps biopsy and cryobiopsy for the diagnosis of mediastinal diseases. Consecutive patients with mediastinal lesions of 1 cm or more in the short axis were enrolled. Following completion of needle aspiration, three forceps biopsies and one cryobiopsy were performed in a randomised pattern. Primary endpoints included diagnostic yield defined as the percentage of patients for whom mediastinal biopsy led to a definite diagnosis, and procedure-related complications. RESULTS: In total, 155 patients were recruited and randomly assigned. Supplementing EBUS-TBNA with either forceps biopsy or cryobiopsy increased diagnostic yield, with no significant difference between EBUS-TBNA plus forceps biopsy and EBUS-TBNA plus cryobiopsy (85.7 % versus 91.6 %, P = 0.106). Yet, samples obtained by additional cryobiopsies were more qualified for lung cancer molecular testing than those from forceps biopsies (100.0 % versus 89.5 %, P = 0.036). When compared directly, the overall diagnostic yield of cryobiopsy was superior to forceps biopsy (85.7 % versus 70.8 %, P = 0.001). Cryobiopsies produced greater samples in shorter procedural time than forceps biopsies. Two (1.3 %) cases of postprocedural pneumothorax were detected. CONCLUSIONS: Transbronchial mediastinal cryobiopsy might be a promising complementary tool to supplement traditional needle biopsy for increased diagnostic yield and tissue harvesting. TRIAL REGISTRATION: ChiCTR2000030373.
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BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.
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Anticorpos Monoclonais Humanizados , Melanoma , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axitinibe/efeitos adversos , Axitinibe/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/cirurgia , Terapia Neoadjuvante/métodos , Estadiamento de NeoplasiasRESUMO
The aim of this study was to investigate the treatment effects of a stabilisation splint (SS) with and without arthroscopic disc repositioning (ADR) on condylar bone remodelling in adolescent patients with anterior disc displacement without reduction (ADDwoR). Cone beam computed tomography and magnetic resonance imaging were used to analyse condylar bone remodelling, condyle position, and disc position. Twenty-two temporomandibular joints of 14 patients who underwent ADR (age range 12-20 years; mean follow-up 12.5 ± 7.8 months) and 21 temporomandibular joints of 14 patients who did not undergo ADR (age range 13-20 years; mean follow-up 11.1 ± 5.1 months) were included. The change in bone volume (P < 0.001), rate of bone volume change (P < 0.001), and change in condyle height (P = 0.031) were significantly greater in patients with ADR than in those without ADR. The changes in posterior joint space (P = 0.013), superior joint space (P = 0.020), and ratio of condyle sagittal position (P = 0.013) were significantly greater in patients with ADR than in those without ADR. All discs in patients who underwent ADR and one disc in those who did not undergo ADR were backward repositioned. In conclusion, in adolescent patients with ADDwoR, ADR with SS therapy achieved better condyle and disc position than SS therapy alone, and also induced bone generation.
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Luxações Articulares , Transtornos da Articulação Temporomandibular , Humanos , Adolescente , Criança , Adulto Jovem , Adulto , Disco da Articulação Temporomandibular/cirurgia , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/terapia , Transtornos da Articulação Temporomandibular/patologia , Contenções , Articulação Temporomandibular/patologia , Imageamento por Ressonância Magnética/métodos , Placas Oclusais , Remodelação Óssea , Luxações Articulares/cirurgiaRESUMO
OBJECTIVE: To investigate the effect of yacon root extract on lipid metabolism in rats with hyperlipidemia (HLP) and its underlying mechanisms. METHODS: SD rat models of HLP induced by high- fat diet feeding for 8 weeks were randomized into the model group, fenofibrate treatment group (27 mg/kg), and yacon extract treatment groups at doses of 5, 2.5 and 1.25 g/kg (n=10). The rats were given corresponding drug treatments via gavage for 8 weeks. After the treatments, the rats were observed for body weight changes, liver coefficient, liver pathology, and serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The mRNA and protein expressions of HMGCR, PPARα, CYP7A1, and CPT-1 in the liver were detected using RT-qPCR and Western blotting. RESULTS: Compared with those in the model group, the rats treated with fenofibrate and 5 g/kg yacon root extract showed significantly slower body weight gain and lower liver coefficient (P < 0.05) with lower serum levels of TG, TC, and LDL- C (P < 0.05) but higher HDL- C level (P < 0.05). The HLP rat models showed obvious fatty degeneration and vacuolar changes in the liver, which were significantly alleviated by fenofibrate treatment and by treatment with yacon root extract in a dose-dependent manner. Both fenofibrate and 5 g/kg yacon root extract significantly lowered the mRNA and protein expression levels of HMGCR (P < 0.001) and increased the expressions of PPARα, CYP7A1, and CPT-1 in the liver of HLP rats (P < 0.001). CONCLUSION: Yacon root extract can reduce serum TG and TC levels in HLP rats possibly by inhibiting HMGCR expression and activating the PPARα/CYP7A1/CPT-1 signaling pathway, thereby promoting fatty acid ß oxidation and bile acid metabolism.
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Fenofibrato , Hiperlipidemias , Animais , Ratos , Peso Corporal , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , LDL-Colesterol , Dieta Hiperlipídica , Hiperlipidemias/tratamento farmacológico , Metabolismo dos Lipídeos , Fígado/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Ratos Sprague-Dawley , RNA Mensageiro/metabolismo , TriglicerídeosRESUMO
Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.
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Timoma , Neoplasias do Timo , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Timoma/genética , Hibridização in Situ Fluorescente , Fatores de Transcrição/genética , Mutação , Neoplasias do Timo/genéticaRESUMO
Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage â A lung cancer. Methods: A total of 1 155 patients with stage â A lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of â A1 to â A3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageâ A1, â A2 and â A3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage â A lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage â A lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage â A lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Biomarcadores Tumorais , Estudos Retrospectivos , Antígenos de Neoplasias , Queratina-19 , Antígeno Carcinoembrionário , Adenocarcinoma/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Fosfopiruvato Hidratase , Tomografia Computadorizada por Raios XRESUMO
Objective: To analyze the efficacy of different targets low-frequency repetitive transcranial magnetic stimulation (rTMS) for the treatment of tremor Parkinson's disease(PD). Method: A total of 82 patients with primary PD who were admitted to the Department of Neurology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 1, 2020 to March 31, 2021 were prospectively collected. According to the clinical characteristics of major movement disorders, 82 patients with tremor type (TD) were selected to enroll.The patients were randomly divided into 3 groups at a 1â¶1â¶1 ratio according to the randomized coding sequence of the trial: the primary motor cortex (M1) group with 26 cases, the cerebellum group with 26 cases and the dual-site (M1, cerebellum) group with 30 cases. All patients were treated with 1 Hz low-frequency stimulation of the corresponding target once a day for 5 days a week for 2 weeks, a total of 10 times; The dosage remained unchanged during the treatment for all groups. Before and after 2 weeks' treatment, the patients were assessed with the Unified PD Rating Scale (UPDRS) and PD Quality of Life Questionnaire-39 (PDQ-39) without medication. Cortical excitability, namely transcranial magnetic stimulation motor evoked potential (TMS-MEP), [including resting motor threshold (rMT) and active motor threshold (aMT) examinations], timed up and go (TUG) and electromyographic tremor were conducted. Result: There were 82 patients, 39 males and 43 females, with an average age of (67±8) years. Before the treatment, there was no statistically significant difference in the evaluation indicators among the three groups (all P>0.05). After the treatment, the differences of the UPDRS-â ¢ score [(38.9±2.5) vs (29.2±3.6) ], UPDRS tremor score [(23.7±2.1) vs (14.6±3.1) ], TUG time [(44.8±3.1) s vs (33.7±4.1) s], tremor amplitude [(480±126) µV vs (276±94) µV], PDQ-39 score [(51±13) vs (45±13) ], rMT [(36±17)% vs (43±13)%], and aMT [(26±16)% vs (31±12)%] were statistically significant (all P<0.01) from those before the treatment. There was no statistical difference in the above factors between the M1 group and cerebellum group (all P>0.05). There was no statistically significant difference in tremor peak frequency among the three groups before and after the treatment (all P>0.05). Conclusions: Dual-site low-frequency rTMS can improve PD tremor, while M1 or cerebellar low-frequency rTMS does not significantly improve PD tremor. Its mechanism may be to improve PD tremor symptoms by regulating cortical excitability.
Assuntos
Córtex Motor , Doença de Parkinson , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Doença de Parkinson/terapia , Estimulação Magnética Transcraniana/efeitos adversos , Tremor/terapia , Tremor/etiologia , Qualidade de Vida , Córtex Motor/fisiologia , ChinaRESUMO
BACKGROUND/AIM: System ASC amino acid transporter-2 (ASCT2) is abnormally highly expressed in tumor cells and closely associated with a poor prognosis, but the regulatory mechanism of abnormally high ASCT2 expression is scarcely investigated. MicroRNAs (miRNAs) that are abnormally expressed regulate gene expression to have either oncogenic or tumor-suppressive effects in pancreatic cancer (PC). MicroRNA-122-5p (miR-122-5p) dysregulation has been seen in various cancer entities, but the biological function of miR-122-5p in PC and its regulation mechanisms remain unknown. MATERIALS AND METHODS: Western blot and quantitative RT-PCR were used to measure the expression of miR-122-5p, ASCT2, and apoptosis-related proteins. CCK-8 assays were used to elucidate the effect on cell proliferation. Flow cytometry (FCM) assays were utilized to evaluate cell apoptosis. A dual-luciferase reporter assay was utilized to determine if miR-122a-5p directly targeted ASCT2. Glutamine consumption and the α-ketoglutarate (α-KG) and adenosine triphosphate (ATP) contents were determined using respective assays. RESULTS: MiR-122-5p expression was low whereas ASCT2 expression was high in PC tissues and cells. Overexpressing miR-122-5p restrained pancreatic cancer cell proliferation, accelerated apoptosis, and decreased glutamine consumption, α-ketoglutarate (α-KG) production and ATP generation, whereas suppressing miR-122-5p had the opposite effect. Moreover, the reporter gene test established ASCT2 as a miR-122-5p target. Overexpression of miR-122-5p decreased ASCT2 expression, whereas miR-122-5p repression increased ASCT2 expression. In addition, miR-122-5p also regulated apoptosis-related pathways. CONCLUSION: MiR-122-5p may function as a tumor suppressor by inhibiting the proliferation, glutamine metabolism, and inducing apoptosis via altering the expression of ASCT2 in pancreatic cancer cells.
Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Glutamina/metabolismo , Ácidos Cetoglutáricos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias PancreáticasRESUMO
To evaluate the effectiveness of intervention plans developed by the evidence base multi-discipline critical strategies (EBPCS) on temperature and clinical outcomes in very preterm infants (VPIs) born at<32 weeks. Clinical data were collected from VPIs born in the delivery room/operating room of Chengdu Women's and Children's Central Hospital from May 1, 2021, to May 31, 2022, who required immediate temperature management and were transferred to the neonatal intensive care unit (NICU) of the hospital. The study population was randomly divided into a control group and an intervention group based on the random number table method, with 108 cases in each group. The control group implemented the conventional temperature management recommended by domestic guidelines, while the intervention group adopted EBPCS interventions compared to the control group. The differences in body temperature and clinical outcomes between the two groups were compared after the implementation of different temperature management strategies. A total of 216 VPIs were included. The intervention group had a lower incidence of hypothermia (30.55% vs. 87.03%, P<0.001), higher mean body temperature admitted to the NICU [(36.56±0.31) â vs. (35.77±0.53) â, P<0.001], a lower dose of pulmonary surfactant [(115.94±36.96) mg/kg vs. (151.41±54.68) mg/kg, P=0.014], shorter duration of mechanical ventilation [(5.77±1.26) days vs. (14.19±4.63) days, P=0.006], and lower incidence of intraventricular haemorrhage (12.04% vs. 23.15%, P=0.032). The implementation of temperature intervention strategies developed by the EBPCS for VPIs after birth could prevent and reduce the incidence of hypothermia and improve clinical outcomes.
Assuntos
Hipotermia , Recém-Nascido Prematuro , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Febre , Hipotermia/prevenção & controle , Recém-Nascido de muito Baixo Peso , TemperaturaRESUMO
Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant â ¡), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Assuntos
Diabetes Mellitus , Gravidez , Criança , Humanos , Feminino , Hemoglobinas Glicadas , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Sensibilidade e Especificidade , Curva ROCRESUMO
Objective: To investigate the epidemiology, clinical characteristics, on-site dust monitoring and individual protection of the patients with artificial stone-related silicosis. Methods: In March 2022, the literature on artificial stone-related silicosis published from January 1965 to February 2022 was searched in China Journal Full-text Database, Wanfang Database, VIP Database, EMbase and PubMed. Chinese and English search terms include "silica dust""silica dust""silicosis""artificial stone""pneumoconiosis", etc. References were included according to inclusion and exclusion criteria, and data were extracted. The epidemiological characteristics, natural course of disease, workplace dust concentration and individual protection level of patients with artificial stone-related silicosis were analyzed by systematic review. Results: A total of 30 literatures were included, including 7 cohort studies, 14 cross-sectional studies, 3 case-control studies and 6 case reports. A total of 1358 patients with artificial stone-related silicosis were diagnosed from 1997 to 2020, with an average age of 41.5 years old and an average dust exposure time of 11.3 years. Among them, 36.2% (282/778) had progressive mass fibrosis or accelerated progressive silicosis at first diagnosis. Chest imaging showed diffuse small nodule shadow, pulmonary fibrosis, and silico-alveolar proteinosis. Pulmonary function showed restricted or mixed ventilation disorder with or without decreased diffusion volume. The disease progressed rapidly, with progressive mass fibrosis, respiratory failure, and even death. Patients engaged in artificial quartz stone processing, with high concentration of silica including ultra-fine particles, most of which were dry operation, lack of on-site ventilation measures and no effective personal protection. Conclusion: The artificial stone processing workers suffer from artificial stone-related silicosis due to dry cutting, lack of on-site dust removal facilities and personal protective measures, and the disease progresses rapidly, leading to poor prognosis.