Objective:To investigate the role of NIMA-related kinase-7 (NEK7) in breast cancer (BC) and its potential molecular mechanism.Methods:Quantitative real-time reverse-transcription (RT-qPCR) was used to detect the expression of NEK7 in BC tissue and cell lines. The effect of NEK7 on BC cell proliferation was examined by CCK-8. Proteins interacted with NEK7 were screened in Biological database. The effect of overexpression of NOD-like receptor protein 3 (NLRP3) on BC cell proliferation was evaluated. Western blot was used to detect NLRP3 protein expression, and ELISA was employed to evaluate IL-1β and IL-18 expression level.Result:NEK7 was upregulated in BC tissues and cells, and enforced-expression of NEK7 promoted BC cell proliferation[NEK7 over-expression group: 24 h: (0.33±0.02) , 48 h: (0.59±0.02) , 72 h: (0.76±0.02) ; Blank group: 24 h: (0.30±0.02) , 48 h: (0.45±0.02) , 72 h: (0.62±0.03) ; NEK7 empty vector group: 24 h: (0.32±0.02) , 48 h: (0.46±0.02) , 72 h: (0.63±0.03) ]. There was a positive correlation between NEK7 and NLRP3 ( R=0.13) . Overexpression of NLRP3 increased the proliferation ability of BC cell[NLRP3 over-expression group: 24 h: (0.35±0.02) , 48 h: (0.65±0.02) , 72 h: (0.80±0.03) ; Blank group: 24 h: (0.33±0.02) , 48 h: (0.51±0.02) , 72 h: (0.66±0.03) ; NLRP3 empty vector group: 24 h: (0.34±0.02) , 48 h: (0.52±0.03) , 72 h: (0.66±0.03) ]. NEK7 could positively regulate NLRP3 protein and up-regulate IL-1β (NEK7 over-expression group: 129.96±7.62 pg/ml, Blank group: 19.80±2.42pg/ml, NEK7 empty vector group: 21.30±1.77 pg/ml) and IL-18 (NEK7 over-expression group: 144.08±17.20 pg/ml, Blank group: 16.84±2.34pg/ml, NEK7 empty vector group: 17.64±1.94 pg/ml) expression. Conclusion:The upregulation of NEK7 was involved in the process of BC progression by inducing NLRP3 inflammasome activation, suggesting that NEK7 might be a promising therapeutic target for BC.

PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. RESULTS: c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC₅₀ values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. CONCLUSION: In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.
Adenosine Triphosphate ; Blotting, Western ; Carcinogenesis ; Carcinoma, Non-Small-Cell Lung* ; Cell Movement ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Hepatocyte Growth Factor ; Lung Neoplasms ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Protein-Tyrosine Kinases

Objective:To investigate the curative efficacy and application value of convalescent plasma (CP)in severe and critical coronavirus disease 2019 (COVID-19) caused by Delta variant.Methods:The treatment process and results of CP therapy for a patient with critical COVID-19 caused by Delta variant were reported. The clinical application value of CP for COVID-19 caused by Delta variant was analyzed along with the literature review.Results:Our case was a 50-year-old male, who was imported from abroad and had not been vaccinated against COVID-19. The novel coronavirus nucleic acid test was negative before entry. On the second day after entry, fever occurred, novel coronavirus nucleic acid test was positive. Chest CT images showed bilateral multiple mottling and ground-glass opacity with symptoms of nausea, headache, loss of appetite, diarrhea, but no running nose, nasal obstruction, dyspnea, abnormal smell and taste. The infection rapidly developed from medium to critical. On the basis of standard treatment, Delta variant CP was intravenous dripped on the 10th day of hospital admission (the 6th day after becoming severe). The patient's condition improved rapidly.Conclusion:The curative efficacy evaluation of this patient proved that CP therapy is of great value in the treatment of severe and critical COVID-19.

Objective:To explore the clinical and imaging features and prognoses of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD).Methods:Thirty-nine MOGAD patients, admitted to our hospital from January 2018 to April 2021, were chosen in our study. The clinical and imaging data and follow-up results of these patients at acute attack period (first-onset or relapse) were collected and their features were analyzed.Results:In these 39 patients with MOGAD, 20 patients (51.3%) had non-reversing course, and 19 patients (48.7%) had relapsing course. The clinical and imaging data of 55 episodes of these 39 patients were collected. In these 55 episodes, optic neuritis was noted in 27 episodes (49.1%), encephalitis was noted in 10 episodes (18.2%), brainstem encephalitis was noted in 8 episodes (14.5%), meningoencephalitis in 2 episodes (14.5%), myelitis in 3 episodes (5.5%), encephalomyelitis in 1 episode (1.8%), optic neuromyelitis in 1 episode(1.8%), optic neuritis+meningoencephalitis in 2 episodes (3.6%), and optic neuritis+encephalitis in 1 episode (1.8%). The positive rate of antinuclear antibody (ANA) was 11.1% (4/36); the cerebrospinal fluid results of 28 samples were collected from 22 patients, and CSF pleocytosis occurred in 67.9% of the samples with value of 54.89±67.70×10 6/L. Twenty-seven brain MRIs of 19 patients at the acute episode were collected; one completely normal MRI was recorded; among the remaining 26 MRIs, 6 were with one single lesion, 5 were with 2 lesions, and 15 were with 3 or more lesions; in terms of distribution, lesions involving brainstem and its adjacent structures were found in 9 MRIs, lesions involving diencephalon and deep gray matter were found in 7 MRIs, supratentorial white matter lesions were found in 13 MRIs, and cortical lesions were found in 13 MRIs. Meningeal enhancement were found in 4 contrast-enhanced brain MRIs (4/20). Long or short segmental myelitis in the spinal MRIs was noted in spinal lesions, involving cervical spinal cord, thoracic spinal cord and conus, and the "H" sign could be seen in the cross section. All patients received steroids therapy at the acute phase and the doses of steroids were tapered down gradually. Thirty-eight patients (97.4%) had good prognosis after 3 months of treatment. Conclusions:MOGAD is a disease entity widely involving the white matter, gray matter and meninges of the central nervous system with various clinical manifestations such as optic neuritis, encephalitis, brainstem encephalitis, meningoencephalitis and myelitis or a combination of the above. Immunotherapy is effective in most patients, but the recurrence rate is high, and some patients require long-term immunotherapy.

Objective:To investigate the prognoses of pulmonary adenocarcinoma patients with leptomeningeal metastases (LM) and explore their influencing factors.Methods:A retrospective analysis was performed. The clinical data, imaging features and treatment plans of pulmonary adenocarcinoma patients with LM admitted to our hospital from January 2010 to June 2021 were collected. Overall survival (OS) was used as the prognostic evaluation criterion and patients were divided into good prognosis group (OS≥6 months) and poor prognosis group (OS<6 months) accordingly. Logistic regression analysis was used to evaluate the influencing factors for prognoses of pulmonary adenocarcinoma patients with LM. These patients were grouped according to different Karnofsky performance status (KPS) scores and different treatment methods, and survival curves were drawn to compare their OS.Results:A total of 173 pulmonary adenocarcinoma patients with LM were enrolled in the study, including 75 with good prognosis and 87 with poor prognosis. There were significant differences in the KPS scores, pulmonary adenocarcinoma lesion controlled status, giving third generation tyrosine kinase inhibitor (TKI) therapy or not, giving systemic chemotherapy and/or whole brain radiotherapy or not between the two groups ( P<0.05). Multivariate Logistic regression analysis showed that KPS scores and pulmonary adenocarcinoma lesion controlled status were independent influencing factors for prognoses ( OR=4.186, 95%CI: 1.583-11.070, P=0.004; OR=4.198, 95%CI: 1.499-11.760, P=0.006). Survival curves showed median OS of 8.2 months for all patients ( 95%CI: 6.5-9.8). The OS in patients with low-risk(KPS scores≥60) was significantly higher than that in patients with high-risk(KPS scores<60), that in patients accepted TKI treatment was significantly higher than that in patients not accepted TKI treatment, and that in patients accepted TKI and systemic chemotherapy was significantly higher than that in patients accepted TKI alone ( P<0.05). Conclusion:Patients with high KPS scores and controlled pulmonary adenocarcinoma can have relatively good prognosis; TKI treatment and combination therapy may prolong OS of these patients.