Objective To explore the levels and the clinical significance of serum soluble Endoglin (sEng) and soluble Fms-like tyrosine kinase (sFlt-1) in patients with preeclampsia (PE). Methods Ninety-six patients with PE were included from June 2009 to June 2014. The patients were divided into mild PE group (n=54) and severe PE group (n=42), while 40 healthy pregnant women were in the control group. The general situation and laboratory testing were recorded and the serum levels of sEng and sFlt-1 were detected. All patients were routinely followed up with the recording of delivery and neonatal situation. Results The sEng and sFlt-1 levels were highest in the severe PE group [(7345.02±772.73) and (866.08±203.24) ng/L], which was followed by mild PE [(5 547.08±564.06) and (603.99±138.37) ng/L] and control group [(1 840.93±300.71) and (252.68±83.03) ng/L] (P<0.01). Levels of sEng were significantly correlated with sFlt-1 in both mild and severe PE groups. There were significantly correlations between sEng and sFlt-1 in mild or severe PE group respectively. The level of sEng and sFlt-1 was considerably positively correlated with mean arterial pressure, 24-hour urinary protein, serum creatinine, fibrinogen, umbilical artery shrink/diastole and resistance index value, but negatively correlated with prothrombin time, birth weight and the placenta weight (P<0.05). PE patients with sEng of <5 000 ng/L and sFlt-1 levels of <700 ng/L had the risk of severe complications of 6.8% and 14.0%; while patients with sEng of ≥5 000 ng/L and sFlt-1 of ≥700 ng/L had the ratio fo 40.4% and 37.0% respectively (P<0.01). Conclusion Serum levels of sEng and sFlt-1 in PE patients indicate that the severity of disease and outcomes of pregnancy.
ObjectiveTo summarize the biological function and molecular regulation mechanism of serine threonine tyrosine kinase 1 (STYK1) in tumor occurrence and development. MethodThe relevant literature about STYK1 and tumor progression in recent years was searched and reviewed. ResultsThe expression of STYK1 was up-regulated in a variety of tumors and was related to the prognosis. STYK1 might regulate the proliferation, apoptosis, migration, metastasis, aerobic glycolysis, drug resistance and other biological functions of tumor cells through MEK/ ERK, PI3K/AKT, JAK/STAT and their targeting proteins, and promote the malignant progress of tumors. Conclusion STYK1is expected to become a new target for the treatment of malignant tumors, but the molecular mechanism of its regulation of tumor progression and its upstream regulators need to be further explored.
ObjectiveTo explore the clinical features of myasthenia gravis (MG) harboring both acetylcholine receptor antibody (AChRAb) and muscle-specific tyrosine kinase antibody (MuSKAb) positivity.MethodsWe searched PubMed, Web of Science, Embase and China National Knowledge Infrastructure databases (from inception to November 2016), to collect the case reports of MG with both AChRAb and MuSKAb positivity. Along with one case discovered in Department of Neurology, West China Hospital, the clinical data of the cases were retrospectively analyzed.ResultsA total of 13 double-seropositive MG patients were enrolled in this study, demonstrating a marked female predominance (including 1 male and 12 females) and a younger age at onset [(31.07±24.77) years]. During the disease course, 10 of the included patients presented severe bulbar involvement, dyspnea and neck weakness, with myasthenic crisis in 6 individuals. Among the 11 patients with detailed records, abnormal thymus glands comprised 4 thymus hyperplasia and one thymoma. While the response to oral pyridostigmine was unsatisfactory in 11 double-seropositive MG patients, ranging from mild benefit to overt intolerance; the patients treated with plasma exchange (3/3), rituximab (1/1) or corticosteroid (7/12) improved dramatically, with other immumosuppressants and intravenous immunoglobulin partially responsive. Moreover, 5 patients undergoing thymectomy improved markedly or partially.ConclusionsCompared with MG patients with MuSKAb positivity merely, the condition of the double-seropositive MG patients seem to be more severe and further inclined to myasthenic crisis. The incidence of abnormal thymus, such as thymus hyperplasia, is higher. Thymectomy may be an effective treatment for such patients.
Waldenstr?m macroglobulinemia (WM) is a rare indolent lymphoplasmacytic lymphoma. Bruton’s tyrosine kinase (BTK) plays a key role in the signaling pathway of WM, which has changed the way of treatment of WM. As a first-generation BTK inhibitor, ibrutinib is an early-stage treatment and a salvage treatment that can control toxicity characteristics. However, in order to overcome the resistance of the first-generation BTK inhibitors, reduce the adverse reactions caused by off-target effects, and improve the efficacy, the research and development of new BTK inhibitors has become a hot topic. This article discusses the clinical studies of the first generation and new BTK inhibitors for WM, aiming to provide a certain basis for the more rational application of BTK inhibitors in WM.
Patients with locally advanced thyroid cancer often face challenges in achieving radical surgery during initial diagnosis. This has become a significant hurdle in the treatment of thyroid cancer. With the continuous development of systemic therapy for thyroid cancer, several studies have demonstrated that neoadjuvant therapy can shrink tumors in some patients, thereby increasing the chances of complete resection and improving prognosis. Targeted therapy plays a crucial role as a core component of neoadjuvant treatment. Simultaneously, the potential efficacy of immunotherapy has gained attention, showing promising prospects. We aim to summarize the research progress and existing issues regarding neoadjuvant therapy for locally advanced thyroid cancer. We look forward to more high-quality clinical studies providing robust evidence for neoadjuvant therapy in locally advanced thyroid cancer, expanding the breadth of treatment options.
The resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been brought into focus. COX-2 signal pathway was found to be closely related to EGFR signal pathway by recent researches, and there has been a growing interest to focus the researches on whether COX-2 pathway inhibition improves the efficacy of EGFR-TKIs in treating advanced NSCLC. In this review, we will illustrate recent advances of combined inhibition of EGFR and COX-2 signal pathways in NSCLC therapy.
ObjectiveTo investigate role and mechanism of protein tyrosine phosphatase 1B (PTP1B) in jejunoileal bypass to treating rats with type 2 diabetes mellitus (T2DM). MethodsTwenty-four T2DM SD rats and 24 normal SD rats were selected randomly by using random number table, then the SD rats with T2DM were randomly divided into jejunoileal bypass operation (DJBO, n=12) group and sham operation (DSO, n=12) group, the SD rats with normal food diet were randomly divided into jejunoileal bypass operation (NJBO, n=12) group and sham operation (NSO, n=12) group. Subsequently, fasting body weight (FBW), fasting plasma glucose (FPG), fasting insulin (FINS), and homeostasis model-insulin resistant (HOMA-IR) index of rats in each group were tested at different time points (before operation, on week 4 and 8 after operation). In addition, expression of PTP1B protein in skeletal muscle was determined by immunohistochemical staining and Western blot method respectively. Results① The FBW before making T2DM model had no significant difference between the rats with high-fat diet and with normal diet (P > 0.05), which on week 4 or 8 after making T2DM model in the rats with high-fat diet was significantly heavier than that in the rats with normal diet (P < 0.05). ② Before jejunoileal bypass operation, the FBW, FPG, FINS, and HOMA-IR index in the DJBO group and the DSO group were significantly higher than those in the NJBO group and the NSO group (P < 0.05), respectively, which had no significant differences between the DJBO group and the DSO group (P > 0.05) and between the NJBO group and the NSO group (P > 0.05). ③ Compared with the values before jejunoileal bypass operation, the FBW, FPG, FINS, and HOMA-IR index on week 4 or 8 after jejunoileal bypass operation were significantly decreased in the DJBO group (P < 0.05); the FBW was significantly increased on week 4 or 8 after jejunoileal bypass operation in the DSO group and the NSO group (P < 0.05), and on week 8 after jejunoileal bypass operation in the NJBO group (P < 0.05). The other indexes had no significant differences between before and after jejunoileal bypass operation in the DSO group, the NSO group, or the NJBO group (P > 0.05). ④ On week 8 after jejunoileal bypass operation, the expression of PTP1B protein in the DSO group was significantly higher than that in the DJBO group, the NSO group or the NJBO group (P < 0.05), which in the DJBO group was significantly higher than that in the NSO group (P < 0.05) or the NJBO group (P < 0.05), which had no significant difference between the NJBO group and the NSO group (P > 0.05). ConclusionJejunoileal bypass could effectively improve insulin resistance and decrease FPG level and FBW of T2DM rats through inhibiting expression of PTP1B protein in skeletal muscle of rat with T2DM.
ObjectiveTo expounded the relationship between phenylalanine, tyrosine and their metabolites and non-alcoholic fatty liver disease (NAFLD). MethodThe literatures related to NAFLD in recent years were reviewed and analyzed. ResultThe levels of phenylalanine, tyrosine and their metabolites had changed significantly in the occurrence and development of NAFLD, and could lead to the progress of NAFLD by affecting the related pathways of lipid metabolism. ConclusionPhenylalanine, tyrosine and their related metabolites are associated with NAFLD, but the specific pathogenesis is still unclear.
The tyrosine kinase activity of epidermal growth factor receptor (EGFR) plays a key role in tumor cell proliferation, invasion, migration, and drug resistance. Studies have shown that non-small cell lung cancer patients with somatic driver gene EGFR mutations are sensitive to and can benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Nevertheless, EGFR-TKIs-related adverse events should not be ignored. Common adverse events such as diarrhea, acne-like rash and paronychia are usually manageable; although the incidence of interstitial lung disease is low, once it occurs, it is a serious threat to patients' life, and its pathogenesis is still unclear. There is very limited animal experimental and clinical research evidence on the potential mechanism of EGFR-TKIs-related interstitial lung disease in the available literature. Based on this, this article reviews the association between EGFR-TKIs and interstitial lung disease, at the same time, also discusses the research progress of EGFR-TKIs-related interstitial lung disease in combination with cytotoxic drugs or immunotherapeutic drugs and EGFR-TKIs, in order to provide a reference for the prevention and treatment of EGFR-TKIs-related interstitial lung disease in clinical practice in the future.
Objective By using small interfering RNAs ( siRNAs) specific for spleen tyrosine kinase ( Syk) , to evaluate the role of Syk in maturation of bone marrow-derived dendritic cells. Methods The fragments of 21-23 bp siRNAs specific for mice Syk were chemo synthesized and transfected into the asthmatic murine bone marrow-derived dendritic cells ( BMDCs) by Lipofectamine 2000 transfection system for 48 hours. Then BMDCs were co-cultured with T cells from the normal mice spleen for 48 hours. The cytokines including IL-4, IL-13, IL-2 and INF-γin supernatant were detect by ELISA. The expression of Syk protein was measured by Western Blot to determine whether the Syk gene was silenced. Results The expression of Syk protein was obviously decreased in the siRNA-interference group. The secretions of IL-4 and IL-13 were significantly inhibited by siRNA interference ( P lt; 0. 05) , but the secretions of IL-2 and INF-γwere not interfered signficantly ( P gt;0. 05) . Conclusion Syk specific siRNA fragments can block the antigen presentation function of dendritic cells and block the activation and differentiation of T cells.