Objective To review recent studies on the research advance of the relationship between RET proto-oncogene and differentiated thyroid carcinoma. Methods The literatures in recent years on the structure of RET gene and coding product,cell signal transduction,relationship between RET proto-oncogene and differentiated thyroid carcinoma were reviewed. Results RET gene encoding tyrosine kinase receptor,involving in cell signal transduction,rearrangement of RET gene was frequently seen in papillary thyroid carcinoma. Conclusion Rearrangement of RET gene was closely correlated with the occurrence and progress of differentiated thyroid carcinoma,RET gene may be considered as a new therapeutic target for differentiated thyroid carcinoma.
Objective To analyze the expressions of galectin-3， human bone marrow endothelial cell-1 （HBME-1），cytokeratin （CK）19， and RET in benign and malignant thyroid tumor and to discuss their clinical significances. Methods The clinicopathologic and immunohistochemical staining data of 131 patients with benign and malignant thyroid tumor were analyzed retrospectively， including 45 patients with malignant thyroid tumor， 86 patients with benign thyroidtumor. The expressions of galectin-3， HBME-1， CK19， and RET in the benign and malignant thyroid tumor were detectedby immunohistochemical staining. Results The positive expression rates of the galectin-3， HBME-1， CK19， and RET in the malignant thyroid tumor were 97.8% （44/45）， 88.9% （40/45）， 100% （45/45）， and 71.1% （32/45）， respectively，which in the benign thyroid tumor were 9.3% （8/86）， 12.8% （11/86）， 37.2% （32/86）， and 8.1% （7/86）， respectively， the differences were statistically significant （P＜0.05）. The diagnostic sensitivity， specificity， and accordance rates were 97.8 %， 90.7%， and 93.1% for the galectin-3， respectively；88.9%， 87.2%， and 87.8% for the HBME-1， respec-tively；100%， 62.8%， and 75.6% for the CK19， respectively；71.1%， 91.9%， and 84.7% for the RET， respectively. Conclusions The expression levels of galectin-3， HBME-1， CK19， and RET in malignant thyroid tumor are significantly higher than those in benign thyroid tumor. Galectin-3， HBME-1， CK19， and RET can be important factors for identifying the benign and malignant tumor and their biological behaviors. Galectin-3 has a high reference value in the diagnosis of thyroid carcinoma.
ObjectiveTo detect the frequency of anaplastic lymphoma kinase (ALK), ROS1 and RET fusion genes in non-small cell lung cancer (NSCLC) patients in Sichuan, and analyze their correlation with clinical features of NSCLC. MethodsReverse transcription-polymerase chain reaction (RT-PCR) was performed to examine gene rearrangement of ALK, ROS1 and RET fusion genes in 310 NSCLC patients who were admitted in Department of Pulmonary Neoplasm of Sichuan Cancer Hospital from March 2009 to March 2012. There were 234 male and 76 female patients with their median age of 60 years (range, 29 to 77 years). There were 164 patients with a smoking history. Histological types included adeno-carcinoma (AC) in 142 patients, squamous cell carcinoma (SCC) in 138 patients, adenosquamous carcinoma in 10 patients, and other types in 20 patients. Patients, gender, age, smoking history, histological types and TNM staging were also collected. Correlations between fusion genes and clinical features were analyzed. ResultsAmong the 310 patient:15 patients with ALK fusion genes were identified (EML4-ALK) with a positive rate of 4.84%, including 14 patients with AC and 1 patient with SCC. ALK fusion genes were more common in patients under 60 years, without a smoking history, and with AC (P < 0.05). ALK fusion genes were not significantly correlated with gender or histodifferentiation. One patient with ROS1 fusion genes (CD74-ROS1) was identified with a positive rate of 0.32%, who was AC patients. Two patients with RET fusion genes (KIF5B-RET) were identified with a positive rate of 0.64%, both of whom were AC patients. ConclusionsGene rearran-gement rates of ALK, ROS1 and RET in NSCLC patients in Sichuan are 4.84%, 0.32% and 0.64% respectively. Patients with negative gene mutation of epithelial growth factor receptor (EGFR), AC, younger age, without a smoking history or with a light smoking history are more common to have ALK gene rearrangement. Gene rearrangement rates of ROS1 and RET are low, and their clinical significance needs more research.
Despite the efficient suppression of HIV-1 replication that can be achieved with combined antiretroviral therapy (cART), low levels of type I interferon (IFN-I) signaling persist in some individuals. This sustained signaling may impede immune recovery and foster viral persistence. Here we report studies using a monoclonal antibody to block IFN-alpha/beta receptor (IFNAR) signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. We discovered that effective cART restored the number of human immune cells in HIV-1-infected hu-mice but did not rescue their immune hyperactivation and dysfunction. IFNAR blockade fully reversed HIV-1-induced immune hyperactivation and rescued anti-HIV-1 immune responses in T cells from HIV-1-infected hu-mice. Finally, we found that IFNAR blockade in the presence of cART reduced the size of HIV-1 reservoirs in lymphoid tissues and delayed HIV-1 rebound after cART cessation in the HIV-1-infected hu-mice. We conclude that low levels of IFN-I signaling contribute to HIV-1-associated immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a potential strategy to enhance immune recovery and reduce HIV-1 reservoirs in individuals with sustained elevations in IFN-I signaling during suppressive cART.
Background: To compare the treatment outcomes between percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) for the management of stones larger than 2 cm in patients with solitary kidney. Methods: One hundred sixteen patients with a solitary kidney who underwent RIRS (n = 56) or PCNL (n = 60) for large renal stones (>2 cm) between Jan 2010 and Nov 2015 have been considered. The patients' characteristics, stone characteristics, operative time, incidence of complications, hospital stay, and stone-free rates (SFR) have been evaluated. Results: SFRs after one session were 19.6% and 35.7% for RIRS and PCNL respectively (p = 0.047), but the SFR at 3 months follow-up comparable in both groups (82.1% vs. 88.3%, p = 0.346). The calculated mean operative time for RIRS was longer (p < 0.001), but the mean postoperatively hospital stay was statistically significantly shorter (p < 0.001) and average drop in hemoglobin level was less (p = 0.040). PCNL showed a higher complication rate, although this difference was not statistically significant. Conclusions: Satisfactory stone clearance can be achieved with multi-session RIRS in the treatment of renal stones larger than 2 cm in patients with solitary kidney. RIRS can be considered as an alternative to PCNL in selected cases.
Proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are used for gastro-esophageal reflux disease (GERD); however, the clinical evidence for treatment is poor. We evaluated the effectiveness and tolerability of different doses of PPIs, H2RAs and placebo in adults with GERD. Six online databases were searched through September 1, 2016. All related articles were included and combined with a Bayesian network meta-analysis from randomized controlled trials (RCTs). The GRADE systems were employed to assess the main outcome. Ninety-eight RCTs were identified, which included 45,964 participants. Our analysis indicated that the full/standard dose of esomeprazole at 40 mg per day was the most efficient in healing among nine different dosages of PPIs and H2RAs. The main efficacy outcome did not change after adjustments for the area, age, level of disease from endoscopy, year of publication, pharmaceutical industry sponsorship, Intention-to-treat (ITT)/per-protocol (PP), withdrawal rate, pre-set select design bias, single blinded and unblinded studies, study origination in China, study arms that included zero events, inconsistency node or discontinued drug were accounted for in the meta-regressions and sensitivity analyses. This research suggests that the full/standard doses (40 mg per day) of esomeprazole should be recommended as first-line treatments for GERD in adults for short-term therapy.
AIM: To assess the neuro-protective effect of bone marrow mesenchymal stem cells (BMSCs) on retinal ganglion cells (RGCs) following optic nerve crush in mice. METHODS: C56BL/6J mice were treated with intravitreal injection of PBS, BMSCs, BDNF-interference BMSCs (BIM), and GDNF-interference BMSCs (GIM) following optic nerve crush, respectively. The number of surviving RGCs was determined by whole-mount retinas and frozen sections, while certain mRNA or protein was detected by q-PCR or ELISA, respectively. RESULTS: The density (cell number/mm(2)) of RGCs was 410.77 +/- 56.70 in the retina 21d after optic nerve crush without any treatment, compared to 1351.39 195.97 in the normal control (P<0.05). RGCs in BMSCs treated eyes was 625.07 +/- 89.64/mm(2), significantly higher than that of no or PBS treatment (P<0.05). While RGCs was even less in the retina with intravitreal injection of BIM (354.07 +/- 39.77) and GIM (326.67 +/- 33.37) than that without treatment (P<0.05). BMSCs injection improved the internal BDNF expression in retinas. CONCLUSION: Optic nerve crush caused rust loss of RGCs and intravitreally transplanted BMSCs at some extent protected RGCs from death. The effect of BMSCs and level of BDNF in retinas are both related to BDNF and GDNF expression in BMSCs.
The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 +/- 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including EnbrelA (R) and local brand Yi Sai PuA (R) and QiangkeA (R)), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 +/- 15.6 mg for 25.5 +/- 47.0 weeks and tocilizumab at 94.5 +/- 21.9 mg for 4.7 +/- 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for < 3 months, those receiving bDMARDs for 3 months exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for 12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA.
Little is known about the objective sleep characteristics of patients with posttraumatic stress disorder (PTSD). The present study examines the association between PTSD symptom severity and objective daytime sleep characteristics measured using the Multiple Sleep Latency Test (MSLT) in therapy-naive patients with earthquake-related PTSD. A total of 23 PTSD patients and 13 trauma-exposed non-PTSD (TEN-PTSD) subjects completed one-night in-lab polysomnography (PSG) followed by a standard MSLT. 8 of the 23 PTSD patients received paroxetine treatment. Compared to the TEN-PTSD subjects, no significant nighttime sleep disturbances were detected by PSG in the subjects with PTSD; however, a shorter mean MSLT value was found in the subjects with PTSD. After adjustment for age, sex, and body mass index, PTSD symptoms, particularly hyperarousal, were found to be independently associated with a shorter MSLT value. Further, the mean MSLT value increased significantly after therapy in PTSD subjects. A shorter MSLT value may be a reliable index of the medical severity of PTSD, while an improvement in MSLT values might also be a reliable marker for evaluating therapeutic efficacy in PTSD patients.