TSH-suppressive therapy can reduce bone mineral density in patients with differentiated thyroid carcinoma: a meta-analysis.

OBJECTIVE: To evaluate the effect of TSH-suppressive therapy on the bone mineral density in patients with differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: The cross-sectional, cohort, prospective controlled, and case-control studies on the bone mineral density change in patients with DTC after TSH-suppressive therapy from databases were searched, including PubMed, Embase, and Cochrane library databases. The effect of TSH-suppressive therapy on bone mineral density of lumbar, femoral neck, femoral greater trochanter, and Ward triangle was analyzed. Data from the database establishment to January 2019 were all reviewed. Meta-analysis was performed with RevMan 5.3 software after two reviewers independently screened the date. The categorical variables were expressed as odds ratios, while the numerical variables were expressed as mean differences. Based on the heterogeneity of the study, a comprehensive analysis was performed by using fixed or random effect models. RESULTS: A total of 11 studies involving 434 patients with differentiated thyroid cancer were included. No significant difference in the bone mineral density of lumbar indications between the experimental and control groups was observed (MD=0.00, 95% CI=-0.03-0.03, p=0.96). The bone mineral density of the femoral neck indications (MD=-0.01, 95% CI=-0.04-0.03, p=0.70). A significant difference between experimental and control groups in the bone mineral density of femoral trochanter indications was observed (MD=-0.11, 95% CI=-0.14-0.07, p<0.00001). The bone mineral density of Ward's triangle indications (MD=-0.06, 95% CI=-0.11-0.01, p=0.02). CONCLUSIONS: TSH-suppressive therapy in patients with DTC mainly reduces the proximal femur bone mineral density.

[Effects of intraoperative graft flow measurements on the early mid-term outcomes after off-pump coronary artery bypass grafting].

OBJECTIVE: To investigate and analyze the relationship between intraoperative graft flow measurements and the early mid-term outcomes after off-pump coronary artery bypass grafting (OPCAB). METHODS: Patients who underwent isolated OPCAB in the Department of Cardiac Surgery of Peking University People's Hospital from January 2013 to June 2016 were included. Perioperative characteristics, graft flow measurements and postoperative follow-up outcomes were retrospectively collected. Comparison was made between flow measurements of grafts and the early mid-term outcomes. Flow measurements of grafts included the mean flow (MF) and the pulsatility index (PI). The early outcomes included peri-operative myocardial infarction (PMI), use of an intra-aortic balloon pump (IABP), reoperation for all causes, new-onset atrial fibrillation and in-hospital or 30-day mortality. RESULTS: A total of 463 patients were included in the study. Mean age was (62.80±8.36) years, and 24.8% were females. The total number of grafts was 1 435, which averaged 3.10 grafts per patient. The MF and PI were separately (32.34±14.45) mL/min and 2.87±0.92. Of all the patients, 23(5%) had PMI, and 11 used IABP. Observed in-hospital or 30-day mortality was 0.86% (4 patients). Compared with non-PMI group, the MF was lower and the PI was higher in the PMI group (P<0.05). However, the differences of other early outcomes had no statistical significance between the PMI group and the non-PMI group. The lower MF (Wald=5.684, P=0.017, 95%CI: 0.894-0.989) and the higher PI (Wald=9.040, P=0.003, 95%CI: 1.252-2.903) were risk factors of PMI in multivariable Logistic regression modeling. The longest follow-up time was 37 months, and 7 patients died. The differences of graft flow measurements between the surviving group and the nonsurvivors had no statistical significance, but overall mid-term survival was lower in patients with poor left internal mammary artery (LIMA) to left anterior descending artery (LAD) graft flow (MF<10 mL/min; OR=9.6, P<0.05). CONCLUSION: Intraoperative graft flow parameters during OPCAB can predict the early mid-term outcomes. The lower MF and the higher PI should increase the rate of PMI. A lower flow of LIMA to LAD graft (<10 mL/min) should increase the rate of midterm mortality, but further research will be needed to confirm and explore the findings.

[Expand prelacrimal recess-maxillary ainus approach for inferior orbital walls fracture treatment].

Objective: To investigate the surgical technique and curative effect of transnasal endoscopic anterior lacrimal approach for the treatment of sacral wall fractures. Method: Retrospective clinical analysis of 5 patients with inferior orbital walls fracture treated by expanding prelacrimal recess-maxillary ainus under nasal endoscope was studied, and the surgical method and its efficacy were annalyzed. Result: After 1 year of follow-up,4 patients' diplopia symptom disappeared, and 1 patient's diplopia symptom was significantly relieved compared with preoperation, the range of eye movement was normal and enophthalmos were totally corrected.Conclusion: Expanding prelacrimal recess-maxillary ainus approach for the treatment of the inferior orbital walls fracture is an effective surgical method.It has the characteristics of less trauma,no incision on the face, clear visual field and wide space of operation, which is worthy of clinical promotion.

[A Meta-analysis of sublingual immunotherapy in the treatment of seasonal allergic rhinitis].

Objective:To systematically evaluate the efficacy and adverse reactions of sublingual immunotherapy for patients with seasonal allergic rhinitis.Method:Literature databases including PubMed, Embase, Cochrane Library, Medline, CBM, Wanfang, CNKI. The time of literature search was limited from January of 2008 to December of 2017.The literature of randomized controlled trials of sublingual immunotherapy for seasonal allergic rhinitis was screened,the quality of the included literature was evaluated,data was extracted,and meta-analysis was performed using RevMan5.3 software.Result:A total of 10 articles were included. The results of meta-analysis showed that for seasonal allergic rhinitis sublingual immunotherapy compared with the control group can reduce symptom scores （SMD=-0.30, 95%CI［-0.39,-0.21］,P<0.000 01) and medication scores (SMD=-0.18, 95%CI［-0.29，-0.08］, P=0.000 8); sublingual immunotherapy for seasonal allergic rhinitis is not restricted by age in the relief of symptoms, and there is no age restriction on reduce medication requirements; sublingual immunotherapy had a higher incidence of adverse reactions than the control group, but it was mostly localized, such as oral pruritus, ear pruritus, throat irritation.Conclusion:Sublingual immunotherapy can alleviate the symptoms and reduce medication requirements in patients with seasonal allergic rhinitis. The adverse reactions are slightly controllable.

[Nasal irrigation with different concentrations of saline as an adjunctive treatment in allergic rhinitis:A systematic review and Meta-analysis].

Objective:To compare the clinical efficacy of different concentrations of saline irrigation in adjuncative treatment of allergic rhinitis by Meta-analysis. Method:According to the inclusion and exclusion criteria, the studies using random controlled trials were retrieved from the Pubmed, Web of science, The Cochrane Library, Embase et al. The Mata-analysis was performed by using RevMan 5.3 software. Result:In total, 1 457 patients were enrolled in 14 randomized controlled trials, including 739 in the isotonic saline group, 350 in the hypertonic saline group,Times New Roman 368 without saline irragation. The results of Meta-analysis showed that the VAS score of saline irrigation group was lower than no saline irrigation group［95%CI (-1.57, -0.15), P=0.02］, the nasal RQLQ score was lower［95%CI (-3.93, -0.43), P=0.01］, and the effective rate was higher［95%CI(1.15, 1.45), P<0.01］; The score of nasal symptoms and signs in hypertonic saline group was lower than that in normal saline group［95%CI(-1.68, -0.63), P<0.01］, and the effective rate was higher［95%CI(1.19, 1.47), P<0.01］. There were significant differences between the two groups. Conclusion:The efficacy of saline irrigation as an adjunctive treatment in allergic rhinitis is significant. The effect of hypertonic saline irrigation was better than that of isotonic saline.

[The clinical efficacy of vidian neurectomy and conservative treatment on moderate-severe allergic rhinitis: a Meta-analysis].

Objective: To compare the clinical effects of vidian neurectomy with conservative management in the treatment for moderate-severe allergic rhinitis. Method: The studies using case controlled trials which were retrieved from Embase, Pubmed, Web of Science, Cochrane Library etc. The Cochrane risk assessment criteria were used to evaluate the quality of the articles that met the inclusion criteria. Manager 5.3 software was used to data analysis. Result: Six articles were included in meta-analysis. Meta-analysis showed that vidian neurectomy group got lower RQLQ scoresï¼»95%CI (-0.98,-0.63),P<0.001ï¼½, less inCIdence of complicationsï¼»95%CI (0.17, 0.67), P=0.002ï¼½, lower VAS scoreï¼»95%CI (-3.97,-3.65), P<0.001ï¼½and higher clinically effective ratioï¼»95%CI (1.18, 50.52), P=0.03ï¼½than conservative treatment group. Conclusion:In summary, we believe that nasal endoscopic vidian neurectomy in the treatment of moderate-severe allergic rhinitis is superior to conservative treatment.

Development of a second-generation oncolytic Herpes simplex virus expressing TNFalpha for cancer therapy.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) therapy is a promising anti-cancer treatment when combined with radiotherapy due to its potent radio sensitising effects, but systemic toxicity has limited its clinical use. Previously, non-replicative adenovirus vectors have been used to deliver TNFalpha directly to the tumour, including under the control of a radiation sensitive promoter. Here, we have used an ICP34.5 deleted, oncolytic herpes simplex virus (HSV) for delivery to increase expression levels and spread through the tumour, and the use of the US11 true late HSV promoter to limit expression to where the virus replicates, i.e. selectively in tumour tissue. METHODS: TNFalpha expression under the CMV or US11 promoter was compared on cell lines CT26, BHK and Fadu. To further compare the activities of the promoters, expression of human TNFalpha was analysed in the presence and absence of acyclovir--an inhibitor of viral DNA replication and on HSV/ICP34.5- non-permissive cell line 3T6. The in vivo efficacy and toxicity of TNFalpha viruses were compared using A20 double flank tumour model in Balb/C mice and Fadu tumour model in nude mice. RESULTS: The results demonstrated that the US11 promoter significantly reduced and delayed TNFalpha expression as compared to use of the CMV promoter, especially in non-permissive cells or in the presence of acyclovir. Despite the reduced and more selective expression levels, US11 driven TNFalpha showed improved anti-tumour effects compared to CMV driven TNFalpha, and without the toxic side effects. CONCLUSIONS: This approach is therefore beneficial in increasing localised TNFalpha expression as compared to the use of non-replicative approaches, and combines the effects of TNFalpha with oncolytic virus replication which is expected to further enhance the efficacy of radiotherapy in a combined treatment approach.

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties.

Herpes simplex virus type-1 (HSV1) in which the neurovirulence factor ICP34.5 is inactivated has been shown to direct tumour-specific cell lysis in several tumour models. Such viruses have also been shown to be safe in Phase I clinical trials by intra-tumoral injection in glioma and melanoma patients. Previous work has used serially passaged laboratory isolates of HSV1 which we hypothesized may be attenuated in their lytic capability in human tumour cells as compared to more recent clinical isolates. To produce ICP34.5 deleted HSV with enhanced oncolytic potential, we tested two clinical isolates. Both showed improved cell killing in all human tumour cell lines tested compared to a laboratory strain (strain 17+). ICP34.5 was then deleted from one of the clinical isolate strains (strain JS1). Enhanced tumour cell killing with ICP34.5 deleted HSV has also been reported by the deletion of ICP47 by the up-regulation of US11 which occurs following this mutation. Thus to further improve oncolytic properties, ICP47 was removed from JS1/ICP34.5-. As ICP47 also functions to block antigen processing in HSV infected cells, this mutation was also anticipated to improve the immune stimulating properties of the virus. Finally, to provide viruses with maximum oncolytic and immune stimulating properties, the gene for human or mouse GM-CSF was inserted into the JS1/34.5-/47- vector backbone. GM-CSF is a potent immune stimulator promoting the differentiation of progenitor cells into dendritic cells and has shown promise in clinical trials when delivered by a number of means. Combination of GM-CSF with oncolytic therapy may be particularly effective as the necrotic cell death accompanying virus replication should serve to effectively release tumour antigens to then induce a GM-CSF-enhanced immune response. This would, in effect, provide an in situ, patient-specific, anti-tumour vaccine. The viruses constructed were tested in vitro in human tumour cell lines and in vivo in mice demonstrating significant anti-tumour effects. These were greatly improved compared to viruses not containing each of the modifications described. In vivo, both injected and non-injected tumours showed significant shrinkage or clearance and mice were protected against re-challenge with tumour cells. The data presented indicate that JS1/ICP34.5-/ICP47-/GM-CSF acts as a powerful oncolytic agent which may be appropriate for the treatment of a number of solid tumour types in man.

The interaction of CGRP and adrenomedullin with a receptor expressed in the rat pulmonary vascular endothelium.

An abundant, seven trans-membrane domain receptor related to the calcitonin receptor has been studied by a number of groups without identification of its ligand. A recent report claimed that the receptor was a type 1 CGRP receptor (Aiyar et al J. Biol. Chem. 271 11325-11329 (1996)). We have studied the equivalent rat sequence in transfected cells. When expressed in 293 cells the receptor interacts with CGRP and adrenomedullin with KD values of 1.2 nM for CGRP and 11 nM for adrenomedullin. Both ligands cause an elevation of intracellular cAMP with EC50 values of 4 nM and 20 nM respectively and these effects are inhibited by the antagonist CGRP8-37. The receptor is expressed at high levels in the pulmonary vascular endothelium. Both the pharmacological data and the localisation are consistent with the conclusion that the orphan receptor is a type J CGRP receptor. However, when expressed in COS-7 cells, no receptor activity could be demonstrated suggesting that 293 cells contain a factor necessary for functional receptor expression.