Aim To explore the characteristic of NO-cGMP signal pathway in the regulation of thoracic aortic relaxation in thyroxine-induced hypertensive rats.Methods Hyperthyroidism was induced by administering Lthyroxine(T4,0.5 mg?kg~-1,sc)daily for 16 days.Sham-treated euthyroid control rats received only vehicle saline for 16 days.SNAP,an NO donor,was used to define the differential relaxation in the thoracic aorta from euthyroid and hyperthyroid rats.To determine the mechanisms involved changes in NO-cGMP signal pathway in the regulation of aortic relaxation from hyperthyroid rats,BAY 41-2272(BAY)was used to activate soluble guanylate cyclase(sGC),ODQ was used to inhibit sGC,and 8-Br-cGMP was used to acti vate protein kinase G(PKG),respectively.Results Thyroid hormone excess for 16 days showed characteristic changes in body weight,heart rate and systolic blood pressure in rats.The body weight was significantly decreased,while heart rate,pulse pressure and systolic blood pressure were increased in T4-treated rats.SNAP caused relaxation in the aorta in both euthyroid and hyperthyroid rats.However,SNAP-induced aortic relaxation was significantly attennuated in hyperthyroid rats than in euthyroid rats.In the presence of ODQ,SNAP-induced aortic relaxation was blocked in both euthyroid and hyperthyroid rats.BAY and 8-BrcGMP-induced aortic relaxation was significantly attennuated in hyperthyroid rats than in euthyroid rats.Conclusion These data suggest that the attenuated effect of NO-cGMP signal pathway is involved in the regulation of aortic relaxation in the pathophysiology of hyperthyroidism,which may be related to the downregulation of sGC and PKG functions.

Aim To investigate the effects of T-and L-type calcium channel blockers on isolated thoracic aorta from thyroxine-induced hypertensive rats.Methods Hyperthyroidism was induced by administering L-thyroxine (T4,0.5 mg·kg~(-1),sc) daily for 16 days.Sham-treated euthyroid control rats were only received vehicle saline for 16 days. Experiments were performed in isolated thoracic aorta rings from euthyroid and hyperthyroid rats. Mibefradil and diltiazem were used to inhibit T-and L-type calcium channels,respectively.Results Thyroid hormone excess for 16 days induced characteristic changes in body weight,heart rate and systolic blood pressure in rats. The body weight was significantly decreased,heart rate and systolic blood pressure were increased in T4-treated rats. Thoracic aorta morphology was altered in T4-treated rats. The thickness of adventitia was increased with hypertrophy and hyperplasia of the smooth musle cells in T4-treated rats. Vasorelaxant effect of T-and L-type calcium channel blockers were accentuated in aortic rings from T4-treated rats.Conclusion These data suggest that T-and L-type calcium channels are functionally upregulated in isolated thoracic aorta from hyperthyroid rats and they,may be a therapeutic target in thyroxine-induced hypertension.

Recent years,chimeric antigen receptor T-cell(CAR-T)therapy has made great strides in enabling better treatment of malig-nant tumors,especially hematological tumors,as well as increasing the research prospects of potential solid tumor therapies.Conse-quently,CAR-T therapy is expected to become the selected treatment for patients with relapsed and refractory tumors.Immune check-point inhibitors also have certain curative effects in the treatment of cancers,such as liver cancer,refractory Hodgkin's lymphoma,and other malignant tumors,which brings promise to patients with advanced cancer.However,both treatments have different degrees of limitations.Recent clinical trials suggest that combined immune checkpoint inhibitors impair the immunosuppressive effects of the tu-mor microenvironment,increase the efficacy of CAR-T therapy,and prolong the survival.This article will review the research progress on the combination of CAR-T immunotherapy and immune checkpoint inhibitors in malignancies theray.

Objective: To investigate the specific cytotoxicities of the second and third generations of chimeric antigen receptor (CAR) -engineered T cells (CAR-T) on different lymphomas. Methods: CAR-Ts were prepared by lentivirus packaging and infection of T cells. CCK-8, ELISA and Lactate dehydrogenase cytotoxicity assay were applied to detect the proliferation capacity, the secretion level of inflammatory factor and the specific cytotoxicity. Flow cytometry assay showed the specific cytotoxicity and residual level of CAR-T in lymphomas of treated mice. Results: The results showed that the third generation CAR-T had greater capacity of the specific cytotoxicity and proliferation capacity than of the second generation CAR-T. But there was no prominent change of the secretion level of inflammatory factor. The specific cytotoxicity of the second generation CAR-T on highly aggressive lymphomas Raji was more prominent than in inert EHEB, but also could achieve satisfactory effect. The tumor burden in the mice injected with Raji was lower than in the mice injected with EHEB from nude mice experiment. But the residual level of CAR-T in the EHEB-injected mice was higher than in the Raji-injected ones. So the second generation CAR-T was more suitable for the treatment of indolent lymphoma. Conclusion The second generation CD19 CAR-T could treat aggressive lymphoma in a relatively short period, while the second generation CD19 CAR-T need a longer time in vivo to achieve satisfactory curative effect on the noble lymphoma.

Objective To investigate ablation characteristics of PVC/VT originating from left ventricle anterior papillary muscles.Methods This study included 10 patients of PVC/VT originating from left ventricle anterior papillary muscles from January 2015 to June 2016 in Beijing Anzhen Hospital.Electrophysiological mapping and radiofrequency ablation were completed using three-dimensional anatomical mapping system combined with three-dimensional intracardiac ultrasound technology.ECG and abaltion target diagram characteristics as well as the special anatomy were explored.Results All the 10 patients were successfully ablated and followed up for 12 months.One patient had recurrence within 12 months and no complications were recorded.The target sites localized at the tip (n =1),middle portion(n =4)or the base (n =5) of the LV-APM.Among 7 patients,the target sites were located at the anterior septal papillary muscle and in 3 patients were located in the free papillary muscle.9 patients were successfully ablated via anterograde trans-septal catheterization after the failure of retrograde approach.Premature QRS wave time were 152.80 ± 11.72 ms and 6 patients presented sharp potential at the targets during PVC/VT.Conclusions PVC/VT originating from left ventricle anterior papillary muscles have similar ECG and diagram characteristics that is different from which originating from left anterior fascicle.It is recommended to get the target via transseptalpuncure approach.Ablation target could be clearly positioned by three-dimensional intracardiac ultrasound technology.