OBJECTIVETo explore the changes in the expression of pineal clock genes in rats with chronic cerebral ischemia and evaluate the effect of intervention with Wulongdan, a traditional Chinese medicinal preparation, on these changes.

METHODSMale SD rats were randomly divided into sham-operated group, chronic cerebral ischemia model group, and treatment group. In the latter two groups, chronic cerebral ischemia was induced by permanent ligation of the bilateral carotid arteries, and in the treatment group, Wulongdan was administered intragastrically on a daily basis for 3 weeks after the operation. Real-time quantitative RT-PCR was employed to examine the changes in the pineal expressions of Clock, Bmal1, and Per1 mRNA after the treatment.

RESULTSIn the model group, the expression levels of Clock and Per1 mRNA were significantly lowered compared to those in the sham-operated group (P<0.01, P<0.05), but Bmal1 mRNA expression showed no significant changes (P>0.05). Wulongdan treatment caused a significant increase in pineal lock mRNA expression compared to the model group (P<0.01), and significantly reduced pineal Bmal1 expression as compared to the sham-operated group (P<0.05). No significant difference was found in Per1 mRNA expression between the treatment group and the model group.

CONCLUSIONSThe changes in the expressions of the pineal clock genes in rats with chronic cerebral ischemia suggest the association between chronic cerebral ischemia and sleep disorders. Wulongdan can mitigate sleep disorders caused by chronic cerebral ischemia.

Animals ; Brain Ischemia ; metabolism ; CLOCK Proteins ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Male ; Pineal Gland ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

Objective To establish a porcine allogeneic left lung orthotopic transplantation model to closely simu-late human lung transplantation.Methods Twelve Huanjiang mini-pigs were used as donors and 12 Bama mini-pigs as recipients.The left lung orthotopic transplantation was completed by the left fourth intercostal thoracotomy.At 1 h, 2 h, 4 h, 6 h, 12 h after transplantation, the left and right pulmonary artery pressure were measured, the left and right pulmonary vein blood gas was analyzed, and samples of the left and right lung tissues were taken to determine the water content and for pathological examination.Results All animals survived, and the transplanted pulmonary vein blood PaO2/FiO2 and PAP were rised along with the prolonged postoperative time, compared with those of the recipient normal lung showing a signifi-cant difference (P<0.05).With the pass of time, there were increasing edema, inflammatory cell infiltration, RBC ooze, thickening of alveolar wall in the transplanted lung tissue, and some alveolar lumen occlusion and lung tissue consolidation. The water content of the transplanted lung tissue was increased significantly compared with that in the recipient lung tissue ( P<0.05 ) .Conclusions The established method in this study provides an ideal animal model for research on lung transplantation ischemia-reperfusion injury and immune rejection mechanism.

Objective To study the value of epidemiology-based mortality score,a novel scoring system,in in-hospital adult patients with status epilepticus (SE) for predicting mortality,and to compare it with the status epilepticus severity score (STESS).Methods The clinical and electroencephalography data of 54 adult patients with SE admitted from June 2013 to June 2016 were derived from a prospective SE database of Zhejiang Provincial Hospital of Traditional Chinese Medicine.The outcome was defined as inhospital death or survival at discharge.When the receiver-operating characteristic (ROC) curves were made,the area under ROC (AUC) and the optimal cutoff value were calculated.Fisher's linear discriminant function analysis was conducted with the outcome as dependent variable and the scores as independent variables.Results Among 54 patients with SE recruited into the study,13 (24.10 ％) died in the hospital.The ROC curve for prediction of in-hospital death based on the STESS had a AUC of 0.705with an optimal cutoff value for discrimination (best match for both sensitivity (0.77) and specificity (0.56) to be ≥ 3 points.The AUC based on the EMSE was 0.800 with an optimal cutoff value for discrimination (best match for both sensitivity (0.92) and specificity (0.61) to be ≥ 79 points.Three elements added in combination with EMSE system (etiology-age-comorbidity,EMSE-EAC) predicted inhospital mortality with the best match for both sensitivity (1.00) and specificity (0.56) as the optimal cutoff point was ≥32 points,and the AUC was 0.814.Four elements added in combination with EMSE system (etiology-age-comorbidity-EEG,EMSE-EACE) predicted in-hospital mortality with the best match for both sensitivity (0.77) and specificity (0.98) as the optimal cutoff point was ≥71 points with an AUC of 0.925.The AUC of EMSE-EACE was larger than that of both STESS and EMSE (Both P ＜ 0.01).Discriminant equations were found by Fisher linear discriminant analysis.The rates of accuracy of the equation for predicting patients' prognosis were 44.44％ (STESS),62.96％ (EMSE),70.37％ (EMSE-EAC) and 81.48％ (EMSE-EACE) respectively,suggesting that the equations of EMSE,EMSE-EAC and EMSE-EACE have superior stability.Conclusions The EMSE is an effective clinical scoring system that focuses on individual mortality.EMSE-EACE is superior over both STESS and EMSE in the prediction of inhospital death.

C-C motif chemokine ligand 2(CCL2)and its receptor CCR2 are closely related to tumorigenesis and tumor progression.The CCL2/CCR2 signaling axis promotes tumor progression through multiple mechanisms:CCL2 binds to CCR2 on the surface of tumor cells,and thus promotes tumor growth/survival and metastasis;more importantly,CCL2 recruits a variety of immunosuppressive cells to aggregate in the tumor microenvironment,and inhibits the function and activity of immune cells,promoting tumor progression.The article reviews the CCL2/CCR2 signaling axis and its role in tumors and tumor microenvironment,with particular focus on the advances in clinical research on drugs targeting CCL2/CCR2 signaling axis,in order to gain an in-depth and overall understanding of the mechanism of action of CCL2/CCR2 axis in tumor progression and develop more effective anti-tumor immunotherapeutic agents.