Elevation of Divalent Metal Transporter 1 Protein in the Cerebellar Cortex of the APP/PS1 Transgenic Mouse / 中国医科大学学报

Objective To investigate the distribution of divalent metal transporter 1 (DMT1) in the cerebellum of APP/PS1 transgenic mouse. Methods Immunohistochemistry, immunofluorescence, and confocal laser scanning microscopy were used to analyze the relationship between DMTl and amyloid beta (Aβ) and their distribution in senile plaques. Western blotting was used to analyze DMT1 protein level in the APP/PS1 transgenic mouse cerebellum. Results DMTl and Aβ were mainly located in the amyloid plaques, which were predominately located in the molecular layer of the cerebellar cortex of the transgenic mouse. Only a few plaques could be seen in the Purkinje cell layer and granular layer. Confocal laser microscopy revealed the DMTl and Aβ were co-localized in senile plaques. Conclusion The abundant expression of DMTl protein suggests that DMTl and the divalent metal ions that it transports might be involved in the formation of Aβ senile plaques and other pathological processes in the cerebellum in Alzheimer' s disease.

Effect of the expressive psychotherapy on the feeling of inadequacy and loneliness of chronic schizophrenia inpatients / 中华行为医学与脑科学杂志

Objective To explore the effect of the expressive psychotherapy on the feeling of inadequacy and loneliness of inpatients with chronic schizophrenia.MethodsTotally 120 chronic schizophrenia inpatients met recruited criteria were randomly divided into study group(n=60) and control group(n=60) according to random number table.57 patients in each group finished all the follow-ups finally.The patients in two groups were received normal medications while the patients in intervention group also attended expressive psychotherapy.All the patients were assessed at baseline,6 weeks and 12 weeks of treatment with the feeling of inadequacy scale (FIS) and the status and trait loneliness scale (STLS).Results(1) The FIS score(F=225.19,P<0.01),STLS total score(F=225.20,P<0.01),STLS status score(F=240.40,P<0.01) and STLS trait score(F=106.75,P<0.01) decreased significantly in both groups after intervention.(2) The FIS score of study group was much lower than those of control group at the at 6-week-follow-up(4.93±20.86,57.89±20.48,t=-2.250,P<0.01) and 12-week-follow-up(38.43±17.50,57.21±22.98,t=-4.900,P<0.01).(3) After 6 weeks treatment and 12 weeks treatment,STLS total score(6 weeks:(54.32±12.30) vs (68.46±15.53),t=-5.425,P<0.01,12 weeks:(44.16±10.81) vs (65.75±16.26),t=-8.386,P<0.01),STLS status score (6 weeks:(25.95±6.41) vs (34.31±7.91),t=-6.239,P<0.01,12 weeks:(19.15±5.49) vs (32.58±8.45),t=-10.103,P<0.01) and STLS trait score (6 weeks:(28.37±6.73) vs (34.15±8.45),t=-4.138,P<0.01,12 weeks:(25.00±6.18) vs (33.15±8.22),t=-6.019,P<0.01) in study group were lower than those in control group,and the difference was statistically significant.ConclusionExpressive psychotherapy can effectively improve the loneliness and inadequacy of patients with chronic schizophrenia.

Model of neuroinflammation associated with cognitive dysfunction established by intraperitoneal injection of LPS / 中国病理生理杂志

AIM:To establish a mouse model of immuno-inflammation in central nervous system (CNS) associated with cognitive dysfunction.METHODS:C57BL/6J male mice were divided into 3 groups.Lipopolysaccharide (LPS) was intraperitoneally injected into the mice to induce cognitive impairment.Morris water maze test, passive avoidance test and pole test were used to observe the behavioral changes of mice.The histomorphology was analyzed by the method of immunofluorescence.The detailed molecular mechanism was determined by Western blot.RESULTS:Compared with saline group, LPS induced mouse sickness behavior and memory loss.Microglia activation and neuronal loss in the hippocampus were observed.The expression of neuroinflammatory proteins COX-2 and iNOS in the brain of LPS-induced mice was increased.CONCLUSION:Intraperitoneal injection of LPS induces cognitive dysfunction in mice.

Process research of synthesis of vildagliptin / 国际药学研究杂志

Objective To optimize the process of vildagliptin based on the principle of quality by design(QBD),so as to con?trol the safety and quality of the product. Methods Process route was confirmed through investigating literature and the advantages or disadvantages of each route were discussed. The key process parameters were determined according to the single factor experiments , which were designed by understanding of product process and process controls. Meanwhile,impurities of intermediates were studied and the safety and quality of the product could be guaranteed. Results and Conclusion Industrial process of vildagliptin was devel?oped by the principle of QBD,which can promise the safety and quality of vildagliptin,improve product quality and meet the registra?tion requirements of State Food and Drug Administration(SFDA).

Value of reactive hyperemia index in predicting postoperative angina pectoris in patients with percutaneous coronary intervention / 重庆医学

Objective To explore the value of reactive hyperemia index (RHI) in predicting the postoperative angina pectoris (AP) in the patients with percutaneous coronary intervention (PCI).Methods Three hundreds and forty-seven patients with coronary heart disease treated by PCI therapy were continuously enrolled in our department from October 10 2015 to August 10 2016.RHI was detected in all cases during hospitalization period by using the noninvasive endothelial function test (Endo-PAT) technique.Then the cases were divided into the control group (RHI≥1.67) and observation group (RHI ＜1.67) according to RHI results.The incidence of AP after discharge from hospital,rehospitalization rate due to AP,frequency and duration of AP were observed in the two groups.Results The AP incidence rates in the control and observation group were 17.04％ and 31.13％ respectively,the difference was statistically significant(P=0.003);the re-hospitalization rate due to AP was 2.22％ and 7.55％ respectively,the difference was statistically significant(P =0.035);the incidence rates of AP attack≥5 times were 6.67 ％ and 16.51 ％ respectively(P=0.008);the duration of AP was (6.39±2.68) min and (8.67±2.58) min,respectively(P=0.001);the Logistic regression analysis showed that the Syntax scores≥23 points and RHI＜1.67 were the risk factors for AP recurrence after PCI(OR=2.265,95％CI:1.354-3.787,P=0.002;OR=2.110,95％CI:1.228-3.628,P=0.007).Conclusion Reduced RHI is closely related with recurrent AP after PCI,increases the incidence,rehospitalization rate due to AP,attack frequency and duration of AP.

Synthesis of vildagliptin:research advances / 国际药学研究杂志

Vildagliptin is a kind of dipeptidyl peptidase Ⅳ(DPP-4) inhibitors. It is a new oral diabetes drug which is developed by Novartis. It reduces blood glucose levels by decreasing the concentration of glucagon,has remarkable advantages in drug safety and is widely used in the treatment of type 2 diabetes in clinic. In this paper,we summarize the synthetic methods of vildagliptin that have been reported in literature in recent years and their advantages and disadvantages.

Atorvastatin inhibits macrophage-derived foam cell formation by suppressing the activation of PPARγ and NF-κB pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate whether atorvastatin inhibits oxidized low-density lipoproteins (Ox-LDL)-stimulated foam cell formation from THP-1 macrophages by regulating the activation of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor-κB (NF-κB). Methods THP-1 macrophages were pretreated with 10, 20, or 40 µmol/L atorvastatin for 2 h, and after washing with PBS twice, the cells were incubated with 60 µg/ml of Ox-LDL for 48 h. The quantity of intracellular lipid of the cells was detected with Oil red O staining and enzymatic fluorometric method. The expression of the scavenger receptors of CD36 and SRA were analyzed with Western blotting. We also examined the effect of atorvastatin on adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and the activation of PPARγ and p-iκB, and further assessed the capacity of the macrophages to bind to Dil-oxLDL.</p><p><b>RESULTS</b>Atorvastatin potently inhibited ox-LDL-induced macrophage-derived foam cell formation, down-regulated the expression of CD36 and SRA, and up-regulated the expression of ABCA1. Atorvastatin markedly suppressed the activation of PPARγ and p-iκB in ox-LDL-stimulated THP-1 macrophages (P<0.05) and significantly decreased the Dil-oxLDL-binding capacity of the macrophages (P<0.05).</p><p><b>CONCLUSION</b>Atorvastatin as an effective anti-atherosclerosis agent can suppress the activation of PPARγ and p-iκB to reduce lipid accumulation in macrophages.</p>

Key points in the surgical treatment of infective endocarditis : a report of 106 cases / 中华胸心血管外科杂志

Objective To review the clinical experience in the surgical treatment of infective endocarditis,and to summarize the key points of how to elevate therapeutic effect.Methods From Jan 2001 to Dec 2010,106 patients with infective endocarditis who underwent operative therapy were retrospectively analyzed.All patients underwent cardiac operation in conventional hypothermic cardiopulmonary bypass.Vegetations and suspicious infective focus were thoroughly cleaned.Endocardium was swabbed with normal sodium repeatedly and with high concentration antibiotic solution.Combined anomalies were rectified and the affected valves were replaced.Artificial valves were preconditioned with antibiotics before implantation.All patients were treated with full dose of sensitive antibiotics for 6-8 weeks after operation.Results Two patients(1.8％) died perioperatively,1 died of severe pulmonary infection 5 days post operation,and 1 died of multisystem organ failure.Other 104 patients recovered smoothly,95 of whom were followed up for 6 months to 10 years.One patient died,and the other patients recovered with Ⅰ-Ⅱ grade heart function(NYHA).Three patients had anticoagulation related complications.There was no relapse of endocarditis occurred during the period of follow-up.Conclusion Early diagnosis and timely operation on infective endocarditis can achieve satisfactory effect.The thorough sterilization,prosthetic valves precondition and post operative regular antibiotics therapy were the key points of successful surgical treatment.

Nervous system protection in the treatment of DeBakey type Ⅰ aortic dissection with hybrid procedure / 中华胸心血管外科杂志

Objective The present study aims to summarize the clinical experience and methods of nervous system protection in the treatment of DeBakey type Ⅰ aortic dissection with hybrid procedure.Methods From Jan 2009 to Jun 2011,56 patients suffering from DeBakey Ⅰ aortic dissection underwent hybrid procedure.The ascending aorta part were replaced under conventional cardiopulmonary bypass,and the0 aortic arch branch vessels were reconstructed,and then a stent graft was implanted to cover the aortic arch and part of the descending aorta.The unilateral antegrade cerebral perfusion(UACP) and/or bilateral antegrade cerebral perfusion (BACP) combined with femoral artery perfusion was used,and the left subclavian arteries were selectively reconstructed according to cerebral arteries and aorta computed tomography angiography scan.Results All the patients went through the procedure successfully.BACP combined with femoral artery perfusion was applied in 16 patients,UACP combined with femoral artery perfusion in 33 patients,and 7 were perfused with only femoral artery cannulation.Of all the patients,19 underwent the innominate artery and left common carotid artery reconstruction and the other 37 patients underwent the innominate artery,the left common carotid artery and the left subclavian artery reconstruction.The cardiopulmonary time was 44 -95 min,mean (65 ±24) min; aortic clamping time was 32 -71 min,mean (48 ±29)min; the cerebral perfusion time was 24 -44 min,mean (32 ± 13) min.One ( 1.8％ ) patient,who was perfused with only femoral artery cannulation,suffered from permanent neurological dysfunction,and 5 (8.9％) had transient neurological dysfunction.One patient died from severe infection,1 patient was given up because of permanent neurological dysfunction,and the rest 54 patients recovered and discharged.The patients were followed up 1 to 25 months,and there was no newly occurred neurological dysfunc tion.The CTA examination 3 months post-operative revealed that the branch bypass vessels were unobstructed.There was no subclavain steal symptom occurred in the 19 patients whose left subclavian arteries were not reconstructed.The left upper limb strength was slightly lessened in 3 patients and recovered 6 - 12 months later.Conclusion In the treatment of DeBakey type Ⅰ aortic dissection with hybrid procedure,the selective use UACP and/or BACP combined with femoral artery perfusion can avoid deep hypothermic and circulatory arrest and provide the continuous cerebral and spinal perfusion.This perfusion strategy in hybrid procedure can decrease the morbidity of post-operative nervous system disorders with satisfactory nervous system protection effect.

Impact of unilateral and bilateral antegrade selective cerebral perfusion on neurological function in patients undergoing a hybrid approach for DeBakey type Ⅰ aortic dissection A prospective randomized controlled study / 国际脑血管病杂志

Objective To compare the effect of brain unilateral and bilateral antegrade selective cerebral perfusion (ASCP) during a hybrid approach to DeBakey type Ⅰ aortic dissection and to provide the clinical evidence for the selection of cerebral perfusion methods of aortic dissection surgery.Methods Among the 56 patients undergoing a hybrid approach to DeBakey type Ⅰ aortic dissection from January 2009 to June 2011,24 were enrolled in the study.They were randomly divided into a unilateral ASCP group (n =11) and a bilateral ASCP group (n =13).The patients in both groups underwent cognitive ability test,brain CT scan,cerebrovascular and aortic CTA examinations before and after procedure.The general information,intraoperative conditions and neurological function in the patients of both groups were compared.Results There was no difference in the general data between the unilateral and bilateral ASCP groups.There were no significant differences among the intraoperative cardiopulmonary bypass time (125.2 ± 34.4 min vs.132.1 ± 45.4 min; t =- 0.278,P =0.784),aortic cross-clamping time (54.5 ± 23.6 min vs.61.6 ± 27.5 min; t =-0.149,P =0.883),cerebral perfusion time (30.9 ± 13.2 min vs.31.7 ± 14.5 min; t =- 1.283,P =0.213),right radial artery pressure (57.6 ± 15.5 mm Hg vs.60.7 ± 14.3 mm Hg; t =0.758,P =0.457),and arterial oxygen pressure (465.6 ± 62.4 mm Hg vs.488.4 ± 72.5 mm Hg; t =- 1.894,P =0.071 ).There were no surgery and recent death in both groups.There were no significant differences among the mechanical ventilation time (33.5 ± 14.6 h vs.37.8 ± 12.3; t =- 1.009,P =0.162),time awake after surgery (5.2 ± 2.4 h vs.5.5 ± 3.1 h; t =0.876,P =0.195),and intensive care unit stay time (7.5 ± 3.1 d vs.8.2 ± 3.5 d; t =-0.186,P =0.427).There was no new permanent neurological dysfunction in both groups.One patient had transient neurological impairment in each group.The cognitive function scores after surgery in the unilateral ASCP group (50.1 ± 14.8 vs.47.3 ± 15.2; t =1.005,P =0.126) and in the bilateral ASCP group (52.1 ± 13.7 vs.48.6 ± 16.5; t =0.576,P =0.254) were slightly lower than those before procedure,however,there was no significant difference; there was also no significant difference in the unilateral and bilateral ASCP groups before (t =-0.887,P =0.385) and after procedure (t =-0.953,P =0.351).Conclusions Under the circumstance of complete circle of Willis,the brain protective effect of the unilateral and bilateral ASCP in patients undergoing a hybrid approach for DeBakey type Ⅰ aortic dissection had no significant difference,and more simple and convenient unilateral ASCP can be used.

Hybrid procedure without deep hypothermic circulatory arrest for DeBakey type Ⅰ aortic dissection / 中华胸心血管外科杂志

Objective Some major procedures for DeBakey type Ⅰ aortic dissection used to be performed with deep hypothermic circulatory arrest, which had been associated with more complications than seen with standard extracorporeal circulation. We reviewed the cases who received the treatment for DeBakey type Ⅰ aortic dissection by hybrid procedure without deep hypothermic circulatory arrest. The procedure consisted of ascending aorta replacement, ascending aorta-aortic arch branch vascular bypass reconstruction and endovascular graft exclusion. Methods From January 2009 to June 2010, 39 patients [mean age (55 ±16) years] who had DeBakey Ⅰ aortic dissection underwent hybrid procedure without deep hypothermic circulatory arrest. The femoral artery and right axillary artery were cannulated for perfusion. The ascending aorta and/or aortic valves were replaced under conventional extracorporeal circulation with Bentall procedure or Wheat procedure. The aortic arch branch vessels were dissected and the proximal part was sealed. Then the ascending aorta-aortic arch branch vascular bypasses were constructed with 4-bifurcation vascular grafts, Y-shape bifurcated vascular grafts or artificial vessels. Finally the endovascular grafts were deployed via the femoral incisions monitored dynamically with DSA, or via the ascending aortic bifurcated vessels monitored with transesophageal echocardiography. Results The operation succeeded in all 39 patients. Eight patients underwent ascending aorta replacement without aortic valve replacement or prosthesis, 20 patients underwent Bentall procedure ( Carbrol procedure were used in 11 cases), and 11 underwent Wheat procedure. For ascending aorta-aortic branch vascular bypass reconstruction, sequential anastomoses were performed in 8, Y-shaped bifurcated grafts were used in 15, and 4-bifurcated grafts were employed in 16 patients. The endovascular stent grafts were deployed via the former femoral incisions in 36 patients and via ascending aortic bifurcated vessels in 3. The cardiopulmonary bypass time was (61 ±22) minutes, the aortic crossclamp time was (48 ±18) minutes, and the post-operative intubation time was (30 ±9) hours. The thoracic drainage from each patient was less than 300 ml in 24 hours. No complication, such as hemiplegia, paraplegia, severe infections, renal failure or coagulation disorder, was observed. The duration of hospitalization was (21 ±6) days. No hospital death occurred. Follow-up was performed 1 to 15 months [mean (8.4 ±7.2) months] postoperatively. All patients survived without any organ dysfunction at follow up. The CTA examination 3 months after operation revealed that the false lumens had been closed in 91.2% of the patients. Conclusion Our findings indicated that the hybrid procedure, which combining ascending aorta replacement,ascending aorta-aortic arch branch vascular bypass reconstruction and endovascular graft exclusion under conventional extracorporeal circulation, may be an option for avoiding the possible complications associated with profound hypothermic circulatory arrest. The novel hybrid operation may improve the surgical outcomes and provide a simplified surgical approach for the treatment of DeBakey Ⅰ aortic dissection.

Construction, expression, purification and polyclonal antibody preparation of Fas extracellular region gene / 中国生化药物杂志

Purpose To construct expression vector of Fas extracellular region gene(eFas) ,to express and purify recombination protein and to prepare polyclonal antibody, which have laid a foundation of studying its function. Methods The eFas gene encoding sequence was acquired through overlapping PCR, and pET-22b ( + )/eFas expression vector was constructed. Then this vector was transformed into E. coli Rosetta-gami. Re-combinant protein was expression being induced by IPTG,and was purified using Ni-NTA matrix of affinity chromatograph. The purity of recombination protein was identified by SDS-PAGE. Hereafter, the purified eFas recombinant protein was immunized to New Zealand white rabbit in order to prepare polyclonal antibody. The titer of polyclonal antibody was determined by ELISA. Results The encoding sequence and expression vector of eFas was obtained while the interest protein was mainly expressed in the inclusion body. The eFas fusion protein's expression quantity accounts for more than 30% proportion of total E. coli protein. The eFas protein we obtained was provided with the purity of at least 95 % . Conclusion The successful constrution, expression and purification of FasL fusion protein and preparation of polyclonal antibody will provide some material for further studies of Fas.

Effect of Benazepril and Candesartan Combination for Treatment of Hypertension With Microalbuminuria / 中国循环杂志

Objective:To compare the effect between benazepril and candesartan combination and single medication in either one of them for treatment of hypertension-combined with microalbuminuria(MCA). Methods:A total of 95 patients were divided into three groups.Benazepril group(n=31),patients were treated with Benazepril 10～20 mg/day;Candesartan group(n=32),patients were treated with Candesartan 4～8 mg/day;and Combination group (n=32),patients were treated with benazepril 10 mg/day and candesartan 4 mg/day.The medication lasted for 8 weeks.Blood pressure(BP),plasma urinary albumin and creatinine ratio(A/C),endothelin-1(ET-1),nitrogen monoxide(NO)and potassium were examined and compared before and after the medication respectively. Results:The levels of BP,plasma A/C and ET-1 were decrease and NO was increased in all three groups(P0.05,respectively). Conclusion:Effect of benazepril and candesartan combination in patients with hypertension-combined microalbuminuria was better than single medication in either benazepril or candesartan.

Surgical treatment of thoracic aortic dissecting aneurysm: A report of 115 cases / 医学研究生学报

Objective: The present study aims to summarize the clinical experience in the surgical treatment of thoracic aortic dissecting aneurysm.Methods: We retrospectively analyzed the clinical data of 115 cases of thoracic aortic dissecting aneurysm treated by surgery from December 1995 to December 2006.Thirty-eight of them were DeBakey type I aortic dissection,18 type Ⅱ,and 59 type Ⅲ.Of the 38 DeBakey type I patients,30 underwent ascending aorta with total aortic arch replacement(2 cases of total thoracic aortic artificial vessel replacement,25 Wheat procedure and 3 aortic valvuloplasty) and the other 8 received ascending aorta with semi-aortic arch replacement.Of the 59 DeBakey type Ⅲ patients,36 underwent descending aortic aneurysm resection with artificial vessel replacement via left posterolateral thoracic incision by left heart bypass or aorta to artery bypass(using Cott tubes),while the other 23 received endovascular stent-graft exclusion in descending aorta via the femoral artery.Results: All the patients were successfully treated except 5 that died during the perioperative period.The survivors were followed up for 3-118 months,among whom 2 died long-term death after the operation and the others were living healthy.Conclusion: Surgical treatment improves the clinical outcome of thoracic aortic dissecting aneurysm.Bilateral perfusion via the carotid artery in aortic arch replacement has a definite cerebral protective effect.Surgical procedures can be simplified by using the modified elephant trunk technique.Endovascular stent-graft exclusion is safe and effective in the treatment of DeBakey type Ⅲ aortic dissection.

Progress in the fructose-1,6-diphosphate on myocardium protection / 医学研究生学报

Fructose-1,6-diphosphate (FDP) is a very important mesne product which links the glucose and hepatin with the oxidation in energy metabolism and keeps the glycolysis functional, which is made use of widely. In addition, FDP has the ability to stabilize the cell membrane, abate inflammatory response, and restrain the oxygen free radical and cell apoptosis, it can protect cell in both structure and function. Recent researches proved that FDP is effective on myocardium protection and cardiac function reviving. This article reviews these research progresses.

Analysis of single-chain antibody against death receptor 5 (ZF1) on murine H22 hepatocellular carcinoma cell / 中国免疫学杂志

Objective:The purpose of this study is to evaluate the effects of a single-chain antibody against death receptor 5 (ZF1) on tumor growth and survival in murine H22 hepatocellular carcinoma tumor model.Methods:Killing effect of ZF1 on H22 cells was analyzed by MTT assay in vitro. The apoptosis rate of H22 cells induced by ZF1 was detected using Flow Cytometry assay. The transplanted model of H22 tumor was developed in mice. The mice were randomly divided into four groups, PBS group, ZF1 group, EPI group and combined treatment group of ZF1/EPI. Tumor growth and body weight changes were observed. After treatment over 13 days, the tumor tissue for HE staining and TUNNEL assay was performed to detect apoptosis.Results:The results showed that ZF1 could inhibit growth of H22 cells in a dose dependent manner. The growth inhibition rate was up to 84.5%. The results showed that ZF1 alone or in combination with ZF1/EPI, the tumor growth was significantly inhibited. HE staining and TUNNEL analysis showed that ZF1 could effectively induce apoptosis of tumor cells without toxic effects, especially in ZF1/EPI combined treatment group.Conclusion:It is showed that ZF1 induces a good inhibition on the proliferation of H22 cell, especially in combined treatment group of ZF1/EPI.