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Based on the analysis of the management of Director 's target responsibility system in China Academy of Chinese Medical Sciences these years, the methods and experience were introduced in this paper. How to further improve the management was also discussed, providing a certain reference for the target responsibility system management of scientific research institutes.
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Objective To explore the effect of dronedaronel on hyperpolarization-activated cyclic-nucleotide-gated(HCN) channel expression by detecting the change of HCN channel mRNA and protein level before and after giving dronedarone in neonatal rat ventricular myocytes.Methods Neonatal rat ventricular myocytes were separated and digested by type Ⅱ collagenase,and then single ventricular myocytes were collected through differential sticking wall separation method.According to the concentrations (0.1,0.5,1.0,5.0,10.0,20.0 μmol/L of dronedaronel for treating myocytes for 48 h) and time(10 μmol/L of dronedaronel for treating myocytes for 1,6,12,24,48 h)the gradient grouping was conducted.The levels of HCN2 and HCN4 channel mRNA and protein level were determined by real-time PCR and Western blot.Results The HCN2 mRNA and HCN4 mRNA expression levels in concentration gradient group and time gradient group were lower than those in the control group(P＜0.05);compared with the control group,the protein level in the 10 umol/L dronedaronel treatment for 12 h group was significantly down-regulated(P＜ 0.01).Conclusion Dronedaronel could inhibit the expression of HCN2/HCN4 channel mRNA and protein,moreover its action shows the concentration dependency and reaches the maximum at 12 h after medication.
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Nrf2,a key transcriptional factor in regulating endog-enous antioxidant signaling pathway,maintains the redox bal-ance by controlling the expression of a battery of antioxidant en-zymes,phase-Ⅱ detoxification enzymes and phase-Ⅲ transport-ers.Furthermore,Nrf2 regulates inflammation.Recent resear-ches have confirmed that Nrf2 provides a vital physiological role in kidney diseases,activation of Nrf2 enhances the antioxidant and anti-inflammatory ability in cellular and tissue levels,thusalleviates renal injury.Here,this article aims to summarize the protective effect of Nrf2 on various models of kidney impairment and explore the potential of Nrf2 as a therapeutic target to pre-vent kidney diseases.
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Objective To detect the efficacy of trimodality treatment combining transurethral resection of bladder tumor (TURBT), chemotherapy and radiotherapy for locally muscle-invasive bladder cancer.Methods From November 2007 to June 2013, 107 local muscle-invasive bladder cancer cases were treated by TURBT.Thirty-six cases ( group A) underwent the bladder-sparing trimodality treatment, aged from 42 to 88 years.Seventy -one cases (group B) underwent radical cystectomy,aged from 38 to 77 years.In group A, there were 19 cases of T2 , 13 cases of T3 , and 4 cases of T4a.Among those patients, 11 patients underwent gemcitabine/cisplatin ( GC ) systemic chemotherapy regimen, 15 patients underwent gemcitabine/cisplatin ( GC ) intrailliac artery chemotherapy regimen, and 10 patients underwent taxane/carboplatin ( TC) systemic chemotherapy regimen.In group B, there were 38 cases of T2 , 27 cases of T3 , 6 cases of T4a.The progress-free survival after 2 years was compared with the only radical cystectomy, and the efficacy among the three chemotherapy regimens was also evaluated.Results There is no statistical difference in age and tumor stage between the two groups.In group A, patients were followed up from 3 to 79 months, and 2 years′progress-free survival was 78.9%(15 cases) in T2 , 46.2%(6 cases) in T3 , and 0 in T4a.In group A, organ-sparing 2 years′progress-free survival was 58.3%, and 6 metastasis (16.7%) and 11 local relapse ( 30.6%) were detected during the follow-up period.In group B, patients were followed up from 2 to 65 months, and 2 years′progress-free survival was 76.3%in T2(29 cases), 55.6%(15 cases) in T3, and 16.7% (1 case) in T4a.Of all the patients in group B, 2 years′progress-free survival was 63.4%, and 22 metastasis ( 31.0%) and 16 local relapse ( 22.5%) were found during the follow-up period.There′s no statistical difference on 2 years′progress-free survival between the two groups, and the efficacy among the three chemotherapy regimens.Conclusions Two years′progress-free survival of bladder-preserving trimodality treatment was similar to that of radical cystectomy for local muscle-invasive bladder cancer.In term of treatment efficacy, stage T2 was much better than T3 and T4a .Each kind of chemotherapy regimen in trimodality treatment was equally effective.
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Objective To develop a new method to expose the stellate ganglion to increase the success rate of establishing a dog model of atrial fibrillation indinced by sympathetic stimulation .Methods A total of 28 adult dogs were randomly divided into traditional group and improvement group , 14 dogs in each group .The stellate ganglions were separated by the two different methods , respectively , to establish a sympathetic stimulation induced atrial fibrillation model in all the dogs .Changes of vital signs , survival rate of the dogs and the voltage required to stimulate the stellate ganglion were recorded intraoperatively .Changes of cardiac electrophysiology were recorded before and after electric stimulation . The levels of released neurotransmitters were detected by immunohistochemistry . Results The survival rate of the improvement group was 100%(14/14), significantly higher than the 64.3%(9/14) of the traditional group (P<0.05). The operation time of the improvement group was 122.71 ±3.62 min, significantly shorter than the 269.44 ±8.79 min of the traditional group (P<0.05).The threshold voltage of the improvement group was significantly lower than that of the traditional group ( P<0.05) .Conclusions Our modified surgical procedure can effectively reduce the mortality of dogs , significantly shorten the operation time , and reduce the intraoperative blood loss , keeping a more intact stellate ganglion , and maintains a more stable voltage of electric stimulation , Therefore, it is a new method more suitable for establishment of a sympathetic stimulation induced atrial fibrillation model in dogs .
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Objective To investigate the safety and clinical significance in presurgical application of tyrosine kinase inhibitor (TKI) targeted therapy in high-risk renal-cell-carcinoma patients.Methods TKI targeted therapy was applied to 33 high-risk renal-cell-carcinoma patients from Jun.2010 to Dec.2013,7 cases with paraneoplastic symdromes and 1 with bilateral lesions received surgical treatments.There were 6 males and 2 females in this group with average age of 50 (42-56) years.They were high-risk patients because of renal tumor and vena caval tumor thrombus in 3 cases,renal tumor and vena caval tumor thrombus and hypercalcinemia in 1 case,renal tumors with metastasis to lung and lymph nodes in 2 cases,renal tumor with metastasis to lung and bones in 1 cases,and bilateral kidney cancer in 1 case.The clinical stages included 3 cases of T3aN1M1 and T3bN0M0 respectively,and 1 case of T3bN0M1 and T3aN0M0,respectively.The primary metastasis sites were lymph nodes and lung (3 cases respectively),and another 1 in bone.4 cases suffered from vena cava tumor thrombi with 3 staged Mayo Ⅲ and 1 Mayo Ⅳ.7 cases with paraneoplastic syndromes were contra-indicated for surgery due to poor ECOG performance score (with score 3 in 3 cases and 2 in 4 cases).4 cases received Sorafinib 400mg po bid and the other 4 Sunitinib 50 mg po qd,4 weeks on and 2 weeks off,with duration of 8-12 weeks.Medical therapy ceased 6 to 16 days (median 12 days) before operation.Results Patients with neoadjuvant therapy experienced good toleration.The 7 cases with poor ECOGs improved during medical therapy.The tumor sizes in the bilateral lesions shrunk remarkably.All 7 patients received surgery:3 radical nephrectomies,4 nephrectomies and resections of Vena Caval tumor thrombus,and 1 bilateral lesions underwent nephron sparing surgery.Operations were successful though with mild to moderate adhesion,and the blood loss ranged from 120 to 500 ml,with averaged of 280 ml.Pathologic results were clear-cell renal carcinomas.All incisions were well-healed.4 patients with metastasis continued TKI therapy.All patients were alive without recurrence during the follow-up of 4 to 42 mon.Conclusions Presurgical application of targeted therapy is safe and may increase the opportunity of surgery for some patients with poor general situation,also patients with bilateral lesions may benefit from it for its possibility of nephron sparing.
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“Three Yin and Three Yang” syndrome differentiation is a method and system generated from “Treatise on Febrile Diseases”. And it is a principle of syndrome differentiation and a criterion of treatment. Modern physicians give many descriptions on levels of “Three Yin and Three Yang” syndrome differentiation. There are a lot of different opinions on it, including “Yin and Yang”, ”three steps of Cluster analysis”, “one divided into two” combining with “one divided into three”, and “three steps of recognizing symptom, understanding disease and differentiating syndrome” theories. The author believes “Three Yin and Three Yang”syndrome differentiation consists of three levels:differentiating syndrome principle, differentiating syndrome category and differentiating syndrome type. Strengthening research on levels of syndrome differentiation helps to improve accuracy of syndrome differentiation, guide drug description and enhance clinical efficacy.
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Objective To explore the clinicopathologic features,diagnosis,treatment and prognosis of ACTH-independent subclinical Cushing syndrome caused by cortisol-secreting and hypo-androgen black adrenal cortical adenomas with lipomatous metaplasis.Methods The clinical and pathologic features of 1 patient presented with hypo-androgen and atypical signs and symptoms of Cushing syndrome were reported.The patient's 24 h UFC (235.62 μg) was higher than normal range,his plasma ACTH concentrations (＜1.1 pmol/L,was lower than normal range and his serum cortisol concentrations lacked diurnal rhythm.There was absence of serum cortisol suppression in overnight dexamethasone suppression tests.Serum levels of androgens (1.2 nmol/L) were lower than normal range.24 h urine catecholamine was normal,NE was 160.5 nmol/24 h (5-591 nmol/24 h),E was 23.1 nmol/24 h (0-82 nmol/24 h),DA was 1496nmol/24 h (424-2612 nmol/24 h).Aldosterone lying and standing test:ALD1 138-415 pmol/L,AT-Ⅱ1 64.54 ng/L,PRA1 0.80 μg · L-1 · h-1 Abdomen CT showed right adrenal mass (3.1 cm).131Ⅰ-MIBG scanning was normal.Adrenocortical carcinoma was considered as a possible diagnosis based on cortisol hypersecretion,hypo-androgen and the imaging characteristics.This patient accepted laparoscopic adrenal adenoma resection.Results The adrenal tumor size was 3.5 cm.Immunohistochemical (IHC) staining showed Melan-A,CgA,α-inhibin and Syn positive and Ki-67 ＜ 1％.Histopathologic results showed black adrenal cortical adenomas with myelolipomatous change.After surgery,patient's serum androgen was normal,and the signs and symptoms of Cushing syndrome and oligo-androgen disappeared.There was recurrence after 1.5 years follow-up.Conclusions Although most patients with corticotropin-independent Cushing syndrome associated with abnormal androgen proved to have adrenocortical carcinoma,the clinician should be aware of the possibility of benign,black adrenal adenoma.
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Objective To investigate the effects of Urotensin Ⅱ(UⅡ)on proliferation of rat pheochromocytoma cell line(PC12) and primary cultured human pheochromocytoma cells.Methods We observed the effects of UⅡ on the proliferation of rat PC12 cells and human pheochromocytoma cells in vitro by MTT method.Results 1.UⅡ had no obvious effect on the proliferation of rat PC12 cells.2.UⅡ(at 10-7 and 10-6mol/L) promoted the proliferation of primary cultured human pheochromocytoma cells. Conclusion UⅡ stimulates the proliferation of human pheochromocytoma cells and probably plays a role in the pathogenesis of pheochromocytoma.