α-Galactosidase A (α-Gal A ) activities in plasma and peripheral blood granulocytes of 100healthy subjects and one patient with Fabry disease was determined by means of fluorogenic substrate.The results showed that the enzymatic activities of peripheral blood granulocytes and plasma in 100 subjects were (51.97 ± 15.24)and(148.08±26.30) nmol · h-1 · ml-1 respectively.The α-Gal A activities in plasma and granulocytes were positively correlated( r=0.533,P＜0.01 ).The enzymatic activities in peripheral blood granulocytes and plasma of the patients with Fabry disease were 1.05 and 10.06 nmol · h-1 · ml-1 respectively,both much lower than those of 100healthy subjects.These results suggest that α-Gal A activity in plasma and peripheral blood granulocytes can be used for diagnosis and screening of Fabry disease.

ObjectiveTo investigate the effect of neoadjuvant chemotherapy in locally advanced cervical cancer on cell cycle,proliferation,and evaluate the feasibility of proportion of cell in different phase 　and proliferating cell nuclear antigen(PCNA) as sensitive indices to assess chemotherapeutical sensitivity and therapeutical effect.MethodsForty-nine cases of locally advanced cervical cancer were divided into response group and no-response group according to the clinical efficacy of neoadjuvant chemotherapy.Compared the proportion of cell in different phase and proliferation index of PCNA between two groups.The clinical therapeutic effect was evaluated after 4 weeks in the second neoadjuvant chemotherapy regimen.Results In 49 patients with locally advanced cervical cancer,clinical effective of 39 cases (response group),no effective of 10 cases(no-response group).The S-phase proportion of cell in the pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy of response group[ (21.47 ± 5.21 )％ and(18.32 ±5.07)％] were higher than those of no-response group [ (9.63 ± 2.58)％ and ( 10.14 ± 2.32)％ ] (P ＜ 0.05 ).The proliferation index of PCNA of cervical cancer in the pre-neoadjuvant chemotherapy of response group [ ( 81.67 ± 7.14)％ ] was higher than that of no-response group [ (66.99 ± 2.29 )％ ] (P ＜ 0.05 ).Conclusion The S-phase proportion of cell and proliferation index of PCNA in the pre-neoadjuvant chemotherapy are important indexes to assess chemotherapeutical sensitivity and therapeutical effect.

Objective To compare proprotein convertase subtilisin/kexin type 9 (PCSK9) levels between premenopausal and postmenopausal women,and to investigate the relationship between serum PCSK9 and metabolic factors.Methods Totally 515 women were enrolled from the study on diabetes of prediction,prevention,and intervention in Nanjing in 2009.Survey,physical examinations,and determination of related metabolic indexes were performed.Serum PCSK9 level was measured by sandwich ELISA.Results Serum PCSK9 level was positively correlated with low density lipoprotein-cholesterol (LDL-C),total cholesterol (TC),triglyceride,fasting plasma glucose,body mass index,waist-hip ratio,and age in women (all P＜0.01).PCSK9 level was significantly lower in premenopausal women than that in postmenopausal women [(58.18 ± 25.44 vs 80.91 ± 33.74) ng/ml,P ＜0.01].Conclusion Higher level of PCSK9 exists in postmenopausal women compared with premenopausal women.The level of PCSK9 is closely correlated with age,TC,and LDL-C.

Objective To establish the population pharmacokinetics(PPK)model of Lamotrigine(LTG)in children with epilepsy in China for promoting individualized dosage regimen. Methods The sparse data of LTG serum concentrations from 60 pediatric patients with epilepsy were collected. One hundred and fourteen serum concentration points were divided into LTG+valproic acid (VPA) group(n=56),LTG+enzymatic inducer(E1)group(n=26),LTG+EI+VPA group(n=16)and single LTG group(n=16).The serum drug concentrations were the clinical routinely tested steadv state concentrations.The LTG PPK parameters were calculated using the non-parametric expectation maximization(NPEM) Program of USC*PACK software,and then a PPK model was established. Based on this model,LTG serum concentrations were predicted with Bayesian fitting program of USC*PACK software.Mean prediction error(MPE)and mean squared prediction error(MSPE) were calculated to evaluate the accuracy and precision of the concentration prediction and to valid the PPK model.Results The greatest likelihood was-192.87.Optimum PPK parameters were:Ka=(1.97 1.66)h~(-1);Vs=(1.07±0.89)L/kg;Kel=(0.05±0.05)h~(-1).The linear regression function Y_(OBS)=-0.09+1.05 Y_(PRED)(R~2=0.98,P<0.001),and determination of coefficient was 0.98.MPE was-0.16 g/mL,and MSPE was 0.28(μg/mL)~2.Conclusion A PPK model of LTG in children with epilepsy in China can be successfully established using the USC*PACK software, based on which LTG serum concentrations can be predicted accurately with a Bayesian approach.

Objective To discuss the clinical efficacy and safety of improved wire- maintaining technique in performing transcatheter closure of ventricular septal defects. Methods During the period from June 2011 to June 2013 at Changhai Hospital, percutaneous transcatheter closure of ventricular septal defect with improved wire-maintaining technique was carried out in 62 patients. According to the manipulation used , the patients were divided into traditional wire-maintaining technique group (group A, n = 30) and improved wire- maintaining technique group (group B, n = 32). The use of occluder during the procedure, the fluoroscopy time, the operation time and the complications were recorded. Follow-up examinations with ECG, echocardiogram and chest radiograph were performed at 24 hours and at 1 , 3 and 6 months after the procedure. The results were analyzed. Results No statistically significant differences in the use of occluder and in the incidence of complications existed between the two groups (P > 0.05). No severe complications occurred in both groups. The fluoroscopy time and the operation time in group A were (11.96 ± 3.63) min and (53.43 ± 14.48) min respectively, while the fluoroscopy time and the operation time in group B were (9.37 ± 2.77) min and (45.34 ± 10.38) min respectively, and the differences between the two groups were statistically significant (P < 0.05). Conclusion In performing transcatheter closure of ventricular septal defects, the practice.

Objective To explore the feasibility and effectiveness of interventional transcatheter destruction of the aortic valve to establish an animal model with acute aortic valve regurgitation. Methods Eight healthy goats were used for this study. A limited sternotomy approach was used to access the apex of the heart. Puncturing of the apex of the heart was performed to establish a wire track, then, under fluoroscopic guidance a 10 F sheath was inserted along this track of hard wire until to the ascending aorta above the aortic valve. The internal sheath was removed. Via the 10 F sheath a 10 mm occluder of ventricular septal defect (VSD) was introduced into the ascending aorta above the aortic valve. The sheath was pulled back to the left ventricle, while the occluder remained in the ascending aorta above the aortic valve. Then the occluder was quickly pulled back into the left ventricle in order to make some certain damage to the aortic valve. And an acute aortic valve regurgitation model was thus established. Angiography of ascending aorta above the aortic Among the 8 animals, two died of acute left ventricular failure on the spot due to excessive regurgitation blood flow after the operation. Macroscopically, damage of the aortic valve was seen. In the six survivors, angiography of ascending aorta above the aortic valve and Doppler echocardiography showed that moderate degree of regurgitation was detected in 5 and small amount of regurgitation in one. Two experimental goats with moderate degree of regurgitation died of heart failure separately at seven days and fifteen days after the operation. The remaining four experimental goats survived for more than three months. Follow- up checkups with echocardiography suggested the presence of mild- moderate degree of regurgitation. Conclusion Acute aortic valve regurgitation model in experimental goats can be established through transapical transcatheter damage of aortic valve by quickly pulling back a VSD occluder which has been placed in the ascending aorta above the aortic valve. This method is clinically feasible, technically simple and repeatable, the result is reliable, and the degree of regurgitation is controllable.

Objective To evaluate the feasibility and safety of a delivery pathway for the performance of percutaneous left atrial appendage (LAA) occlusion in experimental canine models. Methods Transseptal puncture was performed via femoral vein approach under fluoroscopic and angiographic guidance in 12 experimental dogs. A pigtail catheter was advanced into the left atrium (LA), which was followed by LA angiography. The diameters of the neck of LAA were measured on LAA angiogram obtained in appropriate projection. After the delivery sheath was advanced along the wire into LA, a pigtail catheter was inserted into the ostium of the LAA and the sheath was then advanced over the pigtail into the LAA. LAA angiography was then performed through the delivery sheath to confirm the position of the delivery sheath. One hour after the procedure both electrocardiography (ECG) and transthoracic echocardiography (TTE) were carried out in five dogs to check the results, immediately after which the five dogs were sacrificed to macroscopically observe the damages of the puncture site of inter-atrial septum as well as inside the LA and LAA. One hour and 2 weeks after the procedure TTE was conducted in the remaining 7 dogs and these dogs were followed up for one month. Results One dog died of pericardial tamponade during the operation. In 8 dogs the LAA was clearly displayed in the projection position of right anterior oblique (RAO) 30°/cranial (CRA) 20°,while in 3 dogs the LAA was well visualized in the projection position of RAO 30° , and in one dog in the projection position of RAO 30°/caudal (CAU) 20°. The diameter of LAA neck was (13.6 ± 5.2) mm. The delivery sheath was safely advanced into the LAA along the pigtail catheter in all dogs, and no air embolism, thrombus or pericardial tamponade occurred. Hematoma at puncture point of groin occurred in 2 dogs, which was absorbed through pressure dressing. Macroscopic examination of the heart performed immediately after the operation showed that no bloody pericardial effusion was found, and mild hematoma at posterior wall of LA was seen in one dog and mild damage of the upper-margin intima of LAA was noted in 2 dogs. The mean fluoroscopy time was (10.1 ± 2.5) minutes and the mean operation time was (58 ± 12) minutes. TEE showed no pericardial effusion 2 weeks after the procedure. During the follow-up period of one month no sudden death, stroke or infection occurred. Conclusion This method of placing the delivery sheath into the LAA is clinically safe and effective, and it can reliably establish a pathway to advance the LAA occluder into LAA.

OBJECTIVETo evaluate the feasibility and effectiveness of transcatheter aortic valve implantation assisted with snare to fix the delivery system.

METHODSThis study was made in 5 healthy goats. After the abdomen was opened and the abdominal aorta was exposed, a stiff guide wire was advanced into the apex of the left ventricle through abdominal arterial puncture points. The delivery catheter equipped with valved stent was inserted into the descending aorta under fluoroscopy along the stiff guide wire. A minimal thoracic surgery approach was used to access the apex of the heart. A J-type guidewire and 5 F multifunction catheter were placed transapically and across the aortic valve down to the descending aorta. The snare was introduced through the 5 F catheter into the ascending aorta and was controlled to seize the head of stent delivery catheter. Then the delivery catheter was advanced into the left ventricle. The valved stent was positioned in the desired position under aortography and then the balloon was dilated and the valved stent was deployed into the aortic annulus assisted with snare to fix the catheter to prevent stent dispositions. Aortic angiography and echocardiography were performed to evaluate of valve performance post procedure.

RESULTSThe interventional procedure was completed successfully in all 5 goats. The mean aortic annulus diameter was (23.8 ± 2.6) mm, two valved stent of 23 mm diameter and three valved stent of 26 mm in diameter were implanted. The operation duration and X-ray exposure time were (112.3 ± 19.5) min and (16.8 ± 5.2) min, respectively. Immediate observation after procedure showed that the valved stents were in the desired position after implantation by angiography and echocardiography. No moderate to severe aortic regurgitation was observed. All goats were alive at 1 month post procedure.

CONCLUSIONSThe procedure of transcatheter implantation of a balloon-expandable valved stent into the aortic valve position of goats assisted with snare to fix the delivery catheter is feasible and effective. This procedure might be suitable also for patients with noncalcified aortic stenosis.

Animals ; Aorta ; Aortic Valve ; Aortic Valve Insufficiency ; Catheterization ; Echocardiography ; Fluoroscopy ; Goats ; Stents ; Transcatheter Aortic Valve Replacement

Objective:To understand the cognition and attitude of medical staff towards medical ethics review, analyze possible influencing factors, to put forward relevant suggestions for strengthening ethical management in the future.Methods:From November 2021 to May 2022, a self-designed questionnaire and general data questionnaire on the cognition and attitude of medical staff to ethical issues in clinical research were used to investigate 408 medical staff from two first-class ternary hospitals in Hunan Province, data was analyzed to explore the respondents′ cognition and attitude, as well as related influence factors.Results:The average cognitive score of medical staff was 65.41, and the average attitude score was 91.83. Many possible influence actors regarding the cognition were identified, including degree, technical title, professional field, number of clinical research projects engaged as investigators, number of clinical research projects conducted as principle investigators, whether the hospital has established an ethics committee, and research ethics training experiences. While the influence factors of attitude were experiences of conducting and engaging in clinical research, the construction of hospital ethics committee and research ethics trainings.Conclusions:Medical staffs have the willingness to explore more research ethics knowledge, while their cognition of research ethics should be improved. Root-cause analysis should be conducted to identify influencing factors for improvement. The research management department should strengthen the publicity and training of clinical research ethics of medical staff, to improve their clinical research ethics knowledge literacy, and ensure the well-functioning of clinical research ethics review.

OBJECTIVETo evaluate the feasibility and effectiveness of transcatheter transapical implantation of a new domestic balloon-expandable bioprosthetic aortic valve in goats.

METHODSWe developed a new tube-like balloon-expandable bioprosthetic aortic valve which was made from cobalt-chromium alloy and bovine pericardium. Briefly, fresh bovine pericardium was trimmed into artificial leaflets and sutured into the cobalt-chromium alloy stent by hand post cell extracting and anti-calcification treatments. A left anterolateral mini-thoracotomy was performed in the 5(th) intercostal space of 5 goats. After opening the pericardium, the apex of the left ventricle was punctured, a stiff guidewire was positioned across the aortic arch and anchored in the descending aorta. The delivery catheter (22 F) was then introduced through the stiff guidewire into the aorta arch under fluoroscopic guidance. After correct valve position was confirmed by digital subtraction angiography, the valved stent was implanted after rapid inflation of the balloon. The immediate results of implanted valved stents were evaluated with angiography and echocardiography.

RESULTSFour devices were successfully implanted into aortic valve position of goats and one goat died of severe aortic valve regurgitation because the valved stent was implanted below the normal position.Immediate observation after procedure in 4 goats by angiography and echocardiography showed that the valved stents were in the desired position after implantation. Mild paravalvular leakage were found in 3 out of the 4 survived goats and there were no moderate to severe aortic regurgitation in survived goats.

CONCLUSIONThe procedure of transcatheter transapic aortic valve implantation with our new-type domestic balloon-expandable valved stent and delivery system is feasible and effective.

Animals ; Aortic Valve ; Catheterization ; Cattle ; Female ; Goats ; Heart Valve Prosthesis Implantation ; instrumentation ; methods ; Male ; Stents