Comparison on short-term safety outcomes between off-pump and on-pump coronary artery bypass grafting by experienced surgeons: a single center study with 31 075 cases / 中华心血管病杂志

Objective: To compare the short-term outcomes between off-pump and on-pump coronary artery bypass graft (CABG) by experienced surgeons with similar surgical team in a single large-volume cardiac surgery center. Methods: A total of 31 075 patients with multivessel coronary disease who underwent isolated off-pump or on-pump CABG between January 1, 2009 and December 31, 2019 by experienced surgeons in Fuwai hospital were enrolled in this retrospective study. Patients was divided into on-pump CABG group and on-pump CABG group on an intention-to treat basis. Short term safety endpoints, including 30 days mortality, composite endpoint of major morbidity or mortality, prolonged postoperative length of stay (PLOS), and prolonged ICU length of stay (PICULOS), and distal anastomosis were compared between the two groups. Mortality was evaluated on 30 days post operation, other endpoints were collected before discharge. After 1∶1 propensity-score matching of baseline characteristics for on-pump and off-pump CABG, postoperative endpoints were compared with use of McNemar's test and further adjusted with the use of a logistic regression model. Results: After propensity-score matching, 10 243 matched pairs of patients were included in the final analysis, there were 4 605(22.5%) females and mean age was (60.7±8.6) years. The standardized differences were less than 5% for all baseline variables in matched cohort. Univariate analysis indicated lower risk of 30 days mortality (0.2% vs. 0.7%, P<0.001), major morbidity or mortality (5.7% vs. 8.8%, P<0.001), PLOS (3.2% vs. 4.9%, P<0.001), PICULOS (9.4% vs. 12.2, P<0.001), and lower number of distal anastomosis ((3.3±0.8) vs. (3.6±0.8), P<0.001) in off-pump CABG group than in on-pump CABG group. After adjustment of cofounders, multivariate analysis showed that off-pump CABG was still associated with a lower risk of 30 days mortality (OR=0.29, 95%CI: 0.09-0.87, P=0.027), composite endpoint of major morbidity or mortality (OR=0.60, 95%CI: 0.53-0.68, P<0.001), PLOS (OR=0.64, 95%CI 0.54-0.75, P<0.001), PICULOS (OR=0.76, 95%CI: 0.69-0.84, P<0.001). Conclusions: Off-pump CABG is related with superior short-term safety outcomes than on-pump CABG by experienced surgeons in our center.

Two symmetrical unsaturated acids isolated from Viscum album / 中国天然药物

In the present study, two new acetylene conjugate compounds, dibutyl (2Z, 6Z)-octa-2, 6-dien-4-yne dioate (1), and dibutyl (2E, 6E)- octa-2, 6-dien-4-yne dioate (2), were isolated from the dry stem leaves of Viscum album, along with nine known compounds (3 - 11). Their structures were confirmed on the basis of spectroscopic data. Compounds 1 and 8 showed antioxidant activity against xanthine oxidase (XOD) and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydroxyl (DPPH), with the IC of 1.22 and 1.33 μmol·L, and the SC of 4.34 and 8.22 μmol·L, respectively.

Considerations on the dose determination for first-in-human clinical trials with novel biopharmaceuticals / 药物评价研究

In the development process from the preclinical stage to the subsequent clinical phase,one critical risk controlling step is the determination of the first-in-human (FIH) dose.There is difference in the mechanisms of action and toxic risks between biopharmaceuticals and small molecule drugs,therefore different considerations will be involved in the determination of the FIH dose for biopharmaceuticals.This paper presents the overall review of the preclinical studies supporting the determination of FIH dose and the approaches based on the NOAEL,MABLE,and PK/PD model.The experience-based views that the MABLE-based FIH dose for immune activating products would be reasonably safe,although the NOAEL approach remains conservative and widely used for a majority of biopharmaceuticals are also presented.It is suggested that sponsors should determine the appropriate and safe FIH dose by diverse approaches according to the characteristics of product.Early communication between sponsors and regulators is always beneficial.

Considerations on the dose determination for first-in-human clinical trials with novel biopharmaceuticals / 药物评价研究

In the development process from the preclinical stage to the subsequent clinical phase,one critical risk controlling step is the determination of the first-in-human (FIH) dose.There is difference in the mechanisms of action and toxic risks between biopharmaceuticals and small molecule drugs,therefore different considerations will be involved in the determination of the FIH dose for biopharmaceuticals.This paper presents the overall review of the preclinical studies supporting the determination of FIH dose and the approaches based on the NOAEL,MABLE,and PK/PD model.The experience-based views that the MABLE-based FIH dose for immune activating products would be reasonably safe,although the NOAEL approach remains conservative and widely used for a majority of biopharmaceuticals are also presented.It is suggested that sponsors should determine the appropriate and safe FIH dose by diverse approaches according to the characteristics of product.Early communication between sponsors and regulators is always beneficial.

Factors Related with Infection and Local Epidural Hematoma after Cranioplasty: A Retrospective Analysis / 中国康复理论与实践

@#Objective To explore the factors associated with the complications of cranioplasty, infection and local epidural hematoma, such as age, sex, primary disease, skull defect and concomitant hydrocephalus. Methods 211 patients after cranioplasty were reviewed. Results 8 cases (3.8%) complicated one of them, in which 6 cases with local epidural hematoma and 2 cases with infection. The infection was more likely related with the areas of skull defect (P=0.003). No factor was found related with the local epidural hematoma. Conclusion It is necessary to focus the size of the frontal sinus when repairing the the frontal bone, to avoid the screw into the frontal sinus caused infection.

Left ventricular reconstruction with no-patch technique: early and late clinical outcomes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Few studies have evaluated late clinical outcome of no-patch technique in patients with large left ventricular aneurysms. The objectives of this study were to evaluate a no-patch surgical technique to reconstruct the left ventricle in patients with left ventricular aneurysm and to assess early and late clinical outcomes.</p><p><b>METHODS</b>In 1995, we began using a no-patch technique in patients with dyskinetic left ventricular aneurysms. A total of 145 patients underwent left ventricular reconstruction with this technique and were followed up for (59 ± 29) months (range, 1 - 127 months). Risk factors for early mortality were analyzed by bivariate analyses. Cox's proportional hazards model was used to calculate risk factors for all-cause mortality and hospital readmission. Kaplan-Meier methodology was used to analyze late survival.</p><p><b>RESULTS</b>One week after operation, left ventricular end-diastolic diameter had decreased from (61 ± 8) mm to (55 ± 8) mm, and geometry of the left ventricle was restored to a more normal conical shape. Early mortality was 3% and late mortality 11%. Over a 5-year follow-up period, hospital readmission was 28%. One-, 5-, and 10-year survival estimates were 95% (95% confidence interval (CI) 91% - 99%), 86% (95%CI 78% - 94%), and 74% (95%CI 60% - 88%). Readmission-free survival at 1 and 5 years after operation was 87% (95%CI 81% - 93%) and 60% (95%CI 50% - 70%), respectively.</p><p><b>CONCLUSION</b>The no-patch technique for left ventricular reconstruction is an effective and simple procedure that can achieve satisfactory early and late clinical outcomes in patients with left ventricular aneurysms.</p>

Inhibition of 1,3,8-trihydroxy-5-methoxyxanthone on cytochrome P450s / 中南大学学报(医学版)

OBJECTIVE@#To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes.@*METHODS@#Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography.@*RESULTS@#The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX.@*CONCLUSION@#TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.

Using the lesser saphenous vein as graft for coronary revascularization / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the possibility of using the lesser saphenous vein as the alternative bypass graft in coronary artery bypasss graft (CABG).</p><p><b>METHOD</b>Seven pieces of lesser saphenous veins of 6 patients were harvested as the single or sequential grafts of CABG procedure with No-touch technique.</p><p><b>RESULTS</b>The diameter and length of lesser saphaneous vein met the requirement of graft for entire revascularization. All grafts achieved good flow without significant complications.</p><p><b>CONCLUSION</b>The lesser saphenous vein graft is an excellent choice for CABG patient who lacks routine grafts as an alternative material.</p>

Effect of surface modification on surface energy of lactose and performance of dry powder inhalations / 药学学报

<p><b>AIM</b>To investigate the effects of surface modification of lactose carrier on performance of dry powder inhalations (DPIs).</p><p><b>METHODS</b>Modified lactose surface was prepared using a "particle smoothing" process to obtain smooth carrier surface and low surface energy with the presence of magnesium stearate, colloidal silica dioxide and talc. Inverse gas chromatography (IGC) was used to assess the surface energy of treated lactose, and the in vitro deposition of carrier-based IFNa-2b DPIs was evaluated with twin stage impinger.</p><p><b>RESULTS</b>The flowing property of lactose was greatly improved and the surface energy decreased by the "particle smoothing" process. Decreasing surface energy resulted in greater aspiration fraction of IFNa-2b.</p><p><b>CONCLUSION</b>IGC is a potentially useful tool for rapid formulation design and screening.</p>

Pharmacokinetics of erythromycin stinoprate capsule / 中南大学学报(医学版)

OBJECTIVE@#To determine the pharmacokinetics of erythromycin stinoprate capsules and to provide guidance for clinical research.@*METHODS@#Thirty healthy volunteers (15 men and 15 women) were divided into 3 groups randomly, each including 5 men and 5 women. Single oral doses of 250, 500 and 750 mg were given to each volunteer. The concentrations of erythromycin propionate and erythromycin base in the plasma were determined by HPLC-MS.@*RESULTS@#All 30 volunteers completed the experiment without adverse reactions. Using 3P87 we analyzed the model and calculated the pharmacokinetic parameters. Three dose groups taking high, middle and low dose were all single compartment model. The pharmacokinetic parameters of erythromycin propionate after taking erythromycin stinoprate capsules were as follows: Low dose group: Ka (2.007 +/- 1.281 )/h, tmax ( actual value) (1.9 +/- 0.6) h, Cmax (437.0 +/- 295.0) microg/L, AUC0-14 (trapezoid area) (1840.2 +/- 1476.87) microg x h/L, Ke (0.329 +/- 0.119)/h, T1/2 (2.45 +/- 0.9) h. Middle dose group: Ka (1.451 +/- 0.380)/h, tmax (1.7 +/- 0.3) h, Cmax (923.1 +/- 217.5) microg/L, AUC0-14 (4542.44 +/- 1579.4) microg x h/L,Ke (0.237 +/- 0.057)/h, T1/2 (3.1 +/- 1.1) h; High dose group: Ka (2.076 +/- 1.559)/h, tmax (1.7 +/- 0.3) h, Cmax (1336.5 +/- 366.0) microg/L, AUC0-14 (7481.5 +/- 2496.2) microg x h/L, Ke (0.266 +/- 0.051)/h, T1/2 (2.7 +/- 0.5) h. The pharmacokinetic parameters of erythromycin were as follows: Low dose group: Ka (1.410 +/- 0.626)/h, tmax (1.8 +/- 0.5) h, Cmax (197.5 +/- 227.6) microLg/L, AUC0-14 (766.4 +/- 981.0) microg x h/L, Ke (0.519 +/- 0.240)/ h, T1/2 (1.6 +/- 0.8) h. Middle dose group: Ka (1.900 +/- 1.049)/h, tmax (1.6 +/- 0.2) h,Cmax (488.3 +/- 216.7) microg/L, AUC0-14( 488.3 +/- 216.7) microg/L, Ke (0.329 +/- 0.057)/h, T1/2(2.2 +/- 0.4) h; High dose group: Ka (1.934 +/- 0.794)/h, tmax (1.7 +/- 0.3) h, Cmax (749.3 +/- 387.2) microg/L, AUC0-14(3820.1 +/- 1966.4) microg x h/L, Ke (0.373 +/- 0.174)/h, T1/2( 2.2 +/- 0.7) h. AUC of both erythromycin propionate and erythromycin base was linearly correlated to the doses; T1/2 was not correlated to the doses, so they followed the first order processes. The pharmacokinetic parameters of erythromycin The erythromycin stinoprate propionate and erythromycin base had no gender differences. Conclusion was absorbed as erythromycin propionate. Cmax reached at about 1.6 h. T1/2 of elimination was 2.4-3.1 h. The active component of erythromycin propionate was erythromycin. Cmax of erythromycin is 1.8, T1/2 is 2.4-3.1 h. In the range of oral dose of 250 to 750 mg, both erythromycin propionate and erythromycin base accorded the first order processes. The pharmacokinetic parameters were different with those reported in foreign documents while the gender difference did not exist in Chinese adults.

Projections from respiratory neurons of medulla oblongata to the motor neuron pool of phrenic nerve in rat:An HRP retrograde tracing study / 中国康复理论与实践

@#ObjectiveTo observe the projections from respiratory neurons of medulla oblongata to the motor neuron pool of phrenic nerve in rat. MethodsBy using horseradish peroxidase (HRP) retrograde tracing technique after injecting HRP into phrenic nerve, retrograde labelled neurons were found in C3-C5 segment. Then, HRP was injected into the area where the phrenic motor neurons occupied, retrograde labelled neurons were found in medulla oblongata. ResultsPhrenic motor neurons locate in the C3-C5 segment ipsilaterally, occuping the intermediate portion of anterior horn and appearing typical motor neurons. Retrograde labelled neurons were found bilaterally in medulla oblongata, the neurons were located in nucleus retroambigualis (RNA), ventramedial area to nucleus retrofacialis (NRF). ConclusionThe phrenic motor neurons may receive direct projection of respiratory neuron in medulla oblongata, the projecting neurons are distributed in RNA and NRF area.