大环内酯类抗生素麦迪霉素的电化学特性

在K₂HPO₄,NH₄Cl+NH₃和NaOH的10%(v/v)乙醇水溶液中,除0.01mol·L^-1以上NaOH液作为支持电解质外,麦迪霉素的伏安波皆为两个峰。峰A相当于它的甲醛基还原波,峰B为催化吸附氢波。溶液pH对两峰有强烈的影响。实验表明伏安波有吸附特性,且不可逆。两峰的ip与麦迪霉素的浓度成正比,线性范围分别为3×10^-6～3×10^-5mol·L^-1和1×10^-7～4×10^-5mol·L^-1,检测限为:1×10-6mol·L^-1和5×10^-8mol·L^-1。可应用于麦迪霉素的定量测定。研究了两峰的特性和电极机理,测定了有关的物理常数。     

双(2,6-哌嗪二酮)类抗肿瘤药物的研究:2,3-二乙酰氧基-1,4-二(3′,5′-二酮-N4′-取代哌嗪甲基)苯的合成

Seventeen compounds having the structure of 2,3-diacetoxy-1,4-bis(3′,5′- dioxo-N⁴′-substituted piperazinyl methyl)benzene were designed and synthesized based on chelation hypothesis. Their antitumor activities on P388 cells,Hep cells and SGC 7901 cells in vitro were tested. Preliminary results showed that compound 4e has potent antitumor effect against P388 cells and.Hep cells in vitro.     

双（2，6－哌嗪二酮）类抗肿瘤药物的研究：2，3－二乙酰氧基－1，4－二（3′，5′－二酮－N4′－取代哌嗪甲基）苯的合成

双（２，６－哌嗪二酮）类抗肿瘤药物的研究：２，３－二乙酰氧基－１，４－二（３′，５′－二酮－Ｎ４′－取代哌嗪甲基）苯的合成李全，沈旭，邵华武，谢毓元（中国科学院上海药物研究所２０００３１）１９６９年Ｃｒｅｉｇｈｔｏｎ等人试图用ＥＤＴＡ与甲酰胺反应合成...     

五味子醇甲的代谢转化

采用动物肝微粒体体外代谢法对五味子醇甲的代谢转化进行了研究。从体外代谢产物中鉴定其主要的三个代谢物为:7,8-顺二羟基五味子酸甲;7,7-顺二羟基-2-去甲基五味子醇甲及7,8-顺二羟基-3-去甲基五味子醇甲。在此基础上,建立了生物体液中五味子醇甲及其代谢物的反相HPLC分析方法,并用此法检测了服药后大鼠的胆汁及尿样,比较了体外代谢与体内代谢的异同。     

Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies

Aim

To assess composite endpoints combining glycaemic control (HbA1c < 7.0%, ≤ 6.5% or < 5.7%) with weight loss (≥ 5%, ≥ 10% or ≥ 15%) and without hypoglycaemia with tirzepatide in type 2 diabetes (T2D).

Materials and Methods

Data from the phase 3 SURPASS programme were evaluated post hoc by trial. Participants with T2D were randomized to tirzepatide (5, 10 and 15 mg), placebo (SURPASS-1,5), semaglutide 1 mg (SURPASS-2) or titrated basal insulin (SURPASS-3,4). The proportions of participants achieving the composite endpoints were compared between tirzepatide and the respective comparator groups at week 40/52.

Results

The proportions of participants achieving an HbA1c value of less than 7.0% with 5% or more weight loss and without hypoglycaemia ranged from 43% to 82% with tirzepatide across the SURPASS-1 to -5 trials versus 4%-5% with placebo, 51% with semaglutide 1 mg and 5% with basal insulin (P < .001 vs. all comparators). The proportions of participants achieving an HbA1c value of less than 7.0% with 10% or more, or 15% or more weight loss and without hypoglycaemia were significantly higher with all tirzepatide doses versus comparators across trials (P < .001 or P < .05). Similar results were observed for all other combinations of endpoints with an HbA1c value of 6.5% or less, or less than 5.7%, with more tirzepatide-treated participants achieving these endpoints versus those in the comparator groups, including semaglutide.

Conclusions

Across the SURPASS-1 to -5 clinical trials, more tirzepatide-treated participants with T2D achieved clinically meaningful composite endpoints, which included reaching glycaemic targets with various degrees of weight loss and without hypoglycaemia, than those in the comparator groups.     

High-intensity focused ultrasound ablation:An effective bridging therapy for hepatocellular carcinoma patients

AIM:To analyze whether high-intensity focused ultrasound(HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma(HCC).METHODS:From January 2007 to December 2010,49 consecutive HCC patients were listed for liver transplantation(UCSF criteria).The median waiting time for transplantation was 9.5 mo.Twenty-nine patients received transarterial chemoembolization(TACE) as a bringing therapy and 16 patients received no treatment before transplantation.Five patients received HIFU ablation as a bridging therapy.Another five patients with the same tumor staging(within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison.Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores,tumor size and number,and cause of cirrhosis.RESULTS:The HIFU group and TACE group showed no difference in terms of tumor size and tumor number.One patient in the HIFU group and no patient in the TACE group had gross ascites.The median hospital stay was 1 d(range,1-21 d) in the TACE group and two days(range,1-9 d) in the HIFU group(P < 0.000).No HIFU-related complication occurred.In the HIFU group,nine patients(90%) had complete response and one patient(10%) had partial response to the treatment.In the TACE group,only one patient(3%) had response to the treatment while 14 patients(48%) had stable disease and 14 patients(48%) had progressive disease(P = 0.00).Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list(P = 0.559).CONCLUSION:HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis.It may reduce the drop-out rate of liver transplant candidate.     

Factors associated with variability in response of diabetic macular oedema after intravitreal triamcinolone

Purpose:  To identify factors associated with variability in anatomical and functional response of diabetic macular oedema (DMO) after 4 mg of intravitreal triamcinolone acetonide (ivTA), and for recurrence of macular oedema.
Design:  Pooled analysis of individual data from two randomized controlled trials.
Methods:  This was a multicentre study involving 107 eyes with DMO administered 4 mg ivTA. Predictive factors for response to treatment were evaluated with linear regression analysis. Factors associated with time to recurrence of oedema were studied with Cox proportional hazards modelling. Main outcome measures were maximum improvement in optical coherence tomography (OCT)-measured central foveal thickness (CFT) and best-corrected visual acuity (BCVA), final CFT and BCVA at 12 months and time to oedema recurrence.
Results:  Greater reduction of retinal thickening occurred in eyes with worse baseline thickening ( P  < 0.001). There was also greater improvement of visual acuity in eyes with poorer preoperative BCVA levels ( P  < 0.001). Age, duration of oedema and previous macular laser treatment had no significant effect on maximal BCVA or CFT improvement. Eyes given 4 mg triamcinolone alone were more likely to develop recurrence of oedema at 12 months than those given a combination of 4 mg triamcinolone plus sequential laser (hazard ratio 2.60 [95% confidence interval: 1.45–4.67]).
Conclusion:  Baseline OCT-measured retinal thickening and BCVA are important predictors of maximal anatomical and functional response of DMO to ivTA, respectively. Combination treatment strategy using sequential laser therapy may have a role in delaying recurrence of oedema after triamcinolone.