OBJECTIVETo investigate the effects of E 4031, a sodium calcium exchanger (NCX) agonist, on the isolated cardiac function and resting Ca2+ level in myocardial cells from rats with chronic heart failure.

METHODSRats chronic heart failure model was established by abdominal aorta coarctation with; Isolated heart perfusion by Langendorff apparatus was used to detect heart function and the effects of E 4031 on haemodynamic indexes; Myocardial cells of rats in the model group were extracted quickly and co-incubated with calcium fluorescent indicator fluo3/AM and the impact of E 4031 on the fluorescence intensity in myocardial cells were evaluated by confocal microscopy.

RESULTSHeart function of rats in the model group detected by Langendorff perfusion was significantly reduced after 12 weeks, E 4031 at 10 micromol/L could improve their left ventricular developed pressure(LVDP) and systolic / diastolic maximum rate (+/- dp/dtmax). Compared with the control and sham operation groups, the resting Ca2+ fluorescence intensity of the myocardial cells of rats in model group was at a higher level and went through a process of transient rise and drop, then stably remaining at a low level after co-incubated with 10 micromol/L E 4031.

CONCLUSIONE 4031 can improve the isolated heart function of rats with chronic heart failure, which may be associated with its enhancing the activity of NCX in the myocardial cell membrane and stabilizing intracellular Ca2+ level.

Animals ; Calcium ; metabolism ; Disease Models, Animal ; Heart ; physiopathology ; Heart Failure ; metabolism ; physiopathology ; In Vitro Techniques ; Male ; Myocardium ; metabolism ; Myocytes, Cardiac ; metabolism ; Piperidines ; pharmacology ; Pyridines ; pharmacology ; Rats ; Rats, Wistar

Acute Kidney Injury ; chemically induced ; enzymology ; Animals ; Disease Models, Animal ; Gentamicins ; Peptidyl-Dipeptidase A ; metabolism ; Rats

Objective To discuss the enrichment method of fetal DNA from maternal plasma on size-fractionated separation.Methods Antecubital venous blood (5 ml from each pregnant woman) was collected in EDTA-containing tubes.DNA was extracted from plasma and white blood cells, separately.The DNA was fractionated by agarose gel electrophoresis.Three sections of

PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Aza Compounds ; chemical synthesis ; chemistry ; pharmacology ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism

Objective: To systematically evaluate the factors affecting diabetic retinopathy (DR) among Chinese adult patients with type 2 diabetes mellitus (T2DM), so as to provide insights into establishment of personalized risk prediction models for DR. Methods: Case-control studies pertaining to factors affecting DR among Chinese adults were retrieved from international and national databases, including CNKI, Wanfang Data, SinoMed, PubMed, Web of Science, Embase and CINAHL from inception to March 31, 2023. A meta-analysis was performed using the software Stata 17.0, and subgroup analysis was performed to explore the source of heterogeneity. Sensitivity analysis was performed using the leave-one-out method, and the publication bias was evaluated using the Egger's test and trim-and-fill method. Results: Totally 4 969 publications were retrieved, and 35 case-control studies were finally enrolled, including 32 high-quality publications (91.43%). The included studies involved 29 228 participants and 10 568 DR patients, and the prevalence of DR was 36.16%. Meta-analysis revealed that age (OR=1.06, 95%CI: 1.00-1.13), duration of T2DM (OR=1.09, 95%CI: 1.08-1.11), systolic blood pressure (OR=1.02, 95%CI: 1.01-1.03), glycated hemoglobin A1c (OR=1.38, 95%CI: 1.26-1.50), fasting blood glucose (OR=1.57, 95%CI: 1.07-2.31), urinary albumin to creatinine ratio (OR=1.50, 95%CI: 1.10-2.04), serum uric acid (OR=1.01, 95%CI: 1.00-1.01), urine microprotein (OR=2.01, 95%CI: 1.96-2.07), triglyceride (OR=1.77, 95%CI: 1.42-2.21), and total cholesterol (OR=1.82, 95%CI: 1.50-2.21) were risk factors for DR, and glomerular filtration rate (OR=0.98, 95%CI: 0.97-0.98) and C-peptide (OR=0.79, 95%CI: 0.68-0.93) were protective factors for DR. Sensitivity analysis of age effects was not robust. Following adjustment for glomerular filtration rate with the trim-and-fill method, there was still a publication bias, and the publication bias of other influencing factors had no impact on pooled effects. Conclusions Age, course of T2DM, systolic blood pressure, glycated hemoglobin A1c, fasting blood glucose, urinary albumin to creatinine ratio, serum uric acid, urine microprotein, triglyceride and total cholesterol were risk factors, and glomerular filtration rate and C-peptide were protective factors for DR among Chinese adults.

Objective To study the polymorphisms of short tandem repeat (STR) loci in intron 1, 24, 13 and 22 (STR 1,24, 13, 22) of factor Ⅷ (FⅧ) gene in Chinese population, and establish single tube multiple fluorescent PCR method for rapid diagnosis of haemophilina A(HA). Methods Four STRs from genomie DNA of 220 females without blood relationship were amplified in a single tube using quadri-fluorescence PCR. Capillary electrophoresis was analyzed in ABI PRISM 310 Genetic Analyzer. DNA sequencing was used to assay the number of dinueleotide repeats. Gene diagnosis were performed in 96 HA families. Results It was observed that 7, 9, 10 and 7 different alleles were found in STR1, 24, 13 and 22, respectively. The PIC (polymorphism information contents) were 0. 3789, 0. 4055, 0. 5239 and 0. 4713 in STR1,24, 13 and 22, respectively, and the HR (heterozygesity rate) were 34. 55% (76/220), 38. 18% (84/220), 49. 55% (109/220) and 43.64% (96/220). In 96 HA families, the diagnosis rate of STR1, 24, 13 and 22 were 38. 54% (37/96), 38. 54% (37/96), 54. 17% (52/96), 42. 71% (41/96), respectively. Whereas it achieved 79. 17% (76/96) when combining the four STR markers. Conciusion The single tube multiple fluorescent PCR of four STR loci is an effective, simple, quick method for linkage analysis and gene diagnosis of haemophilia A.

Diagnosis, Differential ; Humans ; Parathyroid Glands

Objective To analyze the influential factors of clinical pregnancy rate of the frozen-thawed embryo transplantation. Methods The data of 3 192 FET patients in the reproductive medicine center of our hospital up to May 2014 were analyzed retrospectively. According to ages, reasons of infertility, types of infertility, duration of infertility, drug regimen, the number and the time of embryo transplantation, we divided these patients into six groups for comparing the clinical pregnancy rate. Results The FET clinical pregnancy rate of the under 35 years group was higher than the 35~39 years group and the over 39 years group (33.96%vs. 27.58%and 19.35%; P<0.05, respectively). The duration of infertility in the clinical pregnancy group was significantly shorter than the non-pregnancy group (P<0.05). The clinical pregnancy rate in the group with three embryos transplanted was higher than the group with only two embryos transplanted (41.01% vs. 28.75%; P < 0.05). Among the group with the age of over 40 years, those with three embryos transplanted had a higher clinical pregnancy rate than those with only one embryo transplanted (25.49% vs. 0.00%; P < 0.05). The clinical pregnancy rate of the frozen blastocyst transplantation group was higher than that of the cleavage-stage transplantation group (40.00%vs. 26.27%;P<0.05). Conclusion Age, infertility duration, the number and the time of frozen embryo transplantation may affect the clinical pregnancy rate among the FET patients. An individualized transplantation program based on age may improve the patient′s clinical pregnancy rate.

Objective:To investigate the effects of site specific (124 HNFTAGDLGP STIVGSAAFNMF145 ) antibody of Sodium calcium exchanger ( NCX) on calcium transient in single ventricular myocytes of normal adult rats .Methods: Isolated adult rat hearts were perfused using Langendorff method and single ventricular myocytes were then obtained .The ventricular myocytes were incubated with Fuar-2/AM and 2% bovine serum albumin for about 40 min and then,the fluorescence images were recorded when excitation wavelengths were 340 nm and 380 nm using ion imaging system.Fluorescence value F340/F380,length of cell shortening ,time to 90%restore( TR90 ) and calcium sensitivity ( ratio of F340/F380 and cell shortening ) were calculated.Results:The site specific antibody of NCX increased F340/F380 and decreased TR90 in single ventricular myocytes ,but had no more significant effect on calcium sensitivi-ty.Pretreatment with KB-R7943 or Nicardipine could significantly inhibit the TR 90 decrease or F340/F380 increase induced by the anti-body.Pretreating ventricular myocytes with combination of KB-R7943 and Nicardipine ,the antibody had no more significant effects on calcium transient.Conclusion:Site specific ( 124 HNFTAGDLGPSTIVGSAAFNMF145 ) antibody of NCX could increase calcium transient and accelerate the decrease of intracellular calcium during diastole ,which mainly related to its effects of activating L-type Ca2+channel and NCX.

Objective To evaluate the functional changes in the isometric,concentric and eccentric muscle strength of the knee extensors and flexors in patients with knee osteoarthritis,and to explore the relationship among these contractions.Methods A Biodex System-3 isokinetic test system was used to assess the isometric,concentric and eccentric strength of the knee extensors and flexors of the involved and uninvolved limbs of 54 patients suffering from osteoarthritis.Results The strength of the knee extensors and flexors of the involved limbs was significantly less than that of the uninvolved legs in the different contraction modes(P＜0.05).The difference was especially marked in concentric and eccentric contraction at low angular velocity.The hamstrings/quadriceps ratio and the dy- namic control ratio showed abnormalities in the muscle balance of the hamstrings and quadriceps.Conclusion Iso- kinetic testing should be applied and the hamstrings/quadriceps ratio and the dynamic control ratio should be analyzed in evaluating patients with knee osteoarthritis.