Clinical Phenotype and Gene Mutation Analysis of a Family with Early-Onset Familial Alzheimer′s Disease / 中山大学学报(医学科学版)

@#【Objective】A full exome sequencing of an early-onset family Alzheimer′s disease (EOFAD) was conduct? ed to identify the mutational sites which may cause diseases. The result of the current study may provide suggestion to genetic counseling and prenatal diagnosis.【Methods】Whole exome sequencing was performed on the family members and software PolyPhen-2 as well as SIFT was employed for hazard prediction (Prediction on functional effects of the missense mutation).【Results】The heterozygous mutation c.758A>G (p.Tyr253Cys) in exon 9 of TTC3 gene had been identified in proband whose mother had been proved with heterozygous mutation c.758A>G. According to the family separation and related bioinformatics analysis, the mutant gene was a possible pathogenic mutation. 【Conclusion】 A new mutation was found of c.758A>G in TTC3 gene within a Chinese EOFAD family and a new mutation to the spectrum of genetic mutation in EOFAD was expanded. The finding provides a significant groundwork for future exploration on the mechanisms underlying EOFAD.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study / 中华医学杂志(英文版)

Background@#Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.@*Methods@#A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.@*Results@#In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.@*Conclusions@#R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.@*Trial Registration@#ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

MRI analysis of right ventricular function in rat model of pulmonary artery hypertension induced by monocrotaline / 中国实验动物学报

Objective The aim of this study was to establish a rat models of pulmonary artery hypertention with monocrotaline, and to study the relationship between the evolution of right ventricular function and the evolution of pulmo-nary artery pressure ( PAP) by magnetic resonance ( MR) imaging of the right ventricular function. Methods Rat models of pulmonary artery hypertension were established by monocrotaline (MCT). The model rats were divided into 4 groups:the 1-week-PAH group, 2-week-PAH group, 3-week-PAH group, and 4-week-PAH group, and pulmonary artery pressure in the rats was measured by right heart catheterization. After injection of MCT, we used MRI to evaluate the ventricular function of the rats every week. All the measurement data of right ventricular function in the model group were compared with the average pulmonary pressure using Pearson' s correlation test. Results There were strong correlations between the parameters of RV function in model group with the average pulmonary pressure ( r= -0. 823 for RV EF, r=0. 732 and 0. 803 for RV EDV and RV ESV) . At 2 weeks after injection of monocrotaline, the mean pulmonary pressure, right ven-tricular eject fraction ( RVEF) , the end-diastolic volume ( EDV) and the end-systolic volume ( ESV) of right ventricle be-tween rats in PAH and the control group showed no significant difference (P>0. 05). But three-four weeks after MCT in-jection, all these parameters were significantly different in the PAH rats than in control rats (P<0. 05). Conclusions As the pulmonary arterial pressure is increased in the rats, the right ventricular function is gradually impaired. For the monito-ring of chronic pulmonary artery hypertension in rats, MRI can be used to accurately measure the changes of parameters. The PAH can be indicated by looking at the changes of parameter such as RV EF, RV EDV and RV ESV.

MRI analysis of right ventricular function in rat model of pulmonary artery hypertension induced by monocrotaline / 中国实验动物学报

Objective The aim of this study was to establish a rat models of pulmonary artery hypertention with monocrotaline, and to study the relationship between the evolution of right ventricular function and the evolution of pulmo-nary artery pressure ( PAP) by magnetic resonance ( MR) imaging of the right ventricular function. Methods Rat models of pulmonary artery hypertension were established by monocrotaline (MCT). The model rats were divided into 4 groups:the 1-week-PAH group, 2-week-PAH group, 3-week-PAH group, and 4-week-PAH group, and pulmonary artery pressure in the rats was measured by right heart catheterization. After injection of MCT, we used MRI to evaluate the ventricular function of the rats every week. All the measurement data of right ventricular function in the model group were compared with the average pulmonary pressure using Pearson' s correlation test. Results There were strong correlations between the parameters of RV function in model group with the average pulmonary pressure ( r= -0. 823 for RV EF, r=0. 732 and 0. 803 for RV EDV and RV ESV) . At 2 weeks after injection of monocrotaline, the mean pulmonary pressure, right ven-tricular eject fraction ( RVEF) , the end-diastolic volume ( EDV) and the end-systolic volume ( ESV) of right ventricle be-tween rats in PAH and the control group showed no significant difference (P>0. 05). But three-four weeks after MCT in-jection, all these parameters were significantly different in the PAH rats than in control rats (P<0. 05). Conclusions As the pulmonary arterial pressure is increased in the rats, the right ventricular function is gradually impaired. For the monito-ring of chronic pulmonary artery hypertension in rats, MRI can be used to accurately measure the changes of parameters. The PAH can be indicated by looking at the changes of parameter such as RV EF, RV EDV and RV ESV.

The sleep staging based on HRV analysis / 生物医学工程学杂志

In order to deduce the sleep stages from heart rate, we analyze the heart rate variability (HRV) with hidden Markov model (HMM) for the identification of different characters of HRV within different sleep stages. Special technique is used to compensate the individual diversity. The relationship between the sleep stage and the ultra-low frequency components of HRV is also considered. Since the detection of heart rate hardly disturbs the sleep, the proposed method provides a simple approach to evaluating the sleep stage without disturbing the sleep. Our experiments have proved that this method meets the requirements of wide applications, especially the requirement of routine use in monitoring the normal subjects' sleep.

Clinical observation of gefitinib in treatment of female patients with adenocarcinoma of lung WU / 肿瘤研究与临床

Objective To evaluate the efficacy and adverse effects of gefitinib in the treatment of fe- male patients with advanced adenocarcinoma of lung who had failed to previous chemotherapy.Methods These patients received 250mg of gefitinib orally,once daily until disease progression or development of intol- erable toxic reaction.They were evaluated one month after treatment and every other month thereafter.Results Among the 27 evaluable patients,there were 1 CR(3.7%),11 PR(40.8%),10 SD(37.0%)and 5 PD(18.5%). The overall response rate was 44.5%(95% CI 29%～68%);and 22 patients(81.5%)gained profit(CR+PR+ SD)from the clinical therapy(95% CI 62%～94%);the mean TTP was 7.2 months.Symptomatic improvement rate was 80.0%.The main adverse effects were mild rash and diarrhea.Conclusion gefitinib has significant efficacy in the treatment of female patients with advanced tung cancer who had failed to previous chemother- apy.Adverse effects are mild.gefitinib is a suitable therapy for these patients.

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.

A NOVEL STRATEGY FOR SCREENING MUTANT ENZYMES UNDER NON-GROWTH CONDITIONS / 微生物学通报

The technique of double-layered plate was developed for screening the library of mutant endoglucanase III from Trichoderma reesei generated by the method of directed evolution.The enzyme activity was determined according to the velocity of the formation of halos on the plates.Several mutants with higher activity than the wild type at low temperature or alkaline pH were obtained by using this strategy under different screening conditions.Further results of spectrophotometric determination of the activities of these mutants were consistent with the results of plate screening.The establishment of such strategy will broaden the applications of the directed evolution methods for improving the existing proteins to obtain useful enzymes with new properties for industrial applications.

Inhibitory effect of?-ray irradiation on rat vascular smooth muscle cells / 中华放射肿瘤学杂志

Objective To investigate the mechanism of the inhibitory effect of ?-ray irradiation on rat vascular smooth muscle cells(VSMC). Methods The ef fect of ?-ray irradiation on proliferation of VSMC was observed by 3?H-TdR incor poration. After ?-ray irradiation, the VSMC cell cycle change was detected b y flo w cytometry. The expression of p53, cyclin D and PCNA was investigated by Wester n Blot. Results The inhibitory effect of ?-ray irradiation on VSMC proliferati on was dose-dependent. After ?-ray irradiation, VSMC was arrested in G 1 st age, w ith the expression of p53 increased but the expression of cyclin D and PCNA decr eased. Conclusions ?-ray irradiation can inhibit the proliferation of VSMC. T he main mechanism is probably due to the induction of cell cycle arrest and inhi bition of the VSMC mitosis ,during which process, p53,cyclin D and PCNA all pla y an important role .