Pre-clinical evaluation of a new indirectly labeled 99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide with HYNIC as bifunctional chelator

Background  Technetium-99m or ^99mTc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new ^99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect ^99mTc labeling of depreotide using HYNIC as a bifunctional chelator.

Methods  The cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH₂-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with ^99mTc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new ^99mTc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new ^99mTc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1.

Results  The molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of ^99mTc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95±0.84)%. The labeling rate of the new ^99mTc-HYNIC-depreotide rose to a peak of (20.75±0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new ^99mTc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new ^99mTc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new ^99mTc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05±0.04)% ID/g at 1.5 hpi and remained high ((2.51±0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new ^99mTc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl).

Conclusion  The findings suggested that the new ^99mTc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.     

Experimental studies on imaging of infected site with 99mTc-labeled ciprofloxacin in mice

Background Bacterial infection can pose a substantial diagnostic dilemma. 99m^Tc-labeled ciprofloxacin （CPF） was developed as a biologically active radiopharmaceutical to diagnose infection. In the present research, we studied the biodistribution and imaging properties of infection tracer 99m^Tc-CPF in a mouse model of infection. Methods CPF was labeled with 99m^Tc and the radiochemical purity and labeling rate were measured. A mouse model of infection was established. We then determined the biodistribution of 99m^Tc-CPF and conducted the whole body scintigraphy of the animal model. Results 99m^Tc-Ciprotech was stable for at least 6 hours at room temperature. The labeling rate of CPF by 99m^Tc was over 90%. Clearance of radioactivity mainly occurred in the liver and kidney, and the clearance from blood was rapid. Both biodistribution and imaging results showed higher uptake of 99m^Tc-CPF at sites of infection. The infectious tissue/normal tissue ratio peak was 4.30 at 4 hours after injection. Conclusions 99m^Tc-CPF is a sensitive radiopharmaceutical for scintigraphy of infectious lesions and it is easy to prepare.     

Tissue-targeting lead generation and optimization from random and directed screening of technetium-99m labeled tripeptide complex libraries in vivo

Background Screening libraries against a molecular target in vitro are idealized models that cannot reflect the real state in vivo where biomolecules coexist and interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a unique noninvasive approach to trace a large number of compounds in vivo. Methods The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin using iterative and pooling protocol. Technetium （V） oxo core [TcO^3＋] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form a library of 8000 ^99mTc tripeptoid complexes. The radiocombinatorial screening （RCS） in vivo was carried out on SD rats and A549 tumour bearing mice. Results Signals of tissue distribution and metabolism of libraries were recorded by counting or imaging and tissue targeting leads identified by both random and directed RCS. Among them, ^99mTc RPA, ^99mTc VIG and ^99mTC RES had specific tissue targeting in kidney, liver and tumour respectively. The percent injected dose per gram tissue of ^99mTc labelled leads in their target tissue was highly structure dependent. Because the nontarget tissue binding and the metabolism of ^99mTc tripeptoid sublibraries were simultaneously monitored successfully by RCS, the interference of background activity was limited to the lowest level. Optimization of renal function agent from the labelled libraries was carried out by directed screening. ^99mTc DSG was finally identified the most promising agent for renal function studies. Conclusions RCS in vivo is a powerful tool for the discovery of tissue targeting drugs. The potential screening bias is probably the major limitation of labelled libraries.     

^99mTc-YIGSR as a Receptor Tracer in Imaging the Ehrlich Ascites Tumor-bearing Mice as Compared with ^99mTc-MIBI

The validity of ^99mTc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with ^99mTc by using a bifunctional chelator S-Acetly-NH3-MAG3. The MIBI was labeled with ^99mTc by following the kit instruction. The mice of tumor group were intravenously injected 1-2 mCi of ^99mTc-YIGSR or ^99mTc-MIBI via caudal vein, immobilized and imaged under a Gamma camera. The same procedure was performed in mice of blockade group, in which the unlabeled YIGSR was previously injected to block the receptor-recognition sites, and inflammation group serving as control. The reverse-phase Sep-Pak C18 chromatogram was found to have an essentially complete conjugation between YIGSR and S-Acetly-NH3-MAG3. The conjugated YIGSR could be radio-labeled successfully with ^99mTC at room temperature and neutral pH, with a radio-labeling yield of 62%. Without the chelator S-Acetly-NH3-MAG3, the YIGSR was labeled with ^99mTc at an efficiency of 4%. The imagological study revealed obvious tumor accumulation of ^99mTc-YIGSR 15 min after the injection, and the uptake peaked after 3 h with a tumor-to-muscle ratio （T/M） of 11.36. The radio-tracer was slowly cleared up and resulted in a T/M of 3.01 at the 8th h after the injection. As for blocked group, the tumor uptake of radiotracer was significantly lower, with the highest T/M being 4.61 after 3 h and 0.89 after 8 h. The T/M was 3.72 at the 3rd h and 1.29 at the 8th h after the ^99mTc-YIGSR injection in the inflammatory group. The T/M was significantly higher in tumor group than in inflammatory group or control group （P〈0.001）. In the ^99mTc-MIBI group, the T/M was 1.40 at the 3rd h and 0.55 at the 8th h after the injection, which showed a significant difference as compared with ^99mTc-YIGSR （P〈0.001）. It is concluded that YIGSR can be successfully radiolabelled by using S-Acetly-NH3-MAG3. ^99mTc-YIGSR has many advantages in tumor imaging, such as quick and clear visualization, high sensitivity and sp     

An imaging study using laminin peptide 99mTc-YIGSR in mice bearing Ehrlich ascites tumour

Background The YIGSR is a pentapeptide, from the laminin-1 of the β1 chain, which can mediate cell adhesion and bind the 67 kD laminin receptor. The purpose is to evaluate the usefulness of 99mTc-YIGSR, a novel tumour radiotracer, in the receptor imaging of Ehrlich ascites tumour. Methods Using S-Acetly-NH3-MAG3 as chelate, YIGSR, a pentapeptide from laminin, was tagged with 99mTc. 99mTc-YIGSR was detected in the tumour group bearing Ehrlich ascites tumour and blocked group. Tumour, normal, inflammatory and blocked groups were imaged. Results Through reverse phase Sep-Pak C18 chromatogram, it was revealed that YIGSR could conjugate with S-Acetly-NH3-MAG3, and be radiolabelled at room temperature and neutral pH with a radiolabelling yield of 62%, and of 4% without chelate. 99mTc-YIGSR was rapidly cleared from kidney, then liver. The imaging findings showed tumour tissue accumulated initial radioactivity at fifteen minutes after injection in the tumour group, and the uptake increased to peak at three hours with a tumour/muscle ratio (T/M) of 11.36, then cleared slowly to a T/M of 7.50 at eight hours. The tumour uptake of radiotracer in blocked group was significantly lower with T/M of 4.61 at three hours and 0.89 at eight hours. The T/M was only 3.72 at three hours and 1.29 at eight hours after injection in inflammatory group. Compared with inflammatory group and control obstructive group, the ratio of T/M in tumour group was significantly different (P<0.001). Conclusions Using S-Acetly-NH3-MAG3, we radiolabelled YIGSR with 99mTc. 99mTc-YIGSR possesses many merits of tumour imaging: rapid visualization, high sensitivity and specificity, and satisfactory target/nontarget ratio. Our data suggest 99mTc-YIGSR is a promising tumour radiotracer.     

Determination of Acrylamide Metabolite,Mercapturic Acld by High Performance Liquid Chromatography

A HPLC Assay was developed to identify and measure the metabolite of acrylamide,mercapturic acid,N-Acetyl-s-(propionamid)-cysteine(APC)in urine.O-phthalaldehyde(OPA)was utilized as a precolumn derivatizing agent in the assay.This derivative was isolatedwith a good selectivity by high performance liquid chromatography(HPLC)employingreversed phase ODS columns.The quantitation of the mercapturic acid derivative wasreproducible and with a detection limit of l pmol.The average coefficient of variation for theruns carried out on the same day was approximately 4.6％ at the range of 80-160μmol·L~(-1) ofAPC,and the mean analytical recovery from urine samples was 94％. The metabolite of urine of workers exposed to acrylamide was identified as N-acetyl-s-(propionamide)-cysteine by HPLC chromatography and fluorescence scan and HPLC-Massspectra.All results were identical with the authentic synthesized compound.     

Simultaneous Determination of Six Quaternary Ammonium Alkaloids in Coptidis Rhizoma by UPLC

Objective To establish a new, rapid, and reliable reversed-phase ultra performance liquid chromatography (RP-UPLC) method for the simultaneous determination of six quaternary ammonium alkaloids (QAAs) in Coptidis Rhizoma. Methods The effect of different experimental parameters on the analysis of QAAs by RP-UPLC was evaluated. Results Optimal resolution was achieved with an Acquity UPLC BEH C18 column using a gradient elution profile and a mobile phase consisting of water spiked with 10 mmol/L ammonium bicarbonate (A, pH adjusted to 10.0 by ammonia water) and acetonitrile (B), at a flow rate of 0.30 mL/min and wavelength of 345 nm. The column temperature was set at 30 ℃. The proposed method was found to be reproducible, precise, and rapid according to the method validation. Conclusion The proposed method, which is compatible with MS analysis and the preparation of QAA, provides some helpful insights into the quality control of Coptidis Rhizoma.     

A Novel Technique for the Preparation of ~（125）I-5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabino-furanosyl） Urail and Its Biodistribution Pattern in Kunming Mice

In this study, a novel technique for the preparation of 125I-5-trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) urail (FIAU) was developed, 125I-FIAU biodistribution profile was detected in Kunming mice and the possibility of using FTAU radio-labeling for reporter gene imaging was explored. 5-trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) urail (FTAU) was labeled with radioiodine (125I). A rotary evaporation method was used to remove excess methanol. The reactant was purified through a Sep-Pak C18 reversal phase column. The radiochemical purity and in vivo stability were determined using silica gel thin layer chromatography (TLC). The biodistribution of 125I-FIAU in Kunming mice was also detected. The results showed that 125I-FIAU could be radiolabeled effectively with FTAU, with mean labeling rate being (81±0.38)% (n =5). The mean radiochemical purity of (98.01±0.40)% (n=5) was achieved after a reversal phase Sep-park column purification. 125I-FIAU was stable when incubated in normal human serum or in saline at 37°C, with a radiochemical purity >96% during a 0.5-24 h time period. Biological experiments exhibited rapid clearance of 125I-FIAU from the blood pool. 125I-FIAU was mostly excreted by kidneys. 125I-FIAU in myocardium dropped conspicuously after 8 h and there was hardly retention at 24 h. We were led to concluded that the new method of radioiodinization of FTAU for the preparation of 125I-FIAU is easy, highly effective and stable in vivo. The biodistribution of 125I-FIAU in Kunming mice showed it can serve as an imaging probe for myocardial reporter genes.     

Study on cytomegaloviral infection in acute leukemia patients by polymerase chain reaction.

Polymerase chain reaction (PCR) and blot hybridization by probe labelled with digoxin were used to detect human cytomegalovirus (HCMV) DNA in 31 patients with acute leukemia and 20 controls. The positive rate detected by PCR in acute leukemia was 74.2% and 15.0% in the controls. The difference was statistically significant. The results suggest that acute leukemia patients are the high risk population with high infection rate of HCMV. The positive rate detected by digoxin method in acute leukemia was 58.1%. Six patients showed negative results by digoxin method, but positive by PCR. It was demonstrated that PCR was superior to digoxin method in sensitivity. Anti-HCMV IgM in serum of patients was detected at the same time, the positive rate was 16.1%. Only 6 of the 23 PCR positive patients showed positive anti-HCMV IgM. It suggests that the immune response is weak in acute leukemia patients and HCMV recently infected could not be excluded in the anti-HCMV IgM negative cases.

     

The value of ~(99m)Tc methylene diphosphonate bone scintigraphy in diagnosing relapsing polychondritis

Relapsing polychondritis (RP) is a recurrent disease involving cartilage mainly of the ear, nose, larynx, trachea, and bronchus. The typical manifestations of the disease in the ear and nose can be easily recognized, but the symptoms could be ignored or easily confused with those of other diseases when the cartilage of other sites is involved. Thus, it is necessary to develop a new technique for the diagnosis of this disease. Few cases of abnormal accumulation of radioactivity at cartilage shown by 99mTc methylene diphosphonate (MDP) bone scintigraphy are described in the literature. In this report, we present 4 patients of whom 3 had positive findings on 99mTc MDP bone scintigraphy with an assessment of 99mTc MDP bone scintigraphy in the diagnosis of RP.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.