membrane transporters are a cIass of functionaI membrane proteins and mediate the absorption,distribution and eIimination of many drugs. They are biomoIecuIes responsibIe for the homeo-stasis,and they,however,are easiIy reguIated by many kinds of chemicaIs. The IocaIizations,func-tions,substrates and seIective inhibitors of 18 more understanding transporters among the 26 known ones in the kidney are summarized in this review. The impact of these transporters on drug disposition and the typicaI drug-drug interactions concerned are aIso discussed.

OBJECTIVE To investigate the effect of Radix Isatidis and its constituents indigo and in?dirubin on two principal subtypes of organic cation transporters(OCT)OCT1,OCT2 in vivo in mice. METHODS Decoction of Radix Isatidis (DRI) 1.6 and 6.4 g · kg-1,granules of Radix Isatidis (GRI) 0.615 and 2.460 g·kg-1,indigo 0.008 and 0.640 mg·kg-1 and indirubin 0.0192 and 1.536 mg·kg-1 were ig given to NIH mice(60 mice per group),twice a day for 5 d. Four control groups were set up,including the vehicle of water,0.5% sodium carboxymethyl cellulose(CMC),additives of sucrose plus dextrin (1.5 g · kg-1)and positive control quinidine(0.025 g · kg-1). Sixty minutes after the last dosing,all the mice were iv given metformin(Met)5 mg·kg-1,and at 1.0,2.5,5.0,7.5,10.0 and 20.0 min after Met iv,10 mice in each group were sacrificed to collect whole blood and kidneys respectively. The right kidney was homogenized for Met accumulation test and the left one used to extract total RNA for analysis of OCT1 and OCT2 mRNA expressions by real-time PCR. The contents of Met in sera and kidneys were quantified by HPLC. Major pharmacokinetic parameters of Met in sera were analyzed by pharmacokinetic software(DAS 2.0). RESULTS There was no significant difference between water control group,0.5%CMC group and sucrose plus dextrin group in any examined item. Compared with vehicle control group (water and 0.5%CMC group),all the related pharmacokinetic parameters in DRI 6.4 g · kg- 1,GRI 2.46 g · kg-1,indigo 0.640 mg · kg-1 and indirubin 1.536 mg · kg-1 groups were changed significantly (P<0.05,P<0.01). The elimination half time (t1/2β) was prolonged 13%-97%,volume of distribution reduced by 13%-72%,clearance(Cl)reduced by 9%-65%,and the area under the concentration-time curve (AUC0-20 min) increased by 13%-135%. AUC0-20 min obtained from renal Met accumulations was significantly increased(P<0.01)while Met uptake by kidney slices was reduced(P<0.05,P<0.01). The expressions of OCT1 and OCT2 mRNA were obviously down-regulated(P<0.05,P<0.01). CONCLUSION The mouse renal OCT1 and OCT2 are significantly inhibited by DRI,GRI,indigo and indirubin. The inhibitory effect of Radix Isatidis on OCT1 and OCT2 probably arises from indigo and indirubin contained.

Objective To investigate the clinical manifestations in patients with 22q11.2 deletion syndrome (22q11.2DS) to improve the understanding of the disease.Methods Twenty patients with 22q11.2 DS were enrolled from Children's Hospital of Fudan University between August 2008 and April 2014.Cytogenetic and molecular genetic methods included fluorescence in situ hybridization (10 cases),and multiplex ligation-dependent probe amplification (10 cases).Age at the time of the diagnosis,sex and clinical manifestations were analyzed.Results The subject group consisted of 20 patients.Among them,13 cases (65％) were male and 7 cases (35％) were female.The median diagnostic age was 3.9 months.The presence of congenital heart diseases was identified in 17 patients (85％) and surgical correction was performed in 9 cases of them.The most frequent of complex congenital heart diseases were tetralogy of Fallot (20％) and pulmonary atresia (20％).Ten patients had varying degrees of T-cell immune function defects.Decrease in total lymphocytes and only CD8 counts were present in 45％ and 5％,respectively.Hypogammaglobulinemia was not detected in any patient.Six eases with T-cell immune function defects were treated with thymosin,4 of which were followed up for months,and the prognosis was good.Hypocalcemia was detected in 6 patients (30％),3 of whom presented with hypocalcemic seizures and hypoparathyroidism.Craniofacial dysmorphisms were detected in 3 patients(15％),2 of them only presented with micrognathia.Otorhinolaryngologic abnormalities were found in 4 cases (20％),3 of whom had laryngeal abnormalities,one of whom had cleft palate.Psychomotor developmental delay was found in 9 cases.Conclusions Congenital heart defects,hypocalcemia and/or impaired immune function are diagnostic features for 22q1 1.2 deletion syndrome,and they should be considered for cytogenetic analysis.

OBJECTIVE:To study the effects of 10 kinds of nephrotoxic TCM on three main subtypes(Oat1,Oat2 and Oat3) of kidney organic anion transporter(Oats)in mice. METHODS:A total of 1 840 SPF NIH mice were randomly divided into nor-mal control group(isovolumic pure water),probenecid group(30 kg/mg),sodium carboxymethyl cellulose(CMC)group,Pulsa-tillae radix,Corydalis rhizoma,Aconiti kusnezoffii radix,Aconiti radix,Angelicae pubescentis radix,Gleditsiae spina,Polygo-num cuspidatum,Kansui radix,Platycladi cacumen,Aucklandiae radix high and low dose groups. Mice were treated twice a day for 5 d,ig. After 1 h of the last dosing,they were iv given PAH in tail(30 mg/kg). The PAH pharmacokinetic parameters of the kidney homogenate were determined and the PAH intake in kidney tissue at the time point of 1,5,10,15 and 20 min was detect-ed. The PAH in blood was analyzed by DAS 2.0 software. The grouping and dosing were the same as before,after 1 h of the last dosing,kidney slices were made and put into PAH-buffer. The PAH intake of kidney slices was determined. RESULTS:Compared with normal control group,the t1/2β in C. rhizoma high dose group,A. kusnezoffii high and low dose groups,A. pubescentis high dose group,P. cuspidatum high and low dose groups and P. cacumen group were increased;Vd were all decreased in 10 kinds of TCM high and low dose groups;except for A. pubescentis low dose group,G. spian low dose group and K. radix low dose group, the CL was decreased and AUC0-20 min was increased in all other groups,with significant difference (P<0.01 or P<0.05). Com-pared with normal control group,the content of PAH in kidney tissue in P. radix high dose group,C. rhizoma high dose group,A. kusnezoffii high dose group,A. radix high and low dose groups,A. pubescentis high and low dose groups,G. spina high and low dose groups,P. cuspidatum high and low dose groups,K. radix high and low dose groups,P. cacumen high and low dose groups and A. radix high and low dose groups were increased,with significant difference (P<0.01 or P<0.05). Compared with normal control group,the intake of PAH in kidney slices in C. rhizoma high dose group,A. kusnezoffii high and low dose groups,G. spi-na high and low dose groups,K. radix high dose group,P. ca-cumen high and low dose groups and A. radix high dose group were decreased,with significant difference (P<0.01 or P<0.05). CONCLUSIONS:The 10 kinds of nephrotoxic TCM probably induced kidney injury through inhibiting the Oat1,Oat2 and Oat3 of Oats.

Objective To investigate the clinical and laboratory diagnosis in a rare case with dwarifsm and multisystem abnormalities. Methods Whole-exome sequencing was performed and data was processed using high-throughput data analysis pipeline. Genetic test result is veriifed by Sanger sequencing. Results This is a 14-year-old boy with short stature (the height is 132 cm) and autoimmune hemolytic anemia. He was treated with long-term oral prednisone. Head CT from other hospital found multiple calciifcations on both sides of the basal ganglia, two sides of the frontal lobe, and the left side of parietal lobe. Lateral spinal X-ray photography showed lfat in thoracolumbar vertebral body. Valgus was surgically corrected. He also has facial pigmentation spot and onychomycosis. Whole-exome sequencing combined with Sanger sequencing identiifed a known homozygous pathogenic mutation in ACP 5 genes (c. 643 G>A, p.G 215 R). Identiifcation of such a mutation results in the diagnosis of spondylo enchondrody splasia with immune dysregulation (SPENCDI). Conclusions Whole-exome sequencing is one of the effective methods for detection of rare disease, the SPENCDI case reported here is a good example of it.

OBJECTlVE To investigate the inhibition of Radix lsatidis and its major constituents indigo and indirubin on three principal subtypes of organic anion transporters ( OATs) , Oat1, Oat2 and Oat3 in vivo in mice. METHODS Granules of Radix lsatidis ( GRl) 0.615 and 2.46 g·kg-1 , decoction of Radix lsatidis ( DRl) 1.6 and 6.4 g·kg-1 , indigo 0.008 and 0.64 mg·kg-1 and indirubin 0.0192 and 1.536 mg·kg-1 were ig given to the NlH mice (60 mice per group), twice a day, for 5 d while four control groups were set up, including vehicle of water, 0.5%sodium carboxymethyl cellulose ( CMC) , positive control probe-necid (0.05 g·kg-1) and additives of sucrose plus dextrin (1.5 g·kg-1 each) groups. After the last dosing of the test samples, para-aminohippuric acid ( PAH) clearance test was conducted. All the mice were iv given PAH 0.03 g·kg-1 and 1, 2.5, 5, 7.5, 10 and 20 min later before 10 mice per group were euthanized to collect whole blood and the kidneys were quickly removed. Each right kidney was homoge-nized to analyze the PAH accumulations and each left kidney to extract total mRNA for analysis of Oat1, Oat2 and Oat3 gene expressions using quantitative real-time PCR. The concentrations of PAH in sera and in kidney homogenates were determined by the method of Kiguchi. Major pharmacokinetic parame-ters of PAH in sera were calculated by pharmacokinetic software ( DAS2.0) . PAH uptake test for kidney slices was performed on another group of NlH mice according to the method of Nakakariya. RESULTS There was no significant difference between water control group and 0.5%CMC group in all the examined items. Compared with the vehicle control groups ( water and 0. 5%CMC group ) , elimination half time ( t1/2β) of PAH in GRl 2.46 g·kg-1 ,indigo 0.64 mg·kg-1 and indirubin 1.536 mg·kg-1 groups was signifi-cantly prolonged (P<0.05), the total clearance (Cl) and volume of distribution (Vd) were obviously reduced ( P<0.01) and the area under the curve ( AUC0-20 min ) of PAH in all the tested groups was signifi-cantly increased ( P<0.01) . AUC0-20 min obtained from renal PAH accumulations within the checked time was significantly higher ( P<0.05, P<0.01) than in the vehicle control group. But there was in no signifi-cant difference between all the study groups in kidney-to-plasma AUC ratios. PAH uptake results by kidney slices were significantly lower ( P<0. 05, P<0. 01 ) than in vehicle control group in every two dosages of all the four samples tested. Compared with vehicle control group, the mRNA expressions of Oat1, Oat2 and Oat3 were obviously ( P<0.05, P<0.01) and abnormally regulated in the groups of GRl 2.46 g·kg-1, DRl 6.4 g·kg-1, indigo 0.64 mg·kg-1 and indirubin 1.536 mg·kg-1. CONCLUSlON The renal Oat1, Oat2 and Oat3 of mice are significantly inhibited by GRl, DRl, indigo and indirubin. The inhibitory function of Radix lsatidis probably stems from indigo and indirubin contained in it.

Objective To compare the pressor responses to ephedrine during general anesthesia with different drugs.Methods Sixty ASA physical status Ⅰ or Ⅱ patients,scheduled for elective gastrointestinal tumor resection under general anesthesia,aged 20-64 yr,weighing 45-90 kg,were included in this study.The patients were randomized to receive dexmedetomidine + remifentanil + sevoflurane (group Ⅰ,n =20),propofol + remifentanil + sevoflurane (group Ⅱ,n =20),or dexmedetomidine + propofol + remifentanil + sevoflurane (group Ⅲ,n =20) to maintain the depth of anesthesia.Ephedrine 0.1 mg/kg was injected intravenously when the systolic blood pressure (SBP) was decreased to about 90 mm Hg during anesthesia.Blood pressure was monitored and recorded at 1-min intervals for 10 min after the injection.The onset time (TSBP,TDBP,TMAP) for ephedrine to raise the SBP,diastolic blood pressure (DBP) and mean arterial pressure (MAP) and the maximal amplitude (△SBP,△DBP,△MAP) were also recorded.Results Compared with Ⅱ group,TSBP,TDBP and TMAP were significantly shortened,and △SBP,△DBP and △MAP were increased in Ⅰ and Ⅲ groups (P ＜ 0.05).Conclusion Compared with propofol + remifentanil + sevoflurane combined anesthesia,dexmedetomidine + remifentanil + sevoflurane combined anesthesia and dexmedetomidine + propofol + remifentanil + sevoflurane combined anesthesia augment the pressor responses to ephedrine in patients.

Recent studies have shown that tumor microenvironment (TME) is significantly different from normal tissues, such as the change of abnormal enzyme expression, hypoxia, pH and so on. TME is closely related to the induced proliferation of tumor cells, angiogenesis, immune escape and the production of multidrug resistance. Cancer associated fibroblasts (CAFs) are the main stromal cell types in the TME. A variety of cytokines secreted by CAFs play an important role in tumor growth, invasion and metastasis. Understanding the role and mechanism of CAFs in the development of breast cancer is expected to provide a new target for improving the prognosis of breast cancer patients.

Liquid level detection (LLD) is necessary for eliminating carry-over of needle's outside by limiting the depth the needle probes into liquid in auto clinical laboratory analyzers. This paper listed various demands of liquid-handling system under different situations; reviewed various LLD techniques, such as capacitive, air pressure, mechanical vibration, ultrasound, light reflection, CCD imaging etc.; briefly introduced the working principles, features, and limitation of the LLDs; and recapitulated the characteristics of contact and non-contact LLDs. Lastly, the next generation technique of LLD is prospected.
Automation ; Clinical Laboratory Techniques ; instrumentation ; methods

Objective To evaluate the effect of hypotension factor on endotracheal tube cuff-in-duced damage to tracheal mucous membrane of rabbits. Methods Eighty healthy rabbits of both sexes, aged 3.0-3.5 months, weighing 2.5-3.5 kg, were divided into 16 groups(n=5 each)according to the cuff pressure and mean arterial pressure(MAP): different cuff pressures when MAP did not decrease groups(C1M1group, C2M1group, C3M1group, C4M1group), different cuff pressures when MAP de-creased by 20% of the baseline value groups(C1M2group, C2M2group, C3M2group, C4M2group), dif-ferent cuff pressures when MAP decreased by 30% of the baseline value groups(C1M3group, C2M3group, C3M3group, C4M3group), and different cuff pressures when MAP decreased by 40% of the baseline value groups(C1M4group, C2M4group, C3M4group, C4M4group). Different cuff pressures were 0, 10, 20 and 30 cmH2O.At 2 h of tracheal intubation, the tracheas in the cuff-compressed area were harvested and sliced for examination of the pathological changes of tracheal mucous membrane after haematoxylin and eosin staining(with a light microscope), and the damage to tracheal mucous membrane was scored. Results When at the same low pressure(MAP decreased by 20%, 30% and 40% of the baseline value), the score of damage to tracheal mucous membrane increased with the increasing cuff pressures(P<0.05). When at the same cuff pressure(10, 20 and 30 cmH2O), the score of damage to tracheal mucous membrane in-creased with the increasing MAP(P<0.05). There was interaction between cuff pressure and MAP, F=2.034(P<0.05). Conclusion There is interaction between the effects of hypotension factor and endotra-cheal tube cuff factor on damage to tracheal mucous membrane; hypotension factor can aggravate endotra-cheal tube cuff-induced damage to tracheal mucous membrane of rabbits.