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 normal anatomy and variation of Willis circle by 64-slice volume CT digital subtraction angiography(VCTDSA).Methods VCTDSA data of 174 patients with cephalocervical and cephalic scanning in our hospital from February 2006 to September 2008 were analyzed.Developmental condition,shape,size,integrity,and perforating branches of Willis circle were observed.Results(1) Hypoplasia was displayed in any component vessels of Willis circle.Incidence rate of hypoplasia was 20.1% in left posterior communicating artery,16.1% in right posterior communicating artery,13.8% in right anterior cerebral artery A1,9.2% in right posterior cerebral artery P1,7.3% in anterior communicating artery,6.3% in left posterior cerebral artery P1,and 3.4% in left anterior cerebral artery A1.Congenital arterial absence occurred more frequently in right posterior communicating artery(54.6%),left posterior communicating artery(52.3%),and anterior communicating artery(15.8%).(2) Hypoplasia or congenital absence of posterior circulation and anterior-posterior circulation occurred with a rate of 55.8% and 29.8% respectively.Integrity of Willis circle was only 9.2%.There were 17 perforating branches and 26 heubner inversion arteries observed in 174 Willis circle,with an average diameter of 0.82 mm and 0.94 mm respectively.Conclusion VCTDSA can display Willis circle completely and clearly.Using three-dimensional rotation may detect all kinds of variation and perforating branches of Willis circle.

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 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 influential factors of adverse drug reaction(ADR)in elderly patients during medi-cation,and to provide reference for reducing the incidence of ADR in geriatrics department. METHODS:The clinical data of elder-ly patients admitted to our hospital from Jan. 2011 to Dec. 2015 were collected and analyzed by single factor and unconditional Loigstic multiple regression analysis. The risk influential factors of ADR were investigated. RESULTS:A total of 1 680 patients re-ceived drug therapy,and the incidence of ADR was 7.92%(133/1 680). Organs/systems involved in ADR were mainly allergic re-action(49 cases,36.84%)and digestive system(48 cases,36.09%). The results of single factor analysis showed that the age of patients,drug dosage,route of administration,treatment course,the type numbers of drug combination and others were the inde-pendent influential factors of ADR. By unconditional Loigstic multiple regression analysis,it was found that the risk of ADR in-creased with the drug dosage,treatment course,intraverous administration and various drugs use,etc. CONCLUSIONS:It is nec-essary to pay attention to ADR monitoring,particularly risk factors monitoring of ADR in the elderly patients,strengthen medica-tion guidance to improve medication compliance,take the necessary preventive measures to reduce the incidence of ADR.

Objective To study the effect of olanzapine combined with repetitive transcranial magnetic stimulation(rTMS) in the treatment of phonism dominated schizophrenia.Methods From August 2015 to November 2016,112 patients with phonism based schizophrenia in Ningbo Kangning Hospital were selected in the research . According to the different treatment ,the patients were divided into observation group and control group ,with 56 cases in each group.The observation group was treated with olanzapine combined with rTMS chemotherapy ,the control group was treated with olanzapine.Before and after treatment,the positive and negative symptom scale ( PANSS) score, Wisconsin Card Sorting Test ( WCST) score of the two groups were observed.The clinical efficacy was compared between the two groups.Results Before treatment,there were no statistically significant differences in PANSS score and WCST score between the two groups ( all P＞0.05).After treatment for 1 week,2 weeks,4 weeks,the PANSS scores of the two groups were significantly lower than those before treatment (F＝170.710,106.028,28.530,30.328, 25.806,10.832,203.342,372.253,all P＜0.05).The PANSS scores decreased more significantly in the observation group.After treatment for 1,2,4 weeks,the scores of positive symptoms in the observation group were (25.95 ±3.50)points, (24.72 ±4.50)points and(16.51 ±2.70)points,respectively,which were significantly lower than those in the control group[(27.27 ±2.03)points,(27.80 ±5.37)points,(19.53 ±3.07)points](t＝2.441,3.290,5.528,all P＜0.05).After treatment for 1 week,2 weeks,4 weeks,the continuous response scores in the observation group were (45.62 ±5.41)points,(44.69 ±4.91) points,(35.89 ±3.30) points,respectively,which were significantly lower than those in the control group[(50.61 ±5.35)points,(46.80 ±5.14)points,(42.70 ±5.04)points](t＝4.908, 2.221,8.459,all P＜0.05).The scores of continuous errors in the observation group were (49.47 ±4.59) points, (46.53 ±6.05) points and (36.35 ±5.18) points,respectively,which were lower than those in the control group [(83.1 ±6.58)points,(81.85 ±6.70)points and (76.86 ±76.86)points](t＝31.369,29.279,38.464,all P＜0.05).After treatment for 1 week,2 weeks,the classification scores in the observation group were (4.21 ±2.03) points and (5.35 ±2.23) points,respectively,which were significantly higher than those in the control group [(3.35 ±1.24)points and (3.95 ±1.24)points] (t＝2.705,4.106,all P＜0.05).The effective rate was 91.0%in the observation group ,which was 89.2%in the control group,there was no statistically significant difference (χ2＝0.022,P＞0.05).Conclusion Olanzapine combined with rTMS is effective in the treatment of schizophrenia ,and olanzapine combined with rTMS is more effective in improving the cognitive ability of patients than olanzapine alone .

Objective:To deeply understand the inner experiences of undergraduate nursing interns using Nursing Information Systems (NIS) and provide references for formulating relevant intervention strategies.Methods:A descriptive phenomenological approach was adopted for this qualitative study. Purposeful sampling was used to select undergraduate nursing interns from four comprehensive hospitals in Hangzhou during February to May 2023 for semi-structured interviews. The interview data were analyzed using Colaizzi's seven-step method to extract themes.Results:Four themes were identified in this study: insufficient preparedness of undergraduate nursing interns in using NIS, low engagement of undergraduate nursing interns in using NIS, perceived benefits of using NIS by undergraduate nursing interns, and adaptation strategies of undergraduate nursing interns using NIS.Conclusions:There are issues such as insufficient preparedness and low engagement among undergraduate nursing interns in using NIS. Some respondents experience emotions such as anxiety, fatigue, and decreased enthusiasm. It is recommended that colleges and internship hospitals pay attention to the clinical work demands and the learning needs of nursing interns, thus providing education and support for the use of NIS.

OBJECTIVETo investigate the impact of the regeneration of interstitial cell of Cajal (ICC) on the conduction of slow wave and gastric emptying in rats undergoing Roux-en-Y gastrojejunostomy.

METHODSTwenty male SD rats were randomly divided into experimental group and control group. The experimental group consisted of ten rats undergoing Roux-en-Y gastrojejunostomy. The control group only underwent pyloric transection and anastomosis. Gastric scintigraphy was performed in the two groups respectively to measure the half time of gastric emptying (t1/2) at sixteen weeks after the surgical manipulations, and then the myoelectrical activities near the gastrojejunal anastomosis were recorded. The study also observed the regeneration of ICC by the electron microscopy. The data of the 2 groups was compared by t test.

RESULTSIn the sixteenth postoperative week, the t1/2 was (23.5 ± 4.5) minutes for rats in the Roux-en-Y group and (10.2 ± 2.3) minutes for those in the control group, indicating delayed gastric emptying in the Roux-en-Y group (t=7.978, P=0.000), accompanied with the abnormal myoelectrical activities near the gastrojejunal anastomosis. The morphological detection showed that ICC near the gastrojejunal anastomosis regenerated and reconstructed their network in the rats of the experimental group.

CONCLUSIONThe abnormal myoelectrical activities near the gastrojejunal anastomosis, basing on the regeneration and reconstruction of ICC, may make a significant delay on the gastric emptying.

Anastomosis, Roux-en-Y ; Animals ; Gastric Emptying ; Humans ; Interstitial Cells of Cajal ; cytology ; Jejunum ; surgery ; Male ; Postoperative Period ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Stomach ; surgery

Objective To compare arthroscopic double-row bridging suture and minimally invasive locking plate system in the treatment of simple avulsion fracture of humeral greater tuberosity.Methods A retrospective study was conducted of the 93 patients with avulsion fracture of humeral greater tuberosity who had been treated at Orthopaedic Center,Beijing Luhe Hospital from January 2012 to December 2016.Of them,38 were treated by arthroscopic double-row bridging suture (ADRB) and 55 by open reduction and internal fixation with minimally invasive locking plate system (MIPS).Regular X-ray follow-ups were carried out at 3,6 and 12 months postoperatively and every 6 months afterwards.Surgical time,range of motion (ROM) of the shoulder,American Shoulder and Elbow Surgeons (ASES) score,Visual Analogue Scale (VAS) and complications were recorded preoperatively and at the last follow-up.Results The patients of the arthroscopy and plate groups were comparable because there were no significant differences in the preoperative general data between them (P ＞ 0.05).The average follow-up time for the 93 patients was 35.9months (from 12 to 60 months).The operation time for the arthroscopy group (97.0 ± 20.1 min) was significantly longer than that for the plate group (67.5 ± 19.0 min) (P ＜ 0.05).At the last follow-up,anteflexion lift (152.6° ± 12.9°),abduction lift (154.0° ± 13.5°) and internal rotation angle at 90° (57.7° ±12.2°) in the arthroscopy group were significantly better than those in the plate group (134.9° ± 17.8°,129.5° ± 18.6° and 50.8° ± 12.9°,respectively) (P ＜ 0.05).At the last follow-up,the ASES scores for the arthroscopy and plate groups were 88.5 ± 7.6 and 85.1 ± 11.3,respectively,showing no statistically significant difference (P ＞ 0.05);the VAS scores for the 2 groups were 1.5 ± 1.2 and 2.2 ± 1.5 respectively,showing a statistically significant difference between the 2 groups (P ＜ 0.05).There was no significant difference between the2 groups in improvement of ASES scores (P ＞ 0.05).Ninety fractures healed after 3 months while 3 fractures in the arthroscopy group did after 6 months.In the plate group,7 patients developed shoulder stiffness 3 to 6 months after surgery and 3 ones reported pain during abduction.Conclusions Both ADRB and MIPS are an effective treatment for simple avulsion fracture of humeral greater tuberosity.MIPS fixation needs shorter surgical time while ADRB leads to better postoperative shoulder ROM.

Objective:To investigate the characteristics of clinical, muscle pathology and gene mutation in patients with nemaline myopathy caused by NEB gene mutation.Methods:The clinical and pathological data of patients with nemaline myopathy caused by NEB gene were collected from Neuromuscular Center of Jiaozuo People′s Hospital from January 1997 to January 2020. The next generation sequencing was preformed to detect NEB gene in all patients, and characteristics of gene mutation were analyzed.Results:Among the 11 patients, there were 8 males and 3 females, and 6 of them came from 2 families. The age of seeing a doctor ranged from 11 to 52 years, the age of onset was from 6 to 23 years, and the course of disease ranged from 5 to 35 years. Neurological examination showed that among the 11 patients, 8 patients had high palatal arch and long face. The muscle tone of both upperlimbs was normal, the tendon reflex was depressed, the proximal muscle strength was grade Ⅲ-Ⅴ, and the distal muscle strength was grade Ⅴ. The muscle tone of both lower extremities was reduced and the tendon reflex was absent. The proximal muscle strength was grade Ⅱ-Ⅳ and the distal muscle strength was grade Ⅲ-Ⅴ. No dysphagia or respiratory muscle involvement was found. Muscle biopsies were performed in 7 of the 11 patients, the pathological changes were muscle fibers of different sizes, circular atrophic muscle fibers and compensatory hypertrophic fibers, and occasionally denatured and necrotic muscle fibers were found. Different degrees of rod aggregation could be seen in all the 7 patients. Electron microscopic examination of 5 patients showed that there was rod aggregation between myofibrils, and most of them were located near the Z band, but no intranuclear rod was found. NEB gene was found in all 11 patients, and a total of 9 different mutation sites were detected, including 8 in exon region and 1 in intron region. Among them, c.21522+3A>G was found in 10 cases, c.1623delT was found in 3 cases and c.17611C>T was found in 3 cases. There was 1 case of c.4417C>T, c.2549delA, c.21065dupA, c.3520G>A, c.20943G>A, c.192G>A respectively.Conclusions:The clinical phenotype of nemaline myopathy caused by NEB gene has great heterogeneity. Muscle pathology shows that rod aggregation is an important basis for the diagnosis of this disease. Mutation c.21522+3A>G in intron is the most common mutation in this group of NEB gene. And the novel mutation sites of NEB gene are respectively c.17611C>T, c.2549delA, c.3520G>A, c.21065dupA, c.20943G>A and c.192G>A.