ObjectiveTo investigate the clinical application of tacrulimus (TAC, FK506) in children with primary nephrotic syndrome (NS). MethodsSixty-five primary NS children received routine or decreased-dosage glucocorticosteroid according to clinical NS types after hospitalization. At the same time, TAC was given orally with the dosage of 0.1 to 0.15 mg/kg, once every 12 hours, for 6 to 24 months. And the serum concentration of TAC was monitored during the course. ResultsAfter the treatment of TAC for 1 to 2 months, 65 patients were recovered with gradually reduced urinary protein, rapidly increased serum albumin, and improvement of cholesterol and triglycerides. Total remission rate was 83.1% and onset time was 7 to 54 days. Twelve cases experienced recurrence. Increased CD4, as well as 3/3 or 3/1 TAC genotype, indicated higher remission rate. Various pathological types had different remission rates or ratio, which were as follows: minimal change nephropathy (96.4%), mesangial proliferative glomendonephritis (90.0%), membranous nephropathy (2/3), membranous proliferative glomerulonephritis (3/5), focal segmental glomerulosclerosis (4/9). The patients would recover in the course of treatment under the conditions of TAC initial dose as 0.1 to 0.15 mg /kg per 12 hours and controlled serum concentration as 5 to 10 g/L. During the treatment, 12 cases appeared gastrointestinal symptoms, mainly as anorexia, nausea and vomiting, 1 abdominal pain, 2 headache, 1 tremor, 1 paresthesia, 3 insomnia, 4 transient increased Scr, 8 slightly increased NAG, 6 increased C3 and α-2 macroglobulin. The symptoms disappeared within one week or after stopping TAC. ConclusionsTAC is effective in primary NS children, even with abnormal liver function or tuberculosis infection. TAC can also be a substitute to cyclosporine A.

Objectives: The aim of the study was to evaluate the therapeutic effects of 6-mercaptopurine in the treatment of refractory childhood nephrotic syndrome (NS). Methods: According to the varieties of NS, 6-mercaptopurine (2 mg/kg body weight daily) combined with corticosteroid or 6-mercaptopurine (2 mg/kg body weight daily) alone after tapering of steroids were given to 28 consecutive children with primary NS in our hospital. Results: One month after the use of 6-mercaptopurine, proteinuria was decreased. The duration of improvement was 9～28 days, with mean duration of 17 days. Over-all effective rate was 85.7%. Among different varieties of NS, the best therapeutic effect was noted in steroid-dependent children; the better therapeutic effect in steroid-resistant children; and good therapeutic effect in frequently relapsing children. The effective rates were 100%, 84.6%, 81.8% respectively. All the pathological varieties of 28 children were confirmed by renal biopsy. The better therapeutic effects were noted in slight mesangial proliferative glomerulonephritis (MsPGN) and minimal change nephrotic syndrome (MCNS). The less therapeutic effect was noted in membranoproliferative glomerulonephritis (MPGN). Their therapeutic effective rates were 92.9%, 80%, 66.7% respectively. Unfortunately, drug-induced aplastic anemia was seen in 2 cases. Slight gastrointestinal reactions were present in 6 cases. There were no side reaction on the gonad. Conclusions: The great difference in the therapeutic effects is related to the different pathologic varieties of NS. With regard to the treatment of refractory NS in children, the pathological varieties should be confirmed by renal biopsy as soon as possible. Based on the renal biopsy, 6-mercaptopurine can be considered in the treatment of MsPGN and MCNS. As a result, relapses could be reduced; the duration of remission could be prolonged, and the side reactions from steroid treatment could be avoided. The use of 6-mercaptopurine for the treatment of refractory NS is one of the effective therapy.

Objective To explore the application range and preponderance of different therapeutic methods of traditional medicines in overseas countries with retrospective studies on bibliographies of overseas traditional medicines. Methods All bibliographies were articles written in August 1964 to September 2009 and came from MEDLINE data base through searching 17 inferior words of"replacement therapy" in MeSH subject headings. Results We got altogether 10103 articles in 1633 kinds of periodicals concerned with replacement therapy, and summed up to 9841 effective articles in the end. Conclusion More and more attentions have been paid to traditional medicine in overseas countries; Such kinds of articles were mostly published in American and British medical periodicals; articles with advanced technologies and high reliability have more chances to be adopted by medical periodicals; traditional Chinese medicine plays a leading role in the fields of traditional medicines in the whole world; replacement therapy were increasingly adopted to deal with disease protection and health care.

Biopsy ; Child, Preschool ; Female ; Glomerulonephritis ; pathology ; Humans ; Infant ; Kidney ; pathology ; physiopathology ; Kidney Function Tests ; Male

Objective To analyze MRI features of different cervical flexion positions in Hirayama disease (HD) and discuss the effects on these features by different cervical flexion angles.Methods The cervical MR images of neutral and different flexion positions (20°, 25°, 30°, 35° ,40°) of 20 patients, who were clinically diagnosed as HD,were studied.At flexion positions, the appearance of anterior shifting of the posterior wall of the cervical dural canal and widening of epidural space was recorded.The maximum sagittal diameters (d) of widened cervical epidural space and the cervical canal sagittal diameters (D) on the same level were measured to calculate d/D value for quantitative evaluation of the two signs.Comparisons of appearance of the signs among different flexion positions were made using F/sher's exact test.Repeated measures analysis of variance (rmANOVA) was used to compare mean d/D values among groups with different positions, and paired comparisons were also performed.Results The appearance of anterior shifting of the posterior wall of the cervical dural canal were different between 20° group (70%, 14/20) and other 4 larger angles groups (100%) (χ2 =5.76, P=0.020).The d/D values were 0.51±0.06,0.54±0.08,0.57±0.09,0.61±0.09,0.59±0.07 respectively at abovementioned 5 flexion positions, which were different among groups( F = 3.450 ,P = 0.013 ).The value was greater at 35° than that at 20° and 25°( P <0.05 ), and it was also greater at 40° than that at 20° ( P < 0.05 ).Conclusion Cervical flexion angle has an effect on anterior shifting of the posterior wall of the cervical dural canal and widening of epidural space.

Objective To observe the effects of glucagon like peptide-1 (GLP-1) analogues liraglutide on expressions of nitric oxide synthase (NOS) and cyclo-oxygen-ase (COX)2 in renal medulla of type 2 diabetes rats, and the mechanism of its lowering blood pressure and promoting excretion of water and salt in kidney. Methods Type 2 diabetes model rats were generated by high-fat and high-sugar feeding for 8 weeks followed by intraperitoneal injection of streptozotocin (STZ). Subse?quently, eighteen type 2 diabetes rats were divided into two groups: liraglutide treatment group (DMT) and diabetes group (DM). Twelve normal rats were divided into two groups: liraglutide treatment wild type group (WTT) and wild type group (WT). DMT and WTT groups were given liraglutide (200μg/kg) by subcutaneous injection, DM and WT groups were given equivalent normal saline by the same way. The levels of blood glucose and blood pressure were detected at 0, 2, 4 and 6 weeks after treatment in groups of rats. Samples of urine were collected for detecting ion concentrations (K+, Na+and Cl-) af?ter treatment for six weeks. Rats were sacrificed and blood samples were collected for detecting ion concentrations (K+, Na+and Cl-). The expression levels of NOS and COX2 mRNA and protein in renal medulla were detected by real-time PCR and Western blot assay. Results After treating with liraglutide, the values of blood glucose (F=5.933, P<0.05) and blood pres?
sure (F=22.070, P<0.05) were gradually decreased in DMT group. After treatment with liraglutide for 6 weeks, the values of blood glucose (mmol/L:12.78 ± 3.82 vs. 18.75 ± 1.68) and blood pressure (mmHg:119.98 ± 4.43 vs. 136.42 ± 4.48) were signifi?cantly decreased (P<0.05) in DMT group than those of DM group (P<0.05). There were no significant differences in the concentrations of K+, Na+and Cl-between the two groups. There were higher levels of K+(mmol/L:46.55 ± 6.43 vs. 33.13 ± 9.71), Na+(mmol/L:56.33±8.83 vs. 41.20±7.25) and Cl-(mmol/L:159.81±25.06 vs. 71.44±12.99) in urine in DMT group than those of DM group (P<0.05). The mRNA levels and protein expressions of NOS and COX2 in renal medulla were significant?ly increased in DMT group than those of DM group (P<0.05). Conclusion GLP-1 analogues liraglutide may enhance the expression of COX2 by increasing the expression of NOS to excrete water and salt, and decrease blood pressure.

Objective To explore the feasibility and clinical efficacy of long-segmental bone defects after en bloc tumor resection of lower limb segment with composite of titanium alloy 3D printed prosthesis and vascularized fibular autograft and bioceramics.Methods 5 patients with lower extremity tumor (1 high grade chondrosarcoma,1 Ewing sarcoma,1 single metastatic tumor and 2 osteosarcoma) were treated by en bloc resection and precise reconstruction with segmental 3D-printed,custom-made prosthesis from August 2015 to November 2016,which composed of 1 male and 4 females,ranged from 16 to 56 years old,the average was 32± 19.3 years old.Three-dimensional computed tomography reconstructed images of patients' tumors were built before surgery.Custom-made prostheses were manufactured based on the patients' reconstructed images with micro-pores on the surface.After en bloc tumor resection with the help of osteotomy guide plate,the defects were reconstructed with 3D-printed,custom-made prostheses.Vascularized fibular autografts were put inside the prostheses,and the interval space among them was filled with bioceramics.Results All the 5 cases were performed surgical planning before the surgery with prosthesis and guide plate were designed at the same time.After verification of the finite element analysis SLM (2 cases) and the EBM (3 cases) were used to process prosthesis,and were designed into porous sharp with 210.98±66.16 mm in length and 26 901.76±12 903.96 mm3 in volume.Then the prosthesis would be cleaned and sterilized.All 5 operation were proceeded according to the plan of preoperative.The intra-operative guide plate were installed on the bone surface stably.The bone cutting was guided according to the plan of preoperative.By intra-operative frozen pathological examination,there were no malignant tissues in near and far marrow cavity.Unfolded fibular flap with 168.75±49.07 mm in length and porous tricalcium phosphate particle composite implants with 10±4.08 g were used in 4 cases and bone cement was used in 1 cases of metastatic tumor.The average operation time was 261±85 min and average blood loss was 540±182 ml.After a mean follow-up time of 6.4 months (1-15 months),all 5 cases survived with no local recurrence and pulmonary metastasis tumor.2 cases with vascular pedicle fibular transplant confirmed the survival of fibula via bone scan 3 months after operation.All cases were no infection,fractures,prosthesis loosening,except broken screw in 1 case.The Musculoskeletal Tumor Society (MSTS) 93 score was 17-26.Conclusion Long segment tubular titanium alloy 3D printed prosthesis with vascularized fibular autograft and bioceramics could reconstruct the segmental defects caused by tumor resection.

OBJECTIVETo evaluate the efficacy of cyclosporin A (CyA) therapy in 83 children with nephrotic syndrome of different pathological types.

METHODSEighty-three children enrolled in this study were all hospitalized children with idiopathic nephrotic syndrome, aged 3 to 14 yrs (average 8.3 yrs) and included 52 males and 31 females. There were 35 cases with steroid-dependent, 17 with steroid resistant and 26 with frequent relapses. CyA was given to each patient with dosage of 5 mg/(kg.d) during the corticosteroid was diminished. The renwal biopsy was performed in all patients before the administration of CyA. The duration of CyA therapy lasted for about 3 to 6 months. The plasma concentration of CyA was monitored.

RESULTSEighty-three children with nephrotic syndrome of different pathological types were treated with CyA, including 42 cases of minimal change nephrotic syndrome (MCNS), 31 cases of mesangioproliferative glomerulonephritis (MsPGN), 5 cases of membranoproliferative glomerulonephritis (MPGN) and 4 cases of focal segmental glomerular sclerosis (FSGS). All the 83 patients tolerated well to the CyA treatment. Forty-five cases got complete remission, 23 partial remission, 15 cases no change after one month treatment with CyA in the hospital. The overall response rate was 82%. Patients with different renal pathological types showed different responses. Among them, MCNS and MsPGN exhibited the best response rates of 86% and 84%, respectively; MPGN cases showed a lower response rate and FSGS cases showed the lowest rate. The response time was 7 to 45 days. The blood concentration of CyA was monitored for 1 week and 2 weeks after the drug was given. The effective drug concentration was maintained at 100 to 200 microg/L, and the course lasted for 3 to 6 months. During the follow-up of 83 cases, in 17 of 68 cases the disease relapsed when therapy was tapered or discontinued. The relapse rate was 25%. The results indicated that CyA would be effective to the relapsed cases. The serum creatinine increased temporarily after administration of CyA in 5 cases, N-acetyl-beta-D-glucosaminidase (NAG) in 8 cases and eventually reached the normal range after the adjustment of dosage. The side effects included anorexia, nausea, vomiting and so on.

CONCLUSIONCyA is one of the effective substitutes for the treatment of nephrotic syndrome, especially for the cases with MCNS and MsPGN. And CyA could control refractory nephrotic syndrome effectively and rapidly. The clinical effect was related to the blood concentration of CyA and pathological types.

Adolescent ; Anorexia ; chemically induced ; Child ; Child, Preschool ; Cyclosporine ; adverse effects ; therapeutic use ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Male ; Nausea ; chemically induced ; Nephrotic Syndrome ; drug therapy ; pathology ; Time Factors ; Treatment Outcome ; Vomiting ; chemically induced

AIMTo prepare the sustained-release nitrendipine microspheres with a solid dispersed structure in liquid system.

METHODSThe sustained-release nitrendipine microspheres with a solid dispersed structure was prepared in liquid system by combining spherical crystallization technique and solvent deposition method in one step. The resultant microspheres were evaluated for the recovery, micromeritc properties, incorporation efficiency. The factors of effect on the formation and the release rate of microspheres were also investigated.

RESULTSThe recovery of microspheres (280-900 microns) was more than 70% and the bulk density was around 0.7 kg.L-1. The incorporation efficiency always exceeded 95%. The formation of microspheres was mainly affected by the amount of bridging liquid and the emulsifying agents in poor solvent. The release rate of nitrendipine from the microspheres could be controlled as desired by adjusting the ratio of talc to Eudragit RS PO in the formulation.

CONCLUSIONThe presented method was suitable for preparing sustained-release microspheres of a water insoluble drug.

Delayed-Action Preparations ; Drug Carriers ; Microspheres ; Nitrendipine ; administration & dosage ; Particle Size ; Technology, Pharmaceutical ; methods

OBJECTIVETo observe the influence of Cx26/Cx32 gap junction channel on the antineoplastic effect of etoposide in Hela cervical cancer cells.

METHODSFluorescence trace was used to assay the gap junction intercellular communication mediated by Cx26/Cx32 in Hela cells and its functional modulation by the pharmacological agents (oleamide, retinoid acid). A standard colony-forming assay was applied to determine the cell growth-inhibiting effect of etoposide in Hela cells with functional modulation of the gap junction. Hoechst 33258 staining was used to assess the changes in etoposide-induced apoptosis of Hela cells with altered gap junction functions.

RESULTSOleamide markedly decreased while retinoid acid obviously increased the gap junction function in Hela cells. Standard colony-forming assay showed that etoposide produced a lowered antiproliferative effect in Hela cells with reduced gap junction and an increased antiproliferative effect in cells with enhanced gap junction function. In cells with a reduced gap junction function, etoposide induced a lowered apoptosis rate, which increased obviously in cells with an enhanced gap junction function.

CONCLUSIONThe antineoplastic effect of etoposide is reduced in Hela cells with a decreased gap junction intercellular communication mediated by Cx26/Cx32 and is enhanced in cells with an increased gap junction intercellular communication.

Antineoplastic Agents, Phytogenic ; pharmacology ; Connexin 26 ; Connexins ; genetics ; metabolism ; physiology ; Etoposide ; pharmacology ; Gap Junctions ; physiology ; HeLa Cells ; Humans ; Transfection