The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

PURPOSE: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. METHODS: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. RESULTS: The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. CONCLUSIONS: Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.
Biomarkers ; Biopsy ; Cohort Studies ; Diagnosis ; Early Diagnosis ; Herpes Simplex ; Humans ; Microarray Analysis ; MicroRNAs* ; Passive Cutaneous Anaphylaxis ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia ; Prostatic Neoplasms* ; Sensitivity and Specificity ; Simplexvirus ; Urologic Diseases

Objective To explore the application value and clinical efficacy of the transanal specimen extraction via prolapsing approach in laparoscopic anterior resection for ultra-low rectal cancer.Methods The clinical data of 27 patients with ultra-low rectal cancer who underwent transanal specimen extraction via prolapsing approach in laparoscopic anterior resection for ultra-low rectal cancer at the Shengjing Hospital of China Medical University from July 2010 to July 2013 were analyzed retrospectively.The average operation time, average volume of intraoperative blood loss, average number of lymph nodes dissection, average distance to resection margin, average length of resected specimen, results of postoperative pathological examination, time for postoperative outoff-bed activity, time to anal exsufflation, gastric tube removal time and postoperative complications were recorded.The visual analogue scale (VSA) pain score and Wexner score for evaluating fecal incontinence were performed at postoperative week 1 and at postoperative month 1, respectively.The anal function was tested at postoperative month 3 and 12.The follow-up including tumor metastasis and recurrence, Wexner score and anorectal anometry was performed by outpatient examination and telephone interview once every 3 months for 2 years after operation and then once every year up to October 2014.Measurement data with normal distribution was presented as-x ± s and average (range).Repeated measures data were analyzed by the repeated measures ANOVA.Results All the patients received successful operations without procedure change or intraoperative accident.The average operating time, average volume of intraoperative blood loss, average number of lymph nodes dissection, average distance to distal resection margin and average length of resected specimen were 140 minutes (range, 115-173 mintues), 27 mL(range, 15-55 mL), 17(range, 14-20), 1.7 cm(range, 1.3-2.2 cm) and 18.5 cm(range, 14.7-22.4 cm), respectively.Postoperative TNM stages: T2N0M0 was detected in 19 patients, T2N1M0 in 3 patients,T3N0M0 in 4 patients and T3N1M0 in 1 patients.The time for postoperative out-off-bed activity and time to anal exsufflation were 8.8 hours (range, 7.0-13.0 hours) and 51 hours (range, 30-79 hours).Twenty-seven patients had the gastric tube removal after operation with fluid diet intake at postoperative hour 24 and semi-fluid diet intake at postoperative hour 48.One male patient was complicated with urinary retention at postoperative day 3 and 1 with anastomotic leakage at postoperative day 9, they were cured by symptomatic treatment.VSA pain scores in all patients from 1 day to 6 days postoperatively were 5.6, 4.6, 4.0, 3.2, 2.2 and 1.3.The average duration of hospital stay was 11.1 days (range, 7.0-19.0 days).Patients had good healing of abdominal incision at postoperative week 2.All the patients were followed up for a average time of 24.8 months (range, 15.0-32.0 months) without tumor metastasis and recurrence.Wexner score was 2.6 (range, 1.0-4.0) at postoperative month 1.The results of anorectal anometry: maximum anorectal resting pressure (MARP) and maximum anorectal systolic pressure were (267 ±23)mmHg (1 mmHg =0.133 kPa) and (305 ± 23)mmHg before operation, (266 ± 40)mmHg and (300 ± 38)mmHg at postoperative month 3, (267 ± 33)mmHg and (315 ± 30)mmHg at postoperative month 12, respectively, with no significant difference in the changing trend between pre-and post-operation (F =0.510, 1.390, P ＞ 0.05).Anorectal resting vector volume and anorectal systolic vector volume were (45 594 ± 1 981) cm (mmHg) 2 and (98 480 ± 8 165) cm (mmHg) 2 before operation, (40 310 ±3 465)cm(mmHg)2 and (78 461 ±6 777)cm(mmHg)2 at postoperative month 3, (40 385 ± 3 379) cm(mmHg) 2 and (82 082 ± 10 383) cm(mmHg) 2 at postoperative month 12, respectively, with significant differences in the changing trend between pre-and post-operation (F =26.845, 48.090, P ＜ 0.05).Conclusion Transanal specimen extraction via prolapsing approach in laparoscopic anterior resection for ultra-low rectal cancer is safe, aesthetic and minimally invasive compared with the traditional laparoscopic surgery, with the advantages of radical cure of tumor and protection of anal function.

Objective:To investigate the clinical security and feasibility of neoadjuvant chemotherapy with imatinib following lap-aroscopy-guided intersphincteric resection for patients with gastrointestinal stromal tumor of the low rectum (GSTLR). Methods:Clini-cal data of nine patients with GSTLR who were admitted to the Shengjing Hospital between January 2007 and January 2011 were re-viewed. These patients were treated with neoadjuvant imatinib chemotherapy after laparoscopic intersphincteric resection. Results:Pri-or to neoadjuvant chemotherapy, the tumor diameter ranged between from 5 cm to 9 cm (median=7.0 cm). After imatinib chemothera-py, the tumor diameter decreased to 2-4.5 cm (median=3.5 cm, P<0.001). Laparoscopic surgery through intersphincteric resection was performed after imatinib treatment for 3-24 months (median=7 months). All patients received a protective stoma, which was closed 3 months after the surgery. The Wexner scale scores ranged from 1 and 4 (median=2) prior to neoadjuvant imatinib chemotherapy and changed to 1-5 (median=2) after the chemotherapy (P=0.397). After stomal closure operation, the scores significantly increased to 4-9 (median=7, P<0.001) but were not statistically significantly different from those before the therapy. One year after laparoscopic surgery, the Wexner scale scores ranged from 1 to 5 (median=2, P=0.842). Six patients were treated with imatinib for 24 and 30 months after lap-aroscopic surgery. Recurrence in pelvis occurred in only one patient, who ceased imatinib administration at the 30th month after the sur-gery. Conclusions: Laparoscopic surgery through intersphincteric resection was secure and feasible and thus could be used for treat-ment of GSTLR.

Objective To examine the expression of protein kinase signaling cascade protein kinase B (Akt)-which plays an im-portant role in a number of key biological functions in cellular processes after spinal cord injury (SCI) in rats ,and its effects on SCI induced motor function defects ,and to provide the molecular mechanism for repairing SCI .Methods SCI was produced by extra-dural contusion using modified Allen′s stall with damage energy .The rats were divided into three groups :sham-operated group (Sham) ,interference group (Int) ,and control group (Con) .Using immunostaining studies ,Western blot analyses and real-time qualitative RT-PCR analyses ,we detected the changes of Akt expression at the protein and mRNA level in spinal cord tissues at 1 , 7 ,and 14 d after surgery ,and evaluated the presence and extent of neurological impairment after SCI by the BBB locomotor rating scale .Results The sham operated groups exhibited low expression of the Akt signaling at the protein and mRNA level ,and the ex-pressions increased following SCI .Compared to the animals in the sham operated groups ,prominently elevated level of Akt signaling was detected in the injured spinal cords of SCI group .LY294002 ,an inhibitor of phosphatidylinositol 3-kinase (PI3K) that initiates Akt phosphorylation ,prominently inhibited the expression of Akt produced by SCI and the spontaneous recovery of motor function after SCI .Conclusion Activated protein kinase signaling cascade Akt might be the important intervention aspects of involving in neuroprotective and repair process after SCI .

Objective To investigate the effects of Panax notoginseng saponins(PNS) on penile erection in rats with diabetes-as-sociated erectile dysfunction (ED) .Methods Ninety male Sprague-Dawley rats were established diabetic rats by injecting streptozo-tocin(STZ) ,and observing erectile phenomenon by injecting apomorphine .After 4 weeks of PNS treatment (low-dose ,medium-dose , high-dose group) ,erectile function in each group was assessed by intracavernous pressure (ICP) and mean arterial pressure(MAP) measurement .The level of nitric oxide(NO)and cyclic guanosine monophosphate(cGMP)in cavernous tissue were detected .Immu-nohistochemical staining and TUNEL were performed for detecting endothelial nitric oxide synthase (eNOS) and apoptosis ,respec-tively .Results ICP and ICP/MAP ratio were significantly increased in medium-dose and high-dose PNS treated groups compared with the diabetic untreated group(P<0 .05) .Compared with the diabetic untreated group ,the expression of eNOS and the levels of NO and cGMP were increased in medium-dose and high-dose PNS treated groups(P<0 .05) .The apoptosis ratecorpus of caverno-sum in 3 PNS treatment groups significantly decreased than the diabetic untreated group (P<0 .05) .Conclusion PNS can recovery the endothelial cell function in corpus cavernosum by adjusting the NO/cGMP pathway and controlling the accumulation of AGEs , and may be used for improving in diabetic ED rats .

Objective To analysis influence of perioperative function rehabilitation training combined with drug treatment on uri-nary incontinence recovery after laparoscopic radical prostatectomy .Methods The clinical data of 31 cases of incontinence after lap-aroscopic radical prostatectomy were retrospectively analyzed .Early functional rehabilitation training ,drugs and mental guidance were applied to the patients .Results 31 out of 91 cases who receiving the laparoscopic radical prostatectomy immediately suffered from urinary incontinence when removing catheter .9 cases rehabilitated after 7 days ,12 cases rehabilitated after 1 months ,and 29 cases rehabilitated after 6 months .Conclusion Urinary incontinence occurs more in the early laparoscopic radical surgery ,perioper-ative function rehabilitation training combined with drug treatment could effectively improve the function of patients with urinary continence .

Objective To evaluate the value of cough test in the tension-free vaginal tape (TVT)procedure.Methods A cohort of 85 women with stress urinary incontinence underwent the TVT procedure with cough test (n =41) or without cough test (n =44).Patients in cough test group were performed according to the Ulmsten’s method strictly,with the stress of tape adjusted in light of cough test; whereas in other 44 operations,the tape was placed on the urethral tract without stress,and no cough test was performed.The urine catheter was removed after 48 hours postoperatively and follow-up evaluation was carried out at 12 month postoperatively.Results TVT procedure was carried out successfully in all patients by a single experienced surgeon.Four cases of urinary retention and 5 cases of voiding difficulty were observed in the cough test group.However,urinary retention or voiding difficulty was not detected in the nun-cough test group.Based on the twelve-month follow-up results,the cure rate was 92.6％ (38/41) in the cough test group and 93.1％ (41/44) in the non-cough test group.Flow-pressure study indicated that 11 cases in cough test group were in the obstruction zone,while only 3 cases in the obstruction zone were detected in the non-cough test group.Conclusions TVT is a safe as well as effective minimally invasive surgical procedure to treat female stress urinary incontinence.However,Adjusting stress of tape in accordance with cough test during the TVT may potentially increase the incidence of urinary dysfunction postoperatively.Therefore,no convincing evidence was gained to support the efficacy of cough test during TVT in terms of preventing postoperative voiding dysfunction.

A leukemoid reaction is defined as reactive leukocytosis exceeding 50,000/mm3, with a significant increase in early neutrophil precursors, and can be a paraneoplastic manifestation of various malignant tumors. A 71-year-old male patient complained of decreased appetite, fatigue, and abdominal fullness. He had a palpable, firm liver, and laboratory investigations suggested leukemoid reaction. Liver dynamic computed tomography revealed a hypervascular mass, and an ultrasound-guided fine-needle aspiration of the mass confirmed hepatocellular carcinoma (HCC) with a sarcomatoid component. The leukocyte count of the patient had increased to 147,800/mm3, and he died 10 days after admission. This is a rare case of leukemoid reaction in a patient with sarcomatous HCC.
Aged ; Biopsy, Fine-Needle ; Carcinoma, Hepatocellular/*pathology ; Humans ; Leukemoid Reaction/*diagnosis ; Leukocyte Count ; Liver Neoplasms/*pathology ; Male ; Tomography, X-Ray Computed

Capsid ; Cell Line ; Dependovirus ; genetics ; Genetic Therapy ; Genetic Vectors ; genetics ; Hepatitis B virus ; genetics ; Humans ; Liver Diseases ; therapy ; Plasmids ; Recombination, Genetic ; Transfection