Objective To investigate the in vitro susceptibility of 16 strains of Exophiala dermatitidis to 6 commonly used antifungal agents. Methods The Glinical and Laboratory Standards Institute (CLSI)M27-A2 protocol was carried out to determine the MIGs of terbinafine (TRB), itraconazole (ITC), amphotericin B (AMB), fluconazole (FLC), voriconazole (VRC), and caspofungin (GAS) to 16 strains of E. dermatitidis, and E-test was performed to determine those of VRG, ITC and AMB. Besides, the minimal fungicidal concentrations (MFGs) of the above antifungal agents to the 16 strains of E. dermatitidis were further assessed.The activity of TRB in combination with ITC and VRG against E. dermatitidis was also estimated. Results The MIC ranges of TRB, VRC, ITC, AMB, FLC, and CAS were 0.125 - 0.25 mg/L, 0.25 - 0.5 mg/L, 2.0 mg/L,2.0 mg/L, 16 - 32 mg/L and 16 - 64 mg/L respectively as shown by M27-A2 microdilution assay, while the MIC ranges of VRG, ITG and AMB, as determined by E-test, were 0.032 - 0.094 mg/L, 0.047 - 0.5 mg/L and 0.125 - 3.0 mg/L, respectively. The MFC ranges of TRB, VRC, ITG, AMB and FLG were 0.125 - 0.5 mg/L,0.25 - 0.5 mg/L, 2.0 - 4.0 mg/L, 2.0 - 4.0 mg/L and 16 - 64 mg/L, respectively. No synergism in the acitivity against E. dermatitidis was observed for the combination of TBR with ITC or VRC. Conclusion E. dermatitidis is susceptible to TRB, ITC, AMB, and VRC, but less sensitive to both FLC and GAS.

Objective To investigate the molecular mechanisms of cross-resistance to azoles in a clinical isolate of Aspergillus fumigatus. Methods A. fumigatus was isolated from a patient with invasive aspergillosis.Clinical Laboratory Standard Institute M38-A2 broth microdilution method and E-test method were used to determine the minimum inhibitory concentrations (MICs) or minimum effective concentration (MEC) of itraconazole, voriconazole, amphotericin B, posaconazole and caspofungin for the A. fumigatus isolate. DNA was extracted from the isolate and subjected to the amplification of cyp51A gene encoding the target enzyme of azole antifungal agents followed by sequence analysis. Results The broth microdilution test showed that the MEC of caspofungin was 0.5 mg/L, and MICs of itraconazole, voriconazole and amphotericin B were ≥ 16 mg/L,8 mg/L and 1 mg/L, respectively, for this isolate; while E-test assay revealed that the MICs of caspofungin,itraconazole, voriconazole, amphotericin B and posaconazole were 0.047 mg/L, ≥32 mg/L,≥32 mg/L, 12 mg/L and ≥32 mg/L, respectively. Sequence analysis showed an insertion of a 34-bp tandem sequence in the promoter region of the cyp51A gene as well as a T364A point mutation causing the substitution of leucine 98 (L98H). In addition, there were some other mutations in the cyp51A gene of this isolate, such as A137T,G585A, C814A, G836C, T991C and A1350G, which could result in corresponding amino acid substitutions.Conclusions An A. fumigatus strain with cross-resistance to azole antifungal agents is isolated. There is an insertion of a 34-bp tandem sequence into the promoter region as well as a T364A point mutation in the cyp51A gene, which contribute to the cross resistance to azole antifungal agents including itraconazole, voriconazole,and posaconazole. In addition, other mutations causing amino acid substitutions have also been detected in the cyp51 A gene of this isolate.

Two patients were admitted to the hospital for 2-month history of pruritic eruptions on the forehead and 2-week history of pruritie eruptions on the leg, respectively. Both patients had a history of pet contact. Topical application of glucocorticoids did not work well. Dermatological examination revealed a patch measuring 5 cm ×6 cm on the forehead of one patient and a patch measuring 2 cm × 3 cm on the leg of the other patient. Both patches were surrounded by red papules and scaling. Microscopic examination of skin scales revealed hyphae and chain-like spores, and culture of skin scales grew Microsporum gyeum. Both the isolates of Microsporum gyeum were sensitive to ketoconazole, miconazole, bifonazole, terbinafine, and voriconazole. Both patients were healed after treatment with oral terbinafine and topical ciclopirox olamine.

OBJECTIVETo study the effectiveness of pie-crusting technique in improving the stiff knee.

METHODSFrom February 2012 to December 2013, 13 patients with stiff knee were reviewed retrospectively. There were 6 males and 7 females, ranging in age from 39 to 70 years old (averaged, 55.6 years old). Of the 13 cases, 8 patients had stiffness following fracture (comminuted tibial plateau fracture in 4, femoral supracondylar fracture in 3 and patellar fracture in 1), 5 patients had TKA-related stiffness.

RESULTSA follow-up lasted 8 to 12 months (mean 10 months)in 13 cases. The mean maximum flexion increased from (37 ± 6)° preoperatively to (52 ± 7)° after arthrolysis, and (108 ± 7)° after pie-crusting. At the final follow-up, mean maximum flexion was (105 ± 6)°. According to Judet evaluation system, 10 patients got an excellent result and 3 good. No major complications, such as extensor lag, skin necrosis, deep infection, dislocation of the patella or recurrent stiffness were found.

CONCLUSIONThe percutaneous technique of pie-crusting is a simple, minimally invasive and effective treatment for knee stiffness.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Joint Diseases ; physiopathology ; surgery ; Knee Joint ; physiopathology ; surgery ; Male ; Middle Aged ; Range of Motion, Articular ; Treatment Outcome

OBJECTIVETo explore the clinical effects of Dynesys system combined with posterior lumbar interbody fusion (PLIF) in treating multiple lumbar degenerative disease.

METHODSThe clinical data of 46 patients with multiple lumbar degenerative diseases treated by Dynesys system combined with PLIF from September 2010 to May 2013 were retrospectively analyzed. There were 17 males and 29 females, aged from 38 to 68 years old with an average of (56.38±11.63) years. Operation section was in L2-L5 of 16 patients (6 with fusion of L4,5 and 10 with fusion of L4,5,L5S1) and in L3-S1 of 30 patients (11 with fusion of L5S1 and 19 with fusion of L4,5,L5S1). Patients were followed up for three times: postoperative 3 months, 1 year and final follow-up. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to assess clinical symptoms preoperatively and postoperatively. All patients underwent flexion/extension radiographs examinations before surgery and at final follow-up. Range of motion (ROM) and disc height index (DHI) were recorded.

RESULTSAll patients were followed up from 16 to 48 months with the mean of (23.23±7.34) months. At third follow-up after operation, ODI and VAS of lumbago and leg pain were significant improved than that of preoperative (P<0.01). DHI of fusion segment was significantly increased than that of preoperative (P<0.05). There was no significant difference in adjacent non-fusion segment between preoperative and postoperative (P>0.05). Postoperative ROM of fusion and non-fusion segments were obviously decreased than that of preoperative. There was no significant difference in ROM of upper adjacent non-fusion segment between 3 months and 1 year after operation (P>0.05), but at final follow-up, the ROM was increased (P<0.05).

CONCLUSIONThe preliminary clinical results of the Dynesys system combined with PLIF in the treatment of multiple lumbar degenerative diseases are satisfactory. It can be determined in fusion or non-fusion according to the individual needs and can reserve the some intervertebral motion, prevent the early degeneration of adjacent segments. However, its long-term clinical efficacy should be verified with long time.

Humans ; Lumbar Vertebrae ; surgery ; Range of Motion, Articular ; Retrospective Studies ; Spinal Diseases ; physiopathology ; surgery ; Spinal Fusion ; methods ; Visual Analog Scale

Objective To assess the effect of hemoperfusion (HP) and hemodiafiltration (HDF) on elimination of para?thyroid hormone (PTH) from plasma in long-term hemodialysis patients.Methods MEDLINE (1966—2013.8), Embase (1974—2013.8), Chinese Wanfang database (1996—2013.8),CNKI(1979—2013.8)and the clinical control test database of Cochrane Library were searched. Published reports, unpublished studies and abstract from conference were retrieved manu?ally, all of which include studies of effect of PTH elimination through hemoperfusion and hemodiafiltration. Quality assess?ment and data mining were conducted by two independent investigators who performed meta-analysis using RevMan 5.2. Re?sults A total of 12 reports (400 patients) met the inclusion criteria and were included in this study. The meta-analysis showed that the elimination rate of PTH in long term hemodialysis patients was similar between using hemoperfusion and us?ing hemodiafiltration(WMD=-0.34,95%CI:-12.66-11.98,P=0.96). What’s more the elimination rate ofβ2-MG were also similar(WMD=-2.92,95%CI:-16.64-10.8,P=0.68)between those two treatments. However,The remission rate of pruritus was higher in patients using HP group than in HDF group(RR=1.33,95%CI:1.08-1.62,P=0.006). Conclusion HP and HDF can effectively clear PTH in chronic hemodialysis patients, but there was no statistically different between the two treat?ment methods.

Objective To study the effect and mechanism of increase in radio sensitivity of kidney cancer cells(GRC-1) induced by ?-elemenen in vitro. Methods GRC-1 cells were divided into 3 groups, blank group (added with 2 mL culture medium), emulsion group (added with 2 mL blank emulsion culture medium) and drug group (added with 2 mL 50 mg?L -1 ?-elemenen culture medium). After been cultivated for 24 hours, the cells were irradiated using 6MeV X-linear accelerator in different doses at the rate of 400cGy per minute. Number of cell clones was counted, and radiation-survival curve of GRC-1 cells was drawn. Flow cytometry (FCM) was used to measure cell cycle and apoptosis. Cells of climbing flake were dyed by immunocytochemical method, the gene expression of bcl-2 and PCNA was measured by imaging system. Results The cell cycle showed that the G 2M blocking caused by 50 mg?L -1 ?-elemenen was enhanced with time increase. It reached peak at 24 hours. FCM showed that the level of apoptosis increased with increase in drug dose and action time. The gene expression of bcl-2 was decreased by 20% in drug group than that in blank group, but there was no expression of PCNA in the two groups. Conclusion The radiosensitivity of GRC-1 cells can be enhanced by ?-elemenen. The mechanism of effect may be associated with the cell cycle blocking, inducing cell apoptosis and down-regulating expression of bcl-2 gene.

Objective To evaluate the efficacy and safety of cinacalcet on secondary hyperparathyroidism (SHPT) in patients with end-stage renal disease (ESRD). Methods Patients with ESRD and SHPT for the treatment with calcimimetic agents were included in this study. MEDLINE (1996.1-2014.9), OVID (1963.1-2014.9), Chinese Wanfang database (1996.1-2014.9), CNKI (1996.1-2014.9) and the clinical control test database of Cochrane Library were searched . Related literature, including published or unpublished papers, and meeting procedding were hand-searched. Quality assessment and data extraction were conducted by two independent investigators. Meta-analysis was conducted by RevMan 5.2. Results Nineteen randomized controlled trials involving 7 702 patients were included. The meta-analysis showed that compared with conventional therapy,cinacalcet can significantly decrease serum parathyroid hormone in dialysis patients [WMD=-301.54 μg/L, 95%CI:(-344.38)-(-258.7)μg/L, P<0.05], decrease serum level of calcium [WMD=-8.3 mg/L, 95%CI:(-9.1)-(-7.4)mg/L, P<0.05], and decrease serum level of phosphorus [WMD=-3.4 mg/L, 95%CI:(-4.6)-(-2.3) mg/L, P<0.05]. The total incidence of adverse events was similar (RR=1.03, 95%CI:0.98-1.09, P>0.05). Cinacalcet increased nausea (RR =2.05, 95%CI :1.53-2.75, P<0.05), vomiting (RR =2.00, 95%CI:1.78-2.23, P<0.05), diarrhea (RR=1.15, 95%CI:1.03-1.30, P<0.05), and asymptomatic hypocalcaemia (RR=7.60, 95%CI:5.61-10.30, P<0.05), but they were usually transient, and mild to moderate in severity. The mortality was similar (RR=0.97, 95%CI:0.89-1.05, P>0.05). Conclusion Results confirm that cinacalcet suppresses parathyroid hormone and decreases calcium and phosphorus in secondary hyperparathyroidism patients receiving dialysis. Cinacalcet increases risks of nausea, vomiting, diarrhea and hypocalcaemia,without increasing mortality.

Objective To investigate the clinical effect of treatment with local skin flap after primary surgical resection of non melanoma skin cancer.Methods A total of 176 patients with head and facial skin cancer who were admitted into our hospital from September 2008 to September 2015 were divided into three groups according to different repair plans.Namely,the suture group (41 cases),the local skin flap group (81 cases) and the skin graft group (54 cases).The repair effect of the three groups were compared after the operation.Results The good rate was 68.39%(28/41) in the suture group,98.77%(80/81) in the local skin flap group,and 83.33%(45/54) in the skin graft group,and it was significantly higher than any of the other two groups with statistically significant difference(P<0.05).The satisfaction rate of the local skin flap group was significantly better than that of the suture group,and the difference was statistically significant(P<0.05).But there was no significant difference in the satisfaction rate when compared with the skin graft group(P>0.05).The 3 groups were followed up for a period of 1 year,as a result,there was no recurrence and distant metastasis.Conclusion For patients with head and facial non melanoma skin cancer,repaired with local skin flap healing treatment after primary surgical resection can not only get high healing rate but also significant improvement of patient satisfaction rate.In addition,it can lower the rate of recurrence and distant metastasis after operation.

Model-informed drug development (MIDD) in the development of pediatric drugs is drawing more and more attention due to the insufficiency of subjects, lack of research on ontogeny, and the limitation of ethic. The core of MIDD used for dose selection includes the population pharmacokinetic (PopPK) model and physiologically based pharmacokinetic (PBPK) model, as well as model-based simulation and prediction. PBPK model has the advantage of predicting the optimal pediatric dose before the clinical trials and has the ability of extrapolation from adult model to pediatric model. PopPK model characterizes the pediatric PK feature based on the analysis of clinical data and can be used to explore the significant covariates, which is a power tool for individualized medicine in children. With their own advantages and disadvantages, PBPK and PopPK model should be jointly used in the pediatric drug development to refine the dose regimen for children at different ages. In this study, the pediatric drug development of rivaroxaban was taken as an example to introduce the combined application of PBPK model and PopPK model in the design and validation of pediatric dose regimen in Phase Ⅰ, Ⅱ and Ⅲ trials, which may provide reference to MIDD in other pediatric drug development.