OBJECTIVE: To evaluate the relative factors influencing olfactory dysfunction in patients with chronic rhinosinusitis (CRS). METHOD: Visual analogue scale (VAS) was applied to measure the severity of olfactory dysfunction of 270 patients with CRS. Patients were divided into two groups, one was that the quality of life (QOL) of patients was affected by olfactory dysfunction (VAS > 5), the other was that without QOL affected by olfactory dysfunction (VAS ≤ 5). The association between age, gender, nasal polyps, allergic rhinitis, smoking history, early nasal surgery history and other clinical factors, and serum total IgE level, peripheral blood eosinophil count, peripheral blood mononuclear cell count and olfactory dysfunction was analyzed. RESULT: The number of patients with nasal polyps, allergic rhinitis, previous nasal surgeries, the level of serum total IgE, and the severity of edema were significantly increased in patients with impaired QOL associated with olfactory dysfunction (P < 0.05). Sex distribution, age, smoking history, deviation of nasal septum, eosinophil and mononuclear cell count did no statistically differ between the groups with and without impaired QOL associated with olfactory dysfunctions (P > 0.05). Serum total IgE increased (OR = 1.003, P < 0.01) and severe edema (OR = 2.483, P < 0.01) were the risk factors for the impairment of olfactory function, more notably for edema; whereas previous nasal surgeries was a protective factor (OR = 0.408, P < 0.01). CONCLUSION Sever edema and increased serum total IgE are risk factors, whereas previous nasal surgeries history is a protective factor for the olfactory dysfunction.
Chronic Disease ; Female ; Humans ; Leukocytes, Mononuclear ; Male ; Nasal Polyps ; Olfaction Disorders ; etiology ; Quality of Life ; Rhinitis ; complications ; immunology ; Rhinitis, Allergic ; complications ; immunology ; Risk Factors ; Sinusitis ; complications ; immunology ; Smell ; Smoking ; adverse effects

BACKGROUND: Previous studies have demonstrated that berberine represses multiple tumors and tumor stem cells, but the effect of berberine on lung cancer stem cells (LCSCs) remains unclear. OBJECTIVE: To explore the effect of berberine on the proliferation and apoptosis of LCSCs and the possible mechanism. METHODS: CD133+ LCSCs were separated from A549 cells by immunomagnetic beads. The effects of different concentrations (0, 2.5, 5, 10, 20, 40 mg/L) of berberine on the proliferation and apoptosis of LCSCs were determined by MTT and flow cytometry analysis, respectively. In order to further affirm the effect of berberine on the proliferation and apoptosis of LCSCs, the expression levels of Ki67, Bax and Bcl-2 protein were detected by western blot. In addition, to investigate the potential mechanism by which berberine exerts regulatory effects on LCSCs, the expression levels of Hedgehog signaling pathway-associated proteins (PTCH1, SHH, Gli-1 and SMO) were determined. RESULTS AND CONCLUSION: After magnetic cell sorting, the content of the CD133+ fraction was enriched up to 84.13%. MTT and flow cytometry assays showed that berberine inhibited proliferation and promoted apoptosis of LCSCs in a concentration-dependent manner. Western blot analysis showed that the expression levels of Ki67, Bcl-2, PTCH1, SHH, Gli-1 and SMO proteins of LCSCs cultured in the medium with 20 mg/L berberine were dramatically decreased compared to the control, while the expression level of Bax protein was markedly increased compared to the control. These findings suggest that berberine may inhibit proliferation and promote apoptosis for LCSCs through the Hedgehog signaling pathway.BACKGROUND: Previous studies have demonstrated that berberine represses multiple tumors and tumor stem cells, but the effect of berberine on lung cancer stem cells (LCSCs) remains unclear. OBJECTIVE: To explore the effect of berberine on the proliferation and apoptosis of LCSCs and the possible mechanism. METHODS: CD133+ LCSCs were separated from A549 cells by immunomagnetic beads. The effects of different concentrations (0, 2.5, 5, 10, 20, 40 mg/L) of berberine on the proliferation and apoptosis of LCSCs were determined by MTT and flow cytometry analysis, respectively. In order to further affirm the effect of berberine on the proliferation and apoptosis of LCSCs, the expression levels of Ki67, Bax and Bcl-2 protein were detected by western blot. In addition, to investigate the potential mechanism by which berberine exerts regulatory effects on LCSCs, the expression levels of Hedgehog signaling pathway-associated proteins (PTCH1, SHH, Gli-1 and SMO) were determined. RESULTS AND CONCLUSION: After magnetic cell sorting, the content of the CD133+ fraction was enriched up to 84.13%. MTT and flow cytometry assays showed that berberine inhibited proliferation and promoted apoptosis of LCSCs in a concentration-dependent manner. Western blot analysis showed that the expression levels of Ki67, Bcl-2, PTCH1, SHH, Gli-1 and SMO proteins of LCSCs cultured in the medium with 20 mg/L berberine were dramatically decreased compared to the control, while the expression level of Bax protein was markedly increased compared to the control. These findings suggest that berberine may inhibit proliferation and promote apoptosis for LCSCs through the Hedgehog signaling pathway.

Objective To evaluate the effects of various resection and reconstruction method on pain relief and function restoration for periacetabular metastatic destruction in different grade. Methods This study involved 20 patients, 11 males and 9 females, with the average age of 52 years(range, 43-82 years). The original tumor consisted of 5 renal cell carcinoma, 4 breast carcinoma, 3 lung carcinoma, 2 thyroid carcinoma, 1 prostate carcinoma, 1 rectum carcinoma and 4 unknown primary cancers. A solitary periacetabular metastatic lesion was demonstrated in 14 patients and multi-metastases were seen in 6 patients, and accompanying periacetabular pathologic fractures in 4 patients. As to the Harrington grading system for the periacetabular metastatic destruction, there were 8 grade Ⅰ, 5 grade Ⅱ, and 7 grade Ⅲ. And according to grade Ⅰ, curettage and cement packing (5 cases) as well as stability reconstruction in iliac and acetabulum (3 cases) were performed; grade Ⅱ, curettage, cement packing and total hip arthroplasty with reinforcement ring was performed; grade Ⅲ, en bolc resection of acetabular lesion and modular prosthesis reconstruction was performed. The average score was 5.4(ranged from 3 to 9) according to Tomita scoring system. The pain relief and functional recovery were investigated from the regular follow up postoperatively. Results All patients showed the improvement in pain relief and mobility postoperatively. No prosthetic dislocation, deep infection and leg length discrepancy occurred. The prosthesis or internal fixation loosening happened in 5 of 15 patients at different stage. The median survival time of all patients was 16.5 months (range from 4.2 to 63 months). 2 patients survived over 5 years, 3 over 2 years, 6 over 1 year, 6 over 6 months, and 3 less than 6 months. According to the Enneking functional scoring system, the patients were rated as excellent in 10 cases, good in 8, fair 1 and poor 1 at the 3rd month postoperatively, and for the 7 cases with grade Ⅲ, excellent 2, good 2, and poor 2. The functions of 11 patients survived one year after surgery were excellent in 3, good 4, fair 2 and poor 2. Conclusion The favorable resections and reconstructions for periacetabular metastatic destruction could lead to remarked improvement in pain relief, functional recovery and quality of life.

[Objective]A new limited contact femoral supracondylar interlocking intramedullary nail(LCFSIIN) was made,which was part of a new custom-made hemi-knee joint,to improve the results of childrens' limb salvage.[Method]A new LCFSIIN was performed and the stress of bolts,intramedullary nails and bone were analyzed by finite dement analysis(FEA) while the bolts were implanted in different angulafions-0?,15?,30?,45?and 60?.[Result]The results of FEA show that the stress of bolts,bone and nails with 15? insertion angles of bolt was the tiniest and well distributed.Stress of bone with 0? insertion angles was more obvious than that with 15?,30?and 45?.The more the angles,the stress of proximal bolt became more obvious and the stress of distal bolt decreasing.[Conclusion]This new LCFSIIN can reduce destruction of biological environment of bone and is easy in use in limb salvage surgery of allograft.

Objective To investigate the effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on expression of dopamine and adenosine 3'5'-monophosphate-regulated phosphor-protein(DARPP-32) and its phosphorylated proteins in corpus striatum of rat models with levodopa-induced dyskinesia. Methods The rat models of levodopa-induced dyskinesia were set up and were given STN-DBS (stimulation group). The expression of DARPP-32 and its phosphorylated proteins in corpus striatum (damage side and normal side) were detected and compared with sham-stimulation group and sham-operation group. Results There was no significant difference in the expression of DARPP-32 total protein in corpus striatum of rats with dyskinesia among three groups (P>0.05). The expression of Phosphor-Thr34-DARPP-32 protein in the damage side of corpus striatum in stimulation group was significantly lower than that in sham-stimulation group and sham-operation group (P<0.05), while the expression of Phosphor-Thr75-DARPP-32 protein in the damage side of corpus striatum in stimulation group was significantly higher than that in sham-stimulation group and sham-operation group (P<0.05). Conclusion DARPP-32 and its phosphorylated proteins play an important role in the pathogenesis of levodopa-induced dyskinesia.

Objective: To study the effects of propafenone on action potential (AP) of rabbit ventricular myocytes with the tonic block and use-dependent block of transient sodium current (INa-T). Methods: A total of 10 adult New Zealand white rabbits were sacriifced and 10 individual ventricular myocytes were isolated by enzyme digestion method. Microelectrode technologies were used to record AP-related parameters: maximum diastolic potential (MDP), maximum rate of rise of the action potential upstroke (Vmax), action potential amplitude (APA) and action potential duration at 20%, 50% and 90% (APD20, APD50 and APD90).INa-T was measured, I-V curves and peak currents at different frequencies were detected by whole cell patch clamp before and after propafenone perfusion at 10 μmol/L. Results: There was no statistical difference in MDP at before and after propafenone perfusion as (-80 ± 6) mV vs (-82 ± 5) mV,P>0.05. After perfusion, APA was signiifcantly decreased as (95 ± 12) mV vs ( 125 ± 10) mV,P<0.05, the Vmax slowed down as (330 ± 43) V/s vs (420 ± 54) V/s,P<0.05, while APD20, APD50 and APD90 were unchanged as (8 ± 2) ms vs (6 ± 2) ms,P>0.05, (16 ± 3) ms vs (12 ± 3) ms,P>0.05 and (86 ± 14) ms vs (85 ± 12) ms,P>0.05. After propafenone perfusion, I-V curve ofINa-T was shifted upward and the peak current was decreased as (3001 ± 383) pA vs (4193 ± 378) pA, P<0.05. Before perfusion, when stimulated at 0.06 Hz, 1 Hz, 2 Hz, 5 Hz and 10 Hz, there were no signiifcant use-dependent block inINa-T , and no real difference inINa-T between the 10th and 1st pulse,P>0.05. After perfusion, no significant use-dependent block was observed when stimulated at 0.06 Hz and 1 Hz,P>0.05, while at 2 Hz, 5 Hz and 10 Hz, propafenone perfusion demonstrated signiifcant use-dependent block uponINa-T with the inhibition fractions of (22 ± 11)%, (38 ± 14)% and (52 ± 17)% respectively, those were signiifcantly different from the inhibition fractions at either 0.06 Hz or 1Hz,P<0.05. When the inhibition fractions were compared by each 2 conditions, allP<0.05. Conclusion: Propafenone may slow down the Vmax of AP, reduce APA and without the impact on APD; the effects onINa-T is not only in tonic block, but also more obviously in use-dependent block in isolated ventricular myocytes of New Zealand rabbit. Such inlfuences minimized the impact on QT interval and meanwhile, decreased the incidence of brad arrhythmia.

This paper presented the practice of Zhejiang in introducing the drug zero-profit reform.A comparative analysis was made to the pilot county hospitals regarding their business performance,patients' burden,financial subsidy and medical insurance expenditure.The reform has scored a success as expected with the following outcomes:sharp rise in medical services volume,medical income and financial aid on one hand; drop of the proportion of drug income and changes in the medical income makeup; controlled increase of average cost of outpatient and inpatient care,and significant drop of pharmaceutical costs; increased expenditure yet stable operation of medical insurance funds;proportional increase of medical insurance compensation,with drops of the proportion of both out-ofpocket expenses and visits to doctors out of their county.This reform,however,has such shortcomings as follows:insufficient adjustment toward true costs of medical services,lack of a clear and sustainable financial compensation mechanism,and that of supporting measures.Based on these,the authors call for accelerated payment system reform,dynamic and scientific adjustment of medical service prices,exploration of clear financial compensation methods,optimization of internal management of hospitals,and acceleration of the formation of a medical staff income distribution mechanism.

Objective To explore molecular mechanisms underlying the in vitro counteracting effect of curcumin on malignant melanoma.Methods Cultured A375 and C8161 human melanoma cells were cultivated in vitro,and randomly divided into several test groups and a control group to be treated with different concentrations of curcumin and dimethyl sulfoxide respectively for different durations.Then,methyl thiazolyl tetrazolium (MTT) assay,Transwell assay,flow cytometry and Western blot were performed to evaluate the effect of curcumin on the proliferation,invasion and cell cycle of,as well as expressions of AKT/mTOR signaling pathway-related proteins in A375 and C8161 cells respectively.Statistical analysis was carried out by using t test.Results MTT assay showed that the treatment with curcumin of 5-35 mg/L for 24-96 hours significantly inhibited the proliferation of both A375 and C8161 cells compared with that with dimethyl sulfoxide (all P ＜ 0.001),and the inhibitory effect was in a dose-dependent manner within the range of 5-15 mg/L for A375 cells and within the range of 5-10 mg/L for C8161 cells,and in a time-dependent manner from 0 to 48 hours for both cells.After treatment for 24 hours,the 50％ inhibitory concentration (IC50) of curcumin against A375 cells and C 8161 cells was 10 mg/L and 5 mg/L respectively.Transwell assay demonstrated that the invasion of A375 and C8161 cells was significantly suppressed by 72-hour treatment with curcumin at 10 mg/L and 5 mg/L respectively (both P ＜ 0.001).Flow cytometry showed that the cell cycle of A375 and C8161 cells was arrested at G2/M phase after 24-hour treatment with curcumin at 10 mg/L and 5 mg/L respectively,with significant differences in the proportion of A375 cells and C8161 cells in G2/M phase between the test group and control group (A375 cells:35.00％ ± 3.54％ vs.120.80％ ± 7.46％,P＜ 0.001;C8161 cells:19.33％ ± 4.04％ vs.85.00％ ± 9.53％,P ＜ 0.001).Western blot revealed that the expressions of AKT/mTOR signaling pathway-related proteins were decreased in A375 and C8161 cells after 24-hour treatment with 10 mg/L and 5 mg/L curcumin respectively.Conclusion Curcumin can inhibit the proliferation and invasion of A375 and C8161 cells,likely by blocking cell cycle and inhibiting activation of the AKT/mTOR signaling pathway.

This study is to investigate the effects of ubenimex on tumor cell invasion and apoptosis, dose relationship and mechanism. Immunofluorescence staining was performed to detect the expression of CD13 in HT-1080 cells. MTT assay was used to analyze the effect of ubenimex on cell proliferation. Annexin V-EGFP/PI was used to detect apoptotic cells by flow cytometry. Cell cycle was analyzed using flow cytometry. Ala-pNA was used as substrate to evaluate the effect of ubenimex on the aminopeptidase activity. Transwell assay was used to analyze the effect of ubenimex on cell invasion and migration ability. Western blotting was used to detect the expression level of CD13. MMP activity was analyzed using gelatin zymography. The results showed that ubenimex at high concentration inhibited the proliferation of HT-1080 cells (IC50: 3.8 mg x mL(-1)), and induced cell apoptosis. Cell cycle was blocked at G1 phase. Ubenimex at low concentration inhibited the aminopeptidase activity of HT-1080 cells (IC50: 8.3 microg x mL(-1)) and inhibited cell invasion, but it had no effects on the cell migration and proliferation. Ubenimex had no effects on CD13 expression and MMP activity. In conclusion, ubenimex at low concentration can inhibit the invasion ability of tumor cells by directly inhibiting the aminopeptidase activity; ubenimex at high concentration can inhibit the proliferation of tumor cells and induce cell apoptosis by a CD13-independent pathway.

Objective To analyze the image and histological results of the combined use of allograft/extracorporeally frozen tumor-bearing bone and vascularized fibular flap for the reconstruction of bony defects following tumor resection,guiding clinical practice.Methods From March 2007 to June 2013,we enrolled 63 patients who had combinative biological reconstruction after bone tumor resection (11 in humerus,22 in femur,21 in tibia,4 in calcaneus).There were 36 male and 27 female in this series.The average age at time of operation was 20 years,ranging from 9 to 48 years.The follow-up ranged from 16 to 102 months with average of 48 months.We investigated the X-ray and CT images for all patients and histological findings of two patients.Patients were assessed functionally with the Musculoskeletal Tumor Society 93 score.Results Three patients with local soft tissue recurrence and one patient with infection underwent amputation.The survival of construct was 93.6％.Bone union achieved in all cases with the average MSTS score of 92.8％.Bone union ranged from 11 to 28 months in allograft group and 9 to 14 months in devitalized tumor bearing bone group.Significant difference of bone union time was found between two groups (Z=-3.638,P=0.000).Viability of the fibular grafts was verified in 58 of 63 patients (92％).Three types of images were observed in complex.Osteopenia and spongy change in fibula were found in 51 patients (81％) with stable fixation of the complex.Five complexes with failed blood supply of fibula and stable fixation revealed no density change of fibula,small amount of callous formation and relative delayed union.In seven complexes (11％) with unstable complex due to patients' incompliance,fibula reacted with dense hypertrophy and microfracture.Fusion of grafts with amount of callus was obviously observed.Union at allograft-host bone junctions occurred by residual host bone-derived external callus and fibular-derived internal callus that bridged the junction and filled the gap between abutting cortices.Callus from fibular graft was mature than that from periosteum of residual host bone.Internal repair was observed at the internal surface of the allografts.Fibula showed significant spongy changes.Conclusion Recycled tumor-bearing bone in combined with fibular flap is a reliable reconstruction as an alternative to traditional Capanna technique.The survival of the fibula is a cornerstone in success of complex reconstruction.Sponginess of fibula and internal repair of allograft compromise the intensity of complex,necessitating the strong instrumentation during reconstruction.