OBJECTIVE:To evaluate the affordability of 3 anti-tumor targeted drugs gefitinib,trastuzumab and sunitinib in ur-ban and rural residents of Hubei province,and to provide reference for medical insurance price admission of anti-malignant tumor targeted drugs in China. METHODS:Referring to the incidence of malignant tumor stated in statistical yearbook of Hubei province and income data of urban and rural residents in Hubei province,based on the policy of reducing the price of imported drugs by 50% mentioned in the national drug price negotiations,and assume the drugs are included in the medical insurance reimbursement list,WHO/HAI standard survey method,catastrophic expenditure evaluation method and poverty effect evaluation method were ad-opted to calculate the affordability of 3 drugs. RESULTS:According to WHO/HAI standard survey method,increment of payment for 3 drugs were 64.00%-74.00% before and after 50% discount and reimbursement. According to catastrophic expenditure evalua-tion method,50% discount of gefitinib and reimbursement gefitinib,trastuzumab and sunitinib in urban area would result in cata-strophic expenditures of 20.00%、59.28% and 35.48% patients;in rural area,would result in catastrophic expenditures of 50.63%、74.72% and 75.93% patients. According to poverty effect evaluation method,50% discount of 3 drugs and reimbursement caused less than 31.95% urban and rural patients falling to poverty. CONCLUSIONS:Fifty percentage discount of 3 anti-tumor targeted drugs mentioned in the national drug price negotiations cause the economic burden more serious for rural residents than urban resi-dents. In the formulation of policies,the corresponding reimbursement ratio should be adjusted according to urban and rural areas, drug price and disease types for a balance of patients with different economic burden.

Objective: To analyze the New Cooperative Medical System ( NCMS ) funds and Individual afford-ability of anti-tumor targeted drugs under different medical insurance entry price, and to provide the basis for establis-hing the access price for medical insurance. Methods: Choosing Conmana or Kemer ( the lung cancer targeted drug) and Herceptin (breast cancer targeted drug) to analyze the Wuhan NRCMS operating status from 2012 to 2014, use tumor surveillance data from Hubei Province during the period from 2011 to 2015;consult clinical experts to form expert consensus price, refer to the Jiangsu Province Access Price and National Negotiation Price, and explore the fund bal-ance and individual affordability when the afore-mentioned two kinds of drugs can be compensated by medical insurance under different price. Results:The basic account balances of NRCMS in Wuhan from 2016 to 2018 are-11. 948 million Yuan, 2. 513 million Yuan and 82. 955 million Yuan when Kemer can be compensated by medical insurance under Na-tional Negotiation Price. Taking the compensation of Herceptin under National Price after the bargaining, the basic ac-count balances are -26. 901 million Yuan,-35. 962 million Yuan and 17. 542 million Yuan respectively. The rate of poverty caused by illness falls to 33. 40% from 45. 85% when Conmana can be compensated by Medical Insurance un-der National Negotiation Price, while this rate falls to 45. 42% from 46. 00% for Herceptin. Conclusion:The two kinds of drugs can be afforded by the Wuhan NRCMS after the medical insurance access price is negotiated by the govern-ment, but the individual affordability of Herceptin at the National Negotiation Price is worse.

Objective To evaluate the efficacy and safety of diacerhein in the treatment of patients with knee osteoarthritis.Methods The efficacy and safety of diacerhein was randomly investigated in 42 pa- tients with knee osteoarthritis using parallel group methodology and a double-dummy technique to ensure dou- ble blind status with respect to diacerhein and control drugs diclofenac.Results Significant changes were ob- served in 20 meters walk pain,knee joint tenderness scale,WOMAC index scale,5F-36 health survey,knee joint swelling scale,compared with baseline(P＞0.05)in both diacerhein and diclofenac group respectively.No difference was found between diacerhein group and diclofenae group.The patient global assessment and physi- cian's global assessment were similar in diacerhein group and diclofenac group(P＞0.05).The side effect was similar in two groups.All of these side effects in gastrointestinal tract appeared to be transient.Conclusion Diacerhein can effectively relieve pain and swelling of knee osteoarthritis,and provides us a new effective and safe approach for treating knee osteoarthritis.

Objective To set up a three-dimensional finite element model (FEM) to investigate biomechanics of point contact locking plate (PC-LP) fixating femoral shaft fractures. Methods One intact fresh adult cadaveric femur was scanned by CT at 1 mm interval. Then, the data of CT were utilized to establish three-dimensional FEM by using software Mimics and PRO/E and simulate the different clini-cal loading conditions. The changes of theoretical stress of femur and PC-LP were analyzed under flexion, axial compression and torsion loads. Results (1) Under four-point bending load, the distribution of femur stress was in uniformity, with the largest stress of the PC-LP focused on the edge. (2) Under axial compression load of 250 N, the largest stress of the femur was focused on the screw holes on beth distal ends, with the largest stress of the PC-LP focused on the middle screw holes. (3) Under the torsion load cused on the middlepart and the middle screw holes. Conclusions Under the four-point bending, ax-ial compression and torsion loads, the distribution of femur stress is in uniformity, when the largest stress of the PC-LP focuses on edge or the middle screw holes, while that of the PC-LP on two screw holes of proximal or distal ends.

Objective To evaluate the efficacy and safety profile of a recombinant human tumor necrosis factor receptor: Fc fusion protein in ankylosing spondylitis (AS). Methods This was a multicenter,randomized, double-blind, placebo-controlled trial in the first 6 weeks and then followed by an open-labeled trial in the next 6 weeks. One hundred and forty-three patients of active AS were randomly assigned to receive 25 mg twice-weekly subcutaneous injections of rhTNFR:Fc or placebo for 6 weeks. The primary endpoint was proportion of ASAS20 responders at week 6. The secondary endpoints were the proportion of subjects achieving a BASDAI 20%, BASDAI 50% and BASDAI 70% improvement at week 6. Other secondary endpoints, related to reducing signs and symptoms of AS and improving range of motion and physical function, were evaluated.Results Treatment with rhTNFR:Fc resulted in significant improvement. At 6 weeks, 68% of the 71 patients in the rhTNFR: Fc group had a treatment response, as compared with 28% of those in the placebo group(P＜0.01). Improvements over base-line values for other measures of disease activity were significantly greater in the rhTNFR:Fc group, rhTNFR:Fc was well tolerated, The most frequently treatment related adverse event was injection site reaction. Conclusion rhTNFR:Fc has demonstrated consistent evidence of efficacy and is well tolerated in the treatment of active AS.

To explore the role of dentritic epidermal T lymphocytes ( DETCs) in immune rejection of skin allograft in mice and its related mechanism. Methods (1) Full-thickness skin was harvested from back of one male wild type (WT) C57BL/6 mouse. Epithelial cells were isolated for detection of the expression of DETCs and their phenotype with flow cytometer. Another male WT C57BL/6 mouse was used to harvest full-thickness skin from the back. Epidermis was isolated for observation of the morphological characteristics of DETCs with immunofluorescence technology. (2) Four male green fluorescence protein (GFP)-marked C57BL/6 mice, 7 female WT C57BL/6 mice (group WT), and 7 female ybT lymphocytes 8 gene knock-out (GK) C57BL/6 mice (group GK) were used. Full-thickness skin in the size of 1.4 cm x 1.4 cm on the back of mice in groups WT and GK were excised, and the wounds were transplanted with full-thickness skin in the size of 1.2 cm x 1.2 cm obtained from male GFP-marked C57BL/6 mice. The survival time of skin grafts was affirmed with small animal in vivo imager and naked eyes and recorded. (3) Two male WT C57BL/6 mice were used to isolate epithelial cells. Cells were inoculated into 48-well plate and divided into activation group (A) and control group (C) according to the random number table, with 4 wells in each group. Cells in group A were treated with 10 pL concanavalin A in the concentration of 2 microg/mL for 24 hours, while those in group C with PBS in the same volume as that in group A. The expression of interferon y in DETCs was detected with flow cytometer. (4) Four male GFP-marked C57BL/6 mice were used as donors. Fourteen female WT C57BL/6 mice were used as receptors and divided into interferon gamma neutralizing group (IN) and control group (C) according to the random number table, with 7 mice in each group. The skin transplantation model of C57BL/6 male to C57BL/6 female was established as in part (2). Before surgery and 72 hours after, mice in group IN were intraperitoneally injected with 200 pL interferon y neutralizing antibody in the concentration of 1 mg/mL, and those in group C with normal saline in the same volume as that in group IN. The survival time of skin grafts was observed and recorded using the methods in part (2), and the result of group IN was compared with that of group GK in part (2). The survival curve of skin grafts was processed with Log-rank ( Mantel-Cox) test. Results (1) The positive expression rate of DETCs in epithelial cells of skin in mouse was 7.27%, and they were all CD3 cells. DETCs were found to be scattered in the epidermis of skin in mouse with dendritic morphology. (2) The survival time of skin grafts of mice in group GK was 22-35 d, obviously longer than that in group WT (12-16 d, y2 = 14. 10 , P < 0.001). (3) Expression of interferon gamma was detected in 22. 70% DETCs in group A, which was obviously higher than that in group C (0.51%). (4) The survival time of skin grafts of mice in group IN was 19-24 d, which was obviously longer than that in group C (12-16 d, chi 2 = 13.60, P < 0.001) but close to that in group GK as in part (2) (chi2 = 0.06, P = 0.810). Conclusions DETCs are involved in promotion of immune rejection of skin allograft probably by secretinf interferon gamma.
Allografts ; Animals ; Epidermis ; Female ; Graft Survival ; immunology ; physiology ; Interferon-gamma ; immunology ; metabolism ; Lymphocytes ; Male ; Mice ; Mice, Inbred C57BL ; Skin ; Skin Transplantation ; T-Lymphocytes ; immunology

Objective Non-invasive detection is the focus of intense research in diagnosis of acute renal allograft rejection currently. Urine protein is considered the cue to reflect the pathological changes in kidney disease. In this study, we explored the urine markers for early acute renal allograft rejection. Methods The urine protein of two patients with acute renal allograft rejection were examined by 2D gel electrophoresis and bioinformatics. We adopted pH 4-7 ready strip IPG and stained the gel with Sypro-Ruby. The digitized 2D maps of urine protein were quantitatively analyzed using 2D-analysis software packages. By analyzing the differential expressions of proteome between different time points (1, 2, 3 days before acute rejection and 7, 14, 21 days after acute rejection), 30 protein spots were selected and analyzed by MALDI-TOF-MS/MS. Results We obtained 2D gel electrophoresis maps of urine protein of the patients with acute renal allograft rejection, which are of good reproducibility and resolution. Sixteen protein spots were identified, resulting in thirteen corresponding proteins. Out of these proteins, we screened three proteins (alpha-1-antichymotrypsin, tumor rejection antigen gp96, Zn-Alpha-2-Glycoprotein) closely related to acute rejection. Conclusion The urine protein spots on 2D gel electrophoresis maps for the patients with acute renal allograft rejection were of obvious difference when detected at different time points of acute rejection. Alpha-1-antichymotrypsin, tumor rejection antigen gp96 and Zn-Alpha-2-Glycoprotein might be the candidate protein markers to diagnose acute renal allograft rejection after renal transplantation.

Objective: To analyze the clinical characteristics of patients with ankylosing spondylitis (AS) with inflammation bowel disease (IBD). Methods: AS patients fulfilling the 1984 modified New York diagnostic criteria were recruited in Chinese AS Prospective Imaging Cohort (CASPIC) consecutively from April 2016 to June 2017 in Chinese People′s Liberation Army General Hospital by using smart management system for spondyloarthritis (SpAMS). The diagnosis of IBD was confirmed by tissue pathology via ileocolonoscopy. Demographic, clinical and biochemical data were collected. Results: In total, 893 patients with AS were recruited with the mean age 30.8 years. The majority were men (739, 82.8%). There were 64 (7.2%) patients concomitant with IBD. The mean age [(34.5±7.5) years vs. (30.5±8.8) years, P<0.001] was older and the disease duration [(10.8±6.9) years vs. (8.1±5.9) years, P=0.001] was longer in patients with IBD than patients without. Compared with patients without IBD, patients with IBD had more frequent involvement of the cervical spine [(21.9% (14/64) vs. 10.5% (87/829), P=0.006) and thoracic spine [29.7% (19/64) vs. 12.3% (102/829), P<0.001]. Uveitis [28.1% (18/64) vs. 16.4% (136/829), P=0.017] and psoriasis [7.8% (5/64) vs. 2.3% (19/829), P=0.009] were also more common in patients concomitant with IBD. In addition, patients with IBD had significantly higher scores in BASDAI (3.3±2.1 vs. 2.4±1.8, P<0.001), BASFI [2.2 (1.0,3.3) vs. 1.1(0.2,2.4), P<0.001)] and ASAS HI (7.1±4.3 vs. 5.3±3.7, P= 0.001) than patients without IBD. Conclusions Compared with patients without IBD, AS patients concomitant with IBD have more severe disease activity and organ dysfunction. Furthermore, the uveitis and psoriasis are more frequently accompanied in AS patients with IBD.

Objective The aim of this study was to set up a large,longitudinal and prospective database to compare the clinical manifestations in human leucocyte antigen (HLA)-B27 positive and negative patients with ankylosing spondylitis(AS) based on real-world evidence in Chinese population.Methods A total of 897 outpatients with confirmed AS were recruited consecutively by smart management system for spondyloarthritis (SMSP) from April 13,2016 to June 6,2017 in Chinese PLA General Hospital from 30 provinces and autonomous regions.801 patients with HLA-B27 data were included in the analysis.Demographic and clinical parameters including Bath ankylosing spondylitis disease activity index (BASDAI),Bath ankylosing spondylitis functional index (BASFI),ankylosing spondylitis disease activity score (ASDAS),arthritis,enthesitis,Bath ankylosing spondylitis metrology index (BASMI),erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were compared between HLA-B27 positive and negative groups.Results A total of 801 patients were included in the analysis with an average age of (30.7± 8.8) years.There were 659 males and 142 females and HLA-B27 was present in 88.0％(705/801).Males were significantly more in HLA-B27 positive patients [83.3％ (587/705) vs.75.0％ (72/96);P=0.047].The average age at disease onset was (22.3 ±7.6)years in HLA-B27 positive patients and (24.4 + 8.7) years in HLA-B27 negative ones (P=0.028).There was significant difference in diagnose delay between two groups [14.3(2.5,43.6)months in HLA-B27 positive patients vs.20.3(5.0,67.4) months in HLA-B27 negative ones,P=0.041].Anterior uveitis was found to be significantly more common in HLA-B24 positive patients [18.9％ (133/705) vs.7.3％ (7/96),P=0.005],and knee involvement less common in HLA-B27 positive patients [4.0％ (27/682) vs.10.0％(9/90),P=0.010],conversely.CRP[6.5(3.0,16.4)mg/L vs.3.5(1.6,12.3)mg/L] and ESR[11.0(4.0,24.0)mrn/1h vs.7.0(3.0,16.0)mm/1h] were significantly higher in HLA-B27 positive patients(P=0.005,0.013,respectively).But no differences in BASDAI,ASDAS,BASFI and BASMI were obtained between two groups.Conclusions HLA-B27 positive patients had a higher proportion of males,a younger age of onset and a greater risk for occurrence of anterior uveitis,suggesting a poorer prognosis.

The clinical data of 120 patients admitted to our hospital with renal stones treated by flexible ureteroscopy (FURS) and the imaging-related data measured by virtual reality technology were retrospectively analysed. The results of the univariate analysis showed that stone surface area (S), renal pelvis volume (P), length of calyces funnel (L), pelvic calyceal height (H) and essence of stone (E) were closely related to stone-free rate. The H. L.P.E.S. score was constructed to predict stone-free rate after FURS based on the above factors, and the area under the receiver aperating characteristic curve for the H. L.P.E.S. and S. O.L.V.E. scoring systems was 0.921 and 0.754 respectively.The H. L.P.E.S. scoring system has higher predictive value.