ObjectiveTo investigate the expression and significance of CD28- cells, CD4+ and CD8+T lymphocytes in the peripheral blood and synovial fluid in patients with rheumatoid arthritis ( RA ). Methods The expression of CD28, CD4+, CD8+ T lymphocytes and inducible co-stimulator(ICOS) in the peripheral blood and synovial fluid in 45 patients with RA were detected by three-color flow cytometry. Independent sample's t test was used for statistical analysis between the two groups. ResultsSynovial fluid CD4+CD28+ICOS+, CD4+CD28- ICOS+ , CD8 + CD28 + , CD8 + CD28 + 1COS+ T lymphocytes were significantly increased than the peripheral blood in RA patients[(36±19)％ vs (15±8)％, t=-4.234, P＜0.01; (2.1±2.2)％ vs (0.6±1.4)％, t=-3.143, P＜0.01; (62±15)％ vs (47±18)％, t=-2.885, P＜0.01; (9±9)％ vs (3±3)％,t=-2.131, P＜0.05], Synovial fluid CD8+CD28-T lymphoc-ytes were significantly reduced than the peripheral blood[(38±15)％ vs (54±18)％, t=2.975, P＜0.01], Synovial fluid CD8+ CD28-ICOS+, CD4+CD28+and CD4+ CD28- T lymphocytes had no significant difference than the peripheral blood (P＞0.05). Compared with peripheral blood in the same patients with RA, CD4+CD28+ ICOS+, CD8+ CD28+ T lymphocyteswere significantly increased[(38±18)％ vs (16±10)％, t=-4.065, P＜0.01 ; (61±16)％ vs (41±21)％, t=-4.065,P＜0.01], CD8+CD28-T was significantly reduced[(39±16)％ vs (59±21)％, t=2.949, P＜0.01]. The level of CD4+ CD28-, CD8+ CD28-, CD28-ICOS+ T lymphocytes in the active and remission patients with RA was not significantly different (P＞0.05). ConclusionSynovial fluid CD28T lymphocyte subsets disturbance and the abnormal expression of ICOS in patients with RA may play important roles in the mechanism of joint damage.

Objective To observe the clinical effect of Sangpa Zhike decoction in the treatment of acute exacerbations of chronic bronchitis. Methods 180 patients with acute exacerbation of chronic bronchitis admitted to Autonomous Prefecture Hospital of traditional Chinese medicine(TCM)in Changji,Xinjiang,from August 2012 to August 2013 were enrolled. They were divided into Sangpa Zhike decoction treatment group and western medicine treatment control group by random number table,90 cases in each group. General treatments were given to the two groups. In the Sangpa Zhike decoction treatment group,additionally only oral Sangpa Zhike decoction was given(composition:Morus alba 10 g,loquat leaf 10 g,Houttuynia 10 g,honey aster 15 g,honey coltsfoot flower 6 g,Zhejiang Fritillaria 12 g,perilla 10 g,white mustard seed 6 g,Platycodon grandiflorum 10 g,Rhizoma Cynanchi Stauntonii 12 g,tangerine peel 6 g,Stemona 6 g). The ingredients were mixed in water and boiled to form a decoction,one dose daily,divided into two parts to be taken twice a day. In the western medicine treatment group,the infection was controlled by western medicine and the drugs to eliminate cough and phlegm,etc were used. The therapeutic course in both groups was 7 days. The therapeutic effect for treatment of TCM syndromes and the cough quantized integration score in the two groups were observed after treatment. Results The cure rate of Sangpa Zhike decoction treatment group was significantly higher than that of western medicine treatment control group〔70.00%(63/90)vs. 33.33%(30/90),P<0.01〕. Before treatment,the cough symptom quantization integral scores in the two groups had no statistically significance, but after treatment,the scores in the two groups were significantly lower than those before treatment. And the score in Sangpa Zhike decoction treatment group was decreased more significantly (1.66±1.12 vs. 4.36±2.32, P<0.01). Conclusion Sangpa Zhike Decoction has obvious curative effect in the treatment of acute attack of chronic bronchitis.

Objective To detect mutations in the PTPN11 gene in a family with LEOPARD syndrome (LS).Methods Clinical data were collected from a 7-year-old boy patient with LS.Peripheral blood was obtained from the patient,both of his parents,and 50 healthy controls.All the exons and their flanking sequences of the PTPN11 gene were amplified by PCR followed by direct DNA sequencing.Results A heterozygous missense mutation c.836A ＞ G,which resulted in a substitution of TAT by TGT at codon 279,was found in exon 7 of the PTPN11 gene in the patient.No mutation was detected in the unaffected parents or healthy controls.Conclusion The missense mutation c.836A ＞ G may be the cause of the phenotype of LS in this family.

Objective To evaluate the mechanical stability of alternative reconstruction methods after total en bloc spon?dylectomy in the lower lumbar spine. Methods Eight adult fresh cadaveric lumbosacral spines (L1-S1) were adopted. Total en bloc spondylecotmy of the L4 vertebra was performed after intact testing. Four designed reconstruction samples were tested for the range of motion (ROM) of the spine:1) expandable artificial vertebral body and short posterior instrumentation at L3-L5 (SP), 2) ex?pandable artificial vertebral body and short posterior instrumentation with additional anterolateral fixation at L 3-L5 (ASP), 3) ex?pandable artificial vertebral body and multilevel posterior instrumentation at L2-S1 (MP), 4) expandable artificial vertebral body and multilevel posterior instrumentation with additional anterolateral fixation at L2-S1 (AMP). Nondestructive biomechanical test?ing was performed on each construct under loading control. The ROM for each construct was obtained by applying pure moments in flexion, extension, lateral bending, and axial rotation. Results In flexion, extension and lateral bending, the ROM of all the re?constructed constructs significantly decreased compared to the intact. The ROM of specimens with anterolateral fixation was less when compared to the ones without additional fixation. In lateral bending, MP (L:1.87° ± 0.32° , R:1.97° ± 0.33° ), ASP (L:1.89° ± 0.37°, R:2.08°±0.36°) and AMP (L:1.32°±0.29°, R:1.61°±0.33°) provided significantly less ROM than the SP (L:3.14°±0.35°, R:3.44°±0.34°). In axial rotation, the ROM of ASP (L:4.21°±0.58°, R:4.02°±0.59°) and AMP (L:3.56°±0.55°, R:3.52°±0.48°) was significant decreased when compared to the intact state (L: 7.47° ± 1.00° , R:7.57° ± 0.84° ). MP (L:6.33° ± 0.71° , R:5.88° ± 0.62°), ASP and AMP showed significantly less ROM than the short posterior fixation (L:9.28°±1.01°, R:9.48°±0.98°). AMP sig?nificantly decreased the ROM compared to MP. Conclusion After total en bloc spondylectomy of lower lumbar, long segmental fixation provided more stability to the construct than the short one. Compared to posterior fixation, circumferential fixations showed a higher stability. In contrast, multilevel segmental instrumentation with circumferential fixation did not provided more stability than the short constructs.

ObjectiveTo evaluate the adverse events occurred during tumour necrosis factor (TNF)-αblocker treatment in Chinese Han population patients with ankylosing spondylitis (AS).MethodsThis study had enrolled 369 Chinese Han population patients with ankylosing spondylitis.They all received TNF-αblocker treatment in the hospital.All 1011 administration were recorded in total.All of them were evaluated for adverse events 2 hours after injection,126 of them had received long-term TNF-α blocker injection,and they were followed-up at week 8,12,52,104.Mild immediate adverse events and long-term adverse events were all counted.SPSS 10.0 software package was used for Fisher's exact test.ResultsThree hundred and sixty-nine patients had 1011 administrations in total,652 had received rhTNFR:Fc,316 had infliximab,21had etanercept,22 had adalimumab injections.Adverse events 2 hours after injection were:17 (2.6％) for rhTNFR:Fc,12 (3.8％) for infliximab,0 for etanercept,1 (4.5％) for adalimumab.Twenty adverse events were mild(12 for rhTNFR:Fc,9 for infliximab),5 events were moderate(3 for rhTNFR:Fc,1 for infliximab,1 for adalimumab),4 events were severe(2 for rhTNFR:Fc,2 for infliximab).The frequency of adverse events were comparable between rhTNFR:Fc and Infliximab injection in immediate adverse reactions (P=0.31).One hundred and twenty-six (69 rhTNFR:Fc,57 infliximab) patients had long-term usage,and were followed-up at week 8,12,52,104,39 patients had adverse reactions:20 (51.3％) for rhTNFR:Fc,19(48.7％) for infliximab.Thirty-seven patients had infectious events(94.9％ ),1 neurological event(2.6％),and 1 patient had tuberculosis relapse (2.6％).Outcomes were comparable with rhTNFR:Fc and infliximab in long-term usage(P=0.69).ConclusionAttention should be paid to the above events in Chinese Han patients with ankylosing spondylitis who were treated with TNF-α blocker treatment.Special attention should be paid to those patients who are in their third or fourth injection.The occurrence of immediate reaction or long-term adverse events between rhTNFR:Fc and infliximab are comparable.

Objective To compare the clinical efficacy of ibuprofen arginate,a new nonsteroidal antiinflammatory drug,with that of ibuprofen,in patients with rheumatoid arthritis or knee osteoarthritis and to evaluate the safety and tolerability of ibuprofen argihate.Methods This is a muhicenter,random,open,active comparator-controlled,parallel clinical trail in which 171 patients with rheumatoid arthritis or knee osteoarthritis were enrolled.Patients were randomized to 2 groups:400 mg of ibuprofen arginate three times daily and 400 mg of ibuprofen three times daily respectively.Clinical efficacy and safety were evaluated after 4-week treatment.Results Ibuprofen arginate,at dosages of 400 mg three times daily,had shown significant efficacy in relieving pain,tenderness and swelling of joints and there was no significant difference when compared to that of ibuprofen.There was no difference in clinical adverse effects between the two groups and no serious adverse effects were repofled.But ibuprofen arginate could initiate effectiveness more rapidly than ibuprofen in both rheumatoid arthritisand osteoarthritis patients.Conclusion Ibuprofen arginate has the same clinical efficacy and safety profiles as itmprofen in treating rheumatoid arthritis and osteoarthritis.However,its onset is more rapid than ibuprofen.

Objective To study the feasibility and safety of total en bloc spondylectomy (TES) for bone tumors of the fourth lumbar spine and evaluate the clinical outcomes.Methods From March 2011 to December 2013,21 patients undergone total en bloc spondylectomy in posterior-only approach were retrospectively reviewed.The patients included 9 males and 12 females,with a mean age of 47.1± 15.6 years old (range,15-71 years old).This series included 12 cases of primary bone tumors and 9 cases of solitary metastases.Preoperative evaluation according to clinical,imaging and pathologic features was performed meticulously to select patients.The length of surgery,estimated blood loss,surgical margins,instrumentation failure,perioperative complications,Frankel scale,visual analogue scale (VAS) for pain,local control rate and overall survival were reviewed and analyzed.Results Total en bloc spondylectomy was performed successfully in all patients.Average operative time and estimated blood loss were 297.6±44.6 min (range,225-420 min) and 2 247.1±904.5 ml (range,900-4100 ml),respectively.The mean follow-up time was 50.4± 17.1 mons (range,24-79 mons).All patients encountered nerve roots stretch and 5 patients (23.8％) showed lower extremeties neurological dysfunction.All of them improved in 2-4 weeks postoperatively and recovered completely at 6-month follow -up.Cerebrospinal fluid leak was found in 4 patients (19.0％).The VAS score was 1.5±1.4 at post-operation,which was significantly lower than the 6.2± 1.6 in average at operation (P=0.008).Three patients with metastatic tumors died during the follow-up.Titanium mesh cage subsidence was observed in 7 patients (33.3％).No implant failure was occurred during the follow-up.Conclusion Total en bloc spondylectomy for tumors of the fourth lumbar spine in a posterior-only approach is feasible.However,there are many intraoperative neurological complications and the indications for TES are extremely limited.

The mixed evaluation system uses the network platform as a carrier to construct a dynamic evaluation model that spans time and space between online and offline, between individuals and teams. Mixed evaluation system of physiology was performed for two years, and the process evaluation and the summative evaluation in the mixed evaluation system showed a good correlation, and the students' learning ability and learning effect showed consistency with the evaluation results. Practice has proved that the mixed evaluation system not only optimizes the traditional evaluation system, but also fully expands the five principles of formative evaluation; however, while reflecting the advantages of the network platform, it also exposes the defects of insufficient supervision of the network platform. Thus, we should further improve the mixed evaluation system of physiology.

Objective:To propose and verify a surgical classification system for the axial primary malignant and aggressive benign tumor.Methods:The CZH surgical classification system was originally developed for the axial primary malignant and aggressive benign tumor. The CZH surgical classification system includes seven types, according to the anatomic features and the extension of tumor violation. A total of 136 patients (79 males and 57 females) with axial primary malignant and aggressive benign tumor from multiple tertiary centers who received surgery from July 2006 to July 2019 were included. The average age was 44.40±17.55 years (8-83 years) old. There were 99 malignant tumors and 37 aggressive benign tumors included. The number of patients with each classification was presented as followed, Type I 13, Type II 15, Type IIIa 3, Type IIIb 20, Type IVa 43, Type IVb 12, Type Va 21, Type Vb 3, Type VI 2, Type VIIa 3 and Type VIIb 1. Surgical procedures were selected according to different types in classification. The inter- and intra-observer consistencies were evaluated by the Kendall's W test. The VAS, Frankel score, overall survival and recurrence free survival were recorded during the follow-up. Results:The inter- and intra-observer consistent coefficient was 0.973 and 0.996, respectively ( P<0.05). The single posterior approach was adopted for the Type II tumors. Other patients underwent surgery by the combined antero-posterior approach. The majority in anterior approach (113 cases) was the modified submandibular approach. The reconstruction modes included anterior "T" shape titanium mesh (112 cases) or the 3D printed prothesis (7 cases) combined with the posterior occipto-cervical fusion (92 cases) or the pedicle screw system (44 cases). The average surgical duration and the volume of intraoperative bleeding was 348.40±136.14 min (60-760 min) and 1 225.69±859.40 ml (80-4 000 ml), respectively. The operation duration and volume of intraoperative bleeding among each type were with statistical difference. The patients with Type IV, V tumors had longer operation duration than those with Type II tumors. Those with Type V and VII tumors had longer operation duration than those with Type I tumors. The patients with Type V tumors had more intraoperative bleeding than those with Type I-IV tumors. The average preoperative VAS score was 4.15±2.25 and then was reduced significantly to 0.62±0.71 and 0.38±0.59 at one and three months after operation, respectively. The Frankel score was also significantly ameliorated at one and three months postoperatively. There were 22 postoperative complications (16.2%). The complications included cerebral spinal fluid leak (12.5%), dysphagia and/or dysphonia (7.4%), dyspnea (5.1%), wound infection (3.7%), wound hemorrhage (2.2%) and pharyngeal dehiscence (1.5%). The incidence of postoperative complication was 25.9% in Type IV-VII tumors, while 11.8% in Type I-III tumors. Conclusion:CZH surgical classification system was verified with high observer consistency. This classification system could assist surgeons to select proper surgical approaches, resection modes and reconstruction modes, and thus ensure the safety of surgery and reduce the recurrence. The tumors in Type IV, V and VII may be with more challenging for surgeons. The incidence of postoperative complication in Type IV-VII tumors may be higher than that in Type I-III tumors.

In comparison with the traditional two-dimensional tumor cell culture, the three-dimensional tumor spheroid culture can not only provide with an in vivo-like growth environment for tumor cells, but also maintain maximum cell activities. Therefore, the three-dimensional tumor spheroid culture is widely used in oncology research. In particular, the three-dimensional tumor cells retain the material and structural basis of the microenvironment of tumor in vivo, which is closer to the actual physiological environment, allowing it to be an ideal in vitro model for evaluating the tumor treatment response and drug resistance in tumors. This review summarizes the mechanisms of drug resistance in three-dimensional tumor cells, especially those induced by the morphology and microenvironment of three-dimensional tumor spheres, and puts forward the problems existing in the current three-dimensional tumor cells model, as well as the future development direction.