Histological classification system ( HCS) is an important system in judging and predicting ma-lignant behaviors of breast cancer .This study is aimed to analyze research progress and development direction of HCS by perusing literatures ,including the origin and development progress of HCS ,contents and deficiencies of Nottingham classification system(NCS),and introduction of novel classification system .HCS of breast cancer has a history of more than one hundred years ,among which NCS is the most widely used ,based on morphological fea-tures of cancer cells .However,there are still some shortcomings about NCS ,such as few indexes incorporation , great evaluation variation and low evaluation efficiency .Recently ,many newly evaluation systems have been devel-oped,including“nucleus+proliferation”classification system ,computer assisted classification system and compre-hensive prognostic classification model .Therefore,the future development directions of HCS on breast cancer is to use high throughput analysis technology to extract and analyze the hidden molecular information in cancer cells and the surrounding tumor microenvironment ,so as to better guide personalized therapy and predict clinical prog-nosis.

Objective: To evaluate the association between autoimmune diseases (ADs) and thyroid dysfunction using a Mendelian randomization (MR) approach. Methods: Genetic predictors of hypothyroidism and hyperthyroidism were collected through the UK Biobank, including 337 159 individuals and 10 894 596 single nucleotide polymorphisms (SNPs). Genetic predictors of 6 ADs including systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), and multiple sclerosis (MS) were collected through the GWAS Catalog database, including 14 267 individuals and 7 071 163 SNPs, 22 647 individuals and 99 962 SNPs, 24 840 individuals and 12 783 129 SNPs, 58 284 individuals and 13 108 512 SNPs, 13 239 individuals and 1 124 241 SNPs, and 38 589 individuals and 156 632 SNPs. MR analysis was performed using the inverse-variance weighted (IVW) method. The horizontal pleiotropy was assessed using the MR-Egger regression, and sensitivity analysis was conducted with the leave-one-out. Results: IVW results showed that a higher risk of hypothyroidism was associated with T1DM (OR=1.007, 95%CI: 1.003-1.011, P<0.05), SLE (OR=1.005, 95%CI: 1.002-1.009, P<0.05), and RA (OR=1.013, 95%CI: 1.009-1.016, P<0.05); a higher risk of hyperthyroidism was associated with T1DM (OR=1.002, 95%CI: 1.001-1.003, P<0.05) and SLE (OR=1.002, 95%CI: 1.001-1.003, P<0.05). Conclusions Genetically predicted ADs are associated with an increased risk of thyroid dysfunction. A higher risk of hypothyroidism is associated with T1DM, SLE and RA; a higher risk of hyperthyroidism is associated with T1DM and SLE.

Composite Resins ; therapeutic use ; Dental Restoration, Permanent ; methods ; Humans

Objective To investigate the effects of metal particles produced by metal prosthesis on oxidative stress levels in human mononuclear cells . Methods Mononuclear cells obtained from peripheral blood of 15 healthy volunteers .Coculture mononu-clear cells with iron particles , cobalt particles , chromium particles , titanium particles and physiological saline , respectively .Levels of reactive oxygen species ( ROS) , malondialdehyde ( MDA) , superoxide dismutase ( SOD) and glutathione peroxidase ( GSH) were as-sessed in mononuclear cells at 6 h, 12 h, 24 h, 36 h, 48 h, respectively . Results Levels of ROS and MDA were higher in the parti-cle groups than that in the control group at 6 h, 12 h, 24 h, 36 h, 48 h, respectively (P<0.05).Levels of ROS and MDA were higher in cobalt particle, chromium particle and iron particle groups than that in the titanium particle group (P<0.05).Levels of SOD and GSH were lower in particle groups than that in the control group (P<0.05).Levels of SOD and GSH were lower in cobalt particle , chromium particle and iron particle groups than that in the titanium particle group (P<0.05). Conclusion Oxidative stress levels increased and anti-oxidant levels decreased in mononuclear cells when cocultured with metal debris .Cobalt particles , chromium parti-cles and iron particles induced higher changes than that in titanium particles .Oxidative stress may play an important role in metal deb-ris-mediated osteolysis .

BACKGROUND:Few reports are found about the effect of ovariectomized rats' bone histomorphometry parameters using non-destructive dynamic loading system.OBJECTIVE:To observe the effect of different loads situations on the bone histomorphometry parameters in ovariectomized rats.DESIGN,TIME AND SETTING:A controlled observation on the bone histomorphometry was performed in the Biomedical Engineering Laboratory of Jilin University from April 2007 to August 2007.MATERIALS:A total of 35 9-month-old Sprague-Dawley female rats were randomly divided into five groups,including sham operation group,ovariectomized (OVX) control group,OVX loading 1 N group,OVX loading 2 N group,OVX loading 4 N group.There were 7 rats in each group.METHODS:Rats in OVX control group and castration load group were processed into bilateral OVX on the back. The sham operation group only underwent the excision of fat tissues on back,and then sutured. After castration for 1 week,rats were loaded with non-destructive dynamic loading system in the two sides of the tibia,15 minutes a day. The mechanical loads would continue for 4 weeks and the loads were 1N,2N and 4N.MAIN OUTCOME MEASURES:Changes of proximal tibia bone histomorphometry parameters.RESULTS:The area,number and thickness of trabecular bone in OVX loading group were all higher than OVX control group (P＜0.05,P＜0.01).The trabecular bone area and thickness in OVX 4 N and OVX 2 N groups were significantly higher than OVX control group (P ＜ 0.001).There was a downward trend of trabecular separation in OVX 4 N group compared with OVX control group (P ＜ 0.05). With the increasing loads,there was an increasing trend of the area,number and thickness of trabecular bone,which were close to sham-operated group. The trabecular separation was declined. Single fluorescent labeled surface and double fluorescent labeled surfaces in sham operated group were all lower than that in OVX control group. With the increase in loads,the single fluorescent labeled surface,double fluorescent labeled surface,interlabeled width and mineral apposition rate had been shown to increase. The OVX 2 N and OVX 4 N groups exhibited a remarkably higher level of mineral apposition rate than OVX control group (P ＜ 0.05).CONCLUSION:With the increase in load at the range of 1-4 N,all parameters of bone histomorphometry improve in the OVX rats,the bone microstrcture is greatly ameliorated,bone mass loss is reduced and the process of osteoporosis is delayed.

Objective:To evaluate the clinical effects of short fiber ribbon combined with resin bonding technology for the treatment of food impaction between posterior teeth. Methods:98 cases of vertical food impaction between posterior teeth( total of 135 vertical food impaction units) were included. 73 units were treated by short quartz fiber ribbon combined with resin bonding technology( SQFRB) and 63 by resin bonding(RB). 12, 24 and 36 months after restoration, clinical effects were evaluated referring to the Modified United States Public Health Service (USPHS) Criteria, data were statistically analyzed. Results:12, 24 and 36 months after treatment the cure rate of SQFRB was 97. 3%, 97. 3% and 95. 9%, inefficacy rate was 0, 0 and 0;the cure rate of RB was 85. 5%, 82. 2% and 82. 2%, the inefficacy rate was 4. 8%, 11. 3% and 12. 9%, respectively(between groups, P<0. 05). Conclusion:Minimally inva-sive restorations using short fiber ribbon combined with resin bonding technology is effective in the treatment of vertical food impaction between posterior teeth.

Objective:The aim is to establish L-glutamate specific aminotransferase-L-glutamate dehydrogenase coupling 96-well high throughput screening method,which is applied to molecular evolution of aminotransferase WecE from E.coli.Methods:An optical assay for aminotransferase catalytic activity based on aminotransferase-glutamate dehydrogenase coupling system is established by optimization of coupling enzyme loading,signal molecule NADH concentration and coupling time.Mutants library of WecE is obtained by sitedirected saturation mutagenesis.Positive mutants can be screened out through 96-well preliminary screening and flask second screening.Results:The target transamination reaction is coupled with L-glutamate dehydrogenase indicative reaction system which consists of 0.5 U/ml enzyme loading and 0.4 mmol/L NADH.A positive mutant Y321F whose catalytic activity increases 3.4 fold compared to that of wild type is screened out in Tyr 321 saturation mutagenesis library of WecE.Conclusion:An accurate high throughput screening method with weak background interference is established.It offers feasible solution for molecular evolution of L-glutamate specific aminotransferase.

Aim Toresearchthemolecularmecha-nisms of DADS-induced apoptosis in human leukemia K562cells.Methods Cellviabilitywasmeasuredby MTT. Levels of DADS-induced ROS were measured by 2ˊ, 7ˊ-dichlorofluorescein diacetate ( DCFH-DA) fluo-rescence. DADS-induced mRNA levels of components of the NADPH oxidase were detected by Real-time PCR. The combination of protein Rac2 and p67phox was measured by immunoprecipitation assays. Flow cy-tometry methods were used to determine the percentage of apoptosis cells. DADS-induced Rac2 levels were measuredbyWesternblot.Results TheDADS-trea-ted K562 cells showed a dose-and time-dependent de-crease in cell viability and proliferation. There was sig-nificant up-regulation of the mRNA level of components of the NADPH oxidase complex in K562 cells after treatment with 6 mg·L-1 DADS for 6 h. Western blot results revealed that, compared with the control group, there was a significant up-regulation of Rac2 protein in K562 cells treated with 5. 0 and 10. 0 mg·L-1 DADS for 24h. And Rac2 combined with p67phox in DADS-induced apoptosis in K562 cells. PMA markedly in-creased the percentage of apoptotic cells, and DPI re-duced the percentage of apoptotic cells in DADS-in-duced K562 cells. Levels of DADS-induced ROS, also showed enhancement when exposed in PMA, but there was no DADS-induced ROS production evident when exposed in DPI in DADS induced K562 cells. Conclu-sions TheseresultsindicatethatNADPHoxidaseis the main source of DADS-induced ROS production. Diallyl disulfide induces apoptosis in human leukemia K562 cells through activation of NADPH oxidase.

BACKGROUND:Several researches have highlighted the selective dissolution of Ni ion from the nickel-titanium (NiTi) alloy during the corrosion process,which can lead to potential damage to human body.Different surface treatments will improve the corrosion resistance of NiTi implants.In modern medicines,it is necessary to analyze the characteristics of surface modified NiTi implants.OBJECTIVE:To study the effects of coated and uncoated materials made by elastic nickel-titanium alloy internal fixator on fracture healing and to compare the effects of continuous compressive stress after internal fixator of different types on fracture healing by setting up control group of bone nail internal fixation.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Laboratory of Tissue Engineering,Institute of Orthopedics,Second Hospital Affiliated to Lanzhou University between September 2004 and March 2005.MATERIALS:Diamond-like carbon coated and nickel-titanium alloy and uncoated nickel-titanium alloy embracing fixator (type 4H8-40) were provided by Lanzhou Ximai Memory Co.,Ltd.,China.Intramedullary nails (type ZQY-01) were purchased from Tianjin Jinxingda Industries Co.,Ltd.,China.METHODS:Thirty Chinchilla rabbits of 4-6 months old were randomly divided into 3 groups (n = 10):diamond-like carbon coated nickel-titanium alloy embracing fixator (group A),uncoated nickel-titanium alloy embracing fixator (group B),and intramedullary fixator (group C).Following anesthesia by injection of 1% sodium pentobarbital (25 mg/kg),transverse fracture models in middle part of the femur were made through a lateral femoral incision and fixed with diamond-like carbon coated nickel-titanium alloy embracing fixator,uncoated nickel-titanium alloy embracing fixator,and intramedullary fixator respectively.MAIN OUTCOME MEASURES:The inorganic substance level,osteocalcin,alkaline phosphatase (ALP) and tumor necrosis factor (TNF) expression in callus surrounding fracture site were detected 4 weeks postoperatively.Ni ion level in muscles surrounding fracture site,live tissue,and brain tissue were also detected.RESULTS:Inorganic substance level and ALP,osteocalcin,and TNF expression were significantly higher in the groups A and B than in group C (P＜0.05).Ni ion level in the liver tissue,brain tissue,and muscles surrounding the fracture were significantly lower in the groups A and C than in group B (P＜0.05).CONCLUSION:Elastic fixation promotes fracture healing.Diamond-like carbon coated nickel-titanium alloy embracing fixator has a better histocompatibility than uncoated group.

BACKGROUND: Although shape memory alloy has been extensively used in modem medicine, including orthopaedics and dental surgery, the body fluid could influence the stability of biomaterial and some ions released by materials may cause toxic and side effect to human body. The technology for the modification of shape-memory materials is of crucial importance for clinical use of shape memory alloy.OBJECTIVE: To investigate the biocompatibility of diamond-like carbon (DLC) coated Nickel-Titanium shape memory alloy and uncoated shape memory alloy with osteoblasts cultured in vitro. DESIGN, TIME AND SETTING: A comparative observation. The study was performed at the Institute of Othopaedics of Lanzhou University from March to June 2005.MATERIALS: A total of 30 DLC-coated Nickel-Titanium shape memory alloy disks, 6 minx7 mmx0.5 mm, and the same amount of uncoated ones of equal size were provided by College of Materials, Lanzhou University. METHODS: Rabbit osteoblast suspension of the third passage at density of 10 × 108/L were incubated with DLC-coated Nickel-Titanium shape memory alloy disks and uncoated shape memory alloy in 12-well culture plate in 5% CO2 at 37 ℃.MAIN OUTCOME MEASURES: Culture media were counted at 1, 2, 3, 4 and 5 days of culture to determine alkaline phosphatase (AKP) activity and nickel (Ni2+) concentration.RESULTS: The proliferation of osteoblasts and the concentration of AKP in DLC- coated group were greater than uncoated group; while the uncoated group released more Ni2. into the cells culture media than coated group (P < 0.05). CONCLUSION: DLC-ceated Nickel-Titanium shape memory alloy appears to have better biocompatibility with osteoblast cultured in vitro compared to uncoated ones.