Objective To investigate the effects of cobalt chloride(COCl2)induced rat alveolar epithelial cell apoptosis and the significance of related apoptosis protein hypoxia inducible factor-lalpha(HIF-1 a)expression. Methods Alveolar epithelial cells were cultured in vitro and divided into four groups with 6 samples in each.Hypoxia 4 h group:added 500μmol/L COCl2 for 4 hours inducing alveolar epithelial cell hypoxia;hypoxia 24 h group:co-cultured with COCl2 for 24 hours;hypoxia 48 h group:co-cultured with CoCl2 for 48 hours;control group:no CoCl2 added.The apoptosis rates were detected by fluorescent microscope and flow cytometry.The apoptosis morphological changes of the cell were observed by transmission electron microscopy.The protein expression of HIF-la was detected bv Western Blot. Results (1)Fluorescent microscope results showed that apoptosis rate in hypoxia 4 h、24 h、48 h group[(5.83±0.76)%,(15.00±3.28)%and(51.50±3.00)%],were higher than control group[(1.50±0.50)%](P＜0.05).(2)Flow cytometry analysis reached the same results as with fluorescent microscope.(3)Typical morphological changes of apoptosis were observed in hypoxia 24 h group.(4)HIF-1α expression in hypoxia 4 h、24 h and 48 h groups[0.69±0.035,1.02±0.044 and 0.71±0.046],were higher than control group(0.21±0.026)(P＜0.01).(5)Positive correlations were found between relative amount of HIF-1αprotein and apoptosis rate by fluorescent microscope and flow cytometry analysis(r=0.484,P=0.016;r=0.713,P=0.009).Conclusions Hypoxia could induce apoptosis of alveolar epithelial cells,which may participate in the pathogenesis of hypoxia-induced lung injury.

Objective To evaluate the precise,accurate and specific of two direct methods for measuring low-density lipoprotein cholesterol(LDL-C)based on the principle of selective hydrolysys. Methods Both DAIICHI and Randox reagents were compared with PVS method and the ultracentrifugally separated HDL and LDL fractions were used.Results Both methods all had good precise,the total CV was 3.96%～4.42%(Daiichi)and 0.78%～3.19%(Randox),repectively.The average concentrations of 48 serum samples were 3.68±1.23 mmol/L(PVS method),3.25±1.11 mmol/L(DAIICHI method)and 3.37±1.21 mmol/L(Randox method),respectively.There was no statistics difference between the results from PVS method and other two direct methods.Furthermore it indicated that the results determined by both direct methods had good relationship with that by PVS method.It also indicated that both direct methods had good specific to LDL-C.The dilute test demonstrated that there were good linearity between both direct methods of LDL-C and the linearity range was 9.28 mmol/L at least.Conclusion The direct methods for determining LDL-C based on the principle of selective hydrolysis possessed good precise and accurate and specific to LDL-C,and was meet with clinical application.

Targeting drug delivery system (TDDS) is one of the most concerned research fields in cancer treatment because it can bind selectively and react with the target diseased sites at the cellular or sub-cellular level, making distribution and release of drugs in a controlled manner, thus enhance therapeutic effects and reduce toxic and side-effects on normal cells. Polyamidoamine dendrimer (PAMAMD) is a kind of newly developed polymer in nanometer degree. Hyper-branched, monodispersity, three-dimensional structure and host-guest entrapment ability make it used as drug carrier, gene delivery system and imaging agent. Various targeting ligands, which have high affinity to specific organs, tissues or cells in human body, can be linked to surface functional groups of PAMAMD. And drugs and theoretical gene are carried by encapsulation or chemical conjugation. Finally, PAMAMD targeting drug delivery system can carry drugs and theoretical gene to diseased sites and then release them for targeted therapy. The PAMAMD-based conjugates have small size, ligh permeability and retention effect (EPR), low toxicity and so on. The research progress of PAMAMD modified by different ligands in targeting drug delivery system is reviewed, and research direction of the PAMAMD targeting delivery system in the future is also suggested.

Objective To investigate the clinicopathological characteristics of papillary thyroid carcinoma (PTC), and analyze their relationship with lymph node metastasis (LNM). Methods The clinicopathological data of 914 cases of PTC from January 2012 to December 2016 was analyzed retrospectively byχ2 test andχ2 trend test, including age, gender, tumor size, the number of lesions and LNM, in order to illuminate the characteristics of incidence and variation trend of PTC. Results The numbers of PTC cases in Shanxi Dayi Hospital increased year by year in recent 5 years (χ2=64.009, P=0.001). The rate of LNM was higher in age of ≤40 years old [34.9 % (84/241)] and > 70 years old [44.0 % (11/25)] than age 41-70 years old [15.6 % (101/648)] (χ2 = 39.577 and 14.009, both P= 0.000). It showed a triphasic pattern, which presented a uptrend with age decreasing in patients ≤ 40 years old (χ2= 10.490, P= 0.010), on the contrary, it appeared a rising trend with age increasing in patients>40 years old (χ2=10.170, P=0.010). The sex ratio of male and female was 1:2.97. The rate of LNM for male was higher than female (χ2=5.845, P=0.013). There was approximate risk of LNM between tumor diameter ≤1 cm and>1 cm (χ2=0.070, P=0.610). The rate of LNM in the cases of multiple lesions was apparently higher than that in cases of single lesions (χ2=145.440, P=0.000). Conclusions The incidence of PTC is on the rise. The risk factors of LNM are age (≤40 years old and>70 years old), male and multiple lesions.

AIM:To investigate the mechanism of apoptosis during the process of adult rat mesenchymal stem cells(MSCs)differentiating into neuron-like cells in vitro.METHODS:The MSCs were isolated primarily from adult rats bone marrow by density gradient and then expanded in medium as undifferentiated cells for 3-5 generations.The MSCs were divided into three groups at random.The control group was induced with ?-mercaptoethanol(?-ME).Meanwhile,the U0126 group was given ?-ME and U0126(10 ?mol/L)added at the beginning of induction.The PMA groups were treated with ?-ME and different concentrations of PMA since pre-induction.The effects of U0126 and PMA on the activity of neuron-like cells were observed by MTT.The effects of U0126 and PMA on the expression of neuron specific marker nestin and expression of apoptosis-related protein caspase,Bcl-2,Bax in neuron-like cells were detected by using immunocytochemistry method.TUNEL technique was used to detect apoptosis index.RESULTS:Compared to control group,neuron viability,nestin and Bcl-2 increased and neuron apoptosis decreased in U0126 group(P

With the development of therapeutic monoclonal antibodies, the therapeutic antibodies have increasingly dominated the global pharmacy market in recent years, which are concentrated on the treatment of carcinoma, transplant rejection, auto-immune diseases etc. Meanwhile, the therapeutic antibodies could be categorized on the humanized proportion into several different types, such as murine-derived antibody, chimeric antibody, humanized antibody and human antibody. Herein, we focused both on antibody research hot spots and humanized anti-tumor antibody drugs. Moreover, in accordance with the classical examples of humanized anti-tumor antibody drugs approved by relevant authorities worldwide, we explained the research status and situation from both the humanized technologies and production of humanized antibodies. Additionally, it seemingly rational and reasonable to demonstrate the trend of further humanized anti-tumor antibody drugs in the prospect of the present situation either domestic or overseas.

AIM: To investigate the inhibition of the recombinant human endostatin adenavirus (Ad-Es) on the experimental choroidal neovascularization(CNV) models by intravitreous injection.METHODS: Experimental CNV models were induced by semiconductor laser in 30 male Brown Norway(BN) rats and randomly divided into 3 groups with 10 rats in each group.At 21d after photocoagulation, the single administration group were given intravitreous injection with Ad-Es 0.01mL;the repeated administration group were given intravitreous injection with Ad-Es 0.01mL and a repeated injection 7d later;the saline control group were given intravitreous injection with saline 0.01mL.At 7d after final administration, the leakage of fundus fluorescein angiography (FFA) was observed.Various CNV areas were measured by using laser confocal microscopy of choroidal flatmount method.Pathology and ultrastructure were observed with light microscopy, the expressions of CD105 were measured by immunohistochemistry.RESULTS: The leakage of CNV of the administration group abviously decreased as compared with those in the saline group, the leakage of repeated administration group decreased compared with that of single administration group (P<0.05).Laser confocal microscope quantitative CNV analysis showed that CNV area of the administration group was significantly smaller than that of control group, the area of repeated administration group was smaller than that of single administration group (P<0.05).Under the light microscope, the vascular endothelial cell number and quantity of the administration group were significantly lower than that of the control group, the cell number of repeated administration group was lower than that of single administration group.CD105 expression of the administration group was significantly weaker than that in the saline group;the expression of repeated administration group was weaker than that of single administration group.CONCLUSION: Ad-Es can effectively inhibit semiconductor laser induced CNV in BN rats, and the inhibition effect of repeated administration group is better than that of single administration group.It may be a useful new method in the treatment of CNV.

Objective To examine the prevalence of plasmid mediated quinolone resistance (PMQR) genes and their correlation with the genes encoding β-lactamases in E.coli isolates.Methods A total of 200 levofloxacin-and/or ciprofloxacin-resistant E.coli isolates were collected from Fujian Medical University Union Hospital during the period from July to December 2013.PCR method was used to screen these E.coli isolates for the presence of qnrA,qnrB,qnrC,qnrD,qnrS,aac(6')-Ib-cr,qepA,oqxAB genes,and the blaTEM,blasnv and blacTx-M genes in the PMQR positive strains.Agar dilution method was utilized to measure the antimicrobial susceptibility of PMQR-positive strains.Phylogenetic analysis was conducted by triplex PCR.Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) was used to evaluate the genetic similarity between the PMQR-positive isolates.Results Of the 200 clinical isolates of E.coli,58 (29.0％)were PMQR-positive.And qnr,aac(6')-Ib-cr,oqxAB,and qepA genes were positive in 11 (5.5％),41 (20.5％),16 (8.0％),1 (0.5％) strains,respectively.The genes encoding CTX-M-1,CTX-M-9 and TEM type enzymes was positive in 32 (55.2％),17 (29.3％),and 1 (1.7％) of the PMQR-positive strains,respectively.The blasHv gene was not identified in any isolate.PMQR-positive strains were multi-drug resistant.Phylogenetic analysis indicated that 21 (36.2％),17 (29.3％),11 (19.0％),and 9 (15.5％) of the PMQR-positive strains belonged to group A,group D,group B2 and group B 1,respectively.ERIC-PCR suggested the PMQR-positive isolates belonged to 50 different types.Only one strain was non-typeable.Conclusions Most of the PMQR-related genes in E.coli are aac(6')-Ib-cr,qnr,and oqxAB in our hospital,which are highly relevant to β-1actamase genes.PMQR-positive strains may spread by way of non-clonal dissemination in our hospital.

Objective To explore the efficacy of low tidal volume ventilation strategy in children with acute hypoxia respiratory failure (AHRF).Methods A total of 79 hospitalized children with AHRF from Aug 2006 to Jul 2011 in PICU of Kunming Children's Hospital were enrolled in this study.The observation group in-cluded 55 children who received low tidal volume ventilation strategy (6-8 ml /kg),while the other 24 children (control group)were given traditional mechanical ventilation (10-12 ml /kg).Oxygenation situations such as PaO2 ,PaCO2 ,PaO2 /FiO2 ,oxygen index and blood gas pH value,organ function,mechanical ventilation complica-tions,hospitalization days and expenses in PICU and the mortality were observed.Results (1)PaO2 ,PaO2 /FiO2 and oxygen index in the observation group were better than those in control group after 24 h mechanical ventilation [(68.51 ±7.53)mmHg(1 mmHg =0.133 kPa)vs.(61.64 ±9.28)mmHg,(162.9 ±21.84)mmHg vs.(152.1 ± 19.03)mmHg,and 18.85 ±4.1 vs.26.53 ±5.2,respectively],and there were significant differences between two groups (P ﹤0.05);and there were also significant differences between two groups in the results after 48 h and 72 h mechanical ventilation.(2)The PaCO2 was (47.48 ±10.52)mmHg after 24 h in observation group,while the PaCO2 in control group was (30.17 ±6.59)mmHg,and it suggested excessive ventilation.(3)Mechanical venti-lation time (7.6 ±3.1)d and hospitalization days (12.8 ±3.6)d were shorter in observation group(P ﹤0.01). Barotrauma (7.3%)and mortality (20.0%)in observation group was significantly lower than those in control group (29.2%,41.6%;P ﹤0.01).The number of damaged organs in observation group was lower than that in control group (P ﹤0.05).Conclusion Low tidal volume ventilation with appropriate positive end expiratory pressure could improve oxygenation,prevent alveolar collapse,reduce complications and mortality for children with AHRF,it should be applied for the treatment of children with AHRF.

Objective To analyze the effect of bortezomib together with dexamethsone on the treatment of refractory multiple myeloma.Methods Bortezomib at 1.3 mg/m2 iv drop 1 d,4 d,8 d,11 d.Dexamethasonc 20 mg/d,1～4 d,8～11 d,17～20 d.21 days are used as a course.For bi-course dexamethasone was given by 20 mg/d,at 1～4 d.Results After 2～6 periods,3 cases achieved completely recovery(CR),4 cases are near to completely recovery(CR),3 cases got partially recovery(PR).Conclusion It is a good choice to treat refractory multiple myeloma by Bortezomib together with dexamethagone.