The latest developments of techniques that prolong the half-life of protein drugs were reviewed.The therapeutic potential of several proteins is limited by their rapid clearance from the body,resulting in the need for frequent treatment of individuals to maintain drug levels.Several techniques including chemical modification,protein fusion,microsphere,glycosylation,and protease-resistant variants,and so on,prevent rapid degradation of such drugs and prolong their half-lives in vivo.Several successful protein drugs with prolonged half-life have already been on the market or on clinical trials.The principles,efficiencies and scopes of application of these techniques were described,compared and discussed.

Objective To investigate the distribution of Human Papillomavirus 16 (HPV16) infection and its mixed infection with other HPV subtypes in the Yunnan region. Methods 16 166 cases of women were tested using flow fluorescence Luminex technology. Results (1) HPV16 infection rate and mixed infection rate was 2.2%and 28.0%, respectively; (2) The most common type of HPV16 mixed infection was HPV52, followed by HPV33. The two kinds of mixed infection accounted for 39.8% of the total infection rate; (3) There was a significant difference between each age group of HPV16 mixed infection (Chi=26.39, <0.01) . Conclusion The HPV16 infection was mainly HPV infection in Yunnan region. HPV16 mixed infection merged mainly with HPV52 and HPV33. HPV16 mixed infection was associated with age.

PNS (Panax notoginseng saponins) is the main medical bioactive component in Panax notoginseng. The medical value of PNS cannot be extended because of its low production. With the deep study of saponins biosynthetic pathway, the control of PNS biosynthesis through metabolic engineering has gradually become possible. In this study, the Squalene synthase (SS) over-expression vector was established. By the way of agrobacterium-mediated method, the vector was transfered and integrated into the Panax notoginseng genome. The result of the PCR detection and the saponin content detection shows that over-expression SS is able to produce high level of Panax notoginseng saponins, and confirms the regulatory function of SS in the biosynthesis of ginsenosides in Panax notoginseng. It provides a theoretical basis and technical basis for the construction of PNS homologous or heterologous efficient expression system in the future.

Adolescent ; Bone Marrow Transplantation ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Thalassemia ; surgery ; Transplantation Chimera

Objective To evaluate the therapeutic effect of acupoint catgut embedding on gastrointestinal dysfunction after surgery in patients with severe traumatic brain injury.Methods Sixty-eight consecutively hospitalized patients with gastrointestinal dysfunction after surgery in patients with severe traumatic brain injury admitted to the Department of Intensive Care Unit (ICU) in the First Affiliated Hospital of Zhejiang University of Chinese Medicine from January 2015 to December 2015 were enrolled.Six of those patients were withdrawn from the course of observation,and actually only 62 patients entered the study.They were divided into an observation group (32 cases) and a control group (30 cases) by random number table.All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days.The observation group was additionally treated with acupoint catgut embedding.The control group took mosapride tablets via a nasogastric tube 5 mg,3 times a day.Intra-abdominal pressure (IAP),gastric residual volume (GRV),time for reaching standard enteral nutrition,serum diamine oxidase(DAO),D-Lactate activity,incidence of hospital-acquired pneumonia (HAP),hospitalization days in ICU,28-day mortality and adverse reactions of acupoint catgut embedding were observed in the two groups.Results After treatment,the levels of IAP,DAO,D-lactic acid were lower than those before treatment,GRV was less than that before treatment in the two groups,and after treatment for 7 days the changes were more significant in the observation group [IAP (cmH2O,1 cmH2O =0.098 kPa):12.42±3.11 vs.17.70 ± 2.98,GRV (mL):129.54 ± 57.54 vs.242.91 ± 99.29,DAO (U/L):9.06± 2.84 vs.13.60 ± 7.16,D-Lactate (mg/L):16.47 ± 5.39 vs.26.29 ± 9.62,all P ＜ 0.01].Days of mechanical ventilation (days:6.97 ± 4.13 vs.9.23 ± 4.61),time for reaching standard enteral nutrition (days:4.25 ± 3.15 vs.5.50 ± 3.12) and hospitalization days in ICU (days:9.50± 4.03 vs.12.20 ± 6.38) in observation group were significantly shorter than those in control group (all P ＜ 0.05).The incidence of HAP [15.6％ (5/32) vs.40.0％ (12/30)] and 28-day mortality [3.1％ (1/32) vs.6.7％ (2/30)] in observation group were obviously lower than those in control group.The patients in observation group had no significant adverse reactions of acupoint catgut embedding.Conclusions Acupoint catgut embedding therapy is not only easy to operate,but also can effectively improve gastrointestinal motility and intestinal barrier function in patients with gastrointestinal dysfunction after surgery of severe head injury,thus it is beneficial to reaching the enteral nutritional goal in less time,reducing the incidence of HAP,shortening the hospitalization time in ICU and promoting the recovery of the patients.

Objective To explore the incidence and clinical treatment of related complications caused by implantable venous access port(IVAP) in patients with breast cancer during chemotherapy.Methods The data of 755 patients with breast cancer recieved chemotherapy by which caused some related complications in our hospital from January 2014 to March 2016 were retrospectively analyzed.Results 753 patients IVAPs were implanted succussfully.The total placement time of implantable venous access port was from 110 days to 940 days,with median placement 147.33 days.The related complications of IVAP were catheter malposition(0.79％,6/755),catheter-related thrombosis(27.81％,210/755),catheter fracture(0.13％,1/755),port exposure(0.93％,7/755) and IVAP-related bloodstream infection(0.13％,1/755).The IVAP-related complications and thrombosis rate were significant higher when IVAPs implanted in the left internal jugular veincompared with that in right internal jugular vein(34.88％ vs.25.74％,33.10％ vs.24.68％).Conclusion Application of IVAP in patients with breast cancer during chemotherapy is a safe and effective operation.The most common complication is asymptomatic mural thrombus formation around the catheter,which should be paid attention to.

OBJECTlVE To study the reIationship between microRNA(miRNA)-122 and Iiver injury in-duced by anti-tubercuIosis drugs,and to discover the new biomarkers for earIy diagnosis of this type of Iiver injury. METHODS mice were given 2 mL isoniazid oraIIy at 90 mg·kg-1 . BIood and Iiver tissue sampIes were coIIected at 1,3,5,7,14,21 and 28 d after administration of isoniazid. Serum gIutamic-pyruvic transaminase( GPT)and gIutamic-oxaIoacetic transaminase( GOT)IeveIs were determined using an automatic biochemicaI anaIyzer. Cu/ Zn-superoxide dismutase( Cu/ Zn-SOD ) activity and maIondiaIdehyde( mDA)content were detected by biochemicaI method. ReaI-time qPCR was used to measure the expression of miRNA-122. RESULTS GPT and GOT IeveIs were significantIy higher at 14 and 21 d(P﹤0.05)than in the controI. Cu/ Zn-SOD began to decIine whiIe mDA began to increase after 5 d(P﹤0.05). miRNA-122,which progressiveIy decreased after administration,was reduced to the mini-mum 0.58 ±0.02 at 14 d. There were good correIations between miRNA-122 and GPT,Cu/ Zn-SOD, mDA(the correIation coefficients were -0.370,0.268,and -0.298,respectiveIy),but no correIation with GOT was observed. CONCLUSlON The tissue miRNA-122 profiIe can be used as a sensitive marker for anti-tubercuIosis drug-induced Iiver injury,which couId contribute to the earIy diagnosis of Iiver injury.

AIM: To observe the dynamic changes of interleukin-4(IL-4),IL-10,IL-12 in rat serum and lung tissues during acute respiratory distress syndrome (ARDS). METHODS: The ARDS model of rats was induced by intravenous injection of oleic acid. The levels of IL-4 ,IL-10,IL-12 in serum and the supernatant of lung tissues were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: The Levels of serum and lung IL-10,IL-12 in ARDS rats were increased in 4 h ,8 h,16 h group compared with control group . The levels in IL-10 in serum in 16 h group and IL-10 in lung tissues of 8 h group were lower than that in 4 h group. The Levels of IL-4 in serum in 4 h, 8 h group were higher than that in control group , while IL-4 in 16 h group was lower than that in 8 h group. IL-4 of lung tissues in 4 h,8 h,16 h group were increased significantly,but in 16 h group were lower than that in 8 h group. The biggest changes of pulmonary coefficient and histopathology were observed at 4 h after injection of oleic acid. CONCLUSIONS: IL-4,IL-10 and IL-12 might play important roles in inflammatory reaction induced by oleic acid. The pro- and anti-inflammatory cytokines produced successively during ARDS. The relationship between unbalanced cytokines and lung injury in ARDS needs to be further studied.

The purpose of this study was to fabricate decelluarized valve scaffold modified with polyethylene glycol nanoparticles loaded with transforming growth factor-β1 (TGF-β1), by which to improve the extracellular matrix microenvironment for heart valve tissue engineering in vitro. Polyethylene glycol nanoparticles were obtained by an emulsion-crosslinking method, and their morphology was observed under a scanning electron microscope. Decelluarized valve scaffolds, prepared by using trypsinase and TritonX-100, were modified with nanoparticles by carbodiimide, and then TGF-β1 was loaded into them by adsorption. The TGF-β1 delivery of the fabricated scaffold was measured by asing enzyme-linked immunosorbent assay. Whether unseeded or reseeded with myofibroblast from rats, the morphologic, biochemical and biomechanical characteristics of hybrid scaffolds were tested and compared with decelluarized scaffolds under the same conditions. The enzyme-linked immunosorbent assay revealed a typical delivery of nanoparticles. The morphologic observations and biological data analysis indicated that fabricated scaffolds possessed advantageous biocompatibility and biomechanical property beyond decelluarized scaffolds. Altogether this study proved that it was feasible to fabricate the hybrid scaffold and effective to improve extracellular matrix microenvironment, which is beneficial for an application in heart valve tissue engineering.

Objective Head and neck cancer radiotherapy patients often appear a series of oral complications including mucositis, xerostomia, pain, dysphagia.The purpose of this study was to investigate whether personalization customized positioning oral stent was able to push normal tissue off the high dose target area and maintain accurate repeatable stable positions, thus protecting the normal tissue during radiotherapy of the nasopharyngeal carcinoma patients.Methods 15 newly diagnosed nasopharyngeal carcinoma patients were collected from March to August 2016 in Department of Radiation Oncology, Nanjing General Hospital of Nanjing Military Region and randomly divided into trial group and control group.Two groups of patients were treated with intensity modulated radiation therapy (IMRT).Trial group patients wear personalization customized oral positioning stents during radiotherapy while the control group did not wear.After radiotherapy, we compared the exposure doses of clinical target area(CTV) and normal oral tissue in two groups.ResultsThe left parotid gland radiotherapy doses of the trail group and the control group were 2223.557±294.549 cGy and 2900.563±374.660 cGy, the difference was statistically significant(t=3.847, P=0.002);the right parotid gland radiotherapy doses of the trail group and control group were 2284.957±256.673 cGy and 2994.670±339.264 cGy, the difference was statistically significant(t=4.512, P=0.001).The mean exposure doses of CTV in two groups were no statistically significant difference (6142.829±135.986 cGy vs 173.306±6221.825 cGy, t=0.971, P=0.349.Conclusion During the intensity modulated radiation therapy, patients with personalization customized oral positioning stents can keep the mandible in a precise repeatable stable position.And it can reduce the exposure dose of bilateral parotid without affect the radiotherapy effect of the clinical target area.