Proteolysis-targeting chimera (PROTAC), as an emerging treatment method, has become one of the hottest technologies in the field of new drug research with a near-20-year development. PROTAC utilizes the natural ubiquitin-protease system in cells to induce targeted protein degradation, especially for protein of interest that are difficult to target by traditional small molecules. Moreover, PROTAC is expected to solve the problem of drug resistance that often occurs with small molecule drugs. However, the excessive relative molecular weight, poor solubility and membrane permeability, and low oral absorption of PROTAC make it challenging to druggability study. Currently, take pharmacokinetic characteristics as the entry point to continuously optimize and improve, so as to accelerate the transformation of PROTAC from laboratory to clinical application. Based on the basic structure and mechanism of PROTACs, this review introduces its pharmacokinetic properties, analyzes how to design efficient and stable PROTAC molecules, summarizes its current research progress in various diseases treatments, evaluates the development prospects and limitations of PROTAC, in order to provide more references for further research and application of PROTAC.

Objective To investigate the clinical pathological features of IgA nephropathy with nephrotic syndrome and risk factors for impairment of renal pathology.Methods 121 cases of IgA nephropathy with nephrotic syndrome were selected,all patients had been diagnosed with biopsy.The clinical pathological features wer analyzed, they were divided into two groups according to different kidney disease.The minor pathological changes which Leeˊs classification grade Ⅰ and grade Ⅱ patients belong to group A,with a total of 36 cases,while Leeˊs pathology heavier grade for grade Ⅲ,Ⅳ and Ⅴ grade level in patients belonging to group B,with a total of 85 cases.Clinical character-istics and clinical laboratory indicators of two groups were compared,and risk factors for renal pathological damage were analyzed in multivariate analysis.Results The average duration of group B was significantly longer than the average duration of group A,the difference was statistically significant (t =12.74,P <0.05).Mean arterial pressure of group B was significantly high than that of group A,the difference was statistically significant (t =5.31,P <0.05).Patients with hypertension,urinary erythrocytes with full vision and renal failureof group B were significantly more than those in group A,the differences were statistically significant (χ2 =14.29,9.74,8.26,all P <0.05).Total cholesterol and 24 h urinary protein excretion of group B were significantly lower than those in group A,the differences were statistically significant (t1 =8.75,t2 =6.73,all P <0.05).Serum albumin and hemoglobin levels of group B were significantly higher in group A,the differences were statistically significant (t3 =7.42,t4 =9.15,all P <0.05). Multivariate Logistic regression analysis showed,in IgA nephropathy with nephrotic syndrome,hemoglobin was a protective factor,the mean arterial pressure,24h urinary protein of red blood cells and microscopic urine >5.0 ×107 /Lwere dangerous aggravating factors.Conclusion Hemoglobin protective factors for IgA nephropathy with nephrotic syndrome,the mean arterial pressure,24h urinary protein excretion and urine red blood cells are their risk aggravating factors,they can make a more accurate judgment of the patientˊs condition.

Flow cytometry analysis of DNA ploidy level and S-phase fraction (SPF) was carried out in 24 snap-forzen tissue specimens of ovarian carcinoma. The relationship of DNA ploidy level and SP-F with age,clinical stage, ascites, histologic type,pathological grade,lymphocyte infiltration and psammoma bodies was analyzed.Results showed that the relationship of DNA ploidy level and SPF with ascites and pathological grade was significant. Aneuploid portion and SPF in patients with ascites or pathological grade Ⅲ or Ⅱ were higher than those in patients with no ascites or pathological grade I. The author considers that DNA ploidy level and SPF of ovarian carcinoma can serve as a relatively independent objective index which reflects tumor's biological behaviours,and will be of great auxiliary value to early diagnosis and therapy of ovarian carcinoma.

To understand molecular modules related to polyunsaturated fatty acids (PUFA) synthesis and eventually produce PUFA at high efficiency, we developed a protein complex analysis technology in Synechocystis sp. PCC 6803, and applied it to identify possible partner proteins interacting with the key enzymes that catalyze PUFA biosynthesis. We first constructed a recombinant expression of protein of slr1609 encoding the fatty acid activation enzyme, by fusing 3xFLAG tag with the target protein. Then we verified its expression by Western blotting targeting 3xFLAG tag. To maximize purification of Slr1609 protein complex, we optimized the protein expression conditions of Slr1609 in Synechocystis in a 5 L fermenter by monitoring its gene expression using RT-qPCR. The purification of the Slr1609 protein complexes was demonstrated by a Native-PAGE analysis. Finally, LC-MS/MS proteomic analysis allowed identification of the possible partner proteins interacting with Slr1609.
Bacterial Proteins ; chemistry ; Chromatography, Liquid ; Fatty Acid Synthases ; chemistry ; Fatty Acids, Unsaturated ; biosynthesis ; Proteome ; chemistry ; Proteomics ; Synechocystis ; enzymology ; Tandem Mass Spectrometry

Objective To discuss the effect of the quality control circle(QCC)activities in reducing the incidence of cold in reflux-enema of children.Methods The QCC team was built,reducing the incidence of cold in reflux-enema of children was named as the theme,to grasp the present situation,set the goal,fix the methods and carry out countermeasures.Results Through the development of QCC,making the standards of reflux-enema,the incidence rate of cold reduced from 25.0％(7/28) down to 3.6％(1/28),the nurses' abilities of technical operation and communication improved significantly.Conclusions Application of QCC in reflux-enema of children is practical.It can effectively improve the nurses' awareness of participating in the implementation management and nursing management system.By making the standardization of reflux-enema,nurses can improve the quality and effect of the reflux-enema and ensure the quality and safety of nursing.

Objective To retrospectively describe the technique and review the surgical results of OsteoMed M3 titanium plate and screws used to secure the posterior elements in the open position after expansive unilateral opendoor laminoplasty.Methods Twenty-six patients with multilevel cervical disc herniation and canal stenosis were treated with an expansive unilateral open-door laminoplasty with OsteoMed M3 plate and screws.The follow-up period was over 1 year.The improvement of spinal function after surgeries under JOA was evaluated to analyse the effects and releated factors.Results All of 26 cases' follow-up period was over 1 year.The mean JOA score increased significantly from 9.40 ± 1.658 ( range,5 to 13 ) points before surgery to 13.80 ± 1.958 ( range,7 to 16) points at final follow- up ( t =- 21.137,P =0.000 ).Mean recovery rate was 57.9％.Postoperative radiography,magnetic resonance imaging and computed tomography scan demonstrated significantly increased sagittal diameter and canal expansion.Two cases without relief of nurological symptoms underwent an additional anterior multilevel corpectomy.One case with ossification of the posterior longitudinal ligament had not good enough neurologic improvement after surgery.No neurologic deterioration owing to hinge reclosure or major surgery-related complications were observed.It would reduce the recovery for those with old age,long history,worse symptoms,cervical kyphosis and abnormal signal in MR imaging.It was good for patients to do early active cervical exercises after surgery.Conclusion Unilateral open- door laminoplasty with OsteoMed M3 titanium plate and screws fixation effectively maintains expansion of the spinal canal and resists closure while preserving alignment and stability.This modified technique is easy to perform with a low complication,is and economic,and is good for clinical application.

OBJECTIVE:To improve the management on drug supply in our hospital by using the Six sigma method. METHODS: The quality control of the management on drug supply is achieved by practicing the five steps of Six sigma: concept, measurement, analysis, improvement and control. RESULTS & CONCLUSIONS: Six sigma method did effectively bring down the defect rate of drug supply from 6.66% before the introduction of the method to 0.59% after and raise the degree of satisfaction to the work of medicine provision from 80% before the introduction of the method to 95% after.

Objective To investigate the expression of helper T cells (Th)17/regulatory T cells (Treg) balance associated factors in rheumatoid arthritis (RA) patients and their correlation with serum midkine (MK).Methods A total of 60 RA patients were divided into active RA patients (n=32) and inactive RA patients group (n=28).MK level in sera was detected by enzyme linked immunosorbent assay (ELISA) in 60 patients with RA and 30 healthy controls (HCs).The fraction of CD4+CD25+FOXP3+ Treg cells and IL-17+CD4+ Th17 cells in RA patients and healthy controls were determined by flow cytometry (FCM), and the expreasion of Foxp3, RORγt, Signal transducer and activator of transcription (STAT) 3 and STAT5 mRNA were detected with real-time polymerase chain reaction (PCR).Results were evaluated using ANOVA followed by q tests for comparisons of Th17 population between active RA patients, inactive RA patients and HCs, t test was used for comparing of Foxp3, RORγt, STAT3, STAT5 mRNA between RA group and HCs.The correlations between serum MK concentration and peripheral Treg cells, Th17 cells, Foxp3, RORγt, STAT3, STAT5 mRNA were analyzed by Pearson's correlation analysis.Results The percentages of Treg cells from active RA patients, inactive RA patients and HCs were significantly different (F=129.6, P＜0.01), the percentages of Treg cells of active RA patients [(1.41±1.05)％] were lower than that of the inactive RA patients [(3.6±1.6)％;q =7.92, P＜0.05] and healthy group [(7.7±1.7)％;q=22.45, P＜0.05], and there was significant difference between healthy group and inactive RA group (q=14.53, P＜0.05).The percentages of Th17 cells of the three groups were also significantly different (F=36.3, P＜0.01),the percentage of Th17 cells of active RA patients [(1.84±1.01)％] was significantly higher than that of inactive RA patients [(0.71±0.28)％;q=9.59, P＜0.05] and healthy group (0.53±0.16)％ [(P＜0.05;q=1 1.10, P＜0.05], there was no significant difference between the inactive RA group and healthy group (q=1.51, P＞0.05).The expression of RORγt and STAT3 mRNA in RA patients was higher than that of healthy controls (t=5.84, P＜0.01;t=4.52, P＜0.01).The expression of Foxp3 and STAT5 mRNA in RA patients were lower than healthy controls (t=6.01, P＜0.01;t=2.18, P＜0.05).Serum MK values were correlated with STAT5 (r=-0.55, P＜0.01), but not with Foxp3, RORγt, STAT3 mRNA or the percentage of Treg/Th17 cells.Conclusion Serum MK expression and the percentage of Th17 cells increase, while the percentage of Treg cells decrease in RA patients.Serum MK values are negatively correlated with STAT5 mRNA which is associated with Th17/Treg balance.This may be important in the pathogenesis of RA.

Objective To explore a new training method of nursing skills under 24 hours shift system in the practical training base in the college. Methods The practical training base in the college was rebuilt into a simulated hospital. 120 three-year-course nursing students in grade 2007 were divided into the control class and the experimental class with 60 students in each class. The control class adopted routine teaching method, including teacher demonstration, single project training, concentrated training before clinical practice. The experimental class participated in the tutoring mode of nursing skills under 24 hours shift system in simulated hospital. The cases were pre-designed and students acted as patients by tums. One teacher led 4 students into nursing skill training by day shift, evening shift and mid-night shift. The teaching effect was compared between two classes. Results There was significant difference between the two groups in comprehensive technique test and graduation theoretical test score. Clinical nursing teachers thought the skill training in simulated hospital under 24 hours shift system can help students prepare for the nursing work in hospital ahead of time and improve their comprehensive capability. Conclusions Training mode of nursing skills in simulated hospital under 24 hours shift system is feasible for enhancing nursing skills.

Objective To discuss the role of EPI-DWI unite ASSET in the detection of hepatic colorectal micrometastasis. Methods 29 patients with hepatic colorectal metastasis were examined with EPI-DWI unite ASSET and EPI-DWI. Results In a lesion detection analysis,the overall detection rate was 93% (58/63) for ASSET-EPI-DWI,and 81% (51/63) for diffusion-weighted MR imaging. ASSET and EPI-DWI was more sensitive than diffusion-weighted MR imaging(P = 0.01 1). Conclusion ASSET-EPI-DWI is superior to diffusion-weighted MR imaging in the detection of hepatic colorectal micrometastasis.