Adolescent ; Adult ; Aged ; Aged, 80 and over ; Apolipoproteins E ; blood ; genetics ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Venous Thromboembolism ; blood ; genetics ; Young Adult ; alpha-2-Antiplasmin ; analysis ; genetics

CDKs proteins are a kind of cell cycle protein-dependent kinases, which serve as important roles in controlling cell division and transcriptional stages. Among them, CDK9, as a key regulator responsible for the transcriptional elongation of cells, drives the development of various malignant cells and is considered as an important target in the field of anti-tumor drug development. However, the CDK family proteins feature high conservativeness and similarity in structure, leading to the poor selectivity and severe side effects for traditional small-molecular CDK9 inhibitors, which has limited their clinical applications. In view of this, there is an urgent need to investigate CDK9 targets through a novel strategy. The PROTAC is an emerging drug discovery strategy that the degrader could specifically recognize the target protein through indirect linkage with ubiquitin ligases and ultimately eliminate the target protein through the ubiquitination degradation system. This paper provides a brief overview of the structure and function of CDK9 protein, its relationship with the poor prognosis of clinical diseases, as well as the currently reported small molecular inhibitors. The latest research progress on the targeted degradation of CDK9 protein based on PROTAC technology is highlighted. Finally, the development prospects of this target protein in this novel technology field are summarized and prospected, aiming to provide a reference for the development of antitumor drugs in this direction.

Objective To evaluate the efficacy and tolerance of preoperative concurrent chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer.Methods From June 2007 to June 2013,51 untreated patients with histopathologically proven rectal cancer (T3/T4 or N (+))were included in this study.Three-dimensional radiotherapy was delivered to the whole pelvic cavity at 45.0-50.4 Gy/25-28 fractions.Two cycles of chemotherapy with FOLFOX4 or XELOX were given concurrently at weeks 1 and 4 of radiotherapy.Surgery was performed at 4-8 weeks after chemoradiotherapy.Adjuvant chemotherapy with FOLFOX4 or XELOX was given within one month after surgery.The Kaplan-Meier method was used to calculate survival rates,and the log-rank test was used for univariate analysis;the Cox regression model was used for multivariate prognostic analysis.Results Fortynine patients completed the preoperative chemoradiotherapy and surgery.The median follow-up was 2.9 years.The overall sphincter preservation rate was 65％;the overall downstaging rate was 59％.Ten (20.4％) of all patients achieved a pathologic complete response (pCR).Grade ≥3 toxicities occurred in 25％ of all patients,and the overall postoperative complication rate was 31％.The 3-and 5-year sample sizes were 24,12,respectively.The 3-and 5-year overall survival rates were 81％ and 69％,respectively;the 3-and 5-year disease-free survival (DFS) rates were 76％ and 60％,respectively;the 3-and 5-year local recurrence-free survival (LRFS) rates were 78％ and 70％,respectively;the distant metastasis-free survival rates were 82％ and 74％,respectively.The multivariate analysis showed that tumor downstaging was an independent prognostic factor for 5-year DFS and LRFS.Conclusions For locally advanced middle-low rectal cancer,preoperative radiotherapy with concurrent FOLFOX4/XELOX chemotherapy can increase pathologic downstaging rate,pCR rate,and sphincter preservation rate.Patients with tumor downstaging may have a better survival advantage.

Objective To investigate the protective effects of electroacupuncture on the endothelial tissues of microvessels in the basal ganglia in the rats with cerebral ischemia-reperfusion.Methods The MCAO model was established by using Longa's method.The immunohistochemistry SABC(strepto-avidin-biotin-peroxidase complex) method was employed to detect the expression of ICAM-1,P-selectin in the microvessel of rats'ipsilateral basal gan- glia.Results The number of positive ICAM-1 and P-selectin endothelial cells of model group were significantly in- creased,as compared to normal group and sham operated group(P

Objective To analyze the prognostic factors of patients with leukemia treated with single fraction total body irradiation (SFTBI) followed by hernatopoietic stem cell transplantation (HSCT).Methods From January 2001 to September 2008, 102 patients received HSCT. The differences of the survival rate, relapse rate and incidence of interstitial pneumonia (IP) between groups regarding different genders, ages, pathological types, transplantation methods and TBI parameters were compared and the factors related with the survival rate, relapse rate and incidence of IP were analyzed. Results The followup time ranged from 15 to 1482 days (median, 406 days). The follow-up rate was 95.1%. 86 and 55patients were followed up more than one year and three years. The 1-and 3-year survival rates were 59.0%and 44.0%. In univariate analysis, the 3-year survival rate was signifcantly different between the groups with and without relapse before transplantation (20% vs. 55%, χ2 = 6.33, P = 0. 012), allogeneictranplantation versus autologous tranplantation (39% vs. 68%, χ2 = 8.06, P = 0.005), grade 3 or more acute graft versus host disease (aGVHD) and grade 0 -2 aGVHD (0% vs. 54%, χ2 = 7.52, P = 0.006),with and without relapse after transplantation (19% vs. 58%, χ2 = 10.13, P =0.001), with and without IP (23% vs. 58%, χ2 =8.35, P=0.004). Multivariate analysis showed that grade 3 or more aGVHD was the only statistically significant prognostic factors (χ2 = 12. 74 ,P =0. 000). The l-and 3-year relapse rateswere 30. 0% and 50. 0%. The incidence of relapse was obviously higher in the group with relapse before transplantation than that without (47% vs. 16%, χ2 =7. 32, P=0. 007). Multivariate analysis showed thatrelapse before transplantation was a significant factor predicting relapse after transplantation (χ2 = 9. 39,P =0. 020). The cumulative incidence of IP was 35.0%. The incidence of IP was different between groups with dose homogeneity > 3% and ≤ 3% (27% vs. 4%, χ2 = 5. 21, P = 0. 023), with and without acute parotitis (34% vs. 3%, χ2 = 14. 15, P= 0.000), allogeneic transplantation group and autologous transplantation group (31% vs. 8%, χ2= 7.70, P= 0.006). Multivariate analysis showed that transplantation methods, acute parotitis and dose homogeneity were statistically significant factors in predictingIP (χ2 = 10. 08 , 10. 08 and 7.69 , P = 0. 002 , 0. 002 and 0. 010 , respectively) . Conclusions Patients who develop grade 3 or higher aGVHD have poor prognosis. Dose homogeneity influences the incidence of IP. Patients undergoing allogeneic transplantation are apt to have IP. Acute parotitis is related with IP and might be a predictor.

In this study,we discussed the way of imparting the microbial knowledge and elevating non-biological student's science in public optional course "Microbes and Man" from the teaching practice.During the course,we first chose the material according to students' characteristic,and then introduced several methods like lecturing on subject,visiting factories and making microbial experiments in order to inter-est students in microbiology and get better in teaching effects.

Objective To observe the motions of the rectum and bladder by image?guided radiotherapy ( IGRT) and to analyze their impact on treatment. Methods Eighteen patients with prostate cancer undergoing intensity?modulated radiotherapy ( IMRT) were enrolled in the study and 247 cone?beam computed tomography ( CBCT) images were obtained from this study. The clinical target volume, bladder, and rectum were contoured on all simulated CT and CBCT to examine their volume and position changes. The dose distributions were recalculated based on the data of the x?, y?, and z?axis setup errors. The doses to planning target volume ( PTV) and organs at risk were calculated in the replanning, and their impact on treatment was analyzed. Comparison of the planning and replanning results was made by paired t?test. The effects of displacements and volumes of the bladder and rectum on target doses were analyzed by Pearson correlation method. Results Great changes in the volumes of the bladder and rectum were observed during the treatment. For the planning and replanning results, PTVD95% was 7777. 37 cGy vs. 7628. 56 cGy ( P=0. 027), PTV Dmin was 87. 91 cGy vs. 83. 35 cGy (P=0. 000), and RVP was 5. 89% vs. 8. 31%(P=0. 000). There were correlations between PTVD95% and the motions of the bladder and rectum, with correlation coefficients of 0. 296 and 0. 177, respectively. The correlation coefficient between rectal volume and PTVD95% was 0. 115, indicating a certain correlation. There is a certain correlation between and PTV Dmin and bladder volume, with a correlation coefficient of?0. 128. Conclusions The recovery of the state during localization for the bladder and rectum, especially the latter, has great significance to ensure the target dose and reduce exposure of the rectum in the IMRT for prostate cancer.

Objective To analyze the data from intensity-modulated radiotherapy ( IMRT) for prostate cancer guided by kilovoltage cone-beam computed tomography (CBCT), and to provide a clinical basis for selecting the optimal image registration method and reasonable target volume margins.Methods A total of 16 patients with prostate cancer who received radical IMRT were enrolled, and CBCT for online position verification was performed 214 times.The images were obtained after conventional skin marking and laser alignment, and automatic registration, bone registration, soft tissue registration, and manual registration were performed for CBCT images and planned CT images.The differences between these four registration methods were evaluated, and the margins for extending clinical target volume into planning target volume (PTV) were calculated.Results The setup errors in left-right, anterior-posterior, and cranial-caudal directions for automatic registration, bone registration, soft tissue registration, and manual registration were-0.6±2.8 mm/-0.6±4.5 mm/-0.6±3.8 mm,-0.7±2.7 mm/-0.9±4.5 mm/-0.8±4.1 mm,-0.8± 2.6 mm/-0.3±4.4 mm/-1.1±4.0 mm, and-0.6±2.9 mm/-0.7±5.1 mm/-0.9±3.9 mm, respectively. There were no significant differences between the four registration methods.The margins for extension in the left-right, anterior-posterior, and cranial-caudal directions were calculated as 4.7 mm, 5.2 mm, and 6.5 mm, respectively.Conclusions With a comprehensive consideration of various factors, a default setting of automatic registration and manual fine adjustment is appropriate for CBCT-guided radiotherapy for prostate cancer.The margins for extension in the left-right, anterior-posterior, and cranial-caudal directions are 4.7 mm, 5.2 mm, and 6.5 mm, respectively.

Objective To evaluate the clinical value of color doppler flow image (CDFI) and three-dimension color power angiography(3D-CPA) in the diagnosis of thyroid nodules. Methods A total of 62 pathologically confirmed thyroid nodules of 30 patients were analyzed. All the patients underwent ultrasound examination and operation in the Second Affiliated Hospital of Harbin Medical University between January, 2008 and May, 2009. Both CDFI and 3D-CPA were performed before the operation. All the nodules were divided into three groups including nodular goiters, thyroid adenomas and thyroid cancers according to the pathological results. The hemodynamic features and the vascular morphology characteristics of nodules in different groups were compared. Results 3D-CPA showed that blood vessels of nodular goiters commonly distributed surrounding the mass and the inner vessels were thin and regular, thyroid adenomas were bulb-shaped and netted structure, and malignant thyroid nodules displayed distorted and irregular distributed vessels. Peak systolic velocity (PSV)of the three groups were (39.43±11.17a), (46.39±12.98) and (65.17±9.23)cm/s, respectively. Resistance index(RI) of the three groups were (0.32±0.08), (0.41±0.06) and (0.69±0.07)cm/s, respectively. Both PSV and RI in malignant thyroid nodules were higher than in nodular goiters and in thyroid adenomas and the difference were statistical significant (all P < 0.05). The blood flow grade of malignant nodules was also higher in malignant nodules than in other two groups(χ2 = 17.11, 12.79, 23.05, 15.41, P< 0.01). Conclusions CDFI and 3D-CPA could visually demonstrate the characteristic and distribution of the inner and outer blood vessels, display the vessels structures, and they are benefit the differential diagnosis of thyroid nodules.

Objective The goal of this report was to evaluate the applicability of the da Vinci S surgical system in thoracic surgery.Methods The da Vinci S surgical system consists of a console, a patient cart, and a vision system.The patient cart loading with 3 robot arms and 1 central endoscope arm connects the console which commands the movements of the arm tips.The robot arm tips are introduced via small chest wall ports and attached to the arms of the robot.The surgeon, sitting at the console, manipulates highly sensitive sensors that transfer the surgeon's movements to the arm tips.The so called EndoWrist'technology offers up , down, left, right, and twist, seven degrees of movements, thus exceeding the capacity of a surgeon's hand in open surgery.17 intrathoracic lesion cases, including 12 Myasthenia Gravis, 1 diaphragm hernia, 2 esophageal cancer, 1 pulmonary cancer , 1 pneumothorax, were evaluated for clinical application of the da Vinci S surgical system.Results Out of 17 surgical procedures, 14 procedures were done using the robot from beginning to the end, including 12 thymectomies, 1 diaphragm hernia repair, 1 pulmonary bleb dissection.Only gastric mobilizations, the abdominal part procedures were done using the da Vinci S system, and the thoracic part procedures were done through small incision thoracotomy in 2 cases with esophageal cancer.One resection of left upper lobectomy had to be converted due to surgical problem.The postoperative courses were uneventful.Conclusion The da Vinci operating robot can do nearly all kinds of thoracic operations.Advanced general thoracic procedures can be performed safely and effectively with the da Vinci S robot allowing precise dissection.This benefit becomes evident most elegantly in thymectomies.The robot operation procedures can be done by the doctors with open and assisted thoracopic surgery experiences and other personnels getting trained in a short period of time, but case selection and preparing emergency thoracotomy at any time is needed to ensure the patient safety.