Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion ofbone marrow plasmacytes.It accounts for 10 ％ of all hematological malignancies.The proteasome,an intracellular enzyme complex that degrades ubiquitin-tagged proteins to regulate protein levels within the cell,plays an important role in maintaining cellular homeostasis.Proteasome inhibitors proved to be significantly effective in the clinical treatment of MM.In recent years,the application of the proteasome inhibitor has led to increased survival rates in MM patients.Bortezomib is the first proteasome inhibitor that has been approved by the US Food and Drug Administration due to its ability to reversibly inhibit the 26 s proteasome functions.Despite the fact that Bortezomib improves medical treatment,many patients experience difficulty responding to this drug and some patients who do respond eventually relapse.These results have led researchers to investigate new proteasome inhibitors with mechanisms different from those of Bortezomib.Some drugs that bind to the active site of the proteasome and irreversibly inhibit the complex have recently been developed and are currently being tested in advanced clinical trials.Here,we will elaborate on the proteasome inhibitors targeting MM and focus on newly discovered inhibitors that may overcome the resistance to Bortezomib.

Objective To study the value of Oxytocin challenge test (OCT) in high-risk pregnancy with abnormal umbilical artery resistance and the clinical significance of performing the umbilical velocimetry during OCT. Methods One hundred and seventy patients with abnormal umbilical artery resistance but maintained forward diastolic flow and 178 patients with normal umbilical blood flow received OCT, umbilical velocimetry was conducted during OCT. If the umbilical artery pulsatility index (PI) increased more than 0.5 during contraction and OCT was positive, cesarean section was performed in the same day, otherwise, vaginal delivery was tried. Results The rate of positive OCT was 45.3% and 10.1% respectively and the rate of positive OCT with umbilical artery PI increasing more than 0.5 was 37.4% and 6.7% respectively in abnormal umbilical artery flow resistance group and normal umbilical artery flow group ( P

Objective To investigate the effect of microbubble(Sono Vue) destruction with ultrasound on wound healing in rats. Methods Total 96 SD rats were accepted one rounded whole-layer skin incision on back each other and randomly divided into four groups:microbubble destruction with ultrasound(US + MB),microbubble(MB), ultrasound(US) and control group. Rats in US + MB group were injected with 0.5 ml microbubble contrast agent via tail vein,and then ultrasound irradiated for 3 minutes immediately. MB group were injected with 0.5 ml microbubble contrast agent. US group were injected with 0.5 ml physiological saline,and then ultrasound irradiated for 3 minutes immediately under the same condition. Control group were injected with 0.5 ml physiological saline. Feed each rat in single cage. On day 1,3,5,7,14 and 21 after wound creation,the excised wound tissues were analyzed by histology and VEGF expression in wounds by immunohistochemistry. Results HE staining: On day 7, wounds of US + MB group displayed the most accumulation of granulation tissue and all new capillaries were perpendicular to the wound surface, but the new capillaries of other 3 groups were disordered. Immunohistochemical examination of VEGF expression:the peak expression appeared on day 3 in US + MB group, other 3 groups were on day 5 to day 7.Conclusions US + MB treatment could improve the quality of wound healing and granulation tissues were maturated earlier than MB, US treatment and control group, which could accelerate wound healing. High temperature,high pressure and some kind of chemistry effecs induced by microbubble destruction with ultrasound can stimulate the secretion of endogenous VEGF, which may be the mechanism of promoting angiogenesis and wound healing.

Objective To explore the accuracy and practicability of the three-dimensional ultrasound in real-time intellectual positioning navigation.Methods The phantom was applied in the real-time intellectual positioning guided biopsy of three dimensional ultrasound,free-hand ultrasound-guided biopsy and bracket-guided biopsy with different depths(5 cm,10 cm) and different sizes of the targets (6 mm and 15 mm).The time spent,the length of the sample and the success rate of biopsy were compared among three groups,and statistical analysis was done.Results ①The different sizes of targets with different depths were shown in three kinds of biopsy that the real-time intellectual positioning guided biopsy of three-dimensional ultrasound spent more time than bracket-guided biopsy,less than free hand ultrasound-guided biopsy.The difference was significant (P ＜0.05).The aquired red-dyed sample was longer in the real-time intellectual positioning guided biopsy of three-dimensional ultrasound compared to free-hand ultrasound-guide biopsy and bracket-guided biopsy,the difference was significant (P ＜0.001).②For real-time IP-guided biopsy of three-dimensional ultrasound with same depth,larger size of targets(15 mm) spent less time than smaller saize of targets (6 mm),the difference was significant (P ＜ 0.05).However,compared to smaller saize of targets(6 mm),success rate of biopsy in larger size of targets(15 mm) had no significant difference (P =0.238 at depth of 5 cm,P =0.479 at depth of 10 cm).③For real-time intellectual positioning guided biopsy of three-dimensional ultrasound with same size,time spent was less in the targets at the depth of 5 cm than in the targets at the depth of 10 cm,the difference was significant (P＜0.05).The aquired red-dyed sample was longer in the targets at the depth of 5 cm than in the targets at the depth of 10 cm,and success rate of biopsy in the targets at the depth of 5 cm was higher too (P ＜0.05).Conclusions The real-time intellectual positioning guided biopsy of three dimensional ultrasound spend less time with high accuracy and success rate of biopsy,especially for smaller and deeper targets,can be clinically applied with accuracy and practicability.

Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Bloodletting ; Combined Modality Therapy ; Facial Paralysis ; therapy ; Female ; Humans ; Male ; Middle Aged ; Mouth Mucosa ; blood supply ; Young Adult

Objective To investigate the value and clinical significance of congenital heart diseases (CHD)detection in twins.Methods A total of 1103 twins were included in this study(127 twins were at high risk for CHD).The fetal hearts were scanned by ultrasound using Yagel's heart examination method. Autopsies were done when the pregnancy was terminated.And blood samples from fetal hearts or umbilical veins were used to evaluate fetal chromosomes.A close follow-up was conducted for normal heart cases and another heart examination was done within three months after birth.Results(1)12 twins(1.09%,12/ 1103)had CHD.Among them,4 cases were from the high risk for CHD group(33.3%,4/12),and 8 cases(66.7%,8/12)were from the low risk pregnancy group.(2)Two twins suffered from the same CHD (one pair were both TOF,and the other pair were both rhabdomyoma).One pair of twins had different abnormalities(one baby was TOF,and the other was duodenal atresia with a normal heart).All three pairs of twins chose termination and autopsies were conducted.Unanimous conclusions between prenatal ultrasound and autopsy were obtained.Nine twins were CHD in one baby and a normal heart in the other baby.Seven of them had the same conclusion after delivery.(3)Two twins with CHD were found with fetal abnormal chromosome.(4)1091 cases were not found having any abnormality,however,one fetus from one twin pair was diagnosed with ventricular septal defect(VSD)with abnormal chromosome after birth,and one fetus from another twin pair had patency of ductus arteriosus after birth.(5)The sensitivity of Yagel's heart examination was 82.4% and specificity was 100% in twins.Conclusion Yagel's heart examination is an effective and time-saving method to scan fetal hearts in twins.

Background and purpose:The most clearly recognized benefit of neoadjuvant chemotherapy (NAC) is that it can increase the proportion of patients who can be treated with breast-conserving therapy (BCT). However, the shrinkage modes of the primary breast tumor after NAC have been conifrmed as a predictor of BCT rate and prognosis. This study is to evaluate the accuracy of MRI predicting the shrinkage mode of the primary breast tumor after NAC with three-dimensional reconstruction technique.Methods:Sixty-one women with pathologically proven solitary invasive ductal carcinoma (ⅡA-ⅢC) were recruited. Breast specimens were prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by PHOTOSHOP software. The 3D model of residual tumors was reconstructed with 3D-DOCTOR software based on pathology and MRI imaging characteristics to evaluate the shrinkage mode. We devided the pathological shrinkage modes into surgical pCR (no residual tumors), solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions. Further, the clinical-pathological shrinkage modes were divided into 2 categories: distinct shrinkage mode (DSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC) and non-distinct shrinkage mode (NDSM, the longest diameter of the pathological residual tumors was more than 50% and/or >2 cm in comparison with the primary tumor before NAC).Results:The surgical pCR, solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions were observed in 23, 17, 5, 9, 7 and 18, 3, 13, 20, 7 patients by MRI and pathology, respectively (P=0.001). The accuracy, sensitivity and speciifcity of MRI for predicting pathological shrinkage modes were 86.2%, 65.6% and 91.4%, respectively. The DSM was observed in 36 (59.0%) patients by pathology, and 38 (62.3%) patients by MRI. Two methods had a high consistency in clinical-pathological shrinkage modes (κ=0.863,P=0.000). The accuracy, sensitivity and speciifcity of MRI for predicting clinical-pathological shrinkage modes were 91.0%, 64.0% and 94.8%, respectively. There was not a statistic difference in prediction between DSM and NDSM by MRI (P>0.05). Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.928 (P=0.000) for MRI to predict the clinical-pathological shrinkage mode.Conclusion:Three-dimensional MRI reconstruction after NAC could simulate and predict spatial location of residual tumors, and can be helpful in selecting patients who received BCT after NAC with tumor downstaging.

Objective To evaluate the effect of docosahexaenoic acid (DHA) on hepatic ischemia-reperfusion (I/R) injury in rats.Methods Fifteen male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were randomly divided into 3 groups (n =5 each) using a random number table: sham operation group (group S), hepatic I/R group (group I/R) , and group DHA.Hepatic I/R was induced by clamping the hepatic pedicle supplying the left and middle lobes of the liver for 60 min, followed by 24 h reperfusion in anesthetized rats.DHA 4 mg/kg was injected intravenously at 30 min before ischemia and 10 min of reperfusion in group DHA.The equal volume of solvent was given instead in S and I/R groups.Blood samples were taken from the inferior vena cava at 24 h of reperfusion for determination of serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, and resolvin D1 concentrations.The rats were then sacrificed, and the livers were removed for determination of myeloperoxidase (MPO) activity (by spectrophotometry), and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA expression (by quantitative real-time reverse transcriptase polymerase chain reaction).The livers were cut into sections which were stained with haematoxylin and eosin, and examined under light microscope.Results Compared to group S, the serum ALT and AST activities, serum resolvin D1 concentrations, and MPO activity, and IL-6 and TNF-α mRNA expression in liver tissues were significantly increased in I/R and DHA groups (P＜0.05).Compared to group Ⅰ/R, the serum resolvin 1D1 concentrations, and MPO activity and TNF-α mRNA expression in liver tissues were significantly decreased (P＜0.05) , and no significant difference was found in the serum ALT and AST activities in group DHA (P＞0.05).There was no significant difference in pathological changes of the liver between group DHA and group I/R.Conclusion DHA can attenuate inflammatory responses during hepatic I/R, but it is not sufficient to mitigate liver injury in rats.

Objective To investigate the effect of interleukin 6 (IL-6) on the growth and proliferation of human pancreatic cancer cell line Capan-2 and the signal transduction pathway. Methods MTr method was used to detect the effect of IL-6 of different concentrations on the growth and proliferation of Capan - 2 cells; cell apoptosis was detected by flow cytometry; the intracellular localization of phosphorylated STAT3 (P-STAT3) was determined by immunocytochemistry and western blot were used to detect P-STAT3, bcl-xl and Cyclin D1 in Capan-2 cells stimulated by IL-6. Results IL-6 (100 ng/ml) could remarkably promote the growth of Capan-2 cells from 1 to 4. 965 ± 0. 18 (P < 0. 05) ; the percentage of apoptosis decreased significantly from (3.21 ±0.23)% to (1.98 ±0.67)% (P <0.05) ; the expressions of P-STAT3, bcl-xl, Cyelin D1 increased significantly (P < 0.05), and the expressions of bcl-xl was positively correlated with that of P-STAT3 (r =0.985, P =0.015) ; the expressions of Cyclin DI was also positively correlated with that of P-STAT3(r=0.914,P=0.036),Conclusions IL-6 activate JAK/STAT signal transduction pathway,which played an important role in the growth and proliferation of Capan-2 cells in the presence of IL-6.

Objective To analyze causes for postoperative coxa vara and anti-rotation nail cutting-out after treatment of brittle femoral intertrochanteric fractures with proximal femoral nails ( PFN ).Methods An retrospective study was done on 227 patients with intertrochanteric fracture treated with PFN from June 2006 to February 2009. The causes for postoperative coxa vara and anti-rotation nail cutting-out were analyzed. Harris score was used to evaluate the functional recovery of the hip joint. Results Of all, 221 patients were followed up for 12-48 months (mean 23 months) and six patients were died from serious internal disease within one year. According to Harris evaluation system, the results were excellent and good in 183 patients, fair in 30 and poor in 14. Postoperative coxa vara and anti-rotation nail cuttingout occurred in 16 patients, eight of whom received reoperation to remove internal fixation and skeletal traction at abducent position and the other eight received prosthetic replacement. Conclusions Treatment of proximal femoral fracture with PFN requires a high precision of reduction and operation. Many factors including lateral cortical bone conditions of tuberosity, postoperative patient's cognitive condition,use of improved Jensen-Evans classification and Singh's classification may affect operation outcome.