Protein degradation is fundamental to cell viability,selective elimination of regulatory proteins in the cell is an effective mechanism for regulating vital cell processes.Rapid proteasomal protein degradation is key to activation of repression of many cellular processes,including cell-cycle progression and apoptosis.Bortezomib as a proteasome inhibitor has been approved by FDA for multiple myeloma treatment.This review summarizes current knowledge of the structure and function of the proteasome and its targets.In addition,preclinical findings obtained with Bortezomib are reviewed,and existing clinical data on Bortezomib are presented.

Objective To investigate the effect of a newly developed photosensitizer—chlorophyll derivative combined with irradiation of 650 nm laser for PC3, an androgen independent cell line in vitro. Methods PC3 was cultured and designed to 4 groups,including blank control,laser irradiation,medication of photosensitizer and medication of photosensitizer with laser irradiation (treated).The medicated concentration of chlorophyll was 0.1 g/L and irradation fluence of 650 nm semiconductor laser was 6 J/cm2.Intracellular distribution of photosensitizer and cellular morphological alterations were studied through light microscopy, electron microscopy and laser confocal microscopy. Results It showed the shrinkage, round-up and membrane integrity of treated PC3 under light microscopy.Sable deposits were observed in cytoplasm of cells in both photosensitizer and treated groups.Transmission electron microscopy showed the fragmentation of DNA and condensation of chromatin beneath the karyolemma in treated cells.In cytoplasm,the endoplasmic reticulum and mitochondria swell to form vesicles and vacuoles.It showed the strong red fluorescence in the cytoplasm of treat cells compared with the red fluorescence indifferent to the background through laser confocal microscopy. Conclusions Chlorophyll derivative based photodynamic therapy is able to induce apoptosis of PC3 in vitro.Mitochondria is presumed to be the primary target of photodynamic therapy and trigger the apoptotic pathway.

Objective To observe the anticoagulant effect of low molecular weight heparin on induced hemodialysis in patients with acute renal failure.Method One hundred and eight patients with acute renal failure treated with induced hemodialysis were randomly divided into low molecular weight heparin(LMWH)group and unfractionated heparin(UFH)group.A bolus disc of UFH was given at first and then maintained by continuous infusion in UFH group,whereas a single bolus dose of LMWH with 2000AFXa IU to 4000AFXa IU in LMWH group.Results Anticoagulant effect between LMWH and UFH did not show significant discrepancy during induced hemodialysis.The bleeding from internal jugular vein catheter increased in the UFH group much more than that in the UFH group was significantly higher than that in the LMWH group.Anti-FXa blood levels were significantly higher in LMWH group than in UFH group.Conclusions LMWH has minor influence on aPTT and TT,while its anticoagulation effect approximates to that of UFH.LMWH represents a realistic alternative agent UFH in acute renal failure induced hemodialysis.

Objective To study the immunophenotypic features of NK/T cell lymphoma in children and its association with Epstein-Barr virus (EBV) infection. Methods Five cases of children′s NK/T cell lymphoma were studied. CD45RO, CD3?, CD56, CD20, TIA-1 and granzyme B were detected by immunohistochemistry staining for investigating immunophenotype. The expression of EBV-latent membrane protein (LMP-1) were detected by immunohistochemistry. EBV-encoded RNA (EBER1/2) were detected by in situ hybridization (ISH). Results CD45RO, CD3?, TIA-1 and granzyme B were positive in 5 cases, CD56 was positive in 2 cases, while CD20 negative in 5 cases.EBER1/2 positive in 4 cases and LMP-1 positive in 3 cases.Conclusions NK/T cell lymphoma in children is strong associated with EBV infection,and EBV infection may play an important role in the pathogenesis of children NK/T cell lymphoma.

Objective To study the clinical significance of the mRNA expression level of a novel gene which encodes a kind of transmembrane prostate protein induced by androgen-PMEPA1, as it may predict the progress of prostate cancer from hormone-dependent to hormone-independent. Methods We used Real-time PCR to detect the mRNA expression of PMEPA1 and GSTP1 in prostate cancer cell lines (LNCaP, PC-3), epithelia cells of benign prostatic hyperplasia and tissues from 33 patients with prostate cancers and 16 cases of prostatic hyperplasia. Results We found the mRNA expression of GSTP1 and PMEPA1 were both down-regulated in prostate cancer cell lines. The mRNA expression of GSTP1 was up-regulated in 6.1% of cases, down-regulated in 81.8%, and showed no difference in 12.1%. While PMEPA1 was highly expressed in 27.3% of cases, lowly expressed in 27.3%, and not differently expressed in 45.4%. Statistical analysis showed that the mRNA expression of GSTP1 was relevant to ages, but had no relationship with PSA, TNM stage, osseous metastasis or tumor differentiation, while the mRNA expression of PMEPA1 was relevant to osseous metastasis and tumor differentiation, but had no relationship with age, PSA or TNM stage. Conclusions PMEPA1 is possibly a useful biomarker, as it can identify patients with unfavourable prognosis, however, this hypothesis needs to be further studied with large samples.

Objective To compare the normal anatomy of the anterior cruciate ligament (ACL) of fresh frozen cadaveric knee specimen in oblique coronal thin-slice section with oblique coronal magnetic resonance imaging. Methods One fresh cadaveric knee specimen was scanned with MR T1-weighted spinecho sequence.then the specimen was frozen and sliced with a band saw along the oblique coronal plane into 1.0-mm-thick sections that corresponded to the MR images,MR images including oblique coronal T1-weighted and T2-weighted images of 50 normal the knee joints were retrospectively reviewed to observe the MR imaging features of the cruciate ligament. Results Anteromedial and posterolateral bundles of ACL were clearly depicted on both anatomic slices and MR images.The anteromedial bundles originated from the posteromedial aspect of the lateral femoral condyle,coursing through the lateral intercondylar notch in an anterior,inferior,and medial direction,and inserted on the anteromedial aspect of the intercondylar eminence. The posterolateral bundles originated from the anteromedial aspect of the lateral femoral condyle,passing laterally and inferiorly through the lateral intercondylar notch,and inserted on the posterolateral side of the intercondylar eminence.The full length of ACL of all 50 individuals was showed on MR images.MRI clearly differenitated the anteromedial and posterolateral bundles of ACL and depicted the full length of the bundles.similar to the findings on sectional anatomy.Conclusion Oblique coronal MR imaging is the best way to demonstrate ACL and should be used for clinically suspected injury of ACL.

In industrial glutamate fermentation, intermitted feeding glucose with the help of off-line glucose measurement is generally necessary. This kind of feeding strategy could cause large variations in glucose concentration so that it is not favorable for the achievement of efficient and stable glutamate fermentation. Glutamate fermentation is characterized with typical non-growth association behavior, and during glutamate production phase glucose consumption is closely correlated with ammonia consumption. In this study, glucose concentration was controlled at various pre-determined levels by predicting glucose consumption amount and thus its concentration with the aid of on-line monitoring ammonia consumption. When glucose concentration was controlled around a lower level of 5 g/L~10 g/L, the final glutamate concentration could reach a relatively higher level of 80 g/L. In this way, the huge osmotic stress change due to the large glucose concentration variation with the intermitted feeding method could be avoided and the glutamate fermentation performance enhancement be expected.

Objective To investigate the features of familiar facial palsy,ophthalmoplegia and dysphagia characterized by autosomal dominant inheritance in a family and to discuss the classification and pathogenesis of the disease.Methods Clinical,electrophysiological,pathological examinations were performed and blood samples were obtained from 5 patients and 26 family members.PCR protocol was used to identify a certain gene. Results In the 5 patients receiving physical examination,all had ptosis,external ophthalmoplegia,facial paralysis,dyphagia,hoarseness,decreased pharyngeal reflex;4 had amyotrophy of muscle of tongue,temporal nuscle,masseter and muscles of distal lower limbs;3 had proximal limb asthenia and distal limbs amyotrophy.Compared to those of oculopharyngeal muscular dystrophy(OPMD)with similar symptoms and signs,both electrophysiological manifestation and pathological findings of the family members supported the diagnosis of muscular dystrophy,but the(GCG)6(GCA)3GCG in the first exon of PABPN1 mutated neither in normal family members nor in patients.Conclusions This family presents clinical manifestations somewhat resembling to those of OPMD and distinctive to other disorders,but has a totally different genetic background from OPMD.It may be a new subtype of muscular dystrophy.

AIM:To analyze the characteristics of optical coherence tomography ( OCT ) in diabetic optic neuropathy ( DON ) retrospectively.
●METHODS:Retrospective study. A total of 175 cases of type ll diabetes with fundus lesions from Dec. 2013 to Dec. 2015 were selected and the clinical information was collected. These cases were diagnosed by consultation between Departments of Ophthalmology and Endocrinology in the Second Affiliated Hospital of Xi′an Jiao Tong University. The results of body examination were recorded and cases were examined by color fundus photography, fluorescein fundus angiography ( FFA) and OCT. All these data were analyzed.
●RESULTS: A total of 49 cases ( 90 eyes, 25. 7%) were diagnosed DON through FFA which manifested abnormal fluorescence in optic papilla. Results of OCT showed:among 90 eyes of DON patients, 15 eyes ( 16. 7%) had normal optic nerve form; 20 eyes(22. 2%) of excavation of optic disc became smaller or disappeared, with prelaminar tissue and peripapillary retinal nerve fiber layer (RNFL) swelling;26 eyes (28. 9%) manifested optic cup deep and cup/disc ratio increasing;18 eyes (20. 0%) had tissue hyperplasia in the hollow or on the surface of optic disc; 11 eyes(12. 3%) had symptoms including vitreous traction optic papilla and optic disc rim rising. DON eyes which had similar fluorescence features could manifest different tissue morph by OCT.
●CONCLUSION: FFA defines DON by change of blood circulation in optic nerve. However, OCT can show differences of tissue morph of optic nerve that FFA fails to do. So OCT can manifest the causes and sites of optic neuropathy more clearly and also provide basis for treatment. The advantages of OCT are conducive to reviews and curative effect tracking among DON patients and these advantages including noninvasive, convenient, inexpensive and repeatable.

Objective To establish a method for rapidly detecting the G-protein ?3 subunit (GNB3) 825 site single nucleotide polymorphism (SNP) and to analyse the relationship between GNB3 825 site gene SNP and obesity. Methods The real-time fluorescent PCR was employed to analyse the GNB3 825 site gene SNP of 420 samples from 21 provinces and the the frequencies of genotypes were compared with those detected by gene sequencing. GNB3 825 site genotype, body weight, body mass index (BMI) and fat content were examined from 207 subjects and the correlation between GNB3 825 site gene SNP and obesity was analysed. Results The result by real-time fluorescent PCR showed that the frequencies of 825T and 825C haploid were 46.90% and 53.10%, respectively, and the frequencies of 825TT, 825TC and 825CC genotype were 22.38%, 51.42% and 28.10%, respectively, with no other genotype detected, which was consistent with the result by gene sequencing. BMI and fat content were significantly higher in subjects with GNB3 825TT than in subjects with other genotypes. Body weight was much higher in subjects with GNB3 825TT genotype than in subjects with 825CC genotype, but not significantly different with 825CT genotype. Conclusion A new rapid method for the detection of GNB3 825 site SNP has been successfully established. There existed significant correlation between GNB3 825TT genotype and obesity.