177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

OBJECTIVES: Liver cancer is the sixth most common malignant tumor in the world. Hepatocellular carcinoma (HCC) accounts for 85%-90% of all patients with liver cancer. It possesses the characteristics of insidious onset, rapid progression, early recurrence, easy drug resistance, and poor prognosis. NIMA related kinase 2 (NEK2) is a cell cycle regulating kinases, which regulates cell cycle in mitosis. Cellular senescence is a complex heterogeneous process, and is a stable form of cell cycle arrest that limits the proliferative potential of cells. This study aims to investigate the relationship between the expression level of NEK2 and the senescence in hepatoma cells, and to explore the effect of NEK2 expression on hepatoma cell senescence and the underlying molecular mechanism. METHODS: A total of 581 senescence-relevant genes were obtained from the GenAge website. The gene expression data of tumor tissues of 370 HCC patients were downloaded from the Cancer Genome Atlas database. The co-expression of NEK2 and aging-related genes was analyzed by R-package. KEGG was used to analyze the significant gene enrichment pathway of differentially expressed genes in NEK2 overexpression HEK293. The stable transfected cell lines with overexpression and knockdown of NEK2 were constructed in hepatoma cell line SMMC-7721 and HepG2, and senescence-associated β-galactosidase (SA-β-gal) staining was used to detect senescence, the cell proliferation was detected by CCK-8 method and clone formation experiment, the cell cycle was analyzed by flow cytometry, and the expression of proteins related to p53/p21, p16/Rb, and phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signal transduction pathway was detected by Western blotting. RESULTS: There were 320 senescence related genes co-expressed with NEK2. KEGG analysis showed that the senescence signaling pathway was significantly enriched in HEK293 cells with overexpression of NEK2.Compared with SMMC-7721 or HepG2 without knockdown of NEK2, the senescent cells of SMMC-7721 and HepG2 with knockdown of NEK2 were increased, cell proliferation and clone formation were decreased significantly, the percentage of cells in G₀/G₁ phase was increased, the expression levels of phospho-Akt (p-Akt) and phospho-Rb (p-Rb) protein were decreased significantly, and the expression level of p16 protein was increased significantly (all P<0.05). Compared with SMMC-7721 or HepG2 transfected with blank plasmid, the senescent cells of SMMC-7721 and HepG2 overexpressing NEK2 were decreased, the cell proliferation and clone formation were increased significantly, the percentage of cells in G₀/G₁ phase were decreased, the expression levels of p-Akt and p-Rb protein were increased significantly, and the expression level of p16 protein was decreased significantly (all P<0.05). CONCLUSIONS NEK2 may mediate the anti-aging effect of hepatoma cells through p16/Rb and PTEN/Akt signal transduction pathways, which provides a new theoretical basis for NEK2 to promote the progress of liver cancer and a new idea for the targeting treatment for liver cancer.
Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Proliferation/physiology* ; Cellular Senescence/genetics* ; HEK293 Cells ; Humans ; Liver Neoplasms/pathology* ; NIMA-Related Kinases/genetics* ; Proto-Oncogene Proteins c-akt/metabolism*

Aim To explore the molecular mechanism atherosclerosis by network pharmacology and in vitro of Gualou Xiebai Banxia decoction in the treatment of study.Methods All chemical constituents and targets of Gualou Xiehai Banxia decoction were retrieved from TCMSP database.OMIM, DrugBank and TTD databas¬es were searched with "atherosclerosis" as the search term , and the related targets of atherosclerosis were ob¬tained after eliminating duplicate options.DAVID da¬tabase was used for GO and KEGG pathway enrichment analysis of intersection targets.Finally, the analysis results were confirmed in the ox-LDL induced human aortic endothelial cell injury model.Results A total of 30 active compound molecules in Gualou Xiebai Banxia decoction and 78 potential targets for the treat¬ment of atherosclerosis were retrieved.The therapeutic targets were mainly related to inflammatory pathway, apoptosis and so on.(3-sitosterol was chosen as a po¬tential pharmacodynamic molecule for the treatment of atherosclerosis to verify the correctness of the results of network pharmacological analysis.In vitro experiments showed that, (3-sitosterol could prevent ox-LDL in¬duced apoptosis of human aortic endothelial cells and significantly reduce the level of IL-ip, 1L-6 and TNF- cx in cell culture medium, and protein expression of p- NF-kB/NF-kB, 1L-1 p, 1L-6 and TNF-a in cells.Conclusions The treatment effect of Gualou Xiebai Banxia decoction on atherosclerosis is mainly mediated by regulating inflammation, apoptosis and other path¬ways through multi-component effect, multiple targets and multiple pathways.

Objective:To observe the correlation between the expressions profile of cytokeratin 19/glypican 3 (CK19/GPC3) and recurrence of hepatocellular carcinoma after interventional therapy.Methods:Clinical and pathological information of 251 eligible cases with hepatocellular carcinoma who underwent interventional therapy in You'an Hospital from November 2007 to May 2016 were retrospectively collected. Univariate and multivariate Cox regression analysis was used to analyze the relevant risk factors that may affect their prognosis. Kaplan-Meier survival analysis was used to draw the survival curve. Log-rank test was used to compare the difference in survival rates between the groups.Results:Kaplan-Meier univariate analysis showed that histological grade, CK19/GPC3 expression profile, alpha-fetoprotein level and Hep Parl were closely related to tumor recurrence. Multivariate Cox regression analysis showed CK19/GPC3 expression profile ( HR = 1.634, 95% CI: 1.041 ~ 2.564, P = 0.033), histological grade ( HR = 1.445, 95% CI: 1.037 ~ 2.014, P = 0.030), alpha-fetoprotein level ( HR = 1.410, 95% CI: 1.042 ~ 1.908, P = 0.026), Hep Parl ( HR = 0.570, 95% CI: 0.349 ~ 0.930, P = 0.025) were the four independent factors for prediction of recurrence after interventional therapy. Conclusion:Hepatocellular carcinoma patients with CK19 +/GPC3 + and CK19 -/GPC3 + phenotypes who meet the Milan criteria have a higher risk of recurrence after interventional therapy than CK19 -/GPC3 - phenotypes.

An efficient genetic transformation system and suitable promoters are essential prerequisites for gene expression studies and genetic engineering in streptomycetes. In this study, firstly, a genetic transformation system based on intergeneric conjugation was developed in Streptomyces rimosus M527, a bacterial strain which exhibits strong antagonistic activity against a broad range of plant-pathogenic fungi. Some experimental parameters involved in this procedure were optimized, including the conjugative media, ratio of donor to recipient, heat shock temperature, and incubation time of mixed culture. Under the optimal conditions, a maximal conjugation frequency of 3.05×10^-5 per recipient was obtained. Subsequently, based on the above developed and optimized transformation system, the synthetic promoters SPL-21 and SPL-57, a native promoter potrB, and a constitutive promoter permE^* commonly used for gene expression in streptomycetes were selected and their activity was analyzed using gusA as a reporter gene in S. rimosus M527. Among the four tested promoters, SPL-21 exhibited the strongest expression activity and gave rise to a 2.2-fold increase in β-glucuronidase (GUS) activity compared with the control promoter permE^*. Promoter SPL-57 showed activity comparable to that of permE^*. Promoter potrB, which showed the lowest activity, showed a 50% decrease in GUS activity compared with the control permE^*. The transformation system developed in this study and the tested promotors provide a basis for the further modification of S. rimosus M527.
Conjugation, Genetic ; Glucuronidase/genetics* ; Promoter Regions, Genetic ; Streptomyces rimosus/genetics*

Objective To evaluate the long-term outcomes of total knee arthroplasty (TKA) for end-stage hemophilic arthropathy.Methods Eighteen patients (24 knees) with hemophilic arthropathy underwent TKA from June 2003 to January 2009 were retrospectively reviewed.All patients were hemophilia A with an average age of 33.7± 13.0 years (18-56tyears) old at Surgery.Pharmacokinetic tests of coagulation factors were performed after consultation of hematologist.Based on the guideline of World Federation of hemophilia,the protocol of coagulation factor replacement was adjusted according to our experience and the financial status.Normally,peak level of coagulation factor concentrations were maintained at 100％ on the day of surgery,at about 80％ in the first 3 days after surgery,at 60％ on the postoperative days of 4-6 and at 40％ on postoperative days of 7-10.The dose was then gradually tapered to 20％ or 30％.Zimmer prosthesis was used in three cases (PS prosthesis in two cases,LCCK prosthesis in one case),Centerpulse prosthesis in three cases,and the rest were from Smith & Nephew (including one case of constrained prosthesis and one case of revision prosthesis).Preoperative and last follow-up Hospital for Special Surgery (HSS) score,Knee Society Score (KSS),knee flexion contracture and complications were evaluated.Results Fourteen patients(20 knees) were followed-up,with an average duration of 124±17 months (96-145 months).Knee flexion contracture improved from 16.7°±12.2° (0°-40°) preoperative to 3.3 °±5.0° (0°-10°) at the last follow-up.The average preoperative HSS score was 42.4± 16.0 (t 0-60),whereas postoperative score was 74.8± 10.6 (59-87).The preoperative KSS clinical and functional score were 36.1 ± 10.5 (20-50) and 36.1±5.5 (25-40),which were improved to 85.8±7.1 (70-93) and 80.9±22.4 (40-100) at the last follow-up,respectively.Postoperative infection,aseptic loosening of the implant and hematoma occurred in one patient respectively.All of them recovered after a revision surgery.One patient had secondary skin ulceration due to tension blisters and recovered after anterolateral thigh myocutaneous flap transplantation.Conclusion The long-term outcomes of TKA under coagulation factor substitution for hemophilic arthropathy are promising.However,the effects are inferior to those in non-hemophilic patients,and the risk of infection,aseptic loosening of the implant and hematoma are higher.

Objective To study the protective effect of Rhein on the kidney of type 2 diabetic rats induced by high fat diet.Methods A rat model of type 2 diabetes was induced by high fat diet combined with low dose streptozotocin 35 mg/kg.The diabetic rats were randomly divided into diabetes group, Low, middle and high rhein dose groups (50,100,150 mg/kg), metformin group (300 mg/kg) and normal control group.Blood glucose and urine micro albumin were measured at 0, 2, 4 and 8 weeks respectively.Serum creatinine, urea nitrogen, total cholesterol and triglyceride were measured at 8 weeks.HE staining was used to observe the pathological changes of renal tissue.Effects of rhein on the expression of transforming growth factor-β1 and Smad3 protein in renal tissue of diabetic rats were detected with Western Blot.Results The blood glucose and urine micro albumin in model group were significantly higher than those in normal control group.Each rhein dose group exhibited reduced blood glucose and urinary micro albumin in diabetic rats.The high rhein dose group showed significant reduction of blood glucose and urine micro albumin in diabetic rats (P<0.05).Compared with model group, rhein reduced the serum Cr, BUN, TC and TG values in each dose group, most significantly in the high rhein dose group (P<0.05).The obvious pathological changes of renal tissue in model group were observed with most improved changes in the high rhein dose group.The expression of TGF-β1 and Smad3 protein in renal tissue of diabetic rats decreased significantly (P<0.05).Conclusion Rhein has preventive effect on diabetic nephropathy.The mechanism may relate to the improvement of renal function, regulation of blood lipid and down regulation of TGF-β1 and Smad3 protein expression in renal tissue.

Objective To study the surgical treatment strategy for heamophilic arthropathy and musculoskeletal appara?tus. Methods A total of 120 heamophilic patients underwent 166 primary operations from January 1996 to June 2015 in Pe?king Union Medical College Hospital, with the average age of 29.7±12 years (from 6 to 61 years). Hemophilic type A accounted for 109 patients and hemophilic type B accounted for 11. Eighty?seven patients presented with bleeds within the joints, with 63 cases for knee involved, 29 cases for hip, 11 cases for ankle. Fifteen patients presented with intramuscular bleeds, 21 patients with heamophilic pseudotumors. Strategy of clotting factor replacement therapy was designed according to the different level of opera?tion procedure. The clinical manifestation, operative strategy, clinical outcome and complications were retrospectively recorded. Results 41 cases (34.2%) of patients underwent surgeries for more than one location. Totally, 166 procedures were performed for 120 patients. There were 103 procedures of joint arthroplasty (62.0%, 103/166), 21 procedures of pseudotumor resection (12.7%, 21/166), 15 procedures of tendon lengthening, 12 procedures of ankle arthrodesis, 13 procedures for knee flexion contracture. There were 30 cases of postoperative complications, with the rate of 18.1% (30/166). The coagulation related complication was 4.8%in this group (8/166). The surgical procedure related complication was 7.2%(12/166). All the preoperative symptoms were relieved during the follow?up. Conclusion Surgical treatment was effective for the heamophilic arthropathy and lesion of mus?culoskeletal apparatus, under the reasonable clotting factor replacement therapy. The incidence of perioperative complication in heamophilic patients is higher than that in non?hemophilic patients. Closely inspection was inevitable for perioperative treat?ment in hemophilic patients.

Objective To investigate the therapeutic effect of VSD combined with external fixator in the treatment of open tibial and fibular fractures in Tibet plateau. Methods From August 2014 to August 2015, totally 16 cases of open tibial and fibular fractures were treated in our department, including 12 males and 4 females with an average 39. 4 years-old. There were 4 cases of proximal and mid tibial fractures while 12 cases were distal fractures. Debridement, vacuum sealing drainage combined with external fixator for stabilization of fractures was performed in all patients after general condition was improved. A vacuum sealing drainage change or second stage wound closure or soft tissue coverage was undergone after 7 days. Bone union time by X-ray and complications were recorded. Results All wounds were healed by second stage. Twelve patients months were followed up ( by calling back to the hospital ) for an average 18 months ( 12 to 24 months ) , 4 cases were lost to follow-up. X-ray demonstrated that bone union was obtained at a mean 5. 5th month (3 to 7 months). There were 9 cases (75%) obtained a first phase of fracture healing, while 3 cases ( 25%) of delayed healing. Pin-track infection was occurred in two patients and was cured by conservative treatment. No complications of deep infection, graft skin or flap necrosis, malunion, nonunion or osteomyelitis was seen during follow-up. Conclusions Vacuum sealing drainage combined with external fixator for treatment of open tibial and fibular fracture in Tibet can rapidly and effectively stabilize the fracture, and simultaneously safely and effectively seal the wound, reduce the wound healing time, promote fracture healing and lower the complication rates.

Objective:To investigate frequency and position characteristics of the vestibular dysfunction in vestublar neuritis patients. Method:Colaric test (CT), head impulse test (HIT), cervical vestibular evoked myogenic potential (cVEMP) and ocular vestibular evoked myogenic potential (oVEMP) were applied in 43 vestublar neuritis patients to assess their vestublar dysfunction. Superior vestublar nerve (S-VN), inferior vestibular nerve (I-VN), total vestibular nerve (T-VN) and each vestibular end organ incidence rate were calculated and statistically analyzed. Result:CT incidence rate (93.0%) was statistically higher than that of HIT (72.1%) (P<0.01). Total frequency incidence rate (72.1%) was statistically higher than that of low frequency (20.9%) (P<0.01). No high frequency only case was observed. The incidence rate of S-VN only, I-VN only and T-VN was 44.2%, 4.7% and 51.2% respectively. Among them, the incidence rate of I-VN was significantly lower than the others (P<0.01). The incidence rate of vestibular end organs was 17.4% (S-SCC), 44.2% (H-SCC), 20.9% (P-SCC), 39.5% (utricule) and 26.7% (saccule) respectively. The incidence rate of H-SCC was remarkably higher than the other semicircular canals (P<0.01). The difference between utricule and saccule was not statistically significant. Conclusion:The semicricular canal dysfunction in vestibular neuritis patients mainly involves total frequency of vestibular function, low frequency is more common than high frequency. Total vestibular nerve and single S-VN are mostly involved in vestibular neuritis.