BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

[摘 要] 目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和BCLAF1蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与BCLAF1在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。

Objective To study the changes in biomechanical properties of human cornea after laser in situ keratomileusis (LASIK) and predict corneal stiffness after the LASIK surgery. Methods According to the measurement results from corneal visualization scheimpflug technology (Corvis ST), the corneal tangent stiffness coefficient (STSC) and energy absorbed area (Aabsorbed) were calculated. The change patterns of corneal stiffness and viscosity after refractive surgery were analyzed. Results The difference of corneal STSC and Aabsorbed before and after LASIK had a statistical significance (P<0.05). The obtained formula for predicting corneal stiffness after refractive surgery was: Sbefore surgery =1.055bIOPbefore surgery + 0.015CCTbefore surgery，Safter surgery =0.937Sbefore surgery +0.019CCTafter surgery. Conclusions LASIK surgery not only changes corneal thickness, but also reduces corneal stiffness and viscosity. Prediction of corneal stiffness after surgery can provide guidance for the design of clinical surgery and improve the safety of surgery.

Objective To investigate the short-term safety of raltitrexed intraperitoneal perfusion in patients with rectal cancer undergoing laparoscopic Dixon surgery.Methods Totally 175 patients with rectal cancer at the Department of Colorectal Oncological Surgery,Shengjing Hospital of China Medical University were analyzed retrospectively from June 2016 to December 2017.All the patients were divided into raltitrexed intraperitoneal perfusion group (n =89) and saline intraperitoneal peffusion group (n =86) according to whether given raltitrexed intraperitoneal perfusion or not.The hematological indexes of the two groups before operation and 3 days after operation were recorded.The postoperative exhaust time and postoperative drainage volume within 24 hours were calculated.The postoperative complications including anastomotic leakage,peritoneal irritation sign,incision infection and pulmonary infection were evaluated.Results The surgery was performed successfully in all patients.There were no significant differences in the sex (x2 =0.000,P =0.990),depth of tumor invasion (x2 =0.003,P =0.956),degree of lymph node metastasis (Z =-0.590,P =0.556),TNM stage (Z =0.081,P =0.936) or pathological type (Z =1.092,P =0.896) between the two groups.There were no significant differences in postoperative exhaust time [(75.49 ± 3.97) h vs.(74.28 ±3.46) h,t =0.479,P =0.523],postoperative drainage volume within 24 hours [(201.1 ±54.1) ml vs.(242.8±25.7) ml,t=0.338,P=0.656],anastomotic leakage (1.1％ vs.2.3％,x2 =0.351,P=0.554),peritoneal irritation sign (1.1％ vs.2.3％,x2 =0.351,P =0.554),incision infection (2.2％ vs.3.5％,x2 =0.243,P =0.622) and pulmonary infection (2.2％ vs.2.3％,x2 =0.001,P =0.972) between the two groups.Additionally,there were no significant differences in the counts of erythrocytes [(3.56 ±0.27) × 1012/L vs.(3.63 ±0.26) × 1012/L,t =0.716,P =0.152],leukocytes [(7.63 ±0.20) x 109/L vs.(8.24 ±0.26) × 109/L,t =0.176,P =0.872],blood platelets [(170.13 ±20.12) × 109/L vs.(180.18 ±21.03) × 109/L,t =0.103,P =0.975],glutamic-pyruvic transaminase [(13.25 ± 2.31) U/L vs.(13.28 ± 1.46) U/L,t =0.321,P =0.713],glutamic-oxalacetic transaminase [(16.51 ± 1.28) U/L vs.(16.23 ±2.03) U/L,t=0.131,P=0.894] and creatinine [(77.36 ±6.49) μmol/L vs.(78.39 ±6.64)μmol/L,t =0.499,P =0.519] 3 days after operation between the two groups.Conclusion Raltitrexed intraperitoneal perfusion in Dixon surgery exhibits high safety,and no significant effect on postoperative recovery.It is easy to operate and has good feasibility,which is worthy to be used in clinic.

Objective To explore the value of miniprobe sonography (MPS) in differentiating Crohn??s disease (CD) and ulcerative colitis (UC). Methods 46 patients with active inflammatory bowel disease (IBD) were included into the patient group (16 patients with CD and 30 cases with UC). 20 healthy cases ( underwent physical examination in outpatient department) were recruited as the control group. All cases underwent MPS and high sensitive C-reactive protein (Hs-CRP) test.The MPS measurement index include thetotalwallthickness(TWT), mucosal thickness (MT), submucosal thickness (SMT), muscularispropria thickness (MPT), and the number of enlarged colic and paracolic lymph nodes. Results TheTWT, M, SM, MP(mm)and Hs-CRP(mg/L)in CD, UC and control group are 5.84 ± 1.42, 1.48 ± 0.23, 1.88 ± 0.28, 2.31 ± 0.85, 40.58 ± 19.33, 4.74 ± 1.01, 1.79 ± 0.35, 1.41 ± 0.25, 1.32 ± 0.34, 22.41 ± 15.25,2.86 ± 0.23, 0.97 ± 0.13, 1.06 ± 0.11, 0.64 ± 0.0 and 1.70 ± 0.65. TWT, MT, SMT, MPT and Hs-CRP in UC group has significant different with those in controp group(P<0.05). The mean value of TWT, MT, SMT, MPT and Hs-CRP in CD group are higher than those in UC group. M in UC group is higher than that in CE group. The difference is significant(P<0.05). 5 cases in CD and 2 cases with UC had enlarged colic or paracolic lymph nodes. Conclusions The MPS can distinctly observe the changesof different colonic tissue layers and the surrounding tissue structures in IBD patients,which helps for distinguishing active CD from UC.

BACKGROUND:Neural stem cel (NSC) transplantation is a common method for various ischemicencephalopathies, but inability to survive in the transplantation region limits its further use in clinical practice. OBJECTIVE:To explore the effect of vascular endothelial progenitor cel s (VEPCs) on the proliferation and apoptosis of co-cultured NSCs as wel as vascular remodeling in rats with ischemia reperfusion injury. METHODS:125 Sprague-Dawley rats were randomly divided into five groups, 25 rats in each group, including sham operation, ischemia, NSCs, co-culture, and VEPCs groups. Rat models of ischemia reperfusion injury were made in al groups except for the sham operation group, fol owed by corresponding interventions. The proliferation and apoptosis of neural stem cel s were detected, and vascular remolding in the ischemic region was observed in each group. RESULTS AND CONCLUSION:At different time points after transplantation, BrdU positive cel s were not observed in VEPCs, ischemia and sham operation groups;the number of BrdU positive cel s in the co-culture group was significantly higher than that in the NSCs group (P<0.05);BrdU+/Caspase-3+cel were observed in both co-culture and NSCs groups, and the apoptosis rate of the co-culture group was significantly lower than that in the NSCs group (P<0.05);there were new blood vessels in al the groups except for the sham operation group, and the number of new bone vessels was highest in the co-culture group. To conclude, our experimental results show that VEPCs promotes the proliferation of co-cultured NSCs, inhibits cel apoptosis and and promote angiogenesis in the ischemic penumbra of rats with ischemia reperfusion injury.

Objective To evaluate the safety and effectiveness of a newly domestic bovine pericardium using a juvenile sheep model and to provide proof for clinical use.Methods Under the off-pump condition,8 domestic bovine pericardiums were implanted into the pulmonary artery and the descending aorta of 4 juvenile sheep as the trial group.As the control group,four imported bovine pericardiums were implanted into two juvenile sheep.Before the surgery,the juvenile sheep were given a physical examination and some laboratory tests.Ultrasonic cardiographs were taken after 1 month and 2 months of implantation.Sheep were sacrificed after 90 days and compared with the extent of endothelialization,inflammation and calcification of the two groups.Results (1) All the juvenile sheep survived without any complications.(2) Ultrasonic cardiograph showed the absence of leakage,thrombus,calcification,neoplasm or any structural deterioration.(3) Gross examination showed there was no intimal hyperplasia.The thickness and tenacity of all patches had no change compared with the pre-operation condition.All the patches showed smooth and pliable faces without degeneration,as well as absence of macroscopically calcification.(4) There was not any positive result in microbiological tests in both groups.The degree of inflammation,necrosis and calcification had no significant differencs between the two groups.Conclusions The data shows that the domestic bovine pericardium,a newly developed Chinese domestic-design and manufactured bovine pericardium,can exhibit long-term satisfactory safety and efficacy in the implantation of the pulmonary artery and the descending aorta of juvenile sheep.

Objective To investigate the consistency of mRECIST criterion and RECIST criterion in evaluating the curative effect of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) for primary hepatocellular carcinoma (PHC) which condition exceeds Milan liver transplantation standard in order to determine which criterion can evaluate the curative effect better.Methods A total of 78 PHC patients,whose lesion's extent exceeded Milan standard and who had received TACE combined with RFA therapy,were included in this study.The curative effect was separately evaluated by mRECIST criterion and RECIST criterion.KAPPA coefficient was calculated to determine the consistency of the evaluation results by the two criteria.By using Kaplan-Mier method,the median survival time (MST) of patients achieving different remission degree was calculated.Log-rank test was used to draw survival curve.The MST and the survival curve of patients with different remission degree were statistically compared between the two criteria.Results By using SPSS19.0 software,the KAPPA coefficient of the evaluation results of the two criteria was 0.243 (x2=5.250,P＜0.01).The MST of patients,which was calculated by Kaplan-Mier method,had multiple overlapping parts with SD and PR curves that were drawn by log-rank test based on RECIST criterion,the difference between the two was not statistically significant (P＞0.05).When mRECIST criterion was based on,the survival curve of patients with different remission degree was relatively balanced and showed no overlapping parts,the difference between the two was statistically significant (P＜0.01).Conclusion (1) The mRECIST criterion is not suitable for the evaluation of the curative effect of PHC patients whose lesion's extent exceeds Milan standard,and mRECIST criterion can not apply to make evaluation of the curative effect for PHC when the lesion's border is unclear and its enhancement is not obvious.(2) mRECIST criterion can more accurately evaluate the curative effect of TACE combined with PRA in treating PHC which extent exceeds Milan liver transplantation standard.

Objective To investigate the role of underlying diseases in predicting the length of stay for observation in emergency department of internal medicine by the Charlson weighted index of comorbidities (WIC).Methods A single-center retrospective analysis of clinical data of 2 836 patients admitted in emergency observation room of the Beijing Chaoyang Hospital from January 1 to June 30 in 2013 was carried out.The patients were divided into two groups according to the length of observation time:Group A (time of observation ≥72 h,n =1908) and Group B (time of observation ＜ 72 h,n =928).The data of the length of observation time were recorded,and the WIC and the APACHE Ⅱ score were calculated.Logistic regression analysis was used to determine the independent predictors for 72-hour observation.Receiver operating characteristics (ROC) curve was used to evaluate the value of WIC in predicting 72-hour observation.Results Of 2836 patients,1176 (41.5％) suffered from respiratory disease,709 (25.0％) had cardiovascular and cerebrovascular diseases,423 (14.9％) were contracted digestive system disease,251 (8.8％) had renal and endocrinology system diseases and 277 (9.8％) had diseases arisen from physicochemical factor and miscellaneous causes.Compared with patients in Group B,the average age,the number of elderly patients residing in apartment exclusively for elderly,the WIC and the APACHE Ⅱ score were higher in patients in Group A.The one-variable and multi-variable Logistic regression analyses showed that age,the WIC score,the APACHE Ⅱ score and residing in apartment for elderly people were related with 72-hour observation in emergency observation room.The area under the ROC curve in predicting 72-hour observation was 0.701 for the WIC score,0.788 for APACHE Ⅱ score and 0.853 for their combination.Conclusions The WIC scoring system can be a good predicting method for 72-hour observation in patients in emergency observation room.