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

After the New Coronary Pneumonia pandemic, people^'s social behavior has changed, and the current health management and development approaches should also change accordingly. This article analyzes the changes of social behavior during different anti-epidemic periods, demonstrates the necessity and possibility to change the current health management formats and development paths, and proposes a new concept of family-centered health management. The main target of the current urgent need for family health management is to expand the household entry units, build learning and sports units, etc. This article provides ideas for health management in the post-pandemic era.

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

Objectives To evaluate the predictive value of the revised model for end-stage liver disease in the clinical early stage after liver transplantation.Methods The clinical data of 218 patients were retrospectively analyzed.After calculating the MELD score,ReFit MELD score and ReFit MELDNa score before transplantation,we compared the predictive accuracies of these scoring systems using the area under curve (AUC) of the receiver operating characteristic.The groups were categorized with the cut-offs of the MELD,ReFit MELD and ReFit MELDNa,and the early-stage complications and mortality in the different groups were analyzed.Results The AUC for the MELD,ReFit MELD and ReFit MELDNa were 0.737 (95％CI 0.621～0.854),0.727 (95％CI 0.663～0.785) and 0.735 (95％CI 0.671～0.792),respectively.There was no statistical difference is the AUC among the MELD,ReFit MELD and ReFit MELDNa.Elevated scores in the 3 models predicted higher rates of pulmonary infection,abdominal infection and acute renal dysfunction,as well as a higher mortality.Conclusions The ReFit MELD score and ReFit MELDNa score were relatively useful predictors of short-term survival rates after liver transplantation.The predictive accuracy was similar to the MELD score.Values of the score above the cutoff values indicated higher rates of complication and poorer prognosis.

Animals ; Autoantibodies ; blood ; Cytokines ; biosynthesis ; Dose-Response Relationship, Drug ; Female ; Immunohistochemistry ; Rats ; Rats, Inbred Lew ; Selenium ; administration & dosage ; therapeutic use ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology ; Thyroid Gland ; drug effects ; immunology ; pathology ; Thyroiditis, Autoimmune ; drug therapy ; immunology ; Trace Elements ; administration & dosage ; therapeutic use

Objective To investigate the prognostic relevant factors of hepatocellular carcinoma (HCC) in recipients following liver transplantation (LT).Methods The clinical data of 147 cases of HCC undergoing LT between Aug. 2004 and Feb. 2011 in Nanfang Hospital were studied retrospectively.Those of significance in 14 relevant factors involving gender,age,blood-type,CTP,model of end-stage liver disease (MELD),alpha-fetoprotein (AFP),tumor number,cumulative diameter of tumor,tumor occupying proportion of the liver,bilobar involvement,envelope invasion,macrovascular invasion,and microvascular invasion (MVI),HCC histology differentiation,which were based on univariate analysis with Log-Rank,were analyzed by means of Multivariate Cox proportional hazard regression model to screen out independently relevant ones.Results 143 cases were followed up.The follow-up duration ranged from 6 to 84 months.The 1- and 3-year cumulative survival rate was 75.2％ and 54.7％ respectively.The tumor free 1- and 3-year cumulative survival rate was 70％ and 59％ respectively.Univariate ananlysis revealed that age,AFP,tumor number,cumulative diameter of tumor,tumor occupying proportion of the liver,bilobar involvement,envelope invasion,macrovascular invasion,and MVI had significant difference, In a Cox model,MVI,macrovascular invasion and AFP≥ 400 μg/L were independent prognostic factors.Conclusion MVI,macrovascular invasion and AFP are the main prognostic risk fators.Intervention and non-tumor technique should be performed preoperatively and intraoperatively,respectively.

Objective To investigate the role of alprostadil on hepatic perfusion after transarterial chemoembolization(TACE) for hepatocellular carcinoma. Methods Sixty-four consecutive patients with HCC were randomized to either treatment with PGE_1 after TACE (treatment group, 32 cases) or no additional treatment after TACE (control group, 32 cases). In PGE_1 group, Lipo-PGE_1 was administered intravenously once a day for total of seven days, once after completion of TACE. The dosage of Lipo-PGE_1 was 0.4μg/kg and rote 0.05 μg·kg~(-1)·min~(-1). In control group, regular TACE was used. All patients underwent hepatic CT perfusion within 1 week before TACE and 4 weeks after TACE. The parameters of hepatic perfusion, including hepatic arterial perfusion value (HAP), portal vein perfusion value (PVP), total liver perfusion value (TLP) , and hepatic arterial perfusion index (HPI) were measured and compared. Chi-Square test was used for comparison of CT perfusion parameters in different stage, and t test was used for comparison of each CT porfusion parameter between two groups. Results In control group, HAP of pre-TACE, 4 weeks after first TACE, and 4 weeks after second TACE was (0.18±0.08), (0.22±0.09), (0.32±0.10) ml·min~(-1)·ml~(-1), respectively. Likewise, PVP was (1.11±0.31)、(0.82±0.27)、(0.59±0.25) ml·min~(-1)·ml~(-1), respectively, and TLP was (1.29±0.33), (1.04±0.28), (0.91±0.24) ml·min~(-1)·ml~(-1), respectively, and HPI was (14.31±6.36)%, (21.37±9.07)%, (36.67±13.42)%, respectively. The perfusion parameters at different stages of TACE were statistically different (F=19.71,27.47,14.75,41.41, P<0.05). In PGE1 group, HAP before TACE, after first TACE, and after second TACE was (0.17±0.08), (0.20±0.08), (0.26±0.08) ml·min~(-1)·mi~(-1) respectively, and PVP was (1.09±0.36), (1.03±0.40), (0.91±0.41) ml·min~(-1)·ml~(-1), respectively, and TLP was (1.26±0.38), (1.23±0.40), (1.17±0.44) ml·min~(-1)·ml~(-1) respectively, and HPI was (14.04±6.71)%, (17.26±7.86)%, (23.93±8.96)%, respectively. The difference of HAP and HPI at different stage of TACE was significant (F = 10.78, 13.05, P < 0.05), but there was no significant difference both PVP and TLP (F = 1.73,0.39, P > 0.05). The difference of PVP and TLP between the control and PGE1 group was significant after first TACE(t = -2.37, -2.14, P <0.05)and second TACE (t = 2.55, - 4.49, P < 0.05) In addition, after the second TACE, the HAP and HPI were also significantly different (t = - 3.41,5.09, P < 0.05). Conclusions PVP and TLP decrease while HAP and HPI increase after TACE. Lipo-PGE1 improves hepatic peffusion after TACE, exerting its greatest effect by increasing portal vein perfusion. Consequently, treatment with Lipo-PGE1 appears to increase liver tissue perfusion and thereby alleviate injury induced by TACE.

alterations on liver hemodynamics on IR injury following administration of medication.

Objective To isolate and identify the potential binding partners of LRRK2,a gene linked to both dominant familial form and sporadic form of Parkinson's disease,thus to further our knowledge of its function.Methods We used a sequence containing full-length of COR domain and part of ROC and MAPKKK domain as bait.The bait amplified by polymerase chain reaction(PCR) was then cloned into a yeast expression plasmid pGBKT7.After being sequenced and analyzed,pGBKT7-bait was transformed into the yeast strain AH109.Western blot was performed to confirm the expression of pGBKT7-bait in AH109 yeast strain.Then human fetal brain cDNA library was trarnsformed into that yeast strain.which could express pGBKT7-bait fusion protein.The yeast strain which contained pGBKT7-bait and human fetal brain cDNA library was plated on quadruple dropout medium (SD/-Trp/-Leu/-His/-Ade)containing X-a-gal.We retested these positive colonies using 2 independent yeast strains AH109 contained pGBKT7-bait or pGBKT7,respectively.At last,these plasmids isolated from these true positive colonies were analyzed by bioinformatics.Results We obtained 9 true positive colonies,these colonies were sequenced, and we performed sequence Blast in GenBank.Three colonies of the 9 positive colonies were not in open reading-frames.Among other 6 colonies,there were known proteins including spermatid perinuclear RNA-binding protein(STRBP)and BCL2-associated athanogene 5 isoform b(BAG5),as well as unknown proteins including tyrosine phosphatase non-receptor type(PTPN23),1(3)mbt-like 3 isoform b(L3 MBTL3),RALY RNA binding protein-like isoform 1(RALYL),and Homo sapiens mRNA for KIAA1783 protein,partial cds(KIAA 1783).Conclusion True positive colonies of LRRK2 are successfully obtained by the yeast 2-hybrid.Our screened proteins may provide a new research clue for revealing biological functions of LRRK2,pathogenesis of Parkinson's disease,and other neurodegerations.

Objective To explore the effects of adriamycin-loaded immuno-nanoparticles on multidrug resistance (MDR) of hepatoma cell line SMMC-7721/ADM. Methods The cytotoxicity of the adriamycin-loaded immuno-nanoparticles on the bepatoma cell line SMMC-7721/ADM in vitro and the tumor cell-binding ability of adriamycin-loaded immuno-nanoparticles were detected. Results The effect of the cytotoxicity of adriamycin-loaded immuno-nanoparticles on the hepatoma cell line SMMC-7721/ADM was significantly better than that of adriamycin-loaded nanoparticles. Adriamycin-loaded immuno-nanoparticles had the specific binding ability with the hepatoma cell line SMMC-7721/ADM. Conclusions Adriamycin-loaded immuno-nanoparticles can overcome the MDR of the tumor in vitro. The mechanism may be that immuno-nanoparticles could adhere to the tumor cell membrane, and the release of the loaded adriamycin creates a high local concentration in the extracellular medium. The increased concentration gradient improves the diffusion of adriamycin from the extracellular medium to the intracellular medium.