Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

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.

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

Emergence and Autochthonous Transmission of Dengue Virus Type I in a Low-Epidemic Region in Southeast China.

Background: Dengue fever is a mosquito-borne febrile illness. Southeast Asia experienced severe dengue outbreaks in 2019, and over 1000 cases had been reported in Jiangxi, a previously known low-epidemic region in China. However, the emergence of a dengue virus epidemic in a non-epidemic region remains unclear. Methods: We enrolled 154 dengue fever patients from four hospitals in Jiangxi, from April 2019 to September 2019. Real-time PCR, NS1 antigen rapid test, and IgM, IgG tests were performed, and 14 samples were outsourced to be sequenced metagenomically. Results: Among the 154 cases, 42 were identified as imported and most of them returned from Cambodia. A total of 113 blood samples were obtained and 106 were identified as DENV-1, two as DENV-2, and five were negative through RT-PCR. All DENV-1 strains sequenced in this study were all classified to one cluster and owned a high similarity with a Cambodia strain isolated in 2019. The evolutionary relationships of amino acid were consistent with that of nucleotide genome result. The sequence-based findings of Jiangxi strains were consistent with epidemiological investigation. Conclusion: Epidemiological analysis demonstrated that the emergence of dengue cases led to autochthonous transmission in several cities in Jiangxi, a low-epidemic region before. This study emphasized future prevention and control of dengue fever in both epidemic and non-epidemic regions.

Epidemiological and clinical analysis of the outbreak of dengue fever in Zhangshu City, Jiangxi Province, in 2019.

This study analyzed the epidemiological and clinical features of dengue fever in Zhangshu, Jiangxi Province, in 2019 and provided evidence for the diagnosis, treatment, prevention, and control of dengue fever. A total of 718 dengue fever patients in Zhangshu in 2019 were involved. ELISA and qRT-PCR were used for pathogenic detection of dengue virus. Multiple adjuvant therapies were applied, and the condition of patients after treatment was examined. Patients were between the ages of 0.75 and 92 years old, and all of them had a fever. A total of 519 cases had fatigue, and 413 cases had generalized myalgia and bone ache; 356 cases had dry mouth, 289 cases had bitter taste, and 167 cases felt dry and bitter taste; 279 cases had rash, and 93 cases had pruritus; 587 cases had decreased leukocyte, among which, 7 cases had leukocyte lower than 1 × 10 [9]/L; 380 cases had a low platelet count, and the platelet count of 29 cases was lower than 50 × 10 [9]/L; 488 cases had increased aspartic transaminase, and 460 cases had increased alanine aminotransferase; 5 cases had a severe disease. It proved that the majority of dengue fever sufferers were adults, with the main clinical features being fever and rash and the chief injured organs being the blood system, liver, heart, and gastrointestinal tract. Besides, over 40% of patients had dry and bitter taste, and 12 cases had alopecia after discharge. It indicates that the incidence of dengue fever in Zhangshu is closely related to the sudden population flow and imported cases.

WITHDRAWN: Epidemiology and clinical analysis of the breakout of dengue fever in Zhangshu City, Jiangxi Province in 2019.

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Primary Renal Malignant Fibrous Histiocytoma in an End-Stage Renal Disease Patient.

Besides renal cell carcinoma with increased risk reported in the dialysis population, other unusual types of renal tumors should also be considered. However, to the best of our knowledge, renal sarcomas have never been reported among end-stage renal disease patients undergoing dialysis in the literature. In this study, we present the first case of a primary renal malignant fibrous histiocytoma (MFH, also called undifferentiated pleomorphic sarcoma) in a 41-year-old woman with end-stage renal disease.

HSDL2 Promotes Bladder Cancer Growth In Vitro and In Vivo.

Bladder cancer is a common malignant urinary tumor, and patients with bladder cancer have poor prognosis. Abnormal lipid metabolism in peroxisomes is involved in tumor progression. Hydroxysteroid dehydrogenase-like 2 (HSDL2) localized in peroxisomes regulates fatty acid synthesis. In the present study, we reported that HSDL2 was upregulated in two human bladder cancer cell lines 5637 and T24 compared to normal human urothelial cells. Furthermore, lentiviral-mediated HSDL2 knockdown inhibited the proliferation and colony formation while promoted the apoptosis of human bladder cancer T24 cells in vitro. In nude mice HSDL2 knockdown inhibited the growth of T24 derived xenografts in vivo. In conclusion, our results suggest that HSDL2 plays an oncogenic role in bladder cancer and might serve as a potential target for bladder cancer therapy.

A comprehensive analysis of cancer-driving mutations and genes in kidney cancer.

An accumulation of driver mutations is important for cancer formation and progression, and leads to the disruption of genes and signaling pathways. The identification of driver mutations and genes has been the subject of numerous previous studies. The present study was performed to identify cancer-driving mutations and genes in renal cell carcinoma (RCC), prioritizing noncoding variants with a high functional impact, in order to analyze the most informative features. Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping version 2 (Polyphen2) and MutationAssessor were applied to predict deleterious mutations in the coding genome. OncodriveFM and OncodriveCLUST were used to detect potential driver genes and signaling pathways. The functional impact of noncoding variants was evaluated using Combined Annotation Dependent Depletion, FunSeq2 and Genome-Wide Annotation of Variants. Noncoding features were analyzed with respect to their enrichment of high-scoring variants. A total of 1,327 coding mutations in clear cell RCC, 258 in chromophobe RCC and 1,186 in papillary RCC were predicted to be deleterious by all three of MutationAssessor, Polyphen2 and SIFT. In total, 77 genes were positively selected by OncodriveFM and 1 by OncodriveCLUST, 45 of which were recurrently mutated genes. In addition, 10 signaling pathways were recurrently mutated and had a high functional impact bias (FM bias), and 31 novel signaling pathways with high FM bias were identified. Furthermore, noncoding regulatory features and conserved regions contained numerous high-scoring variants, and expression, replication time, GC content and recombination rate were positively correlated with the densities of high-scoring variants. In conclusion, the present study identified a list of cancer-driving genes and signaling pathways, features like regulatory elements, conserved regions, replication time, expression, GC content and recombination rate are major factors that affect the distribution of high-scoring non-coding mutations in kidney cancer.

Primary adenocarcinoma of the renal pelvis, ureter and the urinary bladder: A case report and review of the literature.

Primary adenocarcinoma is a rare type of urological neoplasm. The present study reports the case of a 55-year-old man with multifocal adenocarcinoma of the renal pelvis, ureter and urinary bladder that occurred in association with a large cystic calculus and perinephric abscess. The patient had suffered from gross hematuria for 2 years and right flank pain for 2 months. Following a series of investigations, a large cystic calculus with multiple tumors in the renal pelvis and ureter was identified. Multifocal tumors and a large calculus were located in the bladder using a cystoscope. The pathological report of 3 individual biopsies revealed a moderately differentiated tubular adenocarcinoma. Right nephrectomy, ureterectomy, radical cystectomy and left ureterocutaneostomy were performed. The pathological investigation revealed a moderately differentiated adenocarcinoma of the renal pelvis, ureter and urinary bladder. No additional treatment was administered and the patient remains alive at follow-up without disease recurrence or metastasis. Although uncommon, the development of a tumor is possible in patients that possess long-standing urolithiasis, particularly when accompanied by hydronephrosis or infection.

Safety and efficacy of a novel disposable circumcision device: a pilot randomized controlled clinical trial at 2 centers.

BACKGROUND: We evaluated the safety and efficacy of a novel disposable male circumcision (MC) device developed by Jiangxi-Yuansheng-Langhe Medical Instrument Co., Ltd. MATERIAL AND METHODS: Adult male patients (n=120; mean age, 26.6 years) with redundant foreskin and/or phimosis were included in a randomized, multicenter pilot clinical trial from October 2011 to February 2012. Patients were divided into 2 groups and subjected to MC with a novel disposable device (Device Group) (n=60) or to conventional dissection technique (CDT) (Control Group) (n=60). Intraoperative bleeding, surgery duration, pain, healing, and satisfaction with penis appearance were assessed. Adverse events (AEs) were noted. RESULTS: Intraoperative bleeding volume [3.5 ± 2.7 (15-35) ml vs. 13.1 ± 6.1 (4-25) ml] and mean surgical time [7.6 ± 4.5 (2-23) min vs. 23.6 ± 4.4 (15-35) min] in the Device Group were significantly less than in the Control Group (P<0.01). No AEs were observed in either group. There were no significant differences in postoperative pain, healing, or satisfaction with penis appearance between groups (P>0.05). CONCLUSIONS: This novel disposable circumcision device produced satisfactory preliminary adult MC results compared with CDT treatments. This device may be broadly used in men, such as those with phimosis, who are ineligible for CDT.

Mu2-acetato-kappa(2)O:O'-tris(mu2-ferrocenecarboxylato-kappa(2)O:O')bis[(N,N-dimethylformamide-kappaO)copper(II)].

The title compound, [Cu(2)Fe(3)(C(5)H(5))(3)(C(2)H(3)O(2))(C(6)H(4)O(2))(3)(C(3)H(7)NO)(2)], belongs to the classic dimeric paddle-wheel structure type. It is an unusual example in that it contains two different carboxylate groups, viz. ferrocenecarboxylate and acetate. With three ferrocenecarboxylate groups and only one acetate group bridging the two Cu centres, a noncentrosymmetric molecular arrangement results.

A new three-dimensional neutral framework of lanthanum oxalate: [La2(C2O4)3(DMF)(H2O)3]n.

In the title complex, poly[triaquabis(dimethylformamide)di-mu3-oxalato-mu2-oxalato-dilanthanum(III)], [La2(C2O4)3(C3H7NO)(H2O)3]n, both La ions are coordinated by nine O atoms, forming slightly distorted tricapped trigonal prisms. The two La ions, the terminal water O atom, and the O and N atoms of the dimethylformamide molecule reside on twofold rotation axes, giving the two La-centered coordination geometries twofold or pseudo-twofold symmetries. The two oxalate ligands, one of which rests on a center of inversion at the mid-point of the C-C bond, adopt different bridging modes, connecting with the La ions to form two types of lanthanide oxalate chains, i.e. anionic {[La(C2O4)2(DMF)(H2O)2]n-}(n) (DMF is dimethylformamide) and cationic zigzag {[La(C2O4)(H2O)]n+}n, respectively. Each zigzag cationic chain is linked to four adjacent anionic chains via the bridging oxalate anions, and each anionic chain connects with four zigzag cationic chains, constructing a three-dimensional neutral framework.