Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Long-read sequencing on the SMRT platform enables efficient haplotype linkage analysis in preimplantation genetic testing for ß-thalassemia.

PURPOSE: This study aimed to evaluate the value of long-read sequencing for preimplantation haplotype linkage analysis. METHODS: The genetic material of the three ß-thalassemia mutation carrier couples was sequenced using single-molecule real-time sequencing in the 7.7-kb region of the HBB gene and a 7.4-kb region that partially overlapped with it to detect the presence of 17 common HBB gene mutations in the Chinese population and the haplotypes formed by the continuous array of single-nucleotide polymorphisms linked to these mutations. By using the same method to analyze multiple displacement amplification products of embryos from three families and comparing the results with those of the parents, it could be revealed whether the embryos carry disease-causing mutations without the need for a proband. RESULTS: The HBB gene mutations of the three couples were accurately detected, and the haplotype linked to the pathogenic site was successfully obtained without the need for a proband. A total of 68.75% (22/32) of embryos from the three families successfully underwent haplotype linkage analysis, and the results were consistent with the results of NGS-based mutation site detection. CONCLUSION: This study supports long-read sequencing as a potential tool for preimplantation haplotype linkage analysis.

Point Cloud Instance Segmentation With Semi-Supervised Bounding-Box Mining.

Point cloud instance segmentation has achieved huge progress with the emergence of deep learning. However, these methods are usually data-hungry with expensive and time-consuming dense point cloud annotations. To alleviate the annotation cost, unlabeled or weakly labeled data is still less explored in the task. In this paper, we introduce the first semi-supervised point cloud instance segmentation framework (SPIB) using both labeled and unlabelled bounding boxes as supervision. To be specific, our SPIB architecture involves a two-stage learning procedure. For stage one, a bounding box proposal generation network is trained under a semi-supervised setting with perturbation consistency regularization (SPCR). The regularization works by enforcing an invariance of the bounding box predictions over different perturbations applied to the input point clouds, to provide self-supervision for network learning. For stage two, the bounding box proposals with SPCR are grouped into some subsets, and the instance masks are mined inside each subset with a novel semantic propagation module and a property consistency graph module. Moreover, we introduce a novel occupancy ratio guided refinement module to refine the instance masks. Extensive experiments on the challenging ScanNet v2 dataset demonstrate our method can achieve competitive performance compared with the recent fully-supervised methods.

[Correlation of sperm DNA fragmentation index with age and semen parameters and its influence on the outcomes of IVF-ET].

OBJECTIVE: To explore the correlation of the sperm DNA fragmentation index (DFI) with age and other semen parameters in infertile men and its influence on the outcomes of in vitro fertilization and embryo transplantation (IVF-ET). METHODS: Semen samples were obtained from 6 162 infertile males in our hospital between July 2017 and December 2018. Sperm concentration, the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS) and sperm DFI were determined by computer-assisted semen analysis, modified Papanicolaou staining and sperm chromatin structure assay, respectively. According to the sperm DFI, the samples were divided into three groups: DFI≤15%, 15%30%. Comparisons were made among different groups in the rates of fertilization, embryo cleavage, embryo formation and pregnancy. RESULTS: Spearman correlation analysis showed that DFI was correlated positively with age (r = 0.508, P < 0.05), but negatively with sperm concentration (r = －0.155, P < 0.05) and the percentages of PMS (r = －0.111, P < 0.05) and MNS (r = －0.315, P < 0.05). With sperm DFI >20%, the clinical pregnancy rate of IVF-ET was significantly reduced, while with sperm DFI >30%, the rate of available embryos markedly decreased and that of biochemical pregnancy remarkably increased. No correlation was found between sperm DFI and the rates of fertilization, embryo cleavage and high-quality embryos in IVF-ET. CONCLUSIONS: In infertile males, sperm DFI is correlated positively with age but negatively with sperm concentration and the percentages of PMS and MNS, and it significantly affects the outcomes of IVF-ET.

Programming of a developmental imbalance in hypothalamic glutamatergic/GABAergic afferents mediates low basal activity of the hypothalamic-pituitary-adrenal axis induced by prenatal dexamethasone exposure in male offspring rats.

This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) in male offspring rats and explore the underlying mechanism. Pregnant rats were subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were sacrificed under anesthesia. Hypothalamic cells were from GD20∼postnatal day (PD) 7 fetal male rats, treated with different concentrations of dexamethasone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus (PVN). This imbalance change was maintained postnatally, leading to the inhibition of parvocellular neurons, and mediating the low basal activity of the HPAA in PDE offspring rats, which was manifested by decreased levels of blood adrenocorticotropic hormone and corticosterone as well as reduced expression levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus. Programming of a developmental imbalance in glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible for low basal activity of the HPAA in male PDE rats.

Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. INTERVENTION: Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. RESULTS AND LIMITATIONS: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p<0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p<0.001), required lower use of analgesics compared with placebo (p<0.001), and significantly relieved renal colic (p<0.001). No differences in the incidence of adverse events were identified between the two groups. CONCLUSIONS: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5mm, but no effect for stones ≤5mm. PATIENT SUMMARY: In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.