Background & Objective: Continuous electroencephalography (cEEG) is valuable in the diagnosis and management of refractory status epilepticus (RSE) but requires intensive skilled interpretation. Density spectral array (DSA) is a quantitative analytic tool used to screen cEEG recordings for seizures. This study aims to determine the optimal amplitude setting and to compare the use of single-averagetrendgraph display and eight-trendgraph display in seizure detection with DSA. Methods: Five excerpts from pediatric cEEG recordings with RSE were identified. In Phase 1 of the study, each of 4 readers determined the DSA amplitude setting one most preferred for each excerpt, and marked all seizures in one excerpt using one’s preferred setting. Inter-rater agreement in seizure detection was measured. In Phase 2, readers marked all seizures in all excerpts, first using single-average-trendgraph display, and then using eight-trendgraph display after a wash-out period. Intra-rater agreement in seizure detection between the two display methods was calculated. Results: In Phase 1, DSA readers’ choice of preferred amplitude settings varied widely but inter-rater agreement in seizure detection was high. In Phase 2, seizure detection using single- and eight-trendgraph displays showed high agreement with each other and, where they disagreed, single-average-trendgraph was more sensitive. Additionally, low seizure-to-background amplitude ratio in EEG recordings was associated with worse detection sensitivity/specificity. Conclusions: DSA amplitude settings do not affect seizure detection. Single-trendgraph display is comparable to eight-trendgraph display in screening cEEG for seizures. Seizure detection with DSA performs better in cEEG recordings with high seizure-to-background amplitude ratio.

Humans ; Medicine, Chinese Traditional ; trends ; Models, Theoretical ; Patient Care ; trends ; Western World

Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized as one of the most important pathogens of pigs throughout the world. In 2006, more than 10 provinces of China have experienced an epizootic outbreak of pig diseases characterized by high fever, reddened skin and high morbidity and mortality. From June 2006 to April 2007, we have investigated some clinical samples in Hubei province by RT-PCR and cloned several major genes, N, GP5 and NSP2 gene, shown in this study. Phylogenetic analysis of these genes revealed that the highly pathogenic PRRSV variant, ZB, was responsible for 2006 emergent outbreak of pig disease in Hubei province similar with those variants isolated from other provinces in China in 2006, and belongs to the NA-type PRRSV. In the PRRSV variants, the N and GP5 shear about 90% identity with prototypic ATCC VR-2332 and some typical NA-type Chinese isolates, except the 2850bp NSP2 gene (only shares 65% identity with ATCC VR-2332). But they all shear more than and 97% identity with other highly pathogenetic Chinese PRRSV strains. Additionally, there are extensive amino acid (aa) mutations in the GP5 protein and 2 deletions in the Nsp2 protein when compared with the previous isolates. Most of the variants found in 2006 epizootic outbreak of pig diseases in China were the farthest variants from the typical NA-type PRRSV in phylogenetic distance, and these diversities may be responsible for the differences in the pathogenicity observed between these variants and original Chinese PRRSV strains.

Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

OBJECTIVETo investigate the virulence characteristics of two fixed strains (CTN and aG) and a street strain (HN10) of rabies viruses isolated in China.

METHODSICR mice of different age groups were inoculated with CTN, aG and HN10 rabies virus strains via the intracracerebral (i.c.) or intramuscular (i.m.) routes, and observed for 20 days.

RESULTSThe CTN strain was pathogenic to 7-day-old suckling mice that received i.c. inoculations and 3-day-old suckling mice that received i.m. inoculations. The aG strain was pathogenic to 4-week-old mice that received i.c. inoculations and 7-day-old suckling mice that received i.m. inoculations. The HN10 strain was pathogenic to mice of all age groups via both inoculation routes. In moribund mice, the viruses had spread to most regions of the brain. The CTN and HN10 strains had similar dissemination patterns in the brain; both viral antigens could be found in the dentate gyrus (DG), whereas few viral antigens were present in the DG from specimens that had been infected with the aG strain.

CONCLUSIONA comprehensive sequence analysis of the G protein suggested that differences in gene sequences may be responsible for producing strain-specific differences in pathogenicity and distribution in the brain.

Animals ; Antigens, Viral ; immunology ; Brain ; immunology ; virology ; China ; Mice ; Mice, Inbred ICR ; Nucleocapsid Proteins ; immunology ; Rabies ; virology ; Rabies virus ; immunology ; isolation & purification ; pathogenicity

PURPOSE: Tumor xenograft model is an indispensable animal cancer model. In esophageal squamous cell carcinoma (ESCC) research, orthotopic tumor xenograft model establishes tumor xenograft in the animal esophagus, which allows the study of tumorigenesis in its native microenvironment. MATERIALS AND METHODS: In this study,we described two simple and reproducible methods to develop tumor xenograft at the cervical or the abdominal esophagus in nude mice by direct injection of ESCC cells in the esophageal wall. RESULTS: In comparing these two methods, the cervical one presented with more clinically relevant features, i.e., esophageal stricture, body weight loss and poor survival. In addition, the derived tumor xenografts accompanied a rapid growth rate and a high tendency to invade into the surrounding structures. This model was subsequently used to study the anti-tumor effect of curcumin, which is known for its potential therapeutic effects in various diseases including cancers, and its analogue SSC-5. SSC-5 was selected among the eight newly synthesized curcumin analogues based on its superior anti-tumor effect demonstrated in an MTT cell proliferation assay and its effects on apoptosis induction and cell cycle arrest in cultured ESCC cells. Treatment of orthotopic tumor-bearing mice with SSC-5 resulted in an inhibition in tumor growth and invasion. CONCLUSION: Taken together, we have established a clinically relevant orthotopic tumor xenograft model that can serve as a preclinical tool for screening new anti-tumor compounds, e.g., SSC-5, in ESCC.
Animals ; Apoptosis ; Body Weight ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cell Cycle Checkpoints ; Cell Proliferation ; Curcumin* ; Epithelial Cells* ; Esophageal Stenosis ; Esophagus ; Heterografts* ; Mass Screening ; Mice ; Mice, Nude ; Therapeutic Uses

Cardiac ion channelopathies encompass a set of inherited or acquired conditions that are due to dysfunction in ion channels or their associated proteins, typically in the presence of structurally normal hearts. They are associated with the development of ventricular arrhythmias and sudden cardiac death. The aim of this review is to provide a historical perspective and recent advances in the research of the cardiac ion channelopathies, Brugada syndrome, long QT syn‑ drome and catecholaminergic polymorphic ventricular tachycardia, in Hong Kong, China. In particular, recent works on the development of novel predictive models incorporating machine learning techniques to improve risk strati‑ fication are outlined. The availability of linked records of affected patients with good longitudinal data in the public sector, together with multidisciplinary collaborations, implies that ion channelopathy research efforts have advanced significantly.

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*