As one of the standard electrophysiological signals in the human body, the photoplethysmography contains detailed information about the blood microcirculation and has been commonly used in various medical scenarios, where the accurate detection of the pulse waveform and quantification of its morphological characteristics are essential steps. In this paper, a modular pulse wave preprocessing and analysis system is developed based on the principles of design patterns. The system designs each part of the preprocessing and analysis process as independent functional modules to be compatible and reusable. In addition, the detection process of the pulse waveform is improved, and a new waveform detection algorithm composed of screening-checking-deciding is proposed. It is verified that the algorithm has a practical design for each module, high accuracy of waveform recognition and high anti-interference capability. The modular pulse wave preprocessing and analysis software system developed in this paper can meet the individual preprocessing requirements for various pulse wave application studies under different platforms. The proposed novel algorithm with high accuracy also provides a new idea for the pulse wave analysis process.
Humans ; Systems Analysis ; Algorithms ; Software ; Heart Rate ; Microcirculation

OBJECTIVES: To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples. METHODS: The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode. RESULTS: The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%. CONCLUSIONS The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.
Gas Chromatography-Mass Spectrometry/methods* ; Electronic Nicotine Delivery Systems ; Illicit Drugs/analysis* ; Indazoles/chemistry* ; Glycerol/analysis* ; Cannabinoids ; Indoles/chemistry* ; Ions

OBJECTIVE: To determine if ARHGEF10 has a haploinsufficient effect and provide evidence to evaluate the severity, if any, during prenatal consultation. METHODS: Zebrafish was used as a model for generating mutant. The pattern of arhgef10 expression in the early stages of zebrafish development was observed using whole-mount in situ hybridization (WISH). CRISPR/Cas9 was applied to generate a zebrafish model with a single-copy or homozygous arhgef10 deletion. Activity and light/dark tests were performed in arhgef10 ^-/-, arhgef10 ^+/-, and wild-type zebrafish larvae. ARHGEF10 was knocked down using small interferon RNA (siRNA) in the SH-SY5Y cell line, and cell proliferation and apoptosis were determined using the CCK-8 assay and Annexin V/PI staining, respectively. RESULTS: WISH showed that during zebrafish embryonic development arhgef10 was expressed in the midbrain and hindbrain at 36-72 h post-fertilization (hpf) and in the hemopoietic system at 36-48 hpf. The zebrafish larvae with single-copy and homozygous arhgef10 deletions had lower exercise capacity and poorer responses to environmental changes compared to wild-type zebrafish larvae. Moreover, arhgef10 ^-/- zebrafish had more severe symptoms than arhgef10 ^+/- zebrafish. Knockdown of ARHGEF10 in human neuroblastoma cells led to decreased cell proliferation and increased cell apoptosis. CONCLUSION Based on our findings, ARHGEF10 appeared to have a haploinsufficiency effect.
Animals ; Annexin A5 ; Apoptosis ; Blotting, Western ; CRISPR-Associated Protein 9 ; CRISPR-Cas Systems ; Cell Line ; Cell Proliferation ; Cells, Cultured ; Flow Cytometry ; Genotype ; Humans ; In Situ Hybridization ; Larva/physiology* ; Phenotype ; RNA/isolation & purification* ; Real-Time Polymerase Chain Reaction/standards* ; Rho Guanine Nucleotide Exchange Factors/metabolism* ; Sincalide/analysis* ; Spectrophotometry/methods* ; Zebrafish/physiology*

Spatial epidemiology focuses on the use of geographic information systems and spatial analysis to study spatial distribution and change tendency of diseases and explore the health status of specific populations. In recent years, spatial epidemiology has been applied in the field of HIV/AIDS prevention and control. This review summarizes the progress in the application of spatial epidemiology in the analysis of spatiotemporal distribution, non-monitoring area data estimation, influencing factors of AIDS and health resource allocation and utilization to provide reference for its application in the prevention and control of AIDS in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; Geographic Information Systems ; HIV Infections/prevention & control* ; Humans ; Spatial Analysis

OBJECTIVES: To establish a combined high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) method to detect the synthetic cannabinoid CUMYL-PEGACLONE in e-cigarette oil and hair. METHODS: HPLC-MS/MS and GC-MS were used to establish the detection method of CUMYL-PEGACLONE, and the hair of drug-involved persons and the seized e-cigarette oil were detected. RESULTS: The main mass spectrometry characteristic ions m/z of CUMYL-PEGACLONE measured by GC-MS were 91, 179, 197, 254 and 372. CUMYL-PEGACLONE had a good linear relationship in the mass concentration range of 2-50 ng/mL, and the linear correlation coefficient (r) was greater than 0.99. The limit of detection (LOD) of CUMYL-PEGACLONE in hair was 0.01 ng/mg, and the limit of quantitation (LOQ) was 0.02 ng/mg. The LOD of CUMYL-PEGACLONE in e-cigarette oil was 1 ng/mg, and the LOQ was 2 ng/mg. The average recoveries of CUMYL-PEGACLONE under the attempt at high, intermediate and low levels in blank human hair and e-cigarette oil matrix were 98.2%-132.4% and 93.5%-110.6%, and the intraday and intraday precision were 1.2%-12.9% and 0.7%-2.9%. CUMYL-PEGACLONE was detected in the hair of 15 drug-involved persons. Except for 1 person who was lower than LOQ, the concentration of CUMYL-PEGACLONE in the hair of other 14 persons was 0.035-0.563 ng/mg. The mass fraction of CUMYL-PEGACLONE in 2 e-cigarette oil were 0.17% and 0.21%, respectively. CONCLUSIONS The established HPLC-MS/MS and GC-MS methods are applied to the detection of HPLC-MS/MS in drug-related cases, which provides strong evidence support for the handling authority to quickly investigate these cases, and also provides a reference for the identification of such substances in future.
Humans ; Illicit Drugs/analysis* ; Tandem Mass Spectrometry ; Electronic Nicotine Delivery Systems ; Cannabinoids ; Hair/chemistry* ; Limit of Detection ; Substance Abuse Detection/methods*

OBJECTIVE: To identify differentiation related miRNA and evaluate roles of miRNA during ATRA induced myeloid differentiation. METHODS: The small RNA sequencing was used to analyze differential expressed miRNAs in ATRA induced NB4 cells. Then the several up or down-regulated miRNA were selected as the research candidates. SgRNAs targeting the genome of each miRNA were designed and NB4 cells with inducible expression of Cas9 protein were generated. After transduced sgRNA into NB4/Cas9 cells, the mutation level by PCR and surveyor assay were evaluated. The cell differentiation level was investigated by surface CD11b expression via flow cytometry. RESULTS: A total of 410 mature miRNAs which expressed in NB4 cells were detected out after treated by ATRA, 74 miRNAs were up-regulated and 55 were down-regulated miRNAs with DNA cleavage generated by CRISPR/Cas9 was assayed directly by PCR or surveyor assay, quantitative PCR showed that the expression of miRNA was downregulated, which evaluated that gene edition successfully inhibitied the expression of mature miRNA. MiR-223 knockout showed the myeloid differentation of NB4 significantly inhibitied, while miRNA-155 knockout showed the myeloid differentation of NB4 cells significantly increased. CONCLUSION CRISPR/Cas9 is a powerful tool for gene editing and can lead to miRNA knockout. Knockouts of miR-223 and miR-155 have shown a differentiation-related phenotype, and the potential mechanism is the integrative regulation of target genes.
CRISPR-Cas Systems ; Cell Differentiation ; Gene Editing ; MicroRNAs/genetics* ; Sequence Analysis, RNA ; Tretinoin

Gene expression labeling and conditional manipulation of gene function are important for elaborate dissection of gene function. However, contemporary generation of pairwise dual-function knockin alleles to achieve both conditional and geno-tagging effects with a single donor has not been reported. Here we first developed a strategy based on a flipping donor named FoRe to generate conditional knockout alleles coupled with fluorescent allele-labeling through NHEJ-mediated unidirectional targeted insertion in zebrafish facilitated by the CRISPR/Cas system. We demonstrated the feasibility of this strategy at sox10 and isl1 loci, and successfully achieved Cre-induced conditional knockout of target gene function and simultaneous switch of the fluorescent reporter, allowing generation of genetic mosaics for lineage tracing. We then improved the donor design enabling efficient one-step bidirectional knockin to generate paired positive and negative conditional alleles, both tagged with two different fluorescent reporters. By introducing Cre recombinase, these alleles could be used to achieve both conditional knockout and conditional gene restoration in parallel; furthermore, differential fluorescent labeling of the positive and negative alleles enables simple, early and efficient real-time discrimination of individual live embryos bearing different genotypes prior to the emergence of morphologically visible phenotypes. We named our improved donor as Bi-FoRe and demonstrated its feasibility at the sox10 locus. Furthermore, we eliminated the undesirable bacterial backbone in the donor using minicircle DNA technology. Our system could easily be expanded for other applications or to other organisms, and coupling fluorescent labeling of gene expression and conditional manipulation of gene function will provide unique opportunities to fully reveal the power of emerging single-cell sequencing technologies.
Alleles ; Animals ; CRISPR-Cas Systems ; DNA End-Joining Repair ; DNA, Circular/metabolism* ; Embryo, Nonmammalian ; Gene Editing/methods* ; Gene Knock-In Techniques ; Gene Knockout Techniques ; Genes, Reporter ; Genetic Loci ; Genotyping Techniques ; Green Fluorescent Proteins/metabolism* ; Integrases/metabolism* ; Luminescent Proteins/metabolism* ; Mutagenesis, Insertional ; Single-Cell Analysis ; Zebrafish/metabolism*

For patients with moderate-to-severe erectile dysfunction, implantable penile prostheses continue to be a viable treatment. Medical device developers apply design controls during the development cycle to ensure that a product performs as intended in the final use environment. This process relies heavily on the principles of systems engineering and documents every facet of performance, unmet need, and risk. To better understand design philosophy, it is important to frame benchmarked performance outcomes in the context of the ideal state. Careful consideration of erectile anatomy and physiology, including flaccid state, transitional phases, and full tumescence, informs penile prosthesis design philosophy and provides the foundation for product advancement.
Biomedical Engineering ; Erectile Dysfunction/surgery* ; Humans ; Male ; Penile Implantation ; Penile Prosthesis ; Prosthesis Design ; Systems Analysis

OBJECTIVE: This study examined the inflow and outflow patterns of emergency department patients with si-gun-gu in the Gwangju, Jeonbuk, and Jeonnam areas. METHODS: Data from the Gwangju, Jeonbuk, and Jeonnam were extracted from the National Emergency Department Information System in 2016. The extracted data (on 42 areas in Gwangju, Jeonbuk, and Jeonnam) using the variables of the patient's address (zip code) and the emergency medical institution code (emergency medical institution address) were used to calculate the relevance index and commitment index. The calculated indices were classified into the regional types by applying NbClust and cluster analysis (K-means) of the R package. RESULTS: The relevance indices ranged from 12.5% to 90.4%, and the commitment indices ranged from 9.2% to 90.3%. The results of cluster analysis with the relevance indices and commitment indices revealed three types for 39 areas. In cluster 1, the relevance indices ranged from 43.5% to 61.6%, and the commitment indices ranged from 9.2% to 49.5%. Three out of the thirty-nine areas were classified as the inflow type. In cluster 2, the relevance indices ranged from 12.5% to 56.0% and the commitment indices ranged from 62.5% to 90.3%; 12 areas were classified as the outflow type. The areas in cluster 3 were classified as the self-sufficient type, with relevance indices ranging from 60.1% to 90.4% and commitment indices ranging from 59.0% to 89.7% for 24 areas. CONCLUSION: Three area types and 11 out of 12 areas classified as outflow types were found to be emergency medical vulnerable areas. The results of this study can be used to establish local emergency medical policies.
Cluster Analysis ; Emergencies ; Emergency Service, Hospital ; Gwangju ; Humans ; Information Systems ; Jeollabuk-do ; Jeollanam-do

OBJECTIVE: To retrospectively determine whether the use of the Prostate Imaging Reporting and Data System (PI-RADS) version 2 (v2) helps predict long-term outcomes for prostate cancer (PCa) patients following radical prostatectomy (RP). MATERIALS AND METHODS: A total of 166 patients with localized PCa evaluated with multiparametric magnetic resonance imaging (mpMRI) at 3T before RP were enrolled. Three groups were created based on PI-RADS v2 score used to predict clinical outcomes: group A, ≥ 3; group B, ≥ 4; group C, 5. We calculated biochemical recurrence-free survival (RFS) and progression-free survival (PFS). Cox proportion hazards models were used to identify variables predictive of biochemical recurrence and disease progression. RESULTS: During a median follow-up of 9.1 years, biochemical recurrence occurred in 67 patients (40.4%) and disease progression occurred in 55 patients (33.1%). In all groups, 10-year RFS and 10-year PFS were significantly lower for PI-RADS scores ≥ 3, ≥ 4 and 5 than for score < 3, < 4 and < 5 (p <0.05), respectively. In multivariate analysis, PI-RADS score ≥ 3 and score 5 were significant independent risk marker for biochemical recurrence (hazard ratio [HR] = 5.58, p = 0.018; HR = 1.75, p = 0.033) and disease progression (HR = 3.99, p = 0.047; HR = 2.31, p = 0.040). Moderate inter-observer agreement was seen for PI-RADS scoring. CONCLUSION: PI-RADS v2 may be used to predict long-term outcomes following RP in PCa.
Disease Progression ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Information Systems ; Magnetic Resonance Imaging ; Male ; Multivariate Analysis ; Passive Cutaneous Anaphylaxis ; Prognosis ; Proportional Hazards Models ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Recurrence ; Retrospective Studies