Abstract Survival analysis has been widely used in the field of medical research. The Cox proportional hazard model is commonly used, but its practical application is limited. Machine learning method can compensate for the shortcomings of the Cox proportional hazard model in terms of nonlinear data processing and prediction accuracy. This article reviewed the advance of machine learning methods represented by neural networks, within the field of survival analysis, and highlighted the principles and benefits of three machine learning methods that DeepSurv, Deep-Hit and random survival forest, providing methodological insights for the analysis of complex survival data.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Objective:To establish and validate reference intervals of serum vitamin K for healthy children in China.Methods:A cross-sectional study was conducted from January 2020 to May 2023, involving 807 healthy children aged 0 to 14 years, selected by stratified random sampling based on the population distribution of children in eastern, central, western, and northeastern China. Sample collection was carried out in 16 hospitals across 12 provinces, autonomous regions, and municipalities. Basic information of the children was collected using a standardized self-design questionnaire. Serum levels of vitamin K 1 and vitamin K 2 (menaquinone-4 (MK-4), menaquinone-7 (MK-7)) were measured using liquid chromatography-tandem mass spectrometry. The reference intervals was established by direct approach. The children were divided into different groups by age. Inter-group comparisons were conducted using the Kruskal-Wallis non-parametric test, and the reference intervals ( P2.5- P97.5) were determined using non-parametric methods. Screening 40 healthy children for small sample validation based on age groups within the reference range(25 from eastern, 10 from central, and 5 from western regions). Results:The age of the 807 children was 5.00 (2.00, 9.81) years, and 495 (61.3%) were males and 312 (38.7%) females. Reference intervals were established for 795 children, of whom 303 children were aged 1 month to 3 years and 492 were aged 4 to 14 years. The reference intervals for serum vitamin K 1 were 0.09-4.54 μg/L for children aged 1 month to 3 years, and 0.10-1.73 μg/L for 4-14 years. For MK-7, the intervals were 0.07-1.42 μg/L for 1 month to 3 years and 0.19-2.03 μg/L for 4-14 years. The reference intervals for MK-4 in children aged 1 month to 14 years were 0-0.42 μg/L. The measured values of serum vitamin K 1, MK-4, and MK-7 in the validation samples did not exceed the reference limit in more than 2 samples. Conclusion:Reference intervals for vitamin K 1, MK-4, and MK-7 in healthy children aged 1 month to 14 years have been established and validated, and can be used to assess vitamin K nutritional status in children.

BACKGROUND: Diabetic wound healing remains a major challenge due to the impaired functionality of angiogenesis by persistent hyperglycemia. Mesenchymal stem cell exosomes are appropriate candidates for regulating the formation of angiogenesis in tissue repair and regeneration. Here, we explored the effects of exosomes derived from human amniotic mesenchymal stem cell (hAMSC-Exos) on the biological activities of human umbilical vein endothelial cells (HUVECs) treated with high glucose and on diabetic wound healing and investigate lncRNAs related to angiogenesis in hAMSC-Exos. METHODS: hAMSCs and hAMSC-Exos were isolated and identified by flow cytometry or western blot. A series of functional assays such as cell counting kit-8, scratching, transwell and tube formation assays were performed to evaluate the potential effect of hAMSC-Exos on high glucose-treated HUVECs. The effect of hAMSC-Exos on diabetic wound healing were tested by measuring wound closure rates and immunohistochemical staining of CD31. Subsequently, the lncRNAs profiles in hAMSC-Exos and hAMSCs were examined to screen the lncRNAs related to angiogenesis. RESULTS: The isolated hAMSC-Exos had a size range of 30–150 nm and were positive for CD9, CD63 and CD81. The hAMSC-Exos facilitate the functional properties of high glucose-treated HUVECs including the proliferation, migration and the angiogenic activities as well as wound closure and angiogenesis in diabetic wound. hAMSC-Exos were enriched lncRNAs that related to angiogenesis, including PANTR1, H19, OIP5-AS1 and NR2F1-AS1. CONCLUSION Our findings demonstrated hAMSC-Exos facilitate diabetic wound healing by angiogenesis and contain several exosomal lncRNAs related to angiogenesis, which may represent a promising strategy for diabetic wound healing.

Objective Iodothyronine deiodinases (DIOs) are important selenoproteins that play a key role in the bone and joint diseases. Osteoarthritis (OA) is the most prevalent joint disease especially in elders. This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis. Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques, including GenCLip 3.0, Database for Annotation, Visualization and Integrated Discovery (DAVID), STRING, Cytoscape, and Network Analyst. The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus (GEO) database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3. Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine; GO analysis showed that DIOs were mainly involved in biological processes, such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling; SULT1A1 was the core node of the PPI network; miRNAs and thyroid hormones had some iterations with DIO1 and DIO2; Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients (SMD = 0.31, 95％CI: 0.03, 0.59, P = 0.03). Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone. And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.

The accelerometry(AMG) muscle relaxant monitor is the most widely used quantitative muscle relaxant monitor to assess the degree of neuromuscular at present. In this study, the ulnar nerve was stimulated by using train of four stimulation(TOF) mode of the AMG muscle relaxant monitor, and the movement of the adductor pollicis muscle was monitored. In this way, the distribution range of key parameters (acceleration peak value, response time, and TOF ratio) of the adductor pollicis muscle during the use of muscle relaxant in clinical practice is analyzed and will provide a practical basis for the development and improvement of the muscle relaxant monitor.
Electric Stimulation ; Muscle, Skeletal ; Neuromuscular Blockade ; Neuromuscular Nondepolarizing Agents ; Ulnar Nerve/physiology*

Objective:To understand the identification and medical observation of close contacts of COVID-19 cases in a city and provide scientific basis for the adjustment of the epidemic prevention and control strategies.Methods:Descriptive epidemiological methods were used to analyze the general characteristics of all the close contacts of COVID-19 cases in a city. Throat swabs were collected from the close contacts for real-time fluorescent RT-PCR. The confirmed cases were diagnosed according to diagnosis and treatment of COVID-19 (trial version 5).Results:Among the 1 665 close contacts of COVID-19 cases in a city, 10 were diagnosed as COVID-19 cases during the medical observation period, accounting for 30.30% of all the confirmed cases in a city, most of them were close relatives of the confirmed cases. The longest contact time with the confirmed cases was 8 days and the shortest was 0 days. Ten COVID-19 cases in close contacts constituted to six family clusters.Conclusions:In COVID-19 prevention and control in a city, the active tracking of the transmission chains of the confirmed cases and timely identification of the close contacts were conducted. The people who had close contacts with the confirmed COVID-19 cases within 14 days before onset were all placed under medical observation, which played a key role in the effective prevention and control of COVID-19 epidemic in a city. Nearly one third of COVID-19 cases occurred during the medical observation period, so the infection sources were effectively controlled and transmission routes were effectively blocked, which greatly facilitated the prevention of the clusters of COVID-19 cases.

Objective To explore the effect of ginsenoside Rd on regulatory T cells (Tregs) /helper T cell 17 (Th17) imbalance in experimental autoimmune encephalomyelitis (EAE) mice models.Methods Fifty-four female C57BL/6 mice,aged 6-8 weeks,were randomly divided into ginsenoside Rd group,phosphate buffered saline (PBS) group and blank-control group (n=18).The EAE mice models in the first two groups were induced by classical Mog35-55 peptide immunoinduction method;ginsenoside Rd of 40 mg/ (kg·d) was dissolved in PBS and intraperitoneally injected into the mice daily in the ginsenoside Rd group on 13th d of immunization;the mice in the PBS group and control group were intraperitoneally injected with same dose of PBS.Daily clinical symptom scale scores were obtained from the first d to the 20th d of immunization,and the lumbar spinal cords of the mice were taken for histological evaluation (inflammation scale and demyelinating scale) after the last symptom scale.On the 20th d of immunization,the spleens of each group were taken for cultivation;splenocytes were cultured in vitro for 48 h,and the culture supematant was taken for detecting interleukin (IL)-10 and IL-17 levels by enzyme-linked immunosorbent assay (ELISA);the proportions of Tregs and Thl7 in spleen tissues were detected by flow cytometry;real-time quantitative PCR was used to detect the mRNA expressions of Janus kinase 1 (JAK1),Janus kinase 2 (JAK2),signal transduction and activator of transcription 3 (STA T3),retinoic acid-related orphan nuclear receptors γt (ROR-γt) and forkhead gene p3 (Foxp3) in the lumbar spinal cords of mice in each group.Results (1) The clinical symptom scale scores and inflammation scale scores of ginsenoside Rd group were significantly lower than those of PBS group (P＜0.05);there were a large number of inflammatory cells infiltration and loss of myelin in the lumbar spinal cord of PBS group,while the loss of myelin sheath in ginsenoside Rd group was obviously decreased as compared with that in PBS group;the demyelination scale scores between the two groups showed statistical differences (P＜0.05).(2) As compared with those in the PBS group,the IL-10 level was significantly increased and the IL-17 level was significantly decreased in the splenocyte culture supernatant of ginsenoside Rd group (P＜0.05).(3) As compared with the PBS group,the ginsenoside Rd group had significantly decreased proportion of CD4+IL-17+ cells and significantly increased proportion of CD4+CD25+Foxp3+ cells in the spleen (P＜0.05).(4) As compared with those in the PBS group,the mRNA expression levels of JAK1,JAK2,STA T3 and ROR-γt were significantly decreased,and Foxp3 mRNA expression level was significantly increased in the lumbar spinal cords of the ginsenoside Rd group (P＜0.05).Conclusion Ginsenoside Rd can improve the condition of EAE mice models by altering the expressions of Foxp3/RORγt/STAT3 signaling pathway molecules related to differentiation of Tregs/Th 17,increasing the IL-10 level and Tregs ratio,and decreasing the IL-17 level and Th 17 ratio.

Objective To investigate the safety and efficacy of holmium laser transurethral enucleation of the prostate (HoLEP) for large volume of prostatic hyperplasia (BPH) with navigation of ultrasonic anatomical landmarks.Methods Data of 242 patients with BPH (≥ 80 cm3) underwent domestic HoLEP from Jan.2016 to Jan.2018 were retrospectively analyzed.General data,IPSS,QOL,prostate volume,PSA were assessed.Their average volume of prostate was (103.2 ± 21.4) cm3,the average PSA was (2.6 ± 1.4) ng/ml,the residual urine volume was (105 ± 75) ml,Qmax was (6.4 ± 5.2) nd/s,IPSS score was 22.5 ± 5.3 and QOL score was 4.8 ± 1.2.Result All patients were completed the operation successfully and their LUTS indicators were greatly improved.The enucleation time was between 25 and 80 min,average (49.0 ± 12.2) min;the mass of wet weight of gland was (70.5 ± 15.3) g;the removal efficiency was (1.6 ±0.3) g/min.The IPSS score dropped to 14.8 ± 6.5,P ＜ 0.01;QOL score dropped to 2.6 ± 1.5,P ＜ 0.01;PSA dropped to (1.1 ± 1.2) ng/ml,P ＜ 0.01;the maximum urinary flow rate growth to (16.5 ±7.1) ml/s,P ＜0.01.Conclusion For large volume of prostatic hyperplasia,holmium laser transurethral enucleation with ultrasonic navigation surgery is safe and efficient.