Machine learning-based prediction model for myocardial ischemia under high altitude exposure: a cohort study.

High altitude exposure increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Machine learning techniques have been used to develop cardiovascular disease prediction models, but no reports exist for high altitude induced myocardial ischemia. Our objective was to establish a machine learning-based MI prediction model and identify key risk factors. Using a prospective cohort study, a predictive model was developed and validated for high-altitude MI. We consolidated the health examination and self-reported electronic questionnaire data (collected between January and June 2022 in 920th Joint Logistic Support Force Hospital of china) of soldiers undergoing high-altitude training, along with the health examination and second self-reported electronic questionnaire data (collected between December 2022 and January 2023) subsequent to their completion on the plateau, into a unified dataset. Participants were subsequently allocated to either the training or test dataset in a 3:1 ratio using random assignment. A predictive model based on clinical features, physical examination, and laboratory results was designed using the training dataset, and the model's performance was evaluated using the area under the receiver operating characteristic curve score (AUC) in the test dataset. Using the training dataset (n = 2141), we developed a myocardial ischemia prediction model with high accuracy (AUC = 0.86) when validated on the test dataset (n = 714). The model was based on five laboratory results: Eosinophils percentage (Eos.Per), Globulin (G), Ca, Glucose (GLU), and Aspartate aminotransferase (AST). Our concise and accurate high-altitude myocardial ischemia incidence prediction model, based on five laboratory results, may be used to identify risks in advance and help individuals and groups prepare before entering high-altitude areas. Further external validation, including female and different age groups, is necessary.

Fever of unknown origin (FUO) in children: a single-centre experience from Beijing, China.

OBJECTIVE: To date, there is no standard diagnostic practice to identify the underlying disease-causing mechanism for paediatric patients suffering from chronic fever without any specific diagnosis, which is one of the leading causes of death in paediatric patients. Therefore, we aimed this retrospective study to analyse medical records of paediatric patients with fever of unknown origin (FUO) to provide a preliminary basis for improving the diagnostic categories and facilitate the treatment outcomes. DESIGN: A retrospective study. SETTING: Beijing Children's Hospital. PARTICIPANTS: Clinical data were collected from 1288 children between 1 month and 18 years of age diagnosed with FUO at Beijing Children's Hospital between January 2010 and December 2017. INTERVENTIONS: According to the aetiological composition, age, duration of fever and laboratory examination results, the diagnostic strategies were analysed and formulated. PRIMARY AND SECONDARY OUTCOME MEASURES: The statistical analyses were carried out using SPSS V.24.0 platform along with the χ2 test and analysis of variance (p<0.05). RESULTS: The duration of fever ranged from 2 weeks to 2 years, with an average of 6 weeks. There were 656 cases (50.9%) of infectious diseases, 63 cases (4.9%) of non-infectious inflammatory diseases (NIIDs), 86 cases (6.7%) of neoplastic diseases, 343 cases (26.6%) caused by miscellaneous diseases and 140 cases (10.9%) were undiagnosed. With increasing age, the proportion of FUO from infectious diseases gradually decreased from 73.53% to 44.21%. NIID was more common in children over 3 years old, and neoplastic diseases mainly occurred from 1 to 6 years of age. Among miscellaneous diseases, the age distribution was mainly in school-aged children over 6 years. Respiratory tract infection was the most common cause of FUO in children, followed by bloodstream infections. Bacterial infection was the most common cause in children with less than 1 year old, while the virus was the main pathogen in children over 1 year old. CONCLUSIONS: The diagnosis of neoplastic diseases and miscellaneous diseases-related diseases still depends mainly on invasive examination. According to our clinical experience, the diagnostic process was formulated based on fever duration and the type of disease. This process can provide a guide for the diagnosis and treatment of paediatric FUO in the future.

Application of Restriction Site-Associated DNA Sequencing (RAD-Seq) for Copy Number Variation and Triploidy Detection in Human.

At present, low-pass whole-genome sequencing (WGS) is frequently used in clinical research and in the screening of copy number variations (CNVs). However, there are still some challenges in the detection of triploids. Restriction site-associated DNA sequencing (RAD-Seq) technology is a reduced-representation genome sequencing technology developed based on next-generation sequencing. Here, we verified whether RAD-Seq could be employed to detect CNVs and triploids. In this study, genomic DNA of 11 samples was extracted employing a routine method and used to build libraries. Five cell lines of known karyotypes and 6 triploid abortion tissue samples were included for RAD-Seq testing. The triploid samples were confirmed by STR analysis and also tested by low-pass WGS. The accuracy and efficiency of detecting CNVs and triploids by RAD-Seq were then assessed, compared with low-pass WGS. In our results, RAD-Seq detected 11 out of 11 (100%) chromosomal abnormalities, including 4 deletions and 1 aneuploidy in the purchased cell lines and all triploid samples. By contrast, these triploids were missed by low-pass WGS. Furthermore, RAD-Seq showed a higher resolution and more accurate allele frequency in the detection of triploids than low-pass WGS. Our study shows that, compared with low-pass WGS, RAD-Seq has relatively higher accuracy in CNV detection at a similar cost and is capable of identifying triploids. Therefore, the application of this technique in medical genetics has a significant potential value.

Hand Hygiene Knowledge and Self-Reported Hand Washing Behaviors among Restaurant Kitchen Chefs in Jiangsu Province, China.

Inadequate hand washing among chefs is a major contributor to outbreaks of foodborne illnesses originating in restaurants. Although many studies have evaluated hand hygiene knowledge (HHK) and self-reported hand washing behaviors (HWBs) in restaurant workers in different countries, little is known about HHK and HWBs in restaurant kitchen chefs, particularly in China. In this study, we interviewed 453 restaurant kitchen chefs in Jiangsu Province in China regarding their HHK and HWBs and used Chi-square tests (Fisher exact tests), pairwise comparisons, and linear regression models to analyze the responses and identify determinants of HHK and HWBs. Results reveal that less frequent hand washing after leaving work temporarily and after touching used cutlery were the main issues among restaurant kitchen chefs in Jiangsu Province. Kitchen hands had lower levels of HHK and engaged less frequently in good HWBs than the other type of chefs. Furthermore, working in a large restaurant and having worked in the restaurant industry for a longer amount of time were correlated with better HHK and HWBs. These findings suggest that close attention should be paid to the HWBs of chefs during food preparation, that kitchen hands are the key group of restaurant kitchen workers who need training in HHK, and that regulatory activities should focus on small-scale restaurants.

Characteristics of Pediatric Recurrent Bacterial Meningitis in Beijing Children's Hospital, 2006-2019.

BACKGROUND: Few data on recurrent bacterial meningitis (RBM) in children are available. Here, we estimated the frequency of RBM in children and investigated the predisposing conditions, etiology, and clinical characteristics of RBM in children. METHODS: Cases of RBM in the Beijing Children's Hospital medical record database between January 2006 and December 2019 were collected. RESULTS: In total, 1905 children with bacterial meningitis (BM) were documented in the Beijing Children's Hospital medical record database. A total of 43 patients had RBM. The rate of RBM in children was 2.3% (43/1905). Forty (93.0%) patients had predisposing conditions, including 15 (34.9%) cases of inner ear malformations, 5 (11.6%) cases of dermal sinus tracts, 9 (20.9%) cases of head injury, 5 (11.6%) cases of congenital cranial meningocele, 3 (7.0%) cases of congenital skull base defects, 3 (7.0%) cases of immunodeficiency, and other 3 (7.0%) cases of unknown reason. Among all the 121 BM episodes, a total of 64 episodes were etiologically confirmed BM and the other 57 episodes were probable BM. Streptococcus pneumoniae (n = 52) was accounted for 81.3% of confirmed BM episodes. Thirty-four of the 37 patients with congenital or acquired anatomical defects were available to follow up after surgeries, and all of them had no BM after surgeries. Three patients with antibody deficiencies got intravenous immunoglobulin therapy and they did not suffer BM anymore. CONCLUSIONS: RBM is rare in children. The majority of children with RBM had predisposing conditions including congenital/acquired anatomical defects and immunodeficiency. Interventions should be implemented to solve the underlying conditions to avoid RBM.

[Advances in quality research of Cinnamomum cassia].

Cinnamomum cassis is one of the commonly used traditional Chinese medicines in China. Its genuine producing areas distribute in Guangdong and Guangxi provinces. As an important edible herb and export variety of China, the quality control and internationalization of quality standards of C. cassis is extremely significant. In the recent years, with the development of the cinnamon industry, relevant academic research and the upgrade of the international standards, it is necessary to summarize the quality-related progress of C. cassis. In the present review, the germplasm resources, specific quality marker(Q-marker) and quality standards of C. cassis were summarized on the basis of published research during the last 10 years.

[Alleles dropout patterns of Y-short tandem repeats in infertile males with Y chromosome microdeletions].

Y chromosomal short tandem repeat (Y-STR) typing is the most commonly used genetic technique in forensic studies. However, there may be a limit to the application of Y-STR in forensic science as Y-STR loci are subject to loss or variation caused by the higher chromosomal structures' spontaneous mutation rate. Located in the long arm of the Y chromosome, azoospermia factor (AZF) have been shown to participate in spermatogenesis and its deletion could cause infertility. However, little is known about the Y-STR dropout pattern in individuals with Y chromosome microdeletions. In this study, 85 infertile males with Y chromosome interstitial deletion were identified and special Y-STR allele dropout patterns were analyzed by employing a Y-STR Commercial Kit and a Y chromosome Deletion Kit. Results demonstrate that AZF a region deletion are related to DYS439-DYS389I-DYS389II alleles dropout, while AZF b region or c region deletions correlate to DYS448 allele dropout. Null DYS385-DYS392-DYS448 alleles were observed in AZF b+c+d region deletion individuals. While null DYS390-Y-GATA-H4-DYS385-DYS392-DYS448 alleles were observed in AZF a+b+c+d large region deletion individuals. Our data suggest that Y chromosome microdeletions may indicate specific Y-STR locus dropout patterns.

Down-regulated long non-coding RNA RNAZFHX4-AS1 suppresses invasion and migration of breast cancer cells via FAT4-dependent Hippo signaling pathway.

Breast cancer is ranked as the second leading cause of cancer-related deaths among women. Accumulating evidences have revealed that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis owing to the regulation of essential pathways for tumor initiation and progression. Herein, the current study aimed to explore the regulatory mechanism of lncRNA ZFHX4-AS1 in breast cancer in relation to the Hippo signaling pathway. Initially, microarray analysis was conducted to screen out differentially expressed lncRNAs related to breast cancer. Next, the functional role of lncRNA ZFHX4-AS1 in breast cancer was determined using ectopic expression, knockdown, and reporter assay experiments. Subsequently, lncRNA ZFHX4-AS1, TAF4, TAZ, and YAP expressions were determined, followed by verification of the targeting relationship between lncRNA ZFHX4-AS1 and TAF4. Then cell proliferation, invasion, migration, cell cycle, and apoptosis were measured. Lastly, tumor growth and metastasis were detected by tumor xenograft in nude mice. LncRNA ZFHX4-AS1 was found to be highly expressed while FAT4 was poorly expressed in breast cancer tissues. FAT4 was the target gene of lncRNA ZFHX4-AS1, and lncRNA ZFHX4-AS1 silencing increased FAT4 expressions, while decreased YAP and TAZ expressions. In addition, knockdown of lncRNA ZFHX4-AS1 suppressed breast cancer cell proliferation, migration, and invasion as well as tumor growth, blocked cell cycle entry, while promoted cell apoptosis by inhibiting the Hippo signaling pathway. In conclusion, our findings reveal that lncRNA ZFHX4-AS1 silencing exerts an inhibitory effect on breast cancer development by suppressing the activation of the Hippo signaling pathway via FAT4.

Microarray-based analysis of whole-genome DNA methylation profiling in early detection of breast cancer.

Emerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole-genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non-cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region-5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection.

The Impact of Cysteine-Rich Intestinal Protein 1 (CRIP1) on Thyroid Carcinoma.

BACKGROUND/AIMS: CRIP1 (cysteine-rich intestinal protein 1) has been found in several tumor types; however, its prognostic impact and role in cellular processes, particularly in thyroid carcinoma, are still unclear. METHODS: To elucidate the prognostic impact of CRIP1, we analyzed tissues from 58 primary invasive thyroid carcinomas using immunohistochemistry. Western blotting was performed to investigate CRIP1 protein expression in the thyrocyte cell line Nthy-ori 3-1 and four different thyroid carcinoma cell lines, K1, TPC-1, TT, and SW579. Endogenous expression of CRIP1 was suppressed using a siRNA (si-CRIP1). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to investigate cell viability. Flow cytometric analysis was used to detect cell cycle progression and cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion were detected using the transwell assay. RESULTS: The immunohistochemistry results showed that CRIP1 was overexpressed in thyroid carcinoma. CRIP1 expression was associated with tumor size, TNM stage, and lymphatic metastasis, but not with age, gender, and tumor location. In addition, the expression of CRIP1 in K1, TPC-1, TT, and SW529 cells was higher than that in the Nthy-ori 3-1 cells. The highest expression was observed in the SW579 and TT cells. Furthermore, silencing CRIP1 inhibited the proliferation, migration, and invasion of thyroid carcinoma cell lines SW579 and TT. We also found that silencing CRIP1 induced G1 arrest and apoptosis of thyroid carcinoma cell lines SW579 and TT. CONCLUSION: In conclusion, CRIP1 acts as an oncogene in the cell proliferation, migration, and invasion processes of thyroid carcinoma. CRIP1 may serve well as an independent prognostic marker with significant predictive power for use in thyroid carcinoma therapy.