Proximity ligation initiated DNAzyme-powered catalytic hairpin assembly for sensitive and accurate microRNA analysis.

MicroRNAs (miRNAs) play a significant role in regulating diverse physiological processes, and are regarded as novel diagnostic biomarkers. However, the sensitive and reliable miRNA detection remains a huge challenge. Herein, we propose a proximity ligated initiated magnesium ion (Mg2+)-dependent DNAzyme-powered signal cascade for sensitive, accurate and reliable detection of miRNAs. Three signal amplification processes are involved in this approach, including the target miRNA recycle, DNAzyme powered substrate cleavage, and catalytic hairpin reaction (CHA). Based on this, the approach shows a low limit of detection of 523 aM and a wide detection range of 7 orders of magnitudes, which is comparable or superior to most of the former miRNA detection methods. In addition, the approach also possesses a high selectivity to target miRNA, suggesting a potential promising future of the approach for rapid detection of miRNAs in the application of developing novel tools for skin cancer diagnosis, and recovery evaluation.

The Epidemiology of Tinea Capitis in Guangxi Province, China.

The aim of this study was to analyze the epidemiological characteristics and pathogen spectrum of tinea capitis in Guangxi, southern China. A multicenter prospective descriptive study was conducted in 8 hospitals across Guangxi. From January 2019 to July 2022, one hundred seventy-one (171) patients diagnosed with tinea capitis were included. Demographic data, risk factors, and fungal data were collected. If necessary, species were further identified by morphological or molecular sequencing in the central laboratory. Of the 171 cases of tinea capitis, 74.3% occurred in patients aged 2-8 years. Children with tinea capitis were mainly boys (59.6%) and were more likely than adults to have a history of animal contact (44.2% vs. 33.3%) and zoophilic dermatophyte infection (76.9% vs. 46.7%, P = 0.008). The adults were mainly female (53%) and were more likely than children to have a history of infection with anthropophilic organisms (53.3% vs. 18.9%). The causative agents of tinea capitis in Guangxi were diverse, and the most common pathogen was Microsporum canis (M. cani, n = 98, 62%), followed by Trichophyton mentagrophytes (T. mentagrophytes n = 18, 11.4%) and Trichophyton tonsurans (T. tonsurans n = 12, 7.6%). In addition, tinea capitis caused by Nannizzia incurvata (N. incurvata) and Trichophyton verrucosum (T. verrucosum) was detected in the study. Notably, the proportion of patients with kerion in the study was 41.5% (n = 71), and most of those patients were children (n = 68), especially neglected children living in the rural mountainous areas of Guangxi, where they were unable to receive timely diagnosis and appropriate treatment. In conclusion, the causative agents of tinea capitis in Guangxi, South China, are diverse, and the incidence of kerion is high, indicating that diagnosis and treatment modalities in the region remain grossly inadequate. Clinicians and policy-makers should collaborate to adopt public health strategies to control the disease.

Prevalence And Correlation Analysis Between Post-Traumatic Stress Disorder And Analgesic Use In Survivors Of ICU In China.

Objectives: To investigate the prevalence of post-traumatic stress disorder in intensive care unit survivors, and disorder's correlation with analgesia use. METHODS: The single-centre retrospective cohort study was conducted at the First Affiliated Hospital of Jinan University, China, and comprised data from February 2021 to January 2022 related to patients of either gender aged =18 years who were admitted to the intensive care unit and were successfully transferred out to the general ward. Post- traumatic stress disorder Checklist-Civilian Version scale was used for follow-up within one month of getting transferred out of intensive care. Data was analysed using Empower Stats. RESULTS: Of the 121 patients with mean age 54.34±18.19 years, 52(43%) were positive for post-traumatic stress disorder; 32(61.5%) males and 20(38.5%) females with mean age 54.48±19.56 years.The remaining 69(57%) patients were negative; 40(58%) males and 29(42%) females with mean age 54.23±17.24 years (p>0.05). The positive rate of re- experiencing symptoms was noted in 68(56.20%) patients. Analgesia usage was positive in 61(50.4%) cases and negative in 60(49.6%) cases. Compared to the non-analgesic group, the risk of post-traumatic stress disorder occurrence in the analgesic group wassignificantly high (p=0.018). The duration of analgesia usage 24-48h was also significant (p=0.017). CONCLUSIONS: There was a high prevalence of post-traumatic stress disorder in intensive care unit survivors, which was affected by the use of analgesicsin intensive care settings.

Integrating Network Pharmacology, Molecular Docking, and Experimental Validation to Investigate the Mechanism of (-)-Guaiol Against Lung Adenocarcinoma.

BACKGROUND Lung adenocarcinoma (LUAD) is the most common type of lung cancer, which poses a serious threat to human life and health. -(-)Guaiol, an effective ingredient of many medicinal herbs, has been shown to have a high potential for tumor interference and suppression. However, knowledge of pharmacological mechanisms is still lacking adequate identification or interpretation. MATERIAL AND METHODS The genes of LUAD patients collected from TCGA were analyzed using limma and WGCNA. In addition, targets of (-)-Guaiol treating LUAD were selected through a prediction network. Venn analysis was then used to visualize the overlapping genes, which were further condensed using the PPI network. GO and KEGG analyses were performed sequentially, and the essential targets were evaluated and validated using molecular docking. In addition, cell-based verification, including the CCK-8 assay, cell death assessment, apoptosis analysis, and western blot, was performed to determine the mechanism of action of (-)-Guaiol. RESULTS The genes included 959 differentially-expressed genes, 6075 highly-correlated genes, and 480 drug-target genes. Through multivariate analysis, 23 hub genes were identified and functional enrichment analyses revealed that the PI3K/Akt signaling pathway was the most significant. Experiment results showed that -(-)Guaiol can inhibit LUAD cell growth and induce apoptosis. Additional evidence suggested that the PI3K/Akt signaling pathway established an inseparable role in the antitumor processes of -(-)Guaiol, which is consistent with network pharmacology results. CONCLUSIONS Our results show that the effect of (-)-Guaiol in LUAD treatment involves the PI3K/Akt signaling pathway, providing a useful reference and medicinal value in the treatment of LUAD.

A Novel Predictive Model Incorporating Ferroptosis-Related Gene Signatures for Overall Survival in Patients with Lung Adenocarcinoma.

BACKGROUND Lung adenocarcinoma (LUAD) is the predominant histological type of lung cancer with high morbidity and mortality. Ferroptosis is regarded as a new pattern of programmed cell death concerned with the progression of lung cancer characterized by lipid peroxidation. Nevertheless, the prognostic role of ferroptosis-related genes for LUAD warrant to be explored. MATERIAL AND METHODS RNA sequencing and relevant clinical patient data were obtained from public-access databanks. A prognostic model was constructed through the LASSO Cox regression in the cancer genome atlas cohort. The diagnostic value of the prognostic model was further evaluated in the gene expression omnibus cohort. RESULTS Most of the ferroptosis-related genes (69.9%) were differentially expressed between tumor and adjacent non-cancerous tissues. 43 differentially expressed genes showed a close association with the prognosis of LUAD patients (adjusted p-value <0.05). An 18-gene signature was built and applied to assign patients into high vs low-risk groups. Compared with the high-risk group, patients defined as the low-risk group suffered significantly prolonged OS. Both uni- and multivariate analyses demonstrated that the signature-based score served as a crucial role in influencing the OS of LUAD patients (hazard ratio >1, p<0.001). The immunity-related signaling pathway was enriched in the functional analysis and the infiltration of the immune cells showed a great difference between groups. CONCLUSIONS The predictive model could be applied for prognostic prediction for LUAD. Targeting ferroptosis could be a possible curative strategy against LUAD, and immunomodulation may be one of the potential mechanisms.

The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease complicated with chronic heart failure: a retrospective cohort study.

The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease (CHD) complicated with chronic heart failure (CHF) is still unclear. The objective of this study was to explore the effects of serum iron level without anemia on long-term prognosis of patients with CHD complicated with CHF. In this retrospective cohort study, 221 patients with CHD complicated with CHF were consecutively investigated. These patients were divided into three groups according to the tertiles of the serum iron level: low-iron group (n = 71), medium-iron group (n = 76) and high-iron group (n = 74). The overall serum iron without anemia was 13.0 ± 5.50 µmol/L and serum iron in each group was 7.58 ± 1.63 µmol/L, 11.94 ± 1.79 µmol/L, and 19.37 ± 3.81 µmol/L, respectively. Composite endpoint events were composed of major adverse cardiovascular and cerebrovascular events (MACCE), including recurrent heart failure, all-cause death, acute coronary syndrome (ACS) and ischemic stroke. The median follow-up duration was 239 days. After adjusting relevant confounding risk factors, we found that excessively low or high serum iron level is correlated to the MACCE in patients with CHD complicated with CHF and that the prognosis of patients with excessively high serum iron level is poorer than that of patients with excessively low serum iron level. We further revealed the effect of serum iron level on MACCE is U-shaped, but not linear relationship. Sensitivity analysis showed that the correlation between serum iron level and MACCE is stable. In addition, according to the test for interaction, the variables that modify the effect including CRP (P for interaction < 0.0001), diuretics (P for interaction = 0.0212) and antiplatelet drugs (P for interaction = 0.0167). This study showed that excessively low or high serum iron level without anemia is an independent risk factor of MACCE in patients with CHD complicating with CHF.

Influence of physical restraint on delirium of adult patients in ICU: A nested case-control study.

AIMS AND OBJECTIVES: To investigate the impact of physical restraint on delirium of adult patients in intensive care unit. BACKGROUND: Delirium is a common clinical syndrome in intensive care unit, correlated with various adverse clinical outcomes. Physical restraint is a precipitating factor for delirium; however, the effect of physical restraint on delirium, such as duration, number and appliance is still unclear. DESIGN: A nested case-control study. METHODS: A cohort of 593 intensive care unit patients were observed for 12 months, and 447 of them who received physical restraint were included for analysis. Delirium was assessed using the Confusion Assessment Method for the intensive care unit. During hospitalisation in intensive care unit, newly-onset delirium patients (the delirium group), and nondelirium patients of similar age, same gender, and conditions of mechanical ventilation and sedative drug usage (the nondelirium group) were included as the matching criteria. Patient data were acquired by reviewing medical and nursing electronic records. RESULTS: Among the 447 patients that had been physically restrained, 178 (39.8%) developed delirium. Delirium risk in patients with restraint ≥6 days was 26.30 times higher than in those <6 days. Patients who had two and three times of restraint had a 2.38-fold and 3.62-fold higher risk of delirium than those with one time of restraint. However, the appliance, site, time to apply and remove restraint had no effect on the incidence of delirium. CONCLUSIONS: The incidence of delirium is high when patients use physical restraint. Duration and number of restraint are positively related to delirium. Restrictions on the use of restraint in intensive care unit are required to reduce the occurrence of delirium. RELEVANCE TO CLINICAL PRACTICE: To reduce delirium risk of patients in intensive care unit, nurses need to assess the risk of physical restraint and consider alternative measures, thereby to achieve the minimisation of the use of restraint.

Bioinformatics analysis-based mining of potential markers for inflammatory bowel disease and their immune relevance.

Background: The incidence of inflammatory bowel disease (IBD) is increasing every year and is characterized by a prolonged course, frequent relapses, difficulty in curing, and a lack of more efficacious therapeutic biomarkers. The aim of this study was to find key core genes as therapeutic biomarkers for IBD. Methods: GSE75214 in Gene Expression Omnibus (GEO) was used as the experimental set. The genes in the top 25% of standard deviation of all samples in the experimental set were subjected to systematic weighted gene co-expression network analysis (WGCNA) to find candidate genes. Then, least absolute shrinkage and selection operator (LASSO) logistic regression was used to further screen the central genes. Finally, the validity of hub genes was verified on GEO dataset GSE179285 using "BiocManager" R package. Results: Twelve well-preserved modules were identified in the experimental set using the WGCNA method. Among them, five modules significantly associated with IBD were screened as clinically significant modules, and four candidate genes were screened from these five modules. Then TIMP1, GUCA2B, and HIF1A were screened as hub genes. These hub genes successfully distinguished tumor samples from healthy tissues by artificial neural network algorithm in an independent test set with an area under the working characteristic curve of 0.946 for the subjects. Conclusions: IBD differentially expressed gene (DEGs) are involved in immunoregulatory processes. TIMP1, GUCA2B, and HIF1A, as core genes of IBD, have the potential to be therapeutic targets for patients with IBD, and our findings may provide a new outlook on the future treatment of IBD.

Meta-analysis of the association of HLA-DRB1 with rheumatoid arthritis in Chinese populations.

BACKGROUND: Individual studies have reported different results regarding the association of HLA alleles with RA in Chinese populations. This study was performed to systematically summarize results on the association of HLA-DRB1 with rheumatoid arthritis (RA) in China. METHODS: We examined the case-control studies concerned about the relationship between HLA-DRB1 and RA and differences of clinical and laboratory parameters between the HLA-DR4 (DR4)+ and DR4- in RA patients in Chinese populations. Odds ratios (ORs) and weighted mean difference (WMD) with corresponding 95% confidence intervals (CI) was used to describe the relationship. RESULTS: 22 studies with 1690 cases and 1793 controls were included. Chinese populations with RA had significantly higher frequencies of HLA-DRB1*04, *0401, *0404, *0405 and *0410 than controls (ORDRB1*04 =4.19, 95% CI =3.44-5.11, p<0.00001; ORDRB1*0401 =2.53, 95% CI =1.54-4.16, p=0.0003; ORDRB1*0404 =2.28, 95% CI =1.28-4.06, p=0.005; ORDRB1*0405=3.71, 95% CI =2.52-5.45, p<0.00001; ORDRB1*0410 =2.99, 95% CI =1.25-7.14, p=0.01 respectively). As to laboratory parameters, Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid factor (RF), Anti-cyclic citrullinated peptide antibodies (Anti-CCP ) in patients with DR4+ were higher than patients with DR4- (WMD=0.26, 95% CI =0.15-0.37, p<0.00001; WMD = 0.26, 95% CI =0.12-0.41, p=0.0005; WMD = 0.44, 95% CI =0.23-0.65, p<0.00001; WMD = 0.58, 95% CI =0.24-0.91, p=0.0007 respectively). As to clinical features, there was no difference in duration of morning stiffness, number of swollen joints, number of joint tenderness, X-ray phases and joint function between the DR4+ and DR4- in RA patients. CONCLUSIONS: It was found that HLA-DRB1*04, *0401, *0404, *0405 and *0410 are risk factors for RA in Chinese populations. ESR, CRP, RF, Anti-CCP are different between the DR4+ and DR4- in RA patients in Chinese populations, while there's no difference for indexes of clinical features.

Elucidation of the anti-lung cancer mechanism of Juan-Liu-San-Jie prescription based on network pharmacology and experimental validation.

Lung cancer is a malignancy characterized by high morbidity and mortality, with lung adenocarcinoma being the most prevalent subtype. Our preliminary studies have demonstrated that the Juan-Liu-San-Jie (JLSJ) prescription, a Traditional Chinese Medicine prescription, possesses anti-lung adenocarcinoma cancer properties. However, the molecular mechanism underlying the therapeutic effects of the JLSJ prescription for lung adenocarcinoma remains incompletely elucidated. To address the knowledge gap, the present study employed network pharmacology to identify potential therapeutic targets. Specifically, the study utilized TCMSP, TCMID, and related references, as well as ChemMapper, to identify and predict the main active components and potential targets. Additionally, differentially expressed genes associated with the disease were obtained from the microarray dataset GSE19804 and GSE118370. The protein-protein Interaction network and Target-pathway network were then constructed. We also conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and subsequently presented the top 20 enriched pathways. The results indicated that the anti-lung cancer effects of JLSJ prescription may be attributed to its ability to mediate apoptosis of tumor cells, potentially through the PI3K/Akt signaling pathway. Then, a series of in vitro and in vivo experiments were conducted to validate the molecular mechanism predicted by network pharmacology. The findings of the in vivo study suggested that the JLSJ prescription could inhibit the growth of xenograft tumors of lung adenocarcinoma with fewer adverse effects. Also, the in vitro experiments corroborated that the JLSJ prescription could induce apoptosis of A549 cells. Furthermore, the upregulation of pro-apoptosis-related proteins and mRNAs, coupled with the downregulation of anti-apoptotic-related proteins and mRNAs, was observed. In conclusion, inducing apoptosis by inhibiting the PI3K/Akt signaling pathway was one of the underlying mechanisms by which the JLSJ prescription exerted its anti-lung adenocarcinoma effect.