Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Exploring the Diagnostic and Prognostic Significance of Alkaline Phosphatase on Neutrophil Surface Membrane in Patients with Sepsis.

Background: Sepsis, characterized by life-threatening organ dysfunction, stems from an unregulated host response. Timely identification is pivotal for enhancing the prognosis of sepsis patients. Objective: This study aims to explore the diagnostic and prognostic values of alkaline phosphatase on the surface membrane of neutrophils (mNAP) in peripheral blood among sepsis patients. Design: The study employed a retrospective design. Setting: This study was conducted at Donghai County People's Hospital. Participants: A total of 180 sepsis patients were selected and categorized into the sepsis shock group (n=45) and the sepsis non-shock group (n=135). Additionally, 35 patients with non-infectious systemic inflammatory response syndrome served as the control group. Interventions: mNAP was assessed via flow cytometry, while serum procalcitonin (PCT) and C-reactive protein (CRP) levels were measured through immunoassay. Primary Outcome Measures: (1) Changes in mNAP, PCT, and CRP. (2) Correlation of mNAP with CRP and PCT in sepsis patients. (3) Diagnostic values of mNAP, PCT, and CRP in sepsis. Results: Statistically significant differences in mNAP, PCT, and CRP were observed between the sepsis shock group, the sepsis non-shock group, and the control group (P = .000). The median value of mNAP (22627 Ab/c) in the 28-day death group was significantly higher than that (5100 Ab/c) in the survival group (P = .000). Spearman rank correlation analysis indicated a positive correlation between mNAP, PCT, and CRP in sepsis patients (P < .01). Conclusions: Both mNAP and PCT exhibit superior diagnostic specificity and sensitivity compared to CRP. While mNAP demonstrates similar sensitivity to PCT in diagnosing sepsis, its diagnostic specificity surpasses that of PCT. mNAP holds promise as a novel marker for the diagnosis and prognosis of sepsis.

Effect of occupational stress and resilience on insomnia among nurses during COVID-19 in China: a structural equation modelling analysis.

OBJECTIVES: To explore the effects of occupational stress and resilience on insomnia among Chinese nurses during the COVID-19 pandemic. DESIGN, SETTINGS AND PARTICIPANTS: A quantitative description study. The data were collected via a cross-sectional survey. A total of 725 front-line nurses at three tertiary hospitals in western China were included from December 2022 to January 2023. The Connor-Davidson Resilience Scale, Job Content Questionnaire, and Athens Insomnia Scale were used to collect data from a self-reported online questionnaire. OUTCOME MEASURES: The outcome variable was insomnia, and structural equation modelling was used to assess the associations among resilience, occupational stress and insomnia. RESULTS: The prevalence of insomnia among the participants was 58.76%. The structural equation model showed that resilience had a negative direct effect on insomnia and occupational stress, and occupational stress had a positive direct effect on insomnia. Involvement in COVID-19-related work has a positive effect on insomnia through occupational stress. In contrast, higher education levels improved insomnia through increased resilience. CONCLUSION: A significantly higher prevalence of insomnia has been observed among Chinese nurses during the COVID-19 pandemic. Our study suggests that better resilience may improve insomnia by relieving occupational stress, and implementing measures to promote resilience is essential to reduce occupational stress in nurses and improve their sleep quality.

Work-related violence, occupational stress and psychological distress among medical staff in China: A structural equation modeling analysis.

BACKGROUND: Psychological issues and work-related violence are the main challenges faced by medical staff. The situation has become even more prevalent during the COVID-19 pandemic. OBJECTIVE: This research aimed to analyze the relationships among work-related violence, occupational stress and psychological distress and to further identify the direct or indirect effects of violence on psychological distress. METHODS: A total of 1,765 medical staff members were surveyed using the Kessler Psychological Distress Scale and Revised Occupational Stress Inventory. Work-related violence was assessed using a self-made 5-question questionnaire. STATA 14.0 and Amos 21.0 software were used for correlation analysis, variance analysis, and structural equation modeling analysis. RESULTS: A total of 66.1% of the medical staff suffered workplace violence, and 61.2% witnessed workplace violence. The psychological distress score (Kessler 10 Scale) of the medical staff was 22.7±7.67. The psychological strain score and physical strain score were 26.8±7.14 and 24.2±6.51, respectively. Work-related violence (suffered: ß= 0.467; witnessed: ß= 0.258) and occupational stress (psychological strain: ß= 0.269; physical strain: ß= 0.317) were predictors of psychological distress, and social support (ß= -0.265) was a protective factor. Work-related violence and social support had both direct and indirect effects on psychological distress, and the intermediate factor was occupational stress. The total effects of suffered workplace violence and witnessed workplace violence were 0.181 and 0.092, respectively, and the total effect of social support was -0.262. CONCLUSIONS: Work-related violence may exacerbate symptoms of occupational stress and psychological distress. Reducing workplace violence and protecting medical staff from work-related violence are extremely important aspects of mental health prevention.

Beneficial effects of the first case of washed microbiota transplantation for postorgasmic illness syndrome: a case report.

Introduction: Postorgasmic illness syndrome (POIS) is characterized by allergic symptoms and flu-like illness after ejaculation. There are still no effective treatments for POIS. Aim: To report the first case of washed microbiota transplantation (WMT) to treat patient with POIS. Methods: Data were collected from a patient with POIS who had received 3 courses of WMT: self-rating scale of POIS symptoms, Self-rating Anxiety Scale, Self-rating Depression Scale, and Symptom Checklist 90. The patient's stool samples for 16sDNA sequencing were collected 1 month after WMT. Results: POIS symptoms improved after WMT. Scores decreased from baseline after WMT: self-rating scale of POIS symptoms (before WMT, 16; after first, 16; after second, 8; after third, 9), Self-rating Anxiety Scale (45, 42.5, 37.5, 45), Self-rating Depression Scale (63.75, 58.75, 47.5, 50), and Symptom Checklist 90 (143, 140, 109, 149). Characteristics of the patient's gut microbiota changed. At the genus level, the relative abundance of beneficial bacteria increased, and some opportunistic pathogenic bacteria decreased. Conclusion: WMT may be an effective and safe choice for the treatment of patients with POIS by changing the gut microbiota of the host.

Comparison of the use of a spiral nasojejunal tube and transendoscopic enteral tubing in washed microbiota transplantation via the mid-gut route.

Background: Methods for washed microbiota transplantation (WMT) through the mid-gut include transendoscopic enteral tubing (TET) and manual spiral nasojejunal tube (SNT) placement have not been studied. Methods: This prospective interventional study was performed at a single centre. Patients were divided into the SNT and mid-gut TET groups based on their conditions and wishes. In the SNT group, an SNT was passively inserted into the stomach, and abdominal X-rays were taken within 24 h to confirm tube placement in the small intestine. In the mid-gut TET group, mid-gut TET was placed in the small intestine for gastroscopy. Data on the clinical efficacy of WMT, intubation time, cost, overall comfort score, adverse reactions, etc., were collected from the two groups. Results: Sixty-three patients were included in the study (SNT group (n = 40) and mid-gut TET group (n = 23)). The clinical efficacy of WMT in the SNT and mid-gut TET groups was 90 % and 95.7 %, respectively (P = 0.644). Compared with the mid-gut TET group, the SNT group showed a shorter operation time (120 s vs. 258 s, P = 0.001) and a lower average cost (641.7 yuan vs. 1702.1 yuan, P = 0.001). There was no significant difference in the overall comfort score or the incidence of common discomfort symptoms between the two groups. Conclusion: The different implantation methods have different advantages; compared with mid-gut TET placement, manual SNT placement provides some benefits.

KLK10/LIPH/PARD6B/SLC52A3 are promising molecular biomarkers for the prognosis of pancreatic cancer through a ceRNA network.

Pancreatic adenocarcinoma (PAAD) remains challenging to diagnose and treat clinically due to its difficult early diagnosis, low surgical resection rate, and high risk of postoperative recurrence and metastasis. SMAD4 is a classical mutated gene in pancreatic cancer and is lost in up to 60%-90 % of PAAD patients, and its mutation often predicts a poor prognosis and treatment resistance. In this study, based on the expression profile data in The Cancer Genome Atlas database, we identified a ceRNA network composed of 2 lncRNAs, 1 miRNA, and 4 mRNAs through differential expression analysis and survival prognosis analysis. Among them, high expression of KLK10/LIPH/PARD6B/SLC52A3 influenced the prognosis and overall survival of PAAD patients. We confirmed the high expression of these target genes in pancreatic tissue of pancreatic-specific SMAD4-deficient mice. In addition, immune infiltration analysis showed that the high expression of these target genes affects the tumor immune environment and contributes to the progression of PAAD. Abnormal overexpression of these target genes may be caused by hypermethylation. In conclusion, we found that KLK10/LIPH/PARD6B/SLC52A3 is a potential prognostic marker for PAAD based on a competing endogenous RNA-mediated mechanism and revealed the potential pathogenic mechanism by which deficient expression of SMAD4 promotes pancreatic cancer progression, which provides a new pathway and theoretical basis for targeted therapy or improved prognosis of pancreatic cancer. These data will help reveal potential therapeutic targets for pancreatic cancer and improve the prognosis of pancreatic cancer patients.

The Developmental Toxicity and Endocrine-Disrupting Effects of Fenpropathrin on Gobiocypris rarus during the Early Life Stage.

In the present study, the developmental toxicity and endocrine-disrupting effects of fenpropathrin on Gobiocypris rarus during the early life stage were studied using a semi-static water exposure method. The results showed that the LOEC (lowest observed effect concentration) of fenpropathrin on the incubation of rare minnow embryos was above 2.5 µg·L-1. The LOEC and NOEC (no observed effect concentration) of fenpropathrin on the developmental malformations and death indicators were 2.0 and 1.5 µg·L-1, respectively. After exposure to 1.5 µg·L-1 of fenpropathrin for 31 days, the expressions of androgen receptor genes (AR) and sex hormone-synthesis-related genes (CYP17 and CYP19a) were significantly decreased and the expressions of thyroid hormone receptor genes (TRß) and aryl hydrocarbon receptor genes (AhR1a and AhR2) were significantly increased in juvenile Gobiocypris rarus. The expression levels of the androgen receptor gene (AR), estrogen receptor gene (ER1), and the sex hormone-synthesis-related genes (HMGR, CYP17, and CYP19a) were significantly decreased, while the estrogen receptor gene (ER2a), thyroid hormone receptor gene (TRß), and aromatic hydrocarbon receptor genes (AhR1a and AhR2) were upregulated in juvenile Gobiocypris rarus under exposure to 2.0 µg·L-1 of fenpropathrin. Relatively low concentrations of fenpropathrin can affect the expression of sex hormone receptor genes, genes related to sex hormone synthesis, thyroid hormone receptor genes, and aromatic hydrocarbon receptor genes, thus interfering with the reproductive system, thyroid system, and metabolic level in Gobiocypris rarus. Therefore, more attention should be paid to the endocrine-disrupting effect caused by the pyrethroid insecticides in the water environment. Furthermore, studies on the internal mechanism of the endocrine-disrupting effect of pyrethroid insecticides on fish is needed in the future.