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Abstract Background Immunocompromised patients face higher risks of Severe Acute Respiratory Syndrome Coronavirus 2 infection and co-infections, leading to a possibility of high disease severity and poor outcomes. Conversely, immunosuppression can mitigate the excessive inflammatory response induced by the virus, potentially reducing disease severity. This study aims to investigate the prognostic differences and early inflammatory response characteristics in various types of immunocompromised patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU), summarize their clinical features, and explore potential mechanisms. Methods A retrospective analysis was conducted on critically ill COVID-19 patients admitted to the ICU of 59 medical centers in mainland China during the Omicron outbreak from November 2022 to February 2023. Patients were categorized into two groups based on their immunosuppression status: immunocompromised and immunocompetent. Immunocompromised patients were further subdivided by etiology into cancer patients, solid organ transplant (SOT) patients, and other immunocompromised groups, with immunocompetent patients serving as controls. The mortality rates, respiratory support, complications, and early inflammatory cytokine dynamics upon ICU admission among different populations were analyzed. Results A total of 2030 critically ill COVID-19 patients admitted to ICU were included, with 242 in the immunocompromised group and 1788 in the immunocompetent group. Cancer patients had a higher median age of 69 years (IQR 59, 77), while SOT patients were generally younger and had less severe illness upon ICU admission, with a median APACHE II score of 12.0 (IQR 8.0, 20.0). Cancer patients had a twofold increased risk of death (OR = 2.02, 95% CI 1.18–3.46, P = 0.010) compared to immunocompetent patients. SOT and cancer patients exhibited higher C-reactive protein and serum ferritin levels than the immunocompetent group in their early days of ICU admission. The CD8+ T cells dynamics were inversely correlated in cancer and SOT patients, with Interleukin-6 levels consistently lower in the SOT group compared to both immunocompetent and cancer patients. Conclusion Critically ill COVID-19 patients admitted to the ICU exhibit distinct clinical outcomes based on their immunosuppression status, with cancer patients facing the highest mortality rate due to variations in inflammatory responses linked to their immunosuppression mechanisms. Monitoring dynamic changes in inflammatory markers and immune cells, particularly CD8+ T lymphocytes and IL-6, may offer valuable prognostic insights for these patients.

Abstract Background Contrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48–72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms. Results mVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb). Conclusions In summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects. Graphical abstract

Abstract Background Non-suicidal self-injury (NSSI) behaviors pose a significant threat to the physical and psychological well-being of adolescents. Recent research suggests that persistent, uncontrollable and repetitive NSSI can be conceptualized as a behavioral addiction. The addictive feature of NSSI behavior can be assessed using Ottawa self-injury inventory (OSI), the higher addiction score indicates the more serious NSSI behavior. This study aims to explore the relationship of impulsivity and decision-making on the addictive features of NSSI in adolescents with depressive disorder, to explore the influencing factors of behavioral addictive features of NSSI and to predict the addictive features of NSSI. Methods Using a cross-sectional design, a total of 126 adolescent outpatients and inpatients with a mean age of 15.49 years old (M = 15.49, SD = 1.56), male students (n = 28, 22.2%) and female students (n = 98, 77.8%) diagnosed with depressive disorders were recruited according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and clinical interviews were completed by two psychiatrists. NSSI addictive features according to the OSI’s addictive features items. The final group was categorized into three groups: depression without NSSI (n = 42), depression with NSSI without addictive features (n = 44), and depression with NSSI and addictive features (n = 40). The present study employed the Hamilton Depression Scale (HAMD-24), Chinese Revised Barratt Impulsiveness Scale Version 11 (BIS-11), OSI, and the Adolescent Non-Suicidal Self-Injury Questionnaire (ANSSIQ). Cognitive decision-making abilities were assessed using the Iowa Gambling Task (IGT). Results The depression with NSSI addictive features group had significantly lower total net scores and net scores of block3, block4, and block5 in the IGT than the depression without NSSI group, whereas there was no statistically significant difference between the two in net scores of block1 and block2. Lower scores mean more unfavorable decisions and strategy adjustments. The addictive features of NSSI behaviors were significantly and positively correlated with the severity of NSSI behaviors, depression, and cognitive impulsiveness, and significantly and negatively correlated with the total net score of the IGT. The severity of NSSI behaviors, severity of depression, cognitive impulsiveness positively predicts the addictive features of NSSI behaviors, the total net score of the IGT negatively predicted the addictive features of NSSI behaviors. Conclusion Adolescents with depressive disorders with NSSI behavioral addictive features had higher severity of depression, exhibited higher cognitive impulsivity, and made more unfavorable decisions when making choices.

Abstract Background The formation of stem cell clones enables close contact of stem cells inside. The gap junctions in such clone spheres establish a microenvironment that allows frequent intercellular communication to maintain self-renewal and functions of stem cells. Nevertheless, the essential gap junction protein for molecular signaling in clones is poorly known. Methods Primary human airway basal cells (hBCs) were isolated from brushing samples through bronchoscopy and then cultured. A tightly focused femtosecond laser was used to excite the local Ca2+ in an individual cell to initiate an internal Ca2+ wave in a clone to screen gap junction proteins. Immunoflourescence staining and clonogenicity assay were used to evaluate self-renewal and functions. RNA and protein levels were assessed by PCR and Western blot. Air–liquid interface assay was conducted to evaluate the differentiation potential. A Naphthalene injury mouse model was used to assess the regeneration potential. Results Herein, we identify Connexin 25 (Cx25) dominates intercellular Ca2+ communications in clones of hBCs in vitro to maintain the self-renewal and pluripotency of them. The self-renewal and in vitro differentiation functions and in vivo regeneration potential of hBCs in an airway damage model are both regulated by Cx25. The abnormal expression of Cx25 is validated in several diseases including IPF, Covid-19 and bronchiectasis. Conclusion Cx25 is essential for hBC clones in maintaining self-renewal and functions of hBCs via gap junctions.

Abstract Objectives Exploring the effect of resilience and self-efficacy in mediating the chain between fatigue and quality of life(QOL) in patients with rheumatoid arthritis (RA). Methods From June 2022 to November 2022, 423 RA patients were chosen by a convenience sample method from two tertiary care facilities in Chengdu, Sichuan Province. General Information Questionnaire, Bristol Multidimensional Scale of Fatigue in Patients with Rheumatoid Arthritis, SF−12 Health Survey Short Form, Chinese version of the ten-item psychological Resilience Scale, and Chinese-language Arthritis Self-Efficacy Scale, an 8-element version, were among the questionnaires used. Results In the physical component summary( PCS), self-efficacy, psychological resilience, and self-efficacy were all significantly mediated by fatigue (total effect mediated 8.88%). In the mental component summary (MCS), fatigue (total effect mediated 10.79%), self-efficacy (total effect mediated 8.99%), psychological resilience, and self-efficacy (total effect mediated 2.01%) were all significantly mediated by fatigue. Conclusion Fatigue in RA patients can affect the quality of life both directly and indirectly through the mediating effects of psychological resilience, self-efficacy, and the chain mediating effect of psychological resilience-self-efficacy.

Objectives: Clostridioides difficile ranks among the primary sources of healthcare-related infections and diarrhoea in numerous nations. We evaluated the drug susceptibility and resistance mechanisms of C. difficile isolates from a hospital in Chongqing, China, and identified resistance rates and resistance mechanisms that differed from previous findings. Methods: The toxin genes and drug resistance genes of clinical strains were detected using Polymerase Chain Reaction (PCR), and these strains were subjected to Multilocus Sequence Typing (MLST). The agar dilution technique was employed for assessing susceptibility of antibiotics. Clinical data collection was completed through a review of electronic medical records. Results: A total of 67 strains of toxin-producing C. difficile were detected. All C. difficile isolates demonstrated susceptibility to both metronidazole and vancomycin. However, resistance was observed in 8.95%, 16.42%, 56.72%, 56.72%, 31.34% and 5.97% of the isolates for tigecycline, tetracycline, clindamycin, erythromycin, moxifloxacin and rifampin, respectively. Among the strains with toxin genotypes A + B + CDT - and belonging to the ST3, six strains exhibited reduced susceptibility to tigecycline (MIC=0.5mg/L) and tetracycline (MIC=8mg/L). The tetA(P) and tetB(P) genes were present in these six strains, but were absent in tetracycline-resistant strains. Resistance genes (ermB, tetM, tetA(P) and tetB(P)) and mutations (in gyrA, gyrB, and rpoB) were identified in resistant strains. Conclusions: In contrast to prior studies, we found higher proportions of ST3 isolates with decreased tigecycline sensitivity, sharing similar resistance patterns and resistance genes. In the resistance process of tigecycline and tetracycline, the tetA(P) and tetB(P) genes may play a weak role.

Abstract Background To explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS, the characteristics of serum metabolomics during the progression of AS in mini‐pigs were observed dynamically. Methods An AS model in Bama miniature pigs was established by a high‐cholesterol and high‐fat diet. Fasting serum samples were collected monthly for metabolomics and serum lipid detection. At the end of the treatment period, pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS, thereby distinguishing the susceptibility of mini‐pigs to AS. The metabolomics was detected using a high‐resolution untargeted metabolomic approach. Statistical analysis was used to identify metabolites associated with AS susceptibility. Results Based on pathological analysis, mini‐pigs were divided into two groups: a susceptible group (n = 3) and a non‐susceptible group (n = 6). A total of 1318 metabolites were identified, with significant shifting of metabolic profiles over time in both groups. Dynamic monitoring analysis highlighted 57 metabolites that exhibited an obvious trend of differential changes between two groups with the advance of time. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated significant disorders in cholesterol metabolism, primary bile acid metabolism, histidine metabolism, as well as taurine and hypotaurine metabolism. Conclusions During the progression of AS in mini‐pigs induced by high‐cholesterol/high‐fat diet, the alterations in serum metabolic profile exhibited a time‐dependent pattern, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. These metabolites may become potential biomarkers for early diagnosis of AS.