Stringent non-pharmaceutical measures to contain the COVID-19 outbreak in China also significantly reduced the spread of influenza in the winter season 2020.

Fibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular disease and is closely related to inflammation over the past decade. This study aimed to assess the relationship between FGF23 and myocardial injury in patients with sepsis. We sequentially measured serum FGF23, Klotho, biomarkers of inflammation (CRP, IL-6 and WBC), myocardial injury (cTnI and N-terminal B-type natriuretic peptide) and sepsis (procalcitonin) at peak of intercurrent septic shock and after complete resolution or before death in a series of 29 patients with septic shock. 29 healthy adults without infections were used as controls. There was a difference in serum FGF23 level between patients with septic shock and healthy adults (p < 0.0001), and the peak level of FGF23 in septic shock in the survivor group was higher than that after complete remission (p < 0.0001). No statistical difference was found in the level of FGF23 before and after treatment in the death group (p = 0.0947). At the peak of septic shock, FGF23 was significantly correlated with inflammatory markers, CRP (r = 0.8063, p < 0.0001), PCT (r = 0.6091, p = 0.0005) and WBC (r = 0.8312, p < 0.0001), while the correlation with IL-6 was not statistically significant (r = 0.0098, p = 0.9598). At the same time, it was found that FGF23 was significantly correlated with myocardial injury markers, cTNI (r = 0.8475, p < 0.0001) and NTproBNP (r = 0.8505, p < 0.0001). Nevertheless, FGF23 and klotho are not correlated (r = 0.2609, p = 0.1717). In conclusion, in patients with septic shock and myocardial injury, the exacerbation of inflammation in the septic process was accompanied by a abnormal increase of circulating FGF23 level. FGF23 also subsided after the improvement of inflammation, and the opposite was true for patients who did not survive. The up-regulation of FGF23 may be involved in the response of patients to septic shocks, and it is also speculated that FGF23 is involved in the myocardial injury of septic shock.

This study focused on the effect and mechanism of Notch signal on pulmonary microvascular endothelial cells (PMVECs) following acute lung injury. PMVECs were cultured in vitro and randomly divided into eight groups. Grouping was based on whether cells were co-cultured with T cells (splenic CD4⁺T cells were isolated using MACS microbeads) and the level of Notch expression: Normal group and Normal+T cells group, Model group and Model+T cells group, Notch low-expression group and Notch low-expression+T cells group, and Notch overexpression group and Notch overexpression+T cells group. Except for the Normal group and Normal+T cells group, all other groups were treated with 500 μL lipopolysaccharide (1 μg/mL). The expression of VE-cadherin and Zo-1 protein in the Model group (with or without T cells) was lower than that in the normal group (with or without T cells), their expression in the Notch low-expression group (with or without T cells) was significantly increased, and their expression in the Notch overexpression group (with or without T cells) was significantly decreased. Compared with the normal+T cells group, the number of Treg cells in the Notch low-expression+T cells group decreased significantly (P<0.01). The number of Th17 cells in the Notch overexpression+T cells group was higher than that in the Model+T cells group (P<0.01), while the number of Treg cells decreased (P<0.01). Our results demonstrated that activated Notch signal can down-regulate the expression of the tight junction proteins VE-Cadherin and Zo-1 in PMVECs and affect Th17/Treg immune imbalance. Autophagy was discovered to be involved in this process.

Many studies have provided significant evidence to suggest that early aggressive fluid resuscitation strategies are acutely beneficial in patients with sepsis. However, most of these studies did not follow up to determine the long-term impacts on patients’ fluid and electrolyte balance after high-volume resuscitation strategies. This study sought to investigate the results of the aggressive fluid resuscitation measures used on patients with sepsis over the course of 7 days following resuscitation. An initial 3528 adult patients with sepsis who met inclusion criteria from the Medical Information Mart for Intensive Care IV database were collected. The total 7-day fluid balance of each patient was calculated and categorized into quartiles. Univariate Cox regression, lasso regression, backward stepwise elimination, and multivariate Cox regression were performed to search for variables related to survival during hospitalization. To determine the critical point of patients’ fluid balance over 7 days, a restricted cubic spline regression model with 4 knots was performed. In addition, an inverse probability of treatment weighting analysis was conducted to confirm our findings. The median 7-day fluid balance is 5321.4 (interquartile range, 848.5–10,404.0) mL. The observed 28-day mortality in this cohort was 21.6%. Both before and after the inverse probability of treatment weighting analysis, the first 7-day fluid balance in the intensive care unit was significantly related to mortality during hospitalization (P < .001). A restricted cubic spline regression analysis indicated when the 7-day fluid balance was equal to 5243.3ml, the heart rate value was ≈1. A 7-day fluid balance < 5243.3 mL was considered a protective factor, while a balance > 5243.3 mL was considered a risk factor for patient mortality. To be clear, this study does not advocate against aggressive fluid resuscitation in patients with sepsis. However, clinicians walk a fine line with the extent of the resuscitation volume given to patients with sepsis. As a result of this study, it is highly advised that fluid resuscitation in patients with sepsis be limited to ≈5200-mL 7-day fluid balance for optimal clinical benefit.

Sepsis-associated intestinal injury involves barrier dysfunction and altered microbial metabolism, but microbiota-associated metabolites have not been systematically prioritized. We integrated curated microbe-metabolite and host-gene records, ligand-based target prediction, disease-gene databases, protein-protein interaction analysis, enrichment, exploratory transcriptomics, ADME/toxicity predictions, and a uniform three-component ranking. The intersection of 1518 predicted targets, 154 gutMGene-supported host targets, and 4402 disease-associated genes yielded 63 genes. GSE202261 included two CLP and two sham intestinal samples, and no hub-gene or pathway result remained significant after FDR correction; it was therefore treated as exploratory. The archived AutoDock4 files lacked sufficient preparation and validation records and were excluded from ranking. In a separate structural assessment, both AKT1 structures failed native-ligand redocking. IL1B structure 8C3U passed redocking, but a literature-derived activity-labelled control panel failed one of five directional tests (AUROC 0.80); candidate docking was therefore not undertaken. Among 19 identity-deduplicated metabolites, 3-(4-HPP) ranked first (F₃=0.814), I3LA second (0.600), and 3-IPA third (0.580). 3-(4-HPP) remained first across 5000 admissible weight schemes. These results prioritize candidates for experimental testing but do not establish binding or biological efficacy.

The diagnosis and treatment process of this case highlights that mNGS, as a powerful pathogen detection tool, provides a rapid method for the early detection of Pneumocystis jirovecii. However, mNGS testing of lavage specimens alone cannot distinguish between colonization and infection by the pathogen, particularly when a high number of sequences are present. Clinicians should therefore interpret laboratory results with caution to avoid unnecessary treatment that may cause adverse effects to the patient. CT scans offer strong evidence for differentiating between Pneumocystis jirovecii infection and/or Mycobacterium tuberculosis infection. Performing a biopsy at the site of infection, collecting pathological samples, and submitting them for mNGS testing can further assist clinicians in making a definitive diagnosis.