Hua Yao

Introduction: Hepatic ischemia-reperfusion injury (HIRI) is a major complication following liver transplantation (LT), contributing to graft dysfunction and rejection. The roles of the Wnt/β-catenin signaling pathway and immune responses in LT-related HIRI remain incompletely elucidated. This study aimed to screen key genes associated with Wnt/β-catenin signaling scores and immune regulation in HIRI after LT. Methods: Three LT-related transcriptomic datasets (GSE151648, GSE12720, and GSE189539) were analyzed. Wnt/β-catenin pathway-related genes (WRGs) and immune-related genes (IRGs) were integrated. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, and machine learning algorithms (Boruta and LASSO) were employed to identify hub genes. CIBERSORT was used to perform deconvolution analysis of bulk transcriptomic data and estimate the relative proportions of 22 immune cell types. Regulatory networks of key gene expression, including TF-mRNA and lncRNA-miRNA-mRNA networks, were constructed. Preliminary expression-level validation was performed in a non-transplant murine HIRI model using qPCR, Western blot, histological analysis, and serological assessment. Results: Four pivotal genes— HSP90AA1 , HSP90AB1 , NFATC1 , and THBS1 —were identified and validated. These genes were significantly upregulated in post-LT samples and showed good discriminatory potential in the analyzed datasets (AUC > 0.9 in training set, >0.7 in validation set). Functional enrichment linked these genes to cytokine activity and pathways such as the Jak-STAT and chemokine signaling pathways. Immune infiltration analysis revealed correlations with M0/M2 macrophages and resting mast cells. Single-cell sequencing delineated their cell-type-specific expression and differentiation-stage dynamics. In the non-transplant murine HIRI model, the mRNA and protein expression levels of all four genes were significantly upregulated at 6 hours after reperfusion, coinciding with peak injury and supporting their association with acute ischemia-reperfusion injury. Conclusion: This study identifies HSP90AA1 , HSP90AB1 , NFATC1 , and THBS1 as crucial biomarkers. Their expression was associated with Wnt/β-catenin signaling scores and immune responses. Results from the non-transplant murine HIRI model supported the upregulation of the four genes during the acute phase of ischemia-reperfusion injury, whereas their potential time-dependent significance and therapeutic value require further validation in LT models and gene functional intervention experiments.

Rationale: The important etiological treatment for hyperlipidemic severe acute pancreatitis is to reduce blood lipid. Statins or fibrates are often selected in clinical practice. Most reports indicate that statins or statin combination therapy can cause serious complications such as rhabdomyolysis syndrome (RM) and even poor prognosis. However, in fact, RM may also occur when fibrates alone are used to reduce blood lipid. Patient concerns: A 25-year-old man was admitted to our hospital for a 2-day history of abdominal pain, nausea, and vomiting. This patient presented with typical clinical manifestations of acute pancreatitis such as abdominal pain, abdominal distension, nausea, vomiting, and difficulty in defecation after a greasy diet. Auxiliary examinations such as blood (urine) amylase, lipase, blood lipid, abdominal computed tomography, and color Doppler ultrasound confirmed hyperlipidemic severe acute pancreatitis. However, after admission, during the treatment for reducing blood lipid, the blood creatine kinase index of the patient continued to increase, reaching more than 200 times the upper limit of normal at the highest. Accompanied by typical clinical manifestations, rhabdomyolysis was considered. After discussions among experts in the department, differentiations were mainly made from drugs after admission, recent history of toxicant exposure, history of trauma, past history of similar rhabdomyolysis, and other etiologies causing elevated myocardial enzyme spectrum. Finally, it was considered related to bezafibrate. Diagnoses: RM. Interventions: Bezafibrate tablets for lowering blood lipids were immediately discontinued. On the second day after discontinuation, there was a small decrease in creatine kinase. Then, appropriate fluid infusion, alkalinization of urine, addition of plasma exchange, and bedside continuous renal replacement therapy were administered. Outcomes: The level of muscle enzymes decreased progressively and finally returned to normal before discharge. Lessons: In clinical practice, it is necessary to dynamically monitor the changes of liver and kidney functions and myocardial enzyme spectrum when using bezafibrate tablets to treat hyperlipidemic pancreatitis.

Sepsis, a complex and multifaceted condition, is a common occurrence with serious implications for critically ill patients in the intensive care unit (ICU). The YWHAH gene encodes the 14-3-3n protein, a member of the 14-3-3 protein family. While existing research primarily focuses on the role of 14-3-3n in conditions such as schizophrenia and various cancers, our study revealed that the expression of the YWHAH gene remained relatively stable in both infected individuals and healthy controls. Through Venn plot analysis following weighted gene correlation network analysis, we observed a potential association between elevated YWHAH expression and the transition from infection to sepsis. In a comprehensive analysis of public single-cell transcriptome databases, the expression of YWHAH was found to be distinctive in cases of sepsis and infection. These findings were corroborated through an in vitro analysis utilizing real-time polymerase chain reaction. This study represents the initial identification of variations in YWHAH gene expression between patients with infection and sepsis, potentially offering insights for the development of early detection and treatment strategies for sepsis.

(1) Background: Studies on the long-term patterns of using vasopressors in patients with shock and their correlations with the risk of feeding intolerance (FI) are limited. This study aimed to characterize the norepinephrine equivalent dose (NEQ) trajectories and explore its correlations with FI in patients with shock. (2) Methods: This study prospectively enrolled patients with shock, who received vasopressors from August 2020 to June 2022. The Growth Mixed Model (GMM) was used to traverse longitudinal NEQ data at six-hour intervals and identify the latent trajectories of NEQ use in these patients. Cox proportional hazards regression models were used to examine the correlations of NEQ trajectories with FI. (3) Results: This study included a total of 210 patients with shock recruited from August 2020 to June 2022. Four trajectories of NEQ dose were identified and characterized by low-dose stable NEQ (L-NEQ, n = 98), moderate-dose stable NEQ (M-NEQ, n = 74), high-dose stable NEQ (H-NEQ, n = 21), and rapidly rising NEQ (R-NEQ, n = 17), with NEQ doses of 0.2, 0.4, 0.4, and 0.5 µg/kg/min at enteral nutrition (EN) initiation, respectively. The incidences of FI were 37.76%, 67.57%, 80.95%, and 76.47% in the L-NEQ, M-NEQ, H-NEQ, and R-NEQ groups, respectively (p < 0.001). As compared to the L-NEQ group, the risk of FI occurrence increased in the M-NEQ, H-NEQ, and R-NEQ groups (all p < 0.05). (4) Conclusions: The risk of FI was significantly associated with NEQ trajectories. It might be appropriate to initiate EN when the NEQ dose is stabilized below 0.2 µg/kg/min in patients with shock.