Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Extracorporeal membrane oxygenation (ECMO) is a key continuous extracorporeal life support technology that can partially or completely replace a patient's cardiopulmonary function, thereby winning valuable time for the diagnosis and treatment of the primary disease. With the widespread application of ECMO, the need for transport has increased. However, during transfers, the standard heater unit is often large and inconvenient to carry, while alternative warming measures tend to be ineffective. This frequently leads to complications such as hypothermia or the inability to maintain body temperature, which can seriously affect the patient's prognosis. In response to this challenge, the medical and nursing staff of the critical care medicine department at Zhongda Hospital Affiliated to Southeast University jointly designed an insulation device for ECMO transport pipelines. The device was successfully granted a National Utility Model Patent of China (patent number: ZL 2021 2 0653569.3). It primarily consists of key components such as a heating pad, velcro straps, a cover layer, a backing layer, an electric heating layer, and a wiring plug. Its advantages include portability, the ability to effectively wrap around and warm the ECMO circuit during transit, and a reduction in the incidence of hypothermia-related complications. Furthermore, its transparent material design allows for real-time monitoring of the ECMO system's status, making it both economical and practical.
Extracorporeal Membrane Oxygenation/instrumentation* ; Humans ; Equipment Design

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods: High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results: Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.

BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

OBJECTIVE: This review summarized the first 10-year progresses and controversies in the concept of anteromedial cortical support reduction, to provide references for further study and clinical applications. METHODS: Relevant domestic and foreign literature on cortical support reduction was extensively reviewed to summarize the definition of positive, neutral, and negative support, anteromedial cortices at the inferior corner, intraoperative technical tips for fracture reduction, radiographic assessment at different periods, comparison between positive versus neutral and medial versus anterior support, and the clinical efficacy of Chang reduction quality criteria (CRQC) and postoperative stability score. RESULTS: Anteromedial cortical support reduction was only focused on the cortex of anteromedial inferior corner, with no concern the status of lateral wall or lesser trochanter. Anteromedial cortex was seldom involved by fracture comminution, it was thicker, denser, and stronger, and was the key for mechanical buttress of the head-neck fragment to share compression load. Positive, neutral, and negative support were also called "extramedullary, anatomic, and intramedullary reduction", respectively. There was hardly seen parallel cortical apposition, but characterized by some kinds of head-neck rotation, for example 10°-15° flexed rotation for positive cortical contact and support. Due to intraoperative compression and postoperative impaction, the status of cortical support may be changed at different time of radiographic examination. The positive medial cortex support was more reliable with less reduction loss than its neutral counterpart, and the anterior cortex contact was more predictive than the medial cortex for final results. As incorporation the bearing of cortex apposition and using a 4-point score, CRQC demonstrated more efficacy and was gradually accepted and applied in the evaluation of trochanteric fracture reduction quality. Postoperative stability score (8 points) provided a assessment tool for early weight-bearing in safety to prevent mechanical failure. CONCLUSION Anteromedial cortical support reduction is a key point for stability reconstruction in the treatment of trochanteric femur fractures. Evidence has definitely shown that non-negative (positive and neutral) is superior to negative (loss of cortical support). There is a tendency that positive cortex support is superior to neutral, but high quality study with large sample size is needed for a clear conclusion.
Humans ; Femur/diagnostic imaging* ; Fracture Fixation, Internal/methods* ; Hip Fractures/diagnostic imaging* ; Treatment Outcome ; Fracture Fixation, Intramedullary/methods*

Objective To explore the action mechanism of dehydrocostus lactone(DHL)on renal interstitial fibrosis(RIF)in rats with unilateral ureteral obstruction(UUO).Methods Forty-four male SD rats were randomly divided into four groups:the sham surgery group(Sham group),the pure drug intervention group(Sham+DHL group),the experimental group(UUO+Vehicle group)and the DHL treatment group(UUO+DHL group),with 11 rats in each group.The rats underwent sham surgery,sham surgery+DHL[10 mg/(kg·d)],UUO modeling+the same volume of solvent and UUO modeling+DHL[10 mg/(kg·d)],respectively.After surgery,DHL or the same volume of solvent was administered by gavage for 14 days starting from day 2 post-surgery.Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological changes in renal tissue.Immunohistochemical staining was performed to detect the expression levels of collagen I,collagen III and α-smooth muscle actin(α-SMA).Western blotting was used to detect the protein levels of the transforming growth factor(TGF)-β1/Smad2/3 pathway.Results Compared with the UUO+Vehicle group,DHL treatment alleviated renal interstitial pathological damage,reduced collagen fiber deposition,and decreased the expression of collagen I,collagen III and α-SMA.It also inhibited the expression of TGF-β1 and Smad2/3 proteins.Conclusions DHL mitigates RIF in rats by inhibiting the TGF-β1/Smad2/3 pathway,providing a new strategy for the treatment of chronic kidney disease.