Current Medical Science最新文献

While biventricular assist devices (BiVADs) remain underutilized in Western countries for biventricular heart failure (BHF), their application is expanding in China. This consensus synthesizes international guidelines, medical evidence, and Chinese clinical expertise to establish standardized protocols for BiVAD management. Key recommendations include: (1) Preoperative right heart catheterization and echocardiography for central venous pressure (CVP): pulmonary capillary wedge pressure (PCWP) ratio and pulmonary artery pulsatility index (PAPi) assessment (Class I); (2) BiVAD indication in refractory BHF or high-risk right heart failure post-left ventricular assist device (LVAD) implantation (Class IIa); (3) Right atrial implantation as the preferred surgical approach (Class IIa); (4) Warfarin-based anticoagulation (INR 2.0-2.5) with aspirin, avoiding direct oral anticoagulants (DOACs) (Class III). The guidance addresses critical gaps in patient selection, pump speed titration, and complication management, positioning integrated BiVAD systems as a promising solution for complex BHF.

Objective: The pathogenesis and progression of heart failure (HF) are governed by complex, interconnected biological pathways, with dysregulated immune responses and maladaptive cardiac remodeling playing central roles. Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling-such as cardiomyocyte hypertrophy and extracellular matrix fibrosis-the precise molecular mechanisms driving these processes remain incompletely characterized.

Methods: Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy (HCM) transcriptomic datasets identified pathologically relevant candidate genes. A protein-protein interaction (PPI) network was constructed from these candidates using the STRING database, followed by module analysis. Serum S100 calcium-binding protein A9 (S100A9) protein expression in HF patients was quantified by Western blotting under reducing conditions. The functional relevance of prioritized genes was subsequently validated through: (i) in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes, and (ii) in vivo pressure overload modeling via transverse aortic constriction (TAC) in mice.

Results: Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling. Using CytoNCA, we identified core genes, among which the top 25 included multiple inflammatory pathway-related factors, such as S100A9 and Toll-like receptor 2 (TLR2). Notably, S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes. This increase correlated with upregulated expression of hypertrophy-related markers, including atrial natriuretic peptide (ANP). Furthermore, mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes. Importantly, TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression, as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.

Conclusion: The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes. This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.

Objective: The middle turbinate axilla (MTA) is a crucial anatomical landmark for localizing the lacrimal sac (LS) during endonasal dacryocystorhinostomy (En-DCR). Despite being a standard surgical procedure, En-DCR may lead to severe complications, such as cerebrospinal fluid (CSF) leakage, which is closely associated with anatomical variations between the LS and the anterior skull base (ASB). This study aimed to investigate the anatomical location of the LS relative to the MTA and ASB in Chinese patients with nasolacrimal duct obstruction (NLDO) and analyze the influencing factors.

Methods: This cross-sectional study enrolled 227 Chinese patients who were diagnosed with NLDO and underwent computed tomographic dacryocystography (CT-DCG). Anatomical distances between LS and MTA, as well as LS and ASB, were measured using CT-DCG images.

Results: The mean distances from the superior and inferior edges of the LS to the MTA were 9.94 ± 4.70 mm and - 0.23 ± 4.15 mm, respectively. Male patients showed significantly more superior-anterior displacement of the LS compared to female patients (P < 0.001), while patients with chronic dacryocystitis (CD) had an inferior and posterior LS position relative to those with simple NLDO (P = 0.005, P = 0.001). The mean distance from the intersection (Point P) of the superior and posterior boundaries of the LS to the ASB (MP) was 18.35 ± 4.48 mm, which was shorter in females and those with frontal sinus aplasia (P = 0.001; P < 0.001). A subgroup (28/227, 12.3%) with a critical anatomical feature was identified, where the distance from Point Q (10 mm posterior to P) to the ASB (NQ distance) was ≤ 10 mm. This subgroup had a higher prevalence of complete supra-MTA LS positioning (71.4% vs. 41.2%, P = 0.003).

Conclusion: Preoperative CT-DCG provides essential anatomical insights into the spatial relationship between the LS and MTA in Chinese patients with NLDO. The LS position varies significantly by gender and disease type, with males showing more superior-anterior and CD patients more inferior-posterior positioning relative to the MTA. Special attention should be paid to patients with frontal sinus aplasia or LS entirely above the MTA to minimize the risk of CSF leakage during En-DCR.

Alcoholic liver disease (ALD), which includes a range of diseases, ranging from alcoholic steatosis, hepatitis, and fibrosis to cirrhosis and hepatocarcinoma, is a process of epigenetic remodeling involving multiple genes and metabolic pathways. ALD is involved in various transcriptional regulatory mechanisms, including lipid metabolism disorders, inflammatory responses, autophagy, fibrogenesis, oxidative stress, fatty acid metabolism, iron metabolism, and endoplasmic reticulum stress. In the occurrence of ALD and its response to the microenvironment, various transcription factors (TFs) play important roles. Targeted therapy involving these TFs may pave a novel avenue for the treatment of ALD. Here, we summarize the molecular characteristics of TFs and their involvement in the biological and pathological processes of ALD. We further discuss the current pharmaceutical treatments targeting these TFs and their mediators. This study provides detailed and accurate regulation maps of TFs for the targeted therapy of ALD.

Objective: Oral squamous cell carcinoma (OSCC) is an aggressive cancer with a high mortality rate. San-Zhong-Kui-Jian-Tang (SZKJT), a Chinese herbal formula, has long been used as an adjuvant therapy in cancer clinical practice. Although its therapeutic effects and molecular mechanisms in OSCC have been previously elucidated, the potential interactions and mechanisms between the active phytochemicals and their therapeutic targets are still lacking.

Methods: The present study employed network pharmacology and topology approaches to establish a "herbal ingredients-active phytochemicals-target interaction" network to explore the potential therapeutic targets of SZKJT-active phytochemicals in the treatment of OSCC. The role of the target proteins in oncogenesis was assessed via GO and KEGG enrichment analyses, and their interactions with the active phytochemicals of SZKJT were calculated via molecular docking and dynamic simulations. The pharmacokinetic properties and toxicity of the active phytochemicals were also predicted.  RESULTS: A total of 171 active phytochemicals of SZKJT fulfilled the bioavailability and drug-likeness screening criteria, with the flavonoids quercetin, kaempferol, and naringenin having the greatest potential. The 4 crucial targets of these active phytochemicals are PTGS2, TNF, BCL2, and CASP3, which encode cyclooxygenase-2, tumor necrosis factor (TNF), BCL-2 apoptosis regulator, and caspase-3, respectively. The interactions between phytochemicals and target proteins were predicted to be thermodynamically feasible and stable via molecular docking and dynamics simulations. Finally, the results revealed that the IL-6/JAK/STAT3 pathway and TNF signaling via NF-κB are the two prominent pathways targeted by SZKJT.

Conclusion: In summary, this study provides computational data for in-depth exploration of the mechanism by which SZKJT activates phytochemicals to treat OSCC.

Objective: Electronic cigarettes (ECs) differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling. Pulmonary hypertension (PH), characterized by pulmonary artery and right ventricle remodeling, poses a significant risk of mortality in infants, children, and adolescents. However, the impact of maternal EC exposure on PH development in offspring remains unclear. To address this, we established a PH rat model with maternal EC exposure.

Methods: Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems. Offspring were administered monocrotaline (MCT) at 6 weeks of age (6-wo) to induce PH. Mechanistic experiments were conducted at 10-week-old (10-wo). Protein expression of NADPH oxidases, DNA methyltransferases, and autophagy-related markers was analyzed by Western blot. Morphological changes and the severity of PH were evaluated via hematoxylin and eosin (HE) staining and echocardiography, respectively. Furthermore, the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA, Western blot, HE staining, and echocardiography. Additionally, ATG5 mRNA expression was measured by qRT-PCR.

Results: Compared with control conditions, maternal EC exposure significantly worsened MCT-induced PH in male offspring. This was associated with increased oxidative stress, DNA hypomethylation, and anomalous autophagy in the offspring. In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC. Furthermore, N-acetylcysteine (NAC), an antioxidant, attenuated maternal EC exposure-induced oxidative stress, DNA hypomethylation, and excessive autophagy, thereby improving PH. DNA hypermethylation also reversed PH development, accompanied by reduced oxidative stress and suppressed autophagy. ATG5, a key regulator of autophagy, was identified as a potential therapeutic target, as its repression mitigated PH in maternal EC-exposed offspring.

Conclusion: Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring, leading to anomalous autophagy and exacerbation of PH development. Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.

Objective: Sepsis-induced acute lung injury (ALI) poses a critical challenge in critical care, yet its immunoregulatory mechanisms remain poorly defined. This study aimed to delineate immune dysregulation networks and identify therapeutic targets through multiomics data integration.

Methods: Transcriptomic datasets (GSE40180 and GSE165226) were analyzed through a multiphase bioinformatics workflow, including gene set enrichment analysis (GSEA), immune cell deconvolution (CIBERSORT), differential gene expression profiling (|log2FC|> 1.5, P.adj < 0.05), and pathway annotation (GO/KEGG). Protein-protein interaction (PPI) networks were constructed to identify hub genes. Experimental validation was done using a murine cecal ligation and puncture (CLP) model with histopathological lung injury scoring and RT-qPCR-based hub gene verification.

Results: Integrated analysis revealed 26 consensus biological processes (24 upregulated, 2 downregulated) dominated by innate immune activation. CIBERSORT revealed significant infiltration of M1 macrophages, neutrophils, activated dendritic cells (DCs), and activated natural killer (NK) cells in septic lungs, which was concurrent with Th17/naive CD8+ T-cell dysregulation. Among the 58 differentially expressed genes (DEG), 7 hub genes (Cxcl1, Cxcl2, Ccl3, Cd14, Saa3, Timp1, and Socs3) were significantly correlated with immune cell dynamics. CLP modeling confirmed severe alveolar damage (lung injury score: 8.11 ± 1.17 vs. 1.97 ± 0.29; P < 0.0001) and upregulated hub gene expression (all P < 0.01) in septic lungs, with hub gene expression levels strongly correlated with the lung injury score (Pearson's r > 0.85, P < 0.001).

Conclusion: Innate adaptive immune crosstalk, particularly dysregulated immune cell infiltration, drives sepsis-induced ALI pathogenesis. The 7 hub genes mechanistically connect immune dyshomeostasis to tissue injury, suggesting novel targets for precision immunomodulation and biomarker development in critical care.

The subnucleus reticularis dorsalis (SRD), also known as the dorsal reticular nucleus (DRt) or dorsal medullary reticular nucleus (MdD), which resides at the caudal end of the medulla, plays a pivotal role in regulating pain perception. Despite extensive research efforts to unravel its mechanisms, the operational intricacies of SRD remain poorly understood. Advances in experimental methodologies such as brain imaging and chemogenetics have facilitated deeper investigations into the involvement of SRD in various pain disorders. This comprehensive review aims to analyze 36 years (1989-2024) of preclinical research highlighting the critical role of SRD in diffuse noxious inhibitory control (DNIC), also known as conditioned pain modulation (CPM) in humans, and its interconnected neural circuits. Moreover, this review explores the neural circuits related to SRD, including locus coeruleus (LC)-SRD, parabrachial nucleus (PBN)-SRD, rostroventromedial medulla (RVM)-ventrolateral medulla (VLM)-SRD, anterior cingulate cortex (ACC)-SRD, medial medullary reticular formation (mMRF)-SRD, and dorsal striatum (DS)-SRD. Their activation also plays a significant role in analgesia. The pivotal roles of neurotransmitters such as μ-opioid receptor (MOR), noradrenaline, and metabotropic glutamate receptor 7 (mGluR7) in modulating SRD responsiveness to pain stimuli are also discussed, as are the influences of SRD on different pain types. This review identified promising avenues for innovative analgesic treatments by shedding light on potential therapeutic strategies targeting SRD.

Neurodegenerative diseases (NDDs) are characterized primarily by progressive impairments in cognition, behavior, and memory. MicroRNAs (miRNAs) are abundantly expressed in the central nervous system and are vital for the normal function and survival of neurons. Mature miRNAs are naturally occurring small noncoding single-stranded RNA molecules that are approximately 21-25 nucleotides in length. They regulate gene expression by pairing with target mRNAs and undergo significant alterations in various physiological and pathological processes. miR-146a, a miRNA dependent on nuclear factor κB (NF-κB), is highly expressed in neurons and functions as an anti-inflammatory miRNA via the Toll-like receptor (TLR) pathway, which is an essential regulatory factor for neuroinflammation expression during the development of NDDs. In this review, we summarize and emphasize the pivotal role of miR-146a in NDDs, highlighting the association between miR-146a polymorphisms and the risk of NDDs. We also discuss how alterations in miR-146a expression levels represent a critical event in the pathogenesis of numerous NDDs. Furthermore, the target genes of miR-146a are involved in regulating the pathophysiological processes of these diseases, particularly in the context of neuroinflammatory responses. In conclusion, miR-146a plays a central role in the progression of NDDs, with its primary function in neuroinflammation. These findings suggest that miR-146a holds promise as both a biomarker and a potential therapeutic target. A deeper understanding of how miR-146a influences neuroinflammatory responses across different types of neurological damage, cell types, and even various stages of certain NDDs will pave the way for its use as a therapeutic target in treating these conditions. Therefore, this article reviews the mechanism of miR-146a in NDDs and discusses the future therapeutic prospects for this type of disease. miR-146a regulates the related genes of the inflammatory signaling pathway and its influence on the development of NDDs. (Created in https://BioRender.com ).

Objective: Sleep is fundamental to the physical and mental health of both the general population and pregnant women. Most studies have focused on the impact of certain trimester sleep behaviors on gestational complications and birth outcomes. This study aimed to explore the association between maternal sleep duration and fetal growth development from as early as 23 gestational weeks to birth.

Methods: A total of 803 pregnant women were prospectively enrolled. The self-reported maternal nocturnal sleep duration during all 3 trimesters was recorded. The outcome measures were reference-population-based Z-scores of fetal biometric measurements obtained through routine ultrasonographic examination.

Results: Using multiple linear regression, a marginally significant negative association was observed between second-trimester sleep duration and second-trimester fetal head circumference (HC) and third-trimester fetal biparietal diameter (BPD). Then the associations of long sleep duration in each trimester with fetal biometry extreme values were evaluated. A significant impact of second-trimester long sleep duration on the second-trimester BPD below the 10th percentile of the reference population was observed. Longitudinal analysis reported similar results for BPD and HC.

Conclusions: Overall, a negative association between sleep duration and fetal biometric measurements was observed. Long sleep durations in the second trimester might negatively impact fetal growth, particularly brain parameters, including BPD and HC.