Perioperative outcomes of robotic versus video-assisted thoracoscopic surgery in non-small cell lung cancer patients after neoadjuvant chemoimmunotherapy.

Background: Limited data are available regarding perioperative outcomes in patients with non-small cell lung cancer (NSCLC) who undergo robotic-assisted thoracic surgery (RATS) after neoadjuvant chemoimmunotherapy. This study aimed to compare the perioperative outcomes of RATS and video-assisted thoracic surgery (VATS) in NSCLC patients after neoadjuvant chemoimmunotherapy. Methods: The study involved consecutive NSCLC patients treated with minimally invasive surgery (MIS) after neoadjuvant chemoimmunotherapy at a high-volume single center from September 2020 to October 2022. Short-term effects, including demographic, perioperative and pathological parameters, were compared between the RATS group and the VATS group. Results: A total of 119 patients were included in this study. Of these, 33 (27.7%) patients received RATS and 86 (72.3%) patients received VATS. Major pathological response (MPR) and pathological complete response (pCR) rates were comparable between the two groups. The RATS group had a higher number of dissected lymph nodes (21 vs. 18, P=0.03) and lymph node stations (7 vs. 6, P=0.004) compared with the VATS group but no differences were found in perioperative outcomes. Conclusions: These findings suggest that both RATS and VATS are safe and feasible options for NSCLC patients who have received neoadjuvant chemoimmunotherapy. Furthermore, RATS may offer advantages over VATS in patients who require a more extensive lymph node dissection.

The detoxification ability of sex-role reversed seahorses determines the sexual dimorphism in immune responses to benzo[a]pyrene exposure.

Sexual dimorphism in immune responses is an essential factor in environmental adaptation. However, the mechanisms involved remain obscure owing to the scarcity of data from sex-role-reversed species in stressed conditions. Benzo[a]pyrene (BaP) is one of the most pervasive and carcinogenic organic pollutants in coastal environments. In this study, we evaluated the potential effects on renal immunotoxicity of the sex-role-reversed lined seahorse (Hippocampus erectus) toward environmental concentrations BaP exposure. Our results discovered the presence of different energy-immunity trade-off strategies adopted by female and male seahorses during BaP exposure. BaP induced more severe renal damage in female seahorses in a concentration-dependent manner. BaP biotransformation and detoxification in seahorses resemble those in mammals. Benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide (BPDE) and 9-hydroxybenzo[a]pyrene (9-OH-BaP) formed DNA adducts and disrupted Ca2+ homeostasis may together attribute the renal immunotoxicity. Sexual dimorphisms in detoxification of both BPDE and 9-OH-BaP, and in regulation of Ca2+, autophagy and inflammation, mainly determined the extent of renal damage. Moreover, the mechanism of sex hormones regulated sexual dimorphism in immune responses needs to be further elucidated. Collectively, these findings contribute to the understanding of sexual dimorphism in the immunotoxicity induced by BaP exposure in seahorses, which may attribute to the dramatic decline in the biodiversity of the genus.

LINC01614 is a promising diagnostic and prognostic marker in HNSC linked to the tumor microenvironment and oncogenic function.

Background: Tumor initiation and metastasis influence tumor immune exclusion and immunosuppression. Long non-coding RNA (lncRNA) LINC01614 is associated with the prognosis and metastasis of several cancers. However, the relationship between LINC01614 and cancer immune infiltration and the biofunction of LINC01614 in head and neck squamous cell carcinoma (HNSC) remain unclear. Methods: The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets were used to analyze the expression difference and diagnostic value of LINC01614 in normal and tumor tissues. The correlation of pan-cancer prognosis and tumor stage of LINC01614 was analyzed based on the TCGA database. The pan-cancer association of LINC01614 expression with the tumor microenvironment (TME) including immune infiltration, expression of immune-related genes, and genomic instability parameters, was analyzed using the Spearman correlation method. The correlation between LINC01614 and tumor stemness evaluation indicators, RNA methylation-related genes, and drug resistance was also analyzed. The functional analysis of LINC01614 was performed using the clusterProfiler R package. The protein-protein interaction (PPI) network and ceRNA network of LINC01614 co-expressed genes and miRNA were constructed and visualized by STRING and Cytoscape, respectively. Finally, the cell location and influence of LINC01614 on cell proliferation and metastasis of HNSC cell lines were evaluated using FISH, CCK-8, wound-healing assay, and transwell assay. Results: LINC01614 was found to be overexpressed in 23 cancers and showed a highly sensitive prediction value in nine cancers (AUC >0.85). LINC01614 dysregulation was associated with tumor stage in 12 cancers and significantly influenced the survival outcomes of 26 cancer types, with only Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC), uterine corpus endometrial carcinoma (UCEC), and bladder urothelial carcinoma (BLCA) showing a benign influence. LINC01614 was also associated with immune cell infiltration, tumor heterogeneity, cancer stemness, RNA methylation modification, and drug resistance. The potential biological function of LINC01614 was verified in HNSC, and it was found to play important roles in proliferation, immune infiltration, immunotherapy response, and metastasis of HNSC. Conclusion: LINC01614 may serve as a cancer diagnosis and prognosis biomarker and an immunotherapy target for specific cancers.

Blocking cGAS-STING pathway promotes post-stroke functional recovery in an extended treatment window via facilitating remyelination.

BACKGROUND: Ischemic stroke is a major cause of worldwide death and disability, with recombinant tissue plasminogen activator being the sole effective treatment, albeit with a limited treatment window. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is emerging as the major DNA-sensing pathway to invoke immune responses in neuroinflammatory disorders. METHODS: By performing a series of neurobehavioral assessments, electrophysiological analysis, high-throughput sequencing, and cell-based assays based on the transient middle cerebral artery occlusion (tMCAO) mouse stroke model, we examined the effects and underlying mechanisms of genetic and pharmacological inhibition of the cGAS-STING pathway on long-term post-stroke neurological functional outcomes. FINDINGS: Blocking the cGAS-STING pathway, even 3 days after tMCAO, significantly promoted functional recovery in terms of white matter structural and functional integrity as well as sensorimotor and cognitive functions. Mechanistically, the neuroprotective effects via inhibiting the cGAS-STING pathway were contributed not only by inflammation repression at the early stage of tMCAO but also by modifying the cell state of phagocytes to facilitate remyelination at the sub-acute phase. The activation of the cGAS-STING pathway significantly impeded post-stroke remyelination through restraining myelin debris uptake and degradation and hindering oligodendrocyte differentiation and maturation. CONCLUSIONS: Manipulating the cGAS-STING pathway has an extended treatment window in promoting long-term post-stroke functional recovery via facilitating remyelination in a mouse stroke model. Our results highlight the roles of the cGAS-STING pathway in aggregating stroke pathology and propose a new way for improving functional recovery after ischemic stroke. FUNDING: This work was primarily funded by the National Key R&D Program of China.

Mitochondrial tRNA pseudouridylation governs erythropoiesis.

Pseudouridine is the most prevalent RNA modification, and its aberrant function is implicated in various human diseases. However, the specific impact of pseudouridylation on hematopoiesis remains poorly understood. In this study, we investigated the role of tRNA pseudouridylation in erythropoiesis and its association with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome (MLASA) pathogenesis. By utilizing patient-specific induced pluripotent stem cells (iPSCs) carrying a genetic PUS1 mutation and a corresponding mutant mouse model, we demonstrated impaired erythropoiesis in MLASA iPSCs and anemia in the MLASA mouse model. Both MLASA iPSCs and mouse erythroblasts exhibited compromised mitochondrial function and impaired protein synthesis. Mechanistically, we revealed that PUS1 deficiency resulted in reduced mitochondrial tRNA levels due to pseudouridylation loss, leading to aberrant mitochondrial translation. Screening of mitochondrial supplements aimed at enhancing respiration or heme synthesis showed limited effect in promoting erythroid differentiation. Interestingly, the mTOR inhibitor rapamycin facilitated erythroid differentiation in MLASA-iPSCs by suppressing mTOR signaling and protein synthesis, and consistent results were observed in the MLASA mouse model. Importantly, rapamycin treatment effectively ameliorated anemia phenotypes in the MLASA patient. Our findings provide novel insights into the crucial role of mitochondrial tRNA pseudouridylation in governing erythropoiesis and present potential therapeutic strategies for anemia patients facing challenges related to protein translation.

Specific lipid magnetic sphere sorted CD146-positive bone marrow mesenchymal stem cells can better promote articular cartilage damage repair.

BACKGROUND: The characteristics and therapeutic potential of subtypes of bone marrow mesenchymal stem cells (BMSCs) are largely unknown. Also, the application of subpopulations of BMSCs in cartilage regeneration remains poorly characterized. The aim of this study was to explore the regenerative capacity of CD146-positive subpopulations of BMSCs for repairing cartilage defects. METHODS: CD146-positive BMSCs (CD146 + BMSCs) were sorted by self-developed CD146-specific lipid magnetic spheres (CD146-LMS). Cell surface markers, viability, and proliferation were evaluated in vitro. CD146 + BMSCs were subjected to in vitro chondrogenic induction and evaluated for chondrogenic properties by detecting mRNA and protein expression. The role of the CD146 subpopulation of BMSCs in cartilage damage repair was assessed by injecting CD146 + BMSCs complexed with sodium alginate gel in the joints of a mouse cartilage defect model. RESULTS: The prepared CD146-LMS had an average particle size of 193.7 ± 5.24 nm, an average potential of 41.9 ± 6.21 mv, and a saturation magnetization intensity of 27.2 Am2/kg, which showed good stability and low cytotoxicity. The sorted CD146 + BMSCs highly expressed stem cell and pericyte markers with good cellular activity and cellular value-added capacity. Cartilage markers Sox9, Collagen II, and Aggrecan were expressed at both protein and mRNA levels in CD146 + BMSCs cells after chondrogenic induction in vitro. In a mouse cartilage injury model, CD146 + BMSCs showed better function in promoting the repair of articular cartilage injury. CONCLUSION: The prepared CD146-LMS was able to sort out CD146 + BMSCs efficiently, and the sorted subpopulation of CD146 + BMSCs had good chondrogenic differentiation potential, which could efficiently promote the repair of articular cartilage injury, suggesting that the sorted CD146 + BMSCs subpopulation is a promising seed cell for cartilage tissue engineering.

Exploring the therapeutic potential of tonic Chinese herbal medicine for gynecological disorders: An updated review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynecological disorders have the characteristics of high incidence and recurrence rate, which sorely affects female's health. Since ancient times, traditional Chinese medicine (TCM), especially tonic medicine (TM), has been used to deal with gynecological disorders and has unique advantages in effectiveness and safety. AIM OF THE REVIEW: In this article, we aim to summarize the research progress of TMs in-vivo and in-vitro, including their formulas, single herbs, and compounds, for gynecological disorders treatment in recent years, and to offer a reference for further research on the treatment of gynecological disorders and their clinical application in the treatment of TMs. MATERIALS AND METHODS: Relevant information on the therapeutic potential of TMs against gynecological disorders was collected from several scientific databases including Web of Science, PubMed, CNKI, Google Scholar and other literature sources. RESULTS: So far, there are 46 different formulas, 3 single herbs, and 24 compounds used in the treatment of various gynecological disorders such as premature ovarian failure, endometriosis breast cancer, and so on. Many experimental results have shown that TMs can regulate apoptosis, invasion, migration, oxidative stress, and the immune system. In addition, the effect of TMs in gynecological disorders treatment may be due to the regulation of VEGF, PI3K-AKT, MAPK, NF-κB, and other signaling pathways. Apparently, TMs play an active role in the treatment of gynecological disorders by regulating these signaling pathways. CONCLUSION: TMs have a curative effect on the prevention and treatment of gynecological disorders. It could relieve and treat gynecological disorders through a variety of pathways. Therefore, the appropriate TM treatment program makes it more possible to treat gynecological disorders.

Corrigendum: Active substances of myxobacteria against plant diseases and their action mechanisms.

[This corrects the article DOI: 10.3389/fmicb.2023.1294854.].

Air oxidation of carbon supports boosts the low-humidity fuel cell performance.

We introduce a straightforward, yet effective strategy to combat the performance decline of proton-exchange membrane fuel cells in low-humidity environments. Our method centers on air-oxidizing carbon supports, significantly improving proton and oxygen transport within the cathode catalyst layer.

M6A methylation-regulated autophagy may be a new therapeutic target for intervertebral disc degeneration.

Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy-related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy-related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.

Meta-analysis of the influence of tracheal intubation with cuff and without cuff on the incidence of total wound complications in ICU intubation patients.

At present, it is still controversial whether patients in intensive care unit (ICU) use tracheal intubation with or without cuff. This paper evaluates the effect of tracheal intubation with and without cuff on overall complication rate of patients with intubation in ICU. The database of PubMed, Embase, Conchrane Library and Web of Science was searched by computer, and the clinical research on intubation with and without cuff in ICU was collected. The time range was from the database establishment to November 2023. Literature was independently screened, information was extracted, and quality was assessed by two researchers. Finally, there were nine studies included, with 11 068 patients (7391 in cuff group and 3677 in non-cuff group). The results showed that the overall complication rate of cuff group was significantly lower than that of non-cuff group, and that of cuff group (RR = 0.53, p < 0.01). In addition, compared with the non-cuff group, the cuff group had a lower number of tracheal intubation changes [RR = 0.05, p < 0.01] and a lower incidence of aspiration pneumonia (RR = 0.45, p = 0.01). Compared with the non-cuff group, the cuff group had a higher incidence of oral mucosal ulcers and pharyngitis (RR = 1.99, p = 0.04), while the cuff group had a lower incidence of laryngeal edema (RR = 0.39, p < 0.01). In ICU intubation patients, the use of cuffs reduces overall complication rate in comparison to patients without cuffs. Therefore, patients with intubation in ICU can recommend tracheal intubation with cuff.

Sestrin2 reduces ferroptosis via the Keap1/Nrf2 signaling pathway after intestinal ischemia-reperfusion.

Sestrins are metabolic regulators that respond to stress by reducing the levels of reactive oxygen species (ROS) and inhibiting the activity of target of rapamycin complex 1 (mTORC1). Previous research has demonstrated that Sestrin2 mitigates ischemia-reperfusion (IR) injury in the heart, liver, and kidneys. However, its specific role in intestinal ischemia-reperfusion (IIR) injury remains unclear. To elucidate the role of Sestrin2 in IIR injury, we conducted an experimental study using a C57BL/6J mouse model of IIR. We noticed an increase in the levels of Sestrin2 expression and indicators associated with ferroptosis. Our study revealed that manipulating Sestrin2 expression in Caco-2 cells through overexpression or knockdown resulted in a corresponding decrease or increase, respectively, in ferroptosis levels. Furthermore, our investigation revealed that Sestrin2 alleviated ferroptosis caused by IIR injury through the activation of the Keap1/Nrf2 signal pathway. This finding highlights the potential of Sestrin2 as a therapeutic target for alleviating IIR injury. These findings indicated that the modulation of Sestrin2 could be a promising strategy for managing prolonged IIR injury.

Therapeutic potential of the medicinal mushroom Ganoderma lucidum against Alzheimer's disease.

Alzheimer's disease (AD) is a high-incidence neurodegenerative disorder, characterized by cognitive impairment, memory loss, and psychiatric abnormalities. Ganoderma lucidum is a famous medicinal fungus with a long history of dietary intake, containing various bioactive components, and have been documented to exhibit antioxidant, anti-inflammatory, anti-tumor, anti-aging, and immunomodulatory effects, among others. Recent studies have shown that G. lucidum and its components have promising therapeutic potential against AD from various aspects, which can delay the progression of AD, improve cognitive function and quality of life. The underlying mechanisms mainly include inhibiting tau hyperphosphorylation, inhibiting Aß formation, affecting activated microglia, regulating NF-κB/MAPK signalling pathway, inhibiting neuronal apoptosis, modulating immune system, and inhibiting acetylcholinesterase, etc. This paper systematically reviewed the relevant studies on the therapeutic potential of G. lucidum and its active components for treatment of AD, key points related with the mechanism studies and clinical trials have been discussed, and further perspectives have been proposed. Totally, as a natural medicinal mushroom, G. lucidum has the potential to be developed as effective adjuvant for AD treatment owing to its therapeutic efficacy against multiple pathogenesis of AD. Further mechanical investigation and clinical trials can help unlock the complete potential of G. lucidum as a therapeutic option for AD.

Prognostic factors of resectable anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients: a retrospective analysis based on a single center.

Background: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) exhibited a higher propensity for lymph node metastasis (LNM). This study aimed to investigate risk factors of occult lymph node metastasis (OLNM) and recurrence in resectable ALK-rearranged NSCLC patients. Methods: This retrospective analysis included patients with ALK-rearranged NSCLC receiving lung resections at Shanghai Pulmonary Hospital from June 2016 to August 2021. Logistic regression analysis was used to ascertain predictors of OLNM, and Cox regression analysis to identify risk factors of recurrence. Results: A total of 603 resectable ALK-rearranged NSCLC patients were included. The mean age was 55 years old. There were 171 patients (28.4%) pathologically confirmed to have LNM, 51.5% of which were occult. Logistic regression analysis identified clinical tumor size and computed tomography (CT) density as independent factors for OLNM. Cox regression analysis showed that pleural invasion and pathological tumor size were independent prognosticators for recurrence in pathologically nodal negative patients. Among pathologically nodal positive patients, adjuvant ALK-tyrosine kinase inhibitors (TKI) showed a similar recurrence-free survival (RFS) to chemotherapy (hazard ratio, 0.454; 95% confidence interval, 0.111-1.864). Conclusions: Assessing the potential risk of OLNM is required for ALK-rearranged NSCLC patients with large tumors characterized by high CT densities. Patients with large pathological tumor size or pleural infiltration should be closely monitored despite being pathologically nodal negative. Additionally, adjuvant ALK-TKI may present a comparable RFS to chemotherapy in pathologically nodal positive patients.

Survival analysis of the duration of rumors during the COVID-19 pandemic.

BACKGROUND: The emergence of the COVID-19 pandemic towards the end of 2019 triggered a relentless spread of online misinformation, which significantly impacted societal stability, public perception, and the effectiveness of measures to prevent and control the epidemic. Understanding the complex dynamics and characteristics that determine the duration of rumors is crucial for their effective management. In response to this urgent requirement, our study takes survival analysis method to analyze COVID-19 rumors comprehensively and rigorously. Our primary aim is to clarify the distribution patterns and key determinants of their persistence. Through this exploration, we aim to contribute to the development of robust rumor management strategies, thereby reducing the adverse effects of misinformation during the ongoing pandemic. METHODS: The dataset utilized in this research was sourced from Tencent's "Jiao Zhen" Verification Platform's "Real-Time Debunking of Novel Coronavirus Pneumonia" system. We gathered a total of 754 instances of rumors from January 18, 2020, to January 17, 2023. The duration of each rumor was ascertained using the Baidu search engine. To analyze these rumors, survival analysis techniques were applied. The study focused on examining various factors that might influence the rumors' longevity, including the theme of the content, emotional appeal, the credibility of the source, and the mode of presentation. RESULTS: Our study's results indicate that a rumor's lifecycle post-emergence typically progresses through three distinct phases: an initial rapid decline phase (0-25 days), followed by a stable phase (25-1000 days), and ultimately, an extinction phase (beyond 1000 days). It is observed that half of the rumors fade within the first 25 days, with an average duration of approximately 260.15 days. When compared to the baseline category of prevention and treatment rumors, the risk of dissipation is markedly higher in other categories: policy measures rumors are 3.58 times more likely to perish, virus information rumors have a 0.52 times higher risk, epidemic situation rumors are 4.86 times more likely to die out, and social current affairs rumors face a 2.02 times increased risk. Additionally, in comparison to wish rumors, bogie rumors and aggression rumors have 0.26 and 0.27 times higher risks of dying, respectively. In terms of presentation, graphical and video rumors share similar dissolution risks, whereas textual rumors tend to have a longer survival time. Interestingly, the credibility of the rumor's source does not significantly impact its longevity. CONCLUSION: The survival time of rumors is strongly linked to their content theme and emotional appeal, whereas the credibility of the source and the format of presentation have a more auxiliary influence. This study recommends that government agencies should adopt specific strategies to counter rumors. Experts and scholars are encouraged to take an active role in spreading health knowledge. It's important for the public to proactively seek trustworthy sources for accurate information. Media platforms are advised to maintain journalistic integrity, verify the accuracy of information, and guide the public towards improved media literacy. These actions, collectively, can foster a collaborative alliance between the government and the media, effectively combating misinformation.

Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.

Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening.

BACKGROUND: Preeclampsia is a life-threatening disease of pregnancy that lacks effective pharmaceuticals which can target its pathogenesis. Since preeclampsia involves complex pathological processes, including autophagy, this study aims to explore autophagy-related mechanisms of preeclampsia and to screen potential drugs. METHODS: Firstly, the datasets GSE75010, GSE24129, GSE66273, and autophagic genes lists were downloaded from public databases. Then, a weighted gene co-expression network analysis (WGCNA) was applied to filter autophagic-related hub genes of preeclampsia. The differential expression levels of the hub genes were validated with datasets GSE24129 and GSE66273. Next, the GO and KEGG enrichment, protein-protein interacting (PPI) network, as well as the downstream pathways was analyzed via the starBase, STRING and Cytoscape to determine the functions and regulatory network of the hub genes. Additionally, the immune microenvironment of preeclampsia was investigated by the CIBERSORTX database. Finally, three herb ingredients, berberine, baicalein, and luteolin were screened by molecular docking in comparison to pravastatin, metformin, and aspirin, to predict potential drugs for treating preeclampsia. RESULTS: A total of 54 autophagy-related genes were filtered by WGCNA. After filtering with |GS| > 0.5 and |MM| > 0.8, three hub genes, namely PKM, LEP, and HK2, were identified and validated. Among these genes, PKM and LEP were overexpressed in women older than 35 years old ( p<0.05; p<0.05); the expression of PKM, LEP, and HK2 differed remarkably in women with different BMI (all p<0.05); PKM overexpressed in women with hypertension (p<0.05). The regulatory network of hub genes demonstrated that they were mainly enriched in metabolic pathways, including the AMPK signaling pathway, glucagon signaling pathway, adipocytokine signaling pathway, and central carbon metabolism. Then, immune microenvironment analysis turned out that M2 macrophages were reduced in preeclampsia women (p<0.0001) and were negatively correlated with the expression of PKM (r=-0.2, p<0.05), LEP (r=-0.4, p<0.0001), and HK2 (r=-0.3, p<0.001). Lastly, molecular docking showed baicalein and luteolin could bind intimately to hub genes. CONCLUSION: PKM, LEP, and HK2 could be promising biomarkers for preeclampsia, which might regulate the pathogenesis of preeclampsia via metabolism pathways and immune microenvironment. Baicalein and luteolin could be potential therapeutics for preeclampsia.

Spread Through Air Spaces in Stage I Pulmonary Large Cell Neuroendocrine Carcinoma.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents an exceptionally aggressive and infrequent variant within the realm of non-small cell lung cancer, necessitating surgical intervention as the primary therapeutic approach. However, the postoperative management strategy for early-stage patients continues to be a subject of intense debate and uncertainty. METHODS: A retrospective analysis was conducted on a cohort of patients diagnosed with LCNEC who underwent surgical resection at Shanghai Pulmonary Hospital between July 2018 and June 2022. Comprehensive assessments, encompassing univariate and multivariate analyses, were performed to evaluate the prognostic significance of these indicators in patient clinical profiles, overall survival (OS), and disease-free survival (DFS). RESULTS: A comprehensive screening effort identified 171 patients with LCNEC, with 70 stage I patients meeting the criteria for inclusion in the final cohort. Of these, 11 patients (15.7%) presented with combined LCNEC, and 59 (84.3%) exhibited pure LCNEC. Univariate and multivariate analyses both unveiled that spread through air spaces (STAS) status emerged as an independent prognostic determinant for both DFS (P = .003) and OS (P = .013), whereas histologic subtype independently predicted OS (P = .011). Subgroup survival analyses further underscored that the advantageous effects of postoperative chemotherapy were significantly pronounced exclusively among STAS-positive patients, showcasing a statistically significant enhancement in DFS (P = .047) and OS (P = .018). CONCLUSIONS: STAS may serve as an adverse prognostic factor in stage I LCNEC patients, potentially offering guidance for postoperative chemotherapy decisions.