Background: Neoadjuvant chemoimmunotherapy is an important therapeutic modality for resectable nonsmall cell lung cancer (NSCLC). The roles of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in predicting the efficacy and prognosis of patients with resectable NSCLC receiving neoadjuvant chemoimmunotherapy remain uncertain. This study aimed to explore the association of baseline and preoperative NLR, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio with the treatment response and survival of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy. Materials and methods: Data of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy between May 2019 and July 2022 at our institute, were retrospectively analyzed. Peripheral blood cell counts were obtained at baseline and before surgery. Data that may affect treatment efficacy were also collected and analyzed, including age, sex, BMI, cumulative smoking exposure, pathological type, clinical stage, PD-L1 tumor proportion score, immune checkpoint inhibitors, dosage of neoadjuvant therapy, duration from final therapy to surgery, and baseline and preoperative oncological markers. The present work has been reported in compliance with REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria and guidelines (Supplemental Digital Content 1, http://links.lww.com/JS9/A860). Results: A total of 116 patients were included in the study. Univariate logistic regression analysis showed that a higher baseline NLR (P=0.001) and preoperative NLR (P=0.001) were associated with a lower incidence of pathological complete response (pCR) following neoadjuvant therapy. Multivariate analysis indicated that a lower incidence of pCR was achieved in the high baseline NLR group (P=0.014). Higher baseline NLR (P=0.021), preoperative NLR (P=0.004) and higher preoperative CEA levels (P=0.059) were associated with shorter disease-free survival (DFS). Multivariate Cox proportional hazard regression analyses showed that shorter DFS was achieved in the high preoperative NLR group (P=0.033). Conclusion: In patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy, a higher baseline NLR was associated with a lower incidence of pCR, and a higher preoperative NLR was associated with a shorter DFS. However, a future prospective study with a large sample size and long-term follow-up is needed to verify the predictive value of NLR in these patients.

Pneumothorax is one of the most common symptoms in patients with lymphangioleiomyomatosis (LAM). However, current management strategies for patients with LAM who present with recurrent pneumothorax remain inadequate. Here, we describe the successful prevention of recurrent pneumothorax by sirolimus treatment in five women with LAM. Before sirolimus treatment, all patients had received supplemental oxygen support, repeated chest tube drainage, or surgeries for management of the recurrent pneumothorax. Sirolimus treatment was initiated when the pneumothorax was completely resolved, and no patient developed pneumothorax during treatment. Moreover, they exhibited a significantly improved subjective quality of life, increased exercise capacity, and mild adverse effects such as mucositis, irregular menstruation, and delayed wound healing. On discontinuation of sirolimus or in the event that the plasma sirolimus level was markedly low, pneumothorax tended to relapse. The findings from these cases provide valuable insights that will aid in the improvement of treatment strategies for patients with LAM and recurrent pneumothorax.

N6-methyladenosine (m6A) modification, a dynamically reversible epigenetic mechanism, is implicated in pulmonary fibrosis (PF) progression. The function and molecular mechanisms of m6A reader, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in PF remain elusive. This study investigates the mechanistic contributions of IGF2BP1 to PF development. We found IGF2BP1 was overexpressed in macrophages of PF mice. IGF2BP1 knockdown markedly attenuated bleomycin (BLM)-induced lung pathology, as evidenced by reduced inflammatory cell infiltration, fibroblast accumulation, Ashcroft fibrosis scores, and hydroxyproline deposition. Furthermore, IGF2BP1 knockdown downregulated PF-associated markers in lung tissues and embryonic lung fibroblasts (ELFs), including TGF-β1, α-SMA, Collagen-I/III, Arg1, CCL18, Ym1, CD163, IL-6, IL-1β, and TIMP1, while decreasing the CD68⁺/CD163⁺ macrophage proportion. Mechanistic studies revealed that IGF2BP1 bound to and stabilized thrombospondin-1 (THBS1) in an m6A-dependent manner. THBS1 overexpression rescued the suppression of macrophage M2 polarization caused by IGF2BP1 knockdown. Additionally, THBS1 overexpression counteracted IGF2BP1 knockdown-mediated inhibition of glycolysis, restoring HK2, LDHA, and PKM2 expression, lactate/glucose metabolism, and ATP production. Intriguingly, THBS1 physically interacted with toll-like receptor 4 (TLR4), and TLR4 overexpression reversed the inhibitory effect of THBS1 knockdown on macrophage M2 polarization and glycolytic reprogramming. Collectively, our findings demonstrate that IGF2BP1 drives PF progression by stabilizing THBS1 mRNA via m6A modification, thereby promoting TLR4-mediated macrophage M2 polarization and glycolytic activation. This study unveils a novel IGF2BP1/THBS1/TLR4 regulatory axis in PF pathogenesis, offering potential therapeutic targets.

Objective: The first-line treatment for epilepsy, a chronic neurological disorder characterized by spontaneous seizures, includes the application of anticonvulsant drug therapy. Only one-third of patients are incapable of complete controlling of their seizures after the administration of ≥2 pharmaceuticals. Here, we aimed to observe the ultrastructure changes and the expression of ZnT3 and GFAP in the hippocampus of drug-resistant epileptic rats. Methods: A total of 50 healthy adult male SD rats were used to generate the model ofepilepsy by amygdala kindling. After the rats were successfully kindled, pharmacoresistant epileptic (PRE) rats were selected according to their response to phenobarbital and phenytoin. The ultrastructure as well as the expression of zinc transporter 3 (ZnT3, a member of a growing family of mammalian zinc transporters) and glial fibrillary acidic protein (GFAP) were compared among PRE, pharmacosensitive epileptic (PRE), and normal (NRC) rats. Results: The PRE rats displayed severe synapses, neuronal degeneration, and necrosis. Moreover, the expression of ZnT3 and GFAP was significantly increased in both PRE and PSE rats; compared with NRC rats, the promotion of this expression was more pronounced in the PRE rats. Conclusions: Taken together, obvious synapses, neuronal degeneration, necrosis, mossy fiber sprouting, and astrogliosis were found in the drug-resistant epileptic rat model induced by amygdala kindling.

抽象: Lymphangioleiomyomatosis (LAM) is a rare, slowly progressing, low-grade metastatic tumor primarily affecting women. Currently, vascular endothelial growth factor–D (VEGF-D) is the only validated diagnostic biomarker, enabling diagnosis of LAM without the need for lung biopsy in appropriate clinical settings. However, VEGF-D concentrations are normal in about 30% of patients, rendering it insufficient for diagnosing all cases of LAM. There remains a need to identify more non-invasive, safe, sensitive, and specific biomarkers associated with LAM. Therefore, it is imperative to explore novel non-invasive, safe, and specific diagnostic methods for LAM. This article aims to review biomarkers associated with LAM, including potential biomarkers newly discovered or showing advancements in classical biomarkers widely used in LAM, and discuss their application in LAM diagnosis, assessment of disease severity, prediction of treatment response, and prognosis.淋巴管平滑肌瘤病 （LAM） 是一种罕见的、进展缓慢的低级别转移性肿瘤，主要影响女性。目前，血管内皮生长因子-D （VEGF-D） 是唯一经过验证的诊断生物标志物，无需在适当的临床环境中进行肺活检即可诊断 LAM。然而，约 30% 患者的 VEGF-D 浓度正常，不足以诊断所有 LAM 病例。仍然需要确定与 LAM 相关的更多无创、安全、敏感和特异性的生物标志物。因此，当务之急是探索新型无创、安全和特异性的 LAM 诊断方法。本文旨在回顾与 LAM 相关的生物标志物，包括新发现的潜在生物标志物或显示出 LAM 中广泛使用的经典生物标志物的进展，并讨论它们在 LAM 诊断、疾病严重程度评估、治疗反应预测和预后中的应用。

Objectives: Lymphangioleiomyoma (LAM) is a rare multisystemic disease with variable clinical manifestations. This study aim to evaluate the potential of neutrophils and neutrophil-to-lymphocyte ratio (NLR) in predicting treatment response and prognosis in LAM.Methods: Lymphangioleiomyoma patients hospitalized in the respiratory department from January 2013 to January 2024 were retrospectively collected. Baseline data, routine blood tests, pulmonary function, and lung computed tomography (CT) were recorded, and the NLR was calculated. Patients were divided into pneumothorax and no-pneumothorax groups based on pneumothorax occurrence. Differences between the two groups were compared, and significantly different indicators were further analyzed.Results: A total of 78 patients with LAM were included in the study, 42 of them developed pneumothorax from registration to the end of follow-up, and 36 did not develop pneumothorax. There were differences in neutrophils, eosinophils, and NLR between the two groups (P < 0.05). Further analysis revealed that neutrophils and NLR were negatively correlated with lung function in LAM patients (P < 0.05), and positively correlated with lung CT grading and pneumothorax occurrence. Sirolimus treatment reduced neutrophil and NLR values in the pneumothorax group of LAM patients in (P < 0.05).Conclusion: Lymphangioleiomyoma patients with higher neutrophil and NLR values have worse lung function and may be more susceptible to spontaneous pneumothorax, and sirolimus treatment reduces neutrophil and NLR values in LAM patients with pneumothorax.