Publications by authors named "Gen Lin"

Lung cancer patients with leptomeningeal metastases (LMs) suffer from severe clinical symptoms, poor quality of life, narrow diagnostic and therapeutic time windows, low response to standard treatments, short survival periods, and poor prognoses. At present, there is a lack of precise diagnosis and treatment pathways and relevant consensus for LMs of lung cancer. In order to better guide the clinical diagnosis and treatment of LMs of lung cancer in an early, reasonable, and safe way, the experts of the Neurological Tumor Specialist Committee of the Chinese Society of Clinical Oncology (CSCO) have formulated this consensus based on the actual diagnosis and treatment of LMs of lung cancer in China, with reference to the latest research data, relevant guidelines and consensus, and the experts' clinical experience, as well as the results of experts' polling on the pre-set issues of LMs.

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Neuronal loss is the ultimate driver of neural system dysfunction in Alzheimer's disease (AD). We used single-nucleus RNA sequencing and neuropathological phenotyping to elucidate mechanisms of neurodegeneration in AD by identifying vulnerable neuronal populations and probing for their differentially expressed genes. Evidenced by transcriptomic analyses and quantitative tau immunoassays of human AD and non-AD brain tissue, we identified a neuronal population especially vulnerable to tau pathology.

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Background: Although advancements in cancer therapies have substantially improved the survival of cancer patients, these treatments may also result in acute or chronic lung injury. Cancer treatment-related lung injury (CTLI) presents with a diverse array of clinical manifestations and can involve multiple sites. Due to the lack of specific diagnostic protocols, CTLI can deteriorate rapidly and may be life-threatening if not promptly addressed.

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Alzheimer's disease (AD) is characterized by the accumulation and spread of Tau intraneuronal inclusions throughout most of the telencephalon, leaving hindbrain regions like the cerebellum and spinal cord largely spared. These neuropathological observations, along with the identification of specific vulnerable sub-populations from AD brain-derived single nuclei transcriptomics, suggest that a subset of brain regions and neuronal subtypes possess a selective vulnerability to Tau pathology. Given the inability to culture neurons from patient brains, a disease-relevant in vitro model which recapitulates these features would serve as a critical tool to validate modulators of vulnerability and resilience.

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Background: Alectinib has been established as a standard of care for patients with treatment-naive anaplastic lymphoma kinase-rearranged (ALK-positive) advanced non-small-cell lung cancer (NSCLC); however, it has rarely been compared with the sequential approach (crizotinib followed by alectinib) in China. This study aimed to compare real-world alectinib upfront data with either real-world sequential approach data or clinical trial first-line alectinib data.

Methods: The patients who received alectinib in the real-world setting were monitored from August 2016 to November 2020.

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Alterations in the mesenchymal-epithelial transition factor () gene are critical drivers of non-small cell lung cancer (NSCLC). In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients. These alterations include exon 14 skipping mutations ( exon 14 skipping), gene amplifications, point mutations (primarily kinase domain mutations), and MET protein overexpression.

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Alveolar type II cells, the primary stem cell population in the distal lung epithelium, are known to be the most common cell of origin for lung adenocarcinoma. A recent study published in Cell Stem Cell reveals that KRASG12D-mutant alveolar type II cells hijack lung regeneration programs to initiate lung adenocarcinoma, resembling "Dr. Jekyll and Mr.

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Introduction: Retrospective studies have indicated the potential benefits of immunotherapy for brain metastases (BMs) in NSCLC. To our knowledge, CTONG 2003 is the first randomized controlled trial to evaluate camrelizumab for untreated BM of NSCLC.

Methods: CTONG 2003 is a multicenter, randomized, double-blind, placebo-controlled trial.

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Background: The proportion and impact of minimal pleural effusion (PE) on prognosis remain blurred in operable non-small cell lung cancer (NSCLC) patients who reported minimal PE on imaging.

Methods: Clinical and prognostic data of operable NSCLC patients who presented no distant metastasis, no direct pleural invasion, but minimal PE on preoperative imaging were retrospectively analyzed. The patients were divided into surgical (81 cases) and non-surgical (10 cases) cohorts.

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Article Synopsis
  • Accurate detection of driver gene mutations is key for treating lung cancer, but traditional methods require high-quality tissue samples and can be too slow or unavailable for many patients, especially in low-resource areas.
  • The study developed an AI model called DeepGEM, which uses routine histological slides to predict gene mutations without needing prior annotation or high-quality samples.
  • The model was trained and tested on a large dataset of lung cancer patients across multiple hospitals in China, showing promising results in predicting gene mutations, which was further validated on external and public datasets.
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The significance of ultrafast laser-induced energy and mass transfer at interfaces has been growing in the field of nanoscience and technology. Nevertheless, the complexity arising from non-linear and non-equilibrium optical-thermal-mechanical interactions results in intricate transitional behaviors. This complexity presents challenges when attempting to analyze these phenomena exclusively through modeling or experimentation.

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Article Synopsis
  • FGFR is a vital receptor involved in growth and tissue repair, but its gene mutations can lead to cancer by disrupting essential processes.
  • Small molecule drugs and antibodies targeting FGFR mutations, like erdafitinib and pemigatinib, have shown clinical efficacy in treating certain cancer types.
  • Effective screening methods for FGFR variants are essential for utilizing FGFR inhibitors in treatment, and a consensus has been developed to standardize diagnosis and treatment processes.
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  • The study focused on analyzing the relationship between Fanconi anemia-related genes and stemness-related genes in lung cancer patients using bioinformatics and data from the TCGA database.
  • A total of eight genes were identified to create a risk score that is an independent prognostic factor for lung cancer, with validation from multiple GEO databases supporting the findings.
  • The research indicated that higher risk scores were linked to lower immune activity and poorer immunotherapy effectiveness, while also identifying SLC2A1 as significantly correlated with B cells and other cancer-related characteristics.
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Article Synopsis
  • * BRAF mutations are common in various cancers, and targeted therapies, especially BRAF inhibitors like dabrafenib and trametinib, are developed for treating solid tumors with these mutations.
  • * An expert consensus has been established to improve the diagnosis and treatment of solid tumors with BRAF mutations, focusing on summarizing their clinical features, recommending genetic testing methods, and creating a systematic approach for patient care.
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Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer's disease (AD) neuropathology remain unexplored. Here we performed single-nucleus RNA sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology across 32 donors spanning the entire normal aging to severe AD continuum. We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across the AD-vulnerable neural network (spatial axis) or AD pathology stage (temporal axis).

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Plasma epidermal growth factor receptor mutation (EGFRm) circulating tumor DNA (ctDNA) dynamics exhibit promise in predicting outcomes in patients with EGFRm-advanced non-small cell lung cancer (NSCLC). However, there remains limited trial-level data on integrating ctDNA monitoring into clinical practice. We performed a prospective, multicenter trial to investigate the relationship between EGFRm ctDNA dynamic changes and clinical outcomes in NSCLC patients with EGFRm.

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We aimed to investigate the immunological significance of M2 macrophage-related genes in lung cancer (LC) patients, specifically focusing on constructing a risk score to predict patient prognosis and response to immunotherapy. We developed a novel risk score by identifying and incorporating 12 M2 macrophage-related genes. The risk score was calculated by multiplying the expression levels of risk genes by their respective coefficients.

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Article Synopsis
  • The study explores how pretreatment pulmonary tumor necrosis (PTN) affects the prognosis of patients with advanced lung squamous cell carcinoma (LSCC) undergoing anti-PD-1/PD-L1 therapy.
  • It analyzed data from 240 patients treated at 27 hospitals in China, finding that PTN was present in 39.6% of the cases, and was associated with worse median progression-free survival (6.5 months vs 8.6 months).
  • The research concluded that PTN is an independent predictor of shorter progression-free survival but did not find a significant difference in overall survival rates between patient groups.
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Purpose: The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations.

Methods: This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with exon 14 skipping (ex14)-mutant NSCLC who had not previously received inhibitors.

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  • The study investigates the relationship between PD-L1 expression levels and the effectiveness of combination therapy in patients with thymic epithelial tumors (TETs).
  • Results show that higher PD-L1 expression is linked to better progression-free survival (PFS) and overall survival (OS) in patients undergoing treatment, indicating that PD-L1 levels might be a crucial factor in therapy response.
  • The findings suggest that assessing PD-L1 expression could inform treatment decisions, emphasizing the need for targeted therapies alongside current combination treatments in clinical practice.
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Background: Although immune checkpoint inhibitor treatment for advanced thymic carcinoma exhibits promising efficacy, factors that affect the efficacy and prognosis, including metastases sites, remain uncertain.

Objectives: Our study aimed to investigate the determinants of survival among patients with advanced thymic carcinoma who underwent immunotherapy in real-world settings, with implications for clinical practice.

Designs: Different therapy regimens of immunotherapy were produced to analyze the influence of liver metastases on survival and prognosis for advanced thymic carcinoma patients.

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Background: In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC.

Methods: From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L).

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Objective: Non-small cell lung cancer (NSCLC) is a prevailing LC characterized by poor outcomes. AlkB homolog 5 (ALKBH5) functions as a tumor suppressor in several cancers. This study delved into the role of ALKBH5 in NSCLC development.

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Human microglia are critically involved in Alzheimer's disease (AD) progression, as shown by genetic and molecular studies. However, their role in tau pathology progression in human brain has not been well described. Here, we characterized 32 human donors along progression of AD pathology, both in time-from early to late pathology-and in space-from entorhinal cortex (EC), inferior temporal gyrus (ITG), prefrontal cortex (PFC) to visual cortex (V2 and V1)-with biochemistry, immunohistochemistry, and single nuclei-RNA-sequencing, profiling a total of 337,512 brain myeloid cells, including microglia.

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