Silent mutations within the RAS  gene have garnered increasing attention for their potential roles in tumorigenesis and therapeutic strategies. Kirsten-RAS ( KRAS ) mutations, predominantly oncogenic, are pivotal drivers in various cancers. While extensive research has elucidated the molecular mechanisms and biological consequences of active KRAS  mutations, the functional significance of silent mutations remains relatively understudied. This review synthesizes current knowledge on KRAS  silent mutations, highlighting their impact on cancer development. Silent mutations, which do not alter protein sequences but can affect RNA stability and translational efficiency, pose intriguing questions regarding their contribution to tumor biology. Understanding these mutations is crucial for comprehensively unraveling KRAS -driven oncogenesis and exploring novel therapeutic avenues. Moreover, investigations into the clinical implications of silent mutations in KRAS -mutant tumors suggest potential diagnostic and therapeutic strategies. Despite being in early stages, research on KRAS  silent mutations holds promise for uncovering novel insights that could inform personalized cancer treatments. In conclusion, this review underscores the evolving landscape of KRAS  silent mutations, advocating for further exploration to bridge fundamental biology with clinical applications in oncology.
Humans ; Mutation/genetics* ; Neoplasms/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Animals

The mesenchymal-epithelial transition factor (MET) gene, located on human chromosome 7, plays a crucial role in the regulation of physiological processes such as cell proliferation, migration, invasion, and angiogenesis. The MET gene is one of the key drivers in non-small cell lung cancer (NSCLC), with various forms of abnormalities including MET exon 14 (METex14) skipping mutations, MET gene amplification, MET fusions, MET protein overexpression, MET activating mutations and etc. With an increasing understanding of the mechanisms underlying MET abnormalities, therapeutic strategies targeting these abnormalities have gained significant attention, and numerous studies have confirmed that NSCLC patients with MET abnormalities can derive substantial benefits from such treatments. Lung Cancer Specialty Committee of Chinese Elderly Health Care Association organized a panel of experts to provide professional recommendations on current clinical issues in the diagnosis and treatment of MET-aberrant NSCLC, combining clinical practice experiences and evidence-based medical evidences. The "Expert Consensus on Diagnosis and Treatment of NSCLC with MET Abnormalities (2025 Version)" has been formulated to provide standardized guidances for clinical practice in China, with the aim of optimizing the treatment outcomes.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Consensus ; Mutation

OBJECTIVE To investigate the protective effects and potential mechanism of penehyclidine hydrochloride （PHC） on myocardial ischemia-reperfusion （I/R） injury in mice through the macrophage migration inhibitory factor （MIF）/adenosine monophosphate-activated protein kinase （AMPK） signaling pathways. METHODS Male C57BL/6 mice were randomly divided into sham operation group， I/R group， I/R+PHC group （PHC 20 μg/kg）， I/R+ISO-1 group （MIF inhibitor 35 mg/kg）， I/R+ PHC+ISO-1 group （with the same dosage as each single drug group）， with 8 mice in each group. Except for the sham operation group， the myocardial I/R injury model was prepared by coronary artery ligation. Thirty minutes before ligation， mice in each drug group were injected with 1 mL of the corresponding drug solution through the tail vein. After 120 min of reperfusion， the levels of cardiac function indexes [heart rate， stroke volume， ejection fraction， cardiac output， left ventricular posterior wall thickness in systole （LVPWs）， left ventricular posterior wall thickness in diastole （LVPWd）]， serum inflammatory factors [interleukin-6 （IL- 6）， IL-10， tumor necrosis factor-α （TNF-α）] in mice were detected in each group； the pathological changes and ultrastructure of myocardial tissue were observed， and the protein expressions of B cell lymphoma-2 （Bcl-2）， phosphorylated AMPKα （p-AMPKα） and MIF in myocardial tissue were detected. RESULTS Compared with the sham operation group， the myocardial cells in the I/R group were loosely arranged， with severe infiltration of inflammatory cells and obvious mitochondrial damage. Serum levels of IL-6 and TNF-α and protein expression of p-AMPKα in myocardial tissue were significantly increased or upregulated， while heart rate， stroke volume， ejection fraction， cardiac output， LVPWd and serum level of IL-10 were significantly decreased （P＜0.05）. Compared with the I/R group， the myocardial tissue lesions in the I/R+PHC group were alleviated； serum levels of IL-6 and TNF-α were decreased significantly， while heart rate， stroke volume， ejection fraction， cardiac output， LVPWs， LVPWd， serum level of IL-10， and protein expressions of Bcl-2， p- AMPKα and MIF in myocardial tissue were significantly increased or upregulated （P＜0.05）. However， myocardial tissue lesions of mice in the I/R+ISO-1 group worsened， with most quantitative indicators significantly deteriorating （P＜0.05）； MIF inhibitor could generally reverse the protective effect of PHC on I/R mice （P＜0.05）. CONCLUSIONS PHC can improve cardiac function， reduce myocardial inflammation， and restore the ultrastructure of myocardial tissue in I/R mice. These effects may be related to the activation of the MIF/AMPK signaling pathway.

Objective·To summarize the clinical features,imaging features,and diagnosis and treatment experience of primary mediastinal yolk sac tumor(YST).Methods·Data of 29 patients with primary mediastinal YST,who attended Shanghai Chest Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to May 2023,were collected and comprehensively analyzed,including imaging examination results,serum indicators,pathology reports and treatment methods.Results·There were 22 cases of pure YST and 7 cases of mixed YST comprising 28 males and 1 female.The mean age of onset was(24.5±5.9)years.The initial symptoms were chest tightness(34.5%),chest pain(27.8%),cough(34.5%),expectoration(34.5%)and no specific symptoms(24.1%).Chest computerized tomography(CT)enhancement showed that all the 29 lesions were located in the anterior mediastinum.The maximum diameter of the lesions ranged from 5.6 cm to 18.2 cm.The lesions were irregular in shape,uneven in density,partially cystic and solid in density.The enhancement scan showed the solid part was slightly and moderately enhanced,and the low-density area was not enhanced.Tumor boundary was not clear because tumors often compressed and invaded surrounding tissues.Among the 29 newly diagnosed patients,serum alpha-fetoprotein(AFP)was significantly increased in 28 cases(1 case was not tested).Patients received multidisciplinary comprehensive treatment,including chemotherapy(25/29),surgery(26/29),and radiotherapy(8/29).Seven patients directly received surgery after diagnosis.Nineteen patients received chemotherapy first and then surgery;16(84.2%)cases were evaluated as lesion shrinkage after chemotherapy.After surgery,73.1%(19/26)patients had a significant decrease in serum AFP.After chemotherapy,56.0%(14/25)patients had decreased serum AFP.Conclusion·Primary mediastinal YST usually occurs in middle-aged and young men,with certain clinical and radiographic features and elevated serum AFP,which requires multidisciplinary comprehensive treatment.

BACKGROUND: Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches. METHODS: We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs. RESULTS: The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling. CONCLUSION We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.
Humans ; Thymoma ; Protein-Tyrosine Kinases/genetics* ; Proto-Oncogene Proteins/genetics* ; China ; Thymus Neoplasms/pathology* ; Prognosis ; Neuroendocrine Tumors/pathology* ; Mutation/genetics*

Objective : To explore the relationship between the methylation level of RABL6 in peripheral blood and early lung cancer (LC) with a case-control study in the Chinese population． Methods : The methylation levels of 7 CpG sites in RABL6 gene in peripheral blood of samples from 275 LC patients (81．5% at stage I) ，and age- and gender-matched 185 benign lung nodule cases and 267 matched healthy controls were measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry．Multinomial Logistic regression adjusted for covariates was used to analyze the association between the RABL6 methylation and LC．Mann-Whitney U test was applied for the comparisons of RABL6 methylation levels between clinical characteristics subgroups of LC. Results : Compared to the healthy controls，the methylation of RABL6 _CpG_ 17 was inversely associated with LC in females ( per - 10% methylation : OR = 2. 47，95% CI = 1. 19－5. 13，P = 0. 016) ，but positively associated with LC in males (per - 10% methylation : OR = 0. 52，95% CI = 0. 29－0. 94，P = 0. 030) ．In addition，hypermethylation of RABL6_CpG _2 and RABL6_CpG_5 was significantly associated with LC in the subjects older than 55 years (for RABL6_CpG_ 2 : per －10% methylation : OR = 0. 77，95% CI = 0. 60－0. 99，P = 0. 038 ; for RABL6_CpG_5 : OR = 0. 58，95% CI = 0. 34－0. 97，P = 0. 038) ． Conclusion The study reveals an association between peripheral blood-based RABL6 methylation levels and early LC，providing a new clue for developing peripheral blood-based DNA methylation as a potential marker for the evaluation of LC risk.

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
Humans ; Lung Neoplasms/drug therapy* ; Treatment Outcome ; Neoplasm Recurrence, Local/chemically induced* ; Quinolines/adverse effects*

Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer (2022 edition) has been published this year. The 2022 edition has been updated in the aspects of lung cancer screening, pathology, standards of thoracic surgery, treatment of metastatic lung cancer. In this study, we tried to introduce those updated aspects in the guideline of 2022 edition.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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