Clinical and Genetic Characteristics of Early-Onset Lung Adenocarcinoma in a Large Chinese Cohort.

BACKGROUND: The characteristics of early-onset lung adenocarcinoma (EOLA) have not been extensively studied. Our research aimed to comprehensively assess the clinical and genetic features of EOLA. METHODS: We conducted a retrospective analysis of surgically resected lung adenocarcinoma patients, categorizing them into the EOLA group (aged <40 years) and the late-onset lung adenocarcinoma (LOLA) group (aged >60 years). A comparative investigation of clinical, germline, and genomic features was conducted. Propensity score matching was used to balance baseline characteristics for gene mutation analysis. RESULTS: We enrolled 487 EOLA and 2507 LOLA patients. EOLA patients exhibited a higher female-to-male ratio (2.55 vs 1.19) and a higher proportion of family history of lung cancer in the ground-grass opacity subgroup (12.7% vs 8.9%). The EOLA group exhibited higher rates of earlier stage in the ground-grass opacity subgroup and solid subgroup. Preinvasive adenocarcinoma was the dominant histologic subtype in the EOLA group within the ground-glass opacity subgroup (73.8% vs 25.6%). After propensity score matching, we analyzed 241 stage 0/I patients with available genetic test results. Significant disparities in gene mutation rates emerged between the EOLA and LOLA patients, including Erb-B2 receptor tyrosine kinase 2 (ERBB2; 38.0% vs 2.8%), epidermal growth factor receptor (EGFR; 36.0% vs 64.5%), MET (0.0% vs 7.1%), neurofibromin 1 (NF1; 0.0% vs. 5.7%), and anaplastic lymphoma kinase (ALK) fusion (10.0% vs 1.4%). CONCLUSIONS: EOLA patients exhibited distinct clinical and genetic characteristics compared with LOLA patients.

Bidirectional Mendelian Randomization of Causal Relationship between Inflammatory Cytokines and Different Pathological Types of Lung Cancer.

Prior research has proposed a potential association between lung cancer and inflammatory cytokines, yet the specific causal relationship remains unclear, especially across various lung cancer pathologies. This study utilized bidirectional Mendelian randomization (MR) to explore these causal connections, unveiling novel insights. Our research revealed distinctive inflammatory cytokine profiles for each subtype of lung cancer and identified potential biomarkers that could refine diagnostic and therapeutic approaches. We applied two-sample Mendelian randomization, leveraging genetic variance data from three extensive genome-wide association studies (GWAS) focusing on different lung cancer types (lung adenocarcinoma: 1590 cases and 314,193 controls of healthy individuals of European descent; lung squamous cell carcinoma: 1510 cases and 314,193 controls of European ancestry; small cell lung cancer: 717 cases and 314,193 controls of European ancestry). A separate GWAS summary on inflammatory cytokines from 8,293 healthy participants was also included. The inverse variance weighting method was utilized to examine causal relationships, with robustness confirmed through multiple sensitivity analyses, including MR-Egger, weighted median, and MR-PRESSO. Our analysis revealed that elevated levels of IL_1RA were associated with an increased risk of lung adenocarcinoma (OR: 1.29, 95% CI: 1.02-1.64, p = 0.031), while higher MCP_1_MCAF levels correlated with a decreased risk of lung squamous cell carcinoma (OR: 0.77, 95% CI: 0.61-0.98, p = 0.031). Furthermore, IL_10, IL_13, and TRAIL levels were positively associated with lung squamous cell carcinoma risk (IL_10: OR: 1.27, 95% CI: 1.06-1.53, p = 0.012; IL_13: OR: 1.15, 95% CI: 1.06-1.53, p = 0.036; TRAIL: OR: 1.15, 95% CI: 1.06-1.53, p = 0.043). No association was found between inflammatory cytokine levels and small cell lung cancer development, whereas SDF_1A and B-NGF were linked to an increased risk of this cancer type (SDF_1A: OR: 1.13, 95% CI: 1.05-1.21, p = 0.001; B-NGF: OR: 1.13, 95% CI: 1.01-1.27, p = 0.029). No significant relationship was observed between the 41 circulating inflammatory cytokines and lung adenocarcinoma or squamous cell carcinoma development. Our findings indicate distinct associations between specific inflammatory cytokines and different types of lung cancer. Elevated IL_1RA levels are a risk marker for lung adenocarcinoma, whereas higher MCP_1_MCAF levels appear protective against lung squamous cell carcinoma. Conversely, elevated levels of IL_10, IL_13, and TRAIL are linked with an increased risk of lung squamous cell carcinoma. The relationships of SDF_1A and B-NGF with small-cell lung cancer highlight the complexity of inflammatory markers in cancer development. This study provides a nuanced understanding of the role of inflammatory cytokines in lung cancer, underscoring their potential in refining diagnosis and treatment strategies.

Efficacy and safety of microwave ablation and its synergistic potential in the treatment of early-stage non-small cell lung cancer.

Lung cancer remains the primary cause of cancer-related mortality globally. In the case of early-stage non-small cell lung cancer (NSCLC), surgical resection, such as lobectomy and sub-lobectomy, continues to be the established standard treatment. However, for patients with insufficient cardiopulmonary function and multiple comorbidities who are unable to undergo surgical resection, nonoperative local therapies, including radiotherapy and thermal ablation, are preferred. In recent years, microwave ablation (MWA) has gained popularity for treating early-stage NSCLC due to its high heating efficiency, good tissue conductance, and heat conduction capabilities. This review provides a comprehensive summary of the current efficacy and safety data regarding MWA for early-stage NSCLC and discusses the potential benefits of combining MWA with other therapies.

Strategies for the Emergency Treatment of Pregnant Women with Neurological Symptoms during the COVID-19 Pandemic.

Coronavirus disease-19 (COVID-19) has been spreading all over the world for more than two years. Though several kinds of vaccines are currently available, emergence of new variants, spike mutations and immune escape have raised new challenges. Pregnant women are vulnerable to respiratory infections due to their altered immune defence and surveillance functions. Besides, whether pregnant persons should receive a COVID-19 vaccine is still under debate because limited data are available on the efficacy and safety of receiving a vaccine during pregnancy. Physiological features and lack of effective protection making pregnant women at high risk of getting infected. Another concern is that pregnancy may trigger the onset of underlying existing neurological disease, which is highly similar to those neurological symptoms of pregnant women caused by COVID-19. These similarities interfere with diagnosis and delay timely and effective management. Therefore, providing efficient emergency support for pregnant women suffering from neurological symptoms caused by COVID-19 remains a challenge among neurologists and obstetricians. To improve the diagnosis and treatment efficiency of pregnant women with neurological symptoms, we propose an emergency management framework based on the clinicians' experience and available resources. This emergency care system aimed at addressing the conundrums faced by the emergency guarantee system under COVID-19 pandemic and could serve as a potential multisystem project for clinical practice and medical education.

Constructing a diversified online neurology teaching model under the COVID-19.

Purpose: To construct a diversified and comprehensive network teaching model to provide highly qualified medical teaching in neurology under COVID-19 pandemic. Materials and methods: Published studies on medical education were systematically reviewed and summarized. Based on previous studies and our experience, we constructed a novel online neurology teaching model and applied it to real scene. Students taking traditional in class lessons and online lessons were asked to finish the test, respectively, to compare the efficiency of learning. Questionnaires were designed and assigned to get the feedback from students. Results: The average test score of students who take online class (84.27 ± 4.64) was significantly higher than those who take in class lessons (82.08 ± 6.17) (P < 0.01). According to the feedbacks from students, online classes were more attractive to students than the conventional one. Conclusion: Traditional single-mode teaching can no longer meet the needs of current medical education, especially under the rampant epidemic. This novel teaching mode, which orchestrates high-tech tools, diverse teaching methods and traditional teaching concepts, provides the solution to the challenge faced by traditional medical education. We believe that this novel online teaching mode will boost neurology education and inspire educators in other fields during this tough period.

Long Noncoding RNA X-Inactive-Specific Transcript Promotes the Secretion of Inflammatory Cytokines in LPS Stimulated Astrocyte Cell Via Sponging miR-29c-3p and Regulating Nuclear Factor of Activated T cell 5 Expression.

Background: Astrocyte activation promotes glutamate accumulation and secretion of inflammatory factors, mainly responsible for epilepsy. Long noncoding RNA (lncRNA) X-inactive-specific transcript (XIST) regulates inflammation; however, the biological role and regulatory mechanism of XIST during astrocyte activation remain unclear. Methods: In the present study, rat epilepsy model and lipopolysaccharide (LPS)-treated CTX-TNA2 were established. XIST and miR-29c-3p expression were evaluated using quantitative real-time polymerase chain reaction. Nuclear factor of activated T cells 5 (NFAT5) was measured using western blot analysis. Interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and L-glutamate levels in the culture supernatants were assessed using enzyme-linked immunosorbent assay. The binding between XIST and miR-29c-3p and between miR-29c-3p and the 3'-UTR of NFAT5 was analyzed using dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and Biotin pull-down assay. The proliferation and apoptosis were evaluated using CCK8 and flow cytometry, respectively. Results: XIST expression and NFAT5 protein level was increased, whereas miR-29c-3p expression was decreased in the epilepsy rat model and LPS-treated CTX-TNA2 cells. Silenced XIST expression, miR-29c-3p overexpression, or silenced NFAT5 expression inhibited the secretion of IL-1ß, IL-6, and TNF-α and promoted glutamate transport in LPS-treated CTX-TNA2 cells. miR-29c-3p was the potential miRNA sponged by XIST. NFAT5 acted as a direct binding target of miR-29c-3p. Silenced miR-29c-3p expression or NFAT5 overexpression reversed the effect of silenced XIST expression on LPS-treated CTX-TNA2.XIST and miR-29c-3p treatment does not affect NFAT5 mRNA expression, but affects NFAT5 protein level. Furthermore, underexpressed XIST or overexpressed miR-29c-3p in LPS-stimulated CTX-TNA2 can attenuate neuronal apoptosis induced by LPS-stimulated CTX-TNA2. Conclusion: LncRNA XIST promotes the secretion of inflammatory cytokines in LPS- treated CTX-TNA2 via sponging miR-29c-3p and regulating NFAT5 expression.

Lynch syndrome-associated repeated stroke with MLH1 frame-shift mutation.

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms. Previous studies showed that MLH1, MSH2, MSH6, and PMS2 mutation in LS were associated with an elevated risk of colorectal, gastric, endometria, ovarian, and other cancers among family members. Patients of these kinds of cancers had high incidence of synchronous and metasynchronus. We describe the case of a 34-year-old female patient with 50 days of sudden dizziness and left limb weakness, whose head CT scan showed large infarction in the right frontal temporal parietal lobe and basal ganglia area. Imaging examinations and pathological biopsy indicated high-grade serous carcinoma (HGSC) IIIA1 of the right ovary. In addition, a novel frame-shift mutation in the MLH1 gene (c.1621dupG, p.A541Gfs*16) was found in the genetic panel sequence. It may render declining of MLH1 protein and also associate with the patient's progressive clinical manifestations of multiple systems. Therefore, the timely use of prenatal diagnosis to prevent unnecessary new cases of this severe genetic disease is available.

Knowledge, attitudes and anxiety toward COVID-19 among domestic and overseas Chinese college students.

BACKGROUND: To investigate the knowledge, attitudes and anxiety toward COVID-19 among Chinese college students studying in China and abroad. METHOD: A structured questionnaire, comprised of demographic characteristics, knowledge and attitudes toward COVID-19 and the State-Trait Anxiety Inventory (STAI), was used to collect data for 566 domestic students and 126 students studying abroad. RESULTS: Domestic students were better than students abroad in knowledge of epidemiology and manifestations. Domestic students showed a significant higher enthusiasm for voluntary services than students abroad, including medical science popularization, community services, traffic dispersion, logistics transportation and being volunteers for vaccine trials. The scores (Mean ± SD) of S-AI and T-AI among students abroad were 59.48 ± 8.63 and 54.10 ± 7.20, respectively, which were significantly higher than those of domestic students (39.46 ± 8.16 and 39.25 ± 7.72). CONCLUSIONS: Our study showed a better understanding of knowledge, more positive attitudes and less anxiety toward COVID-19 among domestic students, compared with students studying abroad. In light of this information, more attention and appropriate psychological and social intervention should be paid to college students with anxiety, especially those studying abroad.

Al-doped α-MnO2 coated by lignin for high-performance rechargeable aqueous zinc-ion batteries.

Zn/MnO2 batteries, one of the most widely studied rechargeable aqueous zinc-ion batteries, suffer from poor cyclability because the structure of MnO2 is labile with cycling. Herein, the structural stability of α-MnO2 is enhanced by simultaneous Al3+ doping and lignin coating during the formation of α-MnO2 crystals in a hydrothermal process. Al3+ enters the [MnO6] octahedron accompanied by producing oxygen vacancies, and lignin further stabilizes the doped Al3+ via strong interaction in the prepared material, Al-doped α-MnO2 coated by lignin (L + Al@α-MnO2). Meanwhile, the conductivity of L + Al@α-MnO2 improves due to Al3+ doping, and the surface area of L + Al@α-MnO2 increases because of the production of nanorod structures after Al3+ doping and lignin coating. Compared with the reference α-MnO2 cathode, the L + Al@α-MnO2 cathode achieves superior performance with durably high reversible capacity (∼180 mA h g-1 at 1.5 A g-1) and good cycle stability. In addition, ex situ X-ray diffraction characterization of the cathode at different voltages in the first cycle is employed to study the related mechanism on improving battery performance. This study may provide ideas of designing advanced cathode materials for other aqueous metal-ion batteries.

Difficulties and Countermeasures in Hospital Emergency Management for Fast-Lane Treatment of Acute Stroke During the COVID-19 Epidemic Prevention and Control.

Background: Coronavirus disease 2019 (COVID-19) has a long incubation period and a high degree of infectivity. Patients may not show specific signs or symptoms of upper respiratory tract infection, and the age of onset is similar to that of stroke. Furthermore, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. Providing emergency treatment for acute stroke in accordance with the strict epidemic control measures is currently one of the main challenges, as acute stroke is rapid onset and a major cause of death and disability globally. We aimed to evaluate the emergency treatment system for acute stroke during the epidemic control period to provide a reference and basis for informing government and medical institutions on improving patient treatment rates during this period. Methods: Difficulties faced in providing emergency treatment for stroke during an epidemic were investigated and combined with medical educational resources and clinical management experiences to construct an emergency treatment framework for acute stroke during the epidemic. Findings: Currently, emergency treatment measures for acute stroke during the epidemic control period are limited because the main focus is on identifying COVID-19 comorbidities during the critical period. Establishing standards for patients in the neurological outpatient consultation rooms and emergency observation and resuscitation zones; implementing a fast-lane system for the emergency treatment of patients with acute stroke, and strengthening ward management and medicine popularization, can improve the treatment efficiency for stroke patients during the epidemic and provide a reference for peers in clinical practice. Interpretation: Emergency treatment for acute stroke during COVID-19 epidemic control period requires a joint promotion of clinical, popularization, and teaching resources.

Differential Diagnosis and Hospital Emergency Management for Fastlane Treatment of Central Nervous System Infection Under the COVID-19 Epidemic in Changsha, China.

Importance: Corona virus disease 2019 (COVID-19) has long latent period, strong infectivity, and non-specific symptoms and signs in the upper respiratory tract. Some initial neurological symptoms appear, including dizziness, headache, seizures, slurred speech, disturbance of consciousness, and limb paralysis among a few COVID-19 patients, which share similar manifestations with central nervous system (CNS) infection. Improving the diagnostic efficiency of suspected CNS infection patients on the basis of preventing and controlling COVID-19 plays a key role in preventing nosocomial and cross infections. This study intends to formulate a hospital emergency management system of fastlane treatment of CNS infection for epidemic prevention and control, aiming at providing references and guidelines for the government and medical institutions to improve the efficiency of treating CNS infection patients in the clinical practice during COVID-19. Observations: This study formulated a framework of a fastlane treatment of CNS infection based on the cooperation of resources and experience, aiming at the key and difficult problems faced by the hospital emergency management system during the COVID-19 outbreak in Changsha, China. The main problem of formulating the hospital emergency management system is efficiently identifying whether CNS infection was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The framework improves the efficiency of diagnosing and treating CNS infections by standardizing the diagnosis and treatment process of patients in emergency observation and strengthening the management of inpatient wards, aiming at assisting medical staff during clinical practice. Conclusions and Relevance: The hospital emergency management system of a fastlane treatment of CNS infection for epidemic prevention and control of the COVID-19 outbreak is a professional and multisystem project, which needs the cooperation of various resources and the experience of clinical leadership.

LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s.

Brain microvascular endothelial cell (BMEC) survival and angiogenesis after ischemic stroke has great significance for improving the prognosis of stroke. Abnormal variants of lncRNAs are closely associated with stroke. In this study, we examined the effects and molecular mechanisms of differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis, migration, and angiogenesis of oxygen-glucose deprivation (OGD)-treated BMECs. We found that DANCR expression significantly increased at 2, 4, 6, 8, and 10 h after OGD. DANCR overexpression promoted cell viability, migration, and angiogenesis in OGD-treated BMECs. Additionally, we found that X-box binding protein l splicing (XBP1s) expression was positively correlated with DANCR expression. DANCR overexpression promoted XBP1s expression in OGD-treated BMECs. Silenced XBP1s reversed the effect of DANCR in OGD-treated BMECs. Furthermore, we found that microRNA (miR)-33a-5p bound to DANCR and the 3'-UTR of XBP1. miR-33a-5p overexpression inhibited proliferation, migration, angiogenesis, and XBP1s expression in OGD-treated DANCR-overexpressing BMECs, reversing the protective effect of DANCR. Finally, we found that XBP1s expression promoted proliferation, migration, and angiogenesis, reversing the damaging effect of miR-33a-5p. In conclusion, DANCR enhanced survival and angiogenesis in OGD-treated BMECs through the miR-33a-5p/XBP1s axis.

Synchrotron Radiation-Based Three-Dimensional Visualization of Angioarchitectural Remodeling in Hippocampus of Epileptic Rats.

Characterizing the three-dimensional (3D) morphological alterations of microvessels under both normal and seizure conditions is crucial for a better understanding of epilepsy. However, conventional imaging techniques cannot detect microvessels on micron/sub-micron scales without angiography. In this study, synchrotron radiation (SR)-based X-ray in-line phase-contrast imaging (ILPCI) and quantitative 3D characterization were used to acquire high-resolution, high-contrast images of rat brain tissue under both normal and seizure conditions. The number of blood microvessels was markedly increased on days 1 and 14, but decreased on day 60 after seizures. The surface area, diameter distribution, mean tortuosity, and number of bifurcations and network segments also showed similar trends. These pathological changes were confirmed by histological tests. Thus, SR-based ILPCI provides systematic and detailed views of cerebrovascular anatomy at the micron level without using contrast-enhancing agents. This holds considerable promise for better diagnosis and understanding of the pathogenesis and development of epilepsy.