Causal relationship between telomere length and risk of intracranial aneurysm: a bidirectional Mendelian randomization study.

Background: Telomere length is closely linked to the aging phenotype, where cellular aging results in the production of a cascade of cell factors and the senescence-associated secretory phenotype (SASP), leading to an inflammatory response. The presence of inflammation plays a crucial role in the formation of intracranial aneurysms. Nevertheless, the relationship between telomere length and intracranial aneurysms remains unclear. This study aims to explore the causal connection between telomere length and intracranial aneurysms through the utilization of Mendelian randomization (MR) analysis. Methods: Data on telomere length were obtained from the genome-wide association studies conducted on the UK Biobank, comprising a total of 472,174 participants. Data on intracranial aneurysms were obtained from the summary dataset of the Global Genome-wide Association Study (GWAS) conducted by the International Stroke Genetics Consortium. The dataset consisted of 7,495 cases and 71,934 controls, all of European descent. Initially, the linkage disequilibrium score was used to investigate the connection between telomere length and intracranial aneurysms. Subsequently, a bidirectional MR was conducted using two-sample analysis to assess whether there is a causal connection between telomere length and intracranial aneurysm risk. The results were analyzed utilizing five MR methods, with the inverse variance weighted method serving as the main methodology. In addition, we did various analyses to evaluate the presence of heterogeneity, pleiotropy, and sensitivity in the study results. A reverse MR analysis was conducted to investigate potential reverse causal links. Results: In the forward MR analysis, it was observed that both the inverse variance-weighted and weighted median analyses implied a potential causal relationship between longer telomere length and a decreased incidence of intracranial aneurysms (IVW: OR = 0.66, 95% CI: 0.47-0.92, p = 1.49 × 10-2). There was no heterogeneity or horizontal pleiotropy. The findings were verified to be robust through the utilization of leave-one-out analysis. The use of reverse MR analysis did not establish a potential causal link between the occurrence of intracranial aneurysms and telomere length. Conclusion: There may exist a potential correlation between longer telomere length and a decreased likelihood of intracranial aneurysms within the European population. The present study offers novel insights into the correlation between telomere length and intracranial aneurysms. Additional research is required to clarify the underlying mechanisms and validate our discoveries in diverse populations.

The Importance of M1-and M2-Polarized Macrophages in Glioma and as Potential Treatment Targets.

Glioma is the most common and malignant tumor of the central nervous system. Glioblastoma (GBM) is the most aggressive glioma, with a poor prognosis and no effective treatment because of its high invasiveness, metabolic rate, and heterogeneity. The tumor microenvironment (TME) contains many tumor-associated macrophages (TAMs), which play a critical role in tumor proliferation, invasion, metastasis, and angiogenesis and indirectly promote an immunosuppressive microenvironment. TAM is divided into tumor-suppressive M1-like (classic activation of macrophages) and tumor-supportive M2-like (alternatively activated macrophages) polarized cells. TAMs exhibit an M1-like phenotype in the initial stages of tumor progression, and along with the promotion of lysing tumors and the functions of T cells and NK cells, tumor growth is suppressed, and they rapidly transform into M2-like polarized macrophages, which promote tumor progression. In this review, we discuss the mechanism by which M1- and M2-polarized macrophages promote or inhibit the growth of glioblastoma and indicate the future directions for treatment.

Tracheal tunica adventitia invasion after lobectomy in patients with non-small cell lung cancer.

BACKGROUND: For patients with non-small cell lung cancer, a negative margin status is required for radical pulmonary surgery. Residual disease of the margin has been thoroughly studied in the past few decades. However, the prognostic significance of tracheal tunica adventitia invasion after lobectomy remains unclear. In this study, we aimed to investigate the clinical influence of tracheal tunica adventitia invasion after lobectomy. METHODS: We retrospectively collected the clinical data of 591 patients who consecutively underwent pulmonary lobectomy, including sleeve lobectomy, between 2012 and 2018 at Shanghai Chest Hospital. According to the tracheal tunica adventitia invasion status, we allocated the patients into 2 groups (tracheal tunica adventitia invasion and non-tracheal tunica adventitia). Disease-free and overall survival were evaluated, and we discussed the necessity of radiotherapy in patients with tracheal tunica adventitia. RESULTS: After propensity score matching to balance baseline characteristics, there were 167 individuals in the tracheal tunica adventitia invasion and non-tracheal tunica adventitia groups. In the hazard analysis, we found that tracheal tunica adventitia increased the risk of recurrence (hazard ratio: 0.652; P = .002) and impaired long-term survival (P < .001). Subgroup analysis revealed that tracheal tunica adventitia was an important risk factor, especially when the hilar lymph nodes were positive. In addition, tracheal tunica adventitia invasion promoted extra-thoracic lymph node metastasis. We discovered that radiotherapy did not improve the prognosis of patients in the tracheal tunica adventitia invasion group. CONCLUSIONS: After lobectomy, tracheal tunica adventitia invasion is a risk factor for non-small cell lung cancer and potentially increases extra-thoracic lymph node metastasis. Moreover, tracheal tunica adventitia invasion is not sensitive to postoperative radiotherapy.

Mucosa­associated lymphoid tissue in the central nervous system presenting as meningioma: A case report.

Mucosa-associated lymphoid tissue (MALT) lymphoma involving meningeal tissue is rare condition, easily mistaken for meningiomas upon imaging. In this report, a case of primary left temporal lobe MALT lymphoma that was initially misdiagnosed as temporal meningioma is presented, with subsequent investigation into the mechanism and treatments. Clinically, MALT lymphomas can be easily confused with meningiomas based solely on imaging and clinical manifestations. MALT lymphomas are indolent, localized lesions that can be cured through surgical resection and radiotherapy. Currently, radiotherapy is the most commonly used treatment; however, the patient in the present report did not receive any chemotherapy or radiotherapy after surgery, and recent related examinations revealed a recurrence of lymphomas that had metastasized throughout the body. As a result, future patients may benefit from chemotherapy or radiotherapy, and clinicians should be more meticulous regarding patient follow-up.

The consideration of surgery on primary lesion of advanced non-small cell lung cancer.

BACKGROUND: Numerous reports have shown that medical treatment confers excellent survival benefits to patients with advanced stage IV non-small cell lung cancer (NSCLC). However, the implications of surgery for primary lesions as palliative treatment remain inconclusive. METHODS: We retrospectively extracted clinical data from the Surveillance, Epidemiology, and End Results Program (SEER) database and selected patients with stage IV NSCLC. Patients were classified into non-surgery and surgery groups, and propensity score matching (PSM) analysis was performed to balance the baseline information. Patients in the surgery group, whose overall survival (OS) was longer than the median survival time of those in the non-surgery group, were deemed to benefit from surgery. We evaluated the efficacy of three surgical techniques, namely, local destruction, sub-lobectomy, and lobectomy, on the primary site in the beneficial population. RESULTS: The results of Cox regression analyses revealed that surgery was an independent risk factor for both OS (hazard ratio [HR]: 0.441; confidence interval [CI]: 0.426-0.456; P < 0.001) and cancer-specific survival (CSS) (HR: 0397; CI: 0.380-0.414; P < 0.001). Notably, patients who underwent surgery had a better prognosis than those who did not (OS: P < 0.001; CSS: P < 0.001). Moreover, local destruction and sub-lobectomy significantly compromised survival compared to lobectomy in the beneficial group (P < 0.001). After PSM, patients with stage IV disease who underwent lobectomy needed routine mediastinal lymph node clearing (OS: P = 0.0038; CSS: P = 0.039). CONCLUSION: Based on these findings, we recommend that patients with stage IV NSCLC undergo palliative surgery for the primary site and that lobectomy plus lymph node resection should be conventionally performed on those who can tolerate the surgery.

The location of visceral pleural invasion in stage IB patients with non-small cell lung cancer: Comparison and prognosis.

OBJECTIVES: Recently, early-stage lung cancer has been drawing more attention, especially in screening and treatment. Visceral pleural invasion in stage IB cancer is considered as risk factor for poor prognosis. Herein, we aimed to study the distinction between the different locations of visceral pleural invasion. METHODS: In this retrospective cohort study, we summarized 58,242 patient cases that underwent surgery from 2015 to 2018 at Shanghai Chest Hospital. Of those patients, 389 met the inclusion criteria. Patients with PL3 pleural invasion were excluded. The patients were dichotomized into the interlobar pleural and peripheral pleural groups. The outcomes measured were overall survival (OS) and recurrence-free survival (RFS) rates. RESULTS: According to the initial analysis, the baseline characteristics of the two groups were largely balanced. In multivariate Cox analyses, we found that the location of visceral pleural invasion was not a risk factor for prognosis in the overall population (RFS: P = 0.726, OS: P = 0.599). However, we discovered that relative to patients with peripheral pleura invasion, those with interlobar pleura invasion, PL1 invasion, lesions with greater than 3 cm solid components, and those who underwent segmentectomy had a compromised prognosis. Additionally, tumors larger than 3 cm in size with interlobar pleura invasion showed poor prognosis in patients who underwent postoperative chemotherapy. CONCLUSIONS: In most cases, the location of tumor invasion did not worsen the postoperative prognosis of stage IB non-small cell lung cancer patients with visceral pleural invasion. However, interlobar pleural invasion still had some potential risks compared to that of peripheral pleural invasion.

Inhibition of NADPH oxidase 2 (NOX2) reverses cognitive deficits by modulating excitability and excitatory transmission in the hippocampus after traumatic brain injury.

Traumatic brain injury (TBI) is a closed or open head injury caused by external mechanical forces that induce brain damage, resulting in a wide range of postinjury dysfunctions of emotions, learning and memory, adversely affecting the quality of life of patients. In this study, we aimed to explore the possible mechanisms of NOX2 on cognitive deficits in a TBI mouse model. Behavioral tests were applied to evaluate learning and memory ability, and electrophysiological experiments were performed to measure synaptic transmission and intrinsic excitability of the CA1 pyramidal cells (PCs) and long-term potentiation (LTP) in the TBI hippocampus. We found that inhibitors of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2; NOX2) (GSK2795039 and apocynin) attenuate neurological deficits, facilitate long-term potentiation (LTP) and decrease spontaneous synaptic transmission and intrinsic excitability of CA1 pyramidal cells (PCs) in traumatic brain injury (TBI) mice. NOX2-/- mice display reduced learning and memory impairment, enhanced LTP and reduced spontaneous synaptic transmission and intrinsic excitability of PCs after TBI. Our study demonstrates that NOX2 is a potential target for learning and memory by modulating excitability and excitatory transmission in the hippocampus after TBI.

The outcomes of margin status after sleeve lobectomy for patients of non-small cell lung cancer.

BACKGROUND: Sleeve lobectomy is recognized as an alternative surgical operation to pneumonectomy because it preserves the most pulmonary function and has a considerable prognosis. In this study, we aimed to investigate the implications of residual status for patients after sleeve lobectomy. METHODS: In this retrospective cohort study, we summarized 58 242 patients who underwent surgeries from 2015 to 2018 in Shanghai Chest Hospital and found 456 eligible patients meeting the criteria. The status of R2 was excluded. The outcomes were overall survival (OS) and recurrence-free survival (RFS). We performed a subgroup analysis to further our investigation. RESULTS: After the propensity score match, the baseline characteristic was balanced between two groups. The survival analysis showed no significant difference of overall survival and recurrence-free survival between R0 and R1 groups (OS: p = 0.053; RFS: p = 0.14). In the multivariate Cox analysis, we found that the margin status was not a dependent risk factor to RFS (p = 0.119) and OS (p = 0.093). In the patients of R1, N stage and age were closely related to OS, but we did not find any significant risk variable in RFS for R1 status. In the subgroup analysis, R1 status may have a worse prognosis on patients with more lymph nodes examination. On further investigation, we demonstrated no differences among the four histological types of margin status. CONCLUSION: In our study, we confirmed that the margin status after sleeve lobectomies was not the risk factor to prognosis. However, patients with more lymph nodes resection should pay attention to the margin status.

Reconstruction of the trachea and carina: Surgical reconstruction, autologous tissue transplantation, allograft transplantation, and bioengineering.

There have been significant advancements in medical techniques in the present epoch, with the emergence of some novel operative substitutes. However, the treatment of tracheal defects still faces tremendous challenges and there is, as yet, no consensus on tracheal and carinal reconstruction. In addition, surgical outcomes vary in different individuals, which results in an ambiguous future for tracheal surgery. Although transplantation was once an effective and promising method, it is limited by a shortage of donors and immune rejection. The development of bioengineering has provided an alternative for the treatment of tracheal defects, but this discipline is full of ethical controversy and hindered by limited cognition in this area. Meanwhile, progression of this technique is blocked by a deficiency in ideal materials. The trachea together with the carina is still the last unpaired organ in thoracic surgery and propososal of a favorable scheme to remove this dilemma is urgently required. In this review, four main tracheal reconstruction methods, especially surgical techniques, are evaluated, and a thorough interpretation conducted.