MCM8 promotes lung cancer progression through upregulating DNAJC10.

MCM8 is a helicase, which participates in DNA replication and tumorigenesis and is upregulated in many human cancers, including lung cancer (LC); however, the function of MCM8 in LC tumour progression is unclear. In this study, we found that MCM8 was expressed at high levels in LC cells and tissues. Further, MCM8 upregulation was associated with advanced tumour grade and lymph node metastasis, and indicated poor prognosis. Silencing of MCM8 suppressed cell growth and migration in vitro and in vivo, while ectopic MCM8 expression promoted cell cycle progression, as well as cell migration, proliferation, and apoptosis. Mechanistically, DNAJC10 was identified as a downstream target of MCM8, using gene array and CO-IP assays. DNAJC10 overexpression combatted the inhibitory activity of MCM8 knockdown on LC progression, while silencing DNAJC10 alleviated the oncogenic function of MCM8 overexpression. MCM8 expression was positively correlated with that of DNAJC10 in LC samples from The Cancer Genome Atlas database, and DNAJC10 upregulation was also associated with poor overall survival of patients with LC. This study indicated that MCM8/DNAJC10 axis plays an important role in in LC development, and maybe as a new potential therapeutic target or a diagnostic biomarker for treating patients with LC.

Re-exploration of prognosis in type B thymomas: establishment of a predictive nomogram model.

OBJECTIVE: To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model. METHODS: A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression. RESULTS: A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1-128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively). CONCLUSION: The best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT.

Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis.

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Thermal Ablation of Pulmonary Nodules by Electromagnetic Navigation Bronchoscopy Combined With Real-Time CT-Based 3D Fusion Navigation:Report of One Case.

A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.

Delayed Discharge after Thoracic Surgery under the Guidance of ERAS Protocols.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been applied in thoracic surgery and are beneficial to patients. However, some issues about ERAS are still pending. METHODS: A total of 1,654 patients who underwent thoracic surgery under the guidance of ERAS protocols were enrolled in this study. We set the length of postoperative stay (LOPS) as our key research indicator. Patients were divided into routine discharge group and delayed discharge group based on LOPS. Causes of delayed discharge were analyzed to improve management of postoperative recovery. RESULTS: Male, old age, underlying disease (coronary artery disease, chronic kidney disease, old cerebral infarction, chronic obstructive pulmonary disease, and arrhythmia), intensive care unit (ICU) stay, type of insurance, and lower forced expiratory volume in one second (FEV1) are the independent impact factors causing delayed discharge. Increased nonchylous drainage (INCD) and prolonged air leakage were the two leading causes for delayed discharge. CONCLUSION: Patients should have personalized recovery goal under the same ERAS protocols. We should accept that patients in poor general condition have a prolonged LOPS. More stringent ICU stay indications should be developed to increase postoperative patients' ERAS protocols compliance. Further research on chest tube management will make a contribution to ERAS protocols.

Single-cell transcriptomics reveals the drivers and therapeutic targets of lymph node metastasis in lung adenocarcinoma.

Lymph node metastasis (LNM) is usually the most common metastatic pathway in lung adenocarcinoma (LUAD) and is associated with a poorer prognosis and higher possibility of recurrence. Therefore, discovering the drivers and therapeutic targets of LNM is important for early and non-invasive detection of patients with a high risk of LNM and guiding individualized therapy. Various cell constitutions of the primary tumor and lymph node microenvironment was characterized based on scRNA-seq data. The copy number variation (CNV) analysis was performed to probe clonal structures and origins of metastatic lymph nodes, and found 6q loss and 20q gain may drive LNM in LUAD. Then a LNM-related cell subset, named Scissor+ cells, was identified using the Scissor algorithm. And cell-cell communication network among Scissor+ cells and microenvironment was further analyzed. Besides, a pro-LNM signature was subsequently constructed based on 27 genes using pseudotime trajectory analysis and gene set variation analysis. The pro-LNM signature showed a significant correlation with N stage and a good predictive ability of LUAD survival. At last, we identified that erastin and gefitinib could potentially inhibit LNM by targeting Scissor+ cells based on the drug sensitivity data of the cancer cell lines, which provided new insights for LUAD therapy.

The 100 most cited papers on thymoma: a bibliometric analysis.

OBJECTIVES: The aim of this bibliometric analysis was twofold: to identify the 100 most cited research articles on thymoma and to highlight future research opportunities in light of past and current research efforts. METHODS: The Web of Science database was queried to identify the 100 most cited articles on thymoma. Imformations relevant to scientific research were extracted and analyzed: first author, journal, impact factor, type of article, year of publication, country, organization and keywords. RESULTS: The publication year of the top 100 most cited articles ranged from 1981 to 2018, and the number of citations ranged from 97 to 1182. Most of the included articles are original (75/100) and are mainly retrospective studies (52/75). The United States has the most published articles and citations, and the Annals of Thoracic Surgery is the most sourced journal (n = 16). Through VOSviewer analysis, high-density keywords mainly come from thymic carcinoma/invasive thymoma management, immune-related diseases, and laboratory research. CONCLUSIONS: To our knowledge, this is the first bibliometric study on thymoma. We found most of the top 100 most cited articles are original and retrospective research. The United States has the published and cited works. Presently, the hot keywords for thymoma research has gradually tilted towards immune-related diseases and laboratory research.

Predictive value of clinical characteristics on risk and prognosis of synchronous brain metastases in small-cell lung cancer patients: A population-based study.

BACKGROUND: Patients with small-cell lung cancer (SCLC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis, which causes a heavy burden of morbidity and mortality. A better understanding of the demographic and tumor-specific characteristics of these patients is critical to guiding clinical practice. The purpose of this study was to investigate the predictive and prognostic value of the clinical characteristics of SCLC patients with SBM at initial diagnosis. METHODS: This is a retrospective study based on the data in the latest Surveillance, Epidemiology, and End Results (SEER) version which was released in 2021 for patients diagnosed with SCLC in the presence or absence of SBM from 2010 to 2018. Multivariable logistic regression was performed to identify predictors of the presence of SBM at the initial diagnosis. Kaplan-Meier curves and multivariable Cox regression models were built to compare the prognosis of patients with different clinical characteristics and treatments. RESULTS: A total of 33,169 SCLC patients were enrolled in this study, including 5711 (17.2%) patients with SBM and 27,458 (82.8%) patients without SBM. Patients who are black(HR = 1.313, 95% CI = 1.167-1.478, p < 0.001), higher T stage (T2, HR = 1.193, 95%CI = 1.065-1.348, p = 0.005; T3, HR = 1.169, 95%CI = 1.029-1.327, p = 0.016; T4, HR = 1.259, 95%CI = 1.117-1.418, p < 0.001), lung metastases (HR = 1.434, 95%CI = 1.294-1.588, p < 0.001) and bone metastases (HR = 1.311, 95% CI = 1.205-1.426, p < 0.001) had greater odds of SBM at initial diagnosis. The median overall survival (OS) for SCLC patients with SBM was 5.0 months. Multivariable Cox regression revealed that age ≥ 65 (HR = 1.164, 95% CI = 1.086-1.247, p < 0.025), singled (HR = 1.095, 95% CI = 1.020-1.174, p = 0.012), higher T stage (T3, HR = 1.265, 95% CI = 1.123-1.425, p < 0.001; T4, HR = 1.192, 95% CI = 1.066-1.332, p = 0.002), higher N stage (N2, HR = 1.347, 95%CI = 1.214-1.494, p < 0.001; N3, HR = 1.452, 95%CI = 1.292-1.632, p < 0.001), liver metastases (HR = 1.415, 95%CI = 1.306-1.533, p < 0.001), and bone metastases (adjusted HR = 1.126, 95%CI = 1.039-1.221, p = 0.004). Analysis of treatment regimens showed that patients who received combinational treatment exhibited longer OS than chemotherapy or radiotherapy alone, and surgery combined with chemotherapy and radiotherapy exhibited the longest OS. CONCLUSIONS: In this study, we identified risk factors for SBM in SCLC patients and prognostic indicators among this patient population. We also found that patients who received different therapeutic strategies exhibited significant difference on OS, which will provide evidence-based support for treatment options.

USP5 knockdown alleviates lung cancer progression via activating PARP1-mediated mTOR signaling pathway.

BACKGROUND: With the rapidly increasing morbidity and mortality, lung cancer has been considered one of the serious malignant tumors, affecting millions of patients globally. Currently, the pathogenesis of lung cancer remains unclear, hindering the development of effective treatment. This study aims to investigate the mechanisms of lung cancer and develop an effective therapeutic approach for intervention in preventing lung cancer progress. METHODS: The USP5 levels are detected in lung cancerous and paracancerous tissue by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to explore their roles in lung cancer progression. MTT, colony assay, and transwell chamber approaches are employed to measure cell viability, proliferation, and migration, respectively. Further, flow cytometry experiments are performed to examine the effect of USP5 on lung cancer. Finally, the investigations in vivo are executed using the mice subcutaneous tumor model to identify the effect of USP5 in promoting lung cancer development. RESULTS: Notably, USP5 is highly expressed in lung cancer, USP5 overexpression promoted the proliferation and migration in the lung cancer cell lines, H1299 and A549, while knockdown of USP5 inhibited these via regulating the PARP1-mediated mTOR signaling pathway. Furthermore, the subcutaneous tumors model was established in C57BL/6 mice, and the volume of subcutaneous tumors was significantly reduced after silencing USP5, while increased after USP5 overexpression and decreased significantly with shRARP1 treatment at the same time. CONCLUSIONS: Together, USP5 could promote the progression of lung cancer cells by mTOR signaling pathway and interacting with PARP1, indicating that USP5 may become a new target for lung cancer treatment.

Identification of predictors of long-term survival and prognostic outcomes in thymic squamous cell carcinoma: A real-world study.

BACKGROUND: Although thymic squamous cell carcinoma (TSCC) is among the most prevalent forms of thymic carcinoma, there are relatively few studies on this tumor type, and its staging, optimal treatment strategies, and relevant prognostic factors remain controversial. METHODS: The present study analyzed 79 patients diagnosed with TSCC between January 2008 and January 2021. Kaplan-Meier curves and Cox univariate and multivariate regression analyses were used to explore factors associated with overall survival (OS) and progression-free survival (PFS) in the overall patient cohort and patient subgroups stratified according to the TNM stage. Time-dependent receiver operating characteristic (ROC) analyses were used to compare the TNM and Masaoka systems as predictors of patient prognosis. RESULTS: The 5- and 10-year OS rates in this study were 65.5% and 49.4%, respectively, with corresponding 5- and 10-year PFS rates of 52.3% and 37.9%. Survival outcomes were better for patients with early-stage disease (p < 0.001) and patients that underwent surgical treatment (p < 0.001). Neither extent of resection (p = 0.820) nor the surgical approach (p = 0.444) influenced patient survival. In individuals with advanced disease, all forms of adjuvant therapy including radiotherapy (p = 0.021), chemotherapy (p = 0.035), and chemoradiation (p = 0.01) significantly improved patient PFS, but only adjuvant chemoradiotherapy improved patient OS (p = 0.035). When predicting the patient survival outcomes, the TNM system was slightly superior to the Masaoka system (area under the ROC curve [AUC] at 5 years: OS, 0.742 vs. 0.723; PFS, 0.846 vs. 0.816). CONCLUSION: TSCC is an orphan malignancy with a poor prognosis. TNM staging may be superior to Masaoka staging as a predictor of TSCC patient prognosis. Surgery is the mainstay of TSCC treatment. Video-assisted thoracoscopy (VATS) should be considered for selected patients. Multimodal therapy was associated with excellent results for patients with advanced TNM stage, particularly when surgery was accompanied by adjuvant chemoradiation.

Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma.

BACKGROUND: Brain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined. METHODS: The cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate the cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data indicating a high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines. RESULTS: Differences in macrophages and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and their biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital. We further evaluated the clinical significance of the BM-index and identified 7 drugs that potentially target BMAECs. CONCLUSIONS: This study clarified possible cellular origins and drivers of metastatic LUAD at the single-cell level and laid a foundation for early detection of LUAD patients with a high risk of BM.

Real-world study of treatment and outcome of type B2 + B3 thymoma: The neglected part of thymoma.

BACKGROUND: This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma. METHODS: We conducted a retrospective analysis of the results of 39 patients with type B2 + B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3 thymoma. The Kaplan-Meier technique was used to generate survival curves. For multivariate analysis, the Cox proportional hazard model was applied. RESULTS: With a median follow-up of 60 months (range: 1-128 months), the percentage of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2, B2 + B3, and B3, respectively, p = 0.045. Twenty-three patients experienced recurrence or metastasis. The total 10-year progression-free survival (PFS) rates were 86.0% overall (85.0% in type B2, 87.2% in type B2 + B3, and 87.5% in type B3). Age, R0 resection, and Masaoka-Koga stage were found to have a significant on PFS in all patients. There was no statistically significant difference in PFS between different histotypes of thymoma, p = 0.650. PFS was predicted by R0 resection in all histotypes and by the Masaoka-Koga stage in the type B2 subgroup. CONCLUSION: Combining the two staging methods to guide the diagnosis and treatment of patients with B2 + B3 thymoma is recommended. R0 resection is recommended to reduce recurrence. Patients with B2 + B3 thymoma have a prognosis similar to those with a B2 thymoma or a B3 thymoma alone.

SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer.

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

Mucosa-associated lymphoid tissue lymphoma in thymus: a SEER analysis.

OBJECTIVES: The present study explores an extremely rare disease, thymic mucosa-associated lymphoid tissue (MALT) lymphoma, for its characteristics and prognostic factors by analyzing the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From 2000 to 2018, cases with a diagnosed thymic MALT lymphoma were extracted. Clinical characteristics, treatments, and survival patterns of these cases were analyzed. RESULTS: Thymic MALT lymphoma (n = 26) accounted for 0.09% of all MALT lymphomas. With a sex ratio of 0.53 (male/female), 68% white population was affected. Most cases were diagnosed with Ann Arbor stage I (50%), yet advanced-stage did not show worse prognosis (p = 0.236). Different treatment protocols did not influence the overall prognosis (p > 0.99). The 5- and 10- year overall survival rates were 83.1% and 78.2%, respectively. Older than 70 years may be an independent risk factor for overall survival (HR = 7.166 [95% CI 1.173-43.756], p = 0.033). CONCLUSION: Thymic MALT lymphoma is a highly rare disease with a favorable prognosis. Ann Arbor staging might not be appropriate to classify severity of this disease or its treatment. Older people may have worse survival. A standardized treatment mode needs to be established, and surgery could remain as the mainstay.

Surgical Treatment of Ectopic Mediastinal Parathyroid Tumors: A 23-Year Clinical Data Study in a Single Center.

Background. Ectopic mediastinal parathyroid glands are parathyroid glands located completely below the clavicle. At present, most literature reports on ectopic mediastinal parathyroid tumors (EMPT) are case reports or small case sequences.Methods. This study conducted a retrospective analysis of ectopic mediastinal parathyroid tumors cases treated over the past 23 years, summarizing and analyzing general conditions, preoperative positioning, postoperative pathology, intraoperative conditions, and long-term follow-up results.Results. This study enrolled 28 patients. Among them, 27 patients underwent preoperative localization diagnosis using 99mTc-sestamibi scan (MIBI) in conjunction with chest computed tomography (CT), including 26 cases of the anterior superior mediastinum and 2 cases of middle mediastinum. Postoperative pathology revealed 23 cases of parathyroid adenoma, 4 cases of parathyroid hyperplasia, and 1 case of parathyroid cyst. In this study, 12 patients underwent video-assisted thoracoscopic surgery (VATS) and thoracotomy approaches. Using Mann-Whitney U test, we discovered that VATS approach group is significantly superior in surgical time (P = 0.039) and intraoperative bleeding (P < 0.001). Within one week of surgery, 26 patients with primary hyperparathyroidism (PHPT) experienced a significant decrease in blood parathyroid hormone (PTH) (P < 0.001) and blood calcium (P < 0.001), and all achieved long-term remission.Conclusions. EMPT is most frequently performed in the anterior superior mediastinum. EMPT is predominantly parathyroid tumors, and most of them are associated with PHPT. MIBI and chest CT combination can be used for preoperative lesion localization (positive rate 96.15%). VATS can be used as a better surgical approach. PHPT patients before surgery can achieve long-term symptom relief with surgical treatment.

Comparative analysis of the long-term outcomes of segmentectomy and lobectomy for stage IA1 lung adenocarcinoma in patients with or without previous malignancy of other organs: a population-based study.

BACKGROUND: For early stage non-small cell lung cancer, whether limited resection can yield comparable outcomes to those of lobectomy hasn't been established. We compared Overall survival (OS) and lung cancer-specific survival (LCSS) after segmentectomy or lobectomy in stage IA1 (≤10 mm) lung adenocarcinoma (LUAD) patients. RESEARCH DESIGN AND METHODS: We retrospectively recruited patients who'd been diagnosed with lung cancer for the first time and treated with segmentectomy or lobectomy, with or without previous other malignancy. RESULTS: 1788 patients were included. After propensity score matching: 5-year OS were 85.6% for segmentectomy and 84.7% for lobectomy (p=0.951); 5-year LCSS were 93.5% for segmentectomy; and 93.0% for lobectomy (p=0.726). Cox regression analysis revealed segmentectomy was comparable to lobectomy in OS and LCSS. Having a second lung cancer later in life was associated with a worse LCSS for lobectomy (p<0.05) rather than segmentectomy. After patients were stratified according to malignancy history, subgroup analyses showed no significant prognosis differences between two surgeries. CONCLUSIONS: For stage IA1 LUAD patients who were diagnosed with lung cancer for the first time, with or without previous other malignancy, segmentectomy yields comparable outcomes to those of lobectomy. It may provide better outcomes for patients with multiple suspicious nodules.

Conservative therapy for spinal epidural hematoma in a child with hemophilia A with high-titer VIII inhibitors.

The occurrence of a spinal epidural hematoma in patients with hemophilia A with high-titer VIII inhibitors is extremely rare and intractable. A 15-year-old male patient presented to our institution with acute back pain and progressive sensorimotor disorder of the bilateral lower extremities. He had hemophilia A with high-titer VIII inhibitors and had experienced recurrent hemorrhagic episodes for many years. Prompt magnetic resonance imaging revealed a spinal epidural hematoma. We administered bypassing agent therapy with prothrombin complex concentrates and performed intensive neurological monitoring. The neurological dysfunction improved with days, and the patient recovered completely within 3 weeks. Magnetic resonance imaging 1 year later showed that the hematoma had been completely absorbed. Spinal epidural hematomas in patients with hemophilia A with high-titer inhibitors can be successfully treated using prothrombin complex concentrates. Multidisciplinary discussions based on intensive neurological monitoring should be performed as early in the clinical course as possible.

Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis-related genes.

BACKGROUND: Lung squamous cell carcinoma (LUSC), one of the main pathological types of lung cancer, has led to consequential socioeconomic burden. Ferroptosis is an iron-dependent form of cell death process with potentials for therapeutic target in various kinds of tumors. However, whether ferroptosis-related genes (FRGs) are associated with the prognosis of LUSC patients is still unclear. The aim of this study was to establish a FRGs-based signature which could stratify patients with LUSC. METHODS: The RNA sequencing profiles and corresponding clinical data of LUSC patients were retrieved from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) dataset. A FRG-based signature was developed using the TCGA-LUSC cohort and validated in the GEO cohort. Gene set enrichment analysis (GSEA) and analysis of immune cell characteristics were conducted to assess the relationship between FRGs and biological function or immune status. A nomogram based on selected clinical factors and the risk scores which were generated from the FRG-based signature was developed using the TCGA cohort and validated in the GEO cohort. RESULTS: A set of 16 FRGs, significantly associated with overall survival (OS) in the TCGA cohort, was identified and could classify LUSC patients into two risk groups. Kaplan-Meier analysis illustrated that the survival rate of the high-risk group was significantly lower than the low-risk group. Assessment and external validation of the signature showed that the survival predictive performance of this signature was adequate. Additionally, multiple pathways and functions were enriched through GSEA and the analysis of immune cell characteristics showed significantly different abundances of immune cells among the two risk groups. Finally, a nomogram integrating the FRG-based signature and selected clinical factors was also developed and assessed in both the TCGA and GEO cohort. CONCLUSION: This study indicated the association between the FRGs and prognosis of patients with LUSC. Targeting ferroptosis may serve as a novel potential therapeutic alternative for LUSC.

Primary desmoplastic fibroblastoma of diaphragm.

Desmoplastic fibroblastoma is an extremely rare benign soft tissue tumor and desmoplastic fibroblastoma originating from the diaphragm has not been documented previously. In our case, we report the first primary diaphragm desmoplastic fibroblastoma.

Surgical treatment is effective in treating thymoma accompanied with non-myasthenia gravis autoimmune diseases: a single-center clinical experience.

BACKGROUND AND AIMS: Although thymoma is inextricably linked to autoimmune disease, its best treatment method remains unclear. In this study, we sought to evaluate therapeutic effect of surgical resection of thymoma on non-myasthenia gravis autoimmune diseases. MATERIALS AND METHODS: This was a retrospective study covering 32 patients with thymoma accompanied with non-myasthenia gravis autoimmune disease. The relationships between surgical treatment, thymoma pathological type, and prognosis of autoimmune diseases were analyzed from postoperative follow-up data. RESULTS: In total, 32 patients in this study underwent surgical treatment. The mean age of the patients was 51.7 years. By the last follow-up, 2 patients had died, while the other 30 patients showed no sign of tumor recurrence and metastasis. According to the postoperative follow-up data, 22 patients (68.75%) showed improvement or even complete recovery of autoimmune disease symptoms, 9 patients (28.13%) showed no significant change, and only 1 patient's (3.12%) postoperative symptom was aggravated. Female patients and patients aged 50 and older were more likely to combine with non-organ-specific autoimmune diseases (p = 0.036, p = 0.017). CONCLUSIONS: In conclusion, this study presents that surgical treatment achieves a satisfactory prognosis for thymoma combined with non-myasthenia gravis autoimmune disease.