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Non-small cell lung cancer (NSCLC) is one of the most malignant cancer types, characterized by a poor prognosis. N6-methyladenosine (m6A) is a prevalent internal modification of mRNA. METTL14, an RNA methyltransferase that mediates m6A modification, is implicated in mRNA biogenesis. However, the biomechanism of METTL14 in NSCLC is not very clear.Here, immunohistochemical (IHC) assay was employed to detect METTL14 in NSCLC tissues. The biological functions of METTL14 were demonstrated using cell transfection, cell proliferation assay, cell clone formation assay, cell cycle analysis, cell death analysis, transwell and wound healing assays. Transcriptome and methylated RNA immunoprecipitation (MERIP)-sequencing were used to explore the pathways and potential mechanism of METTL14 in NSCLC. RNA sequencing, METTL14 rip-sequencing, and METTL14 merip-sequencing were conducted to identify the potential targets of METTL14.METTL14 was significantly correlated with clinical pathological parameters of differentiation and M stage. Additionally, METTL14 promotes cell proliferation, induces cell death, and enhances cell migration and invasion in vitro. Transcriptome and MeRIP-sequencing reveal oncogenic mechanism of METTL14. RIP-sequencing highlights CSF1R and AKR1C1 as targets of METTL14. After validation with TCGA dataset, colony stimulating factor 1 receptor (CSF1R) showed significant positive coefficient with METTL14, and was presumed to be one target of METTl14 in lung cancer and verified by the cellular experiments.In conclusion, our results revealed the clinical significance of m6A RNA modification atlas, the function, and molecular targets CSF1R of METTL14 in NSCLC cell lines. The RNA m6A methyltransferase METTL14 promotes the progression of NSCLC by targeted CSF1R.

At present, with the rapid development of artificial intelligence technology, all industries are facing huge impacts and challenges. The entry of artificial intelligence into the judicial field has also become an unstoppable trend in social development. This paper analyzes and discusses the judicial practice of artificial intelligence, divides the existing legal profession into five echelons according to professionalism and substitutability, and analyzes the possibility and specific reasons for the profession to be replaced by artificial intelligence according to the characteristics of each echelon and the metric examples of substitutability. This paper aims to provide some references for the future study, employment and development direction of those who are interested in law.

We explored the association between the serum level of cystatin C (CysC) at admission and short-term functional outcome in patients with hypertensive intracerebral hemorrhage (HICH) without chronic kidney disease (CKD). A total of 555 patients with HICH were consecutively recruited after admission and were followed-up for 3 months after admission. The primary outcome was poor functional outcome (modified Rankin Scale [mRS] score ≥ 3). The median serum CysC level in our cohort was 1.03 mg/L (interquartile range, .89-1.20). Patients were categorized into four groups according to the serum CysC quartiles. Multivariate logistic regression analysis revealed a negative association between serum CysC and poor functional outcome at 3-month follow-up (quartile [Q]1 vs. Q4: adjusted odds ratio [OR] = .260, 95% confidence interval [CI] = .098, .691, p.001). The negative association between serum CysC and poor functional outcome at 3 months was more pronounced in subgroups with smaller hematoma volume (≤ 30 mL), and absence of secondary intraventricular hemorrhage (IVH). Addition of serum CysC to a model containing conventional risk factors improved the model performance with net reclassification index (NRI) of .426% (p.001) and integrated discrimination improvement (IDI) of .043% (p.001) for poor functional outcome. Serum CysC was found to be a negative predictor of poor short-term functional outcome in HICH patients independent of renal function.

Anjun Song,1,&ast; Hui Yang,2,&ast; Guofeng Wu,1 Siying Ren,1 Likun Wang,1 Guannan Qin,1 Yuanhong Mao1 1Emergency Department, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Guiyang Public Health Treatment Center, Guiyang, Guizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Anjun Song, Email 351815967@qq.comObjective: The present study aimed to evaluate the clinical value of minimally invasive surgery for intracranial hematoma removal and high intracranial pressure (ICP) reduction using a novel three-needle brain puncture technique.Methods: A total of 202 cases with supratentorial hematoma were analyzed, 54 of whom received three-needle brain puncture (study group), and the remaining cases received single-needle (control groups 1 and 2) and two-needle brain puncture (control group 3). The amount of intracranial hematoma removed, changes in ICP, retention time of puncture needle, volume of residual blood, the National Institute of Health Stroke Scale (NIHSS) score, and postoperative survival rate were used as indexes to evaluate patient outcomes.Results: We found that three-needle brain puncture (study group) can remove more intracranial hematoma (P < 0.05) and achieve lower ICP (P < 0.05) than single- and two-needle brain puncture (control group). The needle retention time and volume of residual blood significantly decreased in the study group. Additionally, a statistically significant difference was observed in the NIHSS scores and survival rates between the study and control groups (P < 0.05).Conclusion: These data suggest that three-needle minimally invasive stereotactic puncture can effectively remove hematoma, reduce ICP, decrease the degree of brain damage, and improve prognosis.Keywords: cerebral hemorrhage, intracranial pressure monitoring, minimally invasive procedures, three-needle puncture, National Institute of Health Stroke Scale

Wenjuan Yan,1,&ast; Qi Zhang,1,&ast; Yingjie Zhu,1 Nan Jing,1 Youhua Yuan,1 Yi Zhang,2 Siying Ren,3 Dongmei Hu,4 Wenmin Zhao,5 Xiaojuan Zhang,6 Caiqin Shi,7 Meiyun Wang,8 Yi Li1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of China; 2Department of Clinical Laboratory, Zhengzhou Central Hospital, Affiliated to Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Clinical Laboratory, Kaifeng People’s Hospital, Kaifeng, Henan, People’s Republic of China; 4Department of Clinical Laboratory, Zhumadian First People’s Hospital, Zhumadian, People’s Republic of China; 5Department of Clinical Laboratory, Kaifeng Central Hospital, Kaifeng, Henan, People’s Republic of China; 6Department of Clinical Laboratory, Gongyi People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 7Department of Microbiology Laboratory, KingMed Diagnostics, Zhengzhou, Henan, People’s Republic of China; 8Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi LiDepartment of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of ChinaTel +86 159 39039006Email liyilabmed@henu.edu.cnPurpose: To evaluate polymyxin-resistant Klebsiella pneumoniae and Escherichia coli prevalence and characteristics in the Henan province, China.Materials and Methods: A total of 2301 bacterial isolates collected at six hospitals were assessed. Their response to polymyxin was evaluated by minimum inhibitory concentration (MIC) analysis, and the mobilized colistin resistance (mcr) and carbapenemase gene were explored. Mutations on mgrB, phoPQ, pmrAB, and crrAB in polymyxin-resistant K. pneumoniae were detected by PCR. phoP, phoQ, pmrK, pmrA, pmrB, and pmrC transcriptional levels were quantified by RT-qPCR. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing were performed to determine the phylogenetic relationship between the polymyxin-resistant isolates.Results: Of the E. coli and K. pneumoniae isolates identified, 0.3% and 1.4% were polymyxin-resistant, respectively, with MICs of 4– 64 μg/mL. All polymyxin-resistant isolates were susceptible to tigecycline. Four E. coli isolates were mcr-1-positive and one was carbapenem-resistant, carrying blaNDM-5 and mcr-1. One K. pneumoniae isolate was mcr-1-positive and nine were carbapenem-resistant (PRCRKP), carrying blaKPC-2 but not mcr-1. The five E. coli isolates belonged to four sequence types (ST2, ST132, ST632, and ST983). All PRCRKP isolates belonged to ST11. However, all 16 isolates belonged to different PFGE types with < 95% genetic similarity. Insertion sequences in mgrB were detected in nine (81.8%) polymyxin-resistant K. pneumoniae samples. Colistin resistance was linked with pmrHFIJKLM operon upregulation, with phoP, phoQ, and pmrK being overexpressed in all but one of the polymyxin-resistant K. pneumoniae samples. Furthermore, 33.3% of patients carrying polymyxin-resistant isolates had previously used polymyxin, and 66.7% patients displayed good clinical outcomes.Conclusion: The K. pneumoniae polymyxin resistance rate was slightly higher than that of E. coli and mcr-1 was more common in E. coli than in K. pneumoniae. Moreover, the insertion of ISkpn14 into mgrB may be the main contributor to polymyxin-resistance in K. pneumoniae in Henan.Keywords: polymyxin, Escherichia coli, Klebsiella pneumoniae, mcr, Henan province

Lung cancer is the most common cause of cancer death worldwide. Tobacco smoking is the most predominant etiology for lung cancer. However, only a small percentage of heavy smokers develop lung cancer, which suggests that other cofactors are required for lung carcinogenesis. Viruses have been central to modern cancer research and provide profound insights into cancer causes. Nevertheless, the role of virus in lung cancer is still unclear. In this article, we reviewed the possible oncogenic viruses associated with lung cancer.

Objective To explore the molecular mechanism involved in secondary brain damage caused by intracerebral hemorrhage (ICH), we activated microglia by thrombin, to observe the changes of peroxisome proliferator-activated receptor-gamma (PPARγ), nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) mRNA transcription and protein expression in the microglia cells of primary culturing in vitro. Methods Microglial cells were obtained from the brain tissues of the newborn rats and cultured in vitro. The isolated microglia cells were randomly divided into normal control group (NC group) and thrombin stimulation group (TH group). The expression of PPARγ, Nrf2 and HO-1 was tested by immunofluorescence and real-time PCR. Results The immunofluorescence showed that the numbers of stained positive cells of PPARγ, Nrf2 and HO-1 in TH group was increased remarkably as compared with NC group. The results of RT-qPCR showed that the mRNA expression of PPARγ, Nrf2 and HO-1 in TH group was increased significantly as compared with NC group (P Conclusion The expression of PPARγ, Nrf2 and HO-1 in the microglia cells activated by the thrombin were increased. Therefore, the microglia could be activated by intracerebral hemorrhage and the anti-oxidative stress effects of microglia can be improved.

To distinguish whether multiple lung nodules represent multiple primary lung cancers (MPLC) or intrapulmonary metastases (IPM) is crucial for staging and subsequent therapy. We herein present the first report of a patient with two simultaneously resected metachronous lung adenocarcinomas in the right upper lobe, each with a distinct driver mutation in the KRAS gene identified by targeted next generation sequencing (NGS). The nodules appeared chronologically metachronous, with a 3.7 year interval. Histopathology showed two histologically identical adenocarcinomas, without lymph node metastases. It was hard to decide whether they should be classified as either MPLC or IPM based only on the clinicopathological criteria. Sequencing further revealed distinct KRAS mutation in each tumor, with one tumor harboring the KRAS‐G12C mutation, and the other tumor harboring the KRAS‐Q61H mutation. Incorporation of the molecular data cleared the confusion with regard to staging and spared this patient from adjuvant therapy. This case highlights that molecular profiling allows for better differentiation between MPLC and IPM than histopathology alone. Key points To the best of our knowledge, this is the first case of multiple primary lung cancers harboring distinct KRAS mutations. The case highlights the importance of incorporating molecular profiling using NGS along with the clinicopathological criteria in classifying multiple lung tumors.

Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of non-small-cell lung carcinoma associated with Epstein-Barr virus (EBV) infection. We systematically reviewed the recent research that expands our knowledge about PLELC, with main focus on its genetic profile, tumor-infiltrating environment, PD-L1 expression, circulating EBV-DNA, clinical utility of 18F-FDG PET/CT, and treatment strategy. A low frequency of typical driver mutations and widespread existence of copy number variations was detected in PLELC. Persistent EBV infection may trigger intense infiltration of lymphocytes, representing enhanced tumor immunity and possibly resulting in a better prognosis. Circulating EBV-DNA in the plasma of patients with PLELC may predict disease progression and response to therapy. PLELC is 18F-FDG avid, and 18F-FDG PET may help refine palliation strategies and subsequently improve the prognosis. Most of the reported patients present at early and resectable stage, and surgical resection with curative intent is the preferred approach. There is currently no consensus on the regimen of chemotherapy for patients with advanced stages. EGFR-targeted therapies seem to have no therapeutic effect, and the clinical impact of PD-1/PD-L1 therapy is uncertain but worthy of further research.

Left innominate vein aneurysm is extremely rare, with a limited number of case reports present in the literature. Herein, we report a case of a 50-year-old female patient presenting with an incidental finding of an anterior mediastinal mass on chest radiography during a routine health examination. Contrast-enhanced computerized tomography (CT) of the chest showed a 4.8 × 4.6 cm anterior mediastinal mass with significant homogenous enhancement after injection of the contrast medium, suggesting a diagnosis of Castleman's disease, but not excluding thymoma. The patient underwent surgical resection of the anterior mediastinal mass under a thoracoscopic approach. Postoperative pathology confirmed the diagnosis of a left innominate vein aneurysm. This is the first case reporting a left innominate vein aneurysm resected under thoracoscopy. Despite this successful treatment experience, we need to emphasize that open thoracotomy or median sternotomy should be chosen as the first choice for surgeons who lack experience in thoracoscopic surgery, with the aim of avoiding intraoperative accidents.

BackgroundNeoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) represents an important research topic. Despite the potential benefits of this approach, the inflammatory responses and adverse events associated with neoadjuvant chemoimmunotherapy can present technical challenges and compromise a planned resection. This study assessed the safety and feasibility of neoadjuvant chemoimmunotherapy followed by surgery for resectable NSCLC.MethodsThe study was conducted from May 2019 to March 2021. Patients who were age 18 years or older, were diagnosed with stage Ib–IIIb NSCLC, and received neoadjuvant chemoimmunotherapy followed by surgery were included. Demographic information, clinical and pathologic characteristics, data about neoadjuvant therapy, and surgical details were collected by retrospective chart review. Toxicity profiles were collected retrospectively or by telephone follow-up.ResultsTwenty patients were included in this study. The median age was 56 years (range, 48–72 years), and 18 patients (90%) were men. Squamous carcinoma (14/20, 70%) was the most common cancer type, followed by adenocarcinoma (4/20, 20%), adenosquamous carcinoma (1/20, 5%), and large cell neuroendocrine carcinoma (1/20, 5%). All patients received two to four cycles of neoadjuvant therapy, and the median interval between final therapy and surgery was 49 days (range, 23–133 days). Computed tomography evaluation after neoadjuvant therapy showed partial response in 15 patients (75%) and stable disease in 5 (25%). Final pathologic examinations showed major pathologic response in eight patients, including pathologic complete response in five (25%). Most patients (18/20, 90%) had reduced pathologic staging. Twelve patients (60%) underwent open thoracotomy; the other eight patients underwent minimally invasive surgery, which was uneventful and without intraoperative conversion to open thoracotomy. No perioperative deaths occurred, and only seven patients (35%) developed postoperative complications. Most patients experienced only grade 1–2 adverse effects and laboratory abnormalities during neoadjuvant therapy, and no grade 3 or worse adverse effects or laboratory abnormalities occurred. No patients experienced surgical delays as a result of immune-related adverse events.ConclusionsPreoperative administration of chemoimmunotherapy for patients with resectable NSCLC was safe and feasible.

Background We characterized the clinical features, radiographic characteristics, and response to treatment of immunocompetent and immunocompromised patients with pulmonary cryptococcosis (PC). Methods We retrospectively reviewed the medical records and radiological profiles of patients diagnosed with PC who received surgical resection between May 2015 and November 2020 in a tertiary referral center. Results A total of 21 males and 18 females were included in the study. 23 patients were immunocompetent and 20 out of the 39 were asymptomatic. Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients (48.9 vs 57.1 years, P = 0.02). Single nodule pattern was the most frequent lesion pattern (33 out of 39, 84.6%) and right upper lobe was the most common site of location (15 out of 47, 31.9%). The majority of lesions were located peripherally (38 out of 47, 80.9%) and most lesions were 1–2 cm in diameter (30 out of 47, 63.8%). Cavitation was more likely to occur in immunocompromised patients (5 out of 11, 45.5%) than in immunocompetent patients (6 out of 36, 16.7%) (P = 0.04) and there was complete resolution of PC in all patients treated with anti-fungal therapy. Conclusions Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients. Single nodule pattern was the most frequent lesion pattern in PC patients. Cavitation was more likely to occur in immunocompromised patients than in immunocompetent patients.

A patient with thymoma associated immunodeficiency syndrome (Good's syndrome) and bronchiectasis was retrospectively analyzed. Good's syndrome is a rare condition of immunodeficiency that is characterized by thymoma and hypogammaglobulinemia. It is important to bear in mind that Good's syndrome should be included in the differential diagnosis When patients repeatedly visited for bronchiectasis or infection, we should alert to their immune state and history of thymoma. Early screening of immunological status and aggressive correction of immune deficiency are beneficial to improving the prognosis to patients with Good's syndrome.回顾性分析1例胸腺瘤相关免疫缺陷综合征(Good’s综合征)合并支气管扩张病例，结合最新文献从发病机制分析Good’s综合征患者的常见临床症状、实验室检查结果及治疗策略。因支气管扩张、反复感染就诊时，应警惕其免疫状态，详细了解病史。若当患者有胸腺瘤病史应考虑Good’s综合征作为鉴别诊断。Good’s综合征患者极易出现致死性机会感染，当考虑为Good’s综合征时，应及时给予丙种球蛋白等免疫支持治疗，避免和预防感染。早期免疫状态筛查和积极纠正原发免疫缺陷对于Good’s综合征患者的诊断和预后很有价值。.

Background The increased clinical use of polymyxin led to the emergence of polymyxin-resistant strains, especially those carrying plasmid-borne mobilized colistin resistance (mcr) gene variants. In this study, we aimed to evaluate the prevalence and characteristics of polymyxin-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province, China. Methods A total of 16 polymyxin-resistant isolates among 2301 E. coli and K. pneumoniae isolates collected in 6 local hospitals in the Henan province were studied. The isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the minimum inhibitory concentrations (MICs) were determined using the microbroth dilution technique. Polymyxin-resistant isolates were further analysed for mcr-1 and carbapenemase-mediated resistance using the modified carbapenem inactivation method, the ethylenediaminetetraacetic acid-modified carbapenem inactivation method, and polymerase chain reaction. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed to disclose the phylogenetic relationships of the polymyxin-resistant isolates. The clinical characteristics of patients infected with the polymyxin-resistant isolates were also retrospectively analysed. Results 5/1499 (0.3%) and 11/802 (1.4%) E. coli and K. pneumoniae isolates, respectively, were polymyxin-resistant. The MICs of polymyxin were in the range of 4–64 µg/mL and all of the 16 polymyxin-resistant isolates were susceptible to tigecycline. Additionally, four of the five E. coli polymyxin-resistant isolates were mcr-1 positive; one of them was also carbapenem-resistant, carrying blaNDM−5. Conversely, only 1/11 K. pneumoniae isolates was mcr-1 positive, while 9 polymyxin-resistant isolates were also carbapenem-resistant (PRCRKP), carrying blaKPC−2 but not mcr-1. MLST results showed that the five E. coli isolates belonged to four sequence types (STs), including ST2, ST132, ST632, and ST983, while all PRCRKP isolates belonged to ST11. However, all 16 isolates showed different PFGE types using a genetic similarity of ≥ 95%. Furthermore, 33.3% (5/15) of the patients carrying polymyxin-resistant K. pneumoniae isolates showed a history of polymyxin use, and 10/15 (66.7%) patients displayed good clinical outcomes. Conclusion The polymyxin resistance rate of K. pneumoniae was slightly higher than that of E. coli in the Henan province; however, mcr-1 was only detected in one K. pneumoniae isolate. Thus, close monitoring is needed to prevent and control the spread of PRCRKP.

Background To observe the therapeutic effect of conventional decompressive craniectomy with hematoma evacuation and frame-based stereotactic minimally invasive surgery (MIS) for supratentorial intracranial hematoma with herniation. Methods One hundred forty-nine patients with hypertensive ICH complicated with tentorial herniation were reviewed and analyzed in the present study. The intracranial hematoma was evacuated by emergency surgery within 6 h after admission. According to the authorized representatives’ wishes and consent, 74 of the 149 patients were treated by conventional decompressive craniectomy followed by hematoma removal, defined as the CDC group, and the remaining 75 patients underwent frame-based stereotactic MIS for ICH evacuation, defined as the MIS group. The intervals between the admission to surgery, the duration of surgery, the amount of iatrogenic bleeding, the occurrence of postoperative rebleeding, and the recovery of neurological functions were compared between the two groups. All patients were followed up for 3 months. Secondary epilepsy, survival in a vegetative state, severe pulmonary complications, mortality, and activities of daily living (ADL) classification were also recorded and compared. Results The interval between admission and surgery, the duration of surgery, and intraoperative blood loss in the MIS group were significantly decreased compared to the CDC group. The mortality rate, the rate of rebleeding, prevalence of vegetative state, and severe pulmonary complications in the MIS group were remarkably decreased compared to the CDC group. In the MIS group, the survivors’ (ADL) grade also showed advantages. Conclusions In the surgical treatment of hypertensive ICH complicated with tentorial herniation, frame-based stereotactic MIS for ICH showed advantages compared to conventional open surgery.

Background Malignant peripheral nerve sheath tumours (MPNSTs) of the trachea are extremely uncommon neoplasms with unknown genetic and clinical profiles. Only individual cases have been reported in the literature to date. Case presentation Here, we present a rare case of a 61-year-old female patient with a primary MPNST of the trachea who complained of irritating cough and progressively increasing breathlessness for 4 weeks. This patient initially underwent intraluminal resection of the mass and was misdiagnosed with clear cell sarcoma. Less than a year later, the mass relapsed, and the obstructive symptoms reappeared and gradually worsened. Debulking of the endotracheal tumour mass was performed once again, and an MPNST was definitively diagnosed. Open sleeve tracheal resection and tracheoplasty were later performed with curative intent. This patient was alive without recurrence at her six-month postoperative follow-up. We also compared the clinical outcomes of previously reported cases of MPNSTs and our case. Conclusions This paper emphasizes that thoracic surgeons should be aware that malignant peripheral nerve sheath tumours of the trachea can be misdiagnosed in clinical practice and must be included in the differential diagnosis of tracheal neoplasms.

Chronic obstructive pulmonary disease (COPD) is a chronic debilitating lung disease, characterized by progressive airway inflammation and lung structural cell death. Cigarette smoke is considered the most common risk factor of COPD pathogenesis. Understanding the molecular mechanisms of persistent inflammation and epithelial apoptosis induced by cigarette smoke would be extremely beneficial for improving the treatment and prevention of COPD. A histone methyl modifier, protein arginine N-methyltransferase 6 (PRMT6), is reported to alleviate cigarette smoke extract (CSE)-induced emphysema through inhibiting inflammation and cell apoptosis. However, few studies have focused on the modulation of PRMT6 in regulating inflammation and cell apoptosis. In this study, we showed that protein expression of PRMT6 was aberrantly decreased in the lung tissue of COPD patients and CSE-treated epithelial cells. FBXW17, a member of the Skp1-Cullin-F-box (SCF) family of E3 ubiquitin ligases, selectively bound to PRMT6 in nuclei to modulate its elimination in the proteasome system. Proteasome inhibitor or silencing of FBXW17 abrogated CSE-induced PRMT6 protein degradation. Furthermore, negative alteration of FBXW17/PRMT6 signaling lessened the proapoptotic and proinflammatory effects of CSE in lung epithelial cells. Our study, therefore, provides a potential therapeutic target against the airway inflammation and cell death in CS-induced COPD.

Background Angioleiomyoma of the pulmonary artery is rare in the literature and few studies have been reported. Here we present a rare case of angioleiomyoma arising from the pulmonary artery in a young patient. Case presentation A 27-year-old male patient presented to our clinic due to the incidental finding of a nodule in the right lower lobe of the lung, which was unchanged from the prior year. Preoperative CT scans showed a well-demarcated nodule of soft tissue density penetrated by the basal branch of the right anterior basilar artery (RA8b). Single-port video-assisted RS8 segmentectomy was performed under the guidance of preoperative 3-dimensional reconstruction for histologic confirmation of the tumour. The tumour appeared as a solid tumour of a tube-like structure with vascular endothelium, composed of spindle-shaped smooth muscle cells lacking nuclear atypia and homogenous red-dye substances. The spindle cells were positive for immunostaining for smooth muscle actin (SMA), desmin and Ki-67 and were negative for immunostaining for Dog-1, HMB45, and Melan-A. A pathological diagnosis of primary angioleiomyoma of the pulmonary artery was finally made. Conclusions This report is a reminder for thoracic surgeons that angioleiomyoma should be included in the differential diagnosis of lung neoplasms, especially for the mass of soft tissue density penetrated by pulmonary blood vessels shown by CT. Awareness of this rare entity should potentially prevent underdiagnosis and improper surgical treatment.

Pneumothorax is one of the most common symptoms in patients with lymphangioleiomyomatosis (LAM). However, current management strategies for patients with LAM who present with recurrent pneumothorax remain inadequate. Here, we describe the successful prevention of recurrent pneumothorax by sirolimus treatment in five women with LAM. Before sirolimus treatment, all patients had received supplemental oxygen support, repeated chest tube drainage, or surgeries for management of the recurrent pneumothorax. Sirolimus treatment was initiated when the pneumothorax was completely resolved, and no patient developed pneumothorax during treatment. Moreover, they exhibited a significantly improved subjective quality of life, increased exercise capacity, and mild adverse effects such as mucositis, irregular menstruation, and delayed wound healing. On discontinuation of sirolimus or in the event that the plasma sirolimus level was markedly low, pneumothorax tended to relapse. The findings from these cases provide valuable insights that will aid in the improvement of treatment strategies for patients with LAM and recurrent pneumothorax.

The present study investigated the nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response element (ARE) signaling pathway in patients with moderate to severe obstructive sleep apnea-hypopnea syndrome (OSAHS). Their correlation with neurocognitive impairment metrics was investigated to explore potential pathogenesis in OSAHS. Forty-eight patients with OSAHS and 28 controls underwent testing with the Epworth Sleep Scale (ESS), MATRICS Consensus Cognitive Battery (MCCB), Stroop Color and Word Test, polysomnography (PSG), and measurements of the concentration of plasma superoxide dismutase (SOD) and thioredoxin (Trx). Further, 20 pairs of matched patients with OSAHS and controls were selected for measurement of the expression (protein and mRNA) of Nrf2 and of its downstream antioxidase, heme oxygenase-1 (HO-1), in peripheral mononuclear cells (PBMCs). Finally, correlations between neurocognitive impairment and the above metrics were analyzed. Expression of Nrf2 and HO-1 mRNA and protein in the PBMCs, as well as plasma SOD and Trx levels, were significantly reduced in patients with OSAHS. After adjusting for education, sex, age, and smoking index, the expression of Nrf2-ARE signaling pathway proteins (or mRNA) was closely correlated with sleep respiratory parameters. An inverse relationship was demonstrated between the expression of nuclear Nrf2 in PBMCs, concentration of plasma SOD and Trx, and apnea-hypopnea index (AHI) in patients with OSAHS. Trx, nuclear Nrf2 protein, and HO-1 protein were also negatively correlated with the percent of time that SaO2 was less than 90% (TSat90). Total Nrf2 protein level was positively correlated with AHI and TSat90 and negatively correlated with minimum SaO2 (LSaO2), while nuclear Nrf2 protein and HO-1 protein were positively correlated with LSaO2. Moreover, significant positive correlations were found between maze scores and expression of nuclear Nrf2 protein, HO-1 protein, and SOD and Trx levels. Furthermore, inverse relationships between total Nrf2 protein in PBMCs and HVLT-R and maze scores were found. Multiple linear regression showed plasma Trx concentration as a potential predictor of maze and BVMT-R scores. In conclusion, the expression of Nrf2-ARE molecules and related antioxidases is significantly decreased in patients with OSAHS and is correlated with neurocognitive dysfunction. The Nrf2-ARE signaling pathway may play a crucial role in neurocognitive impairment in patients with moderate to severe OSAHS. Further studies are needed to explore the exact mechanisms and potential treatment interventions.

Objectives Hematoma formed after intracerebral hemorrhage (ICH) could results in secondary brain damage. In vitro thrombin treatment allows investigation of the pathology and mechanisms behind brain injury, and provides extracellular environment that simulates the conditions that result from ICH. Rosiglitazone treatment protects against brain damage through promoting the phagocytosis of red blood cells by microglia. The present study aimed to explore the underlying molecular mechanisms using the thrombin-induced model of ICH. Methods A total of 54 neonatal rats was used in the present study. Primary microglia were obtained from the brain tissues of neonatal SD rats, and then divided into 4 groups: normal control group (NC group), thrombin treatment group(TH group), RSG pretreatment + thrombin treatment group(RSG group), and RSG pretreatment + thrombin treatment together with p38MAPK signaling inhibitor group (SB group). Then, laser scanning confocal microscopywas used to evaluate microglial phagocytosis by observing phagocytizedred fluorescent microspheres. The mRNA and protein expression levels of CD36 were measured by RT-PCR and western blot. Results Microglial phagocytosis was increased in the RSG group compared with the other groups, and phagocytosis in the SB group was decreased compared to the RSG group. The RSG group displayed increased expression of CD36 compared to the other groups, both at protein and mRNA levels (P

Objective: To observe the effects of minimally invasive surgery (MIS) for hematoma of intracerebral hemorrhage (ICH) evacuation followed by rosiglitazone (RSG) infusion therapy on perihematomal tight junction associated proteins occludin and zonula occludens-1 (ZO-1) expression as well as blood brain barrier (BBB) permeability in rabbits. Methods: A total of 50 male rabbits (2.5-3.5 kg) were randomly assigned to a sham group (Sham group, 10 rabbits), an ICH model group (HM group, 10 rabbits), a RSG medication group (RSG group, 10 rabbits), a minimally invasive surgery group (MIS group, 10 rabbits) and a MIS combined with RSG group (MIS+RSG group, 10 rabbits). ICH was induced in all of the rabbits except for those in the Sham group. An MIS was performed to evacuate the hematoma at 6 hours after the successful preparation of the ICH model in the MIS group and the MIS+RSG group. The RSG (0.5mg, dissolved in 0.1 ml of 0.9% sodium chloride solution) was infused into the hematoma area in the RSG group and the MIS+RSG group. All rabbits were sacrificed on day 7 after the relative processes were performed successfully, and the perihematomal brain tissue was removed to determine the occludin and ZO-1 expression and BBB permeability by Evens Blue (EB). Results: The occludin and ZO-1 expression were all significantly decreased and the BBB permeability was increased in the HM group compared with the Sham group. The RSG used alone or performing the MIS alone to evacuate the ICH resulted in a marked increase in the occludin and ZO-1 expression and decrease in BBB permeability. The MIS+RSG group displayed a great increase in the occludin and ZO-1 expression and a more significant decrease in BBB permeability. Conclusions: The MIS combined with RSG medication could significantly increase the perihematomal occludin and ZO-1 expression and decrease in BBB permeability which plays an important therapeutic role in secondary brain damage following ICH.

Xue He,1–3 Tiao Li,1–3 Naixin Kang,1–3 Huihui Zeng,1–3 Siying Ren,1–3 Dandan Zong,1–3 Jinhua Li,1–3 Shan Cai,1–3 Ping Chen,1–3 Yan Chen1–3 1Department of Respiratory Medicine, The Second Xiangya Hospital, 2Research Unit of Respiratory Disease, 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China Background: Cigarette smoke exposure is the most common risk factor for emphysema, which is one of the major pathologies of COPD. Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that specially catalyzes dimethylation of R2 in histone H3 (H3R2me2a). H3R2me2a prevents trimethylation of H3K4 (H3K4me3), which is located in the transcription start sites of genes in mammalian genomes. We attempted to determine the expression of PRMT6 in human samples, and investigate whether the upregulation of PRMT6 expression can attenuate the development of cigarette smoke extract (CSE)-induced emphysema. Further experiments were performed to elucidate the molecular mechanisms involved.Materials and methods: Human lung tissues were obtained from patients undergoing pneumonectomy for benign pulmonary lesions. BALB/c mice were treated with lentiviral vectors intratracheally and injected with CSE three times. The protein expression of PRMT6, H3R2me2a, and H3K4me3 in human and mouse samples, as well as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and endothelial nitric oxide synthase (eNOS) in mice were detected in lung homogenates by Western blotting. The mRNA expression of cyclooxygenase-2, interleukin-6, Bcl-2, Bax, and eNOS in mice was measured by quantitative real-time polymerase chain reaction.Results: The expression of PRMT6 was significantly downregulated in the pulmonary parenchyma in smokers with COPD as well as in mice treated with CSE. Overexpression of PRMT6 was detected in the CSE + Lenti-PRMT6 group of mice, which reversed the expression of H3R2me2a and H3K4me3. Inflammation, apoptosis, and oxidative stress levels were severe in the CSE-treated emphysema mice compared with the control group, which was inhibited by the overexpression of PRMT6.Conclusion: The overexpression of PRMT6 might inhibit inflammation, apoptosis, and oxidative stress in CSE-induced emphysema mediated by H3R2me2a. Keywords: COPD, cigarette smoke extract, inflammation, apoptosis, oxidative stress, PRMT6

The tuberous sclerosis complex (TSC) proteins are critical negative regulators of the mammalian/mechanistic target of rapamycin complex 1 pathway. Germline mutations of TSC1 or TSC2 cause TSC, affecting multiple organs, including the kidney and lung, and causing substantial morbidity and mortality. The mechanisms of organ-specific disease in TSC remain incompletely understood, and the impact of TSC inactivation on mesenchymal lineage cells has not been specifically studied. We deleted Tsc2 specifically in mesoderm-derived mesenchymal cells of multiple organs in mice using the Dermo1-Cre driver. The Dermo1-Cre–driven Tsc2 conditional knockout mice had body growth retardation and died approximately 3 weeks after birth. Significant phenotypes were observed in the postnatal kidney and lung. Inactivation of Tsc2 in kidney mesenchyme caused polycystic lesions starting from the second week of age, with increased cell proliferation, tubular epithelial hyperplasia, and epithelial-mesenchymal transition. In contrast, Tsc2 deletion in lung mesenchyme led to decreased cell proliferation, reduced postnatal alveolarization, and decreased differentiation with reduced numbers of alveolar myofibroblast and type II alveolar epithelial cells. Two major findings thus result from this model: inactivation of Tsc2 in mesoderm-derived cells causes increased cell proliferation in the kidneys but reduced proliferation in the lungs, and inactivation of Tsc2 in mesoderm-derived cells causes epithelial-lined renal cysts. Therefore, Tsc2-mTOR signaling in mesenchyme is essential for the maintenance of renal structure and for lung alveolarization.

Deficiency in pulmonary surfactant results in neonatal respiratory distress, and the known genetic mutations in key components of surfactant only account for a small number of cases. Therefore, determining the regulatory mechanisms of surfactant production and secretion, particularly during the transition from prenatal to neonatal stages, is essential for better understanding of the pathogenesis of human neonatal respiratory distress. We have observed significant increase of bone morphogenetic protein (BMP) signaling in neonatal mouse lungs immediately after birth. Using genetically manipulated mice, we then studied the relationship between BMP signaling and surfactant production in neonates. Blockade of endogenous BMP signaling by deleting Bmpr1a ( Alk3) or Smad1 in embryonic day 18.5 in perinatal lung epithelial cells resulted in severe neonatal respiratory distress and death, accompanied by atelectasis in histopathology and significant reductions of surfactant protein B and C, as well as Abca3, whereas prenatal lung development was not significantly affected. We then identified a new BMP-Smad1 downstream target, Nfatc3, which is known as an important transcription activator for surfactant proteins and Abca3. Furthermore, activation of BMP signaling in cultured lung epithelial cells was able to promote endogenous Nfatc3 expression and also stimulate the activity of an Nfatc3 promoter that contains a Smad1-binding site. Therefore, our study suggests that the BMP-Alk3-Smad1-Nfatc3 regulatory loop plays an important role in enhancing surfactant production in neonates, possibly helping neonatal respiratory adaptation from prenatal amniotic fluid environment to neonatal air breathing.