Bing Li

Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) haploinsufficiency with autoimmune infiltration (CHAI) is an autosomal dominant condition featuring both immunodeficiency and autoimmunity. We describe the first published mainland Chinese patient harboring the heterozygous CTLA4 c.529dupT frameshift variant. While multiple CHAI cases have been documented in mainland China, this specific variant has not been reported in this population to date. The patient developed recurrent thrombocytopenia, recurrent respiratory infections and hypogammaglobulinemia at age 2. She was diagnosed with immune thrombocytopenia (ITP) at age 15. The disease subsequently progressed to Evans syndrome, alongside complications including chronic diarrhea, cerebral vasculitis, biliary tract infection and interstitial pneumonia. She received standard anti-infective therapy, combined glucocorticoids and immunosuppressants, as well as intravenous immunoglobulin (IVIG) replacement; however, these interventions yielded only limited and temporary benefits. After 38 years of disease progression, a primary immunodeficiency was suspected. Whole-exome sequencing (WES) verified the diagnosis of CHAI. Treatment with sirolimus led to amelioration of infection and diarrheal symptoms. This case exhibited phenotypic differences from prior patients carrying the identical variant. Our observations expand the known phenotypic spectrum of this variant and offer clinical references for the management and genetic testing of patients presenting with early-onset multisystem autoimmunity and immunodeficiency.

We report two cases of lung cancer that were surgically resected from patients with underlying bronchiectasis. These cases are unique because the tumors were diagnosed neither through elevated tumor markers, hypermetabolism on PET-CT, nor the presence of typical malignant imaging features. Instead, they were incidentally identified through histopathological examination following lobectomy performed for recurrent bronchiectasis-related infections. We aim to enhance clinicians’ vigilance toward occult malignancies in patients with bronchiectasis by summarizing the treatment course of such concealed tumors. Bronchiectasis maybe associated with lung cancer. Implementing a regular imaging surveillance maybe necessary for these patients. Furthermore, timely surgical intervention should be considered when clinical or radiological findings raise suspicion of malignancy.

We report a case of well-differentiated papillary mesothelial tumor (WDPMT) diagnosed using internal thoracoscopic biopsy in a patient who has suffered from recurrent pleural effusions for over 35 years together with a history of elevated CA125. We hope to provide a case for the diagnosis of this rare benign and preinvasive pleural tumor and recommend that internal thoracoscopy may be a good choice in these recurrent pleural effusion patients especially for those minimal lesions not easily detected using CT scan.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study.Reference:Jin-Cheng Zheng, Ke-Jie Chang, Yu-Xiang Jin, Xue-Wei Zhao, Bing Li, Meng-Hang Yang. Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling. Med Sci Monit 2019; 25:2228-2237. DOI: 10.12659/MSM.913091

Bronchial Dieulafoy's disease (BDD) is a rare disease that causes massive hemoptysis. This paper reports a case of BDD treated surgically. At the same time, we summarize the data of BDD patients reported in domestic and foreign literature to improve the understanding, diagnosis and treatment of this disease. A case of BDD with hemoptysis during bronchoscopy was reported. In addition, we searched for "bronchial Dieulafoy disease" through Pubmed, Web of Science, CNKI and Wanfang databases, covering the literature related to BDD that was definitely diagnosed or highly suspected from January 1995 to December 2021, and summarized the clinical characteristics, chest imaging, bronchoscopic manifestations, angiographic characteristics, pathological characteristics, treatment and outcome of patients. The patient was a 68 year old male. Tracheoscopy revealed nodular and mass like changes in the basal segment of the left lower lobe, which appeared massive hemorrhage when touching the surface. The computed tomography angiophy of the bronchial artery confirmed that the branches of the left bronchial artery were tortuous and dilated, and then the left lower lobe of the lung was resected. During the operation, 3 thick tortuous nutrient artery vessels were sent out from the descending aorta, and 1 thick tortuous nutrient artery was sent out from the autonomic arch. All of them were ligated and cut. The pathology after the operation was in accordance with BDD; The patient did not have hemoptysis after discharge and is still under follow-up. The database identified 65 articles from January 1995 to December 2021. After removing repeated reports, meetings, incomplete information and nursing literature, 60 articles were included to report 88 cases of BDD. BDD can occur at all ages, with a male to female ratio of about 1.6:1. It mainly starts with hemoptysis, and can also be seen due to cough, infection, and respiratory failure; Inflammatory changes such as pulmonary patch shadow, exudation shadow and ground glass shadow of pulmonary hemorrhage were more common in chest imaging; The diagnosis of BDD is mainly based on the bronchoscopy, bronchial angiography and pathological findings of surgical or autopsy specimens. Bronchoscopic findings were mostly non pulsating, smooth nodular or mucosal processes. Bronchial angiography mainly showed tortuous dilatation of bronchial artery, and the lesions were mainly located in the right bronchus, more from the bronchial artery; Diagnosis depends on pathology, showing submucosal expansion of bronchus or abnormal artery rupture and bleeding; 54 cases underwent selective bronchial artery embolization, 39 cases underwent pulmonary lobectomy, 66 cases improved, and 10 cases died (all of them were caused by massive hemorrhage during bronchoscopic biopsy). BDD is rare, but may cause fatal massive hemoptysis. Bronchial angiography is considered to be an effective method to diagnose BDD. Since pathological biopsy may lead to fatal bleeding, the necessity of pathological diagnosis remains controversial. Interventional and surgical treatment plays an important role in patients with cough accompanied by massive hemoptysis.

To clarify whether arsenic could exert inhibitory effects on tumor cells in pleural effusions of patients with non-small cell lung cancer (NSCLC), 36 NSCLC pleural effusion samples were collected from Changzheng Hospital and Ruijin Hospital, from 2019 to 2022. The genotype of epidermal growth factor receptor (EGFR) was identified. Tumor cells were isolated and treated with arsenic trioxide (ATO) or/and gefitinib. Additionally, six patients were intrapleurally administrated with ATO. Results showed that 25 samples bore EGFR wild type (WT) and 11 harbored EGFR mutations, including 6 with L858R, 3 with ΔE746-A750, and 2 with T790M. ATO diminished the number of tumor cells from patients with WT and mutant EGFR, down-regulated the expression or phosphorylation of EGFR, pmTOR, PI3K, PTEN, and p4E-BP1, and up-regulated the expression of LC3. Immunofluorescent experiments showed that ATO enhanced LC3 and P62. By contrast, gefitinib was only effective in those harboring EGFR sensitizing mutations. Notably, in patients with intrapleural ATO injection, the pleural effusion underwent a bloody to pale yellow color change, the volume of the pleural effusion was reduced, and the number of the tumor cells was significantly reduced. In conclusion, arsenic is effective against NSCLC with various EGFR genotypes in vitro and in vivo, and potentially circumvents gefitinib resistance.

Background Small cell lung cancer (SCLC) is the most malignant type of lung cancer. We previously reported that arsenic trioxide (As₂O₃) inhibited tumor initiating cells (TICs) of SCLC in vitro. In the present study, we aimed to identify the above effect in vivo and shed light on its underlying mechanism. Methods and results TICs were enriched by culturing human SCLC cell line as sphere cells in specified serum-free medium. The expression of stem cell markers, CD133 and CD44, and the in vivo tumorigenicity of both TICs and their parental cells were examined. To demonstrate the inhibitory effect of As₂O₃ on TICs, cell proliferation, clone formation and sphere formation assays were performed. CD133 and Notch pathway-related factors were also measured after As₂O₃ treatment. Xenograft models were established by injecting TICs into nude mice. Mice were treated with As₂O₃ for 14 days. Afterwards, the tumor volume and the expression of CD133 and Notch1 were evaluated. TICs obtained by the above-mentioned method showed elevated levels of stem cell markers and increased tumorigenicity compared with their parental cells. As₂O₃ treatment largely inhibited TICs proliferation, sphere formation and clonogenic capacity. As₂O₃ also reduced the expression of CD133 and down-regulated Notch pathway in TICs. Furthermore, As₂O₃ potently inhibited tumor growth, decreased the expression of CD133 and down-regulated Notch1 in tumors originating from TICs. Conclusions Our data demonstrate that As₂O₃ has a remarkable inhibitory effect on TICs of SCLC both in vitro and in vivo, and the mechanism might involve the down-regulation of Notch pathway.

Background: Small cell lung cancer (SCLC) is the most deadly and aggressive type of primary lung cancer, with the 5-year survival rate lower than 5%. The FDA has approved arsenic trioxide (As₂O₃) for acute promyelocytic leukemia (APL) treatment. However, its role in SCLC-derived cancer stem cells (CSCs) remains largely unknown. Methods: CSCs were enriched from SCLC cell lines by culturing them as spheres in conditioned serum-free medium. Then, qPCR, western blot, serial passage, limiting dilution, Transwell, and tumorigenesis assay were performed to verify the cells’ stem phenotypic characteristics. Anticancer efficiency of As₂O₃ was assessed in these cells using CCK8, colony formation, sphere formation, flow cytometry, qPCR, western blot analysis in vitro, and tumor growth curve, immunofluorescence, and TUNEL staining analyses in vivo. Results: The fifth-passage SCLC spheres showed a potent self-renewal capacity, higher clonal formation efficiency (CFE), SOX2, c-Myc, NANOG, and OCT4 levels, and invasion ability, and stronger tumorigenesis capacity than the parental SCLC cells, indicating that the SCLC sphere cells displayed CSC features. As₂O₃ inhibited the proliferation, clonality and sphere forming ability of SCLC-derived CSCs and suppressed the tumor growth of CSCs-derived xenograft tumors. As₂O₃ induced apoptosis and downregulation of SOX2 and c-Myc in vitro and in xenografts. Besides, SOX2 knockdown suppressed SCLC-derived CSCs to self-renew and induced apoptosis. Mechanistically, expression of GLI1 (a key transcription factor of Hedgehog pathway) and its downstream genes increased in SCLC-derived CSCs, compared to the parental cells. As₂O₃ dramatically downregulated GLI1 and its downstream genes in vitro and in vivo. The GLI inhibitor (GANT-61) recapitulated and enhanced the effects of As₂O₃ on SCLC-derived CSCs, including growth suppression, apoptosis induction, and GLI1, SOX2 and c-Myc downregulation. Conclusions: Altogether, As₂O₃ effectively suppressed SCLC-derived CSCs growth by downregulating stem cell-maintenance factors and inducing apoptosis. These effects are mediated at least partly via the Hedgehog signaling blockade.

Gorham-Stout syndrome (GSS) is a rare disease characterized by spontaneous and progressive osteolysis caused by benign proliferation of lymphatic vessels or capillaries. It most commonly occurs in children or young individuals without any inherited predisposition. GSS most commonly affects the shoulder girdle, pelvis, ribs and skull. Its diagnosis is mainly based on radiological and pathological findings. The present study reports on the case of a 22‑year‑old male patient diagnosed with GSS involving the C1‑T1 vertebrae accompanied by bilateral pleural effusion. Resection of the occipital and cervical vertebral lesions and spinal reconstruction using an internal fixator were successfully performed via the posterior approach. After the surgery, the patient received bisphosphonate treatment and vitamin D supplementation. The pleural effusion gradually decreased. At the 18‑month follow‑up visit, no evidence of new bone obstruction was present and the patient had no neurological sequelae.