Background The effects of thymectomy on late-onset non-thymomatous myasthenia gravis (NTMG) remain controversial. The objective of this study was to conduct a systematic review in order to answer two questions pertinent to late-onset NTMG: (1) do patients with late-onset NTMG experience the same effects from thymectomy as their early-onset counterparts? (2) Compared with conservative treatment, does thymectomy have any benefits for late-onset NTMG patients? Methods We searched the PubMed, EMBASE, and Cochrane Library databases for studies published from January 1, 1950 to March 10, 2021. Outcomes were measured via clinical stable remission/pharmacological remission (CSR/PR) and improvement rates. We used Stata software to analyze the data. Results We ultimately included a total of 12 observational articles representing the best evidence answering the questions of our study objective. Of these, nine studies, which included 896 patients overall (766 early-onset and 230 late-onset), compared postoperative outcomes between early- and late-onset NTMG. The remaining three articles, which included 216 patients (75 in the thymectomy group and 141 in the conservative-treatment group), compared thymectomy with conservative treatment for late-onset NTMG. The early- versus late-onset NTMG studies demonstrated that patients in the former category were 1.95× likelier than their late-onset counterparts to achieve clinical remission (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.39–2.73; I2 = 0%). No difference was seen in improvement or remission + improvement rates between these two groups. When comparing thymectomy with conservative treatments in late-onset NTMG patients, neither did we observe any difference in CSR/PR. Conclusion We found that late-onset NTMG patients had a lower chance of achieving CSR after thymectomy than early-onset patients. Thymectomy in late-onset NTMG also yielded no benefit to CSR or PR compared with conservative treatments. In late-onset NTMG patients, thymectomy should therefore be performed with caution, and the appropriate cutoff between early- and late-onset MG should be further explored in order to tailor and execute the proper therapeutic strategies.

BackgroundKIT proto‐oncogene ligand (KITLG) is a pleiotropic factor which is found in diverse cancers and is involved in cell proliferation, differentiation, and survival. However, the value of KITLG in thymoma remains unclear.MethodsA total of 121 thymoma samples from The Cancer Genome Atlas Thymoma (TCGA‐THYM) dataset were used to analyze KITLG related genome‐wide expression profiles, and microRNA profiles and methylation alterations and a GEO dataset‐GSE29695, including 37 samples was used as verification. For cell‐based studies, specific small interfering RNA targeting KITLG or a KITLG overexpression vector were used to clarify the changes of the MAPK pathway in an AB thymoma cell line Thy0517.ResultsBoth datasets showed that high expression of KITLG was significantly associated with type A and AB thymoma. Through multiomic analysis of the TCGA‐THYM, it was found that with the high expression of KITLG, there were 220 upregulated and 72 downregulated genes at the mRNA level, 79 positive and 78 negative miRNAs, 28 hypermethylation and 163 hypomethylation regions. In the thymoma cell line Thy0517, it was found that the expression of GRB2 and the phosphorylation levels of BRAF, MEK1/2, and ERK1/2 in the MAPK pathway were positively correlated with the change in KITLG.ConclusionsHigh expression of KITLG is a new hallmark of WHO type A and AB thymomas in which it might play a critical role through the activation of the MAPK signaling pathway. Additionally, it is hoped that KITLG will become a potential target for the diagnosis of type A and AB thymoma through further research in the future.Key pointsSignificant findings of the studyKIT proto‐oncogene ligand (KITLG) is a new hallmark of type A and AB thymomas which induce a series of aberrant alteration of mRNA, miRNA and DNA methylation. The expression of KITLG is significantly higher in type A and AB than other subtypes of thymoma.What this study addsKITLG activated the MAPK signaling pathway to promote type A and AB thymoma which might be a potential diagnostic biomarker or target.

Although the expression of heparanase is associated with invasion and metastasis of various human cancers, the effects of heparanase on human osteosarcoma have not been evaluated. We showed that down-regulating the expression of heparanase significantly reduced proliferation and invasion of human U-2OS osteosarcoma cells. Furthermore, heparanase silencing by short-hairpin RNA (shRNA) was associated with decreased hypoxia-inducible factor-1α (HIF-1α) level, implying that heparanase was associated with the expression of HIF-1α. This result was confirmed by immunohistochemistry analysis. In osteosarcoma tissues, immunohistochemical results revealed that heparanase expression had a close correlation with that of HIF-1α and they had a strong relation with presence of pulmonary metastasis (P<0.05). Heparanase-positive samples had higher microvessel density (MVD) than heparanase-negative samples. Similarly, compared with HIF-1α-negative samples, HIF-1α-positive samples had higher MVD. Therefore, heparanase and HIF-1α facilitated tumor angiogenesis and promoted pulmonary metastasis of osteosarcoma.

Solitary fibrous tumor (SFT) is a rare clinical tumor, defined as a mesenchymal tumor of fibroblastic origin. A classic SFT is benign in most cases, but its clinical behavior is unpredictable. Lately, molecular analyses has discovered that almost all SFTs harbor an NAB2-STAT6 fusion gene, which is considered specific to this tumor type. Recent studies have suggested that nuclear STAT6 immunoreactivity is a highly sensitive and specific marker of SFTs and can be helpful when diagnosis is inconclusive by conventional methods. We herein report the case of a rare malignant solitary fibrous tumor occurring in the mediastinal pleura. An 82-year-old Chinese man with intermittent breathlessness was referred to our hospital. Chest CT showed a significantly enhanced irregular huge soft tissue mass in the anterior mediastinal area. After radical resection, the immunohistochemistry staining results of the sample showed that STAT6 was negative. The final diagnosis was confirmed by qualitative endpoint reverse transcriptasepolymerase chain reaction technique, showing positive NAB2ex4-STAT6ex2 fusion.

Objective Acute lung injury (ALI) caused by sepsis is clinically a syndrome, which is featured by damage to the alveolar epithelium and endothelium. In this study, we employed mice models of cecal ligation and puncture (CLP) and primary mice pulmonary microvascular endothelial cells (MPVECs) in vitro to investigate the effect of miR-128-3p in ALI caused by sepsis. Methods miR-128-3p agomir or randomized control were injected into adult male C57BL/6 mice 1 week before the CLP surgery. We used miR-128-3p agomir or scrambled control to transfect MPVECs and then employed lipopolysaccharide (LPS) stimulation on the cells. Pellino homolog 2 (PELI2) was predicted to be a direct target of miR-128-3p via luciferase reporter assay. MPVECs were cotransfected with lentiviral vector that expressed PELI2 (or empty vector) as well as miR-128-3p-mimics 1 day before LPS stimulation in rescue experiment. Transcriptional activity of caspase-3, cell apoptosis rate, and the expression levels of miR-128-3p, interleukin-1β (IL-1β), interleukin-6 (IL-6), and PELI2 were analyzed. Results Compared with the sham group, the lung of mice in the CLP group showed pulmonary morphological abnormalities, and the expression of IL-6 and IL-1β, caspase-3 activity, and apoptosis rate were significantly upregulated in the CLP group. Inflammatory factor levels and apoptosis rate were also significantly induced by LPS stimulation on MPVECs. Upregulation of miR-128-3p effectively inhibited sepsis-induced ALI, apoptosis as well as inflammation. miR-128-3p also played a role in antiapoptosis and anti-inflammation in MPVECs with LPS treatment. PEL12 upregulation in MPVECs alleviated miR-128-3p-induced caspase-3 activity inhibition and pro-inflammatory factor production. Conclusions miR-128-3p enabled to alleviate sepsis-induced ALI by inhibiting PEL12 expression, indicating a novel treatment strategy of miR-128-3p for sepsis-induced ALI.