Baló's concentric sclerosis with spontaneous remission and favorable prognosis.

Introduction: Baló's concentric sclerosis (BCS) is a rare type of central nervous system demyelinating disorder. Most patients with BCS are treated with corticosteroids, and spontaneous remission has seldom been described. Case presentation: A 46-year-old man presented with a subacute-onset headache and memory loss. Brain magnetic resonance imaging (MRI) revealed multiple onion-shaped ring lesions with mild enhancement in the outermost ring. A brain biopsy revealed significant myelin loss. The diagnosis of BCS was established based on the MRI results and pathological findings. Interestingly, the patient recovered almost completely without immunotherapy, with repeated brain MRI at the 1-year follow-up showing an obvious reduction in the extent of the lesions. Conclusion: Neurologists should improve the recognition of the typical MRI features of BCS to avoid unnecessary biopsies. Although rare, spontaneous remission can be observed in clinical practice.

[Arthroscopic suspension fixation with Endobutton in treatment of tibial insertion avulsion fractures of posterior cruciate ligament].

Objective: To investigate the effectiveness of arthroscopic suspension fixation with Endobutton in the treatment of tibial insertion avulsion fractures of posterior cruciate ligament (PCL). Methods: A retrospective analysis was conducted on the clinical data of 52 patients (52 knees) with tibial insertion avulsion fractures of PCL, who were treated by arthroscopic suspension fixation with Endobutton between June 2017 and October 2022. There were 29 males and 23 females, with an average age of 40.6 years (range, 19-66 years). There were 24 cases of traffic accident injuries, 17 cases of sports injuries, and 11 cases of fall injuries. The time from injury to operation ranged from 6 to 19 days (mean, 13.3 days). According to the Meyers-McKeever classification, there were 30 cases of type Ⅱ and 22 cases of type Ⅲ fractures. All patients exhibited positive posterior drawer test results. Preoperative knee joint function was assessed with Lysholm score (21.3±6.7), International Knee Documentation Committee (IKDC) score (20.7±5.8), and visual analogue scale (VAS) score (5.3±0.7); and knee joint range of motion was (41.73±3.17)°. Based on preoperative CT three-dimensional reconstruction measurements, the longitudinal diameter of the avulsed bone fragment ranged from 13 to 25 mm (mean, 18.1 mm). Operation time and occurrence of complications were recorded, and postoperative imaging was used to assess fracture healing. Knee joint function and pain severity were evaluated using knee joint range of motion, Lysholm score, IKDC score, and VAS score. Results: The operation time ranged from 46 to 81 minutes (mean, 56.2 minutes). All patients were followed up 12-28 months (mean, 20.1 months). The iatrogenic fractures of bone fragments occurred during operation in 4 cases; and knee effusion occurred in 2 cases and anterior knee pain in 1 case after operation. All incisions healed by first intention. Imaging evaluations at 3 months after operation showed the fracture healing and no internal fixation failure. All patients demonstrated good knee function and had returned to normal activities at 12 months after operation. At last follow-up, the knee joint range of motion was (133.44±4.17)°, Lysholm score 93.6±3.1, IKDC score 93.4±2.5, and VAS score 1.0±0.6, with significant differences compared to preoperative scores ( P<0.05). Conclusion: Arthroscopic suspension fixation with Endobutton in the treatment of tibial insertion avulsion fractures of PCL is simple to operate, and the knee joint function recovers well.

Cytoplasmic expression of UTP23 promotes colorectal cancer progression.

UTP23 (UTP23 small subunit processome component) plays a pivotal role in the intricate processing and maturation of the small subunit of ribosomes within the nucleolus. In cases of nucleolar stress, such as those observed in certain tumor cells, the aberrant nucleolar organization and structure can lead to the translocation of nucleolar proteins into the nucleus or cytoplasm, consequently impacting the physiological processes of the tumor cells through non-ribosome-related functions. Our investigation revealed altered localization of UTP23 protein in colorectal cancer clinical tissue samples. Upon analyzing UTP23 expression and its correlation with patient prognosis in a cohort of 143 colorectal cancer patients, the result suggested that high cytoplasmic expression pattern of UTP23 was occured in early-stage metastasis-free colorectal cancer and was significantly associated with poor prognosis. Furthermore, we demonstrated that cytoplasmic expression of UTP23 significantly promoted the metastatic and invasive capabilities of colorectal cancer cells, which was not showed in the nucleollcalised UTP23. Intriguingly, mass spectrometry result suggested that KRT5 bind to UTP23 and showed a regulatory influence on UTP23 metastatic potential in colorectal cancer cells. Conclusively, our study demonstrated that the localization of UTP23 play a key role in colorectal cancer metastatic progression, which may serve as a novel prognostic indicator.

GPR137 inactivates Hippo signaling to promote gastric cancer cell malignancy.

As the fifth most common cancer in the world, gastric cancer (GC) ranks as the third major cause of cancer-related death globally. Although surgical resection and chemotherapy still remains the mainstay of potentially curative treatment for GC, chemotherapy resistance and adverse side effects limit their clinical applications. Thus, further investigation of the mechanisms of carcinogenesis in GC and discovery of novel biomarkers is of great concern. We herein report that the elevated expression of GPR137 is correlated with GC. Overexpression of GPR137 potentiates human gastric cancer AGS cell malignancy, including proliferation, migration, invasion, colony formation and xenograft growth in nude mice in vivo, whereas knockout of GPR137 by CRISPR/Cas9 gene editing exerts the opposite effects. Mechanistically, GPR137 could bind to MST, the upstream kinases in Hippo pathway, which disrupts the association of MST with LATS, subsequently activating the transcriptional co-activators, YAP and TAZ, and thereby triggering the target transcription and the alterations in GC cell biological actions consequently. Therefore, our findings may provide with the evidence of developing a potentially novel treatment method with specific target for GC.

AI-assisted system improves the work efficiency of cytologists via excluding cytology-negative slides and accelerating the slide interpretation.

Given the shortage of cytologists, women in low-resource regions had inequitable access to cervical cytology which plays an pivotal role in cervical cancer screening. Emerging studies indicated the potential of AI-assisted system in promoting the implementation of cytology in resource-limited settings. However, there is a deficiency in evaluating the aid of AI in the improvement of cytologists' work efficiency. This study aimed to evaluate the feasibility of AI in excluding cytology-negative slides and improve the efficiency of slide interpretation. Well-annotated slides were included to develop the classification model that was applied to classify slides in the validation group. Nearly 70% of validation slides were reported as negative by the AI system, and none of these slides were diagnosed as high-grade lesions by expert cytologists. With the aid of AI system, the average of interpretation time for each slide decreased from 3 minutes to 30 seconds. These findings suggested the potential of AI-assisted system in accelerating slide interpretation in the large-scale cervical cancer screening.

Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a highly malignant tumor arising from the biliary tree. Radical surgery is the only treatment offering a chance of long-term survival. However, limited by the tumor's anatomic location and peri-vascular invasion, most patients lose the chance for curative treatment. Therefore, more methods to increase the resectability of tumors as well as to improve outcomes are needed. CASE SUMMARY: A 68-year-old female patient had a hepatic hilar mass without obvious symptoms. Laboratory results showed hepatitis B positivity. Magnetic resonance imaging indicated that the mass (maximum diameter: 41 mm) invaded the left and right branches of the main portal vein, as well as the middle, left and right hepatic veins; enlarged lymph nodes were also detected in the hilum. The patient was diagnosed with pCCA, and the clinical stage was determined to be T4N1M0 (stage IIIC). Considering the tumor's anatomic location and vascular invasion, systematic conversion therapy followed by ex vivo liver resection and autotransplantation (ELRA) was determined as personalized treatment for this patient. Our original systemic sequential therapeutic strategy (lenvatinib and tislelizumab in combination with gemcitabine and cisplatin) was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment, without severe toxicity. ELRA, anastomotic reconstruction of the middle hepatic vein, right hepatic vein, root of portal vein, inferior vena cava and right hepatic artery, and lymph node dissection were performed at one month after systemic therapy. Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis. Although the middle hepatic vein was partially obstructed four months later, hepatic vein stent implantation successfully addressed this problem. The patient has survived for 22 mo after the diagnosis, with no evidence of recurrence or metastasis. CONCLUSION: An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.

SCGN and STAT3 expressions are associated with the prognosis of ccRCC.

Clear cell renal cell carcinoma (ccRCC) is highly heterogeneous and accounts for about 70% of RCC. Its prognosis is worse than that of most histological types of RCC. In order to find potential biomarkers that may influence the prognosis and survival in ccRCC patients, we explored the expressions of STAT3, PDL1 and SCGN (secretagogin) in ccRCC based on the data of TCGA (n = 529), EMATAB-1980 (n = 99) and our own cohort (n = 99). Our study demonstrated that ccRCC patients with low STAT3 expression and high SCGN expression might have a better prognosis. No significant difference in the positive rate of SCGN expression was found when comparing the primary lesion with the matched metastatic liver lesions. The percentage of high SCGN expression in the primary lesion of metastatic ccRCC patients was significantly lower than that of patients with only the renal lesion. In view of the conclusion that STAT3 high expression cases are resistant to sunitinib, STAT3 immunohistochemistry results are essential for designing non-operative treatments. SCGN has the potential to become an indicator for subtype classification of ccRCC.

Nano spinel NiAl2O4: structure, optical and photocatalytic performance evaluation and optimization.

Four kinds of spinel NiAl2O4were synthesized by the polyacrylamide gel method using Al2(SO4)3·18H2O and Al(NO3)3·9H2O as aluminum salts and anhydrous NiSO4and NiSO4·6H2O as nickel salts. The effects of different aluminum salts and nickel salts on the structure, optical and photocatalytic activity of spinel NiAl2O4were confirmed by various characterizations. There is no NiO impurity in the spinel NiAl2O4synthesized with Al2(SO4)3·18H2O as aluminum salt, while NiAl2O4, NiO and C-O functional group coexist in the target product with Al(NO3)3·9H2O as aluminum salt, and C-O functional group and NiO inhibits the photocatalytic activity of the system. Based on photocatalytic experiment, response surface methodology and free radical verification experiment, the influence of experimental parameters including synthesis pathway, initial drug concentration, initialpHand catalyst content on the photocatalytic activity of spinel NiAl2O4and the main active species involved in the reaction were investigated. The degradation percentage of spinel NiAl2O4synthesized with Al2(SO4)3·18H2O as aluminum salt and NiSO4·6H2O as nickel salt was 86.3% at the initial concentration of 50 mg l-1,pH= 5.33 and catalyst content of 1 g l-1. The mechanism investigation confirmed that the C-O functional group plays the dual role of impurity level and electron transfer in the degradation of tetracycline hydrochloride by spinel NiAl2O4.

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

Clinicopathologic Features of Noninvasive Inverted Urothelial Papillary Tumor.

OBJECTIVES: Clinicopathologic features and recurrence rates of inverted noninvasive urothelial papillary tumors have been poorly characterized to date with few larger studies evaluating long-term outcomes. The spectrum of histomorphology, clinical features, and prognosis of inverted lesions of the urinary bladder are retrospectively reviewed. METHODS: Archived paraffin-embedded urothelial tumor samples from patients diagnosed with inverted urothelial papillary lesions between January 2005 and June 2020 were collated. A matched control population of patients with exophytic papillary lesions of the urothelium diagnosed during the same time period was randomly selected. The conventional clinicopathologic features of inverted urothelial papillary tumor were evaluated retrospectively and patient demographics, tumor characteristics, recurrence, and survival information were recorded. RESULTS: Lower recurrence rates were observed for inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP) relative to papillary urothelial neoplasms of low malignant potential and for low-grade papillary urothelial carcinoma with an inverted growth pattern (LG-PUCI) relative to low-grade papillary urothelial carcinomas. No recurrence was found among the inverted urothelial papilloma cases. The 2- and 5-year disease-free survival rates were 100.0% and 85.2% for IPUNLMP patients; 94.4% and 80.4% for papillary urothelial neoplasms of low malignant potential; 89.5% and 82.0% for LG-PUCI; 73.7% and 54.6% for low-grade papillary urothelial carcinoma; 40.0% and 20.0% for high-grade papillary urothelial carcinoma with an inverted growth pattern patients and 26.7% and 26.7% for high-grade papillary urothelial carcinoma. Multivariate Cox regression analysis of IPUNLMP and LG-PUCI/high-grade papillary urothelial carcinoma with an inverted growth pattern indicated that tumor number (hazard ratio=4.356; 95% CI: 1.145-16.570; P =0.031) was a powerful prognostic factor for disease-free survival. CONCLUSION: Noninvasive, papillary urothelial lesions of the bladder tend to have lower recurrence and a better outcome if an inverted growth pattern is shown.

In Vivo Staging the Progression of Colitis and Associated Cancer by Concurrent Microimaging of Key Biomarkers.

Currently colorectal cancer (CRC) staging (colitis, adenoma, and carcinoma) mainly relies on ex vivo pathologic analysis requiring an invasive surgical process with limited sample collection and increased metastatic risk. Thus, in vivo noninvasive pathological diagnosis is extremely demanded. By verifying the samples of clinical patients and CRC mouse models, it was found that vascular endothelial growth factor receptor 2 (VEGFR2) was barely expressed in the colitis stage and only appeared in adenoma and carcinoma stages with obvious elevation, while prostaglandin E receptor 4 (PTGER4) could be observed from colitis to adenoma and carcinoma stages with a gradient increase of expression. VEGFR2 and PTGER4 were further chosen as key biomarkers for molecular pathological diagnosis in vivo and corresponding molecular probes were constructed. The feasibility of in vivo noninvasive CRC staging by concurrent microimaging of dual biomarkers using confocal laser endoscopy (CLE) was verified in CRC mouse models and further confirmed by ex vivo pathological analysis. In vivo CLE imaging exhibited the correlation of severe colonic crypt structural alteration with a higher biomarker expression in adenoma and carcinoma stages. This strategy shows promise in benefiting patients undergoing CRC progression with in-time, noninvasive, and precise pathological staging, thus providing valuable guidance for selecting therapeutic strategies.

Adjuvant therapy for cholangiocarcinoma after surgery and prognosis factors for cholangiocarcinoma: A single-center retrospective cohort study.

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignant tumor, and more than 60% of patients have recurrence and metastasis after surgery. The efficacy of postoperative adjuvant therapy for CCA remains unclear. This study aimed to explore whether adjuvant therapy benefits patients with CCA and examine the independent prognostic factors for overall survival (OS) and progression-free survival (PFS). Methods: Patients with CCA undergoing surgery were retrospectively enrolled in this study from June 2016 to June 2022. The chi-square test or Fisher exact test was used to analyze the correlation between clinicopathologic characteristics. Survival curves were plotted using the Kaplan-Meier method, and the Cox regression model was used for univariate and multivariate analysis to search for independent prognostic factors. Results: Of the 215 eligible patients, 119 patients received adjuvant therapy, and the other 96 patients did not. The median follow-up was 37.5 months. The median OS of CCA patients with and without adjuvant therapy was 45 and 18 months (P < 0.001), respectively. The median PFS of CCA patients with and without adjuvant therapy was 34 and 8 months (P < 0.001), respectively. The Cox univariate and multivariate regression analysis showed that preoperative aspartate transaminase and carbohydrate antigen 19-9, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for OS (all P values < 0.05). Preoperative carbohydrate antigen 125, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for PFS (all P values < 0.05). The stratified analysis by TMN stage detected significant differences in the early stages (median OS [mOS]: P = 0.0128; median PFS [mPFS]: P = 0.0209) and advanced stages (mOS and mPFS: both P values < 0.001). Adjuvant therapy was also identified as a significantly favorable prognostic factor for OS and PFS in the early stages and advanced stages. Conclusion: Postoperative adjuvant therapy can improve the prognosis of patients with CCA, even in the early stages and advanced stages. All data suggest that adjuvant therapy should be incorporated into the treatment of CCA in all cases, where appropriate.

Epithelioid and spindle rhabdomyosarcoma with TFCP2 rearrangement in abdominal wall: a distinctive entity with poor prognosis.

BACKGROUND: Epithelioid and spindle rhabdomyosarcoma (ES-RMS) with TFCP2 rearrangement is a recently discovered rare variant of rhabdomyosarcoma composed of epithelioid and spindle cells, because it shows extraordinarily adverse prognosis and is easily misdiagnosed as other epithelioid or spindle cell tumors. METHODS: A rare case of ES-RMS with TFCP2 rearrangement was presented and English literatures in Pubmed online up to 01 July 2022 were gathered by two authors for a systematic review according to the inclusion and exclusion criteria. CASE PRESENTATION/RESULTS: We report a case of ES-RMS in an early 30s-years-old female, the neoplastic cells are remarkably immunoreactive with CK(AE1/AE3), and partially with ALK protein. Unexpectedly, the tumor shows TFCP2 rearrangement with coexistence of increased copy numbers of EWSR1 and ROS1 gene and MET gene mutation. Besides, Next-generation sequencing for genetic mutational profiling revealed frequent MET exon14 mutations in chromosome 7, most of which are C > T nonsynonymous SNV, and exon42 of ROS1 in chromosome 6 showed frequent G > T mutation up to 57.54%. In addition, neither MyoD1 mutation nor gene fusions were detected. Moreover, the patient shows high tumor mutational burden (TMB) up to 14.11 counts/Mb. Finally, as many cases of ES-RMS including our case had local progression or metastasis, we find, similar to epithelioid rhabdomyosarcoma (median survival time is 10 month), ES-RMS shows a more aggressive behavior and adverse prognosis (median survival time is 17 month) than spindle cell/sclerosing rhabdomyosarcoma (median survival time is 65 month) according previous studies. CONCLUSIONS: ES-RMS with TFCP2 rearrangement is a rare malignant tumor and easily confused with other epithelioid or spindle cell tumors, it may harbor additional gene alteration in addition to TFCP2 rearrangement, such as MET mutation, increased copy numbers of EWSR1 and ROS1 gene, high TMB. Most importantly, it may show very poor outcome with extensive metastasis.

Correlations of IL-6 and TGF-ß Gene Polymorphisms and Expressions With Osteoporotic, Thoracolumbar, Vertebral Compression Fracture.

Context: Associations between genes and diseases manifest as the influence of gene expression on disease development as well as the impact of variations in the disease-related genes themselves. It's important to determine the genetic variations that can lead to compressed fractures of osteoporotic, thoracic lumbar vertebrae to develop personalized clinical methods to prevent or delay the disease's development. Objective: The study intended to explore the correlations between the gene polymorphisms and gene expressions of the interleukin-6 (IL-6) gene and the transforming growth factor-beta (TGF-ß) gene and osteoporotic, thoracolumbar, vertebral compression fracture. Design: The research team performed an observational study using data from medical records. Setting: The study took place at Xuzhou Medical University in Xuzhou, China. Participants: Participants were 200 patients with an osteoporotic, thoracolumbar, vertebral compression fracture who had been admitted to the hospital at the university between 2019 and 2021 prior to the study and 200 healthy people The research team divided the participants into two groups. The patients became participants in the disease group, and the healthy individuals became participants in the control group. Outcome Measures: The research team: (1) collected peripheral blood from the two groups, (2) extracted genomic deoxyribonucleic acids (DNAs) from karyocytes, (3) examined the IL-6 and TGF-ß gene polymorphisms, and (4) analyzed and correlated participants' clinical data with the gene polymorphisms and expressions. The team used a quantitative polymerase chain reaction (qPCR) to examine the expression levels of IL-6 and TGF-ß. Results: Compared to the control group, the disease group: (1) had allele distributions that were significantly different at the rs2069829 locus of the IL-6 gene (P < .001) and at the rs3087453 of the TGF-ß gene (P = .004); (2) had significantly higher frequencies of allele T at the rs2069829 locus of the IL-6 gene and of allele G at the rs3087453 locus of the TGF-ß gene; (3) had genotype distributions that were significantly different at the rs2069829 locus (P < .001) and the rs2069857 locus (P = .048) of the IL-6 gene and at the rs3087453 locus (P < .001) of the TGF-ß gene; (4) had frequencies that were significantly higher of the TT genotype at the rs2069829 locus, the CC genotype at the rs2069857 locus, and the GC genotype at the rs3087453 locus of the IL-6 gene and the TGF-ß gene; (5) had dominant models that were significantly different at the rs2069829 locus of the IL-6 gene (P = .009) and at rs3087453 locus of the TGF-ß gene (P = .026) and had a recessive model that was significantly different at the rs2069857 locus of the IL-6 gene (P = .040); (6) had significantly different haplotypes CC (P < .001) and TC (P < .001) at the rs2069829 locus and the rs2069857 locus of the IL-6 gene and a significantly different haplotype AC (P = .011) at the rs1800469 locus and the rs3087453 locus of the TGF-ß gene; (7) had an IL-6 gene polymorphism at the rs2069857 locus that was related to the expression of the IL-6 gene (P < .05) and an expression of the IL-6 gene for participants with the AA genotype that was significantly lower than for other genotypes; (8) had a TGF-ß gene polymorphism at the rs1800469 locus that was associated with the expression of the TGF-ß gene (P < .05), and an expression for participants with the GG genotype that was significantly higher than for other genotypes; (9) had an IL-6 gene polymorphism at the rs2069857 locus with an overt correlation with the genotype of osteoporotic, thoracolumbar, vertebral compression fracture (P < .001). Also, participants in the disease group with the genotype CC mainly had type 2 and 3 fractures, while those with genotype AA primarily had type 0 and 1 fractures. Conclusions: IL-6 and TGF-ß gene polymorphisms and expressions are significantly related to osteoporotic, thoracolumbar, vertebral compression fracture.

Clinical, Morphological, and Molecular Study on Grade 2 and 3 Pleomorphic Xanthoastrocytoma.

PURPOSE: Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm2). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs. METHODS: Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%). RESULTS: Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the TERT promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; p = 0.0005) and all mutation sites were C228T. The cases without BRAF V600E mutation or with necrosis in grade 3 PXA had a poor prognosis (p = 0.01). CONCLUSION: These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. TERT promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and BRAF V600E mutation play an important role in the prognosis of grade 3 PXA.

Lymphomatosis cerebri: a rare diffuse leukoencephalopathy you should never miss.

INTRODUCTION: Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma that diffusely involves throughout the brain. In recent years, increasingly reported cases have notably broadened the spectrum of clinical and radiological features; however, it remains a great diagnostic challenge. CASE REPORT: We reported an atypical case of LC presented with subacute onset of focal neurological deficits and diffuse T2 hyperintensities without contrast enhancement on magnetic resonance imaging. He was initially considered as inflammatory leukoencephalopathy and received empirical corticosteroids, showing a dramatically clinical response. Three months later, the patient relapsed with deteriorating symptoms and enlarged brain lesions with mass-like enhancement. A diagnosis of LC was finally established according to the radiological and pathological findings. DISCUSSION: Though rare, LC should always be kept as a differential diagnosis of diffuse leukoencephalopathy. Neurologists should be aware of every detailed information about LC to avoid a delay of diagnostic biopsy in clinical practice.

ENO2 Promotes Colorectal Cancer Metastasis by Interacting with the LncRNA CYTOR and Activating YAP1-Induced EMT.

The glycolytic enzyme enolase 2 (ENO2) is dysregulated in many types of cancer. However, the roles and detailed molecular mechanism of ENO2 in colorectal cancer (CRC) metastasis remain unclear. Here, we performed a comprehensive analysis of ENO2 expression in 184 local CRC samples and samples from the TCGA and GEO databases and found that ENO2 upregulation in CRC samples was negatively associated with prognosis. By knocking down and overexpressing ENO2, we found that ENO2 promoted CRC cell migration and invasion, which is dependent on its interaction with the long noncoding RNA (lncRNA) CYTOR, but did not depend on glycolysis regulation. Furthermore, CYTOR mediated ENO2 binding to large tumor suppressor 1 (LATS1) and competitively inhibited the phosphorylation of Yes-associated protein 1 (YAP1), which ultimately triggered epithelial-mesenchymal transition (EMT). Collectively, these findings highlight the molecular mechanism of the ENO2-CYTOR interaction, and ENO2 could be considered a potential therapeutic target for CRC.

Long Noncoding RNA MIR4435-2HG Suppresses Colorectal Cancer Initiation and Progression By Reprogramming Neutrophils.

MIR4435-2HG, also known as LINC00978, has previously been described as an oncogenic long noncoding RNA (lncRNA). However, we show here that Mir4435-2hg depletion promoted colorectal tumorigenesis and progression in in vivo models of colitis-associated colorectal cancer, spontaneous intestinal adenomatous polyposis, and subcutaneous tumors. Alteration of MIR4435-2HG in colorectal cancer cells did not change the potential for cell proliferation, migration, or invasion in vitro. RNAscope assays showed that most MIR4435-2HG was located in the tumor stroma, which caused high expression of MIR4435-2HG in colorectal cancer tumor tissue. Transcriptome analysis of colorectal cancer tissues from wild-type and Mir4435-2hg-deficient mice revealed Mir4435-2hg as a tumor suppressor gene that regulated the immune microenvironment. Loss of Mir4435-2hg led to a decline in neutrophils and elevation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). In tissue-specific Mir4435-2hg knockout mice, we confirmed that Mir4435-2hg depletion in neutrophils, but not in intestinal epithelial cells, promoted colorectal cancer progression. Mechanistically, Mir4435-2hg depletion enhanced the immunosuppressive ability of PMN-MDSCs by disturbing their fatty acid metabolism. These findings suggest that MIR4435-2HG is a tumor-suppressing lncRNA whose deficiency could increase tumor-infiltrating PMN-MDSCs and enhance the immunosuppressive potential of PMN-MDSCs to promote colorectal cancer development. This provides a theoretical basis for further illustrating the pathogenesis of colorectal cancer and a potential antitumor immunotherapy target.

Constrained least-squares algorithm for active optics correction of a primary mirror.

Active optics technology improves the performance and image quality of large telescopes. To effectively compensate for optical aberrations, the constrained least-squares (CLS) algorithm, which considers the characteristics of the resultant moment, the force budget, and the local force smoothness, is proposed to optimize the force distribution. First, the constraint of the resultant moment is used to decouple the shape control and location control. Then, through the force budget, the surface residual and force amplitude can be balanced. At last, the local smooth constraint is proposed to reduce the mirror's internal stress. Simulations were conducted on a 4 m thin mirror to compare the force distributions obtained by the least-squares, bending modes (BMs), and CLS algorithms. The results show that under equivalent residuals, the proposed algorithm is superior to the BM algorithm and performs better on local force smoothness.