Preoperative prediction of MGMT promoter methylation in glioblastoma based on multiregional and multi-sequence MRI radiomics analysis.

O6-methylguanine-DNA methyltransferase (MGMT) has been demonstrated to be an important prognostic and predictive marker in glioblastoma (GBM). To establish a reliable radiomics model based on MRI data to predict the MGMT promoter methylation status of GBM. A total of 183 patients with glioblastoma were included in this retrospective study. The visually accessible Rembrandt images (VASARI) features were extracted for each patient, and a total of 14676 multi-region features were extracted from enhanced, necrotic, "non-enhanced, and edematous" areas on their multiparametric MRI. Twelve individual radiomics models were constructed based on the radiomics features from different subregions and different sequences. Four single-sequence models, three single-region models and the combined radiomics model combining all individual models were constructed. Finally, the predictive performance of adding clinical factors and VASARI characteristics was evaluated. The ComRad model combining all individual radiomics models exhibited the best performance in test set 1 and test set 2, with the area under the receiver operating characteristic curve (AUC) of 0.839 (0.709-0.963) and 0.739 (0.581-0.897), respectively. The results indicated that the radiomics model combining multi-region and multi-parametric MRI features has exhibited promising performance in predicting MGMT methylation status in GBM. The Modeling scheme that combining all individual radiomics models showed best performance among all constructed moels.

Disseminated Acanthamoeba castellanii infection in a patient with AIDS: a case report and literature review.

Background: Acanthamoeba castellanii infection is a rare condition primarily occurring in immunocompromised patients with extremely high mortality. Currently, there is no standard treatment for this condition, and successful treatment reports are scarce. Case presentation: We present a case of Acanthamoeba castellanii infection in a 63-year-old female patient with AIDS, who was admitted to our hospital with symptoms of fever, skin ulcers, subcutaneous nodules, and food regurgitation from the nose while eating. After initial empirical treatment failed, a biopsy of the subcutaneous nodule was performed, and metagenomic next-generation sequencing (mNGS) technology was used to detect pathogenic microorganisms in both the biopsy specimen and blood samples. The results revealed Acanthamoeba castellanii infection. Additionally, histopathological examination of the biopsy specimen and cytological examination of the secretions from the ulcer surface also confirmed this pathogenic infection. The patient's symptoms significantly improved upon discharge after adjusting the treatment regimen to a combination of anti-amebic therapy. Conclusion: Immunocompromised patients presenting with unexplained fever and skin or sinus lesions should be evaluated for Acanthamoeba castellanii infection. Multi-drug combination therapy is required for this organism infection, and a standard treatment protocol still needs further research. Metagenomic next-generation sequencing is a valuable tool for early diagnosis of unknown pathogen infections.

Combination of MRI-based prediction and CRISPR/Cas12a-based detection for IDH genotyping in glioma.

Early identification of IDH mutation status is of great significance in clinical therapeutic decision-making in the treatment of glioma. We demonstrate a technological solution to improve the accuracy and reliability of IDH mutation detection by combining MRI-based prediction and a CRISPR-based automatic integrated gene detection system (AIGS). A model was constructed to predict the IDH mutation status using whole slices in MRI scans with a Transformer neural network, and the predictive model achieved accuracies of 0.93, 0.87, and 0.84 using the internal and two external test sets, respectively. Additionally, CRISPR/Cas12a-based AIGS was constructed, and AIGS achieved 100% diagnostic accuracy in terms of IDH detection using both frozen tissue and FFPE samples in one hour. Moreover, the feature attribution of our predictive model was assessed using GradCAM, and the highest correlations with tumor cell percentages in enhancing and IDH-wildtype gliomas were found to have GradCAM importance (0.65 and 0.5, respectively). This MRI-based predictive model could, therefore, guide biopsy for tumor-enriched, which would ensure the veracity and stability of the rapid detection results. The combination of our predictive model and AIGS improved the early determination of IDH mutation status in glioma patients. This combined system of MRI-based prediction and CRISPR/Cas12a-based detection can be used to guide biopsy, resection, and radiation for glioma patients to improve patient outcomes.

Metagenomic next-generation sequencing-assisted diagnosis of a rare case of primary cutaneous acanthamoebiasis in an HIV patient: a case report.

Pathogenic and free-living Acanthamoeba are widely distributed in the environment and have been reported to cause keratitis and universally fatal encephalitis. Primary cutaneous acanthamoebiasis caused by Acanthamoeba is exceedingly rare and presents as isolated necrotic cutaneous lesions without involvement of the cornea or central nervous system. Cutaneous acanthamoebiasis often occurs in immunocompromised patients and is likely overlooked or even misdiagnosed only by cutaneous biopsy tissue histopathological analysis. Here, we report a HIV-infected 63-year-old female with oral leukoplakia for 4 months and scattered large skin ulcers all over the body for 2 months. The cause of the cutaneous lesions was unclear through cutaneous specimens histopathological analysis, and subsequently Acanthamoeba were detected by metagenomic next-generation sequencing (mNGS), which may be the cause of cutaneous lesions. Based on the mNGS results, a pathologist subsequently reviewed the previous pathological slides and found trophozoites of Acanthamoeba so that the cause was identified, and the skin ulcers improved significantly after treatment with multi-drug combination therapy. Acanthamoeba is also a host of pathogenic microorganisms. The presence of endosymbionts enhances the pathogenicity of Acanthamoeba, and no other pathogens were reported in this case. mNGS is helpful for rapidly diagnosing the etiology of rare skin diseases and can indicate the presence or absence of commensal microorganisms.

Engineered AAV13 variants with enhanced transduction and confined spread.

Precise targeting of specific regions within the central nervous system (CNS) is crucial for both scientific research and gene therapy in the context of brain diseases. Adeno-associated virus 13 (AAV13) is known for its restricted diffusion range within the CNS, making it an ideal choice for precise labeling and administration within small brain regions. However, AAV13 mediates relatively low expression of target genes. Here, we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction efficiency. We first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 capsid. We then inserted the 7m8 peptide, known to enhance cell transduction, into positions 587/588 and 585/586 of the AAV13 capsid, resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8, respectively. We found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13, while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice, with AAV13-587-7m8 infection retaining a limited spread range. These modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

Improving Molecule-Metal Surface Reaction Networks Using the Meta-Generalized Gradient Approximation: CO2 Hydrogenation.

Density functional theory is widely used to gain insights into molecule-metal surface reaction networks, which is important for a better understanding of catalysis. However, it is well-known that generalized gradient approximation (GGA) density functionals (DFs), most often used for the study of reaction networks, struggle to correctly describe both gas-phase molecules and metal surfaces. Also, GGA DFs typically underestimate reaction barriers due to an underestimation of the self-interaction energy. Screened hybrid GGA DFs have been shown to reduce this problem but are currently intractable for wide usage. In this work, we use a more affordable meta-GGA (mGGA) DF in combination with a nonlocal correlation DF for the first time to study and gain new insights into a catalytically important surface reaction network, namely, CO2 hydrogenation on Cu. We show that the mGGA DF used, namely, rMS-RPBEl-rVV10, outperforms typical GGA DFs by providing similar or better predictions for metals and molecules, as well as molecule-metal surface adsorption and activation energies. Hence, it is a better choice for constructing molecule-metal surface reaction networks.

General anesthesia versus local anesthesia for deep brain stimulation targeting of STN in Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is a viable therapeutic for advanced Parkinson's disease. However, the efficacy and safety of STN-DBS under local anesthesia (LA) versus general anesthesia (GA) remain controversial. This meta-analysis aims to compare them using an expanded sample size. METHODS: The databases of Embase, Cochrane Library and Medline were systematically searched for eligible cohort studies published between 1967 and 2023. Clinical efficacy was assessed using either Unified Parkinson's Disease Rating Scale (UPDRS) section III scores or levodopa equivalent dosage requirements. Subgroup analyses were performed to assess complications (adverse effects related to stimulation, general neurological and surgical complications, and hardware-related complications). RESULTS: Fifteen studies, comprising of 13 retrospective cohort studies and 2 prospective cohort studies, involving a total of 943 patients were included in this meta-analysis. The results indicate that there were no significant differences between the 2 groups with regards to improvement in UPDRS III score or postoperative levodopa equivalent dosage requirement. However, subgroup analysis revealed that patients who underwent GA with intraoperative imaging had higher UPDRS III score improvement compared to those who received LA with microelectrode recording (MER) (P = .03). No significant difference was found in the improvement of UPDRS III scores between the GA group and LA group with MER. Additionally, there were no notable differences in the incidence rates of complications between these 2 groups. CONCLUSIONS: Our meta-analysis indicates that STN-DBS performed under GA or LA have similar clinical outcomes and complications. Therefore, GA may be a suitable option for patients with severe symptoms who cannot tolerate the procedure under LA. Additionally, the GA group with intraoperative imaging showed better clinical outcomes than the LA group with MER. A more compelling conclusion would require larger prospective cohort studies with a substantial patient population and extended long follow-up to validate.

Synthesis of narrow-spectrum anti-mycobacterial molecules without effect on the diversity of gut microbiota in mice based on the structure of rifampicin.

Rifampicin (RIF) is a broad-spectrum antimicrobial agent that is also a first-line drug for treating tuberculosis (TB). Based on the naphthyl ring structure of RIF this study synthesized 16 narrow-spectrum antimicrobial molecules that were specifically anti-Mycobacterium tuberculosis (Mtb). The most potent candidate was 2-((6-hydroxynaphthalen-2-yl) methylene) hydrazine-1-carbothioamide (compound 3c) with minimum inhibitory concentration (MIC) of 1 µg/mL against Mtb. Synergistic anti-Mtb test indicated that none of the combinations of 3c with the major anti-TB drugs are antagonistic. Consistent with RIF, compound 3c induced large amounts of reactive oxygen radicals (ROS) in the cells of Mtb. The killing kinetics of compound 3c and RIF are very similar. Furthermore, molecular docking showed that compound 3c was able to access the RIF binding pocket of the ß subunit of Mtb RNA polymerase (RNAP). Experiments in mice showed that compound 3c increased the variety of intestinal flora in mice, while RIF significantly decreased the diversity of intestinal flora in mice. In addition, compound 3c is non-toxic to animal cells with a selection index (SI) much more than 10. The evidence from this study suggests that the further development of 3c could contribute to the development of novel drug for TB treatment.

19 Schiff bases as antimycobacterial agents: synthesis, molecular docking and a plausible mechanism of action.

Aim: To discover novel anti-Mycobacterium tuberculosis (Mtb) drugs, 19 compounds were synthesized; their anti-Mtb effects were evaluated and mechanisms of action were preliminarily explored. Materials & methods: The compounds were synthesized and their anti-Mtb activity was elucidated using resazurin microtiter assays. The plausible target of the potential compound was investigated by microimaging techniques, gas chromatography-mass spectrometry analysis and molecular docking. Results: 19 compounds inhibited Mtb growth with minimum inhibitory concentrations ranging from 1 to 32 µg/ml. Compounds 1-17 showed inhibition of Mtb KatG enzyme. Compound 19, the most potent, might be an inhibitor of Pks13 polyketide synthase. Conclusion: This study suggests that 2-((6-fluoropyridin-3-yl)methylene) hydrazine-1-carbothioamide (19) is a potential anti-Mtb lead compound with a novel mechanism of action.

Globally, more than 1.6 million people die of tuberculosis (TB) and about 11 million new cases occur each year. The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) has made it difficult to effectively treat TB. Therefore, 19 drugs were synthesized and assayed in the laboratory to verify whether they could inhibit the growth of Mtb. All compounds exhibit anti-Mtb effects at relatively low concentrations. Among them, compound 19 had a strong anti-Mtb effect, and its bactericidal effect on Mtb even exceeded that of isoniazid. In addition, it was preliminarily determined that compound 19 is a novel inhibitor of a key enzyme in the biosynthesis of Mtb cell walls. These findings demonstrate a potential new treatment option for TB but more research is needed to confirm the safety of these drugs.

A systematic review of ginsenoside biosynthesis, spatiotemporal distribution, and response to biotic and abiotic factors in American ginseng.

American ginseng (Panax quinquefolius) has gained recognition as a medicinal and functional food homologous product with several pharmaceutical, nutritional, and industrial applications. However, the key regulators involved in ginsenoside biosynthesis, the spatiotemporal distribution characteristics of ginsenosides, and factors influencing ginsenosides are largely unknown, which make it challenging to enhance the quality and chemical extraction processes of the cultivated American ginseng. This review presents an overview of the pharmacological effects, biosynthesis and spatiotemporal distribution of ginsenosides, with emphasis on the impacts of biotic and abiotic factors on ginsenosides in American ginseng. Modern pharmacological studies have demonstrated that American ginseng has neuroprotective, cardioprotective, antitumor, antidiabetic, and anti-obesity effects. Additionally, most genes involved in the upregulation of ginsenoside biosynthesis have been identified, while downstream regulators (OSCs, CYP450, and UGTs) require further investigation. Futhermore, limited knowledge exists regarding the molecular mechanisms of the impact of biotic and abiotic factors on ginsenosides. Notably, the nonmedicinal parts of American ginseng, particularly its flowers, fibrous roots, and leaves, exhibit higher ginsenoside content than its main roots and account for a considerable amount of weight in the whole plant, representing promising resources for ginsenosides. Herein, the prospects of molecular breeding and metabolic engineering based on multi-omics to improve the unstable quality of cultivated American ginseng and the shortage of ginsenosides are proposed. This review highlights the gaps in the current research on American ginseng and proposes solutions to address these limitations, providing a guide for future investigations into American ginseng ginsenosides.

Spatial and temporal heterogeneity of tumor immune microenvironment between primary tumor and brain metastases in NSCLC.

BACKGROUND: Brain metastasis is a common outcome in non-small cell lung cancer, and despite aggressive treatment, its clinical outcome is still frustrating. In recent years, immunotherapy has been developing rapidly, however, its therapeutic outcomes for primary lung cancer and brain metastases are not the same, suggesting that there may be differences in the immune microenvironment of primary lung cancer and brain metastases, however, we currently know little about these differences. METHODS: Seventeen paired samples of NSCLC and their brain metastases and 45 other unpaired brain metastases samples were collected for the current study. Immunohistochemical staining was performed on all samples for the following markers: immune checkpoints CTLA-4, PD-1, PD-L1, B7-H3, B7-H4, IDO1, and EphA2; tumor-infiltrating lymphocytes (TILs) CD3, CD4, CD8, and CD20; tumor-associated microglia/macrophages (TAMs) CD68 and CD163; and tumor proliferation index Ki-67. The differences in expression of these markers were compared in 17 paired samples, and the effect of the expression level of these markers on the prognosis of patients was analyzed in lung adenocarcinoma brain metastases samples. Subsequently, multiplex immunofluorescence staining was performed in a typical lung-brain paired sample based on the aforementioned results. The multiplex immunofluorescence staining results revealed the difference in tumor immune microenvironment between primary NSCLC and brain metastases. RESULTS: In 17 paired lesions, the infiltration of CTLA-4+ (P = 0.461), PD-1+ (P = 0.106), CD3+ (P = 0.045), CD4+ (P = 0.037), CD8+ (P = 0.008), and CD20+ (P = 0.029) TILs in brain metastases were significantly decreased compared with primary tumors. No statistically significant difference was observed in the CD68 (P = 0.954) and CD163 (P = 0.654) TAM infiltration between primary NSCLC and paired brain metastases. In all the brain metastases lesions, the expression of PD-L1 is related to the time interval of brain metastases in NSCLC. In addition, the Cox proportional hazards regression models showed high expression of B7-H4 (hazard ratio [HR] = 3.276, 95% confidence interval [CI] 1.335-8.041, P = 0.010) and CD68 TAM infiltration (HR = 3.775, 95% CI 1.419-10.044, P = 0.008) were independent prognosis factors for lung adenocarcinoma brain metastases patients. CONCLUSIONS: Both temporal and spatial heterogeneity is present between the primary tumor and brain metastases of NCSLC. Brain metastases lesions exhibit a more immunosuppressive tumor immune microenvironment. B7-H4 and CD68+ TAMs may have potential therapeutic value for lung adenocarcinoma brain metastases patients.

Application of intraoperative ultrasound in the resection of high-grade gliomas.

The incidence of gliomas is approximately 3-5/100,000, with high-grade gliomas accounting for approximately 30-40% of these tumors. Surgery is a confirmed positive factor in prolonging the survival of these patients, and a larger resection range means a longer survival time. Therefore, surgery for high-grade glioma patients should aim to maximize the extent of resection while preserving neurological function to achieve a better quality of life. There is consensus regarding the need to lengthen progression-free survival (PFS) and overall survival (OS) times. In glioma surgery, methods such as intraoperative computed tomography (ICT), intraoperative magnetic resonance imaging (IMRI), navigation, 5-aminolevulinic acid (5-ALA), and intraoperative ultrasound (IOUS) are used to achieve an expanded resection during the surgical procedure. IOUS has been increasingly used in the surgery of high-grade gliomas and various tumors due to its convenient intraoperative use, its flexible repeatability, and the relatively low cost of operating room construction. With the continuous upgrading of ultrasound equipment, IOUS has been able to better assist surgeons in achieving an increased extent of resection. This review aims to summarize the application of ultrasound in the surgery of high-grade gliomas in the past decade, its improvement in patient prognosis, and its prospects.

Early prediction of remaining useful life for lithium-ion batteries based on CEEMDAN-transformer-DNN hybrid model.

A reliable and safe energy storage system utilizing lithium-ion batteries relies on the early prediction of remaining useful life (RUL). Despite this, accurate capacity prediction can be challenging if little historical capacity data is available due to the capacity regeneration and the complexity of capacity degradation over multiple time scales. In this study, data decomposition, transformers, and deep neural networks (DNNs) are combined to develop a model of RUL prediction for lithium-ion batteries. Complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) is used for battery capacity sequential data to account for the capacity regeneration effect. The transformer networks are leveraged to predict each component of capacity regeneration thus improving the model's ability to handle long sequences while reducing the amount of data. The global degradation trend is predicted using a deep neural network. We validated the early prediction performance of the model using two publicly available battery datasets. Results show that the prediction model only uses 25%-30% data to achieve high accuracy. In the two public data sets, the RMSE errors were 0.0208 and 0.0337, respectively. A high level of accuracy is achieved with the model proposed in this study, which is based on fewer capacity data.

Probiotics Alleviate Chemotherapy-Associated Intestinal Mucosal Injury via the TLR4-NFκB Signaling Pathway.

Introduction: Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of Lactobacillus rhamnosus GG (LGG) in relieving intestinal mucosal injury induced by TMZ. Methods: Glioblastoma mice were divided into four groups: CON (control), LGG (109 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1ß, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKß, IκBα, and P65 with their phosphorylation in jejunum were measured. Results: Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos-IKKß and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group. Conclusion: LGG inhibits the activation of the TLR4-NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.

AAV11 enables efficient retrograde targeting of projection neurons and enhances astrocyte-directed transduction.

Viral tracers that enable efficient retrograde labeling of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Currently, some recombinant adeno-associated viruses (rAAVs) based on capsid engineering are widely used for retrograde tracing, but display undesirable brain area selectivity due to inefficient retrograde transduction in certain neural connections. Here we developed an easily editable toolkit to produce high titer AAV11 and demonstrated that it exhibits potent and stringent retrograde labeling of projection neurons in adult male wild-type or Cre transgenic mice. AAV11 can function as a powerful retrograde viral tracer complementary to AAV2-retro in multiple neural connections. In combination with fiber photometry, AAV11 can be used to monitor neuronal activities in the functional network by retrograde delivering calcium-sensitive indicator under the control of a neuron-specific promoter or the Cre-lox system. Furthermore, we showed that GfaABC1D promoter embedding AAV11 is superior to AAV8 and AAV5 in astrocytic tropism in vivo, combined with bidirectional multi-vector axoastrocytic labeling, AAV11 can be used to study neuron-astrocyte connection. Finally, we showed that AAV11 allows for analyzing circuit connectivity difference in the brains of the Alzheimer's disease and control mice. These properties make AAV11 a promising tool for mapping and manipulating neural circuits and for gene therapy of some neurological and neurodegenerative disorders.

Synthesis, antimycobacterial evaluation, and molecular docking study of 1,2,4-triazole derivatives.

Fifteen 1,2,4-triazole derivatives were synthesised in this study and their MIC values against Mycobacterium tuberculosis (Mtb) ranged from 2 to 32 µg/mL. Furthermore, their antimycobacterial activity was positively correlated with the KatG enzyme docking score. Among the 15 compounds, compound 4 showed the strongest bactericidal activity with an MIC of 2 µg/mL. The selectivity index of compound 4 is more than 10, indicating that the compound has low toxicity to animal cells and has the potential to become a drug. Molecular docking indicates that compound 4 can bind firmly to the Mtb KatG active site. The experimental results showed that compound 4 inhibited Mtb KatG and caused the accumulation of ROS in Mtb cells. We speculate that compound 4 causes the accumulation of ROS by inhibiting KatG, and ROS produces oxidative destruction, leading to the death of Mtb. This study provides a new idea for the development of novel anti-Mtb drugs.

Primary intracranial sarcomas: a clinicopathological investigation.

Background: The purpose of this study is to present a series of primary intracranial sarcomas (PIS), a rare type of tumor of the central nervous system, in order to improve our understanding of the disease. These tumors are heterogeneous and prone to recurrence after resection, exhibiting a high mortality rate. As PIS has yet to be understood and studied on a large scale, it is vital for further evaluation and research. Methods: Our study included 14 cases of PIS. The patients' clinical, pathological, and imaging features were retrospectively analyzed. Additionally, targeted DNA next-generation sequencing (NGS) was applied for the 481-gene panel to detect gene mutations. Results: The average age for PIS patients was 31.4 years. Headache (7, 50.0%) was the most common symptom leading to the hospital visit. Twelve cases had PIS located in the supratentorial area and two in the cerebellopontine angle region. The maximum tumor diameter ranged from 19.0 mm to 130.0 mm, with an average diameter of 50.3 mm. Pathological types of tumors were heterogeneous, with chondrosarcoma being the most common, followed by fibrosarcoma. Eight of the 10 PIS cases that underwent MRI scanning showed gadolinium enhancement; 7 of these cases were heterogeneous, and 1 of them was garland-like. Targeted sequencing was performed in two cases and identified mutations in genes such as NRAS, PIK3CA, BAP1, KDR, BLM, PBRM1, TOP2A, DUSP2, and CNV deletions of SMARCB1. Additionally, the SH3BP5::RAF1 fusion gene was also detected. Of the 14 patients, 9 underwent a gross total resection (GTR), and 5 chose subtotal resection. Patients who underwent GTR displayed a trend toward superior survival. Among the 11 patients with available follow-up information, one had developed lung metastases, three had died, and eight were alive. Conclusion: PIS is extremely rare compared to extracranial soft sarcomas. The most common histological type of intracranial sarcoma (IS) is chondrosarcoma. Patients who underwent GTR of these lesions showed improved survival rates. Recent advancements in NGS aided in the identification of diagnostic and therapeutic PIS-relevant targets.

Meningioangiomatosis Combined with Calcifying Pseudoneoplasms of Neuraxis.

Meningioangiomatosis (MA) is a rare hamartomatous or meningovascular lesion involving the central nervous system, and is sometimes associated with intracranial meningiomas. Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing benign tumor-like lesions that can occur anywhere along the neuraxis. Here, we report a rare case of MA combined with CAPNON. A 31-year-old woman was admitted to our hospital because of a high-density mass in the left frontal lobe, detected by computed tomography (CT) during a physical examination. She had a 3-year history of obsessive-compulsive disorder. We describe the imaging, histopathological, and molecular characteristics of the patient. To our knowledge, this is the first report describing MA combined with CAPNON. We reviewed the literature on MA and CAPNON over the last decade and summarized the points for differential diagnosis and treatment. It is difficult to preoperatively distinguish between MA and CAPNON. However, this coexisting condition should be considered when intra-axial calcification lesions are observed on radiological imaging. Accurate diagnosis and appropriate treatment are likely to benefit this patient group.

MiR-506 targets polypyrimidine tract-binding protein 1 to inhibit airway inflammatory response and remodeling via mediating Wnt/ß-catenin signaling pathway.

BACKGROUND: Airway remodeling, which contributes to the clinical course of childhood asthma, occurs due to airway inflammation and is featured by anomalous biological behaviors of airway smooth muscle cells (ASMCs). microRNA (miRNA) plays an essential role in the etiopathogenesis of asthma. OBJECTIVE: This research was aimed to characterize miR-506 in asthma and uncover potential regulatory machinery. MATERIAL AND METHODS: The asthmatic cell model was established by treating ASMCs with transforming growth factor-beta1 (TGF-ß1) and assessed by the levels of interleukin (IL)-1ß and interferon gamma (IFN-γ). Using real-time quantitative polymerase chain reaction, mRNA expression of miR-506 and polypyrimidine tract-binding protein 1 (PTBP1) was measured. Cell counting kit-8 and Transwell migration tests were used for estimating the capacity of ASMCs to proliferate and migrate. Luciferase reporter assay was used to corroborate whether miR-506 was directly bound to PTBP1. Expression of PTBP1, collagen I and III, and essential proteins of the wingless-related integration (Wnt)/ß-catenin pathway (ß-catenin, c-MYC and cyclin D1) was accomplished by Western blot analysis. The involvement of Wnt/ß-catenin signaling in asthma was confirmed by Wnt signaling pathway inhibitor (IWR-1). RESULTS: miR-506 was poorly expressed in asthmatic tissues and cell model. Functionally, overexpression of miR-506 reduced aberrant proliferation, migration, inflammation and collagen deposition of ASMCs triggered by TGF-ß1. Mechanically, miR-506 directly targeted the 3' untranslated region (3-UTR) of PTBP1 and had a negative regulation on PTBP1 expression. Moreover, overexpression of miR-506 suppressed the induction of Wnt/ß-catenin pathway. The administration of IWR-1 further validated negative correlation between miR-506 and the Wnt/ß-catenin pathway in asthma. CONCLUSION: Our data indicated that targeting miR-506/PTBP1/Wnt/ß-catenin axis might point in a helpful direction for treating asthma in children.

MiR-506 targets polypyrimidine tract-binding protein 1 to inhibit airway inflammatory response and remodeling via mediating Wnt/airway smooth -muscle cells, childhood asthma, miR-506, PTBP1, Wnt/B-catenin-catenin signaling pathway

Background: Airway remodeling, which contributes to the clinical course of childhood asthma, occurs due to airway inflammation and is featured by anomalous biological behaviors of airway smooth muscle cells (ASMCs). microRNA (miRNA) plays an essential role in the etiopathogenesis of asthma. Objective: This research was aimed to characterize miR-506 in asthma and uncover potential regulatory machinery. Material and methods: The asthmatic cell model was established by treating ASMCs with transforming growth factor-beta1 (TGF-β1) and assessed by the levels of interleukin (IL)-1β and interferon gamma (IFN-γ). Using real-time quantitative polymerase chain reaction, mRNA expression of miR-506 and polypyrimidine tract-binding protein 1 (PTBP1) was measured. Cell counting kit-8 and Transwell migration tests were used for estimating the capacity of ASMCs to proliferate and migrate. Luciferase reporter assay was used to corroborate whether miR-506 was directly bound to PTBP1. Expression of PTBP1, collagen I and III, and essential proteins of the wingless-related integration (Wnt)/β-catenin pathway (β-catenin, c-MYC and cyclin D1) was accomplished by Western blot analysis. The involvement of Wnt/β-catenin signaling in asthma was confirmed by Wnt signaling pathway inhibitor (IWR-1). Results: miR-506 was poorly expressed in asthmatic tissues and cell model. Functionally, overexpression of miR-506 reduced aberrant proliferation, migration, inflammation and collagen deposition of ASMCs triggered by TGF-β1. Mechanically, miR-506 directly targeted the 3’ untranslated region (3-UTR) of PTBP1 and had a negative regulation on PTBP1 expression. Moreover, overexpression of miR-506 suppressed the induction of Wnt/β-catenin pathway. The administration of IWR-1 further validated negative correlation between miR-506 and the Wnt/β-catenin pathway in asthma (AU)