SPP1 could be an immunological and prognostic biomarker: From pan-cancer comprehensive analysis to osteosarcoma validation.

Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan-cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan-Meier survival analyses to analyze overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.

Molecular identification and functional characterization of a transcription factor GeRAV1 from Gelsemium elegans.

BACKGROUND: Gelsemium elegans is a traditional Chinese medicinal plant and temperature is one of the key factors affecting its growth. RAV (related to ABI3/VP1) transcription factor plays multiple roles in higher plants, including the regulation of plant growth, development, and stress response. However, RAV transcription factor in G. elegans has not been reported. RESULTS: In this study, three novel GeRAV genes (GeRAV1-GeRAV3) were identified from the transcriptome of G. elegans under low temperature stress. Phylogenetic analysis showed that GeRAV1-GeRAV3 proteins were clustered into groups II, IV, and V, respectively. RNA-sequencing (RNA-seq) and real-time quantitative PCR (qRT-PCR) analyses indicated that the expression of GeRAV1 and GeRAV2 was increased in response to cold stress. Furthermore, the GeRAV1 gene was successfully cloned from G. elegans leaf. It encoded a hydrophilic, unstable, and non-secretory protein that contained both AP2 and B3 domains. The amino acid sequence of GeRAV1 protein shared a high similarity of 81.97% with Camptotheca acuminata CaRAV. Subcellular localization and transcriptional self-activation experiments demonstrated that GeRAV1 was a nucleoprotein without self-activating activity. The GeRAV1 gene was constitutively expressed in the leaves, stems, and roots of the G. elegans, with the highest expression levels in roots. In addition, the expression of the GeRAV1 gene was rapidly up-regulated under abscisic acid (ABA), salicylic acid (SA), and methyl jasmonate (MeJA) stresses, suggesting that it may be involved in hormonal signaling pathways. Moreover, GeRAV1 conferred improved cold and sodium chloride tolerance in Escherichia coli Rosetta cells. CONCLUSIONS: These findings provided a foundation for further understanding on the function and regulatory mechanism of the GeRAV1 gene in response to low-temperature stress in G. elegans.

Hypergravity stimulates mechanical behavior and micro-architecture of tibia in rats.

INTRODUCTION: The bone tissue is susceptible to hypergravity (+ G) environment. It is necessary to discuss the extent to which specific + G values are beneficial or detrimental to bone tissue. The objective of this study was to characterize the effects of high + G values on mechanical properties, microstructures, and cellular metabolism of bone. MATERIALS AND METHODS: 30 male Wistar rats aged 12 weeks were randomly divided into 5 groups, and bore different + G (namely + 1G, + 4G, + 8G, + 10G and + 12G) environments respectively for 4 weeks, 5 days each week, and 3 minutes each day. The macro-mechanical parameters, microstructure parameters, and mRNA transcription levels of the tibia were determined through the three-point bending method, micro-CT detection, and q-PCR analysis, respectively. RESULTS: As the + G value increases, hypergravity becomes increasingly detrimental to the macro-mechanical performance of rat tibia. Concerning the microstructure of cancellous bone, there appears to be a favorable trend at + 4G, followed by a progressively detrimental trend at higher G values. In addition, the mRNA transcription levels of OPG and RANKL show an initial tendency of enhanced bone absorption at +4G, followed by an increase in bone remodeling capacity as G value increases. CONCLUSION: The higher G values correspond to poorer macro-mechanical properties of the tibia, and a + 4G environment benefits the microstructure of the tibia. At the cellular level, bone resorption is enhanced in the + 4G group, but the bone remodeling capability gradually increases with further increments in G values.

Treadmill exercise promotes bone tissue recovery in rats subjected to high + Gz loads.

INTRODUCTION: High + Gz loads, the gravitational forces experienced by the body in hypergravity environments, can lead to bone loss in pilots and astronauts, posing significant health risks. MATERIALS AND METHODS: To explore the effect of treadmill exercise on bone tissue recovery, a study was conducted on 72 male Wistar rats. These rats were subjected to four weeks of varying levels of periodic high + Gz loads (1G, 8G, 20G) experiments, and were subsequently divided into the treadmill group and the control group. The treadmill group underwent a continuous two-week treadmill experiment, while the control group rested during this period. The mechanical properties, microstructure, and molecular markers of their tibial bone tissue were measured using three-point bending, micro-CT, and PCR. RESULTS: The results showed that treadmill exercise improved the elastic modulus, ultimate deflection, and ultimate load of rat bone tissue. It also increased the number, density, and volume fraction of bone trabeculae, and decreased their separation. Moreover, treadmill exercise enhanced osteogenesis and inhibited osteoclastogenesis. CONCLUSION: This study demonstrates that treadmill exercise can promote the recovery of bone tissue in rats subjected to high + Gz loads, providing a potential countermeasure for bone loss in pilots and astronauts.

Choline Dehydrogenase Contributes to Salt Tolerance in Dunaliella through Betaine Synthesis.

In Dunaliella tertiolecta, a microalga renowned for its extraordinary tolerance to high salinity levels up to 4.5 M NaCl, the mechanisms underlying its stress response have largely remained a mystery. In a groundbreaking discovery, this study identifies a choline dehydrogenase enzyme, termed DtCHDH, capable of converting choline to betaine aldehyde. Remarkably, this is the first identification of such an enzyme not just in D. tertiolecta but across the entire Chlorophyta. A 3D model of DtCHDH was constructed, and molecular docking with choline was performed, revealing a potential binding site for the substrate. The enzyme was heterologously expressed in E. coli Rosetta (DE3) and subsequently purified, achieving enzyme activity of 672.2 U/mg. To elucidate the role of DtCHDH in the salt tolerance of D. tertiolecta, RNAi was employed to knock down DtCHDH gene expression. The results indicated that the Ri-12 strain exhibited compromised growth under both high and low salt conditions, along with consistent levels of DtCHDH gene expression and betaine content. Additionally, fatty acid analysis indicated that DtCHDH might also be a FAPs enzyme, catalyzing reactions with decarboxylase activity. This study not only illuminates the role of choline metabolism in D. tertiolecta's adaptation to high salinity but also identifies a novel target for enhancing the NaCl tolerance of microalgae in biotechnological applications.

Targeting RNA oxidation by ISG20-mediated degradation is a potential therapeutic strategy for acute kidney injury.

Oxidative stress plays a central role in the pathophysiology of acute kidney injury (AKI). Although RNA is one of the most vulnerable cell components to oxidative damage, it is unclear whether RNA oxidation is involved in the pathogenesis of AKI. In this study, we found that the level of RNA oxidation was significantly enhanced in kidneys of patients with acute tubular necrosis (ATN) and in the renal tubular epithelial cells (TECs) of mice with AKI, and oxidized RNA overload resulted in TEC injury. We further identified interferon-stimulated gene 20 (ISG20) as a novel regulator of RNA oxidation in AKI. Tubule-specific deficiency of ISG20 significantly aggravated renal injury and RNA oxidation in the ischemia/reperfusion-induced AKI mouse model and ISG20 restricted RNA oxidation in an exoribonuclease activity-dependent manner. Importantly, overexpression of ISG20 protected against oxidized RNA overproduction and renal ischemia/reperfusion injury in mice and ameliorated subsequent protein aggresome accumulation, endoplasmic reticulum stress, and unfolded protein response. Thus, our findings provide direct evidence that RNA oxidation contributes to the pathogenesis of AKI and that ISG20 importantly participates in the degradation of oxidized RNA, suggesting that targeting ISG20-handled RNA oxidation may be an innovative therapeutic strategy for AKI.

Phenome-wide causal associations between osteoarthritis and other complex traits through the latent causal variable analysis.

BACKGROUND: Individuals with osteoarthritis present with comorbidities, and the potential causal associations remain incompletely elucidated. The present study undertook a large-scale investigation about the causality between osteoarthritis and variable traits, using the summary-level data of genome-wide association studies (GWAS). METHODS: The present study included the summary-level GWS data of knee osteoarthritis, hip osteoarthritis, hip or knee osteoarthritis, hand osteoarthritis, and other 1355 traits. Genetic correlation analysis was conducted between osteoarthritis and other traits through cross-trait bivariate linkage disequilibrium score regression. Subsequently, latent causal variable analysis was performed to explore the causal association when there was a significant genetic correlation. Genetic correlation and latent causal variable analysis were conducted on the Complex Traits Genomics Virtual Lab platform ( https://vl.genoma.io/ ). RESULTS: We found 133 unique phenotypes showing causal relationships with osteoarthritis. Our results confirmed several well-established risk factors of osteoarthritis, such as obesity, weight, BMI, and meniscus derangement. Additionally, our findings suggested putative causal links between osteoarthritis and multiple factors. Socioeconomic determinants such as occupational exposure to dust and diesel exhaust, extended work hours exceeding 40 per week, and unemployment status were implicated. Furthermore, our analysis revealed causal associations with cardiovascular and metabolic disorders, including heart failure, deep venous thrombosis, type 2 diabetes mellitus, and elevated cholesterol levels. Soft tissue and musculoskeletal disorders, such as hallux valgus, internal derangement of the knee, and spondylitis, were also identified to be causally related to osteoarthritis. The study also identified the putative causal associations of osteoarthritis with digestive and respiratory diseases, such as Barrett's esophagus, esophagitis, and asthma, as well as psychiatric conditions including panic attacks and manic or hyperactive episodes. Additionally, we observed osteoarthritis causally related to pharmacological treatments, such as the use of antihypertensive medications, anti-asthmatic drugs, and antidepressants. CONCLUSION: Our study uncovered a wide range of traits causally associated with osteoarthritis. Further studies are needed to validate and illustrate the detailed mechanism of those causal associations.

[Effects of removing superficial layer of cartilage on the surface morphology and mechanical behavior of cartilage].

Superficial cartilage defect is an important factor that causes osteoarthritis. Therefore, it is very important to investigate the influence of superficial cartilage defects on its surface morphology and mechanical properties. In this study, the knee joint cartilage samples of adult pig were prepared, which were treated by enzymolysis with chymotrypsin and physical removal with electric friction pen, respectively. Normal cartilage and surface treated cartilage were divided into five groups: control group (normal cartilage group), chymotrypsin immersion group, chymotrypsin wiping group, removal 10% group with electric friction pen, and removal 20% group with electric friction pen. The surface morphology and structure of five groups of samples were characterized by laser spectrum confocal microscopy and environmental field scanning electron microscopy, and the mechanical properties of each group of samples were evaluated by tensile tests. The results show that the surface arithmetic mean height and fracture strength of the control group were the smallest, and the fracture strain was the largest. The surface arithmetic mean height and fracture strength of the removal 20% group with electric friction pen were the largest, and the fracture strain was the smallest. The surface arithmetic mean height, fracture strength and fracture strain values of the other three groups were all between the above two groups, but the surface arithmetic mean height and fracture strength of the removal 10% group with electric friction pen, the chymotrypsin wiping group and the chymotrypsin soaking group decreased successively, and the fracture strain increased successively. In addition, we carried out a study on the elastic modulus of different groups, and the results showed that the elastic modulus of the control group was the smallest, and the elastic modulus of the removal 20% group with electric friction pen was the largest. The above study revealed that the defect of the superficial area of cartilage changed its surface morphology and structure, and reduced its mechanical properties. The research results are of great significance for the prevention and repair of cartilage injury.

Venous thromboembolism incidence associated with pegylated asparaginase (ASP) compared to the native L-ASP: A retrospective analysis with an ASP-based protocol in adult patients with acute lymphoblastic leukaemia.

Venous thromboembolism (VTE) is a well-known complication in patients with acute lymphoblastic leukaemia (ALL) receiving asparaginase (ASP)-based chemotherapy, including the ASP-intensive Dana-Farber Cancer Institute (DFCI) 91-01 protocol for adults. Since 2019, native L-ASP is no longer available in Canada and was replaced by pegylated (PEG)-ASP. To determine whether the incidence of VTE has changed since switching from L-ASP to PEG-ASP, we conducted a single-centred retrospective cohort study. We included 245 adult patients with Philadelphia chromosome negative ALL between 2011 and 2021, with 175 from the L-ASP group (2011-2019) and 70 from the PEG-ASP group (2018-2021). During Induction, 10.29% (18/175) of patients who received L-ASP developed VTE, whereas 28.57% (20/70) of patients who received PEG-ASP developed VTE (p = 0.0035; odds ratio [OR] 3.35, 95% confidence interval [CI] 1.51-7.39), after adjusting for line type, gender, history of VTE, platelets at diagnosis. Similarly, during Intensification, 13.64% (18/132) of patients had VTE on L-ASP while 34.37% (11/32) of patients on PEG-ASP developed VTE (p = 0.0096; OR 3.96, 95% CI 1.57-9.96 with multivariable analysis). We found that PEG-ASP is associated with a higher incidence of VTE compared to L-ASP, both during Induction and Intensification, despite the administration of prophylactic anticoagulation. Further VTE mitigation strategies are needed in particular for adult patients with ALL receiving PEG-ASP.

Adjustable short-term memory of SiOx:Ag-based memristor for reservoir computing.

Temporal information processing is critical for a wide spectrum of applications, such as finance, biomedicine, and engineering. Reservoir computing (RC) can efficiently process temporal information with low training costs. Various memristors have been explored to demonstrate RC systems leveraging the short-term memory and nonlinear dynamic behaviours. However, the short-term memory is fixed after the device fabrication, limiting the applications to diverse temporal analysis tasks. In this work, we propose the approaches to modulating the short-term memory of Pt/SiOx:Ag/Pt memristor for the performance improvement of the RC systems. By controlling the read voltage, pulse amplitude and pulse width applied to the devices, the obtainable range of the characteristic time reaches three orders of magnitude from microseconds to around milliseconds. Based on the fabricated memristor, the classification of 4-bit pulse streams is demonstrated. Memristor-based RC systems with adjustable short-term memory are constructed for time-series prediction and pattern recognition tasks with different requirements for the characteristic times. The simulation results show that low normalized root mean square error of 0.003 (0.27) in Hénon map (Mackey-Glass time series) and excellent classification accuracy of 99.6% (91.7%) in spoken-digit recognition (MNIST image recognition) are achieved, which outperforms most memristor-based RC systems recently reported. Furthermore, the RC networks with diverse short-term memories are constructed to address more complicated tasks with low prediction errors. This work proves the high controllability of memristor-based RC systems to handle multiple temporal processing tasks.

Design of Orally-bioavailable Tetra-cyclic phthalazine SOS1 inhibitors with high selectivity against EGFR.

KRAS mutations (G12C, G12D, etc.) are implicated in the oncogenesis and progression of many deadliest cancers. Son of sevenless homolog 1 (SOS1) is a crucial regulator of KRAS to modulate KRAS from inactive to active states. We previously discovered tetra-cyclic quinazolines as an improved scaffold for inhibiting SOS1-KRAS interaction. In this work, we report the design of tetra-cyclic phthalazine derivatives for selectively inhibiting SOS1 against EGFR. The lead compound 6c displayed remarkable activity to inhibit the proliferation of KRAS(G12C)-mutant pancreas cells. 6c showed a favorable pharmacokinetic profile in vivo, with a bioavailability of 65.8% and exhibited potent tumor suppression in pancreas tumor xenograft models. These intriguing results suggested that 6c has the potential to be developed as a drug candidate for KRAS-driven tumors.

Achievements and perspectives of synthetic biology in botanical insecticides.

Botanical insecticides are the origin of all insecticidal compounds. They have been widely used to control pests in crops for a long time. Currently, the commercial production of botanical insecticides extracted from plants is limited because of insufficient raw material supply. Synthetic biology is a promising and effective approach for addressing the current problems of the production of botanical insecticides. It is an emerging biological research hotspot in the field of botanical insecticides. However, the biosynthetic pathways of many botanical insecticides are not completely elucidated. On the other hand, the cytotoxicity of botanical pesticides and low efficiency of these biosynthetic enzymes in new hosts make it still challenging for their heterologous production. In the present review, we summarized the recent developments in the heterologous production of botanical insecticides, analyzed the current challenges, and discussed the feasible production strategies, focusing on elucidating biosynthetic pathways, enzyme engineering, host engineering, and cytotoxicity engineering. Looking to the future, synthetic biology promises to further advance heterologous production of more botanical pesticides.

Bone marrow mesenchymal stem cell-derived exosomes shuttling miR-150-5p alleviates mechanical allodynia in rats by targeting NOTCH2 in microglia.

BACKGROUND: This study probes into the function and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosomes loaded with miR-150-5p in mechanical allodynia. METHODS: BMSCs were infected with miR-150-5p inhibition lentiviruses to obtain exosomes with low miR-150-5p expression. A L5 spinal nerve ligation (SNL) model was established in rats where exosomes, NOTCH2 overexpression/inhibition plasmids, or microglial cells were intrathecally administered. Hind paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of rats were measured. TUNEL staining was used to measure the apoptotic rate in rat spinal dorsal horn (SDH), ELISA to evaluate pro-inflammatory factor levels, and RT-qPCR, western blotting, and immunohistochemistry to detect miR-150-5p and NOTCH2 expression. Immunofluorescence was used for localizing exosomes and NOTCH2 and detecting the expression of OX42, a maker for microglia. Dual luciferase reporter and RNA pull down assays were performed to validate the putative binding between miR-150-5p and NOTCH2. RESULTS: NOTCH2 expressed at a high level and miR-150-5p was downregulated in SDH of SNL rats. Exosomes injected were localized in rat SDH. BMSC-exosomes or NOTCH2 downregulation increased PWT and PWL of SNL rats and reduced apoptosis and inflammation in SDH. In contrast, NOTCH2 overexpression aggravated mechanical allodynia and SDH injury. Moreover, inhibiting miR-150-5p in BMSC-exosomes offset the therapeutic effects of BMSC-exosomes. Microglia activation induced mechanical allodynia in wild rats, while intrathecal injection of microglial cells incubated with BMSC-exosomes showed alleviated mechanical allodynia in SNL rats. NOTCH2 was targeted by miR-150-5p. CONCLUSION: BMSC-derived exosomal miR-150-5p alleviates mechanical allodynia by targeting NOTCH2 in microglial cells.

Clinical characteristics of intracranial aneurysms in elderly patents over 70 years old: a retrospective observational study.

BACKGROUND: Although the characteristics of intracranial aneurysms (IAs) in different age groups have been well documented, they remain relatively unclear in elderly patients due to a lack of large sample studies. METHODS: Data from IA patients aged more than 70 years who were treated in our centre from January 2016 to January 2020 were retrospectively collected. RESULTS: A total of 290 elderly patients (75.9% female) with a mean age of 74.0 ± 4.7 years were analysed. Rupture occurred in 60.7% of patients, 38.6% of whom presented with meningeal irritation, and seizures were noted in 2.3%. A total of 48.9% of the patients with ruptured IAs had initial symptoms presenting with slow development, and the mean delay from ictus was prolonged to 264.2 ± 914.0 hours. In addition, 61.9% of the patients with ruptured IAs had lesions with a maximum diameter of less than 5 mm. A total of 30.3% of the patients had multiple aneurysms, 35.5% had aneurysms with irregular shapes and 54.8% had cerebrovascular atherosclerotic stenosis (CAS). Pulmonary infection (n = 138, 47.6%), hydrocephalus (n = 72, 24.8%), and thrombosis (n = 35, 12.1%) were common complications during hospitalization. By the end of the 1-year follow-up, 22.1% of the patients had unfavourable clinical outcomes, and the mortality rate was 23.4%. CONCLUSIONS: Several characteristics regarding IAs in elderly patients were reported, including an obvious female predominance; mild, slow initial symptom development causing prolonged admission delay; a low incidence of meningeal irritation and seizures due to decreased electrophysiological activity of the neurons; increased percentages of CAS, multiple aneurysms, and aneurysms with daughter sacs causing a high risk of rupture even for small lesions; a high risk of complications during hospitalization; and relatively poor clinical outcomes.

The prognostic value of the Charlson comorbidity index in aged patients with intracerebral hemorrhage.

BACKGROUND: Comorbidities are common in aged intracerebral hemorrhage patients. The purpose of this study was to assess whether the Charlson Comorbidity Index (CCI) was associated with in-hospital death and short-term functional outcome in elderly patients (age ≥ 70) with intracerebral hemorrhage (ICH). METHODS: This was a retrospective cohort of aged ICH patients (≥70 years old) admitted within 24 hours of ICH onset. The CCI was derived using hospital discharge ICD-9 CM codes and patient history obtained from standardized case report forms. Multivariable logistic regression was used to determine the independent effect of the CCI score on clinical outcomes. RESULTS: In this cohort of 248 aged ICH patients, comorbid conditions were common, with CCI scores ranging from 2 to 12. Logistic regression showed that the CCI score was independently predictive of 1-month functional outcome (OR = 1.642, P < 0.001) and in-hospital death (OR = 1.480, P = 0.003). Neither ICH volume nor the presence of IVH was an independent predictive factor for 1-month functional outcome or in-hospital mortality (P < 0.05). CONCLUSION: Comorbid medical conditions as assessed by the CCI independently influence short-term outcomes in aged ICH patients. The characteristics of the hematoma itself, such as ICH volume and the presence of IVH, seem to have a reduced effect on it.

A comparison of three preoperative nutritional assessment methods for predicting ovarian cancer patient prognosis: which is better?

BACKGROUND: The study aimed to compare the predictive values of three widely used nutritional assessment methods, body mass index (BMI), Nutritional Risk Screening 2002 (NRS 2002), and the prognostic nutritional index (PNI), for different clinical prognostic indicators of ovarian cancer patients. METHODS: Patients diagnosed with ovarian cancer treated in our hospital between January 2017 and March 2019 were retrospectively included. The three nutritional assessment methods were assessed, and multivariable analysis was conducted to explore predictive factors for clinical prognoses. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUROC) were generated to evaluate the discriminative abilities of the three nutritional assessment tools. RESULTS: A total of 442 patients were recruited. Multivariable analysis revealed that the PNI value predicted 1-year death and 1-year recurrence and that both the NRS 2002 score and the PNI value predicted 30-day readmission (P < 0.05). For PNI, AUROCs were 0.834 for predicting 1-year death and 0.719 for 1-year recurrence prediction; for NRS, the AUROC was 0.820 2002 for predicting 30-day readmission. The optimal cutoff values that maximized the prognostic prediction ability were PNI values of 47.75 g/L and 50.40 g/L for 1-year death and 1-year recurrence, respectively, and an NRS 2002 score of 3 points for 30-day readmission following discharge. CONCLUSION: For ovarian cancer patients, the PNI is better at predicting 1-year death and 30-day readmission after discharge, and the NRS 2002 is superior for predicting 1-year recurrence.

A propensity score-matched study on the short-term outcome of ruptured blood blister-like aneurysm treated by microsurgery or endovascular surgery: a single-center study of 155 cases.

Treating blood blister-like aneurysms (BBA) is a major neurosurgical challenge. Whether endovascular repair serves as a better strategy than microsurgery remains controversial. We aim to perform a propensity score-matched (PSM) retrospective study to analyze the short-term outcome in BBA patients who received microsurgery and endovascular treatment. One hundred fifty-five eligible patients with internal carotid artery BBA were retrospectively collected with demographic and angiographic baseline in a single center. Three-month outcome and adverse events were set as outcome endpoints. PSM was used to match the microsurgery and endovascular group. Matching effect was evaluated by distribution variation analysis and love plot. The outcome of neurosurgery and endovascular treatment was then compared before and after PSM. Better WFNS levels (p = .017) and modified Fisher grade (p = .027) were noted in endovascular group before matching. Other baseline including angiographic features were comparable between two groups. Before matching, the 3-month outcome of endovascular repair surgery was more favorable than microsurgery (p < .0001). The occurrence of adverse events was also higher in the microsurgery group (p = .0079). In PSM-adjusted groups, the superior outcome effect of endovascular treatment still existed but with a reduced significance (p = .004). Similar trend was also observed in the adverse event rate (p = .038). Fatality rate was comparable between two adjusted groups regardless of PSM adjustment. Endovascular surgery of BBAs exhibits overall more favorable short-term outcome regardless of PSM matching. Microsurgery does not cause a higher fatality rate, hence it could be considered a salvage plan for those high-grade BBA patients.

Risk factors for intracranial aneurysm rupture in pediatric patients.

BACKGROUND: Intracranial aneurysm (IA) rupture in pediatric patients is a rare but fatal condition. Although risk factors for aneurysm rupture in adults have been well documented, they remain unknown in pediatric patients. METHODS: Data for 94 pediatric patients with IAs were retrospectively analyzed. The patients were divided into ruptured and unruptured groups. Risk factors for aneurysm rupture were analyzed through univariable and multiple logistic regression analyses. Typical patients with risk factors were described. RESULTS: Univariable analyses showed that the unruptured group had significantly higher percentages of giant aneurysms (43.2% vs 12.3%, P = 0.002), wide-neck aneurysms (67.6% vs 29.8%, P = 0.001), and aneurysms located in the internal carotid artery (40.5% vs 3.5%, P < 0.001), while the ruptured group had significantly higher percentages of patients younger than 5 years old (28.1% vs 5.4%, P = 0.013) and aneurysms located in the anterior cerebral artery (24.6% vs 5.4%, P = 0.032), posterior cerebral artery (14.0% vs 0%, P = 0.045), and distal arterial region (DAR) (46.8% vs 27.0%, P < 0.001). Multiple logistic regression analysis confirmed that age 0-5 years (OR = 6.844, P = 0.042) and IAs located in the DAR (OR = 4.162, P = 0.029) were independently related to an increased risk of rupture. Wide-necked aneurysms (OR = 0.235, P = 0.047) were independently associated with a lower risk of rupture. CONCLUSIONS: Among pediatric patients, age younger than 5 years and lesions located in the DAR are independent risk factors for IA rupture, while an IA with a wide neck acts as a protective factor.

Fast-developing fatal diffuse leptomeningeal dissemination of a pineal germinoma in a young child: a case report and literature review.

BACKGROUND: Intracranial germinomas are uncommon and constitute less than 1% of all intracranial tumors. They usually arise in the midline of the brain, most commonly in the pineal region. Pineal germinomas tend to spread through the cerebrospinal fluid (CSF). However, pineal germinomas with fast-developing diffuse subarachnoid/leptomeningeal dissemination are extremely rare, especially in young children. METHODS: The case of a 4-year-old boy with a pineal germinoma who died of diffuse subarachnoid/leptomeningeal dissemination 1 month after radiotherapy is reported. A PubMed search with specific key terms was used to review cases of pineal germinomas with metastasis. RESULTS: The patient presented with a two-week history of worsening headache, visual disturbances and nonprojectile vomiting. Parinaud's sign was positive on physical examination. Head computed tomography (CT)/magnetic resonance imaging (MRI) revealed a lesion in the pineal region with eccentric calcification and obvious supratentorial hydrocephalus. Pineal germinoma was suspected. A ventriculoperitoneal (VP) shunt followed by focal radiotherapy ameliorated the headaches and visual disturbances. The patient was discharged home without further treatment due to financial difficulties. One month after discharge, he was readmitted due to worsening headache, vomiting and lethargy. MRI showed a decrease in the size of the pineal lesion but revealed a diffuse leptomeningeal enhancement including the sulcus, basal cistern, prepontine cistern, and supravermian cistern. The patient's condition deteriorated rapidly, and he died 26 hours after readmission. The characteristics of pineal germinomas with metastasis are reported based on a review of the literature. CONCLUSIONS: Metastases in pineal germinomas predominately occur in adolescents or young adults, most commonly as spinal "drop metastases." Dissemination usually develops several years after the initial tumor diagnosis and has a relatively good clinical prognosis. However, fast widespread subarachnoid/leptomeningeal dissemination and sudden death may occur in a young child before salvage treatment, as in the presented case.

Compound Capecitabine Colon-Targeted Microparticle Prepared by Coaxial Electrospray for Treatment of Colon Tumors.

To improve the antitumor effect of combined capecitabine (CAP) and osimertinib (OSI) therapy and quickly and efficiently reduce tumor volumes for preoperative chemotherapy, we designed a compound CAP colon-targeted microparticle (COPMP) prepared by coaxial electrospray. COPMP is a core-shell microparticle composed of a Eudragit S100 outer layer and a CAP/OSI-loaded PLGA core. In this study, we characterized its size distribution, drug loading (DL), encapsulation efficiency (EE), differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, formula ratio, cellular growth inhibition, and in vivo antitumor efficacy. COPMP is of spherical appearance with a size of 1.87 ± 0.23 µm. The DLs of CAP and OSI are 4.93% and 4.95%, respectively. The DSC showed that the phase state of CAP and OSI changed after encapsulation. The FTIR results indicated good compatibility between the drug and excipients. The release curve showed that CAP and OSI were released in a certain ratio. They were barely released prior to 2 h (pH 1.0), less than 50% was released between 3 and 5 h (pH 6.8), and sustained release of up to 80% occurred between 6 and 48 h (pH 7.4). CAP and OSI demonstrated a synergistic effect on HCT-116 cells. In a colon tumor model, the tumor inhibition rate after oral administration of COPMP reached 94% within one week. All the data suggested that COPMP promotes the sustained release of CAP and OSI in the colon, which provides a preoperative chemotherapy scheme for the treatment of colon cancer.