The natural course, treatment outcomes, and long-term prognosis of cervical spinal cord arteriovenous shunts.

OBJECTIVE: The highly intricate nature of the cervical spinal cord can cause arteriovenous shunts in these segments that may be associated with heightened clinical risks and treatment complexities. In this article, the authors aimed to provide a comprehensive analysis of the detailed natural course, treatment, and clinical outcomes of cervical spinal cord arteriovenous shunts (SCAVSs) based on the largest cohort to date. METHODS: Two hundred forty consecutive patients were included. Data on clinical presentation, angioarchitecture, treatment, and follow-up were retrospectively reviewed. RESULTS: The cohort demonstrated a greater prevalence of acute onset (63.3% vs 36.7%). Spontaneous recovery was observed in 63.7% of patients after onset, with a significantly elevated recovery rate observed among patients experiencing acute onset (72.4% vs 48.9%, p < 0.001). The risks of acute and gradual clinical deterioration after onset was 11.9%/year and 13.4%/year, respectively. Microsurgery was performed in 39.6% of patients, while the remaining 60.4% exclusively underwent embolization. The complete obliteration rate was 65.3% after microsurgery and 21.4% after embolization. The rate of treatment-related deterioration was 14.7% after microsurgery and 6.2% after embolization. After partial treatment, the acute and gradual deterioration rates were 4.1%/year and 6.6%/year, respectively. Lack of spontaneous recovery after onset was an independent predictor of embolization-related deterioration (OR 17.905, p = 0.007) and long-term gradual deterioration after partial treatment (HR 2.325, p = 0.021). After a median follow-up period of 32.55 months, prognosis was unfavorable in 16.7% of patients, with the sole independent risk factor being the absence of spontaneous recovery after onset (OR 2.476, p = 0.018). CONCLUSIONS: The outcomes of patients with cervical SCAVS were generally favorable, even in patients with only partial obliteration of the lesions. However, patients who did not show a trend toward spontaneous recovery after onset had a significantly elevated risk of unfavorable prognosis, highlighting the need for prompt clinical intervention.

GNA14 and GNAQ somatic mutations cause spinal and intracranial extra-axial cavernous hemangiomas.

Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their vascularity and diffuse nature, and their genetic underpinnings remain incompletely understood. Our approach involved genetic analyses on 31 tissue samples of ECHs employing whole-exome sequencing and targeted deep sequencing. We explored downstream signaling pathways, gene expression changes, and resultant phenotypic shifts induced by these mutations, both in vitro and in vivo. In our cohort, 77.4% of samples had somatic missense variants in GNA14, GNAQ, or GJA4. Transcriptomic analysis highlighted significant pathway upregulation, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways, while GNA14 c.614A>T (p.Gln205Leu) mutation led to MAPK and angiogenesis-related pathway upregulation. Using a mouse xenograft model, we observed enlarged vessels from these mutations. Additionally, we initiated rapamycin treatment in a 14-year-old individual harboring the GNAQ c.626A>G (p.Gln209Arg) variant, resulting in gradual regression of cutaneous cavernous hemangiomas and improved motor strength, with minimal side effects. Understanding these mutations and their pathways provides a foundation for developing therapies for ECHs resistant to current therapies. Indeed, the administration of rapamycin in an individual within this study highlights the promise of targeted treatments in treating these complex lesions.

Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations.

Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides).

This study evaluated effects of high starch (20%) on hematological variations, glucose and lipid metabolism, antioxidant ability, inflammatory responses, and histopathological lesions in largemouth bass. Results showed hepatic crude lipid and triacylglycerol (TAG) contents were notably increased in fish fed high starch. High starch could increase counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils and serum contents of TAG, TBA, BUN, and LEP (p < 0.05). There were increasing trends in levels of GLUT2, glycolysis, gluconeogenesis, and LDH in fish fed high starch through the AKT/PI3K signal pathway. Meanwhile, high starch not only triggered TAG and cholesterol synthesis, but mediated cholesterol accumulation by reducing ABCG5, ABCG8, and NPC1L1. Significant increases in lipid droplets and vacuolization were also shown in hepatocytes of D3-D7 groups fed high starch. In addition, high starch could decrease levels of mitochondrial Trx2, TrxR2, and Prx3, while increasing ROS contents. Moreover, high starch could notably increase amounts of inflammatory factors (IL-1ß, TNF-α, etc.) by activating NLRP3 inflammasome key molecules (GSDME, caspase 1, etc.). In conclusion, high starch could not only induce metabolic disorders via gluconeogenesis and accumulation of glycogen, TAG, and cholesterol, but could disturb redox homeostasis and cause inflammatory responses by activating the NLRP3 inflammasome in largemouth bass.

All-inorganic lead halide perovskites for photocatalysis: a review.

Nowadays, environmental pollution and the energy crisis are two significant concerns in the world, and photocatalysis is seen as a key solution to these issues. All-inorganic lead halide perovskites have been extensively utilized in photocatalysis and have become one of the most promising materials in recent years. The superior performance of all-inorganic lead halide perovskites distinguish them from other photocatalysts. Since pure lead halide perovskites typically have shortcomings, such as low stability, poor active sites, and ineffective carrier extraction, that restrict their use in photocatalytic reactions, it is crucial to enhance their photocatalytic activity and stability. Huge progress has been made to deal with these critical issues to enhance the effects of all-inorganic lead halide perovskites as efficient photocatalysts in a wide range of applications. In this manuscript, the synthesis methods of all-inorganic lead halide perovskites are discussed, and promising strategies are proposed for superior photocatalytic performance. Moreover, the research progress of photocatalysis applications are summarized; finally, the issues of all-inorganic lead halide perovskite photocatalytic materials at the current state and future research directions are also analyzed and discussed. We hope that this manuscript will provide novel insights to researchers to further promote the research on photocatalysis based on all-inorganic lead halide perovskites.

Isolated spinal artery aneurysm: etiology, clinical characteristics, and outcomes.

OBJECTIVE: Isolated spinal aneurysms (ISAs) are rare causes of subarachnoid hemorrhage (SAH), which encompass a highly heterogeneous group of clinical entities with multifarious pathogeneses, clinical characteristics, and treatment strategies. Therefore, knowledge about the ISAs remains inadequate. In this study, the authors present a comprehensive analysis of clinical data associated with ISAs at their institutions to enhance the understanding of this disease. METHODS: Patients with ISAs confirmed by spinal angiography or surgery at the authors' institutions between 2015 and 2022 were included. Data regarding clinical presentation, lesion location, aneurysm morphology, comorbidities, treatment results, and clinical outcomes were reviewed. RESULTS: Seven patients with ISAs were included in the study. Among them, 4 patients (57.1%) experienced severe headache, and 3 patients (42.9%) reported sudden-onset back pain. Additionally, lower-extremity weakness and urinary retention were observed in 2 of these patients (28.6%). Four of the aneurysms exhibited fusiform morphology, whereas the remaining were saccular. All saccular aneurysms in this series were attributed to hemodynamic factors. Conservative treatment was administered to 3 patients, 2 of whom underwent follow-up digital subtraction angiography, which showed spontaneous occlusion of both aneurysms. Four patients ultimately underwent invasive treatments, including 2 who underwent microsurgery and 2 who received endovascular embolization. One patient died of recurrent SAH, while the remaining 6 patients had a favorable prognosis at the latest follow-up assessment. CONCLUSIONS: The morphology of aneurysms may be associated with their etiology. Saccular ISAs are usually caused by pressure due to abnormally increased blood flow, whereas fusiform lesions may be more likely to be secondary to vessel wall damage. The authors found that a saccular spinal aneurysm in young patients with a significant dilated parent artery may be a vestige of spinal cord arteriovenous shunts. ISAs can be managed by surgical, endovascular, or conservative procedures, and the clinical outcome is generally favorable. However, the heterogeneous nature of the disease necessitates personalized treatment decision-making based on specific clinical features of each patient.

High-performance plastic-derived metal-free catalysts for organic pollutants degradation via Fenton-like reaction.

The preparation of waste plastics-derived catalysts is an effective strategy for the waste reclamation. However, plastic-derived material is unsuitable for wastewater purification due to its small specific surface area (SSA) and inadequate active sites (such as N/O sites). Herein, we synthesized graphene-like nanosheets using g-C3N4 as the self-sacrificing soft template and plastic as the carbon precursor. Consequently, this strategy greatly promoted the efficiencies of the emerging organic pollutants degradation with the SSA and N content of the plastic-derived biochar increasing up to 1043.4 m2/g and 17.53 at.%, respectively. In detail, 100 % sulfadiazine (SD) removal could be achieved in 180 s via the activation of peroxymonosulfate (PMS) and the catalytic activity is far higher than previous research. Mechanism experiments corroborated that such a striking performance was attributed to the generation of SO4•-, O2•- and 1O2. Meanwhile, kinds of plastic precursors, even medical waste (i.e., masks, gauze, operating caps and degreasing cotton) were also applicable. And the practical application of the plastic-derived catalyst was further demonstrated by treating pollutants in a continuous flow mode with in situ fabricated membrane. This work provides valuable insights into waste plastics processing and water pollutants removal.

Target-Site and Metabolic Resistance Mechanisms to Penoxsulam in Late Watergrass (Echinochloa phyllopogon) in China.

Echinochloa phyllopogon, a malignant weed in Northeast China's paddy fields, is currently presenting escalating resistance concerns. Our study centered on the HJHL-715 E. phyllopogon population, which showed heightened resistance to penoxsulam, through a whole-plant bioassay. Pretreatment with a P450 inhibitor malathion significantly increased penoxsulam sensitivity in resistant plants. In order to determine the resistance mechanism of the resistant population, we purified the resistant population from individual plants and isolated target-site resistance (TSR) and nontarget-site resistance (NTSR) materials. Pro-197-Thr and Trp-574-Leu mutations in acetolactate synthase (ALS) 1 and ALS2 of the resistant population drove reduced sensitivity of penoxsulam to the target-site ALS, the primary resistance mechanisms. To fully understand the NTSR mechanism, NTSR materials were investigated by using RNA-sequencing (RNA-seq) combined with a reference genome. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis further supported the enhanced penoxsulam metabolism in NTSR materials. Gene expression data and quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation confirmed 29 overexpressed genes under penoxsulam treatment, with 16 genes concurrently upregulated with quinclorac and metamifop treatment. Overall, our study confirmed coexisting TSR and NTSR mechanisms in E. phyllopogon's resistance to ALS inhibitors.

Surgical timing and long-term outcomes in patients with severe haemorrhagic spinal cord cavernous malformations.

BACKGROUND: Surgical resection of the lesions remains the main treatment method for most symptomatic spinal cord cavernous malformations (SCCMs) to eliminate the occupation and associated subsequent lifelong haemorrhagic risk. However, the timing of surgical intervention remains controversial, especially for patients in the acute stage after severe haemorrhage. METHODS: Patients diagnosed with SCCMs who were surgically treated between January 2002 and December 2021 were selected and retrospectively reviewed. The Modified McCormick Scale (MMS) was used to evaluate neurological and disability status. All medical information was reviewed, and all patients were followed up for at least 6 months. RESULTS: A total of 279 patients were ultimately included. With regard to long-term outcomes, 110 (39.4%) patients improved, 159 (57.0%) remained unchanged and 10 (3.6%) worsened. For patients with an MMS score of 2-5 on admission, in univariate and multivariate analyses, a ≤6 weeks period between onset and surgery (adjusted OR 3.211, 95% CI 1.504 to 6.856, p=0.003) was a significant predictor of improved MMS. Among 69 patients who first presented with severe haemorrhage, undergoing surgery within 6 weeks of the onset of severe haemorrhage (adjusted OR 4.901, 95% CI 1.126 to 21.325, p=0.034) was significantly associated with improvement of MMS score. CONCLUSION: Surgical timing can influence the long-term outcome of SCCMs. For patients with symptomatic SCCMs, especially those with severe haemorrhage, early surgical intervention within 6 weeks can provide more benefit.

Ultrafast and energy-saving microwave-assisted conversion of inert carbon nanomaterials to highly efficient Fenton-like metal-free catalysts for pollutants degradation.

Carbon-driven persulfate (PDS)-based Fenton-like reactions have been widely viewed as prospective strategies to cope with the water pollution. However, high cost, harsh condition and complex modification processes are usually required to boost the catalytic activities of carbocatalysts. Herein, we proposed an ultrafast, energy-efficient, and convenient approach to convert various low-performance carbon materials into highly efficient catalysts by microwave treatment in just 1 min without any other tedious treatment. This process only requires 57 kJ/g energy input, 5 orders of magnitude lower than the traditional calcination process. The catalytic performance of microwave-treated materials could increase by more than 380 times, which is even better than those of the single-atom catalysts. Moreover, DFT calculations and QSARs analyses reveal that the negatively charged carboxyl group is not conducive to the adsorption of PDS (S2O82-) due to electrostatic repulsion, and also increases the work function of the carbocatalysts, which hinders the electron transfer process.

High diagnostic performance of time-resolved MR angiography in spinal arteriovenous shunts.

BACKGROUND AND PURPOSE: In comparison with the limited efficacy of conventional MR imaging and the invasiveness of catheter-based digital subtraction angiography (DSA), time-resolved MR angiography (TR-MRA) has been proposed as a promising examination for early diagnosis of spinal arteriovenous shunts (SAVSs). This paper aims to investigate the diagnostic performance of TR-MRA with scan parameters optimized for SAVSs evaluation in a large number of patients. METHODS: One hundred patients with suspected SAVSs were enrolled. Each patient underwent preoperative TR-MRA with optimized scan parameters followed by DSA. The presence or absence of SAVS, the types and the angioarchitecture of SAVSs in the TR-MRA images were diagnostically analyzed. RESULTS: Among the final 97 patients, 80 cases (82.5 %) were diagnosed and classified by TR-MRA as spinal cord arteriovenous shunts (SCAVSs; n = 22), spinal dural arteriovenous shunts (SDAVSs; n = 48), and spinal extradural arteriovenous shunts (SEDAVSs; n = 10). The agreement for classifying SAVSs between TR-MRA and DSA was excellent (κ = 0.91). The sensitivity, specificity, PPV, NPV, and accuracy of TR-MRA for the diagnosis of SAVSs were 100 % (95 % CI, 94.3-100.0 %), 76.5 % (95 % CI, 49.8-92.2 %), 95.2 % (95 % CI, 87.6-98.5 %), 100 % (95 % CI, 71.7-100.0 %), and 95.9 % (95 % CI, 89.9-98.4 %). The accuracy rates of TR-MRA for the detection of feeding arteries were 75.9 %, 91.7 %, and 80.0 % for SCAVSs, SDAVSs, and SEDAVSs respectively. CONCLUSION: Time-resolved MR angiography showed excellent diagnostic performance for SAVSs screening. Additionally, this method can classify SAVSs and identify feeding arteries in SDAVSs with high diagnostic accuracy.

Unified ICH quantification and prognosis prediction in NCCT images using a multi-task interpretable network.

With the recent development of deep learning, the regression, classification, and segmentation tasks of Computer-Aided Diagnosis (CAD) using Non-Contrast head Computed Tomography (NCCT) for spontaneous IntraCerebral Hematoma (ICH) have become popular in the field of emergency medicine. However, a few challenges such as time-consuming of ICH volume manual evaluation, excessive cost demanding patient-level predictions, and the requirement for high performance in both accuracy and interpretability remain. This paper proposes a multi-task framework consisting of upstream and downstream components to overcome these challenges. In the upstream, a weight-shared module is trained as a robust feature extractor that captures global features by performing multi-tasks (regression and classification). In the downstream, two heads are used for two different tasks (regression and classification). The final experimental results show that the multi-task framework has better performance than single-task framework. And it also reflects its good interpretability in the heatmap generated by Gradient-weighted Class Activation Mapping (Grad-CAM), which is a widely used model interpretation method, and will be presented in subsequent sections.

Angioarchitecture and prognosis of pediatric intracranial pial arteriovenous fistula.

OBJECTIVE: Pial arteriovenous fistulas (PAVFs) are rare and mostly observed in children. However, the overall angioarchitecture, clinical features, treatments and long-term prognosis for pediatric patients remain unclear. METHODS: Clinical data of consecutive 42 pediatric PAVFs were documented and analysed. According to the differences of age distribution and clinical features, they were split into a younger group (≤3 years old; 20 cases) and an older group (3-14 years old; 22 cases). RESULTS: Their mean age was 4.9±3.9 years, and the mean preoperative modified Rankin Scale (mRS) score was 1.64±1.57. Fourteen patients (33.3%) were asymptomatic, followed by epilepsy (21.4%), intracranial haemorrhage (16.7%), hydrocephalus (9.5%), developmental delay (7.1%), intermittent headache (7.1%) and congestive heart failure (4.8%). Annual bleeding rate and rebleeding rate before treatment reached 3.86% and 3.17%. Poor venous drainage including sinus dynamic obstruction (21 cases, 50.0%) and sinus occlusion (17 cases, 40.48%) were found with high frequency among these patients. Finally, 33 cases were cured (78.57%), and 4 cases faced surgery-related complications (9.52%). During 24-140 months' follow-up, the mean mRS score reduced to 0.57±0.40. However, only 22 cases (52.38%) recovered to absolutely normal, and poor venous drainage was the risk factor for patients' incomplete recovery (p=0.028, Exp(B)=14.692, 95% CI 1.346 to 160.392). Compared with the older group, younger group showed more chronic symptoms, more secondary pathological changes, more times treatment and worse prognosis (p=0.013, 0.002, 0.000 and 0.032, respectively). CONCLUSIONS: Pediatric PAVF has different angioarchitectures, clinical features and prognoses in different age groups. Poor venous drainage is an important factor leading to poor prognosis, and it accounts for incomplete recovery in nearly half of patients.

Filum terminale arteriovenous shunt with nidus structure: a report of rare condition and treatment consideration.

BACKGROUND:  In the literature, filum terminale arteriovenous shunts (FTAVSs) always feature a single shunt point. Nidus-type FTAVSs have rarely been reported, and the best treatment strategy is unclear. This is a report of one exceptional case of a nidus-type FTAVS and surgical treatment of the lesion. CASE DESCRIPTION: The patient suffered from cauda equina syndrome for 9 months. Magnetic resonance imaging and spinal angiography revealed a nidus-type FTAVF at the L2 level. Surgical resection was performed in the hybrid operating room, and the nidus was completely resected with the assistance of intraoperative methylene blue angiography and neurophysiological monitoring. The postoperative neurological function was stable. CONCLUSIONS: A nidus-type arteriovenous shunt could originate from the FT, and in such cases, complete surgical resection with intraoperative neurophysiological monitoring in a hybrid operating room should be suggested.

Clinical features and outcomes of perimedullary arteriovenous fistulas: comparison between micro- and macro-type lesions.

BACKGROUND: Although the angioarchitecture of perimedullary arteriovenous fistulas (PMAVFs) is straightforward, their size and blood flow are highly heterogeneous. This study aimed to evaluate the differences in clinical features and outcomes of PMAVFs based on lesion size and blood flow. METHODS: 114 consecutive patients with PMAVFs from two institutes were retrospectively reviewed. The lesions were classified as either micro-PMAVFs (shunt point diameter <1 cm) or macro-PMAVFs (shunt point diameter ≥1 cm). RESULTS: The patients with micro-PMAVFs were older at the first presentation (33.50 vs 13.50 years, p<0.001). Macro-PMAVFs were more commonly associated with spinal metameric arteriovenous shunts (6.9% vs 28.6%, p=0.003). Compared with the macro-PMAVFs, the micro-PMAVFs showed a significantly higher risk of gradual clinical deterioration after initial onset (73.6%/year vs 10.0%/year; HR 3.888, 95% CI 1.802 to 8.390, p=0.001). A total of 58.6% of the micro-PMAVFs were treated surgically, whereas 85.7% of the macro-PMAVFs were treated via endovascular approaches. Complete obliteration was 73.7% for the whole cohort, and was more common for the micro-PMAVFs than for the macro-PMAVFs (87.9% vs 58.9%, p=0.001). At the last follow-up, spinal function was significantly improved compared with the pretreatment status, and the rate of severe disability of patients with macro-PMAVFs was slightly but not significantly higher than that of patients with micro-PMAVFs (16.1% vs 8.6%, p=0.315) CONCLUSIONS: The clinical risks, treatment strategies and obliteration rates of PMAVFs differ based on their size and blood flow.

Gene coexpression networks allow the discovery of two strictosidine synthases underlying monoterpene indole alkaloid biosynthesis in Uncaria rhynchophylla.

Plant-derived monoterpene indole alkaloids (MIAs) from Uncaria rhynchophylla (UR) have huge medicinal properties in treating Alzheimer's disease, Parkinson's disease, and depression. Although many bioactive UR-MIA products have been isolated as drugs, their biosynthetic pathway remains largely unexplored. In this study, untargeted metabolome identified 79 MIA features in UR tissues (leaf, branch stem, hook stem, and stem), of which 30 MIAs were differentially accumulated among different tissues. Short time series expression analysis captured 58 pathway genes and 12 hub regulators responsible for UR-MIA biosynthesis and regulation, which were strong links with main UR-MIA features. Coexpression networks further pointed to two strictosidine synthases (UrSTR1/5) that were coregulated with multiple MIA-related genes and highly correlated with UR-MIA features (r > 0.7, P < 0.005). Both UrSTR1/5 catalyzed the formation of strictosidine with tryptamine and secologanin as substrates, highlighting the importance of key residues (UrSTR1: Glu309, Tyr155; UrSTR5: Glu295, Tyr141). Further, overexpression of UrSTR1/5 in UR hairy roots constitutively increased the biosynthesis of bioactive UR-MIAs (rhynchophylline, isorhynchophylline, corynoxeine, etc), whereas RNAi of UrSTR1/5 significantly decreased UR-MIA biosynthesis. Collectively, our work not only provides candidates for reconstituting the biosynthesis of bioactive UR-MIAs in heterologous hosts but also highlights a powerful strategy for mining natural product biosynthesis in medicinal plants.

Prognostic Significance of Tumor Mutation Burden among Patients with Non-small Cell Lung Cancer Who Received Platinum-based Adjuvant Chemotherapy: An Exploratory Study.

This study aimed to investigate the prognostic significance of tumor mutation burden (TMB) among patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Tumor tissue specimens after surgical resection were collected for DNA extraction. Somatic mutation detection and TMB analysis were conducted using next-generation sequencing (NGS). Recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and long-term survival data of patients were obtained by telephone follow-up. Univariate analysis between TMB status and prognosis was carried out by survival analysis. A retrospective review of 78 patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy showed a median disease-free survival of 3.6 years and median overall survival (OS) of 5.3 years. NGS analysis exhibited that the most common mutated somatic genes among the 78 patients were tumor suppressor protein p53 (TP53), epidermal growth factor receptor, low-density lipoprotein receptor related protein 1B, DNA methyltransferase 3 alpha and FAT atypical cadherin 3, and their prevalence was 56.4%, 48.7%, 37.2%, 30.7%, and 25.6%, respectively. TMB status was divided into TMB-L (≤ 4.5/Mb) and TMB-H (> 4.5/Mb) based on the median TMB threshold. Relevance of TMB to prognosis suggested that the median OS of patients with TMB-L was significantly longer than that of patients with TMB-H (NR vs. 4.6, P = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy.

Multimodality Treatment of Deep-seated Cerebral Arteriovenous Malformations: The Experiences of One Center.

OBJECTIVE: Treatment of deep-seated cerebral arteriovenous malformations (AVMs) remains challenging for neurosurgeons or neuroradiologists. This study aims to review the experiences of one center in using multimodality treatment for deep-seated AVMs. METHODS: The AVM database of Xuanwu Hospital, Capital Medical University was searched, and 96 patients who were diagnosed with a deep-seated cerebral AVM between 2010 and 2020 were identified. The following information was collected and analyzed: patients' clinical features, treatment modality used, posttreatment complications, AVM obliteration rate, rebleeding rate, and functional outcome during follow-up. The patients' posttreatment modified Rankin scale (mRS) scores were split into two groups: good outcome (mRS score ≤ 2) and poor outcome (mRS score ≥ 3). Univariate and multivariate logistic regression analyses were applied to test the predictors of clinical outcomes and AVM obliteration. RESULTS: Eighty-eight out of 96 patients (91.7%) presented with initial hemorrhaging. The pretreatment mRS score was ≤ 2 in 80 patients (88.3%) patients and ≥ 3 in 16 patients (16.7%). Limb weakness was present in 42 patients (43.8%). In this sample, 210 hemorrhages occurred during 2056 person-years before diagnosis, yielding an annual hemorrhage rate of 10.2% per person-year. Angiographic obliteration was achieved in 29 patients (30.2%). At the last follow-up, 80 patients (83.3%) had good clinical outcomes, whereas 16 (16.7%) had a deterioration in their clinical presentation following treatment. Multivariate analyses indicated that pretreatment limb weaknesses and a high Spetzler-Martin grade predicted poor clinical outcomes (P = 0.003 and 0.008, respectively). Fewer feeding arteries were a predictor for AVM obliteration (P = 0.034). CONCLUSION: Good outcomes can be achieved through multimodal treatment of deep-seated AVMs. A single supplying artery is a predictor of AVM obliteration. Pretreatment limb weaknesses and high Spetzler-Martin grades predict poor clinical outcomes.

Identification and Validation of Three-Gene Signature in Lung Squamous Cell Carcinoma by Integrated Transcriptome and Methylation Analysis.

Since DNA methylation (DNAm) is associated with the carcinogenesis of various cancers, this study aimed to explore potential DNAm prognostic signatures of lung squamous cell carcinoma (LUSC). First, transcriptomic and methylation profiles of LUSC were obtained from The Cancer Genome Atlas database (TCGA). DNAm-related genes were screened by integrating DNAm and transcriptome profiles via MethylMix package. Subsequently, a prognostic signature was conducted with the least absolute shrinkage and selector operation (LASSO) Cox analysis. This signature combined with the clinicopathological parameters was then utilized to construct a prognostic nomogram via the rms package. A signature based on three DNAm-related genes claudin 1 (CLDN1), ATP-binding cassette subfamily C member 5 (ABCC5), and cystatin A (CSTA) that were hypomethylated and upregulated in LUSC was constructed. Univariate and multivariate Cox regression analysis suggested that this signature, combined with age and TNM.N stage, was significantly correlated with survival rate. Time-dependent receiver operating characteristics and calibration curves suggested the nomogram constructed with age and TNM.N stage variables could accurately evaluate the 3- and 5-year outcome of LUSC. Finally, the average mRNA and protein expression levels of CLDN1, ABCC5, and CSTA in LUSC were verified to be significantly higher than those in paracancerous tissues. Moreover, silencing CLDN1, ABCC5, and CSTA expressions could significantly reduce the carcinogenesis of the A549 cell line. The DNAm-driven prognostic signature consists of CLDN1, ABCC5, and CSTA incorporated with age and TNM. N stage could facilitate the prediction outcome of LUSC.

Safety Evaluation of Heavy Metal Contamination and Pesticide Residues in Coix Seeds in Guizhou Province, China.

The coix seed is a medicinal and edible plant with rich nutritional and medicinal values. With the expansion of the coix seed consumption market, the problem of coix seed safety has attracted attention worldwide. The aims of this work were to evaluate the contamination of mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), chromium (Cr) and 116 pesticides in coix seeds collected from 12 main producing regions of coix seeds in the Guizhou Province of China and to analyze the major contributors of heavy metal and pesticide contamination in coix seed. The results show that the average contents of Pb, Cd, As and Cr in the 123 coix seed samples were 0.0069, 0.0021, 0.0138 and 0.1107 mg/kg, respectively, while Hg was not detected in all coix seed samples. Among the five heavy metals detected, only the Cr contents of three samples were found to be higher than the contaminant limit of Chinese standard GB2762-2017 (CSGB). A total of 13 pesticides were detected in 29 samples from seven main production regions of coix seeds, accounting for 23.6% of all the samples. The detection rates of chlorpyrifos were the highest (8.13%), followed by fenpropathrin (4.06%), bifenthrin (2.43%) and phoxim (1.62%), while the detection rates of the remaining pesticides were below 1%. Moreover, the residual risk score of dichlorvos was the highest of all the pesticides detected. The pollution index and risk assessment of heavy metals and pesticide residues indicates that coix seeds were at safe levels for consumption. In the production process of coix seeds, the local government should control the soil in areas heavily polluted by heavy metals and strengthen the monitoring and guidance on the scientific and rational use of pesticides.