The FGF6 amplification mutation plays an important role in the progression and treatment of malignant meningioma.

Meningioma is a benign tumor with slow growth and long course. However, patients with recurrent malignant meningioma still face a lack of effective treatment. Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Retrospective molecular analysis revealed the frequent amplification of FGF6 in primary and metastatic lesions. Then we constructed the FGF6 over-expressed IOMM-LEE and CH157MN malignant meningioma cell lines, and in vitro and vivo experiments showed that overexpression of FGF6 can promote the proliferation, migration and invasion of malignant meningioma cells. Based on the Western analysis, we revealed that FGF6 can promote the phosphorylation of FGFR, AKT, and ERK1/2, which can be inhibited by anlotinib. Together, we were the first to verify that overexpression of FGF6 promotes the progression of malignant meningiomas by activating FGFR/AKT/ERK1/2 pathway and pointed out that anlotinib may effectively inhibit the disease progression of patients with FGF6 amplification.

Mechanism of pruritus ani lotion combined with Huajiao-Gancao-Bingpian oil for pruritus ani treatment based on network pharmacology and molecular dynamics.

Introduction: Pruritus ani lotion combined with a Chinese medicine formula named Huajiao (Pericarpium Zanthoxyli Bungeani)-Gancao (Radix Glycyrrhizae)-Bingpian (Borneol) is effective in treating pruritus ani. Aim: To investigate the mechanism of traditional Chinese medicine (TCM) in pruritus ani via network pharmacology and molecular dynamics (MD). Material and methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilised to screen active ingredients and their corresponding targets. Genes associated with pruritus ani were collected through GeneCards. Protein-protein interaction (PPI) network between target genes of the active ingredients of this formula and genes associated with pruritus ani was established through the STRING database. A drug-active ingredient-gene interaction network was constructed using Cytoscape with the top 50 genes in affinity coefficients. Molecular docking and MD simulation analysis were performed. Results: Epidermal growth factor receptor (EGFR) and Signal Transducer and Activator of Transcription 3 (STAT3) were core genes. Direct targeting of EGFR by the active ingredients (quercetin and luteolin) and direct targeting of STAT3 by the active ingredient (licochalcone A) may be key molecular mechanisms for the treatment of pruritus ani. Simulated trajectories of structural nuclear motion by MD also revealed that the binding of two pairs of molecules was relatively stable. Conclusions: This study unravels potential targets, active ingredients, and mechanisms of pruritus ani lotion combined with Huajiao-Gancao-Bingpian oil in the treatment of pruritus ani, providing a reference for future treatment.

Positive profile of natural small molecule organic matters on emerging antivirus pharmaceutical elimination in advance reduction process: A deep dive into the photosensitive mechanism of triplet excited state compounds.

Natural small molecular organic matter (NSOM), ubiquitous in natural waters and distinct from humic acid or fulvic acid, is a special type of dissolved organic matter (DOM) which is characterized as strong photosensitivity and simple molecular structure. However, little study had been directed on the role of NSOM in eliminating emerging contaminants in advanced reduction process (ARP). This study took three small molecular isomeric organic acids (p-hydroxybenzoic acid, pHBA; salicylic acid, SA; m-hydroxybenzoic acid, mHBA) as the representative substances of NSOM to explore these mechanisms on promoting Ribavirin (RBV, an anti COVID-19 medicine) degradation in ultraviolet activated sulfite (UV/Sulfite) process. The results demonstrated that the observed degradation rate constant of RBV (kobs-RBV) was 7.56 × 10-6 s-1 in UV/Sulfite process, indicating that hydrated electron (eaq-) from UV/Sulfite process could not effectively degrade RBV, while it increased by 178 and 38 times when pHBA and SA were introduced into UV/Sulfite process respectively, suggesting that pHBA and SA strongly promoted RBV degradation while mHBA had no promotion on RBV abatement in UV/Sulfite process. Transient absorption spectra and reactive intermediates scavenging experiment indicated that the triplet excited state pHBA and SA (3pHBA* and 3SA*) contributed to the degradation of RBV through non-radical process. Notably, eaq- played the role of key initiator in transforming pHBA and SA into their triplet states. The difference of kobs-RBV in UV/Sulfite/pHBA and UV/Sulfite/SA process was attributed to different generation pathways of 3pHBA* and 3SA* (high molar absorptivity at the wavelength of 254 nm and photosensitive cycle, respectively) and their second order rate constants towards RBV (kRBV-3pHBA* = 8.60 × 108 M-1 s-1 and kRBV-3SA* = 6.81 × 107 M-1 s-1). mHBA could not degrade RBV for its lack of intramolecular hydrogen bond and low molar absorptivity at 254 nm to abundantly transform into its triplet state. kobs-RBV increased as pH increased from 5.0 to 11.0 in UV/Sulfite/SA process, due to the high yield of eaq- in alkaline condition which promoted the generation of 3SA* and the stable of the absorbance of SA at 254 nm. By contrast, kobs-RBV underwent a process of first increasing and then decreasing in UV/Sulfite/pHBA process as the increase of pH, and its highest value achieved in a neutral condition. This lied in the exposure of eaq- increased as the increase of pH which promoted the generation of 3pHBA*, while the molar absorptivity of pHBA at 254 nm decreased as the increase of pH in an alkaline condition which inhibited the yield of 3pHBA*. The RBV degradation pathways and products toxicity assessment indicated that UV/Sulfite/pHBA had better detoxification performance on RBV than UV/Sulfite/SA process. This study disclosed a novel mechanism of emerging contaminants abatement through non-radical process in NSOM mediated ARP, and provide a wide insight into positive profile of DOM in water treatment process, instead of only taking DOM as a quencher of reactive intermediates.

Experimental research on the transport-transformation of organic contaminants under the influence of multi-field coupling at a site scale.

Organic-contaminated shallow aquifers have become a global concern of groundwater contamination, yet little is known about the coupled effects of hydrodynamic-thermal-chemical-microbial (HTCM) multi-field on organic contaminant transport and transformation over a short time in aquifers. Therefore, this study proposed a quick and efficient field experimental method for the transport-transformation of contaminants under multi-field coupling to explore the relationship between organic contaminants (total petroleum hydrocarbon (TPH), polycyclic aromatic hydrocarbons (PAHs), benzene-toluene-ethylbenzene-xylene (BTEX) and phthalates acid esters (PAEs)) and multi-field factors. The results showed that hydrodynamics (affecting pH, p < 0.001) and temperature (affecting dissolved oxygen, pH and HCO3-, p < 0.05) mainly affected the organic contaminants indirectly by influencing the hydrochemistry to regulate redox conditions in the aquifer. The main degradation reactions of the petroleum hydrocarbons (TPH, PAHs and BTEX) and PAEs in the aquifer were sulfate reduction and nitrate reduction, respectively. Furthermore, the organic contamination was directly influenced by microbial communities, whose spatial patterns were shaped by the combined effects of the spatial pattern of hydrochemistry (induced by the organic contamination pressure) and other multi-field factors. Overall, our findings imply that the spatiotemporal patterns of organic contaminants are synergistically regulated by HTCM, with distinct mechanisms for petroleum hydrocarbons and PAEs.

Polyimide-based porous carbon and cobalt nanoparticle composites as high-performance electromagnetic wave absorbers.

This study successfully utilized a straightforward approach, choosing liquid-liquid phase separation to build a porous structure and synthesize composite absorbers based on polyimide-based porous carbon and cobalt nanoparticles (designated as PPC/Co-700 and PPC/Co-800). A fine porous structure was achieved as a result of the excellent heat resistance of polyimide resulting in an excellent electromagnetic wave absorption ability of PPC/Co composites. The results obtained clearly indicated that PPC/Co-700 and PPC/Co-800 exhibit a porous structure with coral-like pores, enhancing both impedance matching properties and microwave attenuation abilities. This improvement in impedance matching conditions and dissipation capability is attributed to the synergistic effect of dielectric loss induced by carbon and magnetic loss induced by Co nanoparticles. PPC/Co-700 showed the strongest absorption performance with a minimum reflection loss of -59.85 dB (30 wt% loading, thickness of 3.42 mm) and an effective absorption bandwidth (EABW, RL ≤ -10 dB) of 6.24 GHz (30 wt% loading, thickness of 2.78 mm). Therefore, this work provides a facile strategy for the development of a promising absorbing material with outstanding electromagnetic wave absorption performance.

Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function.

Microglia are versatile regulators in brain development and disorders. Emerging evidence links microRNA (miRNA)-mediated regulation to microglial function; however, the exact underlying mechanism remains largely unknown. Here, we uncover the enrichment of miR-137, a neuropsychiatric-disorder-associated miRNA, in the microglial nucleus, and reveal its unexpected nuclear functions in maintaining the microglial global transcriptomic state, phagocytosis, and inflammatory response. Mechanistically, microglial Mir137 deletion increases chromatin accessibility, which contains binding motifs for the microglial master transcription factor Pu.1. Through biochemical and bioinformatics analyses, we propose that miR-137 modulates Pu.1-mediated gene expression by suppressing Pu.1 binding to chromatin. Importantly, we find that increased Pu.1 binding upregulates the target gene Jdp2 (Jun dimerization protein 2) and that knockdown of Jdp2 significantly suppresses the impaired phagocytosis and pro-inflammatory response in Mir137 knockout microglia. Collectively, our study provides evidence supporting the notion that nuclear miR-137 acts as a transcriptional modulator and that this microglia-specific function is essential for maintaining normal adult brain function.

Up-regulation of RAN by MYBL2 maintains osteosarcoma cancer stem-like cells population during heterogeneous tumor generation.

Intratumor heterogeneity is one of the major features of cancers, leading to aggressive disease and treatment failure. Cancer stem-like cells (CSCs) are believed to give rise to the heterogeneous cell types within tumors. Hence, understanding the regulatory mechanism underlying the recurrence process of heterogeneous tumor by CSCs could facilitate the development of CSC-targeted therapies. Here, utilizing single-cell transcriptomics, we present the molecular profile of osteosarcoma CSCs-derived heterogeneous tumors consisting of CSC clusters, osteoprogenitor and differentiated cell types, such as pre-osteoblasts, osteoblasts and chondroblasts. Furthermore, by constructing the comprehensive map of modulated genes during CSCs self-renewal and differentiation, we identify RAN exhibiting specific peak expression in osteosarcoma CSCs clusters which is transcriptionally up-regulated by MYBL2. Functionality, MYBL2-RAN pathway promotes the CSCs self-renewal by enhancing the nuclear accumulation of MYC protein, which in turn boosts the overexpression of RAN as a positive feedback. Importantly, blockage of MYBL2-RAN pathway sensitizes CSCs to cisplatin treatment and synergistically enhanced the cisplatin-induced cytotoxicity. Both MYBL2 and RAN are highly expressed in clinical osteosarcoma tissues which indicate poor prognosis. Collectively, our study provides advanced insights into the regeneration process of heterogeneous tumor originating from CSCs and highlights the MYBL2-RAN pathway as a promising target for CSC-based therapy in osteosarcoma.

Partial Multilabel Learning Using Noise-Tolerant Broad Learning System With Label Enhancement and Dimensionality Reduction.

Partial multilabel learning (PML) addresses the issue of noisy supervision, which contains an overcomplete set of candidate labels for each instance with only a valid subset of training data. Using label enhancement techniques, researchers have computed the probability of a label being ground truth. However, enhancing labels in the noisy label space makes it impossible for the existing partial multilabel label enhancement methods to achieve satisfactory results. Besides, few methods simultaneously involve the ambiguity problem, the feature space's redundancy, and the model's efficiency in PML. To address these issues, this article presents a novel joint partial multilabel framework using broad learning systems (namely BLS-PML) with three innovative mechanisms: 1) a trustworthy label space is reconstructed through a novel label enhancement method to avoid the bias caused by noisy labels; 2) a low-dimensional feature space is obtained by a confidence-based dimensionality reduction method to reduce the effect of redundancy in the feature space; and 3) a noise-tolerant BLS is proposed by adding a dimensionality reduction layer and a trustworthy label layer to deal with PML problem. We evaluated it on six real-world and seven synthetic datasets, using eight state-of-the-art partial multilabel algorithms as baselines and six evaluation metrics. Out of 144 experimental scenarios, our method significantly outperforms the baselines by about 80%, demonstrating its robustness and effectiveness in handling partial multilabel tasks.

Prognostic and metabolic characteristics of a novel cuproptosis-related signature in patients with hepatocellular carcinoma.

Cuproptosis is a novel discovered mode of programmed cell death. To identify the molecular regulatory patterns related to cuproptosis, this study was designed for exploring the correlation between cuproptosis-related genes (CRGs) and the prognosis, metabolism, and treatment of hepatocellular carcinoma (HCC). Cancer Genome Atlas (TCGA) database was used to screen 363 HCC samples, which were categorized into 2 clusters based on the expression of CRGs. Survival analysis demonstrated that overall survival (OS) was better in Cluster 1 than Cluster 2 which might to be relevant to differences in metabolic based on functional analysis. With LASSO regression analysis and univariate COX regression, 8 prognosis-related genes were screened, a differently expressed genes (DEGs) were then constructed (HCC patients' DEGs)-based signature. The signature's stability was also validated in the 2 independent cohorts and test cohorts (GSE14520, HCC dataset in PCAWG). The 1-year, 3-year, and 5-year area under the curve (AUC) were 0.756, 0.706, and 0.722, respectively. The signature could also well predict the response to chemotherapy, targeted and transcatheter arterial chemoembolization (TACE) by providing a risk score. Moreover, the correlation was uncovered by the research between the metabolism and risk score. In conclusion, a unique cuproptosis-related signature that be capable of predicting patients' prognosis with HCC, and offered valuable insights into chemotherapy, TACE and targeted therapies for these patients has been developed.

Emergent TIPS for acute gastroesophageal variceal bleeding in cirrhotic patients with hepatocellular carcinoma.

OBJECTIVES: To estimate the safety and effectiveness of emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for acute variceal bleeding (AVB) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Data of thirty-three patients with AVB and HCC undergoing emergent TIPS creation from January 2016 to January 2022 were enrolled and were retrospectively analyzed. The primary outcomes were the safety of emergent TIPS creation, the bleeding control rate, and the rebleeding rate. The secondary outcomes included overall survival (OS), liver function, overt hepatic encephalopathy (HE), and shunt dysfunction. RESULTS: Emergent TIPS creation was technically successful in 33 patients (100%) and one (3.0%) patient suffered a major procedure-related adverse event. The control rate of bleeding (within 5 days) was 100%. During a median follow-up period of 26.3 months, rebleeding occurred in 6 (18.2%) patients. The median OS was 20.0 months. The 6-week and 1-year survival rates were 87% and 65%, respectively. Laboratory tests showed no significant impairment of liver function following TIPS creation. The incidences of overt HE and shunt dysfunction were 24.2% and 6.1%, respectively. CONCLUSION: Emergent TIPS creation is feasible and effective for treatment of AVB in cirrhotic patients with HCC.

Mutational landscape of head and neck cancer and cervical cancer in Chinese and Western population.

BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.

Prognosis Prediction of CRAFITY Score in HCC Undergoing TACE Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapy.

Background: The CRAFITY (C-reactive protein and alpha-fetoprotein in immunotherapy) score has demonstrated prognostic significance in hepatocellular carcinoma (HCC) patients undergoing immunotherapy. The study aimed to validate accuracy of CRAFITY score on predicting prognosis for patients with HCC treated with transarterial chemoembolization (TACE) combined with PD-(L)1 inhibitors and molecular targeted therapy. Methods: Eighty-five HCC patients who underwent TACE in combination with molecular targeted therapy (MTT) and PD-(L)1 Inhibitors were consecutively enrolled from November 2019 to November 2022. Patients were divided into CRAFITY 0 score (n=32), CRAFITY 1 score (n=31), and CRAFITY 2 score (n=22), respectively. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes included tumor response rate and treatment-related adverse events (TRAEs). Factors affecting survival were identified via Cox regression analysis. Results: The median overall survival (OS) for HCC patients with CRAFITY scores of 0, 1, and 2 was 33.4 months (95% confidence interval [CI]: 27.1-39.7), 34.5 months (95% CI: 23.1-45.9), and 24.2 months (95% CI: 13.9-39.3), respectively, there were statistical differences among the three groups (p<0.05). The progression-free survival (PFS) was 14.1 months (95% CI: 10.0-18.2), 14.1 months (95% CI: 9.0-19.2), and 9.3 months (95% CI: 7.2-11.4) for patients with CRAFITY scores of 1, 2, and 3, respectively, with a significant difference between the three groups (p<0.05). In patients with CRAFITY scores of 1, 2, and 3, the disease control rates (DCR) were 94%, 84%, and 73%, respectively (p < 0.05), while the overall response rates (ORR) were 78.1%, 67.7%, and 59.1%, respectively (p = 0.318). A higher CRAFITY score showed a correlation with an increased frequency of fatigue and grade 3 fever (p<0.05). Moreover, CRAFITY 2 score was an independent risk factor for both OS (HR = 2.610(1.281-4.564), p = 0.014) and PFS (HR = 2.419(1.281-4.564), p = 0.006). Conclusion: The CRAFITY score may provide an efficient predictive capacity for prognosis in HCC patients undergoing TACE combined with PD-(L)1 inhibitors and molecular targeted therapy.

Transarterial Chemoembolization for Patients with Unresectable Hepatocellular Carcinoma with Child-Pugh B7.

Background and Objectives: This study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) in patients with unresectable early or intermediate hepatocellular carcinoma (HCC) and Child-Pugh (CP)-B liver dysfunction. Methods: This multicenter retrospective study enrolled patients with treatment-naïve HCC treated with TACE monotherapy between January 2012 and December 2020 at six Chinese hospitals. The primary outcome was overall survival (OS), and the secondary outcomes included the objective response rate (ORR) according to the modified RECIST and adverse events (AEs). Propensity score matching (PSM) was performed to reduce bias between the CP-B and CP-A groups. Results: A total of 847 patients were included in the study. CP-A patients had significantly longer OS (median, 22.0 vs 19.3 months, P = 0.032) than CP-B (score of 7-9) patients, but a non-significant trend compared with CP-B (score of 7) patients (median, 22.0 vs 20.5 months, P = 0.254). After PSM, the median OS was 22.7 months for CP-A patients, while it was 19.3 months for CP-B (score of 7-9) patients (p = 0.026) and 20.5 months for CP-B (score of 7) patients (p = 0.155). CP-A patients achieved a significantly better ORR (53.0% vs 35.8%, P < 0.05) compared to CP-B (score of 7-9) patients, but a non-significant trend was observed in CP-B (score of 7) patients (53.0% vs 51.1%, P > 0.05). The post-embolization syndrome rates in the CP-A and CP-B (score of 7) cohorts were 52.1% and 53.3%, respectively. No new safety concerns were observed. Conclusion: Patients with HCC with a CP score of 7 receiving TACE showed a similar prognosis and safety profile to CP-A patients.

Template free preparation of graphene tubes from polyimide catalyzed by calcium carbonate.

This work reports a new means of preparing graphene tubes (GTs) without relying on chemical vapor deposition (CVD) and it's template-free. Surprisingly, we found that under the action of calcium oxide (CaO) and after 1500 °C heat treatment, a large amount of GTs grew on the surface of polyimide (PI). These nanotubes have a maximum diameter of about 600 nm and a length of up to millimeters, and some nanotubes even have a branching structure. We propose a simple, effective and green method which exhibits prospects for large-scale production of GTs using polymeric materials.

Limit Cycle of a Single-Neuron System With Smooth Continuous and Binary-Value Activation Functions and Its Circuitry Design.

In this brief, we investigate the limit cycle of a single-neuron system with smooth continuous and binary-value activation functions and its circuit design. By transforming the system into Liénard-type and using Poincaré-Bendixson theorem as well as the symmetry of these systems, we obtain the existence conditions of limit cycle of the system. Then, by comparing the integral value of the differential of positive definite function along two assumed limit cycles, we prove that the system cannot produce two coexisting limit cycles, which means that the system has at most one limit cycle. In addition, according to the two specific functions, i.e., smooth continuous and binary-value activation functions of the system, we give the numerical simulation and realize the circuit design of the single-neuron system by using Multisim modeling, respectively. The waveform diagram and phase diagram of the numerical simulation and circuit simulation are obtained. By comparing the results of numerical and circuit simulation, the effectiveness of our mathematical analysis and the feasibility of circuit design are better illustrated.

Expert consensus on the diagnosis and treatment of RET gene fusion non-small cell lung cancer in China.

The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell-surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non-small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second-generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first-generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET-targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next-generation sequencing (NGS), reverse transcription-polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Prognostic Performance of the China Liver Cancer Staging System in Hepatocellular Carcinoma Following Transarterial Chemoembolization.

Background and Aims: To validate prognostic performance of the China liver cancer (CNLC) staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer (BCLC) staging system for Chinese hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Methods: This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals. Based on overall survival (OS), the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination [C statistic and Akaike information criterion (AIC)], monotonicity of the gradient (linear trend chi-square test), homogeneity (likelihood ratio chi-square test), and calibration (calibration plots). A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes. Results: Median OS was 19.1 (18.2-20.0) months, with significant differences in OS between stages defined by the CNLC and BCLC observed (p<0.001). The CNLC performed better than the BCLC regarding model discrimination (C-index: 0.661 vs. 0.644; AIC: 10,583.28 vs. 10,583.72), model monotonicity of the gradient (linear trend chi-square test: 66.107 vs. 57.418; p<0.001), model homogeneity (159.2 vs. 158.7; p<0.001). Both staging systems had good model calibration. Similar results were observed in the prospective cohort. Conclusions: Combining model discrimination, gradient monotonicity, homogeneity, and calibration, the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.

Road traffic flow prediction based on dynamic spatiotemporal graph attention network.

To improve the prediction accuracy of traffic flow under the influence of nearby time traffic flow disturbance, a dynamic spatiotemporal graph attention network traffic flow prediction model based on the attention mechanism was proposed. Considering the macroscopic periodic characteristics of traffic flow, the spatiotemporal features are extracted by constructing spatiotemporal blocks with an adjacent period, daily period, and weekly period respectively. The spatiotemporal block is mainly composed of a two-layer graph attention network and a gated recurrent unit to capture the hidden features of space and time. In space, based on considering adjacent road segments, the Pearson correlation coefficient is used to capture the hidden correlation characteristics between non-adjacent road segments according to a certain time step. In terms of time, due to the random disturbance of traffic flow at the micro level, the attention mechanism is introduced to use the adjacent time as the query matrix to weight the output characteristics of daily cycle and weekly cycle, and the three are connected in series to output the prediction results through the linear layer. Finally, the experimental results on the public data sets show that the proposed model is superior to the six baseline models.

Transarterial chemoembolization combined with molecularly targeted agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma: a retrospective cohort study.

Purpose: To retrospectively evaluate and compare treatment effectiveness and safety between transarterial chemoembolization (TACE) combined with molecularly targeted agents plus immune checkpoint inhibitors (TACE+T+I) and TACE combined with molecularly targeted agents (TACE+T) for unresectable hepatocellular carcinoma (uHCC). Methods: We retrospectively analyzed the data of patients with unresectable HCC from January 2018 to June 2022. The patients were screened based on the inclusion criteria and were divided into the triple combination group (TACE+T+I) and the double combination group (TACE+T). The primary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events (AEs). The secondary outcomes were objective response rate (ORR) and disease control rate (DCR). Risk factors associated with PFS and OS were determined by Cox regression analysis. Results: A total of 87 patients were enrolled in this study, including 42 patients in the TACE+T+I group and 45 patients in the TACE+T group. Over a median follow-up of 29.00 and 26.70 months, patients who received TACE+T+I therapy achieved a significantly longer median OS (24.00 vs. 21.40 months, p = 0.007) and median PFS (9.70 vs. 7.00 months, p = 0.017); no grade 4 AEs or treatment-related death occurred in the two groups. Grade 3 AEs attributed to systemic agents in the two groups showed no significant difference (19.0% vs. 15.6%, p = 0.667). Patients in the TACE+T+I group demonstrated better tumor response when compared with patients in the TACE+T group, with an ORR of 52.4% vs. 17.8% (p = 0.001). No significant difference was observed in DCR between the two groups (83.3% vs. 77.8%, p = 0.514). Cox regression analysis showed that only the treatment method was an independent factor of OS, and both age and treatment method were independent factors related to PFS. Conclusion: Compared with TACE plus molecularly targeted agents (TACE+T), the triple therapy (TACE+T+I) could improve survival and tumor response in unresectable HCC with manageable toxicities.

Feasibility of computed tomography portal venography in the preoperative evaluation of emergent TIPS creation for cirrhotic patients with acute variceal bleeding.

OBJECTIVES: To evaluate the feasibility of computed tomography portal venography (CTPV) in the preoperative evaluation of emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for cirrhotic patients with acute variceal bleeding (AVB). METHODS: One hundred and forty-eightcirrhotic patients with AVB undergoing emergent TIPS creation from January 2016 to December 2022 in our institution were enrolled in the retrospective study. The primary outcome was the consistency between CTPV and endoscopy in the classification and grading of gastroesophageal varices (GEVs). The second outcome was extraluminal CTPV findings. The consistency of CTPV and endoscopy in the classification and grading of GEVs was determined by Kappa values. RESULTS: Emergent TIPS creation was technically successful in all patients. Forty-five patients underwent preoperative endoscopy. The results of CTPV diagnosis of GEVs classification were that 112, 28, and 8 patients were classified as gastroesophageal varices type 1 (GOV1), GOV2, and isolated gastric varices type 1 (IGV1), respectively. In diagnosing the classification and grading of GEVs, CTPV showed substantial agreement with preoperative endoscopy, with Kappa values of 0.823 and 0.625, respectively. CTPV provided the afferent and afferent vessels of GEVs for emergent TIPS creation. CONCLUSION: CTPV is feasible and effective to act as an alternative preoperative evaluation method to endoscopy for cirrhotic patients with AVB undergoing emergent TIPS creation.