Added value of arterial enhancement fraction derived from dual-energy computed tomography for preoperative diagnosis of cervical lymph node metastasis in papillary thyroid cancer: initial results.

OBJECTIVES: To explore the added value of arterial enhancement fraction (AEF) derived from dual-energy computed tomography CT (DECT) to conventional image features for diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC). METHODS: A total of 273 cervical LNs (153 non-metastatic and 120 metastatic) were recruited from 92 patients with PTC. Qualitative image features of LNs were assessed. Both single-energy CT (SECT)-derived AEF (AEFS) and DECT-derived AEF (AEFD) were calculated. Correlation between AEFD and AEFS was determined using Pearson's correlation coefficient. Multivariate logistic regression analysis with the forward variable selection method was used to build three models (conventional features, conventional features + AEFS, and conventional features + AEFD). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. RESULTS: Abnormal enhancement, calcification, and cystic change were chosen to build model 1 and the model provided moderate diagnostic performance with an area under the ROC curve (AUC) of 0.675. Metastatic LNs demonstrated both significantly higher AEFD (1.14 vs 0.48; p < 0.001) and AEFS (1.08 vs 0.38; p < 0.001) than non-metastatic LNs. AEFD correlated well with AEFS (r = 0.802; p < 0.001), and exhibited comparable performance with AEFS (AUC, 0.867 vs 0.852; p = 0.628). Combining CT image features with AEFS (model 2) and AEFD (model 3) could significantly improve diagnostic performances (AUC, 0.865 vs 0.675; AUC, 0.883 vs 0.675; both p < 0.001). CONCLUSIONS: AEFD correlated well with AEFS, and exhibited comparable performance with AEFS. Integrating qualitative CT image features with both AEFS and AEFD could further improve the ability in diagnosing cervical LN metastasis in PTC. CLINICAL RELEVANCE STATEMENT: Arterial enhancement fraction (AEF) values, especially AEF derived from dual-energy computed tomography, can help to diagnose cervical lymph node metastasis in patients with papillary thyroid cancer, and complement conventional CT image features for improved clinical decision making. KEY POINTS: • Metastatic cervical lymph nodes (LNs) demonstrated significantly higher arterial enhancement fraction (AEF) derived from dual-energy computed tomography (DECT) and single-energy CT (SECT)-derived AEF (AEFS) than non-metastatic LNs in patients with papillary thyroid cancer. • DECT-derived AEF (AEFD) correlated significantly with AEFS, and exhibited comparable performance with AEFS. • Integrating qualitative CT images features with both AEFS and AEFD could further improve the differential ability.

Emodin as an Inhibitor of PRV Infection In Vitro and In Vivo.

Pseudorabies (PR) is an acute and severe infectious disease caused by pseudorabies virus (PRV). Once the virus infects pigs, it is difficult to eliminate, resulting in major economic losses to the global pig industry. In addition, reports of human infection with PRV suggest that the virus is a potential threat to human health; thus, its significance to public health should be considered. In this paper, the anti-PRV activities of emodin in vitro and in vivo, and its mechanism of action were studied. The results showed that emodin inhibited the proliferation of PRV in PK15 cells in a dose-dependent manner, with an IC50 of 0.127 mg/mL and a selection index of 5.52. The addition of emodin at different stages of viral infection showed that emodin inhibited intracellular replication. Emodin significantly inhibited the expression of the IE180, EP0, UL29, UL44, US6, and UL27 genes of PRV within 48 h. Emodin also significantly inhibited the expression of PRV gB and gD proteins. The molecular docking results suggested that emodin might form hydrogen bonds with PRV gB and gD proteins and affect the structure of viral proteins. Emodin effectively inhibited the apoptosis induced by PRV infection. Moreover, emodin showed a good protective effect on PRV-infected mice. During the experimental period, all the control PRV-infected mice died resulting in a survival rate of 0%, while the survival rate of emodin-treated mice was 28.5%. Emodin also significantly inhibited the replication of PRV in the heart, liver, brain, kidneys and lungs of mice and alleviated tissue and organ damage caused by PRV infection. Emodin was able to combat viral infection by regulating the levels of the cytokines TNF-α, IFN-γ, IL-6, and IL-4 in the sera of infected mice. These results indicate that emodin has good anti-PRV activity in vitro and in vivo, and is expected to be a new agent for the prevention and control of PRV infection.

Optimizing the Extraction and Enrichment of Luteolin from Patrinia villosa and Its Anti-Pseudorabies Virus Activity.

Luteolin from Patrinia villosa exhibits strong antiviral activity. Here, the conditions for extracting and enriching luteolin from P. villosa were optimized. Response surface methodology was used to determine the optimal extraction parameters in terms of reflux time, solvent ratio, extraction temperature, material-to-liquid ratio, and number of extractions. Thereafter, a macroporous resin method was used to enrich luteolin from P. villosa. Finally, the following optimal extraction and enrichment conditions were established: an extraction time of 43.00 min, a methanol/hydrochloric acid solvent ratio of 13:1, an extraction temperature of 77.60 °C, a material/liquid ratio of 1:22, and a total of two extractions. NKA-9 was determined to be the most appropriate resin for enrichment. The ideal adsorption conditions were as follows: a pH of 5.0, a temperature of 25 °C, an initial luteolin concentration of 19.58 µg/mL, a sample loading volume of 2.9 BV, and a sample loading rate of 2 BV/h. The ideal desorption conditions were as follows: distilled water, 30% ethanol and 80% ethanol elution, and 5 BV at a flow rate of 2 BV/h. After optimization, the enrichment recovery rate was 80.06% and the luteolin content increased 3.8-fold. Additionally, the enriched product exhibited a significant inhibitory effect on PRV (Porcine pseudorabies virus) in vitro and in vivo, providing data for developing and applying luteolin from P. villosa.

Flexible 2D Materials beyond Graphene: Synthesis, Properties, and Applications.

2D materials are now at the forefront of state-of-the-art nanotechnologies due to their fascinating properties and unique structures. As expected, low-cost, high-volume, and high-quality 2D materials play an important role in the applications of flexible devices. Although considerable progress has been achieved in the integration of a series of novel 2D materials beyond graphene into flexible devices, a lot remains to be known. At this stage of their development, the key issues concern how to make further improvements to high-performance and scalable-production. Herein, recent progress in the quest to improve the current state of the art for 2D materials beyond graphene is reviewed. Namely, the properties and synthesis techniques of 2D materials are first introduced. Then, both the advantages and challenges of these 2D materials for flexible devices are also highlighted. Finally, important directions for future advancements toward efficient, low-cost, and stable flexible devices are outlined.

Efficacy and safety analyses of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy in the treatment of advanced non-small-cell lung cancer with an EGFR/TP53 co-mutation.

PURPOSE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with cytotoxic chemotherapy are highly effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study is to evaluate the efficacy and safety of this combination in advanced NSCLC patients with an EGFR/TP53 co-mutation. METHODS: Ninety-five advanced NSCLC patients with an EGFR/TP53 co-mutation were enrolled in this study. Treatments with either EGFR-TKI monotherapy (T group, n = 61) or EGFR-TKI combined with chemotherapy (TC group, n = 34) were evaluated in relation to objective response rate (ORR), disease control rate (DCR), median time to progression (TTP), and median overall survival (OS). RESULTS: There were no statistically significant differences in DCR between the treatment groups. The ORR was significantly improved in the TC group versus the T group (55.9% vs. 34.4%, P = 0.042). A higher median TTP was noted in TC group compared with T group (16.1 vs. 11.1 months, P = 0.002). Patients without brain metastases in TC group had a longer median OS than in T group (48.4 vs. 28.8 months, P = 0.003). However, there was a non-significant trend towards longer OS in TC group in the entire cohort (36.9 vs. 28.2 months, P = 0.078). Cox multivariate regression analysis showed that clinical stage, brain metastases, EGFR21 L858R mutation, and T790M status at first progression were independent risk factors for OS. However, the incidence of grade 3 or higher adverse events were higher in the TC group than in the T group (32.4% vs. 13.1%, P = 0.025). CONCLUSION: Our study indicates that EGFR-TKIs combined with chemotherapy could significantly improve the ORR and TTP of advanced NSCLC patients with an EGFR/TP53 co-mutation. Combination therapy may be a promising treatment for advanced NSCLC patients with an EGFR/TP53 co-mutation without brain metastases.

Comparison of Cd subcellular distribution and Cd detoxification between low/high Cd-accumulative rice cultivars and sea rice.

Salt-tolerant rice cultivar (sea rice) is a research hotspot worldwide due to its high yield in high salinity soil. However, knowledge regarding the cadmium (Cd) effects on the growth of sea rice is limited. To determine the short-term and long-term impact of Cd stress, relatively low/high Cd-accumulative rice cultivars and sea rice were grown to compare their growth responses to Cd stress over time. The results showed that sea rice presented the highest Cd concentrations in the root, stem, and leaves under 32-days of Cd stress. Cd stress shortened and thickened the rice root, and decreased the proportion of root diameters in the 0-0.2 mm range. Cd stress remarkably increased the Cd and Fe concentration in dithionite-citrate-bicarbonate (DCB) extracts, and the DCB-Cd and DCB-Fe concentrations were the highest in sea rice. The subcellular distribution of Cd in the rice roots indicated that Cd accumulated the most in the soluble fraction and cell wall. The contents of pectin and hemicellulose 2 in the root cell wall of the low-Cd accumulative rice variety CL755 were higher than those in MXZ and sea rice. Collectively, this work provides a general understanding of the Cd effects on sea rice growth and indicates that sea rice has a relatively high Cd accumulation compared with the other two rice cultivars. However, the specifically-related mechanism remains to be further studied.

RS-MAE: Region-State Masked Autoencoder for Neuropsychiatric Disorder Classifications Based on Resting-State fMRI.

Dynamic functional connectivity (DFC) extracted from resting-state functional magnetic resonance imaging (fMRI) has been widely used for neuropsychiatric disorder classifications. However, serious information redundancy within DFC matrices can significantly undermine the performance of classification models based on them. Moreover, traditional deep models cannot adapt well to connectivity-like data, and insufficient training samples further hinder their effective training. In this study, we proposed a novel region-state masked autoencoder (RS-MAE) for proficient representation learning based on DFC matrices and ultimately neuropsychiatric disorder classifications based on fMRI. Three strategies were taken to address the aforementioned limitations. First, masked autoencoder (MAE) was introduced to reduce redundancy within DFC matrices and learn effective representations of human brain function simultaneously. Second, region-state (RS) patch embedding was proposed to replace space-time patch embedding in video MAE to adapt to DFC matrices, in which only topological locality, rather than spatial locality, exists. Third, random state concatenation (RSC) was introduced as a DFC matrix augmentation approach, to alleviate the problem of training sample insufficiency. Neuropsychiatric disorder classifications were attained by fine-tuning the pretrained encoder included in RS-MAE. The performance of the proposed RS-MAE was evaluated on four publicly available datasets, achieving accuracies of 76.32%, 77.25%, 88.87%, and 76.53% for the attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), Alzheimer's disease (AD), and schizophrenia (SCZ) classification tasks, respectively. These results demonstrate the efficacy of the RS-MAE as a proficient deep learning model for neuropsychiatric disorder classifications.

The Value of Chemokine and Chemokine Receptors in Diagnosis, Prognosis, and Immunotherapy of Hepatocellular Carcinoma.

Background: Chemokines and chemokine receptors (CCRs) are involved in a variety of anti-tumour and pro-tumour immune processes in vivo, such as angiogenesis, metastasis, proliferation and invasiveness, and influence patient prognosis and response to therapy. Methods: CCRs differentially expressed in HCC and associated with prognosis were extracted from TCGA and GEO databases, and the obtained CCRs were then used to construct signature genes, and the signature gene were selected for expression validation as well as functional experiments to explore the role of CCRs in the treatment and prognosis of HCC. Results: We constructed a prognostic model including five CCRs (CCL20, CCL23, CCR3, CCR10, and CXCR3) and validated the expression of signature genes. The model's risk score is an independent prognostic factor for HCC. We have also developed prognostic model nomograms for clinical use. In addition, we validated that CCR3 expression is associated with poor prognosis in HCC, and the proliferation and migration ability of HCC cells was significantly inhibited after interfering with the expression of CCR3 in MHCC-LM3. We also looked at differences in pathway enrichment, immune infiltration and immune checkpoints. Finally, we found that risk scores were also correlated with drug sensitivity, the high-risk group had a better sensitivity to sorafenib. Conclusion: The CCRs-related gene signature may better assess HCC prognosis and response to immunotherapy and tyrosine kinase inhibitors such as sorafenib in HCC, providing prospective solutions for diagnosis and treatment.

Optimal virtual monochromatic images for assessing metastatic lateral cervical lymph nodes in patients with papillary thyroid carcinoma using dual­layer spectral detector computed tomography.

PURPOSE: To determine the optimal virtual monochromatic images (VMIs) from dual-layer spectral detector computed tomography for the visualization and diagnosis of metastatic lateral cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). METHODS: Ninety-five lateral cervical LNs (49 metastatic and 46 non-metastatic) derived from 24 patients (16 females; mean age, 40.0 ± 13.4 years) were included. 40-100 kiloelectron voltage (keV) VMIs, 120 keV VMI and conventional 120 kV peak (kVp) polyenergetic image (PI) were reconstructed. Five-point scale of subjective image quality, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of LNs were assessed and compared among each VMI and 120 kVp PI. Receiver operating characteristic (ROC) curves and Delong tests were used to assess and compare the diagnostic efficacy of arterial enhancement fraction (AEF) based on each VMI and 120 kVp PI. RESULTS: 40 keV VMI showed significantly higher SNR and CNR in both arterial and venous phases, and better image quality in arterial phase than 70-100 keV VMIs, 120 keV VMI, and 120 kVp PI (all p < 0.05). In all sets of images, AEF values of metastatic LNs were significantly higher than those of non-metastatic LNs (all p < 0.05). When using AEF value of 40 keV VMI to diagnose metastatic lateral cervical LNs, an area under ROC curve (AUC) of 0.878, sensitivity of 87.8 % and specificity of 80.4 % could be obtained, while the AUC of AEF value of 120 kVp PI was 0.815 (p = 0.154). CONCLUSION: 40 keV VMI might be optimal for displaying and diagnosing the metastatic lateral cervical LNs in patients with PTC.

Hepatic arterial infusion chemotherapy, lenvatinib plus programmed cell death protein-1 inhibitors: A promising treatment approach for high-burden hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients. METHODS: We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths. CONCLUSION: The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.

Lenvatinib Plus PD-1 Inhibitors versus Regorafenib in Patients with Advanced Hepatocellular Carcinoma After the Failure of Sorafenib: A Retrospective Study.

Purpose: To evaluate the clinical outcomes of lenvatinib plus PD-1 inhibitors (LP) and regorafenib (R) in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure. Methods: From June 2018 to September 2021, 68 patients from a single center who received lenvatinib combined with PD-1 inhibitors or regorafenib after sorafenib treatment failure were analyzed. The tumor response and survival outcomes were compared between the LP group and R group. Prognostic factors for OS and PFS were determined using Cox proportional hazard regression models. Results: The ORR increased in the LP group (19.5% vs 7.4%, p =0.294), and the DCR was better in the R group (73.2% vs 44.4%, p =0.017). Additionally, median PFS and OS were not significantly different between the LP group and R two groups in survival analysis (PFS: 5.3 months vs 3.0 months, p =0.633; OS: 11.8 months vs 8.0 months, p =0.699). The common adverse events (≥grade 3) were hand-foot skin reactions (13.1%). In multivariate analyses, AFP≥400 ng/mL and ECOG PS 2 were independent risk factors for poor prognosis. Conclusion: The LP group appeared to have a trend of greater tumor response and a higher disease control rate than the R group among patients with sorafenib-resistant HCC, although PFS and OS did not differ significantly between the two groups.

MicroRNA 211-5p inhibits cancer cell proliferation and migration in pancreatic cancer by targeting BMP2.

MicroRNAs (miRNAs) are essential to the tumour growth and metastasis of several cancers. However, the implied functions of miR-211-5p in pancreatic cancer (PC) remains poorly known. In the present study, we discovered that miR-211-5p was a significantly downregulated miRNA in PC tissues compared to adjacent non-tumour tissues. Moreover, we revealed that miR-211-5p overexpression suppressed the proliferation and metastasis of PC cells. Mechanistically, miR-211-5p directly bond to 3'UTR of bone morphogenetic protein-2 (BMP2) and negatively regulated its expression. Rescue experiments showed that the biological function of miR-211-5p was reversed by BMP-2 overexpression in PC cells. Clinical data indicated that BMP2 expression was negatively correlated with miR-211-5p levels in PC patients. Our study provided evidence that miR-211-5p served as a significant suppressor in PC, provided potential targets for prognosis and treatment of patients with PC.

Piceatannol as an Antiviral Inhibitor of PRV Infection In Vitro and In Vivo.

Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiviral activity of piceatannol. The results showed that piceatannol could restrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. Piceatannol could exert an anti-PRV effect by reducing the transcription level of viral genes, inhibiting PRV-induced apoptosis and elevating the levels of IL-4, TNF-α and IFN-γ in the serum of mice. Animal experiments showed that piceatannol could delay the onset of disease, reduce the viral load in the brain and kidney and reduce the pathological changes in the tissues and organs of the mice to improve the survival rate of the mice (14.3%). Therefore, the anti-PRV activity of piceatannol in vivo and in vitro was systematically evaluated in this study to provide scientific data for developing a new alternative measure for controlling PRV infection.

Virome analysis of ticks and tick-borne viruses in Heilongjiang and Jilin Provinces, China.

Ticks transmit diverse human and animal pathogens, leading to an increasing number of public health concerns. In the forest area of northeast China, the spread of tick-borne diseases (TBDs) is severe; however, little is known about the tick virome composition and evolution. Herein, we investigate the geographical distribution of tick species and related viruses in Heilongjiang and Jilin Provinces in Northeast China. To reveal the diversity of tick-borne viruses in parts of Heilongjiang and Jilin, ticks were collected at 9 collection points in these provinces in 2018. Morphology and molecular biology were used to identify tick species, and 1411 ticks from nine sampling sites were collected and analysed by next-generation sequencing (NGS). Four Ixodidae were identified, including Ixodes persulcatus, Haemaphysalis japonica, Dermacentor silvarum, and Haemaphysalis concinna. After removal of host genome sequences, 13,003 high-quality NGS reads were obtained and annotated as viruses. Further phylogenetic analysis based on amplicons revealed that these viral sequences belong to Beiji nairovirus, Alongshan virus, bovine parvovirus-2, and tick-associated circovirus; some distinct sequences are closely related to Songling virus, Changping tick virus, Norway luteo-like virus 2, and Norway partiti-like virus 1. In summary, this study describes the prevalence of local ticks and variety of tick-borne viruses in northeastern China, providing a basis for further research on tick-borne viruses in the future.

CKLF as a Prognostic Biomarker and Its Association with Immune Infiltration in Hepatocellular Carcinoma.

The Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family, comprising nine members, is involved in the tumorigenesis and progression of various cancers. However, the expression profiles and clinical significance of CMTM family members in hepatocellular carcinoma (HCC) are not fully clarified. In this study, the RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas (TCGA) databases. The Kaplan-Meier method and the Cox proportional hazards regression analysis were used to evaluate the prognostic significance of CMTM family members. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were employed to explore the relationship between CMTM family genes and the tumor microenvironment in HCC. Finally, the prognostic CMTM family gene expression was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining in clinical HCC tissue specimens. The results indicated that, compared with normal tissues, the expression of CKLF, CMTM1, CMTM3, CMTM4, CMTM7, and CMTM8 were significantly upregulated in HCC, while the expression of CMTM2, CMTM5, and CMTM6 were significantly downregulated in HCC. Univariate and multivariate Cox regression analysis demonstrated that CKLF was an independent prognostic biomarker for the overall survival (OS) of HCC patients. In HCC, the expression of CKLF was found to be correlated with immune cell infiltration, immune-related functions, and immune checkpoint genes. The qRT-PCR and IHC confirmed that CKLF was highly expressed in HCC. Overall, this research suggested that CKLF is involved in immune cell infiltration and may serve as a critical prognostic biomarker, which provides new light on the therapeutics for HCC.

Texture analysis of diffusion kurtosis imaging for differentiating malignant from benign sinonasal lesions: added value to conventional imaging features.

OBJECTIVES: To evaluate the performance of texture analysis (TA) of diffusion kurtosis imaging (DKI) in differentiating malignant from benign sinonasal lesions, and its added value to the conventional imaging features. METHODS: Fifty-eight patients with malignant and 40 patients with benign sinonasal lesions were retrospectively enrolled. Conventional CT and MRI features were reviewed. Texture parameters were obtained and compared between two groups. Multivariate logistic regression analysis was used to identify the most valuable variables. Receiver operating characteristic curves were performed to assess the differentiating performance of independent variables and their combination. RESULTS: There were significant differences in tumor necrosis, bone erosion and soft tissue invasion between the two groups (all p < 0.05). There were significant differences in the 10th and entropy of Apparent diffusion coefficient map, the mean, 10th and entropy of D map, the mean and 90th of K map between the two groups (all p < 0.002). The bone erosion, entropy of D, and mean of K were independent variables associated with malignant tumors. Receiver operating characteristic analyses indicated that the combination of three features possessed better differentiating performance than bone erosion alone (p = 0.003). CONCLUSION: TA of DKI could supply incremental value to conventional imaging features for pre-operative differential diagnosis between benign and malignant sinonasal lesions. ADVANCES IN KNOWLEDGE: The present study is the first to combine conventional imaging features and the TA of DKI in the differential diagnosis between benign and malignant sinonasal lesions. Our findings suggest that TA of DKI could supply incremental value to conventional imaging features.

Validity of chronic restraint stress for modeling anhedonic-like behavior in rodents: a systematic review and meta-analysis.

BACKGROUND: Chronic restraint stress (CRS) is widely used to recapitulate depression phenotypes in rodents but is frequently criticized for a perceived lack of efficacy. The aim of this study was to evaluate anhedonic-like behavior in the CRS model in rodents by performing a meta-analysis of studies that included sucrose preference tests. METHODS: This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. We comprehensively searched for eligible studies published before June 2021 in the PubMed, Embase, Medline, and Web of Science databases. We chose sucrose preference ratio as the indicative measure of anhedonia because it is a core symptom of depression in humans. RESULTS: Our pooled analysis included 34 articles with 57 studies and seven rodent species/strains and demonstrated decreased sucrose preference in the stress group compared with controls. The duration of CRS differentially affected the validity of anhedonic-like behavior in the models. Rats exhibited greater susceptibility to restraint stress than mice, demonstrating inter-species variability. CONCLUSIONS: Our meta-analysis of studies that used the CRS paradigm to evaluate anhedonic-like behavior in rodents was focused on a core symptom of depression (anhedonia) as the main endpoint of the model and identified species-dependent susceptibility to restraint stress.

Diagnostic Accuracy of Artificial Intelligence Based on Imaging Data for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: The presence of microvascular invasion (MVI) is considered an independent prognostic factor associated with early recurrence and poor survival in hepatocellular carcinoma (HCC) patients after resection. Artificial intelligence (AI), mainly consisting of non-deep learning algorithms (NDLAs) and deep learning algorithms (DLAs), has been widely used for MVI prediction in medical imaging. Aim: To assess the diagnostic accuracy of AI algorithms for non-invasive, preoperative prediction of MVI based on imaging data. Methods: Original studies reporting AI algorithms for non-invasive, preoperative prediction of MVI based on quantitative imaging data were identified in the databases PubMed, Embase, and Web of Science. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) scale. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model with 95% CIs. A summary receiver operating characteristic curve and the area under the curve (AUC) were generated to assess the diagnostic accuracy of the deep learning and non-deep learning models. In the non-deep learning group, we further performed meta-regression and subgroup analyses to identify the source of heterogeneity. Results: Data from 16 included studies with 4,759 cases were available for meta-analysis. Four studies on deep learning models, 12 studies on non-deep learning models, and two studies compared the efficiency of the two types. For predictive performance of deep learning models, the pooled sensitivity, specificity, PLR, NLR, and AUC values were 0.84 [0.75-0.90], 0.84 [0.77-0.89], 5.14 [3.53-7.48], 0.2 [0.12-0.31], and 0.90 [0.87-0.93]; and for non-deep learning models, they were 0.77 [0.71-0.82], 0.77 [0.73-0.80], 3.30 [2.83-3.84], 0.30 [0.24-0.38], and 0.82 [0.79-0.85], respectively. Subgroup analyses showed a significant difference between the single tumor subgroup and the multiple tumor subgroup in the pooled sensitivity, NLR, and AUC. Conclusion: This meta-analysis demonstrates the high diagnostic accuracy of non-deep learning and deep learning methods for MVI status prediction and their promising potential for clinical decision-making. Deep learning models perform better than non-deep learning models in terms of the accuracy of MVI prediction, methodology, and cost-effectiveness. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID=260891, ID:CRD42021260891.

PD-1 inhibitors plus lenvatinib versus PD-1 inhibitors plus regorafenib in patients with advanced hepatocellular carcinoma after failure of sorafenib.

Background: Lenvatinib, regorafenib and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising clinical outcomes in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure, respectively. However, the combination of the two treatments has not been reported. We compared the efficacy of PD-1 inhibitors with lenvatinib (PL) and PD-1 inhibitors plus regorafenib (PR) in patients with advanced HCC in this study. Methods: We conducted a retrospective study of advanced HCC patients who undergone PD-1 inhibitors combined with lenvatinib or regorafenib after failure of sorafenib at Second Affiliated Hospital of Nanchang University from July 2018 and December 2020. The overall survival (OS), progression-free survival (PFS), effective rates and treatment-related adverse events (TRAEs) were investigated. Results: In total, 61 patients met the criteria and were included in the present study, and they were divided into the PL group (n = 32) and PR group (n = 29). The overall response rate (ORR) (12.5%vs. 10.3%, respectively; p = 0.557) and disease control rate (DCR) (71.9%vs. 58.6%, respectively; p < 0.207) were higher in the PL group than in the PR group, but there was no statistical difference.Furthermore, median PFS and OS were not significantly different between the two groups in Kaplan-Meier survival analysis (PFS: 5.3 months vs 4.0 months, p = 0.512; OS: 14.1 months vs 13.7 months, p = 0.764 for the PL group vs PR group). The most common treatment-related adverse events (TRAEs) were hand -foot skin reaction (24/61,39.3%), hypertension (20/61,32.8%) and hypothyroidism (13/61,21.3%). The frequent TRAEs (≥Grade 3) during PD-1 inhibitors plus lenvatinib or regorafenib treatment were hand-foot skin reaction (5/29,12.4%), thrombocytopenia (2/29 6.90%) and proteinuria (n =2/32,6.25%). Conclusions: Combination of lenvatinib/regorafenib and PD-1 inhibitors is a promising therapy for HCC patients after sorafenib failure.

A case report on a child with fracture and dislocation of the upper cervical spine accompanied by spinal cord injury.

RATIONALE: This study describes an 8-year-old boy with a C2 fracture and dislocation with a left C2-C3 articular process interlocking and spinal cord injury who underwent open reduction and internal fixation using the posterior cervical approach and achieved satisfactory results. PATIENT CONCERNS: An 8-year-old boy underwent an emergency transfer from a previous hospital after a car accident. DIAGNOSES: Axial fracture and dislocation with spinal cord injury (American Spinal Injury Association grade C), traumatic shock, brain contusion, intracranial hemorrhage, mandibular fracture, pulmonary contusion and hemorrhage, left vertebral artery stenosis, and multiple fractures throughout the body. Radiological examination revealed a fracture of the lower edge of the C2 vertebral body, fourth-degree anterior spondylolisthesis of the C2 vertebral body, interlocking of the left C2-C3 articular processes, widening of the C2-C3 vertebral space, and occlusion of the V1 and 2 segments of the left vertebral artery. INTERVENTIONS: The boy was immediately intubated and transferred to the pediatric intensive care unit for rescue treatment. However, the reduction was unsuccessful with 2 weeks of cranial traction. Thus, an open reduction was performed under general anesthesia. One month after the surgery, the boy was discharged from the hospital on foot after rehabilitation treatment. OUTCOMES: The boy was discharged from the hospital 1 month after surgery. At the 8-month follow-up, a radiological examination showed that the corrected C2 vertebral body fracture and dislocation were satisfactorily reduced, and the spinal cord was adequately decompressed. The internal fixation position was also good, and the spinal sequence had recovered well. In summary, except for the muscle strength of the right upper limb, which was slightly worse, the other clinical symptoms were significantly improved. LESSONS: In treating cervical fracture and dislocation with unilateral facet lock, the posterior open reduction of pedicle screw and lateral mass screw internal fixation achieved satisfactory results. Consequently, treating complex cervical spine injuries in children requires an accurate diagnosis and careful treatment strategy.