Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial.

BACKGROUND: Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. METHODS: Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. RESULTS: A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group. CONCLUSIONS: Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT00230503 and China Drug Trials CTR2018042.

A role for the NPM1/PTPN14/YAP axis in mediating hypoxia-induced chemoresistance to sorafenib in hepatocellular carcinoma.

BACKGROUND: Tumor microenvironments are characterized by resistance to chemotherapeutic agents and radiotherapy. Hypoxia plays an important role in the development of tumor resistance, as well as the generation of metastatic potential. YAP also participates in the regulation of hypoxia-mediated chemoresistance, and is negatively regulated by protein tyrosine phosphatase non-receptor type 14 (PTPN14). METHODS: The PTPN14 expression in hepatocellular carcinoma (HCC) tissues were evaluated by qRT-PCR, western blot and tissue microarrays. The effect of PTPN14 on HCC progression was investigated in vitro and in vivo. RESULTS: Here, we report that PTPN14 expression was downregulated in HCC tissues and cell lines. Silencing PTPN14 significantly enhanced proliferation, migration, invasion of HepG2 cells in vitro and tumor growth and metastasis in vivo, whereas overexpression of PTPN14 significantly inhibited these abilities in SK-Hep1 cells. We also found that hypoxia-induced nuclear translocation and accumulation of PTPN14 led to resistance to sorafenib in HCC cells. Further mechanistic studies suggested that NPM1 regulates PTPN14 localization, and that NPM1 regulates YAP by retaining PTPN14 in the nucleus under hypoxic conditions. CONCLUSIONS: These data suggest that a therapeutic strategy against chemoresistant HCC may involve disruption of NPM1-mediated regulation of YAP by retaining PTPN14 in the nucleus under hypoxic conditions.

Piperlongumine synergistically enhances the antitumour activity of sorafenib by mediating ROS-AMPK activation and targeting CPSF7 in liver cancer.

Sorafenib, a multikinase inhibitor, is the first-line agent for advanced liver cancer. Sorafenib strongly inhibits both cell proliferation and tumour angiogenesis. However, the development of drug resistance hampers its anticancer efficacy. To improve the antitumour activity of sorafenib, we demonstrate that piperlongumine (PL), an alkaloid isolated from the fruits and roots of Piper longum L., enhances the cytotoxicity of sorafenib in HCCLM3 and SMMC7721 cells using the cell counting kit-8 test. Flow cytometry analysis indicated that PL and sorafenib cotreatment induced robust reactive oxygen species (ROS) generation and mitochondrial dysfunction, thereby increasing the number of apoptotic cells and the ratio of G2/M phase cells in both HCCLM3 and SMMC7721 cells. Furthermore, AMP-protein kinase (AMPK) signalling was activated by excess ROS accumulation and mediated growth inhibition in response to PL and sorafenib cotreatment. RNA-sequencing analysis indicated that PL treatment disrupted RNA processing in HCCLM3 cells. In particular, PL treatment decreased the expression of cleavage and polyadenylation specificity factor 7 (CPSF7), a subunit of cleavage factor I, in a time- and concentration-dependent manner in HCCLM3 and SMMC7721 cells. CPSF7 knockdown using a gene interference strategy promoted growth inhibition of PL or sorafenib monotherapy, whereas CPSF7 overexpression alleviated the cytotoxicity of sorafenib in cultured liver cancer cells. Finally, PL and sorafenib coadministration significantly reduced the weight and volume of HCCLM3 cell xenografts in vivo. Taken together, our data indicate that PL displays potential synergistic antitumour activity in combination with sorafenib in liver cancer.

Important Hormones Regulating Lipid Metabolism.

There is a wide variety of kinds of lipids, and complex structures which determine the diversity and complexity of their functions. With the basic characteristic of water insolubility, lipid molecules are independent of the genetic information composed by genes to proteins, which determine the particularity of lipids in the human body, with water as the basic environment and genes to proteins as the genetic system. In this review, we have summarized the current landscape on hormone regulation of lipid metabolism. After the well-studied PI3K-AKT pathway, insulin affects fat synthesis by controlling the activity and production of various transcription factors. New mechanisms of thyroid hormone regulation are discussed, receptor α and ß may mediate different procedures, the effect of thyroid hormone on mitochondria provides a new insight for hormones regulating lipid metabolism. Physiological concentration of adrenaline induces the expression of extrapituitary prolactin in adipose tissue macrophages, which promotes fat weight loss. Manipulation of hormonal action has the potential to offer a new therapeutic horizon for the global burden of obesity and its associated complications such as morbidity and mortality.

Sophoridine suppresses lenvatinib-resistant hepatocellular carcinoma growth by inhibiting RAS/MEK/ERK axis via decreasing VEGFR2 expression.

Hepatocellular carcinoma (HCC) is one of the most lethal cancer types with insufficient approved therapies, among which lenvatinib is a newly approved multi-targeted tyrosine kinase inhibitor for frontline advanced HCC treatment. However, resistance to lenvatinib has been reported in HCC treatment recently, which limits the clinical benefits of lenvatinib. This study aims to investigate the underlying mechanism of lenvatinib resistance and explore the potential drug to improve the treatment for lenvatinib-resistant (LR) HCC. Here, we developed two human LR HCC cell lines by culturing with long-term exposure to lenvatinib. Results showed that the vascular endothelial growth factor receptors (VEGFR)2 expression and its downstream RAS/MEK/ERK signalling were obviously up-regulated in LR HCC cells, whereas the expression of VEGFR1, VEGFR3, FGFR1-4 and PDGFRα/ß showed no difference. Furthermore, ETS-1 was identified to be responsible for VEGFR2 mediated lenvatinib resistance. The cell models were further used to explore the potential strategies for restoration of sensitivity of lenvatinib. Sophoridine, an alkaloid extraction, inhibited the proliferation, colony formation, cell migration and increased apoptosis of LR HCC cells. In vivo and in vitro results showed Sophoridine could further sensitize the therapeutic of lenvatinib against LR HCC. Mechanism studies revealed that Sophoridine decreased ETS-1 expression to down-regulate VEGFR2 expression along with downstream RAS/MEK/ERK axis in LR HCC cells. Hence, our study revealed that up-regulated VEGFR2 expression could be a predicator of the resistance of lenvatinib treatment against HCC and provided a potential candidate to restore the sensitivity of lenvatinib for HCC treatment.

LncRNA-SNHG6 promotes the progression of hepatocellular carcinoma by targeting miR-6509-5p and HIF1A.

BACKGROUND: Accumulating evidences have been reported that long noncoding RNAs play crucial roles in the progression of hepatocellular carcinoma (HCC). SnoRNA host gene 6 (SNHG6) is believed to be involved in several human cancers, but the specific molecular mechanism of SNHG6 in HCC is not well studied. METHODS: In this study, we experimentally down-regulated the SNHG6 in two hepatocellular carcinoma cell lines in vitro, and then measured the proliferation, migration and invasion abilities and the apoptotic levels. Also, we performed the xenograft assay to investigate the function of SNHG6 during the tumor growth in vivo. RESULTS: We found SNHG6 was highly expressed in HCC tissues. Next, using Hep3B and Huh7 cells, we confirmed knockdown of SNHG6 reduced the proliferation, migration and invasion abilities in vitro. Also, by bioinformatics analysis, further molecular and cellular experiments, we found miR-6509-5p bound to SNHG6 directly, and the expression level of HIF1A was regulated through SNHG6/miR-6509-5p axis. Finally, we found that down-regulation of SNHG6 dramatically reduced the tumor growth ability of Huh7 cells in vivo. CONCLUSIONS: We concluded that SNHG6/miR-6509-5p/HIF1A axis functioned in the progression of hepatocellular carcinoma, and could be the promising therapeutic targets during the development of hepatocellular carcinoma drugs.

Radiofrequency Ablation (RFA) Combined with Transcatheter Arterial Chemoembolization (TACE) for Patients with Medium-to-Large Hepatocellular Carcinoma: A Retrospective Analysis of Long-Term Outcome.

BACKGROUND The aim of this study was to investigate the prognostic value of radiofrequency ablation (RFA) plus transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with tumor size ranging from 3.0 to 10.0 cm. MATERIAL AND METHODS We retrospectively analyzed data on 201 patients with medium-to-large HCC. According to treatment procedure, the patients were divided into the TACE group (n=124) and the TACE+RFA group (n=77). We recorded data on patient safety, subcapsular hepatic hematoma, large amount of ascites, liver abscess, gallbladder injury, and local skin infection. The overall survival (OS) and progression-free survival (PFS) in the 2 groups were analyzed and compared between groups. RESULTS The median PFS was 4.00 months (3.00-5.00 months) in the TACE group and 9.13 months (6.64-11.62 months) in the TACE+RFA group (P<0.001). Median OS was 12.00 months (8.88-15.13 months) in the TACE group and 27.57 months (20.06-35.08 months) in the TACE+RFA group (P<0.001). In the TACE+RFA group, multivariate Cox regression analysis showed that tumor size ≤5 cm) (HR: 1.952, 95% CI: 1.213-3.143, P=0.006), hepatitis B (HR: 2.323, 95% CI: 1.096-4.923, P=0.028), TACE times (1 or >1) (HR: 1.867, 95% CI: 1.156-3.013, P=0.011), alpha-fetoprotein (AFP) level >200 ng/ml (HR: 2.426, 95% CI: 1.533-3.839, P<0.001), and AST level >40 U/L (HR: 1.946, 95% CI: 1.196-3.166, P=0.007) were independent prognostic factors for overall survival. CONCLUSIONS Combination therapy of TACE with RFA is a safe and effective treatment for patients with medium-to-large HCC, with the long-term beneficial effect of retarding tumor progression and improving PFS and OS.

Waveguide-Integrated, Plasmonic Enhanced Graphene Photodetectors.

We present a micrometer-scale, on-chip integrated, plasmonic enhanced graphene photodetector (GPD) for telecom wavelengths operating at zero dark current. The GPD is designed to directly generate a photovoltage by the photothermoelectric effect. It is made of chemical vapor deposited single layer graphene, and has an external responsivity ∼12.2 V/W with a 3 dB bandwidth ∼42 GHz. We utilize Au split-gates to electrostatically create a p-n-junction and simultaneously guide a surface plasmon polariton gap-mode. This increases the light-graphene interaction and optical absorption and results in an increased electronic temperature and steeper temperature gradient across the GPD channel. This paves the way to compact, on-chip integrated, power-efficient graphene based photodetectors for receivers in tele- and datacom modules.

Bistability of Cavity Magnon Polaritons.

We report the first observation of the magnon-polariton bistability in a cavity magnonics system consisting of cavity photons strongly interacting with the magnons in a small yttrium iron garnet (YIG) sphere. The bistable behaviors emerged as sharp frequency switchings of the cavity magnon polaritons (CMPs) and related to the transition between states with large and small numbers of polaritons. In our experiment, we align, respectively, the [100] and [110] crystallographic axes of the YIG sphere parallel to the static magnetic field and find very different bistable behaviors (e.g., clockwise and counter-clockwise hysteresis loops) in these two cases. The experimental results are well fitted and explained as being due to the Kerr nonlinearity with either a positive or negative coefficient. Moreover, when the magnetic field is tuned away from the anticrossing point of CMPs, we observe simultaneous bistability of both magnons and cavity photons by applying a drive field on the lower branch.

ShRNA knock-down of CXCR7 inhibits tumour invasion and metastasis in hepatocellular carcinoma after transcatheter arterial chemoembolization.

To investigate the effects of lentiviral vector-mediated shRNA suppressing CXCR7 on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured and assigned into the CXCR7-shRNA, negative control (NC) and blank groups. The qRT-PCR and Western blotting were applied to detect the mRNA and protein expressions of CXCR7, CXCR4 and MMP-2 in HCCLM3 cells. Cell proliferation and invasion were evaluated by MTT and Transwell assays. A Buffalo rat model of HCC was established. Fifty model rats were divided into the CXCR7-shRNA + TACE, CXCR7-shRNA, TACE, NC and control groups. Immunohistochemistry was performed to detect the expressions of CXCR7, MMP-2, vascular endothelial growth factor (VEGF) and intratumoral CD31-positive vessel count in tumour tissues of mice. Compared with the blank and NC groups, the mRNA and protein expressions of CXCR7 and MMP-2 were decreased in the CXCR7-shRNA group. The cell proliferation and invasion rates of the CXCR7-shRNA group were lower than the blank and NC groups. At the 4th week after TACE, tumour weight of the CXCR7-shRNA + TACE group increased continuously. The CXCR7-shRNA + TACE group showed longer survival time and smaller tumour sizes than other groups. Compared with other groups, the CXCR7-shRNA + TACE and CXCR7-shRNA groups had less number of lung metastatic nodules and lower expressions of CXCR7, MMP-2, VEGF and CD31-positive vessel count. CXCR7-shRNA inhibits tumour invasion and metastasis to improve the efficacy of TACE in HCC by reducing the expressions of CXCR7, MMP-2 and VEGF.

Evaluation of the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis using 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Our study aims to evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of patients with liver metastasis using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A total of 97 liver metastasis patients treated by transcatheter arterial chemoembolization were enrolled in this study. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography images of liver metastasis patients were collected before and after transcatheter arterial chemoembolization treatment. The efficacy of transcatheter arterial chemoembolization for the treatment of liver metastasis was evaluated according to the revised Response Evaluation Criteria in Solid Tumors guidelines. The receiver operating characteristic curve analysis was used to determine cut-off values of 18F-fluorodeoxyglucose positron emission tomography parameters (Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean) for predicting the efficacy of transcatheter arterial chemoembolization. Progression-free survival and the incidence of postoperative complications were compared. Correlation of Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean with blood supply and lipiodol deposition in the lesion was analyzed. Among three 18F-fluorodeoxyglucose positron emission tomography parameters, the receiver operating characteristic analysis showed that Tsuvmax/Lsuvmax with a cut-off value of 3.56 was the best predictor of transcatheter arterial chemoembolization efficacy. According to the cut-off value of Tsuvmax/Lsuvmax, liver metastasis patients were divided into the Tsuvmax/Lsuvmax ≤ 3.56 and Tsuvmax/Lsuvmax > 3.56 groups. Compared with the Tsuvmax/Lsuvmax > 3.56 group, the Tsuvmax/Lsuvmax ≤ 3.56 group showed a longer progression-free survival and a lower incidence of postoperative complications. The Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with abundant blood supply were significantly lower than those in peripheral liver parenchyma, while the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with lack of blood supply were significantly higher than those in peripheral liver parenchyma. Spearman correlation analysis indicated that lipiodol deposition in the lesion was positively correlated with the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean. The Tsuvmax/Lsuvmax of 18F-fluorodeoxyglucose positron emission tomography/computed tomography may be a good tool for predicting the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis.

Development and psychometric properties of an informant assessment scale of theory of mind for adults with traumatic brain injury.

Impairment of theory of mind (ToM) is a common phenomenon following traumatic brain injury (TBI) that has clear effects on patients' social functioning. A growing body of research has focused on this area, and several methods have been developed to assess ToM deficiency. Although an informant assessment scale would be useful for examining individuals with TBI, very few studies have adopted this approach. The purpose of the present study was to develop an informant assessment scale of ToM for adults with traumatic brain injury (IASToM-aTBI) and to test its reliability and validity with 196 adults with TBI and 80 normal adults. A 44-item scale was developed following a literature review, interviews with patient informants, consultations with experts, item analysis, and exploratory factor analysis (EFA). The following three common factors were extracted: social interaction, understanding of beliefs, and understanding of emotions. The psychometric analyses indicate that the scale has good internal consistency reliability, split-half reliability, test-retest reliability, inter-rater reliability, structural validity, discriminate validity and criterion validity. These results provide preliminary evidence that supports the reliability and validity of the IASToM-aTBI as a ToM assessment tool for adults with TBI.

[Efficacies of ¹³¹I-chTNT plus radiofrequency ablation for the treatment of advanced hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacies of radiofrequency ablation (RFA) plus iodine (¹³¹I) tumor necrosis therapy monoclonal antibody (¹³¹I-chTNT) for advanced stage hepatocellular carcinoma. METHODS: The clinical data of 38 hepatocellular carcinoma patients confirmed clinically or pathologically were retrospectively analyzed. They were divided into 2 groups (RFA group, n = 22; combination group, n = 16) according to the treatment mode. The median follow-up period was 31 (8-49) months.Survival was estimated with the Kaplan-Meier method and the survival curve compared by log-rank test. RESULTS: Thirteen cases in RFA group and 7 cases in combination group died of tumor progression or complications of liver cirrhosis. The median survival time in combination group was significantly than RFA group (43 vs 37 months) (P = 0.039). The overall survival rates at 1, 2 and 3 years (100%, 87.5%, 75% respectively) were higher than those in RFA group (81.8%, 58.2%, 51.7% respectively). CONCLUSION: For hepatocellular carcinoma with a special site and a diameter ≥ 5 cm, RFA plus ¹³¹I-chTNT treatment can prolong progression-free survival time. And its short-term curative effect is better than that of RFA therapy. And the long-term outcomes may be further explored by a large-sample, multi-center and randomized trial.

Effect of UV exposure and natural aging on the in vitro PAHs bioaccessibility associated with tire wear particles in soil.

Tire wear particles (TWP), as an emerging type of microplastics, are a significant source of contaminants in roadside soils due to their high concentration of pollutants, including polycyclic aromatic hydrocarbons (PAHs). This study explored the impact of ultraviolet (UV) exposure and natural aging on the in vitro bioaccessibility of PAHs associated with TWP in soil on a China-wide scale. Our findings suggested that UV exposure amplified the negative charge of TWP by 75 % and increased the hydrophobic groups on the particle surface. The bioaccessibility of 3- and 4-ring PAHs in TWP was significantly (p < 0.05) heightened by UV exposure. After 20 types of soils containing 2 % UV-exposed TWP underwent natural aging, the bioaccessibility of PAHs saw a significant decrease (p < 0.05) to 16-48 %, compared to 28-96 % in the unaged group. Soil pH and electrical conductivity (EC) were the two primary soil properties positively influencing the reduction of in vitro PAHs concentration and PAHs bioaccessibility. According to the prediction results, soils in southern China presented the highest potential region for the release of bioaccessible PAHs from TWP, highlighting the regional specificity of environmental impact. Our study provides valuable insights into the biological impact of PAHs associated with TWP on a regional scale, and offers scientific evidence for targeted soil risk management strategies.

Prediction of PFAS bioaccumulation in different plant tissues with machine learning models based on molecular fingerprints.

Due to the wastewater irrigation or biosolid application, per- and polyfluoroalkyl substances (PFASs) have been widely detected in agriculture soil and hence crops or vegetables. Consumption of contaminated crops and vegetables is considered as an important route of human exposure to PFASs. Machine learning (ML) models have been developed to predict PFAS uptake by plants with majority focus on roots. However, ML models for predicting accumulation of PFASs in above ground edible tissues have yet to be investigated. In this study, 811 data points covering 22 PFASs represented by molecular fingerprints and 5 plant categories (namely the root class, leaf class, cereals, legumes, and fruits) were used for model development. The Extreme Gradient Boosting (XGB) model demonstrated the most favorable performance to predict the bioaccumulation factors (BAFs) in all the 4 plant tissues (namely root, leaf, stem, and fruit) achieving coefficients of determination R2 as 0.82-0.93. Feature importance analysis showed that the top influential factors for BAFs varied among different plant tissues, indicating that model developed for root concentration prediction may not be feasible for above ground parts. The XGB model's performance was further demonstrated by comparing with data from pot experiments measuring BAFs of 12 PFASs in lettuce. The correlation between predicted and measured results was favorable for BAFs in both lettuce roots and leaves with R2 values of 0.76 and 0.81. This study developed a robust approach to comprehensively understand the uptake of PFASs in both plant roots and above ground parts, offering key insights into PFAS risk assessment and food safety.

Bronchial arterial chemoembolization with Drug-Eluting beads plus sequential chemotherapy for the treatment of stage III and IV lung squamous cell carcinoma.

PURPOSE: This retrospective study aimed to investigate the effectiveness and safety of bronchial arterial chemoembolization with drug-eluting beads (DEB-BACE) plus chemotherapy versus chemotherapy alone in patients with stage III and IV lung squamous cell carcinoma (LSCC) who are not appropriate candidates for radiochemotherapy. MATERIALS AND METHODS: In this retrospective analysis, we screened all adult patients undergoing either DEB-BACE plus chemotherapy or chemotherapy alone for stage III or IV LCSS at authors' center from January 2018 to August 2021. Each 21-day chemotherapy cycle consisted of intravenous injection of gemcitabine (1.0 g/m2) on days 1 and 8 and cisplatin 75 (mg/m2) on day 1. The planned cycles were 4. DEB-BACE consisted of microcatheter infusion of CalliSpheres beads carrying cisplatin (75 mg/m2) and gemcitabine (1.0 g/m2), at 3 weeks prior to chemotherapy. The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS), pulmonary response, and adverse events (AEs). RESULTS: The final analysis included 95 patients in the chemotherapy group and 41 patients in the combination treatment group. The median OS was 14 months (95 % CI 11.0-17.0) in the chemotherapy group and 19 months (95 % CI 18.0-24.0) in the combination group (P = 0.015). In multivariate Cox regression analysis, DEB-BACE plus chemotherapy was associated with lower risk of death versus chemotherapy only (HR 0.16, 95 % CI 0.05-0.52; log rank test P = 0.003). The median PFS was 6 months (95 % CI 4.0-7.0) in the chemotherapy group and 8 months (95 % CI 6.0-8.0) in the combination group (P = 0.015). The pulmonary objective response rate (ORR) and disease control rate (DCR) were 48.4 % and 62.1 % in chemotherapy group versus 82.9 % and 90.2 % in combination group (P < 0.001 and = 0.001, respectively). AEs occurred in 133 patients (97.8 %). The rate of bone marrow suppression was 48.4 % (46/95) in the chemotherapy group versus 7.3 % (3/41) in the combination group (P < 0.001). CONCLUSION: Compared with chemotherapy alone, DEB-BACE plus chemotherapy was associated with longer survival outcomes and lower rate of bone marrow suppression.

Dual-energy computed tomography for predicting cervical lymph node metastasis in laryngeal squamous cell carcinoma.

Rationale and objectives: We constructed a dual-energy computed tomography (DECT)-based model to assess cervical lymph node metastasis (LNM) in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methods: We retrospectively analysed 164 patients with LSCC who underwent preoperative DECT from May 2019 to May 2023. The patients were randomly divided into training (n = 115) and validation (n = 49) cohorts. Quantitative DECT parameters of the primary tumours and their clinical characteristics were collected. A logistic regression model was used to determine independent predictors of LNM, and a nomogram was constructed along with a corresponding online model. Model performance was assessed using the area under the curve (AUC) and the calibration curve, and the clinical value was evaluated using decision curve analysis (DCA). Results: In total, 64/164 (39.0 %) patients with LSCC had cervical LNM. Independent predictors of LNM included normalized iodine concentration in the arterial phase (odds ratio [OR]: 8.332, 95 % confidence interval [CI]: 2.813-24.678, P < 0.001), normalized effective atomic number in the arterial phase (OR: 5.518, 95 % CI: 1.095-27.818, P = 0.002), clinical T3-4 stage (OR: 5.684, 95 % CI: 1.701-18.989, P = 0.005), and poor histological grade (OR: 5.011, 95 % CI: 1.003-25.026, P = 0.049). These predictors were incorporated into the DECT-based nomogram and the corresponding online model, showing good calibration and favourable performance (training AUC: 0.910, validation AUC: 0.918). The DCA indicated a significant clinical benefit of the nomogram for estimating LNM. Conclusions: DECT parameters may be useful independent predictors of LNM in patients with LSCC, and a DECT-based nomogram may be helpful in clinical decision-making.

[Disability identification for cases with clinical diagnosis of diffuse axonal injury due to traffic accidents: a study of 89 cases].

OBJECTIVE: To study the disability identification for cases with clinical diagnosis of diffuse axonal injury (DAI) due to traffic accidents, and to explore the possible effects of DAI on identification results. METHODS: Five hundred and fifty-six cases of cerebral injury due to traffic accidents were collected, including 467 cases diagnosed with cerebral contusion or laceration and 89 cases diagnosed with DAI. The identification results of different groups with diagnosis of DAI diagnosis, diagnosis of DAI with cerebral contusion (laceration), and diagnosis of cerebral contusion or laceration without DAI were compared and statistically analyzed, based on the results of CT and MRI re-review. RESULTS: The disability identification levels in DAI group (20 cases), DAI group (69 cases) with cerebral contusion (laceration) and DAI group (467 cases) not complicated by cerebral contusion (laceration) were 7.72 +/- 1.09, 7.78 +/- 1.11, and 8.86 +/- 0.66, respectively. The disability levels of the two groups diagnosed with DAI were higher than those of the group without DAI diagnosis (P < 0.05). CONCLUSION: Patients with DAI diagnosis might have more severe cerebral injury. In the identification process, one should pay attention to the possible missed diagnosis and misdiagnosis, and meanwhile avoid relying on those evidences provided only by CT and MRI.

Considerations on the impact of "source-sink" landscape pattern changes on urban thermal environment and cooling efficiency: a case study of Nanjing, China.

The urban heat island effect caused by rapid urbanization has had a great impact on human health and ecological environment. The evolution of landscape patterns often affects regional thermal characteristics at the local scale. How to rationally allocate land cover types from the perspective of urban planning is a huge challenge. This paper takes Nanjing, a typical "stove city" in China, as an example to study the impact of landscape pattern changes on the urban thermal environment. Firstly, based on the "source" landscape "/sink" landscape identified by the "source-sink" landscape index, on this basis, the contributions of the "source-sink" landscape and its effects are calculated, and the temporal and spatial evolution laws are analyzed. Second, we study the cooling effect of different characteristic landscapes. The results show that the change of landscape pattern is closely related to the urban thermal environment, and the expansion of built-up areas is the main reason for the urban thermal environment. With the development of urbanization, the "source-sink" landscape structure in most districts and counties has aggravated the heat island effect, and the ratios of "sink" and "source" landscape contribution ratios with strong levels are concentrated in the suburban areas. The results of cooling efficiency research show that the cooling range of forest land is larger than that of water bodies. At the same time, we found that the cooling efficiency of the sink landscape is the highest when the area of the sink landscape is 0.18-0.9 hm2 and the shape index is between 1 and 4. The research results can provide feasible and practical scientific suggestions for the planning and ecological construction of Nanjing.

Multi-algorithms analysis for pre-treatment prediction of response to transarterial chemoembolization in hepatocellular carcinoma on multiphase MRI.

OBJECTIVES: This study compared the accuracy of predicting transarterial chemoembolization (TACE) outcomes for hepatocellular carcinoma (HCC) patients in the four different classifiers, and comprehensive models were constructed to improve predictive performance. METHODS: The subjects recruited for this study were HCC patients who had received TACE treatment from April 2016 to June 2021. All participants underwent enhanced MRI scans before and after intervention, and pertinent clinical information was collected. Registry data for the 144 patients were randomly assigned to training and test datasets. The robustness of the trained models was verified by another independent external validation set of 28 HCC patients. The following classifiers were employed in the radiomics experiment: machine learning classifiers k-nearest neighbor (KNN), support vector machine (SVM), the least absolute shrinkage and selection operator (Lasso), and deep learning classifier deep neural network (DNN). RESULTS: DNN and Lasso models were comparable in the training set, while DNN performed better in the test set and the external validation set. The CD model (Clinical & DNN merged model) achieved an AUC of 0.974 (95% CI: 0.951-0.998) in the training set, superior to other models whose AUCs varied from 0.637 to 0.943 (p < 0.05). The CD model generalized well on the test set (AUC = 0.831) and external validation set (AUC = 0.735). CONCLUSIONS: DNN model performs better than other classifiers in predicting TACE response. Integrating with clinically significant factors, the CD model may be valuable in pre-treatment counseling of HCC patients who may benefit the most from TACE intervention.