Phase-resolved MRI for measurement of pulmonary perfusion and ventilation defects in comparison with dynamic contrast-enhanced MRI and 129Xe MRI.

INTRODUCTION: This meta-analysis aims to evaluate the agreement and correlation between phase-resolved functional lung MRI (PREFUL MRI) and dynamic contrast-enhanced (DCE) MRI in evaluating perfusion defect percentage (QDP), as well as the agreement between PREFUL MRI and 129Xe MRI in assessing ventilation defect percentage (VDP). METHOD: A systematic search was conducted in the Medline, Embase and Cochrane Library databases to identify relevant studies comparing QDP and VDP measured by DCE MRI and 129Xe MRI compared with PREFUL MRI. Meta-analytical techniques were applied to calculate the pooled weighted bias, limits of agreement (LOA) and correlation coefficient. The publication bias was assessed using Egger's regression test, while heterogeneity was assessed using Cochran's Q test and Higgins I2 statistic. RESULTS: A total of 399 subjects from 10 studies were enrolled. The mean difference and LOA were -2.31% (-8.01% to 3.40%) for QDP and 0.34% (-4.94% to 5.62%) for VDP. The pooled correlations (95% CI) were 0.65 (0.55 to 0.73) for QDP and 0.72 (0.61 to 0.80) for VDP. Furthermore, both QDP and VDP showed a negative correlation with forced expiratory volume in 1 s (FEV1). The pooled correlation between QDP and FEV1 was -0.51 (-0.74 to -0.18), as well as between VDP and FEV1 was -0.60 (-0.73 to -0.44). CONCLUSIONS: PREFUL MRI is a promising imaging for the assessment of lung function, as it demonstrates satisfactory deviations and LOA when compared with DEC MRI and 129Xe MRI. PROSPERO REGISTRATION NUMBER: CRD42023430847.

Prognostic and predictive value of interstitial lung abnormalities and EGFR mutation status in patients with non-small cell lung cancer.

BACKGROUND: To determine the predictive value of interstitial lung abnormalities (ILA) for epidermal growth factor receptor (EGFR) mutation status and assess the prognostic significance of EGFR and ILA in patients with non-small cell lung cancer (NSCLC). METHODS: We reviewed 797 consecutive patients with a histologically proven diagnosis of primary NSCLC from January 2013 to October 2018. Of these, 109 patients with NSCLC were found to have concomitant ILA. Multivariate logistic regression analysis was used to identify the significant clinical and computed tomography (CT) findings in predicting EGFR mutations. Cox proportional hazard models were used to identify significant prognostic factors. RESULTS: EGFR mutations were identified in 22 of 109 tumors (20.2%). Multivariate analysis showed that the models incorporating clinical, tumor CT and ILA CT features yielded areas under the receiver operating characteristic curve (AUC) values of 0.749, 0.838, and 0.849, respectively. When combining the three models, the independent predictive factors for EGFR mutations were non-fibrotic ILA, female sex, and small tumor size, with an AUC value of 0.920 (95% confidence interval[CI]: 0.861-0.978, p < 0.001). In the multivariate Cox model, EGFR mutations (hazard ratio = 0.169, 95% CI = 0.042-0.675, p = 0.012; 692 days vs. 301 days) were independently associated with extended overall survival compared to the wild-type. CONCLUSION: Non-fibrotic ILA independently predicts the presence of EGFR mutations, and the presence of EGFR mutations rather than non-fibrotic ILA serves as an independent good prognostic factor for patients with NSCLC.

Alloying enhanced negative Poisson's ratio in two-dimensional aluminum gallium nitride (AlxGa1-xN).

The negative Poisson's ratio (NPR) effect usually endows materials with promising ductility and shear resistance, facilitating a wider range of applications. It has been generally acknowledged that alloys show strong advantages in manipulating material properties. Thus, a thought-provoking question arises: how does alloying affect the NPR? In this paper, based on first-principles calculations, we systematically study the NPR in two-dimensional (2D) GaN and AlN, and their alloy of AlxGa1-xN. It is intriguing to find that the NPR in AlxGa1-xN is significantly enhanced compared to the parent materials of GaN and AlN. The underlying mechanism mainly originates from a counter-intuitive increase of the bond angle θ. We further study the microscopic origin of the anomalies by electron orbital analysis as well as electron localization functions. It is revealed that the distribution and movement of electrons change with the applied strain, providing a fundamental view on the effect of strain on lattice parameters and the NPR. The physical origin as revealed in this study deepens the understanding of the NPR and shed light on the future design of modern nanoscale electromechanical devices with fantastic functions based on the auxetic nanomaterials and nanostructures.

Phase III study of HR-positive/HER2-negative/lymph node-positive breast cancer non-responsive to primary chemotherapy: a randomized trial.

There are few studies focus on post-neoadjuvant treatment in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-)/lymph node-positive (LN+) breast cancer, a multi-center, open-label, randomized, controlled phase III trial was conducted to evaluate pathological response-guided non-cross-resistant adjuvant chemotherapy in patients with HR+/HER2-/LN+ breast cancer who were non-responsive to primary chemotherapy. Patients received four cycles of non-cross-resistant adjuvant chemotherapy plus endocrine therapy (ET), or ET alone. Forty patients responsive to neoadjuvant chemotherapy and with Miller and Payne G4 or G5 and LN- status were assigned to the observation group. Distant disease-free survival was the primary endpoint. The final intention-to-treat analysis comprised 379 patients. After a median follow-up period of 72.4 months, the 5-year distant disease-free survival was 92% and 90% in the chemotherapy plus ET and ET-alone groups, respectively. Comparatively, the observation group showed a trend towards better distant disease-free survival. For patients non-responsive to neoadjuvant chemotherapy, adjuvant non-cross-resistant chemotherapy did not significantly improve distant disease-free survival compared to ET alone.

Observation Effectiveness of Dose-Dense Neoadjuvant Anthracycline Sequential Weekly Paclitaxel for Triple-Negative Breast Cancer Patients.

INTRODUCTION/BACKGROUND: To investigate the differences in pathological response and survival outcomes between dose-dense and conventional-interval neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with TNBC who received NAC including epirubicin plus cyclophosphamide followed by weekly paclitaxel were included. A total of 494 patients were divided into either the dose-dense anthracycline (ddEC-wP) group or conventional interval anthracycline (EC-wP) group. RESULTS: The breast pathological complete response (bpCR, ypT0/is) rate was 45.3% (n = 101) in the dose-dense group and 34.3% (n = 93) in the conventionally scheduled group, which was a significant difference (P = .013), and in the 251 pN+ cases, the lymph node pathological complete response (LNpCR, ypN0) rate was 57.9% (n = 62) in the dose-dense group and 43.7% (n = 63) in the conventionally scheduled group, which was a significant difference (P = .026) in the univariate analysis. In the multivariate logistic regression analysis, 3 variables were predictive of bpCR: pathological type, surgical methods and type of chemotherapy, with P values of .012, .001 and .021, respectively. Two variables were predictive of LNpCR: type of chemotherapy and Her-2 expression, with P values of .039 and .020, respectively. After a median follow-up of 54 months, there was no significant difference in survival for disease-free survival (DFS) (hazard ratio [HR], 0.788; 95% confidence interval [CI], 0.508 to 1.223; P = .288), distant disease-free survival (DDFS) (HR, 0. 709; 95% CI, 0.440 to 1.144; P = .159) or overall survival (OS) (HR, 0. 750; 95% CI, 0.420 to 1.338; P = .330) between the 2 groups. CONCLUSION: Our study demonstrated that TNBC achieved a higher bpCR rate and LNpCR rate after dose-dense neoadjuvant chemotherapy than the conventional scheme. The survival benefit of the 2 groups did not reach statistical difference.

CT Radiomics for Predicting Pathological Complete Response of Axillary Lymph Nodes in Breast Cancer After Neoadjuvant Chemotherapy: A Prospective Study.

BACKGROUND: The diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful. PATIENTS AND METHODS: Prospective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers. RESULTS: A total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000. CONCLUSION: The pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.

Transarterial viroembolization improves the therapeutic efficacy of immune-excluded liver cancer: Three birds with one stone.

OBJECTIVE: To investigate the mechanism and efficacy of transarterial viroembolization (TAVE) with an oncolytic virus (OH2) for the treatment of liver cancer in rabbit VX2 tumor models. MATERIALS AND METHODS: Subcutaneous tumor and liver cancer models were established to determine the optimal viral titer and administration modality of OH2. Different liver cancer models were established to evaluate the locoregional tumor response, synergistic and standby effects, survival benefit, and specific antitumor immune memory after TAVE treatment. The immune cell densities in tumor tissues were measured. RESULTS: The optimal viral titer of OH2 was 1 × 107 CCID50. TAVE was the most effective modality with greater homogeneous OH2 distribution and therapeutic efficacy compared to other administration routes of transarterial virus infusion (TAVI), commonly adopted intratumor injection (TI), and intravenous injection (IV). Additionally, TAVE treatment significantly improved the locoregional tumor response, standby effect, and survival benefit compared to the TAVI, transarterial embolization (TAE), and control groups. TAVE modified the immune cell densities for immune-excluded liver cancer, partially destroyed vessel metastases, and established antitumor immune memory. The synergistic treatment efficacy of TAVE was superior to the simple addition of two independent monotherapies. CONCLUSION: TAVE was the optimal and a safe modality for treating immune-excluded liver cancer, and its synergistic effect achieved a remarkable tumor response, standby effect, survival benefit, and antitumor immune memory, which providing an innovative therapeutic modality for clinical practice. DATA AVAILABILITY: Data is available from the corresponding author upon requirement.

Impact of Sentinel Lymph Node Biopsy on Treatment Decision and Survival in Patients Aged ≥70 Years with Breast Cancer: A Retrospective Study.

Background: Whether sentinel lymph node biopsy should be performed in patients ≥70 years old with early-stage invasive breast cancer is controversial. We examined the effect of sentinel lymph node biopsy on the treatment and outcomes in this population. Materials and Methods: In this retrospective study, patients aged ≥70 years who were treated for invasive breast cancer with sentinel lymph node biopsy followed by mastectomy or lumpectomy between 2010 and 2019 were identified from our database. Patients were compared according to sentinel lymph node status. Outcomes were analyzed using the Kaplan-Meier method and Cox multivariate analysis. Results: Of the 376 patients enrolled in this study, 311 (82.7%) were sentinel lymph node-negative and 65 (17.3%) were sentinel lymph node-positive. The median follow-up duration for all patients was 70 months. Systemic treatment and radiation were similar between sentinel lymph node-negative and -positive groups. Disease-free survival, distant disease-free survival, breast cancer-specific survival, overall survival were not significantly different between groups (88.2% vs 87.6%, 96.7% vs 94.8%, 96.2% vs 93.6%, and 93.5% vs 90.0%, respectively). Sentinel lymph node status, tumor size, chemotherapy, endocrine therapy, and adjuvant radiation were included in Cox multivariate analysis. None of the variables were found to significantly affect disease-free survival, distant disease-free survival, breast cancer-specific survival, and overall survival. Conclusions: Our analysis indicated that sentinel lymph node status may not affect systemic treatment decisions or survival in patients aged ≥70 years with breast cancer.

Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study.

PURPOSE: For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI). METHODS: We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0-1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0-1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician. RESULTS: A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4-104 months), patients who had PEPI 0-1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5-99.9%) for PEPI 0-1 or pCR group vs. 93.7% (95% CI 89.6-97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases. CONCLUSION: PEPI 0-1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted. CLINICAL TRIAL REGISTRATION: NCT01613560.

Risk of ipsilateral breast tumor recurrence and contralateral breast cancer in patients with and without TP53 variant in a large series of breast cancer patients.

BACKGROUND: The association between breast cancer patients with a TP53 pathogenic variant and risk of local recurrence and contralateral breast cancer remains largely unknown. METHODS: The study population of 11093 patients was derived from two cohorts at the Breast Center of Peking University Cancer Hospital in China from November 2003, to March 2018. TP53 germline variants were determined for all patients. RESULTS: In the study, forty-one (0.37%) carried a TP53 germline pathogenic variant, and 11052 were non-carriers (99.63%). Nineteen TP53 carriers (46.3%) and 4173 non-carriers (37.8%) were treated with breast-conserving therapy (BCT), while the remaining were treated with mastectomy. After a median follow-up of 6.7 years, the rate of ipsilateral breast tumor recurrence (IBTR) in TP53 carriers was significantly higher than that in non-carriers when treated with BCT (21.1% vs 3.8%, P = 0.006). No difference in the rate of IBTR was found between TP53 carriers and non-carriers when treated with mastectomy (0.0% vs 2.6%, P = 1.0). Furthermore, the rate of IBTR in TP53 carriers treated with BCT was significantly higher than that in those treated with mastectomy (21.1% vs 0.0%, P = 0.038). The 10-year cumulative risk of contralateral breast cancer in TP53 carriers was significantly higher than that in non-carriers (17.9% vs 3.6%, hazard ratio (HR) = 7.0, 95% CI: 3.3-14.9, P < 0.001). CONCLUSIONS: Patients with TP53 variants have a high risk of IBTR when treated with BCT, and exhibit a very high risk of contralateral breast cancer. TP53 carriers may not be suitable for BCT and prophylactic contralateral mastectomy might be considered.

Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: Monotherapies and Combined Therapies.

Hepatocellular carcinoma (HCC) is an important cause of cancer death and is considered the 3rd most lethal around the world. Hepatectomy, liver transplantation, and ablation therapy are considered curative treatments for early-stage HCC. Transarterial chemoembolization is the preferred therapy for intermediate stage HCC. Ssystemic therapy is recommended for advanced HCC. For more than a decade, sorafenib and lenvatinib were used as the first-line treatment for the advanced HCC. For the great success of immunotherapy in melanoma and lung cancer, some immune-based treatments, such as immune checkpoint inhibitors (ICIs), have been applied in the treatment of HCC. The anti-programmed cell death protein 1 (PD1) antibodies, including nivolumab and pembrolizumab, have been approved by the Food and Drug Administration for sorafenib-pretreated patients. Moreover, due to the results of durable antitumor responses attained from the phase 3 trials, atezolizumab in combination with bevacizumab is now the standard therapy for advanced HCC. Recently, there are a lot of clinical trials involving the ICIs, as monotherapy or combination therapy, with tyrosine kinase inhibitors, antiangiogenic drugs, cytotoxic agents, and locoregional treatments, providing a promising outcome for advanced HCC. Thus, this review summarized the role of ICIs for HCC patients with monotherapy or combination therapy. The success and failures of monotherapy and combination therapy involving ICIs have provided advanced insights into HCC treatment and led to novel avenues to improve therapy efficacy in HCC.

Preoperative MRI features predict failed breast-conserving surgery: construction of a predictive model.

Background: Breast-conserving surgery (BCS) is the preferred method for early breast cancer, and the accurate preoperative prediction of the feasibility of BCS can formulate the surgical plan and reduce the violation of the patient's will. The present study proposed to explore the preoperative magnetic resonance imaging (MRI) features associated with failed BCS and constructed an MRI-based model to predict BCS. Methods: This retrospective study included patients between March 2015 and July 2016, who planned to undergo BCS, had preoperative MRI examination, and had at least 2 years of follow-up. A total of 30 patients with failed BCS were identified and matched with 90 patients with successful BCS (ratio 1:3) according to age, neoadjuvant therapy, and hormone receptor expression. The patients were divided into the training group for model construction and the testing group for model validation. The MRI features, including the site of the tumor, the lesion type, and the lesion and breast volume, were compared between failure and successful BCS groups. A multivariate logistic model for predicting failed BCS was constructed using independent factors associated with failed BCS from the training group and was evaluated in the testing group. The performance of the model was evaluated using the receiver operating characteristic (ROC) curve. Results: The mean age of the cohort was 45.7±10.3 years. A significantly more non-mass lesion and multifocality, the larger volume of lesion, and the ratio of lesion and breast volume were observed in failed BCS group compared to the successful BCS group. The ratio of lesion and breast volume and multifocality were independent factors associated with failed BCS, odds ratios were 1.044 (95% CI: 1.016-1.074) and 11.161 (95% CI: 1.739-71.652), respectively. An MRI-based model for predicting failed BCS was established, the area under the ROC curves in the training and testing group were 0.902 and 0.821, respectively. Conclusions: This model might help clinicians predict failed BCS preoperatively and make an accurate surgical strategy.

Effect of Local Versus General Anesthesia in Breast-Conserving Surgery on Cancer Recurrence and Cost.

BACKGROUND: The association between the type of anesthesia used and the recurrence of cancer remains controversial. This study aimed to compare the effects of local vs general anesthesia on recurrence-free survival and cost after breast-conserving surgery. MATERIALS AND METHODS: We reviewed the data of 2778 patients who underwent breast-conserving surgery followed by radiation at our center between 1999 and 2014. We analyzed the data of 994 patients with hormone receptor-positive and Her2-negative tumors who underwent breast-conserving surgery without axillary lymph node dissection under local or general anesthesia. Patients were grouped according to whether local or general anesthesia was used for the surgery. RESULTS: Of the 994 patients enrolled in this study, 367 received local anesthesia and 627 patients received general anesthesia. The median follow-up duration for all patients was 93 months. The Kaplan-Meier survival curves did not reveal significant differences between the recurrence-free survival of the two groups, with 5-year recurrence-free survival rates of 96.3% (95% CI, 94.3-98.3%) in the local anesthesia group and 97.3% (95% CI, 95.9-98.7%) in the general anesthesia group. The total cost of hospitalization in the local anesthesia group was significantly lower than that in the general anesthesia group (P <.001). The difference in the cost between the two groups remained significant, irrespective of the type of hospitalization, after excluding 165 patients receiving chemotherapy during their hospitalization. CONCLUSIONS: Our analysis indicated no association between the type of anesthesia used during breast-conserving surgery and the long-term prognosis of breast cancer. However, breast-conserving surgery under local anesthesia may be a less expensive option than that under general anesthesia.

Comparison of the Efficacy Among Transcatheter Arterial Chemoembolization (TACE)-Radiofrequency Ablation Plus Apatinib, TACE Plus Apatinib, and TACE Alone for Hepatocellular Carcinoma: A Retrospective Study.

BACKGROUND: This study aimed to investigate the efficacy and safety of apatinib plus transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) in the therapy of hepatocellular carcinoma (HCC) patients. METHODS: From December 2015 to June 2018, 175 eligible participants were included in our research. Twenty-four patients who received apatinib plus TACE and RFA were categorized as the TACE + RFA-A group, 82 patients who received apatinib plus TACE were categorized as the TACE-A group, and 69 patients who received TACE alone were categorized as the TACE group. Treatment complications, treatment response, overall survival (OS), and time to progression (TTP) were recorded. Survival analyses were compared. Univariate and multivariate Cox analyses were conducted to investigate the predictive factors for OS and TTP. A subgroup analysis was carried out. RESULTS: The median TTP was 8.0 months (95% CI 6.7-9.3) in the TACE + RFA-A, which was longer than the TACE-A group (6.0 months, 95% CI 4.8-7.2) and TACE group (3.0 months, 95% CI 2.3-3.7); the difference was statistically significant (P < 0.001). The median OS was 23.0 months (95% CI 12.6-33.4) in the TACE + RFA-A group, 18.0 months (95% CI 16.2-19.8) in the TACE-A group, and 8.0 months (95% CI 5.3-10.7) in the TACE group; the difference was statistically significant (P < 0.001). The objective response rate (ORR) was higher in TACE + RFA-A t group (M1, 70.8% vs 65.9% vs. 46.4%, P = 0.023; M3, 58.3% vs. 53.7% vs. 26.1%, P = 0.001). Multivariate Cox analysis demonstrated that treatment strategy and tumor size were independent prognostic factors for the OS and TTP, whereas the Child-Pugh stage was predictive factor of OS. No treatment-related death was observed. The toxicity was comparable between the two groups. CONCLUSION: TACE combined with RFA plus apatinib is a safe three-modality treatment for the intermediate or advanced HCC, and it demonstrated better efficacy than TACE plus apatinib or TACE alone.

Tumor feeding artery contraction and metastasis inhibition after transarterial chemoembolization combined with apatinib for hepatocellular carcinoma: A propensity score matching study.

AIM: To investigate the change of tumor feeding artery diameter and the efficacy of metastasis inhibition after transarterial chemoembolization (TACE) combined with apatinib or TACE monotherapy for patients with advanced hepatocellular carcinoma who without metastasis. MATERIALS AND METHODS: A total of 616 consecutive patients who received the treatment of TACE-apatinib or TACE in our center was enrolled. Propensity score matching (PSM) analysis was used to reduce bias. The overall survival (OS), OS-after-metastasis (OSM), time to progression (TTP), time to metastasis (TTM), time to vessel or organ metastasis (TVOM), time to lymph node metastasis, and tumor feeding artery diameter between the two treatment groups were compared. RESULTS: A total of 113 pairs of patients were eligible after the PSM. Time to lymph node metastasis between the two groups was not significantly different (P > 0.05). The tumor feeding artery diameter was significantly smaller after TACE-apatinib management (P < 0.001). Median OS (P < 0.001) and OSM (P < 0.001) were significantly longer in the TACE-apatinib group compared with the TACE group. Median TTP (P < 0.001), TTM (P < 0.001), and TVOM (P < 0.001) were significantly prolonged in TACE-apatinib group. CONCLUSION: TACE-apatinib treatment could improve the prognosis compared with TACE alone, and inhibit metastasis after TACE procedure with contracted tumor feeding artery for advanced HCCs without metastasis.

Transcriptome analysis of host response to porcine epidemic diarrhea virus nsp15 in IPEC-J2 cells.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an enveloped positive-sense ssRNA virus which is highly lethal to piglets, causing enormous economic losses to swine industry worldwide. Nsp15 protein is an endoribonuclease of PEDV and plays an indispensable role in the viral proliferation. We reported the transcription files of nsp15 transfected IPEC-J2 cells for the first time to broaden our understanding of PEDV pathogenesis. METHODS: RNA-seq was performed to compare gene expression profiles between pCAGGS-HA-nsp15 transfected IPEC-J2 cells and pCAGGS-HA (empty vector) transfected IPEC-J2 cells. Immune-related genes and pathways were identified and analyzed to deepen our understanding of nsp15 for PEDV pathogenicity. IPEC-J2 cells transfected with pCAGGS-HA-CCL5/CXCL8/CXCL10 were infected with CV777 and the virus load of PEDV was detected by qRT-PCR. RESULTS: A total of 21,654 genes were obtained by RNA-Seq and 415 differential expressed genes (DEGs) were identified, including 136 up-regulated and 279 down-regulated genes. A number of effect genes involved in immune responses and inflammation were differentially expressed. GO and KEGG enrichment analysis showed that 32 GO terms were significantly enriched and the DEGs were mainly enriched in immune-related pathways such as TNF signaling pathway, RIG-I-like receptor signaling pathway and Cytosolic DNA-sensing pathway. qRT-PCR results indicated the overexpression of selected chemokines, CCL5/CXCL8/CXCL10, can inhibit PEDV proliferation in IPEC-J2 cells. CONCLUSIONS: Our transcriptome profile illustrated a number of genes involving in immune responses and inflammation were inhibited by nsp15, such as CCL5, CXCL8, CXCL10, OAS, MXs, STAT1 and IRF9. The results suggested that nsp15 can antagonize IFNs and block chemokine system to provide an adequate intracellular environment for viral proliferation.

Drug-Eluting Bead Transarterial Chemoembolization versus Conventional Transarterial Chemoembolization Both Combined Apatinib for Hepatocellular Carcinoma: A Retrospective, Propensity-Score Matched Study.

PURPOSE: This study aims to compare the efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus conventional TACE (cTACE), both combined with apatinib, and to establish predictive nomograms to support individualized survival prediction in hepatocellular carcinoma (HCC) patients. PATIENTS AND METHODS: This retrospective study assessed HCC patients from June 2015 to December 2019. Patients were classified as DEB-TACE plus apatinib (D-apatinib) and cTACE plus apatinib (c-apatinib). The endpoints were overall survival (OS) and progression-free survival (PFS). The nomograms were constructed, and the C-index, receiver operating characteristic (ROC) curve, and calibration curves were used to validate the nomograms. Propensity score matching (PSM) analysis was applied to reduce patient selection bias. RESULTS: A total of 174 patients were included. After PSM analysis, 58 pairs of patients were selected. Before PSM analysis, the median OS and PFS were 21.0 and 8.0 months in the D-apatinib group, respectively, which were better than the 18.0 and 5.0 months observed in the c-apatinib group (P < 0.05). The complete response (CR) rate and objective response rate (ORR) of the D-apatinib group were higher than those of the c-apatinib group. The C-index values of the nomograms in the D-apatinib group and the c-apatinib group were 0.826 and 0.802, and the area under the curve (AUC) values in the ROC curve were 0.934 and 0.892. After PSM analysis, the survival of patients treated with D-apatinib was better than that of patients treated with c-apatinib (P < 0.05). The C-index values were 0.854 and 0.794 in the D-apatinib group and the c-apatinib group, respectively, and the AUC values were 0.960 and 0.890. The incidence of adverse events was higher in the c-apatinib group. CONCLUSION: DEB-TACE in combination with apatinib showed better treatment effectiveness for unresectable HCC. The nomograms can identify HCC patients who may benefit most from the treatment.

Prognostic Value of Plasma Epstein-Barr Virus DNA Levels Pre- and Post-Neoadjuvant Chemotherapy in Patients With Nasopharyngeal Carcinoma.

BACKGROUND: In this study, we evaluated the prognostic value of the plasma levels of Epstein-Barr virus (EBV) DNA in patients with nasopharyngeal carcinoma (NPC) at different treatment stages. METHODS: We retrospectively analyzed the Data of 206 patients with NPC. Pre-neoadjuvant chemotherapy (pre-NACT), post-NACT, post-radiotherapy, and post-treatment plasma EBV DNA levels were used to establish prognostic nomograms. The concordance index (C-index) and calibration curves were used to compare the prognostic accuracy of the nomograms. The results were confirmed in a validation cohort consisting of patients who were tested for EBV DNA levels at all four stages of treatment. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Survival differences were calculated using the log-rank test. RESULTS: EBV DNA-positive patients had worse 3-year PFS and 5-year OS than EBV DNA-negative patients; this was true for pre-NACT (PFS: 82.7% vs. 57.3%, P < 0.001; OS: 90.9% vs. 68.7%, P = 0.08) and post-NACT (PFS: 85.0% vs. 50.6%, P < 0.001; OS: 91.7% vs. 65.7%; P = 0.001) EBV DNA levels but not for post-radiotherapy (PFS: 72.2% vs. 60.9%, P = 0.192; OS: 73.1% vs. 77.2%, P = 0.472) or post-treatment (PFS: 77.3% vs. 59.2%, P = 0.063; OS: 77.5% vs. 79.7%, P = 0.644) levels. Nomograms combining pre-NACT and post-NACT EBV DNA levels had a superior prognostic ability than those of post-radiotherapy and post-treatment EBV DNA levels. CONCLUSION: Pre-NACT EBV DNA levels combined with post-NACT EBV DNA levels can more reliably predict survival outcomes in patients with NPC.

Sorafenib Versus Apatinib Both Combined Transarterial Chemoembolization for Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis: A Comparative Retrospective Study.

OBJECTIVE: To compare the efficacy and safety of transarterial chemoembolization (TACE) combining with sorafenib or apatinib for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). METHODS: From June 2015 to March 2020, a total of 89 consecutive advanced HCC patients with PVTT who were treated with sorafenib-TACE (S-TACE) or apatinib-TACE (A-TACE) in our center were enrolled. The overall survival (OS), time to progression (TTP), tumor response, and adverse events in the two groups were compared. RESULTS: There were 32 and 41 patients included in the S-TACE group and A-TACE group, respectively. The median follow-up was 10.0 months (range, 3.0-36.0 months) in the whole study. The median OS (11.0 vs. 10.0 months, P = 0.419), median TTP (5.0 vs. 6.0 months, P = 0.073), and tumor response (P = 0.529) between the S-TACE group and the A-TACE group were not significantly different. The adverse events related to sorafenib or apatinib were tolerable. CONCLUSION: S-TACE and A-TACE exhibited comparable prognosis for HCC patients with PVTT, which provide another effective and safe method of A-TACE for these patients except for conventional S-TACE.