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Guang-Zhi Wang,1,2 Ling-Fei Guo,3 Gui-Hua Gao,3 Yao Li,4 Xi-Zhen Wang,2 Zhen-Guo Yuan1,3 1Cheeloo College of Medicine, Shandong University, Jinan 250021, People’s Republic of China; 2Department of Medical Imaging Center, Affiliated Hospital, Weifang Medical University, Weifang 261053, People’s Republic of China; 3Department of MRI, Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University, Jinan 250021, People’s Republic of China; 4Zhucheng People’s Hospital Affiliated to Weifang Medical University, Weifang 262200, People’s Republic of ChinaCorrespondence: Zhen-Guo YuanShandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University, No. 324, Jing-wu road, Huaiyin District, Jinan 250021, People’s Republic of ChinaEmail yuanzg88@126.comPurpose: To investigate the diagnostic efficacy of diffusion kurtosis imaging (DKI) and conventional diffusion-weighted imaging (DWI) for pathological grading.Methods: From December 2015 to January 2017, consecutive patients suspected of having hepatocellular carcinoma (HCC) without prior treatment were prospectively enrolled in this study. MRI examinations were performed before surgical treatment. HCC patients confirmed by surgical pathology were included in the study. The mean diffusivity (MD) values, mean kurtosis (MK) values, and apparent diffusion coefficient (ADC) were calculated. The differences and correlations of these parameters among different pathological grades were analyzed. The diagnostic efficiency of DKI and DWI for predicting high-grade HCC was evaluated by receiver operating characteristic (ROC) curves. Logistic regression analyses were used to evaluate the predictive factors for pathological grade.Results: A total of 128 patients (79 males and 49 females, age: 56.9± 10.9 years, range, 32– 80) with primary HCC were included: grade I: 22 (17.2%) patients, grade II: 37 (28.9%) patients, grade III: 43 (33.6%) patients, grade IV: 26 (20.3%) patients. The MK values of stage I, II, III, and IV were 0.86± 0.13, 1.06± 0.11, 1.27± 0.17, and 1.57± 0.13, respectively. The MK values were significantly higher in the high-grade group than in the low-grade group and were positively correlated with pathological grade (rho =0.7417, P< 0.001). The MK value demonstrated a larger area under the curve (AUC), with a value of 0.93 than the MD value, which had an AUC of 0.815 (P< 0.001), and ADC, which had an AUC of 0.662 (P=0.01). The MK value (> 1.19), ADC (≤ 1.29× 10– 3 mm2/s), and HBV (+) were independent predictors for the pathological grade of HCCs.Conclusion: The MK values derived from DKI and the ADC values obtained from traditional DWI were more valuable than the MD values in predicting the histological grade of HCCs and could potentially guide clinical treatment before surgery.Keywords: hepatocellular carcinoma, pathology, diffusion kurtosis imaging, diffusion-weighted imaging, predictor

Toxoplasma gondii ( T. gondii ), an obligate intracellular protozoan parasite, is increasingly recognized for its role in various human diseases, including periodontal diseases. Periodontal diseases comprise a wide range of inflammatory conditions that not only affect the supporting structures of the teeth and oral health but also contribute to systemic diseases. The parasite's ability to modulate the host's immune response and induce chronic inflammation within the periodontium is a key factor in periodontal tissue damage. Through its virulence factors, T. gondii disrupts the balance of inflammatory cytokines, leading to dysregulated immune responses, and exacerbates oxidative stress in periodontal tissues. And T. gondii invasion could affect specific proteins in host cells including HSP70, BAGs, MICs, ROPs, SAGs, and GRAs leading to periodontal tissue damage. The indirect role of the host immune response to T. gondii via natural killer cells, monocytes, macrophages, neutrophils, dendritic cells, T cells, and B cells also contributes to periodontal diseases. Understanding these complex interactions of T. gondii with host cells could unravel disease mechanisms and therapeutic targets for periodontal diseases. This review delves into the pathogenic mechanisms of T. gondii in periodontal diseases, offering a detailed exploration of both direct and indirect pathways of its impact on periodontal health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Lin, Yuan, Yang, Nie, Pathak, Yuan and Yu.)

Purpose: To investigate the application value of support vector machine (SVM) model based on diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) and amide proton transfer- weighted (APTW) imaging in predicting isocitrate dehydrogenase 1(IDH-1) mutation and Ki-67 expression in glioma., Methods: The DWI, DCE and APTW images of 309 patients with glioma confirmed by pathology were retrospectively analyzed and divided into the IDH-1 group (IDH-1(+) group and IDH-1(-) group) and Ki-67 group (low expression group (Ki-67 ≤ 10%) and high expression group (Ki-67 > 10%)). All cases were divided into the training set, and validation set according to the ratio of 7:3. The training set was used to select features and establish machine learning models. The SVM model was established with the data after feature selection. Four single sequence models and one combined model were established in IDH-1 group and Ki-67 group. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the model. Validation set data was used for further validation., Results: Both in the IDH-1 group and Ki-67 group, the combined model had better predictive efficiency than single sequence model, although the single sequence model had a better predictive efficiency. In the Ki-67 group, the combined model was built from six selected radiomics features, and the AUC were 0.965 and 0.931 in the training and validation sets, respectively. In the IDH-1 group, the combined model was built from four selected radiomics features, and the AUC were 0.997 and 0.967 in the training and validation sets, respectively., Conclusion: The radiomics model established by DWI, DCE and APTW images could be used to detect IDH-1 mutation and Ki-67 expression in glioma patients before surgery. The prediction performance of the radiomics model based on the combination sequence was better than that of the single sequence model., (© 2024. The Author(s).)

Background: Cardamine violifolia is a significant Brassicaceae plant known for its high selenium (Se) accumulation capacity, serving as an essential source of Se for both humans and animals. WRKY transcription factors play crucial roles in plant responses to various biotic and abiotic stresses, including cadmium stress, iron deficiency, and Se tolerance. However, the molecular mechanism of CvWRKY in Se accumulation is not completely clear., Results: In this study, 120 WRKYs with conserved domains were identified from C. violifolia and classified into three groups based on phylogenetic relationships, with Group II further subdivided into five subgroups. Gene structure analysis revealed WRKY variations and mutations within the CvWRKYs. Segmental duplication events were identified as the primary driving force behind the expansion of the CvWRKY family, with numerous stress-responsive cis-acting elements found in the promoters of CvWRKYs. Transcriptome analysis of plants treated with exogenous Se and determination of Se levels revealed a strong positive correlation between the expression levels of CvWRKY034 and the Se content. Moreover, CvWRKY021 and CvWRKY099 exhibited high homology with AtWRKY47, a gene involved in regulating Se accumulation in Arabidopsis thaliana. The WRKY domains of CvWRKY021 and AtWRKY47 were highly conserved, and transcriptome data analysis revealed that CvWRKY021 responded to Na 2 SeO 4 induction, showing a positive correlation with the concentration of Na 2 SeO 4 treatment. Under the induction of Na 2 SeO 3 , CvWRKY021 and CvWRKY034 were significantly upregulated in the roots but downregulated in the shoots, and the Se content in the roots increased significantly and was mainly concentrated in the roots. CvWRKY021 and CvWRKY034 may be involved in the accumulation of Se in roots., Conclusions: The results of this study elucidate the evolution of CvWRKYs in the C. violifolia genome and provide valuable resources for further understanding the functional characteristics of WRKYs related to Se hyperaccumulation in C. violifolia., (© 2024. The Author(s).)

Toxoplasma gondii is a successful parasite capable of infecting a wide range of warm-blooded animals, including people, livestock, and wildlife. In individuals with intact immune function, T. gondii can invade the host brain tissue by altering the blood-brain barrier permeability, leading to chronic infection. Proteins play crucial regulatory roles in disease progression. By monitoring changes in proteins, a deeper understanding of the molecular mechanisms underlying host resistance to infection and the potential pathogenic mechanisms of pathogens can be gained. This study analyzed differential protein expression and associated signaling pathways in mouse brain tissues during acute and chronic T. gondii infection using proteomic and bioinformatics methods. The results showed that during acute and chronic T. gondii infection stages, 74 and 498 differentially expressed proteins (DEPs) were identified in mouse brain tissue, respectively. Among them, 45 and 309 were up-regulated, while 29 and 189 were down-regulated. GO and KEGG analyses revealed that some of these DEPs were implicated in host immunity, pathogen immune evasion, and T. gondii invasion of the central nervous system, particularly interleukin production and secretion, complement system activation, and alterations in tight junction pathways. Notably, the upregulation of Rab13 was identified as a potential molecular mechanism for T. gondii to regulate blood-brain barrier permeability and facilitate central nervous system invasion. Our findings provided fundamental data for understanding host control of Toxoplasmosis infection and offered new insights into parasite immune evasion and invasion mechanisms within the central nervous system. These insights are crucial for developing strategies to prevent the establishment of chronic T. gondii infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is a common type of poorly prognosticated malignant tumor. Surgical resection is the preferred treatment method for early-stage HCC. However, at the time of the initial diagnosis, fewer than 30% of patients with liver cancer are suitable for radical therapy. Systemic therapy plays an important role in the treatment process of patients with intermediate- to advanced-stage HCC, as it can effectively extend patients' survival time. With an emphasis on the status and role of systemic therapy for comprehensive management of HCC, this article summarizes the latest progress at home and abroad in the past five years, including first-line combined immunotherapy for advanced-stage HCC, second-line therapy selection, perioperative systemic therapy application, and combined therapy of systemic and local. Currently, the treatment model combined with local therapy has already become a new research hotspot in the treatment of advanced-stage HCC. Nevertheless, in the future, individualized and precise systemic therapeutic strategies will need further exploration.

Background: Toxoplasma gondii is an intracellular protozoan parasite that is widely distributed in humans and warm-blooded animals. T. gondii chronic infections can cause toxoplasmic encephalopathy, adverse pregnancy, and male reproductive disorders. In male reproduction, the main function of the testis is to provide a stable place for spermatogenesis and immunological protection. The disorders affecting testis tissue encompass abnormalities in the germ cell cycle, spermatogenic retardation, or complete cessation of sperm development. However, the mechanisms of interaction between T. gondii and the reproductive system is unclear. The aims were to study the expression levels of genes related to spermatogenesis, following T. gondii infection, in mouse testicular tissue., Methods: RNA-seq sequencing was carried out on mouse testicular tissues from mice infected or uninfected with the T. gondii type II Prugniaud (PRU) strain and validated in combination with real-time quantitative PCR and immunofluorescence assays., Results: The results showed that there were 250 significant differentially expressed genes (DEGs) (P < 0.05, |log 2 fold change| ≧ 1). Bioinformatics analysis showed that 101 DEGs were annotated to the 1696 gene ontology (GO) term. While there was a higher number of DEGs in the biological process classification as a whole, the GO enrichment revealed a significant presence of DEGs in the cellular component classification. The Arhgap18 and Syne1 genes undergo regulatory changes following T. gondii infection, and both were involved in shaping the cytoskeleton of the blood-testis barrier (BTB). The number of DEGs enriched in the MAPK signaling pathway, the ERK1/2 signaling pathway, and the JNK signaling pathway were significant. The PTGDS gene is located in the Arachidonic acid metabolism pathway, which plays an important role in the formation and maintenance of BTB in the testis. The expression of PTGDS is downregulated subsequent to T. gondii infection, potentially exerting deleterious effects on the integrity of the BTB and the spermatogenic microenvironment within the testes., Conclusions: Overall, our research provides in-depth insights into how chronic T. gondii infection might affect testicular tissue and potentially impact male fertility. These findings offer a new perspective on the impact of T. gondii infection on the male reproductive system., (© 2024. The Author(s).)

Background: The interplay between Toxoplasma gondii infection and tumor development is intriguing and not yet fully understood. Some studies showed that T. gondii reversed tumor immune suppression, while some reported the opposite, stating that T. gondii infection promoted tumor growth., Methods: We created three mouse models to investigate the interplay between T. gondii and tumor. Model I aimed to study the effect of tumor growth on T. gondii infection by measuring cyst number and size. Models II and III were used to investigate the effect of different stages of T. gondii infection on tumor development via flow cytometry and bioluminescent imaging. Mouse strains (Kunming, BALB/c, and C57BL/6J) with varying susceptibilities to tumors were used in the study., Results: The size and number of brain cysts in the tumor-infected group were significantly higher, indicating that tumor presence promotes T. gondii growth in the brain. Acute T. gondii infection, before or after tumor cell introduction, decreased tumor growth manifested by reduced bioluminescent signal and tumor size and weight. In the tumor microenvironment, CD4 + and CD8 + T cell number, including their subpopulations (cytotoxic CD8 + T cells and Th1 cells) had a time-dependent increase in the group with acute T. gondii infection compared with the group without infection. However, in the peripheral blood, the increase of T cells, including cytotoxic CD8 + T cells and Th1 cells, persisted 25 days after Lewis lung carcinoma (LLC) cell injection in the group with acute T. gondii. Chronic T. gondii infection enhanced tumor growth as reflected by increase in tumor size and weight. The LLC group with chronic T. gondii infection exhibited decreased percentages of cytotoxic CD8 + T cells and Th1 cells 25 days post-LLC injection as compared with the LLC group without T. gondii infection. At week 4 post-LLC injection, chronic T. gondii infection increased tumor formation rate [odds ratio (OR) 1.71] in both KM and BALB/c mice., Conclusions: Our research elucidates the dynamics between T. gondii infection and tumorigenesis. Tumor-induced immune suppression promoted T. gondii replication in the brain. Acute and chronic T. gondii infection had opposing effects on tumor development., (© 2024. The Author(s).)

Introduction: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients., Methods: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m 2  on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1., Results: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0., Conclusions: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC., Highlights: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors., Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL., Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy., Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Pan, Ye, Zhu, Xue, Li, Yuan, Zhang, Xu, Chen, Wang, Sun, Liu and China Liver Cancer Study Group Young Investigators (CLEAP).)

Background: Toxoplasma gondii ( T. gondii ) is a significant protozoan pathogen among food animals. Despite the threat to public health by T. gondii infections, there's limited understanding of its seroprevalence and trends in food animals across mainland China. This study aimed to estimate the seroprevalence of T. gondii infections among swine, sheep, goats, chickens, and cattle in mainland China from 2010 to 2023., Methods: We searched cross-sectional studies published between 2010 and 2023 that reported the prevalence of T. gondii in food animals from databases including PubMed, Embase, Web of Science, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang data, and the China Science and Technology Journal Database (CQVIP). We performed subgroup analyses to explore the impact of different factors on the seroprevalence of T. gondii . Pooled estimates of T. gondii seroprevalence were calculated with a random-effects model., Results: An analysis of 184 studies involving 211985 animals revealed a T. gondii overall seroprevalence of 15.3% (95% CI: 13.1-17.8). Although the seroprevalence of food animals across mainland China was relatively stable from 2010 to 2023, notable variations were observed across different animal types and regions ( P < 0.01), along with changes in geographical distribution. Sample type, detection method, animal age, and history of abortion were identified as key risk factors for T. gondii seroprevalence., Conclusion: The study conducted a meta-analysis on the seroprevalence of T. gondii in mainland China's Food Animals from 2010 to 2023, and identified key risk factors. These findings advance our understanding of T. gondii infection dynamics, offering critical insights for developing control strategies and guiding public health policies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Yuan, Nie, Wen, Li, Yang, Song, Luo, Zhang and Yuan.)

Background: Despite EIF5A upregulation related to tumor progression in LUAD (lung adenocarcinoma), the underlying mechanisms remain elusive. In addition, there are few comprehensive analyses of EIF5A in LUAD., Methods: We investigated the EIF5A expression level in LUAD patients using data from the TCGA and GEO databases. We employed qRT-PCR and western blot to verify EIF5A expression in cell lines, while immunohistochemistry was utilized for clinical sample analysis. We analyzed EIF5A expression in tumor-infiltrating immune cells using the TISCH database and assessed its association with immune infiltration in LUAD using the "ESTIMATE" R package. Bioinformatics approaches were developed to discover the EIF5A-related genes and explore EIF5A potential mechanisms in LUAD. Proliferation ability was verified through CCK-8, clone formation, and EdU assays, while flow cytometry assessed apoptosis and cell cycle. Western blot was used to detect the expression of pathway-related proteins., Results: EIF5A was significantly upregulated in LUAD. Moreover, we constructed a MAZ-hsa-miR-424-3p-EIF5A transcriptional network. We explored the potential mechanism of EIF5A in LUAD and further investigated the cAMP signaling pathway and the cell cycle. Finally, we proved that EIF5A silencing induced G1/S Cell Cycle arrest, promoted apoptosis, and inhibited proliferation via the cAMP/PKA/CREB signaling pathway., Conclusion: EIF5A serves as a prognostic biomarker with a negative correlation to immune infiltrates in LUAD. It regulated the cell cycle in LUAD by inhibiting the cAMP/PKA/CREB signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5 th edition of the World Health Organization Classification of Tumours of the Digestive System., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Introduction: Pseudorabies (PR) is a highly contagious viral disease caused by the pseudorabies virus (PRV), which can cause disease in a wide range of domestic and wild animals. Studies have shown that new mutant strains have emerged in pig farms in many regions and that commercial inactivated and live attenuated vaccines are becoming less effective at protecting pigs., Methods: Porcine pseudorabies glycoprotein D (gD) gene (GenBank: QEY95774.1) with hexa-His tag to the C terminus for further purification processes was cloned into the lentiviral expression plasmid pLV-CMV-eGFP by restriction enzyme, the resulting plasmid was designated as pLV-CMV-gD. HEK-293T cells with robust and stable expression of recombinant gD protein was established by infection with recombinant lentivirus vector pLV-CMV-gD. We expressed porcine pseudorabies virus gD protein using HEK-293T cells., Results: We describe in this study that individual gD proteins produced by a mammalian cell expression system are well immunogenic and stimulate high levels of PRV-specific and neutralizing antibodies in mice and piglets. All mice and piglets survived lethal doses of PRV, significantly reducing the amount of PRV virus in piglets' lymph nodes, lungs, spleen, and other tissues. It also significantly reduced the time cycle and amount of viral excretion from piglets to the environment through the nasal and anal cavities., Discussion: The results suggest that PRV gD protein is expected to be a potential candidate for the preparation of genetically engineered PR vaccines for the prevention of PRV infection and the control of PR epidemics., Competing Interests: HL and RY was employed by Guangzhou Bioneeds Biotechnology Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Chen, Luo, Yan, Zhang, Ren, Chen, Wang, Xiang, Cai, Huang, Li, Li, Yuan and Wang.)

Introduction: The masked palm civet ( Paguma larvata ) serves as a reservoir in transmitting pathogens, such as Toxoplasma gondii , to humans. However, the pathogenesis of T. gondii infection in masked palm civets has not been explored. We studied the molecular changes in the brain tissue of masked palm civets chronically infected with T. gondii ME49., Methods: The differentially expressed proteins in the brain tissue were investigated using iTRAQ and bioinformatics., Results: A total of 268 differential proteins were identified, of which 111 were upregulated and 157 were downregulated. KEGG analysis identified pathways including PI3K-Akt signaling pathway, proteoglycans in cancer, carbon metabolism, T-cell receptor signaling pathway. Combing transcriptomic and proteomics data, we identified 24 genes that were differentially expressed on both mRNA and protein levels. The top four upregulated proteins were REEP3, REEP4, TEP1, and EEPD1, which was confirmed by western blot and immunohistochemistry. KEGG analysis of these 24 genes identified signaling cascades that were associated with small cell lung cancer, breast cancer, Toll-like receptor signaling pathway, Wnt signaling pathways among others. To understand the mechanism of the observed alteration, we conducted immune infiltration analysis using TIMER databases which identified immune cells that are associated with the upregulation of these proteins. Protein network analysis identified 44 proteins that were in close relation to all four proteins. These proteins were significantly enriched in immunoregulation and cancer pathways including PI3K-Akt signaling pathway, Notch signaling pathway, chemokine signaling pathway, cell cycle, breast cancer, and prostate cancer. Bioinformatics utilizing two cancer databases (TCGA and GEPIA) revealed that the four genes were upregulated in many cancer types including glioblastoma (GBM). In addition, higher expression of REEP3 and EEPD1 was associated with better prognosis, while higher expression of REEP4 and TEP1 was associated with poor prognosis in GBM patients., Discussion: We identified the differentially expressed genes in the brain of T. gondii infected masked palm civets. These genes were associated with various cellular signaling pathways including those that are immune- and cancer-related., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuan, Jiang, Zhang, Yang, Luo, Wang, Zhu, Qi, Mahmmod, Zhang and Yuan.)

Gemcitabine is a nucleoside analog that has been successfully used in the treatment of multiple cancers. However, intrinsic or acquired resistance reduces the chemotherapeutic potential of gemcitabine. Here, we revealed a previously unappreciated mechanism by which phosphatase and tensin homolog (PTEN), one of the most frequently mutated genes in human cancers, dominates the decision-making process that is central to the regulation of gemcitabine efficacy in cholangiocarcinoma (CCA). By investigating a gemcitabine-treated CCA cohort, we found that PTEN deficiency was correlated with the improved efficacy of gemcitabine-based chemotherapy. Using cell-based drug sensitivity assays, cell line-derived xenograft, and patient-derived xenograft models, we further confirmed that PTEN deficiency or genetic-engineering down-regulation of PTEN facilitated gemcitabine efficacy both in vitro and in vivo. Mechanistically, PTEN directly binds to and dephosphorylates the C terminus of the catalytic subunit of protein phosphatase 2A (PP2Ac) to increase its enzymatic activity, which further dephosphorylates deoxycytidine kinase (DCK) at Ser 74 to diminish gemcitabine efficacy. Therefore, PTEN deficiency and high phosphorylation of DCK predict a better response to gemcitabine-based chemotherapy in CCA. We speculate that the combination of PP2A inhibitor and gemcitabine in PTEN-positive tumors could avoid the resistance of gemcitabine, which would benefit a large population of patients with cancer receiving gemcitabine or other nucleoside analogs.

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification., (© 2023. The Author(s).)

Background: The current meta-analysis was conducted to determine whether antithrombotic drug use would affect the diagnostic accuracy of fecal occult blood testing for advanced colorectal neoplasia., Methods: Articles published between 2000 and 2019 were systematically retrieved and screened according to the inclusion and exclusion criteria by two reviewers independently. Pooled analyses were conducted with a fixed-effect model if no apparent heterogeneity (I 2 ≥ 50%) was found between studies; otherwise, the random effects model would be used. Sensitivity analysis and subgroup analysis were also conducted using Review Manager 5.3., Results: Pooled analysis revealed that aspirin and nonsteroidal anti-inflammatory drugs were associated with a decrease in the positive predictive value of fecal occult blood testing for advanced colorectal neoplasia screening, with a RR of 0.89 (95% CI: 0.84-0.94) and 0.88 (95% CI: 0.84-0.93, p<0.001) respectively. Subgroup analysis based on data limited to high-quality studies, fecal immunochemical testing, or in Caucasians also showed that the use of aspirin/NSAID drugs decreased the accuracy for advanced colorectal neoplasia screening., Conclusion: Aspirin/NSAIDs and direct oral anticoagulants rather than warfarin may decrease the diagnostic accuracy of fecal occult blood testing for advanced colorectal neoplasia screening., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Toxoplasma gondii (T.gondii) is a widespread protozoan with significant economic losses and public health importance. But so far, the protective effect of reported DNA-based vaccines fluctuates widely, and no study has demonstrated complete protection., Areas Covered: This review provides an inclusive summary of T. gondii DNA vaccine antigens, adjuvants, and some other parameters. A total of 140 articles from 2000 to 2021 were collected from five databases. By contrasting the outcomes of acute and chronic challenges, we aimed to investigate and identify viable immunological strategies for optimum protection. Furthermore, we evaluated and discussed the impact of several parameters on challenge outcomes in the hopes of developing some recommendations to assist better future horizontal comparisons among research., Expert Opinion: In the coming five years of research, the exploration of vaccine cocktails combining invasion antigens and metabolic antigens with genetic adjuvants or novel DNA delivery methods may offer us desirable protection against this multiple stage of life parasite. In addition to finding a better immune strategy, developing better in silico prediction methods, solving problems posed by variables in practical applications, and gaining a more profound knowledge of T.gondii -host molecular interaction is also crucial towards a successful vaccine.

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Biliary tract cancers (BTCs) comprise a heterogeneous group of aggressive malignancies with unfavorable prognoses. The benefit of chemotherapy seems to have reached a bottleneck and, therefore, new effective therapeutic strategies for advanced BTCs are needed. Molecularly targeted therapies in selected patients are rapidly changing the situation. However, the low frequency of specific driver alterations in BTCs limits their wide application. Recently, immunotherapeutic approaches are also under active investigation in BTCs, but the role of immunotherapy in BTCs remains controversial., Data Sources: PubMed, Web of Science, and meeting resources were searched for relevant articles published from January 2017 to May 2022. The search aimed to identify current and emerging immunotherapeutic approaches for BTCs. Information on clinical trials was obtained from https://clinicaltrials.gov/ and http://www.chictr.org.cn/., Results: Immunotherapy in BTC patients is currently under investigation, and most of the investigations focused on the application of immune checkpoint inhibitors (ICIs). However, only a subgroup of BTCs with microsatellite-instability high (MSI-H)/DNA mismatch repair-deficient (dMMR) or tumor mutational burden-high (TMB-H) benefit from monotherapy of ICIs, and limited activity was observed in the second or subsequent settings. Nevertheless, promising results come from studies of ICIs in combination with other therapeutic approaches, including chemotherapy, in advanced BTCs, with a moderate toxicity profile. Recent studies demonstrated that compared to GEMCIS alone, durvalumab plus GEMCIS significantly improved patient survival (TOPAZ-1 trial) and that ICIs-combined chemoimmunotherapy is poised to become a new frontline therapy option, regardless of TMB and MMR/MSI status. Adoptive cell therapy and peptide- or dendritic-based cancer vaccines are other immunotherapeutic options that are being studied in BTCs. Numerous biomarkers have been investigated to define their predictive role in response to ICIs, but no predictive biomarker has been validated, except MSI-H/dMMR., Conclusions: The role of immunotherapy in BTCs is currently under investigation and the results of ongoing studies are eagerly anticipated. Several studies have demonstrated the safety and efficacy of ICIs in combination with chemotherapy in treatment-naive patients, such as the phase III TOPAZ-1 trial, which will change the standard care of first-line chemotherapy for advanced BTCs. However, further research is needed to understand the best combination with immunotherapy and to discover more predictive biomarkers to guide clinical practice., (Copyright © 2022. Published by Elsevier B.V.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Immune checkpoint inhibitor (ICI)-combined chemotherapy in advanced intrahepatic cholangiocarcinoma has been proved to have more efficacy in a series of clinical trials. However, whether the tumor microenvironment (TME) plays a vital role in immune-combined therapy has not been rigorously evaluated., Methods: Firstly, we assayed the immunogenic properties of GEM-based chemotherapy. Then, 12 ICC patients treated with PD-1 inhibitor (sintilimab) combined with gemcitabine and cisplatin (GemCis) from a phase 2 clinical trial (ChiCTR2000036652) were included and their immune-related gene expression profiles were analyzed using RNA from baseline tumor samples. Immune-related signature correlating with clinical outcome was identified according to the 12 ICC patients, and its predictive value was validated in an ICC cohort with 26 patients. Multiplexed immunofluorescence (mIF) and flow cytometry (FCM) analysis were performed to evaluate the immune-related molecules with therapeutic outcomes., Results: GEM-based chemotherapy induced immunogenic cell death of cholangiocarcinoma cells, together with increased CD274 expression. In an ICC cohort, we found that upregulation of immune-checkpoint molecules and immune response-related pathways were significantly related to better clinical outcome. On the contrary, baseline immune-cell proportions in tumor tissues did not show any correlation with clinical benefit between responders and non-responders. Immune-related signature (including six genes) correlating with clinical outcome was identified according to the 12 ICC patients, and its predictive value was validated in a small ICC cohort with 26 patients., Conclusion: Immune-related RNA signature predicts the outcome of PD-1 inhibitor-combined GEMCIS therapy in advanced intrahepatic cholangiocarcinoma, which could be tested as a biomarker for immune-chemotherapy in the future., Competing Interests: Authors YS and DC were employed by Jiangsu Simcere Diagnostics Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zeng, Pan, Yuan, Chen, Song and Gao.)

Pangolins are endangered animals and are listed in the CITES Appendix I of the Convention International Trade Endangered Species of Wild Fauna and Flora as well as being the national first-level protected wild animal in China. Based on a few reports on pangolins infected with pestiviruses of the Flaviviridae family, Pestivirus infections in pangolins have attracted increasing attention. Pangolin pestivirus is a pathogen that may cause diseases such as acute diarrhea and acute hemorrhagic syndrome. To better understand the epidemiology and genomic characterization of pestiviruses carried by pangolins, we detected pestiviruses in dead Malayan pangolin using metavirome sequencing technology and obtained a Pestivirus sequence of 12,333 nucleotides (named Guangdong pangolin Pestivirus , GDPV). Phylogenetic tree analysis based on the entire coding sequence, NS3 gene or RdRp gene sequences, showed that GDPV was closely related to previously reported pangolin-derived Pestivirus and clustered into a separate branch. Molecular epidemiological investigation revealed that 15 Pestivirus -positive tissues from two pangolins individuals with a positivity rate of 5.56%, and six Amblyomma javanense carried pestiviruses with a positivity rate of 19.35%. Moreover, the RdRp gene of the Pestivirus carried by A. javanense showed a high similarity to that carried by pangolins (93-100%), indicating A. javanense is likely to represent the vector of Pestivirus transmission. This study expands the diversity of viruses carried by pangolins and provides an important reference value for interrupting the transmission route of the virus and protecting the health of pangolins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Li, Zhou, Hua, Zeng, Yu, Liu, Yuan and Chen.)

Background: Toxoplasma gondii , an intracellular protozoan parasite, exists in the host brain as cysts, which can result in Toxoplasmic Encephalitis (TE) and neurological diseases. However, few studies have been conducted on TE, particularly on how to prevent it. Previous proteomics studies have showed that the expression of C3 in rat brains was up-regulated after T. gondii infection., Methods: In this study, we used T. gondii to infect mice and bEnd 3 cells to confirm the relation between T. gondii and the expression of C3. BEnd3 cells membrane proteins which directly interacted with C3a were screened by pull down. Finally, animal behavior experiments were conducted to compare the differences in the inhibitory ability of TE by four chemotherapeutic compounds (SB290157, CVF, NSC23766, and Anxa1)., Results: All chemotherapeutic compounds in this study can inhibit TE and cognitive behavior in the host. However, Anxa 1 is the most suitable material to inhibit mice TE., Conclusion: T. gondii infection promotes TE by promoting host C3 production. Anxa1 was selected as the most appropriate material to prevent TE among four chemotherapeutic compounds closely related to C3.

Background: The aim of this study was to gain an understanding of the transcriptomic changes that occur in a wild species when infected with Toxoplasma gondii. The masked palm civet, an artifically domesticated animal, was used as the model of a wild species. Transcriptome analysis was used to study alterations in gene expression in the domesticated masked palm civet after chronic infection with T. gondii., Methods: Masked palm civets were infected with 10 5  T. gondii cysts and their brain tissue collected after 4 months of infection. RNA sequencing (RNA-Seq) was used to gain insight into the spectrum of genes that were differentially expressed due to infection. Quantitative reverse-transcription PCR (qRT-PCR) was also used to validate the level of expression of a set of differentially expressed genes (DEGs) obtained by sequencing., Results: DEGs were screened from the sequencing results and analyzed. A total of 2808 DEGs were detected, of which 860 were upregulated and 1948 were downregulated. RNA-Seq results were confirmed by qRT-PCR. DEGs were mainly enriched in cellular process and metabolic process based on gene ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that transcriptional changes in the brain of infected masked palm civets evolved over the course of infection and that DEGs were mainly enriched in the signal transduction, immune system processes, transport and catabolic pathways. Finally, 10 essential driving genes were identified from the immune signaling pathway., Conclusions: This study revealed novel host genes which may provide target genes for the development of new therapeutics and detection methods for T. gondii infection in wild animals., (© 2022. The Author(s).)

Synovium has widely participated in induced inflammation, suggesting that it is a potential target to reduce aromatase inhibitors (AIs) causing joint inflammation or pain. Exercise and mechanical stimulation are important strategies for precaution and treatment of bone inflammation. In this work, we developed a novel thermo-sensitive hydrogel, which could be injected intra-articularly. The aim of this research was to investigate the role of various mechanical strength hydrogels in reducing synovium inflammation. The effect of different mechanical strength hydrogels on regulating synovium inflammation was used to stimulate human fibroblast-like synoviocytes (FLS) under a cyclic mechanical compression environment in vitro . Cytokine and metalloprotease expression in FLS was analyzed by the western blot and q-PCR method, in which FLS were cultured with the different mechanical strength hydrogels. The results showed that a moderate-intensity hydrogel mechanical stimulation might be suitable in reducing AI-induced FLS inflammation via the NK-κB pathway. In addition, we built an AI-treated rat model and injected the different mechanical strength hydrogels. Similarly, the moderate-strength mechanical hydrogel could reduce the inflammatory factor and metalloproteinase expression in synovial tissues and intra-articular synovia., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: This study aimed to explore relevant factors of hemorrhagic contusions following decompressive craniotomy (DC) in traumatic brain injury (TBI) and create an artificial neural network (ANN) prediction model of the risk factors of hemorrhagic contusions., Methods: This study analyzed 425 patients with TBI who underwent DC in the Neurosurgery Department of Shaoxing People's Hospital between 2009 and 2014. Patients were divided into two groups according to the first postoperative CT scans: hemorrhage group and non-hemorrhage group. Gender, age, preoperative situations (Initial Rotterdam CT Score, GCS Score, pupillary response, laboratory data and preoperative hematoma), the time gap between trauma and DC, postoperative CT scans, and Glasgow Outcome Scale (GOS) scores were recorded. ANN was used to predict hematoma. Correlation analysis was used to state the relationship between increased hemorrhage volumes and GOS scores., Results: The ANN prediction model was established. This model included 11 parameters: initial Rotterdam CT score, GCS score, C-reactive protein, age, the time gap between trauma and DC, pupillary response, platelet count, bone-flap size, glucose level, hernia magnitude and preoperative hematoma volume. The overall predictive accuracy of the model was 73.0%., Conclusions: Initial Rotterdam CT scores and GCS scores may predict the risk of expansion contusions following DC. The ANN prediction model has a high accuracy to forecast hemorrhage.

Patient-derived xenografts (PDXs) and PDX-derived cells (PDCs) are useful in preclinical research. We performed a drug screening assay using PDCs and identified proteasome inhibitors as promising drugs for cholangiocarcinoma (CCA) treatment. Furthermore, we determined that phosphate and tensin homology deleted on chromosome ten (PTEN) deficiency promotes protein synthesis and proteasome subunit expression and proteolytic activity, creating a dependency on the proteasome for cancer cell growth and survival. Thus, targeting the proteasome machinery with the inhibitor bortezomib inhibited the proliferation and survival of CCA cells lacking functional PTEN. Therapeutic evaluation of PDXs, autochthonous mouse models, and patients confirmed this dependency on the proteasome. Mechanistically, we found that PTEN promoted the nuclear translocation of FOXO1, resulting in the increased expression of BACH1 and MAFF BACH1 and MAFF are transcriptional regulators that recognize the antioxidant response element, which is present in genes encoding proteasome subunits. PTEN induced the accumulation and nuclear translocation of these proteins, which directly repressed the transcription of genes encoding proteasome subunits. We revealed that the PTEN-proteasome axis is a potential target for therapy in PTEN-deficient CCA and other PTEN-deficient cancers., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Toxoplasma gondii ( T. gondii ) infection in female mammals during pregnancy can result in poor pregnancy. Similarly, it can result in male reproductive disorders in male mammals. Although the testes and uterus have very different biological makeup, they are still both attacked by T. gondii resulting in reproductive dysfunctions. We hypothesized that there are significant common genes in the testes and uterus that interact with T. gondii . Finding out and studying these genes is vital to understand the infection mechanism of T. gondii and the induced disease pathogenesis. To achieve this goal, we built a mice model of acute infection with T. gondii and the testes and uterus of the mice were sequenced by RNA-Seq. A total of 291 and 679 significantly differently expressed genes (DEGs) were obtained from the testes and the uterus, respectively. In the Gene Ontology (GO) analysis, part of the DEGs in the testes and uterus were related to 35 GO functions. When compared with the KEGG database, seven pathways affecting both the testes and uterus during the course of T. gondii infection were identified. In addition, Toxoplasmosis can significantly affect the expression of Nlrp5 and Insc leading to negative outcomes in the host. On the other hand, the host regulates Gbp7 , Gbp2b , and Ifit3 to defend against T. gondii infection.

Background: Toxoplasma gondii ( T. gondii ) is an obligate intracellular parasite, which can affect the pregnancy outcomes in infected females by damaging the uterus, and the intrauterine environment as well as and the hypothalamus resulting in hormonal imbalance. However, the molecular mechanisms underlying the parasite-induced poor pregnancy outcomes and the key genes regulating these mechanisms remain unclear. Therefore, this study aimed to analyze the gene expression in the mouse's uterus following experimentally-induced acute infection with T. gondii RH strain. Three groups of female mice were intraperitoneally injected with tachyzoites as follow; 3 days before pregnancy (FBD6), after pregnancy (FAD6), and after implantation (FID8) as the experimental groups. Another corresponding three groups served as control, were injected with normal saline at the same time. Transcriptome analysis of the total RNA extracted from both infected and non-infected mouse uterus samples was performed using RNA sequencing (RNA-Seq)., Results: The three experimental groups (FBD6, FAD6, and FID8) had a total of 4,561, 2,345, and 2,997 differentially expressed genes (DEGs) compared to the controls. The significantly upregulated and downregulated DEGs were 2,571 and 1,990 genes in FBD6, 1,042 and 1,303 genes in FAD6 and 1,162 and 1,835 genes in FID8 group, respectively. The analysis of GO annotation, and KEGG pathway showed that DEGs were mainly involved in anatomical structure development, transport, cell differentiation, embryo development, hormone biosynthetic process, signal transduction, immune system process, phagosome, pathways in cancer, and cytokine-cytokine receptor interaction pathways., Conclusion: T. gondii infection can induce global transcriptomic changes in the uterus that may cause pregnancy hypertension, destruct the intrauterine environment, and hinder the normal development of placenta and embryo. Our results may help to understand the molecular mechanisms of the acute T. gondii infection, which could promote the development of new therapeutics or prophylactics for toxoplasmosis in pregnancy., (Copyright © 2020 Zhou, Zhang, Mahmmod, Hernandez, Li, Huang, Wang, Zheng, Li and Yuan.)

Objective : This study aimed to evaluate the therapeutic response of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) with diffusion kurtosis imaging (DKI). Methods : Forty-three patients with fifty-nine hepatic cancer nodules were recruited for this study. All patients were treated by TACE. Magnetic resonance imaging (MRI) and DKI (b=0, 800, 1,500, 2,000mm 2 /s) were performed before and one month after initiating TACE. Patients were classified as either progressing groups or non-progressing groups. Mean kurtosis (MK), mean diffusion (MD), and apparent diffusion coefficient (ADC) values of the tumor tissue were analyzed. Results : Twenty-three HCCs were classified as progressing groups, and thirty-six HCCs were non-progressing groups. After TACE, the values of MD and ADC in non-progressing groups (1.92±0.36×10 -3 mm 2 /s, 1.36±0.23×10 -3 mm 2 /s) were greater than progressing groups (1.44±0.32× 10 -3 mm 2 /s, 1.10±0.23×10 -3 mm 2 /s), however, the MK values in non-progressing groups (0.47±0.12) were lower than progressing groups (0.72±0.14). The MK values of tumor among non-progressing patients decreased one month after TACE (0.47±0.12) relative to the preoperative values (0.71±0.12) ( P <0.05). In the non-progressing groups, the MD and ADC values of tumor after TACE (1.92±0.36×10 -3 mm 2 /s, 1.36±0.23×10 -3 mm 2 /s) became higher than their preoperative values (1.44±0.35×10 -3 mm 2 /s, 1.09±0.22×10 -3 mm 2 /s) ( P <0.05). In the progressing groups, the MK, MD, and ADC values of tumor after TACE remained similar before TACE ( P >0.05). The sensitivity, specificity, and AUC of the ROC curve for the assessment of HCC progress after TACE by MK (85.2%, 97.5%, and 0.95, respectively) were greater than by ADC (78.6%, 66.5%, and 0.75, respectively) and MD (76.2%, 64.3%, and 0.71, respectively). Conclusions : DKI for assessing the therapeutic response of TACE in HCC shows great promise. MK is more advantageous in the assessment of HCC progress after TACE., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Some researchers have reported that Toxoplasma gondii can cause serious reproductive impairment in male animals. Specifically, T. gondii destroy the quality of sperm in the epididymis, which affects their sexual ability. However, among such studies, none have investigated the male reproductive transcriptome. Therefore, to investigate the relationship between T. gondii and sperm maturation, we infected mice with T. gondii prugniaud (PRU) strain and performed transcriptome sequencing of the epididymis., Results: Compared with the control group, 431 upregulated and 229 downregulated differentially expressed genes (DEGs) were found (P-value < 0.05, false discovery rate (FDR) < 0.05 and |log2 (fold change)| ≥ 1). According to results of a bioinformatics analysis, Gene Ontology (GO) function is divided into three categories: cellular component, molecular function and biological process. Upon performing GO analysis, we found that some DEGs correlated with an integral part of membrane, protein complex, cell surface, ATP binding, immune system process, signal transduction and metabolic process which are responsible for the epididymal injury. DEGs were mapped to 101 unique KEGG pathways. Pathways such as cytokine-cytokine receptor interaction, glycolysis/gluconeogenesis and apoptosis are closely related to sperm quality. Moreover, Tnfsf10 and spata18 can damage the mitochondria in sperm, which decreases sperm motility and morphology., Conclusions: We sequenced the reproductive system of male mice chronically infected with T. gondii, which provides a new direction for research into male sterility caused by Toxoplasma infection. This work provides valuable information and a comprehensive database for future studies of the interaction between T. gondii infection and the male reproductive system.

Objective: We aimed to perform a systematic review and meta-analysis to compare the treatment effects of unstable shoes and flat shoes on lower back pain patients., Data Sources: Literature databases, including PubMed, Web of Science, and EMBASE (up to June 2019), were searched systematically., Review Methods: Two authors independently screened the retrieved records and identified the randomized controlled trials where patients with lower back pain who wore unstable shoes as intervention and wore flat shoes as a control. Relevant data were extracted for meta-analysis using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the pooled outcome evidence levels., Results: Five randomized controlled trials and 251 patients were included in the analysis. The meta-analysis results showed that there was a tendency toward a reduction in the Roland-Morris disability questionnaire score (mean difference (MD) -2.16, 95% confidence interval (CI) -4.28 to -0.03, I 2  = 53%) and pain score (MD -0.84, 95% CI -1.66 to -0.02, I 2  = 84%) in patients wearing unstable shoes compared to those wearing flat shoes. There was no significant difference in the life quality scores between the unstable shoe and flat shoe groups (MD -0.59, 95% CI -6.18 to 5.01, I 2  = 0%). Functional disability and pain scores were determined to have very low-quality evidence, and life quality scores were determined to have low-quality evidence according to the Grading of Recommendations Assessment, Development and Evaluation analysis., Conclusion: Unstable shoes may be effective in treating lower back pain in the clinic, but the conclusion was limited by the current low-quality studies.

Background: Lumbar fusion is considered to the gold standard for treatment of spinal degenerative diseases but results in adjacent segment degeneration and acquired spinal instability. Total disc replacement is a relatively new alternative avoiding the occurrence of the above complications. The systematic review and meta-analysis was designed to evaluate whether total disc replacement exhibited better outcomes and safety., Methods: PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure Database(CNKI), Wangfang database, and VIP database were searched for RCTs comparing total disc replacement with lumbar fusion. All statistical analyses were carried out using the RevMan5.3 and STATA12.0 software., Results: Of 1116 citations identified by our search strategy, 14 RCTs met the inclusion criteria. Compared to lumbar fusion, total disc replacement significantly improved ODI, VAS, SF-36, patient satisfaction, overall success, reoperation rate, ODI successful, reduced operation time, shortened duration of hospitalization, decreased postsurgical complications. However, total disc replacement did not show a significant difference regarding blood loss, consumption of analgesics, neurologic success and device success with lumbar fusion. And charges were significantly lower for total disc replacement compared with lumbar fusion in the 1-level patient group, while charges were similar in the 2-level group., Conclusion: Total disc replacement is recommended to alleviate the pain of degenerative lumbar diseases, improve the state of lumbar function and the quality of life of patients, provide a high level of security, have better health economics benefits for 1-level patients.

Objective: This study aimed to compare the diffusion kurtosis imaging (DKI) versus diffusion weighted imaging (DWI) in predicting the recurrence of early stage single nodules of hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA)., Materials and Methods: A retrospective analysis of 107 patients with early stage single nodules of HCC was performed, all patients treated by RFA. Recurrence rate of HCC was recorded after a median follow-up of 36 months. During follow-up, the data of magnetic resonance imaging (MRI), DWI and DKI were obtained in multiple time points. The predictive values of DWI and DKI were analyzed using ROC curves., Results: The overall recurrence rate was 66.3% (71/107). The sensitivity, specificity, and AUC for ADC, MD and MK after RFA (78.6, 73.3% and 0.842; 85.7, 83.3% and 0.839; 85.7, 96.7% and 0.956) were higher than before RFA (44.3, 53.3% and 0.560; 51.2, 56.7% and 0.543; 43.6, 67.3% and 0.489). The sensitivity, specificity, and AUC for MK after RFA were 85.7, 96.7%, and 0.956, respectively, which were significantly greater than those of ADC (78.6, 73.3% and 0.842; P < 0.05) and MD (85.7, 83.3% and 0.839)., Conclusions: The prediction efficacy of DKI for the recurrence of early stage single nodules of HCC was better than that of DWI. And, MK was the most sensitive predictor among the DKI.

Sprague Dawley rats and Kunming (KM) mice are artificially infected with type II Toxoplasma gondii strain Prugniaud (Pru) to generate toxoplasmosis, which is a fatal disease mediated by T. gondii invasion of the central nervous system (CNS) by unknown mechanisms. The aim is to explore the mechanism of differential susceptibility of mice and rats to T. gondii infection. Therefore, a strategy of isobaric tags for relative and absolute quantitation (iTRAQ) is established to identify differentially expressed proteins (DEPs) in the rats' and the mice's brains compared to the healthy groups. In KM mice, which is susceptible to T. gondii infection, complement component 3 (C3) is upregulated and the tight junction (TJ) pathway shows a disorder. It is presumed that T. gondii-stimulated C3 disrupts the TJ of the blood-brain barrier in the CNS. This effect allows more T. gondii passing to the brain through the intercellular space., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Rabies virus is an enveloped negative-stranded RNA virus belonging to the family Rhabdoviridae. It can be successfully controlled by vaccination however, there are still tens of thousands of deaths each year caused by rabies virus due to its mutations and complexity. A better understanding of the interaction between the rabies virus and the host might help solve this problem. Therefore, in this study, we used two-dimensional electrophoresis to investigate the protein expression of rabies virus-infected mice. This can help us to understand the impact of rabies virus on host protein expression during infection. For our experiment, two-dimensional electrophoresis was used to analyze the differential proteomics of the brain of 10- and 20-day-old suckling mice infected with attenuated rabies virus strain SRV9. The results showed that the expression levels of 10 protein spots had been up- or down-regulated at least 2-fold. Using MALDI-TOF-MS, we identified 8 differentially expressed proteins. We have identified proteins, namely hnRNP L, DPYSL3, NECAPs, and transaldolase that might be closely related to the susceptibility of SRV9 in suckling mice. Keywords: rabies virus; attenuated strain; suckling mouse; two-dimensional electrophoresis; proteomics.

The study aimed to develop simulation models including intracranial aneurysmal and parent vessel geometries, as well as vascular branches, through 3D printing technology. The simulation models focused on the benefits of aneurysmal treatments and clinical education. This prospective study included 13 consecutive patients who suffered from intracranial aneurysms confirmed by digital subtraction angiography (DSA) in the Neurosurgery Department of Shaoxing People's Hospital. The original 3D-DSA image data were extracted through the picture archiving and communication system and imported into Mimics. After reconstructing and transforming to Binary STL format, the simulation models of the hollow vascular tree were printed using 3D devices. The intracranial aneurysm 3D printing simulation model was developed based on DSA to assist neurosurgeons in aneurysmal treatments and residency training. Seven neurosurgical residents and 15 standardization training residents received their simulation model training and gave high assessments for the educational course with the follow-up qualitative questionnaire. 3D printed simulation models based on DSA can perfectly reveal target aneurysms and help neurosurgeons select therapeutic strategies precisely. As an educational tool, the 3D aneurysm vascular simulation model is useful for training residents.

We constructed a new plasmid pIRESneo/ROP18/PLP1 that was injected intramuscularly into Kunming mice to evaluate its immune efficacy. The immunized mice exhibited significantly increased serum IgG2a levels, lymphocyte counts and Th1-type cytokine (IL-2, IL-12 and IFN-γ) levels. Moreover, the immunized mice exhibited longer survival times (44.7 ± 2.1 days for ROP18/PLP1 and 47.2 ± 2.9 days for ROP18/PLP1 + IL-18) and lower brain cyst burden (68.9% for ROP18/PLP1 and 72.4% for ROP18/PLP1 + IL-18) than control mice after T. gondii challenge. Our results demonstrate that the multiple-gene DNA vaccine including both ROP18 and PLP1 elicits greater protection against T. gondii challenge and stronger immunogenicity than single-gene vaccines., (Copyright © 2018 Elsevier Inc. All rights reserved.)

China has made significant achievements in social-economic development in the last three decades, and the numbers of livestock and companion animals are rapidly increasing. Some advances have been made in the control and prevention of animal parasitic diseases, but there are still some significant challenges, particularly in relation to foodborne parasitic zoonoses and vector-borne diseases. In addition, new molecular (e.g., genomic and transcriptomic) technologies have been developed and are gradually being introduced into the veterinary parasitology field. Therefore, teaching of veterinary parasitology in Chinese universities has undergone significant changes over the years, in terms of topics, depth and breadth, and also in the ways in which courses are delivered. In this article, we describe the current status of veterinary parasitology teaching at the undergraduate and postgraduate levels in Chinese universities, summarise changes and improvement in veterinary parasitology teaching, and discuss the challenges and opportunities for veterinary parasitology teaching in the 21st century, including the use of new teaching technologies and the integration of the "One Health" concept into veterinary parasitology courses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The aim of our study was to detect differentially regulated proteins and specific signaling pathways in Mongolian gerbil brains during chronic Toxoplasma gondii (T.gondii) PRU strain infection. We use a iTRAQ-based strategy to detecte 4935 proteins, out of which 110 proteins were differentially expressed (>/=2.0-fold, p value <0.05) when the brain of gerbils infected with T.gondii was compared to control brain tissues. We confirmed the authenticity and the accuracy of iTRAQ results through quantitative real-time PCR and western blot (WB), which was consistent with mass spectrometry analysis. Pathway analysis and GO (Gene Ontology) annotations indicated the deregulation of several pathways related to immune response, metabolism and neurological processes, like neuronal growth and neurotransmitter transport. Through the iTRAQ-based strategy, we obtained a comparative proteome profile of brain tissues from Mongolian gerbils with chronic infection of T.gondii. Several differentially expressed proteins involved in neurological pathways, like Parvalbumin, Drebrin or Synaptotagmin, can be further investigated to enhance our understanding of central nervous system (CNS) injury caused by T.gondii., Biological Significance: T.gondii can infect almost all nucleated cells with a preference for the CNS, which can induce Toxoplasma encephalitis (TE). However, the pathogenesis and mechanisms between the parasite and host associated with TE are largely unexplored. Around 30% of the world population is considered to have latent infection with T.gondii and >90% patients died of TE, while the proportion of secondary paralysis is also high. Patients of TE may have highly varied neurological symptoms with both focal and diffuse neurological lesions, while mental symptoms and behavior disorders are frequently accompanied, like the Alzheimer's disease (AD). We present a comparative proteomics analysis to explore the differences of protein expression caused by chronic T.gondii infection. The results of this analysis can be helpful for identifying key proteins involved in the pathogenesis of TE. In addition, the study can contribute to a better understanding of molecular mechanisms underlying the host-parasite relationship in chronic infection of T.gondii and facilitate further development of new therapies for TE., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We previously demonstrated that the survival time of BALB/c mice challenged with Toxoplasma gondii RH strain was prolonged by immunising the mice with a eukaryotic vector expressing the protein ROP16 of T. gondii. Building upon previous findings, we are exploring improved vaccination strategies to enhance protection. In this work, a novel recombinant canine adenovirus type 2 expressing ROP16 (CAV-2-ROP16) of T. gondii was constructed and identified to express ROP16 in Madin-Darby canine kidney cells (MDCK) cells by western blot (WB) and indirect immunofluorescence (IFA) assays. Intramuscular immunisation of BALB/c mice with CAV-2-ROP16 was performed to evaluate the humoral and cellular immune responses. This vaccination triggered significant humoral and cellular responses, including ROP16-stimulated lymphoproliferation (P<0.05). Compared to control groups, the CAV-2-ROP16 immunised mice had high production of IFN-γ, IL-2 and IL-12 (P<0.05), with a predominance of IgG2a production, but not IL-10 (P>0.05), revealing that a predominant Th1-type response had developed. The cell-mediated cytotoxic activity with high levels of IFN-γ and TNF-α was significantly increased in both CD4 + and CD8 + T-cell compartments in the mice immunised with CAV-2-ROP16 (P<0.05), compared to three control groups. In addition, when immunised mice were challenged with the RH strain of T. gondii, they showed a significantly increased survival rate (25%) 80days post infection compared with control mice that all died within seven days (P<0.05). The 25% protection rate elicited by the recombinant virus CAV-2-ROP16 has not been achieved in the field of anti-T. gondii vaccination until now. Our work presents the successful use of recombinant virus CAV-2-ROP16 in vaccination protocols to protect against intraperitoneal challenge with the virulent RH strain of T. gondii. This system was shown to be extremely efficient in eliciting humoral and cellular immune responses that led to a significant improvement in survival time in mice., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Thrombospondin-1 (TSP-1) acts as an anti-angiogenic factor, and its expression in rat brain is upregulated after intracerebral hemorrhage. The current study was designed to investigate the change of plasma TSP-1 levels and assess the prognostic predictive effect of plasma TSP-1 level and it is associated with head trauma severity in the patients with severe traumatic brain injury (STBI)., Materials and Methods: The plasma TSP-1 levels of 134 patients and 134 healthy controls were measured using enzyme-linked immunosorbent assay. The relationships between plasma TSP-1 levels and trauma severity reflected by Glasgow Coma Scale (GCS) scores as well as between plasma TSP-1 levels and short-term and long-term clinical outcomes were analyzed using multivariate analysis., Results: Plasma TSP-1 levels were statistically significantly higher in patients than in healthy controls. The multivariate analysis demonstrated close association of TSP-1 with GCS scores and also identified TSP-1 as an independent predictor for 1-week mortality, 6-month mortality, and 6-month unfavorable outcome. Plasma TSP-1 levels had high prognostic predictive value based on receiver operating characteristic curve. The difference between its prognostic predictive value and GCS scores was not statistically significant., Conclusions: Plasma TSP-1 levels are elevated and are highly associated with head trauma severity and short-term and long-term outcomes of STBI. TSP-1 may be a good prognostic biomarker of STBI., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)