The core protein (CP) of the classical swine fever virus (CSFV) is one of its structural proteins. Apart from forming the nucleocapsid to protect internal viral genomic RNA, this protein is involved in transcriptional regulation. Also, during viral infection, the CP is involved in interactions with many host proteins. In this review, we combine study of this protein with its disorders, structural/functional characteristics, as well as its interactions with the non-structural proteins NS3, NS5B and host proteins such as SUMO-1, UBC9, OS9 and IQGAP1. We also summarize the important part played by the CP in CSFV pathogenicity, virulence and replication of genomic RNA. We also provide guidelines for further studies in the CP of the CSFV.
Animals ; Classical Swine Fever ; virology ; Classical swine fever virus ; genetics ; metabolism ; pathogenicity ; Genome, Viral ; Swine ; Viral Core Proteins ; chemistry ; genetics ; metabolism ; Virulence

Objective To study the relationship between the expression level of PLK1 in castration-resistant prostate cancer (CRPC) tissues, and its relationship with pathological features. Methods Forty-four CRPC specimens including 28 samples from patients with prostate adenocarcinoma, 14 samples from patients with neuroendocrine prostate cancer (NEPC) and 2 samples from patients with other types of prostate cancer, and 10 normal prostatic hyperplasia specimens were collected from January 2010 to September 2016 in the Second Hospital of Tianjin Medical University. The expression levels of PLK1 in these tissues were detected by S-P immunohistochemistry. The relationship between PLK1 expression and pathologic factors was discussed. Results The positive expression of PLK1 was located in cytoplasm of carcinoma cells, and no express of PLK1 was found in benign prostatic hyperplasia tissues. The expression levels of PLK1 showed no significantly differences between different groups of age, local tumor invasion and regional nodal status, and the level of prostate-specific antigen (PSA, P>0.05). The expression level of PLK1 in patients with Gleason score>8 was higher than that in patients with Gleason score≤8. The PLK1 expression level was positively correlated with Gleason score (rs=0.441,P<0.05). Conclusion PLK1 protein is over-expressed in CRPC tissues, which can reflect the proliferation and differentiation of cancer cells and may be a potential marker of CRPC.

Objective To systematically evaluate the efficacy and safety of 125I seed implantation for treatment of advanced pancreatic cancer.Methods An electronic literatuire search was performed about randomized controlled trials(RCTs) of 125I implantation for treamtent of advanced pancreatic cancer in CNKI,Wanfang Data,CBM,Cochrane Library,PubMed and Embase (from the date of building the database to November 2016).Two investigators independently screened literature,extracted data and assessed the risk bias of included studies,and the Meta-analysis was performed by using Revman 5.3software.Results There were 12 RCTs (n =689) included.Meta-analysis showed that the objective respond rate(ORR) (OR =3.24,95％CI2.33-4.52,P＜0.001),the 6-month survival rate(OR =3.61,95％ CI 1.53-8.52,P =0.003),the 12-month survival rate(OR =4.80,95％ CI 2.40-9.57,P ＜ 0.001) and the relief rate of pain were higher than those in the control group.However,there were no significant differences between both groups in the 2-year survival rate and the adverse reaction rate,which were (OR=2.36,95％ CI 0.47-11.74,P =0.29) and (OR =4.94,95％ CI 1.05-23.23,P =0.04),respectively.Conclusions The limited current evidence showed that 125I implantation for treatment of advanced pancreatic cancer is effective and safety.125I implantation can improve the ORR,short-time survival rate and pain relief rate.In addition,there was no significant increase in the incidence of related adverse events except for seed malposition.Although the quality and quantity of evidences is limited,it merits further study to provide high quality evidences.

Objective To evaluate the clinical effectiveness and safety of stents loaded with 125I seeds compared to conventional stents.Methods Literatures were searched in PubMed,EMbase,Cochrane Library,CBM,CNKI,Wanfang Data and other electronic databases from inception to November 2016.Two reviewers independently screened the literature according to the inclusion and exclusion criteria,extracted data and assessed quality of the included studies independently.Meta-analyses were performed using RevMan 5.3.Results A total of five RCTs and 14 CCTs involving 1 211 patients were included.The mean survival time of the 125I stent group was significantly higher than that of the control group [mean difference =4.11,95％ CI (2.16-6.07)P ＜0.001].The incidence of restenosis after 3:The available data showed that the incidence of re-staging of 125I stent in the treatment group was lower than that of the normal stent group [RR =0.23,95％ CI(0.12-0.62),P =0.002].Postoperative bleeding [RR =0.80,95％CI (0.52-1.23),P=0.30];Postoperative pain[RR=1.06,95％CI(90.88-1.27),P=0.55];postoperative stent shift [RR =0.53,95％ CI(0.27-1.05),P =0.07].The difference of incidence of complications was not statistically significant.There was no difference in the incidence of complications between the two groups.Conclusions The available data suggest that 125I stent is superior to common stent in the treatment of advanced esophageal cancer.There are no differences found in the incidence of complications between 125I stent and conventional stent.However,due to the limited quality of the included studies,more high-quality and multicenter-based studies are needed to verify the above conclusion.

OBJECTIVETo evaluate the sensitivity and specificity of nested PCR combined with pyrosequencing in the detection of HBV drug-resistance gene.

METHODSRtM204I (ATT) mutant and rtM204 (ATG) nonmutant plasmids mixed at different ratios were detected for mutations using nested-PCR combined with pyrosequencing, and the results were compared with those by conventional PCR pyrosequencing to analyze the linearity and consistency of the two methods. Clinical specimens with different viral loads were examined for drug-resistant mutations using nested PCR pyrosequencing and nested PCR combined with dideoxy sequencing (Sanger) for comparison of the detection sensitivity and specificity.

RESULTSThe fitting curves demonstrated good linearity of both conventional PCR pyrosequencing and nested PCR pyrosequencing (R(2)>0.99, P<0.05). Nested PCR showed a better consistency with the predicted value than conventional PCR, and was superior to conventional PCR for detection of samples containing 90% mutant plasmid. In the detection of clinical specimens, Sanger sequencing had a significantly lower sensitivity than nested PCR pyrosequencing (92% vs 100%, P<0.01). The detection sensitivity of Sanger sequencing varied with the viral loads, especially in samples with low viral copies (HBV DNA ≤3log10 copies/ml), where the sensitivity was 78%, significantly lower than that of pyrosequencing (100%, P<0.01). Neither of the two methods yielded positive results for the negative control samples, suggesting their good specificity.

CONCLUSIONCompared with nested PCR and Sanger sequencing method, nested PCR pyrosequencing has a higher sensitivity especially in clinical specimens with low viral copies, which can be important for early detection of HBV mutant strains and hence more effective clinical management.

Adolescent ; Adult ; Aged ; DNA, Viral ; genetics ; Drug Resistance, Viral ; genetics ; Female ; Hepatitis B virus ; drug effects ; genetics ; isolation & purification ; Humans ; Male ; Middle Aged ; Phosphoric Acids ; Plasmids ; Polymerase Chain Reaction ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; Young Adult

Objective:To investigate the value of an MRI and digital pathology images based omics nomogram for the prediction of recurrence risk in soft tissue sarcoma (STS).Methods:This was a retrospective cohort study. From January 2016 to March 2021, 192 patients with STS confirmed by pathology in the Affiliated Hospital of Qingdao University were enrolled, among which 112 patients in the Laoshan campus were enrolled as training set, and 80 patients in the Shinan campus were enrolled as validation set. The patients were divided into recurrence group ( n=87) and no recurrence group ( n=105) during follow-up. The clinical and MRI features of patients were collected. The radiomics features based on fat saturated T 2WI images and pathomics features based on digital pathology images of the lesions were extracted respectively. The clinical model, radiomics model, pathomics model, radiomics-pathomics combined model, and omics nomogram which combined the optimal prediction model and the clinical model were established by multivariate Cox regression analysis. The concordance index (C index) and time-dependent area under the receiver operating characteristic curve (t-AUC) were used to evaluate the performance of each model in predicting STS postoperative recurrence. The DeLong test was used for comparison of t-AUC between every two models. The X-tile software was used to determine the cut-off value of the omics nomogram, then the patients were divided into low risk ( n=106), medium risk ( n=64), and high risk ( n=22) groups. Three groups′ cumulative recurrence-free survival (RFS) rates were calculated and compared by the Kaplan-Meier survival curve and log-rank test. Results:The performance of the radiomics-pathomics combined model was superior to the radiomics model and pathomics model, with C index of 0.727 (95% CI 0.632-0.823) and medium t-AUC value of 0.737 (95% CI0.584-0.891) in the validation set. The omics nomogram was established by combining the clinical model and the radiomics-pathomics combined model, with C index of 0.763 (95% CI 0.685-0.842) and medium t-AUC value of 0.783 (95% CI0.639-0.927) in the validation set. The t-AUC value of omics nomogram was significantly higher than that of clinical model, TNM model, radiomics model, and pathomics model in the validation set ( Z=3.33, 2.18, 2.08, 2.72, P=0.001, 0.029, 0.037, 0.007). There was no statistical difference in t-AUC between the omics nomogram and radiomics-pathomics combined model ( Z=0.70, P=0.487). In the validation set, the 1-year RFS rates of STS patients in the low, medium, and high recurrence risk groups were 92.0% (95% CI 81.5%-100%), 55.9% (95% CI 40.8%-76.6%), and 37.5% (95% CI 15.3%-91.7%). In the training and validation sets, there were statistically significant in cumulative RFS rates among the low, medium, and high groups of STS patients (training set χ2=73.90, P<0.001; validation set χ2=18.70, P<0.001). Conclusion:The omics nomogram based on MRI and digital pathology images has favorable performance for the prediction of STS recurrence risk.

OBJECTIVETo study the molecular mechanism of TAp63gamma-induced cell apoptosis.

METHODSTranscription and protein expression of apoptosis inducing factor and p63 were investigated by immunohistochemistry and RT-PCR in human esophageal squamous carcinoma cell line EC9706 respectively. Twenty-four hours after transfection with pcDNA3.1-TAp63gamma, the apoptosis and translocation of apoptosis inducing factor in EC9706 cells were studied by flow cytometry, laser confocal microscopy and mitochondrial/cytosol/nuclear extraction analysis respectively. Down-regulation of apoptosis inducing factor protein was achieved by RNAi and pretreatment with caspase inhibitor zVAD.fmk of EC9706 cells.

RESULTSPresence of protein expressions of apoptosis inducing factor and absence of TAp63gamma was observed in the cytoplasm of untransfected cells. RT-PCR verified the subtype of p63 in EC9706 cells was DeltaNp63. After 24 hours of transfection, both nuclear and cytoplasmic expression of apoptosis inducing factor protein were observed in cells transfected with TAp63gamma and p53 expression vectors, but not in cells transfected with control vector. Cell apoptosis rates were 1.37%, 13.64%, 4.52%, 4.03% and 1.91% in the pcDNA3.1 transfection group, pcDNA3.1-TAp63gamma transfection group, apoptosis inducing factor siRNA and pcDNA3.1-TAp63gamma transfection group, zVAD.fmk treatment group, and the group receiving apoptosis inducing factor siRNA, plus zVAD.fmk treatment and pcDNA3.1-TAp63gamma transfection, respectively.

CONCLUSIONSApoptosis inducing factor of EC9706 cells is released from mitochondria into both the cytoplasm and nucleus during TAp63gamma induced apoptosis. Down-regulation of apoptosis inducing factor inhibits TAp63gamma-induced apoptosis. Overall, TAp63gamma-induced apoptosis is dependent on the expression of apoptosis inducing factor and caspase.

Amino Acid Chloromethyl Ketones ; pharmacology ; Apoptosis ; Apoptosis Inducing Factor ; genetics ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Caspase Inhibitors ; Cell Line, Tumor ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Down-Regulation ; Esophageal Neoplasms ; metabolism ; pathology ; Humans ; Mitochondria ; metabolism ; Plasmids ; Protein Transport ; RNA Interference ; RNA, Small Interfering ; genetics ; Trans-Activators ; genetics ; metabolism ; Transcription Factors ; Transfection ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo evaluate the feasibility of kidney biopsy by transgastric and transvesical combined approach in the porcine model.

METHODSFive female pigs (20 to 30 kg) were included in this study. All procedures were performed with pigs under general anesthesia. The transvesical access was established by the ureteroscope. Then monitored by ureteroscopy, the transgastric access was established by a needle knife with cautery. The puncture dilation was performed with balloon through the gastroscope. The vesical hole was enlarged with the dilator of ureteroscope sheath. The kidney biopsy was finished by the scissor from the transvesical access and the grasping forcep from the work channel of gastroscope.

RESULTSAmong five cases the procedure were successful in three cases with 380 min, 180 min, 78 min respectively. Establishment of transvesical and transgastric accesses took place without complications. The exposure and biopsy of the kidney were easily achieved during operation. The transgastric and transvesical access were not closed in the end.

CONCLUSIONSThis new method is a technically feasible procedure in a porcine model. But the safety and the clinical future of it needs more study.

Animals ; Biopsy, Needle ; methods ; Female ; Gastroscopy ; Kidney ; pathology ; Swine ; Ureteroscopy

BACKGROUND: Osteoarthritis (OA) is a kind of chronic bone and joint disease which seriously endangers human health. Cell therapy for OA has aroused widespread concern and gotten rapid development in recent years. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have the advantages of easy amplification and differentiation, anti-inflammation and recruiting function such as MSCs from other sources. Furthermore, UC-MSCs are young cells that have large quantity, no ethical problems, high proliferative potential and pluripotent differentiation. UC-MSCs have been the most commonly used seed cells in clinical cell therapy. OBJECTIVE: To evaluate the efficacy and safety of UC-MSCs in the treatment of human knee OA to provide theoretical and clinical basis for stem cell therapy of OA. METHODS: The trail will be completed in Arthritis Clinic & Research Center, Beijing, China. Participants will be recruited according to established inclusion/exclusion criteria after obtaining the informed consent and the approval of the Ethics Committee (the first and second parts of the trial have been registered (https://register.clinicaltrials.gov/), with the identifier No. NCT03357770 and NCT03358654, and the third part will be carried out according to the conclusion of the first and second parts). The clinical trial will be divided into three parts: in the first part three groups will be recruited. Each group will contain three participants. The three groups of participants will be treated with high, medium and low dose of MSCs, respectively. Participants will be followed up to evaluate dose-limiting toxicity so as to determine the maximum tolerated dose. The second part will be a single-arm clinical trial. Nine participants will be recruited. The injection dose will be the maximum tolerated dose determined in the first part. Participants will be followed up to evaluate the safety and efficacy of the treatment. The third part will be a randomized controlled trial. Participants will be randomly divided into two groups (n=7 per group) and treated with MSCs and hyaluronic acid, respectively. During the trial, evaluators, participants and interveners will be unaware of grouping information and interventions. Participants will be followed up at designed time points after treatment to evaluate the safety and efficacy of the intervention. The trial will be terminated if there are unexplained local and systemic symptoms or death according to the NCI-CTCAE criteria. EXPECTED RESULTS: With reference to the previous literature, the knee pain will be relieved, the score of knee joint function will increase, and the cartilage defect area will decrease on MRI at 1-2 years after the intervention. The trail is expected to spend 3 years and 6 months.