V1-Cal hydrogelation enhances its effects on ventricular remodeling reduction and cardiac function improvement post myocardial infarction.

Myocardial infarction (MI) is a major cause of disability and mortality worldwide. A cell permeable peptide V1-Cal has shown remarkable therapeutic effects on ML However, using V1-Cal to improve long-term cardiac function after MI is presently limited by its short half-life. Herein, we co-assembled V1-Cal with a well-known hydrogelator Nap-Phe-Phe-Tyr (NapFFY) to obtain a new supramolecular hydrogel V1-Cal/NapFFY. We found that the hydrogel could significantly enhance the therapeutic effects of V1-Cal on ventricular remodeling reduction and cardiac function improvement in a myocardial infarction rat model. In vitro experiments indicated that co-assembly of V1-Cal with NapFFY significantly increased mechanic strength of the hydrogel, enabling a sustained release of V1-Cal for more than two weeks. In vivo experiments supported that sustained release of V1-Cal from V1-Cal/NapFFY hydrogel could effectively decrease the expression and activation of TRPV1, reduce apoptosis and the release of inflammatory factors in a MI rat model. In particular, V1-Cal/NapFFY hydrogel significantly decreased infarct size and fibrosis, while improved cardiac function 28 days post MI. We anticipate that V1-Cal/NapFFY hydrogel could be used clinically to treat MI in the near future.

Clinical value of MRI T2-mapping quantitative assessment of carotid plaque.

BACKGROUND: Stroke is a severe health problem, and magnetic resonance imaging (MRI) plays a significant role in stroke. PURPOSE: To investigate the clinical value of MRI T2-mapping in carotid artery plaque. MATERIAL AND METHODS: To locate the plaque in the carotid artery, 25 patients with carotid atherosclerosis were examined by 3.0-T MRI with three-dimensional (3D) time-of-flight and 3D fast spin-echo (FSE) T1-weighted scanning. The original images were obtained after T2-mapping (multi-spin-echo sequence) scanning. The T2 values of the plaque in the narrowest lumen were measured on T2 maps after postprocessing of the original images. Based on the symptoms, the patients were divided into two sub-groups; independent sample t-test was employed to compare the difference between the T2 values of the plaque in the two groups. We evaluated the optimal threshold and diagnostic efficacy of T2 values in predicting cerebrovascular symptoms by the receiver operating characteristic (ROC) curve. RESULTS: The T2 values of the carotid artery plaque in symptomatic and asymptomatic patients were 111.43 ± 46.54 ms and 59.25 ± 39.77 ms, respectively (t = -3.421, P < 0.01). ROC analysis showed that the T2 value of 65.38 ms was the optimal threshold to predict cerebrovascular symptoms. The specificity, sensitivity, and accuracy attained were 94.1% (16/17), 93.3% (14/15), and 93.8% (30/32), respectively. CONCLUSION: We quantitatively assessed carotid plaque components by MRI T2-mapping technology. The T2 values of the carotid plaque were associated with cerebrovascular symptoms. The T2 values of the symptomatic plaque group were significantly higher than those of the asymptomatic group.

Radioimmunoimaging and targeting treatment in an immunocompetent murine model of triple-negative breast cancer using radiolabeled anti-programmed death-ligand 1 monoclonal antibody.

The overall aim of this study was to evaluate whether iodine-131 radiolabeled monoclonal antibody (mAb) targeting programmed death-ligand 1 (PD-L1) can be used for imaging of PD-L1 expression noninvasively in vivo and playing synergistic effect combined with immunotherapy. Anti-PD-L1 mAb was radiolabeled with iodine-131 (131 I-PD-L1 mAb) and was characterized in vitro. Biodistribution and imaging in vivo were performed periodically. Therapy study was conducted in triple-negative breast cancer-bearing BALB/c mice. As results, the labeling efficiencies of 131 I-PD-L1 mAb reached 80% ± 3%, with radiochemical purity of 97% ± 1%. 131 I-PD-L1 mAb preserved the capacity to bind living PD-L1-expressing cells specifically in vitro. Tumor radioactivity uptake of 131 I-PD-L1 mAb was significantly higher than that of control groups. The xenografts were clearly imaged from 48 to 72 hours noninvasively after injection of 131 I-PD-L1 mAb, while the xenografts were not imaged in control groups. Tumor growth was significantly inhibited, and median survival time was remarkably prolonged in combination therapy group compared with control groups. It was concluded that 131 I-PD-L1 mAb can be a potential theranostic candidate for visualizing of PD-L1 expression noninvasively and performing synergistic therapy in carcinomas.

Advancements of molecular imaging and radiomics in pancreatic carcinoma.

Despite the recent progress of medical technology in the diagnosis and treatment of tumors, pancreatic carcinoma remains one of the most malignant tumors, with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation. This paper focuses on the research progress of magnetic resonance imaging, nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma. We also briefly described the achievements of our team in this field, to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

Modelling outbreak response impact in human vaccine-preventable diseases: A systematic review of differences in practices between collaboration types before COVID-19.

BACKGROUND: Outbreak response modelling often involves collaboration among academics, and experts from governmental and non-governmental organizations. We conducted a systematic review of modelling studies on human vaccine-preventable disease (VPD) outbreaks to identify patterns in modelling practices between two collaboration types. We complemented this with a mini comparison of foot-and-mouth disease (FMD), a veterinary disease that is controllable by vaccination. METHODS: We searched three databases for modelling studies that assessed the impact of an outbreak response. We extracted data on author affiliation type (academic institution, governmental, and non-governmental organizations), location studied, and whether at least one author was affiliated to the studied location. We also extracted the outcomes and interventions studied, and model characteristics. Included studies were grouped into two collaboration types: purely academic (papers with only academic affiliations), and mixed (all other combinations) to help investigate differences in modelling patterns between collaboration types in the human disease literature and overall differences with FMD collaboration practices. RESULTS: Human VPDs formed 227 of 252 included studies. Purely academic collaborations dominated the human disease studies (56%). Notably, mixed collaborations increased in the last seven years (2013-2019). Most studies had an author affiliated to an institution in the country studied (75.2%) but this was more likely among the mixed collaborations. Contrasted to the human VPDs, mixed collaborations dominated the FMD literature (56%). Furthermore, FMD studies more often had an author with an affiliation to the country studied (92%) and used complex model design, including stochasticity, and model parametrization and validation. CONCLUSION: The increase in mixed collaboration studies over the past seven years could suggest an increase in the uptake of modelling for outbreak response decision-making. We encourage more mixed collaborations between academic and non-academic institutions and the involvement of locally affiliated authors to help ensure that the studies suit local contexts.

Blocking the CXCL1-CXCR2 axis enhances the effects of doxorubicin in HCC by remodelling the tumour microenvironment via the NF-κB/IL-1ß/CXCL1 signalling pathway.

Inflammation is a core mechanism for oncogenesis. Chemokines act as important mediators of chronic inflammation and the tumour inflammatory response. However, there is limited information on chemokines in hepatocellular carcinoma (HCC), a disease for which almost all cases are derived from chronic liver inflammation. Here, we explored the protumor effects of CXCL1, a commonly elevated inflammatory chemokine in cirrhosis, in HCC. The protumor role was confirmed in clinical samples from HCC patients. CXCL1 enhanced tumorigenesis in the hepatic inflammatory microenvironment directly by acting on tumour cells and indirectly through promoting the recruitment of macrophages. The increase in the number of macrophages in the tumour microenvironment (TME) promoted tumour cell epithelial-mesenchymal transition (EMT) and significantly increased CXCL1 levels in the TME partly through NF-κB/IL-1ß activation. To investigate the potential therapeutic value of CXCL1 in HCC with an inflammatory background, an antibody blocking CXCL1 was used alone or combined with the chemotherapy agent doxorubicin (DOX), with the goal of reshaping the TME. It has been shown that blocking CXCL1-CXCR2 inhibits tumour progression and reduces macrophage recruitment in the TME. The combination regimen has been shown to synergistically reduce the number of pro-tumour macrophages in the TME and suppress tumour progression. This provides insight into therapeutic strategies for treating HCC patients with high CXCL1 expression.

Case Report: A rare case of primary hepatic Castleman's disease mimicking a liver tumor.

Castleman's disease (CD) is a primary lymphoproliferative disorder of the lymph nodes with rare extra-nodal primary affection. Solid organ involvement is rare, and isolated liver involvement is extremely rare. Here we presented a case of a 59-year-old woman with a hepatic lesion accidentally found by ultrasound. The MRI result indicated primary liver malignancy or liver metastases. 18F-FDG PET/CT could not exclude hepatic malignant tumor due to its high metabolism. Finally, the hepatic CD was confirmed by postoperative pathology.

A Novel Method for Accurate Quantification of Split Glomerular Filtration Rate Using Combination of Tc-99m-DTPA Renal Dynamic Imaging and Its Plasma Clearance.

PURPOSE: To precisely quantify split glomerular filtration rate by Tc-99m-DTPA renal dynamic imaging and plasma clearance in order to increase its consistency among doctors. METHODS: Tc-99m-DTPA renal dynamic imaging was performed according to the conventional radionuclide renal dynamic imaging by five double-blinded doctors independently and automatically calculated split GFR, namely, gGFR. Moreover, the conventional radionuclide renal dynamic imaging was assessed to only outline the kidney, blank background, and automatically calculated split GFR, gGFR'. The total GFR value of patients, tGFR, was obtained by the double-plasma method. According to the formula, Precise GFR (pGFR) = gGFR'/(gGFR' + gGFR') × tGFR. The precise GFR value of the divided kidney, pGFR, was calculated. The Kendall's W test was used to compare the consistency of gGFR and pGFR drawn by five physicians. RESULTS: According to Kendall's W consistency test, Kendall's coefficient of concordance was 0.834, p = 0.0001 using conventional method. The same five doctors used blank background again and the same standard Gates method to draw the kidneys, which automatically calculated gGFR'. Using input formula, the pGFR was calculated and Kendall's W consistency test (Kendall's coefficient of concordance = 0.956, p = 0.0001). CONCLUSION: The combination of Tc-99m-DTPA renal dynamic imaging combined with the double-plasma method could achieve accurate split GFR, and because of the omission of influence factors, the consistency of pGFR obtained by different doctors using this method was significantly higher than that of conventional Tc-99m-DTPA renal dynamic imaging.

m5C Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Papillary Thyroid Carcinoma.

Recently, immune response modulation at the epigenetic level is illustrated in studies, but the possible function of RNA 5-methylcytosine (m5C) modification in cell infiltration within the tumor microenvironment (TME) is still unclear. Three different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above three identified patterns. A low m5C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. A small amount of effective immune infiltration was seen in the high m5C-score subtype, indicating the dismal patient survival. Our study constructed a diagnostic model using the 10 signature genes highly related to the m5C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out five potential drugs for PTC based on this m5C-score model. m5C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m5C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME.

Outbreak response intervention models of vaccine-preventable diseases in humans and foot-and-mouth disease in livestock: a protocol for a systematic review.

INTRODUCTION: Outbreaks of vaccine-preventable diseases continue to threaten public health, despite the proven effectiveness of vaccines. Interventions such as vaccination, social distancing and palliative care are usually implemented, either individually or in combination, to control these outbreaks. Mathematical models are often used to assess the impact of these interventions and for supporting outbreak response decision making. The objectives of this systematic review, which covers all human vaccine-preventable diseases, are to determine the relative impact of vaccination compared with other outbreak interventions, and to ascertain the temporal trends in the use of modelling in outbreak response decision making. We will also identify gaps and opportunities for future research through a comparison with the foot-and-mouth disease outbreak response modelling literature, which has good examples of the use of modelling to inform outbreak response intervention decision making. METHODS AND ANALYSIS: We searched on PubMed, Scopus, Web of Science, Google Scholar and some preprint servers from the start of indexing to 15 January 2020. Inclusion: modelling studies, published in English, that use a mechanistic approach to evaluate the impact of an outbreak intervention. Exclusion: reviews, and studies that do not describe or use mechanistic models or do not describe an outbreak. We will extract data from the included studies such as their objectives, model types and composition, and conclusions on the impact of the intervention. We will ascertain the impact of models on outbreak response decision making through visualisation of time trends in the use of the models. We will also present our results in narrative style. ETHICS AND DISSEMINATION: This systematic review will not require any ethics approval since it only involves scientific articles. The review will be disseminated in a peer-reviewed journal and at various conferences fitting its scope. PROSPERO REGISTRATION NUMBER: CRD42020160803.

Using statistics and mathematical modelling to understand infectious disease outbreaks: COVID-19 as an example.

During an infectious disease outbreak, biases in the data and complexities of the underlying dynamics pose significant challenges in mathematically modelling the outbreak and designing policy. Motivated by the ongoing response to COVID-19, we provide a toolkit of statistical and mathematical models beyond the simple SIR-type differential equation models for analysing the early stages of an outbreak and assessing interventions. In particular, we focus on parameter estimation in the presence of known biases in the data, and the effect of non-pharmaceutical interventions in enclosed subpopulations, such as households and care homes. We illustrate these methods by applying them to the COVID-19 pandemic.

Noninvasive PET Imaging of a Ga-68-Radiolabeled RRL-Derived Peptide in Hepatocarcinoma Murine Models.

PURPOSE: Tc-99m- and I-131-labeled arginine-arginine-leucine (RRL) peptides have shown the feasibility of tumor imaging in our previous studies. However, there have been no reports using RRL peptide for positron emission tomography (PET) imaging. In this study, RRL was radiolabeled with Ga-68 under optimized reaction conditions to develop a better specific and effective tumor imaging agent. PROCEDURES: RRL was synthesized and conjugated to a bifunctional chelating agent (DOTA-NHS), then radiolabeled with Ga-68. Labeling yield was optimized by varying pH, temperature, and reaction time and the stability was evaluated in human fresh serum. Cellular uptakes of [68Ga]DOTA-RRL and FITC-conjugated RRL in HepG2 cells were evaluated using a gamma counter, confocal microscopy, and flow cytometry. PET images and biodistribution were performed in HepG2 tumor-bearing mice after injection of [68Ga]DOTA-RRL or [68Ga]GaCl3 at different time points. Further, blocking study was investigated using cold RRL. RESULTS: The labeling yield of [68Ga]DOTA-RRL was 80.6 ± 3.9 % with a pH of 3.5-4.5 at 100 °C for 15 min. The cellular uptake of [68Ga]DOTA-RRL in HepG2 cells was significantly higher than that of [68Ga]GaCl3 (P < 0.05). Moreover, the high fluorescent affinity of FITC-conjugated RRL in HepG2 cells was shown using confocal microscopy and flow cytometry. After injection of [68Ga]DOTA-RRL in HepG2 tumor-bearing mice, tumor regions exhibited high radioactive accumulation over 120 min and the highest uptake at 30 min. After blocked with cold RRL, HepG2 tumors could not be visualized. [68Ga]GaCl3 was unable to show tumor images at any time point. The biodistribution results confirmed the PET imaging and blocking results. CONCLUSIONS: Our study successfully prepared [68Ga]DOTA-RRL with a high labeling yield under the optimized reaction conditions and demonstrated its potential role as a PET imaging agent for tumor-targeted diagnosis.

Splenic artery embolization with detachable balloons for hypersplenism.

Objective This study was performed to investigate the efficacy of proximal splenic artery embolization using detachable balloons for patients with hypersplenism and portal hypertension. Methods Twelve patients diagnosed with hypersplenism with thrombocytopenia or leukocytopenia caused by portal hypertension were treated by proximal splenic artery embolization with detachable balloons and metallic fibered coils. All patients were followed for up to 6 months. Blood parameters, coagulation factors, and liver function indicators were measured. Enhanced computed tomography and abdominal ultrasonography examinations were also performed in advance to confirm the infarction area and evaluate the changes in spleen size. Results Postoperative angiography demonstrated complete embolization of the proximal splenic artery in all 12 patients. Thrombocyte and leukocyte counts rose significantly in all patients in 2 weeks and stayed significantly higher than those before embolization throughout the 6-month follow-up. The total bilirubin concentration and prothrombin activity recovered significantly and returned to normal levels 6 months later. Computed tomography revealed partial infarction and liquefaction of the splenic parenchyma in nine patients. Conclusions Proximal splenic artery embolization using detachable balloons could be considered a safe and effective therapeutic modality in alleviating hypersplenism secondary to portal hypertension.

[A clinical study on the treatment of mucocele by bleomyin A5 combined with phosphorus-32 colloid].

OBJECTIVE: To evaluate the effect of bleomyin A5 combined with phosphorus-32 colloid in the treatment of mucocele. METHODS: A total of 214 patients divided into three groups, bleomyin A5 (50 cases), phosphorus-32 colloid (50 cases) and bleomyin A5 combined with phosphorus-32 colloid (114 cases). RESULTS: The efficacy of bleomyin A5 group, phosphorus-32 colloid group, and bleomyin A5 combined with phosphorus-32 colloid group was 84% (42/50), 82% (41/50) and 98% (112/114), respectively. There were significant difference in efficacy among the three groups (P < 0.05). The phosphorus-32 colloid group and the bleomyin A5 group had no significant difference in efficacy (P > 0.05). CONCLUSIONS: The independent use of bleomyin A5 and phosphorus-32 colloid is effective, but the combined use of the two methods is more effective.