[The application value of Gd-EOB-DTPA enhanced MRI based radiomics in the differential diagnosis of iso-or hyperintensity HCC and focal nodular hyperplasia in hepatobiliary phase].

Objective: To investigate the application value of Gd-EOB-DTPA enhanced MRI based radiomics model in the differential diagnosis of iso-or hyperintensity HCC and focal nodular hyperplasia (FNH) in hepatobiliary phase. Methods: A total of 88 patients with HCC or FNH confirmed by surgical or puncture pathology who underwent preoperative Gd-EOB-DTPA enhanced MRI (all lesions showed iso-or hyperintensity in hepatobiliary phase) between January 2015 and February 2023 in The First Affiliated Hospital of Soochow University and Nantong No.3 People's Hospital were retrospectively evaluated, which including 58 males and 30 females, aged [M(Q1, Q3)]56 (40, 67) years, including 61 patients with HCC and 27 patients with FNH. The included cases were divided into training (43 cases of HCC, 19 cases of FNH) and validation cohort (18 cases of HCC, 8 cases of FNH) in the ratio of 7∶3 using the random seeding method. A total of 1 781 radiomics features were extracted from Gd-EOB-DTPA enhanced MRI in the arterial, portal and hepatobiliary phases, respectively. The independent three phase models, combined three phases model and combined clinical-radiomics model was established using Auto-Encoder (AE) and Native Bayes (NB) classifier, respectively. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of these models. DeLong test was used to compare the areas under curve (AUC). Results: In the validation cohort, the combined clinical-radiomics model had the highest AUC (AUC=0.938, 95%CI: 0.828-1.000). The AUC, accuracy, sensitivity, specificity of the clinical-radiomics combined model using AE classifier in the validation cohort were 0.896 (95%CI: 0.760-1.000), 88.5%, 88.9%, 87.5%. The AUC of the clinical-radiomics combined model using NB classifier in the validation cohort were 0.938 (95%CI: 0.828-1.000), 92.3%, 88.9%, 100.0%. Conclusion: Gd-EOB-DTPA enhanced MRI combined clinical-radiomics model has certain value in preoperative differentiation of iso-or hyperintensity in the hepatobiliary phase HCC and FNH, with a high accuracy, sensitivity and specificity.

Mesenchymal stem cells-derived exosomal miRNA-28-3p promotes apoptosis of pulmonary endothelial cells in pulmonary embolism.

OBJECTIVE: Pulmonary embolism (PE) is a primary clinical manifestation of venous thromboembolism (VTE). It has been demonstrated that pulmonary endothelial cells (PECs) are apoptotic-resistant in PE. MATERIALS AND METHODS: In this study, PECs were collected from PE patients and mouse models. Western blot, RT-PCR, flow cytometry, H&E and TUNEL assay, confocal and TEM microscopy, and Luciferase reporter assay were performed to determine the effects of miR-28-3p on PECs apoptosis and if exosomes can act as the shuttle to transport miR-28-3p to PECs. RESULTS: The results revealed that apoptosis and miR-28-3p were downregulated in PECs of PE. The miR-28-3p mimics and inhibitor enhanced and further inhibited apoptosis in PECs, respectively. Both miR-28-3p-modified adipose tissue-derived mesenchymal stem cells (AMSCs) and AMSC-derived exosomes upregulated miR-28-3p expression in PECs, leading to elevated apoptosis of PECs. Apoptosis inhibitor 5 (API5) was a direct target gene of miR-28-3p, and the overexpression of API5 in miR-28-3p-modified PECs further suppressed apoptosis. Furthermore, the administration of miR-28-3p-modified exosomes to PE mouse model promoted apoptosis in PECs. CONCLUSIONS: Exosomal miR-28-3p could ameliorate PE-associated apoptosis-resistance in PECs through targeting API5 in vitro and in vivo. Therefore, AMSCs-derived exosome is a promising way to deliver functioning miRNA to PECs, providing insight into novel therapy of PE.

[Etiology and molecular-epidemiological characteristics of viral meningo-encephalitis in Zhejiang province, 2002-2018].

Objective: To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018. Methods: All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis. Results: 871 (40.1%) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1%) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7%) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions: HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.

FBLN3 inhibited the invasion and metastasis of colorectal cancer through the AKT/mTOR pathway.

Fibulin-3(FBLN3) levels are different in different types of cancers. We found that fibulin-3 was downregulated in colorectal (CRC) cells, particularly in the SW480 cell line. By comparison, transfecting SW480 cells with a lentivirus overexpressing fibulin-3 RNA could inhibit proliferation, induce G1/S arrest, and promote cell apoptosis. Fibulin-3 overexpression further suppressed the invasion and metastasis of CRC. These effects were regulated through the AKT/mTOR signaling pathway.

Rapid detection of H5 avian influenza virus by TaqMan-MGB real-time RT-PCR.

AIMS: Real-time reverse transcription-polymerase chain reaction (RT-PCR) assay based on a TaqMan-minor groove binder (MGB) probe was developed for the rapid detection of avian influenza virus subtype H5. METHODS AND RESULTS: Conserved regions in the haemagglutinin genes of avian influenza viruses subtype H5 served as targets for the primers and TaqMan-MGB probe design. Concentrations of primers and probe were optimized to improve the sensitivity and specificity of the reactions. A plasmid containing the haemagglutinin gene was constructed and in vitro transcribed for a quantitative assay of copy numbers of the target gene. The results revealed that the optimal concentration of primers and probe was 640 and 480 nmol l(-1), respectively. The threshold of 100 copies of target molecules could be detected. The linear range for detection was determined as 10(2) to 10(8) molecules in reaction. CONCLUSIONS: It took less than 3 h to complete the detection from viral RNA extraction, with good sensitivity and repeatability. SIGNIFICANCE AND IMPACT OF THE STUDY: Real-time RT-PCR assay with MGB probe was an effective means for quick and quantitative laboratory detection and monitoring of H5 avian influenza viruses.

Catalytic kinetic simultaneous determination of iron, silver and manganese with the Kalman filter by using flow injection analysis stopped-flow spectrophotometry.

A catalytic differential kinetic method with Kalman filter for the simultaneous determination of multi-component is described. The oxidization of Rhodamine B (RB) by potassium periodate in a slightly acid solution is a slow reaction. But iron(III), silver(I) or manganese(II) has a differential catalytic effect on the oxidation reaction of RB in the presence of 1,10-phenanthroline as the activator. So iron, silver and manganese can be simultaneously determined by measuring the decreasing absorbance of the dye (RB) at 555 nm. A flow injection analysis stopped-flow spectrophotometric system with a microcomputer performs the determinations. This method has been applied to determining iron, silver and manganese of alloy samples with satisfactory results.

[Effects of propafenone on electrophysiologic changes caused by alteration of left ventricular afterload in anesthetized rabbits].

AIM: To study effects of propafenone (Pro) on ventricular electrophysiologic changes caused by alteration of left ventricular afterload of rabbit heart. METHODS: Before and after i.v. Pro 3 mg.kg-1, changing afterload of left ventricle (LV), occurrence of ventricular arrhythmia, left ventricular diastolic thresholds (VDT), relative refractory period (RRP), effective refractory period (ERP), dispersion of refractory period, and ventricular fibrillation threshold (VFT) were recorded. RESULTS: Increasing afterload of LV increased temporal dispersion of RRP and ERP [from 11 +/- 4 and 6 +/- 3 ms to 18 +/- 8 and 13 +/- 8 ms (+delta P = 8.4 +/- 2.9 kPa) individually (P < 0.05)] and decreased VFT [from 5.5 +/- 1.0 V to 3.9 +/- 0.9 V (P < 0.01)]; Ventricular arrhythmia was seen in all rabbits. But reducing left ventricular afterload did not alter the electrophysiologic parameters in LV and did not induce ventricular arrhythmia. Pro i.v. prolonged RRP and ERP, increased VDT and VFT (P < 0.01); Increasing or decreasing left ventricular afterload did not cause much alteration of ventricular electrophysiologic parameters (P > 0.05). CONCLUSION: Pro inhibited increase of dispersion of refractory period and decrease of VFT caused by increase of left ventricular afterload and has an effect of anti-ventricular arrhythmia.

[Effects of amiodarone on ventricular refractory period caused by subthreshold electric stimulation].

Effects of amiodarone (Ami) 25 mg.kg-1 iv on ventricular refractory period caused by subthreshold single or train stimulations were studied in rabbits. Before Ami i.v., the refractory period was prolonged by S1-St (P < 0.05, P < 0.01) and by Ss (St) which was intercalated to S1-S2 interval [S1-Ss (St)-S2 methods]. After Ami iv, the refractory period was shortened by S1-St (50 ms, 330 Hz, 6 V) (P < 0.01) and minimal inhibitory voltage of Ss was higher than that of pre-medication in different Ss-S2 intervals (20, 25 ms). These results suggested Ami may change the mode of terminating tachycardia by electric stimulation.

Negative behavior during marital conflict is associated with immunological down-regulation.

Although increased morbidity and mortality have been reliably associated with social isolation and less satisfying personal relationships, relatively little is known about the underlying biopsychosocial mechanisms. We assessed problem-solving behaviors and changes in immune function in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. Subjects who exhibited more negative or hostile behaviors during a 30-minute discussion of marital problems showed greater decrements over 24 hours relative to low negative subjects on four functional immunological assays (natural killer cell lysis, blastogenic response to two mitogens, and the proliferative response to a monoclonal antibody to the T3 receptor), as well as larger increases in the numbers of total T lymphocytes and helper T lymphocytes. High negative subjects had higher antibody titers to latent Epstein-Barr virus than low negative subjects, consistent with down-regulated immune function. Women were more likely to show negative immunological changes than men. The discussion of marital problems also led to larger increases in blood pressure that remained elevated longer in high negative subjects than low negative subjects. Positive or supportive problem-solving behaviors were not related to either immunological or blood pressure changes. These physiological differences were particularly noteworthy because marital satisfaction was high in both groups, and couples had been selected on the basis of stringent mental and physical health criteria. These data provide additional support for the link between personal relationships and immune function.

[Rotundium in the treatment of atrial fibrillation].

L-tetrahydropalmatine (Rotundium) is an alkaloid of Corydalis turtschaninovii. Some animal experiments had demonstrated that Rotundium had a good antiarrhythmic effect in blocking the calcium channel and that it was a class IV antiarrhythmic agent, similar to that of Bepridil in literatures. This is a clinical report of Rotundium (oral given) on an atrial fibrillation (AF) patients. The therapeutical results were evaluated by 24 hours ambulatory electrocardiographic monitoring and ECG. The results showed that the effective rate of Rotundium on paroxysmal atrial fibrillation and sustained atrial fibrillation of 45 mm (left atrium diameter) or more was 30%, while LAD of less than 45 mm was 80% (P < 0.01). Among 8 cases' duration of AF were 6 months or more, 3 cases were effective, the effective rate 37.5%, while among 10 cases' duration of AF were less than 3 weeks, 3 cases were converted to sinus rhythm, 5 cases were effective. There was a significant difference between two groups. Age and sex exerted no effect on efficacy. During taking Rotundium, blood pressure had no apparent changes and no severe side effects were found. The results showed that Rotundium is an effective, safe new drug to treat AF, especially in paroxysmal atrial fibrillation. The antiarrhythmic mechanism of Rotundium might be related to its prolonging of the effective refractory period of atrial and atrioventricular node.

Stress-related activation of Epstein-Barr virus.

Herpesviruses characteristically persist in a latent state in the body over the lifetime of an individual. Under certain conditions, any one of the herpesviruses can be reactivated. The mechanisms underlying the establishment of latent virus infection or viral reactivation are not well understood; however, it is known that the cellular immune response plays a very important role in the maintenance of latency and in virus reactivation. One of the factors thought to be associated with the reactivation of latent herpes-viruses is psychological stress. Using an examination stress model with medical student subjects, we previously demonstrated the reactivation of latent Epstein-Barr virus (EBV), as measured by increases in antibody titers. In this follow-up study using the same group of medical students, we found evidence for incomplete reactivation of latent EBV, with only selective expression of the latent virus genome.

Impedance cardiography-dipyridamole test in detecting coronary artery disease.

Thallium-201 dipyridamole test (Tl-201DT) has high sensitivity and specificity in the assessment of coronary disease (CAD), but is not always available. We proposed impedance cardiography DT (IDT)instead. To determine the characteristic changes of impedance cardiogram (ICG) in patients with typical angina and to compare with those in normal subjects, 37 subjects undergoing IDT were divided into 3 groups: typical angina (15), suspected chest pain (11) and normals (11). Dipyridamole (DP) was infused intravenously for over 10 minutes at a total dose of 0.75 mg/kg. Simultaneous recording of ECG, PCG, and ICG were repeated immediately 2 minutes and 4 minutes after infusion of DP, and immediately and 5 minutes after intravenous infusion of aminophylline. Eleven parameters, HR, SPRP, QZ/ZA2, HI, SV, CO, A wave, A/C, O wave, O/C, A + O/C were observed. Only in O/C and A + O/C there were changes of significant differences (P less than 0.01) between groups. Specificity was 100% (0/11 positive) in normals. Sensitivity was 80% (12/15 positive) in the angina group, but only 46.7% (7/15) with ECG. The characteristic changes in CAD patients during IDT were angina induced by DP, abnormal O wave on ICG and change from deep A wave to abnormal O wave. No serious complication occurred after IDT. Our results indicate that IDT is a simple, practical and valuable method for detecting CAD.