Objective To evaluate the clinical efficacy of artificial intelligence(AI)-assisted imaging diagnostic trials using multi-reader multi-case(MRMC)design,so as to provide a scientific basis for clinical evaluation of imaging diagnostic trials.Methods The MRMC design,widely used in imaging diagnostic trials,was adopted in this study.The Obuchowski-Rockette(OR)method of MRMC design was detailed,including model construction and test methods.A case study was conducted,collecting imaging data of 200 subjects from 3 hospitals,with 133 cases of rib fractures and 68 cases of non-rib fractures.Three radiologists reviewed all CT images of the subjects.The area under curve(AUC)value,sensitivity and specificity in detecting rib fractures between 2 reading modalities(radiologists with AI assistance vs radiologists reading independently)were compared.Results The AI-assisted reading group had an AUC value of 0.958,while the radiologist-independent reading group had an AUC value of 0.902,showing a significant difference(P＜0.001).The overall sensitivity and specificity of the AI-assisted reading group were 0.970 and 0.946,respectively;while the sensitivity and specificity of the radiologist-independent reading group were 0.838 and 0.966,respectively.The difference of sensitivity between groups was 0.131(95％confidence interval[CI]0.091-0.171),and the difference of specificity was-0.020(95％CI-0.059-0.020),indicating a significant difference in sensitivity but not in specificity between AI-assisted and radiologist-independent reading groups.Both groups had positive likelihood ratios(+LR)greater than 10 and negative likelihood ratios(-LR)less than 0.2,with positive predictive values approaching 1,suggesting that the diagnostic accuracy of the AI-assisted imaging diagnostic trials was high.Conclusion The AI-assisted reading method demonstrates a significant advantage in enhancing diagnostic efficiency,not only improving the diagnostic accuracy and detection rate of rib fractures,but also improving the work efficiency of radiologists and optimizing hospital services.

Objective To estimate the sample size of radiological diagnostic tests in multireader multicase(MRMC)design,and to explore the numbers of readers and cases under 3 different inference situations:random-reader random-case,fixed-reader random-case,and random-reader fixed-case.Methods The images of 114 participants(45 cases diagnosed as aortic coarctation by the gold standard)in the Van Dyke dataset were used,and 5 radiologists read these images under 2 different magnetic resonance imaging(MRI)sequences(Spin-echo and Cine MRI)to obtain the pre-experiment data.Then Obuchowski-Rockette method was used to estimate sample size.Results The mean area under curve(AUC)of aortic coarctation determined by radiologists was 0.941(95%confidence interval[CI]0.899-0.983)with the Spin-echo MRI sequence,and 0.897(95%CI 0.837-0.957)with the Cine MRI sequence.When the effect size was 0.044 and the number of readers was 5,we needed 337 participants for random-reader random-case,162 participants for fixed-reader random-case,and 282 participants for random-reader fixed-case.Conclusion In MRMC design,we need both the number of readers and cases;the larger the number of readers,the smaller the cases required.We need more samples under the situation of random-reader random-case,when the number of readers is≥5.

Perinatal depression, one of the most common complications in the perinatal period, has a significant impact on the physical and mental health of mothers and children.At present, it is difficult to diagnose perinatal depression at an early stage, so objective and effective biomarkers are of great significance for the early detection and treatment of perinatal depression. In recent years, the exploration of biomarkers for early diagnosis of perinatal depression has become a hot research topic, mainly in sex hormones, neuroendocrine-related hormones, immuno-inflammatory molecules, genetics, and epigenetics.This article reviews the research progress of the biomarkers of perinatal depression in recent years.

OBJECTIVE: To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity. METHODS: Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents. RESULTS: WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3). CONCLUSION The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.
Abnormalities, Multiple/genetics* ; Child ; Histone-Lysine N-Methyltransferase/genetics* ; Humans ; Intellectual Disability/genetics* ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Syndrome

OBJECTIVE： To study on the effects of prophylactic administration of Ramulus mori polysaccharides （RMP） on inflammatory response of renal ischemia reperfusion injury （RIRI） model mice and to explore its possible mechanism. METHODS： Totally 60 C57BL/6 mice were randomly divided to sham operation group， model group， atorvastatin group （positive control， 15 mg/kg）， RMP low-dose， medium-dose and high-dose groups （300， 600， 1 200 mg/kg）. Except for sham operation group， RIRI model was induced in other 5 groups. 24 h before surgery， they were given relevant medicine intragastrically， once a day， for consecutive one week. 24 h after reperfusion， the mice were sacrificed. The serum levels of Scr and BUN were detected. The morphological changes of renal tissue were observed under optical microscope. The serum levels of IL-1β， IL-6， IL-10 and TNF-α were determined by ELISA. Western blot assay was used to determine the protein expressions of Toll-like receptor 4 （TLR4）， p38 mitogen-activation protein kinase （p38MAPK） and p-p38MAPK. RESULTS： Compared with sham operation group， the serum levels of Scr and BUN were significantly elevated in model group  （P＜0.01）. RIRI led to typical inflammatory response of renal tissue， widespread renal tubular epithelial cell degeneration and necrosis， and inflammatory cells infiltration. Serum levels of IL-1β， IL-6， IL-10 and TNF-α were increased significantly （P＜0.01）. The protein expressions of TLR4， p38MAPK and p-p38MAPK were increased significantly in renal cortex （P＜0.01）. Compared with model group， serum levels of Scr and BUN were decreased significantly in administration groups （P＜0.05 or P＜0.01）. The pathological damage of renal tissue was improved in varying degrees， especially in the RMP medium-dose and high-dose groups. Serum levels of IL-1β and IL-6 were decreased significantly in administration groups （P＜0.05 or P＜0.01）. Serum levels of IL-10 were further increased in atorvastatin group and RMP high-dose group （P＜0.01）， and serum level of TNF-α was decreased significantly in atorvastatin group and RMP medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The protein expressions of TLR4 and p-p38MAPK in renal cortex were decreased significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS： RMP prophylactic administration can improve RIRI of mice， the mechanism of which may be associated with relieving the inflammatory response through inhibition of TLR4/p38MAPK signaling pathway.

OBJECTIVE:To study the protective effect of fingolimod on renal ischemia reperfusion injury (RIRI) model mice and its mechanism.METHODS:A total of 60 mice were randomly divided into sham operation group,model group,fingolimod group (1 mg/kg) and fingolimod+wortmannin group [fingolimod 1 mg/kg+phosphatidylinositol 3-kinase (PI3K) specific blocker wortmarmin 1.4 mg/kg],with 15 mice in each group.Except for sham operation group,RIRI model was induced in other 3 groups,and those model mice were given relevant medicine via caudal vein at once 24 h before surgery.Serum of mice were collected in each group after 24 h perfusion.Serum levels of Scr and BUN were measured by automatic biochemical analyzer.The pathological changes of renal tissue were observed under light microscope.The protein expression of intercellular cell adhesion molecule-1 (ICAM-1),monocyte chemoattractant protein-1 (MCP-1) and phosphorylated protein kinase B (p-Akt) in renal tissue were measured by Western blot assay.RESULTS:Compared with sham operation group,the serum levels of Scr and BUN in model group were increased significantly (P＜0.01).Pathological changes were found in the kidney,and RIRI led to widespread renal tubular epithelial cell injury,apoptosis and inflammatory cells infiltration.The protein expression of ICAM-1 and MCP-1 in renal tissue were increased significantly (P＜0.01),the protein expression of p-Akt was increased slightly (P＞0.05).Compared with model group,other indexes of fingolimod group were improved significantly (P＜0.01) except that the protein expression of p-Akt in renal tissue was increased significantly (P＜0.01).Compared with fingolimod group,above indexes of fingolimod+wortmannin group were reversed (P＜0.05 or P＜0.01).CONCLUSIONS:Fingolimod can obviously ameliorate renal injury induced by RIRI in mice,the mechanism of which may be associated with the activation of PI3K/Akt signaling pathway.

Objective To study the characteristics of immune function,Epstein-Barr virus(EBV) antibodies and EBV-DNA in children with different clinical types of EBV infection,which provide basis for prevention and treatment of EBV infection.Methods Clinical data of 103 patients suffering from EBV infection were retrospectively analyzed in Xijing Hospital of the Fourth Military Medical University.A total of 103 children were divided into infectious mononualeosis(IM) group(n=68),chronic active Epstein-Barr virus infection(CAEBV) group(n=13) and Epstein-Barr virus-related hemophagocytic lymphohistiocytosis(EBV-HLH) group(n=22).The changes of EBV antibodies,EBV-DNA,immunoglobulin levels,lymphocyte subpopulation and complement series were detected and compared among the three groups.A total of 26 healthy children at the same stage were enrolled as a control group,immunoglobulin levels,lymphocyte subpopulation and complement series were detected in control group,then compared with the rest of the three groups.Results The levels of C3 and C4 in CAEBV group and EBV-HLH group were significantly decreased than those in the control group(P<0.05).The levels of IgA,IgG and IgE in EBV-HLH group,CAEBV group,IM group and control group gradually increased(P<0.05,respectively).The levels of IgA,IgG and IgE in EBV-HLH group and CAEBV group significantly decreased than those in control group(P<0.05,respectively).The levels of IgA,IgG and IgE in IM group decreased than those in control group,while there were no statistically significant differences(P>0.05).CD8+T cells in IM group significantly increased than those in the rest of the three groups(P<0.05,respectively).T cells,CD8+T cells,CD4+ T cells,CD4+/CD8+ ratios,NK cells,B cells of EBV-HLH group significantly decreased than those in the rest of the three groups(P<0.05).The positive rates of EBV antibodies in CAEBV group and IM group were significantly higher than those in EBV-HLH group(P<0.05).EBV-DNA in EBV-HLH group were significantly higher than those of CAEBV group and IM group(P<0.05).Conclusion EBV-DNA levels in the serum are positively correlated with disease types and severity,the pathogenesis of IM,CAEBV and EBV-HLH induced by EBV infection are associated with immune dysfunction.Dynamic monitoring of EBV load and cell immune function can reflect disease status and progress risk.

Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.
Adjuvants, Immunologic ; pharmacology ; Administration, Intranasal ; Administration, Oral ; Antigens ; administration & dosage ; Drug Delivery Systems ; Humans ; Proteins ; administration & dosage ; Vaccination

Objective To construct a plasmid DNA encoding G glycoprotein of respiratory syncytial virus(RSV) and investigate the protective immune response against RSV infection. Methods Recombinant plasmid DNA of pcDNA3.1~G was constructed by standard RT-PCR based cloning procedure. The immunogenicity of recombinant G protein transiently expressed in HEK293 cells was detected by Western blot. BABL/c mice were intramuscularly immunized with pcDNA3.1~G. Samples of lung, sera, bronchoalveolar lavage fluid(BALF) were collected before and after RSV challenge; virus titer in lung was detected by viral titration; sections of paraffin embedding lung tissues were stained by haematoxylin and eosin(HE) for histological analyses; sera anti-RSV IgG levels were examined by ELISA; Th1/Th2 cytokine were detected by ELISA kit, the T lymphocyte subsets of BALF was determined by immunefluorescence staining followed by flow cytometry. Results Plasmid DNA of pcDNA3.1~G was successfully constructed. The expressed target protein possesses immunogenicity. After challenge, pcDNA3.1~G immunized mice presented relieved pathological changes in lung as well as reduced lung viral titers. The RSV specific IgG was detected in sera of immunized mice. There was significantly increased number of CD25~+CD4~+ T cells in mice BALF. Conclusion We constructed a pcDNA3.1~G plasmid DNA vaccination which can induce evident protective cellular immunity against RSV infection in mice with the increased number of CD25~+CD4~+ T cell subpopulation.

The relationship between visfatin.endothelin, and insulin resistance in the pathogenesis of type 2 diabetes mellitus was explored. Endothelin, visfatin, and other markers were compared. Plasma visfatin was reduced after therapy. Endothelin was positively correlated with fasting insulin, HOMA-IR, HOMA-p, and visfatin. Visfatin was positively correlated with endothelin, HbA1C , fasting insulin, and HOMA-IR. HOMA-IR was an independent related factor in influencing visfatin. The visfatin is related to endothelin and insulin resistance, which may contribute to the pathogenesis of insulin resistance and type 2 diabetes mellitus.