Association of IL-4 and IL-18 genetic polymorphisms with atopic dermatitis in Chinese children

BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease, adversely affecting nearly 20% of the pediatric population worldwide. Interleukin-4 (IL-4) and interleukin-18 (IL-18) are considered to be involved in the pathogenesis and development of AD. The aim of this study was to investigate the association of IL-4 and IL-18 gene polymorphisms with the susceptibility and severity of AD in Chinese children.MethodsSix candidate single nucleotide polymorphisms (SNPs) in IL-4 and IL-18 genes were genotyped through multi-PCR combined with next-generation sequencing in 132 AD children and 100 healthy controls, and all the analyses were performed on blood genome DNA.ResultsThe frequencies of G allele, CG genotype and CG + GG genotype of IL-4 rs2243283, as well as the haplotype IL-4/GTT (rs2243283-rs2243250-rs2243248) were all significantly decreased in AD patients compared with the controls [G vs. C: P = 0.033, OR = 0.59; CG vs. CC: P = 0.024, OR = 0.47; CG + GG vs. CC: P = 0.012, OR = 0.49; GTT vs. CCT: P = 0.011, OR = 0.65]. Moreover, the frequencies of A allele, AA genotype and AG + AA genotype of IL-18 rs7106524, along with the haplotype IL-18/CAA (rs187238-rs360718-rs7106524) were statistically increased in the severe AD patients (A vs. G: P < 0.001, OR = 2.79; AA vs. GG: P = 0.003, OR = 5.51; AG + AA vs. GG: P = 0.036, OR = 2.93; CAA vs. CAG: P = 0.001, OR = 2.86).ConclusionsOur findings suggested that genetic variation in IL-4 rs2243283 such as G allele, CG genotype and CG + GG genotype might confer the reduced susceptibility to AD in Chinese children. Furthermore, A allele, AA genotype and AG + AA genotype of IL-18 rs7106524 explored the strong association with severity in Chinese AD children

A Network-Based Approach to Investigate the Pattern of Syndrome in Depression

In Traditional Chinese Medicine theory, syndrome is essential to diagnose diseases and treat patients, and symptom is the foundation of syndrome differentiation. Thus the combination and interaction between symptoms represent the pattern of syndrome at phenotypic level, which can be modeled and analyzed using complex network. At first, we collected inquiry information of 364 depression patients from 2007 to 2009. Next, we learned classification models for 7 syndromes in depression using naïve Bayes, Bayes network, support vector machine (SVM), and C4.5. Among them, SVM achieves the highest accuracies larger than 0.9 except for Yin deficiency. Besides, Bayes network outperforms naïve Bayes for all 7 syndromes. Then key symptoms for each syndrome were selected using Fisher's score. Based on these key symptoms, symptom networks for 7 syndromes as well as a global network for depression were constructed through weighted mutual information. Finally, we employed permutation test to discover dynamic symptom interactions, in order to investigate the difference between syndromes from the perspective of symptom network. As a result, significant dynamic interactions were quite different for 7 syndromes. Therefore, symptom networks could facilitate our understanding of the pattern of syndrome and further the improvement of syndrome differentiation in depression

Functional Analysis of a Dominant Negative Mutation of Interferon Regulatory Factor 5

BACKGROUND: Interferon regulatory factor (IRF) family members have been implicated as critical transcription factors that function in immune response, hematopoietic differentiation and cell growth regulation. Activation of IRF-5 results in the production of pro-inflammatory cytokines such as TNFalpha, IL6 and IL12p40, as well as type I interferons. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we identify a G202C (position relative to translation start codon) missense-mutation transcript of IRF-5 in transformed B and T cell lines, which were either infected or non-infected by viruses, and peripheral blood from ATL or CLL patients. The mutated transcript encodes a novel protein in which the sixty-eighth amino acid, Alanine, is substituted by Proline (IRF-5P68) in the DNA binding domain of IRF-5. IRF-5P68 phenotype results in a complete loss of its DNA-binding activity and functions as a dominant negative molecule through interacting with wild type IRF-5. Co-expression of IRF-5P68 inhibits MyD88-mediated IRF-5 transactivation. Moreover, Toll-like receptor (TLR)-dependent IL6 and IL12P40 production induced by lipopolysaccharide (LPS), R837 or CpG ODN 1826 was reduced in IRF-5 (P68) expressing cells as compared to the control cells. CONCLUSION: IRF-5P68 acts as a dominant negative regulator that interferes with IRF-5-mediated production of pro-inflammatory cytokines. The functional characterization of the novel IRF-5 mutant in transformed B and T cell lines and in ATL and CLL patients may lead to a better understanding of the role of these transcriptional regulators in hematopoietic malignancies

Deep learning-based image segmentation model using an MRI-based convolutional neural network for physiological evaluation of the heart

Background and Objective: Cardiovascular disease is a high-fatality health issue. Accurate measurement of cardiovascular function depends on precise segmentation of physiological structure and accurate evaluation of functional parameters. Structural segmentation of heart images and calculation of the volume of different ventricular activity cycles form the basis for quantitative analysis of physiological function and can provide the necessary support for clinical physiological diagnosis, as well as the analysis of various cardiac diseases. Therefore, it is important to develop an efficient heart segmentation algorithm.Methods: A total of 275 nuclear magnetic resonance imaging (MRI) heart scans were collected, analyzed, and preprocessed from Huaqiao University Affiliated Strait Hospital, and the data were used in our improved deep learning model, which was designed based on the U-net network. The training set included 80% of the images, and the remaining 20% was the test set. Based on five time phases from end-diastole (ED) to end-systole (ES), the segmentation findings showed that it is possible to achieve improved segmentation accuracy and computational complexity by segmenting the left ventricle (LV), right ventricle (RV), and myocardium (myo).Results: We improved the Dice index of the LV to 0.965 and 0.921, and the Hausdorff index decreased to 5.4 and 6.9 in the ED and ES phases, respectively; RV Dice increased to 0.938 and 0.860, and the Hausdorff index decreased to 11.7 and 12.6 in the ED and ES, respectively; myo Dice increased to 0.889 and 0.901, and the Hausdorff index decreased to 8.3 and 9.2 in the ED and ES, respectively.Conclusion: The model obtained in the final experiment provided more accurate segmentation of the left and right ventricles, as well as the myocardium, from cardiac MRI. The data from this model facilitate the prediction of cardiovascular disease in real-time, thereby providing potential clinical utility

Sensitivity of Vegetation Productivity to Extreme Droughts across the Yunnan Plateau, China

Extreme drought has negative impacts on the health of vegetation and the stability of ecosystems. In this study, the CASA model was employed to estimate the net primary productivity of vegetation over the Yunnan Plateau. The time-lag effects on vegetation were observed within a 0–6 month period of extreme droughts using the Pearson correlation coefficient. The resistance of vegetation during extreme droughts was quantified, and the recovery capability of vegetation following these events was analyzed using the ARIMA model. Moreover, the study investigated the response of vegetation to extreme droughts across diverse altitudinal gradients. The results showed that: (1) This round of extreme drought led to a decrease in the NPP of vegetation in the Yunnan Plateau. (2) Vegetation exhibits a 1–3-month lag period in response to extreme drought, with forests showing slower responses than grasslands and shrubs and higher resistance to the drought. Except for agricultural vegetation, most other vegetation types are able to recover their productivity within a year. (3) Vegetation above 3000 m is less susceptible to the impacts of extreme drought. With increasing elevation, forests exhibit an earlier lag period in response to extreme drought and an increase in resistance, but lower elevation vegetation demonstrates better recovery from extreme drought events. Shrub vegetation shows the highest resistance at elevations between 3000–4000 m, and shrubs at middle to high elevations have better recovery capacity than those at low elevations. Grassland vegetation exhibits increased resistance to extreme drought with higher elevation and shows better recovery. Agricultural vegetation demonstrates higher resistance at middle to high elevations, with no significant elevation differences in recovery capacity. Extreme drought events not only have a lag effect on the vegetation ecosystem, but also affect its stability and resilience to future drought events. To adapt to climate change, future research should emphasize the role of small-scale climate in vegetation’s response to drought

Autoimmune gastritis associated diseases: report of 3 cases and literature review

Objective: To analyze the clinical characteristics of autoimmune gastritis associated diseases, and review the related literatures so as to provide reference for clinical practice. Methods: Three cases of autoimmune gastritis were diagnosed by endoscopy and serological examination due to gastrointestinal symptoms accompanied with anemia, gastric neuroendocrine tumor or abnormal index of liver function respectively, and the correlation between autoimmune gastritis and associated diseases was explore. Results: Case 1 presented with " nausea accompanied by intermittent vomiting and anemia for 1 month", and serological examination indicated megaloblastic anemia postoperative pathology of gastric hyperplasia lesions showed local high-grade neoplasia tubular adenoma after admission. Case 2 presented with "repeated middle and upper abdominal discomfort for several months". Postoperative pathology of gastric hyperplasia lesions was neuroendocrine tumor (G1 stage) after admission to hospital. Case 3 presented with "abnormal index of liver function", and liver biopsy confirmed the diagnosis of primary biliary cholangitis after admission to hospital. Due to the thin mucosal layer of fundus and submucosal vessel penetration of gastric mucosa atrophy, chronic atrophic gastritis was observed in gastric pathology in all patients. Therefore, all serum tests showed positive results for endogenous factor antibody and parietal cell antibody, and all patients were diagnosed as autoimmune gastritis. Subsequent literature analysis suggested that autoimmune gastritis was associated with the development and progression of megaloblastic anemia, neuroendocrine tumor, primary biliary cholangitis and so on. Conclusions: Three cases reported were treated as megaloblastic anemia or gastric neuroendocrine tumor or abnormal index of liver function on first visit, and subsequently were diagnosed as having autoimmune gastritis. Attention should be paid to autoimmune gastritis associated diseases

Video_11_Immune myocarditis related to sintilimab treatment in a patient with advanced lung adenocarcinoma: A case report.AVI

Immune checkpoint inhibitors (ICI) have improved clinical outcomes of patients with advanced lung cancer, but may lead to fatal cardiac injury. We describe a 66-year-old man with advanced lung adenocarcinoma who presented with chest pain and dyspnea 3 weeks after the first dose of sintilimab. The initial electrocardiogram (ECG) demonstrated ST-elevation in leads V5-V9, and a high-sensitivity troponin level was significantly elevated. However, coronary angiography did not reveal any significant stenosis. The patient was successfully treated with methylprednisolone and immunoglobulin. Cardiac MRI was carried out before discharge and late gadolinium enhancement (LGE) was found to be in the mid layer of the septal segment and the subepicardial layer of the inferolateral wall. Due to the high fatality, ICI-related myocarditis requires close surveillance, prompt management and long-term follow-up.</p

Video_2_Immune myocarditis related to sintilimab treatment in a patient with advanced lung adenocarcinoma: A case report.AVI

Immune checkpoint inhibitors (ICI) have improved clinical outcomes of patients with advanced lung cancer, but may lead to fatal cardiac injury. We describe a 66-year-old man with advanced lung adenocarcinoma who presented with chest pain and dyspnea 3 weeks after the first dose of sintilimab. The initial electrocardiogram (ECG) demonstrated ST-elevation in leads V5-V9, and a high-sensitivity troponin level was significantly elevated. However, coronary angiography did not reveal any significant stenosis. The patient was successfully treated with methylprednisolone and immunoglobulin. Cardiac MRI was carried out before discharge and late gadolinium enhancement (LGE) was found to be in the mid layer of the septal segment and the subepicardial layer of the inferolateral wall. Due to the high fatality, ICI-related myocarditis requires close surveillance, prompt management and long-term follow-up.</p

Video_7_Immune myocarditis related to sintilimab treatment in a patient with advanced lung adenocarcinoma: A case report.AVI

Immune checkpoint inhibitors (ICI) have improved clinical outcomes of patients with advanced lung cancer, but may lead to fatal cardiac injury. We describe a 66-year-old man with advanced lung adenocarcinoma who presented with chest pain and dyspnea 3 weeks after the first dose of sintilimab. The initial electrocardiogram (ECG) demonstrated ST-elevation in leads V5-V9, and a high-sensitivity troponin level was significantly elevated. However, coronary angiography did not reveal any significant stenosis. The patient was successfully treated with methylprednisolone and immunoglobulin. Cardiac MRI was carried out before discharge and late gadolinium enhancement (LGE) was found to be in the mid layer of the septal segment and the subepicardial layer of the inferolateral wall. Due to the high fatality, ICI-related myocarditis requires close surveillance, prompt management and long-term follow-up.</p

Video_6_Immune myocarditis related to sintilimab treatment in a patient with advanced lung adenocarcinoma: A case report.AVI

Immune checkpoint inhibitors (ICI) have improved clinical outcomes of patients with advanced lung cancer, but may lead to fatal cardiac injury. We describe a 66-year-old man with advanced lung adenocarcinoma who presented with chest pain and dyspnea 3 weeks after the first dose of sintilimab. The initial electrocardiogram (ECG) demonstrated ST-elevation in leads V5-V9, and a high-sensitivity troponin level was significantly elevated. However, coronary angiography did not reveal any significant stenosis. The patient was successfully treated with methylprednisolone and immunoglobulin. Cardiac MRI was carried out before discharge and late gadolinium enhancement (LGE) was found to be in the mid layer of the septal segment and the subepicardial layer of the inferolateral wall. Due to the high fatality, ICI-related myocarditis requires close surveillance, prompt management and long-term follow-up.</p