BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Objective:To investigate the effect of autophagy on the Treg/Th17 cell imbalance in mice with acute lung injury (ALI).Methods:Twenty-four male SD mice were randomly divided into the sham operation group (S group), sepsis group (Sep group) and autophagy inhibitor 3-methyladenine group (Sep +3-MA group). ALI model was prepared by LPS tracheal dripping method. The mouse pathological injury score mice were evaluated under light microscopy and the W/D ratio was calculated. The counts of Th17 cells and Treg cells in tracheoalveolar lavage fluid (BALF) of mice and the levels of related cytokines were detected by flow cytometry. The expressions of LC3-Ⅱ, Beclin-1 and p62 in Th17 cells and Treg cells in BALF were determined by Western blot.Results:CCompared with the S group, the lung histopathological score and W/D ratio of the Sep group and Sep+3-MA group increased ( P<0.05). Compared with the Sep group, the count of Th17 cells in BALF of the Sep +3-MA group decreased, while the count of Treg cells increased significantly with the progression of sepsis( P<0.05), and the levels of IL-17, IL-10 and TNF-α were significantly decreased ( P<0.05). TGF-β1 levels increased in the early stages of sepsis, but decreased significantly with the progression of sepsis( P<0.05). Compared with the Sep group, LC3-Ⅱ expression in BALF Th17 cells and Treg cells of the Sep+3-MA group showed a downward trend, but there was no statistical difference, while Beclin-1 expression significantly decreased ( P<0.05), and the expression of p62 significantly increased ( P<0.05). Conclusions:Abnormal activation of autophagy in Th17 cells and Treg cells is involved in the immune imbalance of Th17/Treg cells in ALI with sepsis. Inhibition of autophagy can restore the functions of Th17 cells and Treg cells, and improve the imbalance of Th17/Treg by inhibiting autophagy may become a new idea to control the pathogenesis and progression of immune disorders with sepsis.

The construction of clinical teaching faculty team in the practice base for master of nursing specialist plays an important role in the clinical practice and training process of nursing postgraduates with professional master's degree. This study comprehensively retrieves relevant domestic literature, summarizes the current status, core competence, access standards, training requirements and other research progress of teaching faculty team construction in the domestic practice base for master of nursing specialist and explores the urgent need for teaching faculty team construction in practice bases for master of nursing specialist, so as to provide a reference for construction of teaching faculty team in the practice base for master of nursing specialist.

OBJECTIVE: To analyze the molecular etiology of a Chinese child affected with dihydropyrimidinase deficiency. METHODS: Genomic DNA was extracted from peripheral blood samples of the family members. Pathogenic variant was determined by whole exome sequencing and verified by Sanger sequencing. RESULTS: The child was found to harbor homozygous c.905G>A (p.Arg302Gln) variants in exon 5 of the DPYS gene, for which her parents were both heterozygous carriers. CONCLUSION The homozygous c.905G>A (p.Arg302Gln) variants of the DPYS gene probably underlies the dihydropyrimidinase deficiency in the child. Above result has enabled genetic counseling and prenatal diagnosis for this family.
Amidohydrolases/genetics* ; Asian Continental Ancestry Group/genetics* ; Child ; Exons ; Female ; Humans ; Metabolism, Inborn Errors/genetics* ; Mutation ; Pedigree

The optometrist education system in the United States has a history of more than 100 years and has become a complete and mature system. It contains five parts: optometry admission test (OAT); a complete curriculum of optometry, including basic medical lectures, optometric theories and skills, large amount of clinical practices; the National Board Exam of Optometry (NBEO) which is mandatory for every licensed optometrist/practitioner, a one-year optional resident program; continue education in every year for renewing optometric licenses. We analyzed differents such as the enrollment requirements, the training time, the graduation requirements and the career perspective of the optometry education system between China and the United States were analyzed, we want to develop a optometrist training system with Chinese characteristics.

Objective To investigate the changes of Caprini score, plasma D-D and FIB levels in patients with post-fracture DVT and its diagnostic significance.Methods Sixty patients with post-fracture DVT (DVT group) and 120 patients without DVT after fracture were selected (control group).The Caprini score, plasma D-D and FIB levels were compared between the two groups.The relationship between Caprini score and plasma D-D and FIB in the DVT group was analyzed.Results The Caprini score, D-D and FIB levels in the DVT group[7.26±1.88, (3.31±1.52) mg/L, (4.48±0.72) g/L] were significantly higher than those in the control group[3.39±0.80, (0.46±0.11) mg/L, (3.60±0.68) g/L], and the difference was statistically significant (P＜0.05).There was a significant positive correlation between Caprini score and D-D and FIB levels in patients with DVT (P＜0.05).There was a positive correlation between Caprini score and level of D-D and FIB (r=0.748、r=0.662, P＜0.05).The sensitivity of Caprini score combined with D-D and FIB levels in the diagnosis of DVT in fracture patients was 97.83％, specificity was 92.00％, missed diagnosis rate was 2.17％, misdiagnosis rate was 8.00, and area under ROC curve was 0.947 (P＜0.05).Conclusion Caprini score, D-D and FIB levels in patients with lower limb fracture have certain clinical value for the diagnosis of DVT.

Mitochondrial dynamics, the processes of mitochondrial fusion and fission maintain homeostasis, are precisely regulated by fusion/fission-related proteins, and play an important physiological role in mitochondrial metabolism, quality and function. The aberrant changes of these proteins can trigger mitochondrial dynamics imbalance, which cause mitochondrial dysfunctions and result various disease states. This article focuses on gene knockout technology, and reviews the role and application progress of genes encoding for fusion and fission knockout mice in insulin resistance researches, in order to lay a foundation for future studies on signal transduction mechanism of mitochondrial dynamics imbalance in insulin resistance.
Animals ; Gene Knockout Techniques ; Insulin Resistance ; Mice ; Mitochondria ; Mitochondrial Dynamics ; Mitochondrial Proteins

Objective To compare the diagnostic accuracies of deep convolutional neural network (CNN) and dermatologists for pigmented nevus and seborrheic keratosis.Methods CNN network ResNet-50 was trained with 5 094 dermoscopic images of pigmented nevus and seborrheic keratosis using transfer learning,so as to establish a CNN two-classification model.Then,this model was applied to the automatic classification of 30 dermoscopic images of pigmented nevus and 30 dermoscopic images of seborrheic keratosis.Meanwhile,in combination with clinical photos of skin lesions,95 experienced dermatologists who had received dermoscopy training gave their diagnosis for the above 60 dermoscopic images.The diagnostic accuracies were compared between the two methods,and misclassified images were further analyzed.Results The CNN automatic classification model had the diagnostic accuracies of 100％ (30/30)and 76.67％ (23/30) for pigmented nevus and seborrheic keratosis respectively,and the total accuracy was 88.33％ (53/60).The average diagnostic accuracies of 95 dermatologists were 82.98％ (25.8/30) and 85.96％ (24.9/30) for pigmented nevus and seborrheic keratosis respectively,and the total accuracy was 84.47％ (50.7/60).There were no significant differences in the diagnostic accuracies for pigmented nevus or seborrheic keratosis between the CNN automatic classification model and 95 dermatologists (x2 =0.38,P ＞ 0.05).The dermoscopic images misclassified by CNN were divided into 3 categories:special-type lesions with high pigment content and marked keratosis,typical skin lesions with interference factors,and typical skin lesions without definite reasons for misclassification.Conclusions The performance of CNN automatic classification model is similar to that of experienced dermatologists in the two classification of pigmented nevus and seborrheic keratosis.The reasons for misclassification by CNN still need to be explored by dermatologists and professionals in artificial intelligence.

Objective To assess the value of transesophageal echocardiography (TEE) in left atrial appendage (LAA) closer with Amplatzer Cardiac Plug (ACP).Methods Consecutive 32 atrial fibrillation patients (CHADS2≥1) with high risk bleeding underwent LAA occlusion with ACP LAA occlusion device under the guidance of TEE.Measurements of LAA anchoring area diameter (AAD) and LAA anatomical orifice diameter (AOD) including maximum,minimum values,and LAA depth on 2 dimentional TEE (2D TEE) were conducted before closer device implantation.The outcomes of LAA occlusion were analyzed.Results Among 32 patients,27 cases achieved successful LAA occlusion,including 2 cases with peripheral leakage ≤5 mm,and 5 cases failed occlusion.Among 5 failed closed patients,3 cases with LAA AAD≥ 30 mm,1 case with LAA of short depth,and 1 case with anatomical variation of LAA of low position that access sheath could not be positioned in the LAA.LAA AAD maximum,minimum and LAA depth were (25.9±4.9)mm,(20.0±3.8)mm,(31.0±5.6)mm,respectively,and LAA AOD maximum,minimum diameters were (26.2±6.2)mm,(19.4±4.3)mm,respectively.Among 10 cases with LAA AAD≥30 mm,7 cases achieved successful LAA occlusion,but 3 cases failed.The implanted device diameter was (26.4±3.8)mm,and device compression rate was (7.6±5.5)%.The coefficient of correlation between device diameter and large LAA AAD and AOD is 0.770 and 0.717,respectively.There was no complication but 1 case with pericardial effusion.Conclusions Two dimentional TEE measurements of LAA have clinical guiding significance in the selection of proper size of ACP LAA occluder.The AAD of 2D TEE has the good correlation with ACP occluder′s size,the AADs are important factors which affect the success of LAA occlusion.

Objective Henoch-Sch?nlein purpura(HSP)is a common multisystemic vasculitis in children ,but the exact pathogenesis remains unknown. Pentraxin 3(PTX3),a new kind of inflammatory cytokines,has a strong inflammatory effect,and is involved in occurrence and develop-ment of a variety of autoimmune diseases. The objective of this study is to evaluate the expression of PTX3,interleukin-8(IL-8),tumor necrosis fac-tor-α(TNF-α)and high sensitivity C-reactive protein(hs-CRP)in children with HSP,and explore the clinical significance of PTX3 in HSP devel-opment. Methods Thirty-six children(HSP group)and 17 healthy children(control group)were enrolled in the study. Serum levels of PTX3,IL-8 and TNF-α were detected by enzyme-linked immunosorbent assay. Serum hs-CRP levels were measured by automatic biochemical analyzer. Re-sults The serum levels of PTX3,IL-8,TNF-α,and hs-CRP were up-regulated in HSP group compared with the control group(P<0.05). The levels of PTX3,IL-8,TNF-α,and hs-CRP in patients with joint symptoms,or/and gastrointestinal symptoms,or/and kidney injury were significant-ly higher than those patients without joint symptoms,or/and gastrointestinal symptoms,or/and kidney injury(P<0.05). The expression of PTX3 was positively correlated with the expression of IL-8 and TNF-α(r=0.514,0.833,all P<0.05),but there was no correlation between PTX3 and hs-CRP(r=0.292,P>0.05). The expression of PTX3,IL-8,TNF-α and hs-CRP in HSP patients had no gender difference(all P>0.05). Con-clusion The high expression of PTX3 is related to the degree of inflammation in children with HSP. The up-regulated expression of PTX3 may play an important role in pathogenesis of HSP in children.