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

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.

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.

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 investigate the effects of Qigong pills decoction combined with chemical drugs on hormone levels of polycystic ovarian syndrome(PCOS)patients complicated with infertility. METHODS:A total of 98 PCOS patients complicated with infertility selected from gynaecology department of our hospital during Jul. 2015-Jun. 2016 were divided into observation group and control group according to random number table,with 49 cases in each group. Control group was given Clomiphene ci-trate tablet 50 mg orally,qd,for consecutive 5 d;B-ultrasonography for follicle development was monitored at the 11th day of menstruation,and then they were given Chorionic Gonadotropin for injection 2000 U intramuscularly,qod,if there was not domi-nant follicle >10 mm till the diameter of follicle reached 18 mm. Observation group was additionally given one dose of Qigong pills decoction,every day 400 mL after decocted with water,each 200 mL for morning and night,on the basis of control group. After 3 months of treatment,the levels of FSH,LH,PRL,E2,T,DHEA-S and SHBG,the endometrial thickness,the number of mature follicle and pregnancy rate were compared between 2 groups. RESULTS:Before treatment,there was no statistical signifi-cance in the levels of FSH,LH,PRL,E2,T,DHEA-S or SHBG between 2 groups(P>0.05). 3 months after treatment,the lev-els of PRL,T and DHEA-S in 2 groups were decreased and E2,SHBG were increased significantly;the levels of FSH,PRL,T and DHEA-S in observation group were significantly lower than control group,while the levels of E2 and SHBG were significantly higher than control group,with statistical significance (P<0.05). Endometrial thickness of observation group were significantly higher than that of control group;pregnancy rate (18.37%) was significantly higher than control group (4.08%),with statistical significance (P<0.05). CONCLUSIONS:Qigong pills decoction combined with chemical drugs can help to improve pregnancy rate and regulate serum hormone level in the treatment of PCOS complicated with infertility.

Objective To evaluate the effects of a traditional Chinese medicine Rubia cordifolia L.aqueous extract (RCAE) on body weight, fat mass and parameters of glucose and lipid metabolism in high fat diet (HFD)-induced obese rats and its mechanism.Methods pGL3-Enhancer-PPARγ2 (625 bp)-Luc plasmid, a luciferase reportergene expression plasmid containing PPARγ2 promoter was constructed and stably transfected 3T3-L1 preadipocytes were established.PPARγ2 promoter`s activities in these cells were detected after administration with different concentration (0.1 mg/L~1 000 mg/L) of RCAE or with 100 mg/L RCAE for different action time.PPARγ2 mRNA expression in human adipocytes were detected after administration with 100 mg/L RCAE.Meanwhile, HFD-induced obese rats were administrated with low or high dose RCAE to investigate the effects of RCAE on serum glucose, lipid and insulin levels, body weight, visceral fat mass and so on.Results 10 mg/L RCAE could increase luciferase expression in 3T3-L1 cells to 1.43 folds of that in control group (P<0.01) and it reached 3.24 folds of that in control group when the concentration of RCAE was 1000 mg/L (P<0.01).With the administration with 100 mg/L RCAE, the luciferase activity of 3T3-L1 cells peaked at 28 h where it was 2.72 folds of that in control group (P<0.01), and the expression of PPARγ2 mRNA in human adipocytes increased to 2.27 folds of that in control group (P<0.01).Compared with HFD group, low dose RCAE significantly reduced the fasting insulin level, HOMA-IR and visceral fat mass (P<0.05).Conclusions Low dose RCAE significantly reduces the visceral fat mass and ameliorates insulin resistance in HFD-induced obese rats.The potential mechanism may be explained by the stimulation of PPARγ2 promoter activities and the increased expression of PPARγ2 gene.