Objective To investigate the effects of Dermatophagoides pteronyssinus ( Der p) on the expression of TLR4 and IL-4 in P815 mast cells and to further analyze the immunoregulatory effects of 1,25-(OH)2D3 on Der p treated P815 mast cells.Methods Different concentrations of Der p and 1,25-( OH) 2 D3 were used alone or in combination to stimulate P815 mast cells.The supernatants of the stimulated cell culture were analyzed by enzyme-linked immunosorbent assay ( ELISA) for the detection of IL-4.The stimulated cells were collected and analyzed by real-time PCR and Western blot assays for the detection of TLR4atmRNAandproteinlevels,respectively.Results (1)TLR4expressionwasdetectedinP815 cells.The expression of TLR4 was enhanced in P815 cells treated with various concentrations of Der p.A significant dose-dependent up-regulation of TLR4 was observed in P815 cells after incubation with Der p for 36 h.(2) Der p promoted the release of IL-4 in P815 cells (P<0.05).(3) No significant differences with the expression of TLR4 and IL-4 were observed among 1,25(OH)2D3 treatment groups as compared with the control group (P>0.05).(4) 10-8 mol/L of 1,25(OH)2D3 promoted the Der p-induced expression of TLR4 in P815 cells (P<0.01).However, 1,25(OH)2D3 inhibited the release of IL-4 in a dose-dependent manner(P<0.05orP<0.01).Conclusion (1)Derpcouldpromotetheinflammationandallergicreac-tion through up-regulating TLR4 and IL-4 in mast cells.(2) The possible mechanism for the inhibitory of 1, 25(OH)2D3 on Der p-induced immune responses was due to the suppression of Th2-type immune responses through inhibiting the synthesis and secretion of IL-4 in mast cells.

The use of whole exome sequencing (WES) for the detection of disease-causing variants of genetic diseases and for non-invasive prenatal screening (NIPS) of fetal aneuploidies are two major clinical applications of next generation sequencing (NGS). This article has summarized the official documents developed and updated by the American College of Medical Genetics and Genomics (ACMG) on governing WES and NIPS. These include the development of expert consensus policies and position statements on an ongoing basis to guide clinical application of NGS technology and variant analysis, establish evidence-based practical resources, as well as standards and guidelines to govern diagnosis and screening. These ACMG documents are valuable references to Chinese geneticists, but direct adoption of these standards and guidelines may not be practical due to the differences in disease-associated variant frequencies in Chinese population, socioeconomic status, and medical practice between the two countries. It is hoped that this review could facilitate the development of NGS and NIPS standards and guidelines that are consistent with international standards and concordant with medical genetics practice in China to provide high-quality, efficient and safe clinical services for patients and their families with genetic diseases.
China ; Consensus ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Pregnancy ; Technology ; United States

OBJECTIVE：To provide reference for clinical empirical treatme nt of non-fermentative Gram-negative bacilli （NFGNB）infection. METHODS ：All kinds of clinical specimens were collected from Jan. 2010 to Dec. 2019 in a tertiary hospital from Hanzhong city of Shaanxi province ；the distribution and drug resistance of NFGNB were analyzed retrospectively. RESULTS ： A total of 26 386 strains of pathogenic bacteria were detected in the hospital during 2010-2019，including 4 077 strains of NFGNB （15.45％），mainly from patients ≥60 years old （1 836 strains，45.05％）. During the 10 years，the detection rate of NFGNB decreased from 20.14％ in 2010 to 15.36％ in 2019 （P＜0.001）. Acinetobacter baumannii （1 359 strains），Pseudomonas aeruginosa （1 269 strains），Stenotrophomonas maltophilia （447 strains） and Burkholderia cepacia （351 strains） were main pathogens. The detected NFGNB mainly came from hospitalized patients （4 001 strains），and most of them were found in ICU （17.05％），neurosurgery department （14.52％），respiratory department （12.41％），and respiratory tract （66.69％），secretion （7.80％）specimens. The detection rates of A. baumannii and P. aeruginosa in oncology department ，blood specimens and urine specimens showed an overall upward trend ，while the detection rates in ICU of the hospital showed a downward trend （P＜0.05）； the detection rate of P. aeruginosa in neurosurgery department showed an upward trend （P＜0.05），and that of A. baumannii in respiratory department showed an upward trend （P＜0.05）. The resistance rate of A. baumannii to carbapenems increased from about 10％ in 2010 to about 75％ in 2019，and the guyh3201@163.com resistance rate to cephalosporins exceeded 78％. The resistance rates of P. aeruginosa to imipenem and me ropenem were lower than 35％ and 30％ respectively，and the trend of drug resistance did not change significantly （P＞0.05）；the resistance rates to 12 kinds of clinically commonly used antibiotics as piperacillin and aztreonam were lower than 40％. The resistance rate of S. maltophilia to compound sulfamethoxazole showed a decreasing trend （P＜0.001），and the resistance rate to ceftazidime was high （54.70％-74.10％）. The resistance rates of B. cepacia to compound sulfamethoxazole，meropenem and ceftazidime showed a downward trend （P＜0.01），and were lower than 15％ after 2014. CONCLUSIONS：Although the detection rate of NFGNB in our hospital showed a downward trend ，the multi-drug resistance and pan-drug resistance of A. baumannii are serious ，and the resistance rate to carbapenems is increased. Sensitive drugs such as cefoperazone/sulbactam，amikacin，levofloxacin and ceftazidime should be selected for NFGNB infection according to the results of drug sensitivity tests.