OBJECTIVEWiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and an increased incidence of autoimmunity and malignancies. The patients always have a severe clinical phenotype that can result in death if not diagnosed and treated early in life. The treatment of choice with the best outcome is hematopoietic stem cell transplantation, preferably from a matched related donor. But uncertain treatment effect and high treatment cost limit its clinical application. It is the best strategy that avoiding birth of a fetus with defect through prenatal diagnosis at present. This study aimed to analyze the mutation of WASP gene in 4 Chinese families with WAS and to provide prenatal diagnosis for the high-risk fetus.

METHODThe probands of the four WAS families were all males, one of whom was deceased but had a family history and clinical datas integrated. All the patients were detected with blood routine tests, immunological tests and bone marrow examination. PCR and bilateral direct sequencing of PCR product was carried out in the regions of exon and exon-intron boundaries of WASP gene for 3 probands, 4 mothers and 100 unrelated healthy individuals as control. Prenatal diagnosis was provided for the two fetuses at the first trimester by mutation analysis.

RESULTFour WASP gene mutations were detected: c.91A > G (p.E31K), c.665C > T (p.R211X), c.397G > A (p.E133K), c.952-953delCC (p. P317fsX18), among which c.952-953delCC (p. P317fsX18) was first reported. Mothers in Family 2, 3 and 4 were carriers of WASP gene mutation, but family 1 was considered as a de-novo mutation. None of the 100 unaffected subjects had the above mutants. Prenatal diagnosis indicated that the fetus in family 2 was male and carried the same mutation as the proband, so the fetus was presumably to be a patient. The parents decided to receive an induced abortion. Following the termination of the pregnancy, the result of gene analysis of the aborted tissues was consistent with prenatal diagnosis. The fetus in family 3 was normal male confirmed by normal test results six months after birth.

CONCLUSIONThe 4 mutations of the WASP gene probably were causative to the families of WAS, among which c.952-953delCC was reported for the first time. Prenatal diagnosis by DNA sequencing is the effective method to avoid birth of WAS patient.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Fetal Diseases ; diagnosis ; Heterozygote ; Humans ; Male ; Mutation ; genetics ; Polymerase Chain Reaction ; Pregnancy ; Prenatal Diagnosis ; Sequence Analysis, DNA ; Wiskott-Aldrich Syndrome ; diagnosis ; genetics ; Wiskott-Aldrich Syndrome Protein ; genetics ; X-Linked Combined Immunodeficiency Diseases

Objective: To explore the effect of PDCA nursing model combined with token reward on the compliance and negative emotions of children with hypospadias. Methods: A total of 120 children with hypospadias who were admitted to Children′s hospital affiliated to Zhengzhou University from February 2017 to December 2017 were selected as study subjects. According to the time of admission, they were divided into observation group and control group, with 60 cases in each group. The control group was given routine nursing care, the observation group was given PDCA nursing mode combined with token rewards intervention on the basis of routine care. The self-made children's behavioral compliance assessment table was used to compare the compliance of the two groups of children. Achenbach Child Behavior Check List (CBCL) scores were performed before and after the intervention. The hospitalization time and the incidence of complications were calculated. Results: There was no significant difference in CBCL scores between the two groups at admission (t=0.965, P=0.102). The scores of compliance and CBCL scores of the observation group were (43.12±3.99) points and (17.62±7.30) points respectively, the scores of control group were (30.67±4.53), (24.23±6.67), the difference was statistically significant (t=15.977, 5.184, P<0.01). The hospitalization time and complication rate of the observation group were (18.73±0.84)d, 15.00% (9/60), which were significantly lower than (20.92±1.90) d, 31.67% (19/60) of the control group, and the difference was statistically significant (t=8.166, χ²=4.658, P<0.01 or 0.05). Conclusions The PDCA nursing model combined with token reward can improve the compliance of children with hypospadias and improve their negative emotions.

Cervical cancer is the fourth most common cancer among women worldwide,and several screen-ing methods are currently available,with DNA testing for human papillomavirus(HPV)considered to be the most effective technique compared to other screening methods.However,due to the lack of organized screen-ing programs and facilities in developing countries,effective screening of cervical cancer is difficult to imple-ment,thereby delaying disease prediction and contributing to the high incidence of cervical cancer.In order to improve cervical cancer screening coverage in women,a simple,time-saving and non-invasive screening method is needed.At present,more and more evidence supports the validity and practicability of self-sampling as an al-ternative method for primary HPV screening.In this paper,we reviewed the application progress of HPV self-sampling in cervical cancer screening from three aspects:vaginal self-collection,initial urine sample self-collec-tion and menstrual blood sample self-collection.

The secretion of melatonin (MT) is obviously different in the younger and the senior sectors of the population, and the maximum plasma concentration of seniors is only half of that in the younger population group. If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system (DDS), an improved therapeutic effect and reduced side effects can be expected. Based upon this hypothesis, the pharmacokinetic parameters of MT, namely, the absorption rate constant (k a), the elimination rate constant (k e), and the ratio of absorption rate (F) to the apparent volume of distribution (V) were obtained by a residual method depending on the plasma concentration curve of immediate release preparations in the healthy younger population. The dose-division method was applied to calculate the cumulative release profiles of MT achieved by oral administration of a controlled release drug delivery system (DDS) to generate plasma MT profiles similar to the physiological level-time profiles. The in vivo release of MT deduced from the healthy younger population physiological MT profiles as the pharmacokinetic output of the bio-mimetic DDS showed a two-phase profile with two different zero order release rates, namely, 4.919 μg/h during 0-4 h (r=0.9992), and 11.097 μg/h during 4-12 h (r=0.9886), respectively. Since the osmotic pump type of DDS generally exhibits a good correlation between in vivo and in vitro release behaviors, an osmotic pump controlled delivery system was designed in combination with dry coating technology targeting on the cumulative release characteristics to mimic the physiological MT profiles in the healthy younger population. The high similarity between the experimental drug release profiles and the theoretical profiles (similarity factor f 2>50) and the high correlation between the predicted plasma concentration profiles and the theoretical plasma concentration profiles (r=0.9366, 0.9163, 0.9264) indicated that a prototype bio-mimetic drug delivery system of MT was established. The similarity factors between the experimental drug release profiles and the theoretical release profile were all larger than 50 both in periods of 0-4 h and 4-12 h, namely, 68.8 and 57.3 for the first batch (Batch No. 20131031), 76.7 and 50.2 for the second batch (Batch No. 20131101), and 73.7 and 51.1 for the third batch (Batch No. 20131126), respectively. The correlation coefficients between the predicted plasma concentration profiles based on the release profiles of the bio-mimetic DDS and physiological profiles were 0.9366 (Batch No. 20131031), 0.9163 (Batch No. 20131101), 0.9264 (Batch No. 20131126), respectively. Since the pharmacokinetic profile of MT in any kind of animal differs markedly from that of human beings, it is impossible to test the bio-mimetic DDS in animals directly. Therefore, the predicted pharmacokinetic profile based upon the in vitro release kinetics is an acceptable surrogate for the conventional animal test. In this research, a bio-mimetic DDS for replacement of MT was designed with in silico evaluation.