Objective To analyze the functional alteration of natural killer (NK) cells from patients with macrophage activation syndrome (MAS) in active phase and after treatment.Methods Peripheral blood samples were collected from 12 healthy subjects,12 patients with systemic onset juvenile rheumatoid arthritis (SoJIA) but without an episode of MAS and 12 patients with MAS.Flow cytometry analysis was performed to detect NK cells and their expression of perforin,granzyme B,interferon (IFN)-γand tumour necrosis factor (TNF)-α.The cytotoxicity of NK cells to K562 cell was also analyzed.All of the patients with MAS were diagnozed by clinical features and the pathologic examination of hemophagocytosis in bone marrow.The function of NK cells were analyzed before any treatment and on the fifth day as well as in third month after treatment with glucocorticoid,intravenous immunoglobulin and/or cyclosporin A.Results Compared with healthy subjects and patients with SoJIA,patients with MAS had lower NK cell counts,reduced cytotoxicity and decreased expression of perforin and granzyme B before or on the fifth day after treatment (P＜0.05).However,increased production of IFN-γ and TNF-α by NK cells were observed (P＜ 0.05).In the third month after treatment,the cytotoxicity of NK cells and the expression of perforin and granzyme B in patients with MAS were lower than those in healthy subjects and patients with SoJIA (P＜ 0.05),but no statistically significant differences with NK cell counts and production of IFN-γand TNF-α were observed beween the patients with MAS and healthy subjects (P＞0.05).Conclusion NK cells from patients with active MAS were characterized by reduced cytotoxicity and enhanced production of IFN-γ and TNF-α.Upon medical treatment,the number of NK cells in patients with MAS were up-regulated and their production of IFN-γand TNF-α were down-regulated.However,the cytotoxicity of NK cells and the expression of perforin and granzyme B were not affected.Reduced cytotoxicity and decreased production of perforin and granzyme B with NK cells might be the durative features for the patients with MAS.

The clinical thoughts of interns have some features such as insufficiency of initiative and enthusiasm and the absence of systemic. It is necessary to develop their good habits of active and diligent thinking as well as comprehensive thinking ability. Clinical teaching rounds, small lectures,discussion of complicated cases and interactive teaching are the specific measures for our medical interns to improve their ability of clinical thoughts effectifally.

Objective To discuss the role of teachers in the integrated PBL teaching of pediatrics in the light of the investigation of students after PBL teaching.Method The multidisciplinary integrated PBL course established by the Department of Pediatrics of Chongqing Medical University has been implemented for more than two years in the teaching of the five year program in the Department of clinical medicine (pediatric direction).From September 28,2016 to October 25th,the researchers conducted a survey of 26 undergraduate students in the college who received PBL teaching at the professional probation stage.After the end of each PBL class,the teaching evaluation questionnaire recommended by Fudan University and Qian Ruizhe was distributed through the network teaching platform of Chongqing Medical University.The questionnaire was retrieved by students without a name,and the survey was carried out 3 times.The data of the questionnaire were summarized with Excel 2007.Result 77 questionnaires were issued and 77 were recovered,with a recovery rate of 100％.In the multidisciplinary integrated PBL class,94.8％-97.4％ students gave high score evaluation,and all the evaluation of teachers reached "excellent" level.In response to open-ended questions,students believed that teachers in teaching could inspire students to think positively,encourage students to express different views,create a mutually trusted environment for students,and cultivate students' interpersonal communication,communication and cooperation ability.Conclusion In pediatric multidisciplinary integrated PBL teaching,teachers should teach students correct learning methods,judge each student's knowledge and thinking level,and individualize teaching for each student's problems and characteristics.

Objective:To summarize the clinical and genetic features of children with intellectual developmental disorder with seizures and language delay (IDDSELD) due to 12q24.31 deletion and SETD1B locus variants. Methods:The clinical data of a child with 12q24.31 deletion diagnosed in the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in September 2022 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) and copy number variations sequencing (CNV-seq) were used for genetic analysis. The relevant literatures were reviewed to summarize the clinical features of the disease.Results:The proband was a 7 years and 9 month old girl who had clinical features of global developmental delay, epilepsy, hyperactivity, hypertonia, gait disorder, special facial features (high eyebrow arch, big ears, upper lip protrusion), funnel chest, lumbar lordosis. Karyotypic analysis showed 46XX in the proband. CNV-seq showed 12q24.31 (chr12: 121895654-122449092) position had a deletion of about 553.44 kb which contained the SETD1B gene. Trio-WES showed deletion of all exons 1-16 of the SETD1B gene. CNV-seq results of her parents were normal: the SETD1B gene was wild-type. This type has not been reported in China. Four children with IDDSELD caused by 12q24.31 deletion (including the SETD1B gene) were retrieved (totally 5 cases including this case), with male to female ratio of 1∶4, all with de novo mutations, and all with mental retardation, cephalo-facial and skeletal malformations. Three cases had seizures, 2 cases still had developmental backwardness after treatment, and 1 case was seizure controlled. Forty-seven cases of IDDSELD due to point mutation in the SETD1B gene were retrieved: male to female ratio was 31∶16, missense mutations (38/47) were predominant, most were de novo mutations (36/47), and a few were inherited from their fathers/mothers (6/47) or of unknown origin (5/47), with clinical manifestations of speech delay (43/47), growth retardation (43/47), intellectual disability (37/41), behavioral problems (37/47), facial malformations (34/47), skeletal malformations (23/47), obesity (16/47), skin abnormalities (11/47), etc. Thirty-nine cases were combined with seizures, 23 of whom were under control after treatment, and 8 cases were recorded as still having developmental backwardness after treatment. Conclusions:IDDSELD patients are rare at home and abroad, with diverse clinical phenotypes and difficult diagnosis. Symptomatic treatment is the main approach. And the patients can leave behind seizures and varying degrees of developmental backwardness. Among them, patients with 12q24.31 deletion are relatively rare and have not been reported in China, and this type is more common in females, all of whom have de novo mutations, and genetic testing is helpful for the early diagnosis of IDDSELD.