Autism spectrum disorder（ASD）is a heterogeneous group of neurodevelopmental disorders.The prevalence of ASD increases year by year.Sleep disorder is the common comorbidity of ASD.The pathogenesis is still unknown.The imbalance of excitation / inhibition（E/I）and neuroplasticity changes are the possible pathogenesis of ASD.Early childhood sleep is an important factor affecting E/I balance and neuroplasticity.ASD and sleep disorder may share common pathogenesis.Various genetic variants（such as Shank3，SynGAP，et al）and related chromosomal disease（such as 16p11.2 deletion）and their associated syndromes such as Rett syndrome，Smith-Magenis syndrome，and Angelman syndrome，ect，all manifest both ASD and sleep disorder phenotypes.In addition，melatonin，oxytocin，hypothalamic hormone，serotonin，etc，may participate in the neural pathways of sleep disorder，ASD pathology and neuroplasticity，promoting the incidence of ASD and sleep disorder.Some treatments such as supplementing with melatonin，oxytocin，zinc，iron，and dietary supplements can improve the clinical symptoms of ASD while treating sleep disorder in children with ASD.This article reviews the mechanism of comorbid sleep disorder in children with ASD to improve clinical diagnosis and treatment.

Objective To explore the clinical curative effect of azithromycin combined with high-dose vitamin C (VC) in children with Mycoplasma pneumoniae pneumonia (MPP)and its influences on peripheral blood T lymphocyte subsets, serum interleukin (IL)-17, high-sensitivity C-reactive protein (hs-CRP), E2-associated factor 2 (Nrf2) in peripheral blood mononuclear cells and P1 proteins in throat swab. Methods A total of 240 children with MPP confirmed in the hospital were enrolled as observation objects between June 2020 and June 2023. They were randomly divided into high-dose VC group, low-dose VC group and control group, with 80 cases in each group. The control group was treated with azithromycin, low-dose VC group was treated with azithromycin plus low-dose VC, and high-dose VC group was treated with azithromycin plus high-dose VC, the three groups all treated for 2 weeks. The clinical curative effect and duration of clinical symptoms in the three groups were recorded. Before and after treatment, fasting venous blood and throat swabs were collected in the three groups. T lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺) in peripheral blood were detected by flow cytometry. The levels of serum IL-17, hs-CRP and VC were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of Nrf2 protein in peripheral blood mononuclear cells and P1 protein in throat swabs were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The adverse reactions during treatment in the three groups were recorded and compared. Results After treatment, time of fever, cough, expectoration and lung moist rale, and length of hospital stay were shorten in high-dose VC group and low-dose VC group when compared with those in the control group (P < 0.05), and were shorten in the high-dose VC group when compared with those in the low-dose VC group (P < 0.05). After treatment, levels of peripheral blood T lymphocyte subsets (CD3⁺, CD4⁺, CD4⁺/CD8⁺) were increased when compared with those before treatment in the three groups (P < 0.05). The levels of CD3⁺, CD4⁺ and CD4⁺/CD8⁺ in the high-dose VC group were higher than those in the low-dose VC group and control group (P < 0.05), and CD4⁺ level in the low-dose VC group was higher than that in the control group (P < 0.05). After treatment, levels of serum IL-17 and hs-CRP were decreased as compared with those before treatment in the three groups (P < 0.05). The levels of serum IL-17 and hs-CRP in the high-dose VC group were lower than those in the low-dose VC and control group, but there was no difference between low-dose VC group and control group (P>0.05). After treatment, levels of serum VC were increased as compared with that before treatment in high-dose VC group and low-dose VC group, and it was higher in the high-dose VC group than low-dose VC group (P < 0.05). There were no differences in IL-17 and hs-CRP between low-dose VC group and control group (P>0.05). After treatment, mRNA levels of Nrf2 protein in peripheral blood mononuclear cells and P1 protein in throat swabs were decreased compared with those before treatment in the three groups (P < 0.05). The expression level of Nrf2 mRNA in the high-dose VC group was higher than that in the low-dose VC group and control group (P < 0.05), but there was no significant difference in mRNA expression of PI protein among the three groups (P>0.05). There were no obvious adverse reactions in any group during treatment. Conclusion Azithromycin combined with high-dose VC can effectively improve clinical symptoms, enhance immunity, reduce IL-17 and hs-CRP levels, maintain Nrf2 mRNA level and improve clinical curative effect in MPP children, and has higher safety.

Objective:To screen the differentially expressed exosomal miRNAs derived from liver cancer stem cells (LCSCs) and its effect on the malignant biological characteristics of liver cancer cells.Methods:miRNA expression profile chip was used to analyze the differentially expressed exosomal miRNA derived from LCSCs. The effects of miRNA on malignant phenotypes of LCSCs were identified. The cells were further treated with doxorubicin at different concentrations (0, 150, 300 μmol/L), and the expression level of miR-196a was detected by quantitative real-time PCR (qRT-PCR). The apoptosis of liver cancer cells cultured by exosomes derived from LCSCs (Exo-NC group) and exosomes derived from miR-196a inhibited LCSCs (Exo-Inhibitor group) and the activity of caspase3/7 under the action of exosomes from LCSCs were detected. Nude mice were randomly divided into Do-PBS group, Do-Exo-Inhibitor group and Do-Exo-NC group using random number table method, with 5 mice in each group, and the effect of miR-196a on nude mice xenograft tumor model with liver cancer cells was analyzed.Results:In this study, exosomes were isolated and purified from CD133 + Huh7 stem cell culture supernatant. miR-7162-3p, miR-1910-5, miR-3613-3p, miR-196a and miR-155-5p were up-regulated, while miR-1246 and miR-3613-5p were down-regulated. miR-7162-3p, miR-196a and miR-155-5p in exosomes had important effects on the self-renewal ability of LCSCs. miR-1910-5p, miR-196a and miR-155-5p had important effects on the invasion ability of liver cancer stem cells, among which miR-196a had the most significant inhibitory effect. Treatment for 24 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin was 0.96±0.05, 1.23±0.05 and 2.33±0.03 respectively, with a statistically significant difference ( F=996.90, P<0.001). Treatment for 48 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin were 1.02±0.07, 2.35±0.05 and 2.89±0.55 respectively, with a statistically significant difference ( F=303.00, P<0.001). When the concentration of doxorubicin was 0 and 300 μmol/L, the apoptosis rates of the Exo-NC group were 9.37%±0.19% and 11.64%±0.27%, and those of the Exo-Inhibitor group were were 18.80%±1.91% and 22.79%±1.57%, with statistically significant differences ( t=4.41, P=0.048; t=4.96, P=0.038). When doxorubicin was not used, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.94±0.08 and 0.97±0.09, and those in the Exo-Inhibitor group were 1.56±0.01 and 1.58±0.01, with statistically significant differences ( t=11.41, P=0.008; t=6.07, P=0.026). Under 300 μmol/L doxorubicin, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.95±0.07 and 1.36±0.08, and those in the Exo-Inhibitor group were 2.84±0.08 and 3.20±0.14, with statistically significant differences ( t=24.20, P=0.002; t=15.78, P=0.004). The results of xenograft tumor in nude mice showed that the tumor volumes of Do-PBS, Do-Exo-Inhibitor and Do-Exo-NC groups increased successively, which were (1 051.86±89.90) mm 3, (1 310.91±86.66) mm 3 and (2 185.14± 352.34) mm 3 respectively, with a statistically significant difference ( F=30.28, P<0.001). The weights of the transplanted tumors in the 3 groups increased successively, which were (0.36±0.10) g, (0.39±0.12) g and (0.76±0.16) g respectively, with a statistically significant difference ( F=11.81, P=0.002). The expression of miR-196a in tumors was significantly decreased after miR-196a inhibitor transfection. The expression levels of the 3 groups were 1.05±0.16, 0.38±0.08 and 2.17±0.26, with a statistically significant difference ( F=48.93, P<0.001). Conclusion:The exosomal secreted by LCSCs can enhance the resistance of liver cancer cells to doxorubicin by miR-196a.

Objective To explore the effects of stage-based nursing on preventing prosthesis dislocation after artificial hip replacement.Methods By sampling, we selected 56 patients with artificial hip replacement of Shandong Provincial Hospital, the Affiliated Hospital of Shandong University, from July 2014 to July 2015 in control group with routine nursing; and we selected 56 patients with artificial hip replacement from August 2015 to August 2016 in observation group with comprehensive and targeted holistic nursing by postoperative stage-based nursing based on routine nursing. The activities of living, extremity motor function, incidence of prosthesis dislocation and recovery of hip joint of patients between two groups before and six months after surgery.Results Before surgery, there was no statistical difference in the scores of activities of living and extremity motor function of patients between two groups (t=0.233, -0.791;P>0.05). Six months after surgery, the scores of activities of living and extremity motor function all increased in observation group with statistical differences compared with those in control group (t=2.388, 2.142;P<0.05). The rate of prosthesis dislocation and the score of Harris hip score was 1.79％ and (76.89±12.30) in observation group with statistical differences compared with those in control group (P<0.05).Conclusions Postoperative stage-based nursing can improve patients' activities of living and extremity motor function, and reduce the rate of prosthesis dislocation and effective improve hip joint after artificial hip replacement.

Objective To compare the efficacy and safety of humidified high-flow nasal cannula (HHFNC)and nasal continuous positive airway pressure (nCPAP) for moderate and severe bronchiolitis treatment in infants.Methods Thirty-two infants who were diagnosed as moderate and severe bronchiolitis admitted to Department of Pediatric Critical Care Medicine,the Affiliated Hospital of Qingdao University from September 2016 to May 2017 were selected,and they were randomly assigned into HHFNC group(17 cases) and nCPAP group(15 cases).The heart rate,breathing,oxygen saturation (SpO2),arterial partial pressure of oxygen [Pa (O2)],partial pressure of carbon dioxide [Pa (CO2)],pH value after treatment for 12 h,the duration of non-invasive ventilation and the incidence rates of invasive ventilation use,complications were compared between the 2 groups.Results After the treatment for 12 h,in HHFNC group,the heart rate was (130.88 ± 2.87) times/min,respiratory rate was (37.35 ± 3.55) times/min,SpO2 was(97.06 ± 1.43)％,pa(O2) was (99.65-±8.07) mmHg,pa(CO2) was (35.88 ±4.27) mmHg,pH was 7.42 ± 0.03;while in the nCPAP group,the heart rate was (135.73 ± 6.29) times/min,respiratory rate was (41.40 ± 4.40)times/min,SpO2 was (96.00 ± 1.13) ％,Pa (O2) was (91.33 ± 9.45) mmHg,pa (CO2) was (40.13 ± 3.72)mmHg,pH was 7.39 ± 0.03.The breathing,heart rate,oxygen saturation and arterial blood gas in both groups after treatment were improved significantly compared with those before treament,and the differences were statistically significant (all P ＜ 0.05);after treatment for 12 h,the heart rate,breathing,oxygen saturation and arterial blood gas of HHFNC group were improved more than those of the nCPAP group,and the differences had statistical significance (all P ＜ 0.05).The duration of non-invasive ventilation was (45.88-± 6.49) hours in HHFNC group,and (49.33 ± 8.99) hours in nCPAP group,so there was no difference between the 2 groups (t =1.254,P =0.219).There was 12 cases (80.0％) of mild complication in nCPAP group and 5 cases(29.4％) in HHFNC group,while the incidence rate of invasive ventilation use was 3 cases(20.0％) in nCPAP group and 1 case (5.9％) in HHFNC group.Conclusion The efficacy and security of HHFNC on moderate and severe bronchiolitis are better than those of nCPAP,and it is recommended for clinical application widely.

Objective To analyze the cognition, utilization and satisfaction on pregnancy health management of basic public health services. and to find out potential problems and provide suggestions for promoting equality in rural basic public health. The Weishan Lake area was selected as the sample point and the left behind pregnant women in the countryside as control. Methods In the period from May 2016 to July, questionnaires were designed for the pregnancy health management of basic public health services, 330 left-behind pregnant women and 300 rural immigrating pregnant women were selected as our target interviewees. The average age of rural immigrating pregnant women and the left-behind pregnant women was (28.6 ± 3.7) years, and (28.3 ± 3.4) years old, respectively; the degree of education of rural immigrating pregnant women and the left-behind pregnant women was secondary specialized school or high school and junior middle school, respectively. The occupation of rural immigrating pregnant women was mainly workers;accounting for 31.4%, while the occupation of the left-behind pregnant women was farming, accounting for 36.7%. Results The awareness rate ofgeneral pregnancy examination and gynecological examinationin health management items of rural immigrating pregnant women and left-behind pregnant women was the highest, which were 77.7% and 78.3%, respectively, and the lowest awareness rate of the 2 prenatal follow-up was the lowest in the third trimester, which was 22.6% and 23.0%, respectively. The difference was not statistically significant. The maternal health management service understanding rate of rural immigrating pregnant women and left-behind pregnant women were 24.7% and 17.9% respectively , the difference was statistically significant (Z=-1.993, P=0.046);the awareness rate of delivery and breastfeeding in late pregnancy were 36.2% and 47.6% respectively, and the difference was statistically significant (χ2=7.933, P=0.005). The rate of the registering of the maternal health care handbook of rural immigrating pregnant women and left-behind pregnant women were 40.4%and 54%respectively, and the difference was statistically significant (χ2=11.065, P=0.001), Among them, the rate of registering in township hospitals was 46.6% and 73.3% respectively, and the difference was statistically significant (χ2=21.104, P=0.0000); the utilization rate of 3 or more antepartum examination and follow-up services was 8.4%and 23%respectively, and the difference was statistically significant (χ2=23.878, P=0.000). The growth and development of the health of pregnant women and fetal assessment and utilization rates were 9.8% and 23.6%, the difference was statistically significant (χ2=20.460, P=0.000); prenatal guidance (childbirth preparation, breastfeeding) utilization rate were 8%, 13.7%, the difference was statistically significant (χ2=5.011, P=0.027);abnormal or critical maternal referral utilization rate were 22%and 34.8%, the difference was statistically significant (χ2=12.133, P=0.001). Conclusion Imbalance exists in acquiring basic public health services of the two pregnant women cohort, the left-behind pregnant women are better than the rural immigrating pregnant women. Therefore, the government should propagate this service by multi-channel to improve their cognition and utilization of this policy implemented, and to promote the development of the services.

Objective To explore the clinical features and treatment strategy of severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children. Methods The clinical data and follow-up information of 4 children with severe anti-NMDAR encephalitis were retrospectively analyzed. Results Four patients (one male and 3 females) were 10 to 13 years old and one child had teratoma combined. In all patients symptoms at onset mainly were psychiatric syndrome and movement disorder, and then progressed to seizures, disturbance of consciousness and central hypoventilation respiratory failure in one month. The anti-NMDAR antibodies in cerebrospinal fluid were positive in all patients. The EEG showed focal or diffuse slow waves. The brain MRI showed no pathological changes at the diagnosis. The treatment included methylprednisolone and large doses of intravenous immunoglobulin (IVIG), ventilator for 5-95 days, and tracheotomy in 2 cases. One case died because of serious infection. In 21-27 months of the follow-up, one case had clinical recovery; 2 cases had the sustained use of immunosuppressive agents and anti-epileptic drugs and the clinical symptoms were significantly improved. The EEG and anti-NMDAR antibodies continued abnormal in the patient combined with teratoma. One patient relapsed. Conclusions The severe anti-NMDAR is more likely in older female children. The central hypoventilation respiratory failure occurs in the early course of the disease. Combination with tumor is high risk factor. Conventional hormone therapy and ventilator treatment is effective. The recovery is slow. It may be relapsed even one year later.

Objective To investigate the feasibility of low-tube-voltage in combination with the three-dimensional adaptive iterative dose reduction (AIDR-3D) algorithm in performing lower extremity computed tomography angiography (CTA).Methods A total of 60 patients suspicious of lower extremity arterial occlusion were randomized into control group (120 kV,a =30) and experimental group (100 kV,n =30).The CTA was undertaken with a 320-row scanner (Toshiba Aquilion ONE),and the images was reconstructed with filtered back projection (FBP) algorithm in control group and FBP as well as the AIDR-3D algorithm in experimental group.The subjective image quality,vascular density (VD),noise,signal-to-noise ratio (SNR),contrast-to-noise ratio (CNR),and dose length product (DLP) were compared between two groups.Results The DLP was significantly lower in experimental group than that in control group [(503.5± 104.7) vs.(1 099.4 ± 151.7) mGy·cm,t =15.7,P ＜0.05].The images in experimental group with 100 kV and FBP protocol had significantly increased VD and noise (t =-3.13,-3.61,P ＜ 0.05) than that in the control.The images in experimental group with AIDR-3D had significantly lower noise and higher SNR and CNR than that with FBP (t =13.59,2.14,P ＜ 0.05),also significantly lower noise and significantly higher VD,SNR,and CNR than that in the control (t =-3.75,-4.19,-4.15,P ＜ 0.05).Conclusions Low-tube-voltage (100 kV) combined with AIDR-3D reconstruction could significantly improve the image quality and reduce radiation dose in lower extremity CTA with a 320-row CT scanner.Trial registration Chinese clinical trial registry,ChiCTR-DPD-16008054.

Objective To analyze the miss rates of colorectal adenomas during colonoscopy as well as risk factors influencing the adenoma miss rates and to take corresponding measures. Methods A total of 432 patients who underwent index and follow-up colonoscopy in 18 months were randomized and investigated. The results of two colonoscopies were compared and the missed adenomas were defined as the adenomas de-tected only during the second colonoscopy. Miss rates were calculated according to patient-based methods. Chi-square test was used to analyze the relative factors influencing the adenoma miss rate of per-patient. Then the meaningful factors were chosen into the logistic regression model for multiple factors analysis. Results Of 432 patients,116(26. 9%)had missed adenomas on first colonoscopy. Single factor analysis found that the size of adenoma( χ2 = 89. 686,P = 0. 000),the shape of adenoma( χ2 = 68. 488,P = 0. 000),the location of adenoma(χ2 = 77. 055,P = 0. 000)and adenoma tissue types(χ2 = 417. 000,P = 0. 000)were the risk factors for miss rates of colorectal adenomas. Number of polyps(χ2 = 8. 450,P= 0. 038),the organi-zation type of polyp(χ2 = 10. 718,P= 0. 013)and proficiency of colonoscopists(χ2 = 56. 069,P= 0. 000), the quality of bowel preparation(χ2 = 39. 195,P = 0. 000),insertion time(χ2 = 13. 133,P = 0. 001)were also the risk factors for miss rates of colorectal adenomas. Logistic regression analysis showed that the bigger the adenoma size,the less missed adenomas(OR= 0. 341,95%CI:0. 173-0. 671). Also,the longer insertion time took,the lower the adenoma miss rate(OR = 0. 987,95% CI:0. 981-0. 994). Per-patient miss rates were lower for high-risk adenomas compared with low-risk adenomas(OR = 0. 324,95%CI:0. 154-0. 680). Adenomas happening in multiple parts of bowel easily leads to missing(OR= 3. 791,95%CI:1. 505-9. 546). Conclusion The missed diagnosis of adenomas is not only significantly associated with features of missed adenomas,but also with skills of colonoscopists,insertion time,and bowel preparation. The key is high-quality index colonoscopy to avoid adenomas missing.

Objective:To detect the expression of microRNA-218 (miR-218) in human acute lymphocyte leukemia (ALL) T lymphocytes ( CCRF-CEM) ,explore its effects on the biological features of CCRF-CEM cells and the expression of its target gene c-kit, so as to provide new insights for leukemia treatment.Methods: Using the quantitative real-time polymerase chain reaction ( qRT-PCR) ,we detected the expression of miR-218 in the normal peripheral blood T lymphocytes and CCRF-CEM cells.Forty-eight hours after the miR-218 mimic was transfected into the CCRF-CEM cells,the expression of miR-218 in the CCRF-CEM cells was detected by qRT-PCR.The effect of miR-218 on the CCRF-CEM cell viability was detected using MTT.The effect of miR-218 on the proliferation and apoptosis of CCRF-CEM cell was analyzed using flow cytometry.c-kit gene was identified to be a target gene of miR-218 by luciferase reporter enzyme system,and the effect of miR-218 on the expression of KIT protein in cells were determined using Western blot.Results:As shown by qRT-PCR,compared with that in the normal peripheral blood T lymphocytes,the expressions of miR-218 in ALL T lymphocytes cell lines were significantly decreased ( P<0.01 ) .Compared with the control group, the expression of miR-218 increase significantly in CCRF-CEM cells transfected with miR-218 mimic for 48 hours ( P<0.01).MTT showed that the cell viability decreased significantly after the over-expression of miR-218 in the CCRF-CEM cells ( P<0.05 ) .Flow cytometry showed that the S-phase fraction significantly declined after the over-expression of miR-218 ( P<0.01 ) , and meanwhile the apoptosis of cells also significantly increased (P<0.01).Luciferase reporter gene assay showed that,compared with the control group,the relative luciferase activity significantly declined in the miR-218 mimic transfection group (P<0.01).Compared with the control group,the expression of KIT protein in the CCRF-CEM cells transfected with miR-218 mimic for 48 hours significantly decreased ( P<0.01).Conclusion:The expression of miR-218 decreases in ALL T lymphocytes cell lines.MiR-218 can negatively regulate the expression of KIT protein,inhibit the proliferation and increase the apoptosis of CCRF-CEM cells.Treatment based on the enhanced expression of miR-218 may be a promising strategy for leukemia.