T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Objective:To investigate the prevalence of autism spectrum disorders (ASD)among children in kindergartens in Xi′an urban districts.Methods:A stratified cluster sampling method was adopted, and selected all children from 12 kindergartens in 6 urban districts of Xi′an.Primary screening positive children with ASD were identified by filling out the Autism Behavior Checklist (ABC) by their parents and the guardians reports, and then the beha-vioral observations were made to identify suspicious ASD children.Finally these children were diagnosed in the hospital through the autism diagnostic observation schedule, 2 nd edition (ADOS-2). The data were calculated with SPSS 18.0. Results:Totally, 38 cases with ASD were diagnosed among 5 178 children, the prevalence of children ASD in kindergartens in Xi′an urban districts was 7.3‰, and the 95% confidence interval was 4.98‰-9.62‰.The prevalence of ASD in children was statistically significant in different age groups ( χ2=9.914, P<0.05) and gender groups ( χ2=18.812, P<0.05). The accuracy of ASD screening by guardians reports is better than that by ABC. Conclusions:(1)The prevalence of ASD children in kindergartens in Xi′an urban districts is at high level in similar reports in China.If ASD children at the special education institutions and home are considered, the overall prevalence rate is higher, indicating that the prevalence of ASD children in China may be underestimated.(2)With the increase of age, the attendance rate of ASD children in kindergartens has a decreasing trend.

Objective:To investigate the clinical features of ocular involvement and the application of Rose criteria in patients with relapsing polychondritis (RP).Methods:The data from RP patients with ocular involvement were collected and analyzed. Patients included must have at least one major criteria of Michet criteria and the application Rose criteria was also investigated. Demographic data of these patients was presented as percentages. The difference between types of disease onset was tested by Mann-Whitney U and comparison among groups was tested by False Discovery Rate. Results:A total of 192 patients were enrolled 98 males and 94 females. The mean age of disease onset was (42±14) (0.5-79) years old, the median disease duration (DD) was 13(0.5, 600) months. The median RP disease activity index (RPDAI) was 39(9-74) and the median RP organ damage index (RPODI) was 2.5(0.1, 108). The median RP damage index (RPDAM) was 3(1-6). The statistical significant difference was identified in median DD between groups of nose and pinna ( Z=10.775, P<0.01), nose and OEH ( Z=9.277, P<0.01), in RPODI between groups of nose and pinna ( Z=7.999, P=0.031), nose and and extra-cranial organs ( Z=8.115, P=0.030) and eye and airway involvement of RPDAM could be seen between groups ( Z=7.683, P=0.037) respectively. Ocular involvement(50.0%), auricular chondritis(21.4%) and airway chondritis(13.5%) were the top three most common symptoms at disease onset. The ocular involvement(100%), airway chondritis (75.0%) and inner ear involvement(69.3%) were the top three most frequent affected organs. All parts of eye could be involved in RP ocular damage. Single-organ involvement was 59.9%; and multi-organ involvement could be seen in 40.1% patients. Diagnostic strength was enhanced by application of Rose criteria in 171 cases fulfilled Michet criteria and 21(10.9%) cases partially fulfilled Michet criteria fulfilled Rose criteria. Active screening for organ (especially inner ear and airway) involvement would improve the rate of early diagnosis. The pinna and airway involvement suggested nose and middle-ear might be involved. Conclusion:Ocular involvement in RP can involve all parts of the eye ball. Examining the inner ear and airway may help to confirm the diagnosis. It is worthy to apply this to clinical practice.

Objective:Lung ultrasound (LUS) has been used in the diagnosis of neonatal respiratory distress syndrome(RDS) successfully, but there have been no multicenter prospective studies to verify its reliability or determine how to grade RDS with LUS findings.This study aimed to discuss the necessity and feasibility of using LUS findings to determine RDS grades through a multicenter prospective study.Methods:Every researcher participated in the National Neonatal Lung Ultrasound Training Course and receiving 3-6 months of lung ultrasound system training at the National Neonatal Lung Ultrasound Training Center.Patients between June 2018 and May 2020 who met the RDS ultrasound diagnostic criteria and had full available clinical data were included in this study.The LUS examination was completed immediately after the patients were admitted to the hospital.Some of them also underwent chest X-ray examination.Arterial blood gas analysis was completed immediately before or after the LUS ultrasound examination.RDS grading was performed according to the LUS findings and whether the patient had serious complications.Results:A total of 275 qualifying cases were included in this study, which included 220 premature infants and 55 full-term infants, and the primary RDS occurred in 117 cases (42.5%), and secondary RDS occurred in 158 cases (57.5%). LUS manifestations of RDS patients can be divided into three categories: (1)A ground-glass opacity sign: which could be found among 50 infants when they were admitted to the hospital (that was, at their first LUS examination). Twenty-eight of these infants were considered to have wet lungs and were not sent for special management on admission, but LUS showed typical snowflake-like lung consolidation within 0.5 to 4 hours.Twenty-two of them were given mechanical ventilation with exogenous pulmonary surfactant; Eighteen cases were controlled within 6-12 hours, but the lung lesions became more severe in the other 4 infants (due to severe intrauterine infection). (2)Snowflake-like lung consolidations: the first LUS on admission showed typical snowflake-like lung consolidation involving areas ranging from 1-2 intercostal spaces to 12 lung divisions in 204 cases.Thirty-eight infants among them the lung consolidation only had involvement of 1-2 intercostal spaces at the time of admission; Fifteen of them received invasive respiratory support and recovered within 4-12 hours.Twelve patients received noninvasive respiratory support; Seven of them recovered, while five cases developed severe lung illness.The remaining 11 patients who were not given any form of ventilator support developed severe conditions within 1-4 hours.Thirty of them showed snowflake signs involving 12 lung regions at admission.The remaining 136 patients had lung consolidation degree between the two degree above condition.(3)Snowflake-like sign with complications: Twenty-one patients had severe complications such as pneumothorax, pulmonary hemorrhage or/and persistent pulmonary hypertension of the newborn or large area atelectasis, etc, although snowflake lung consolidation did not involve all lung regions.Conclusion:(1) LUS is reliable and accurate for diagnosing RDS.RDS has the same characteristics on ultrasound for both preterm and full-term infants, both primary and secondary RDS.(2) To facilitate the management of RDS, it is necessary to classify RDS according to the ultrasound findings and the presence of severe complications.(3) Based on the results of this study, it is recommended that RDS can be divided into mild, moderate and severe degrees.The exact standards for grading are as follows: Mild RDS: the early stage of RDS, in which lung consolidation shows as a ground-glass opacity sign on ultrasound; Moderate RDS: lung consolidation shows a snowflake sign on ultrasound, not all of the lung fields are involved; Severe RDS meets one or more of the following criteria: lung consolidation shows as a snowflake sign on ultrasound and all lung regions are involved, or regardless of its degree and extent, lung consolidation has caused serious complications, such as pulmonary hemorrhage, pneumothorax, persistent pulmonary hypertension of the newborn, or/and a large area of pulmonary atelectasis.

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.

Aim To investigate the change of miR-124 expression in methamphetamine-induced addiction in PC12 cells and the possible regulatory mechanism that it involves.Methods PC12 cells were randomly divided into 6 groups as follows: control group, methamphetamine group, agomir Negative Control group, miR-124 agomir group, agomir Negative Control+methamphetamine group and miR-124 agomir+methamphetamine group.After the treatment, the total RNA and protein were extracted in PC12 cells.The expression of miR-124 was measured by Real-time PCR and the expression of GluR2 was determined by Western blot in PC12 cells.Results Compared with those in the control group, the expression of miR-124 was remarkably decreased and the expression of GluR2 was significantly increased in the methamphetamine group in PC12 cells.Compared with those in the agomir Negative Control+methamphetamine group, the expression of miR-124 was remarkably increased and the expression of GluR2 was significantly decreased in the miR-124 agomir+methamphetamine group in PC12 cells.Conclusion MiR-124 might involve in methamphetamine-induced addiction in PC12 cells by inhibiting GluR2.

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

Objective To investigate the effect of Nestin gene silencing on the proliferation of human esophageal cancer ECA109 cells and possible mechanism .Methods Lenti-Nestin was constructed and transfected into ECA109 cells to establish a stable Nestin-silencing cell line Lenti-Nestin.Blank group , scrambled group , Lenti-Nestin group were set up .The expressions of Nestin , c-myc and cyclin D1 mRNA and protein levels were detected by qRT-PCR and Western blot .The cell proliferation was analyzed by CCK 8 assay .Results The stable Nestin-si-lencing cell line was successfully established .The expression of Nestin mRNA ( P<0.01 ) and protein ( P<0.05 ) levels were reduced significantly and the downregulation evidently suppressed cell proliferation ( P<0.01 ) and col-ony forming capacity ( P<0.05 ) compare with the scrambled group and blank group .However ,The c-myc and cy-clin D1 expression levels in ECA 109 cells in Lenti-Nestin group were significantly lower than that of scrambled group and blank group ( P<0.05 ) .Conclusions Knockdown Nestin expression significantly inhibits the level of esophageal cancer ECA109 cells proliferation,which may act via influencing the expression of c-myc, cyclin D1.

Objective To study the influence of local administration of Icariin on orthodontically induced inflammatory root resorption (OIIRR ).Methods After rat models of orthodontic root movement were successfully established,rats were injected with 200 mg/kg Icariin (Icariin group)or saline (positive control group), respectively.Left maxillary served as the negative control group.The resorption pit of root surface was measured using scanning electron microscopy (SEM), HE staining, and tartrate resistant acid phosphatase (TRAP ). Results The level of TRAP positive cells and root resorption score in Icariin group were significantly lower than those in the positive control group (P < 0.05 ).Each measured value differed significantly between thenegative control group and the positive control group (P <0.05).The level of TRAP positive cells was significantly different (P <0.05),while root resorption scores did not differ between Icariin group and the negative control group (P >0.05).Conclusion Local administration of Icariin may reduce the degree of orthodontically induced resorption.

Objective:To survey the relation of different vertical skeletal facial type and the third molar agenesis.Methods:The vertical face type of 207 subjects was divided into high angle(n=45),average angle(n=99)and low angle(n=63)groups by the assessments of MP-SN angle.The assessment of the third molar was made from panoramic radiographs,then the third molar agenesis rate of different vertical skeletal facial types was analysed.Chi-square criterion examination was conducted with SPSS 17.0 software. Results:In the high angle group,whether in the maxillary or mandibular,unilateral or bilateral,the absent percentage of third molar was higher than that in low angle group(P<0.05).In the females the bilateral maxillary third molar absent percentage was higher than in the males(P<0.05).The absent percentage of maxillary third molar was higher than that of the mandibular third molar(P<0.05).Conclusion:The third molar absence depends on vertical skeletal facial type.The absent percentage of third molar in the in-dividuals with high angle type is higher than that in those with low angle type(P<0.05).