AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

This article reports a case of prenatal diagnosis of fetal Costello syndrome. At 11 weeks of gestation, the fetal nuchal translucency thickness was 2.5 mm. At 26 +1 weeks of gestation, ultrasound indicated that the fetal abdominal circumference was significantly enlarged, suggesting fetal overgrowth. Subsequent regular ultrasound follow-ups revealed polyhydramnios, enlarged fetal kidneys, and macroglossia after 30 +5 weeks of gestation. Whole-exome sequencing of the family detected a c.34G>A(p.Gly12Ser) mutation in the fetal HRAS gene, which was pathogenic and not present in either parent. Based on clinical manifestations, the fetus was diagnosed with Costello syndrome. After genetic counseling, the pregnant woman opted for termination of the pregnancy.

Objective: To understand the detection rate, epidemic pattern of respiratory syncytial virus (RSV) in hospitalized children with acute lower respiratory tract infection (ALRTI) in China. Methods: From June 2017 to March 2020, a prospective multi-center study on the viral aetiology among hospitalized children with ALRTI was conducted in six pediatrics hospital of North China, Northeast, Northwest, South China, Southeast, and Southwest China. A total of 2 839 hospitalized children with ALRTI were enrolled, and the respiratory specimens were collected from these cases. A multiplex real-time RT-PCR assay were employed to screen the respiratory viruses, and the molecular epidemiological and clinical characteristics of children infected with RSV were analyzed. Results: The positve rate of RSV was 18.6% (528/2 839), and the positive rate of RSV in different regions ranged from 5.5% to 44.3%. The positive rate of RSV in male was higher than that in female (20.2% vs 16.3%), and there was a significant statistically difference between two groups (χ2=6.74, P=0.009). The positive rate of RSV among children under 5 years old was higher than that among children older than 5 years old (22.3% vs 4.5%), and there was a significant statistically difference between two groups (χ2=97.98,P<0.001). The positive rate of RSV among the <6 months age group was higher than that of other age groups (all P<0.05). During January 2018 and December 2019, RSV was detected in almost all through the year, and showed peaks in winter and spring. RSV-positive cases accounted for 17.0% (46/270) among children with severe pneumonia, including 36 cases infected with RSV alone. Conclusion: RSV is an important viral pathogen in children under 5 years old with ALRTI in China. The virus can be detected almost all through the year and reached the peak in winter and spring. RSV could lead to severe pneumonia in children and caused huge threaten to children's health.
Child ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Respiratory Syncytial Virus Infections/epidemiology* ; Child, Hospitalized ; Prospective Studies ; Respiratory Tract Infections/epidemiology* ; Respiratory Syncytial Virus, Human ; China/epidemiology*

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.

Myasthenia gravis crisis (MC) often involves respiratory muscles and requires mechanical ventilation urgently. As non-invasive mechanical ventilation (NIV) technology unceasing development, its use in acute respiratory failure caused by MC shows obvious advantages. However, how to identify the occurrence of MC at early stage, predict the relevant indicators of NIV for MC treatment, and apply different ventilation strategies to improve the effect of treatment are worthy of attention. In addition, the new development of NIV modes in recent years also provides new direction for the treatment of MC. Therefore, this article reviews recent advance in the clinical application of NIV in MC to provide clinical references.

Asthma is one of the chronic diseases with the highest incidence in childhood. At present, comprehensive treatments such as glucocorticoid inhalation and bronchodilators can effectively control asthma. Parents' compliance with asthma treatment is closely related to the prognosis of children. This article reviews the influencing factors of treatment compliance and nursing strategies in children with asthma, aiming to provide a theoretical basis for effective control and management of childhood asthma in the future.

Objective To analyze the impact of canceling drug price markup policy on hospitalization expenses of urban public hospitals in Sichuan province and provide decision-making basis. Methods Data of hospitalization expenses of the top 50 diseases among inpatients discharged in 2016 and 2017 were collected, totaling 2 732 022 inpatient cases. Based on hospitalization expenses, these disease were divided into seven categories ( A-G) using dynamic clustering analysis, which represent respectively dominant diseases of different expense makeups, to compare such indicators as hospitalization expenses and composition ratios of these diseases before (2016) and after the reform (2017). Results The study found drastic changes among the medical expenses of different categories of dominant diseases. For example, per-hospitalization cost of categories E ( featuring high drug and examination expenses ) and G ( featuring balanced expenses distribution) diseases decreased since the reform, while the other categories rose instead. The proportion of drugs of different disease categories decreased to various extents. For example, category A ( high drug ratio of 5.60% ) and category E (5.15% ) diseases of which were found with the sharpest drop. Proportion of service expenses, on the other hand, rose to different extents. For example, the proportion of service expenses of all disease categories increased to varying degrees, among which category E (3.46% ), category F (3.37% ) and category D (3.36% ) accounted for the largest share of increase.Conclusions The reform is moving the cost structure of dominant diseases in Sichuan towards a rational level, yet with significant differences among disease categories. The authorities should target various categories to adjust their reimbursement policies, minimize financial burden on patients, strengthen their supervision on drug use and medical behavior, prevent such misbehaviors as the inducing demands and transferring drug markups.

Objective To evaluate the performance of medical services of 18 tertiary hospitals in Sichuan province in 2016 based on DRGs, to identify objective methods to evaluate service quality and performance of medical institutions.Methods Based on the homepage data of inpatient medical records from 18 tertiary hospitals in Sichuan in 2016, using diagnosis-related groups as a risk-adjustment tool, the study evaluated the medical service quality and performance from three dimensions:medical ability,service efficiency and medical Quality.Results In the evaluation of medical service capacity, hospital I had the highest number of discharged cases and total weight(83 405 cases and 126 522.22),and hospital G had the lowest discharge cases and total weight(2 350 cases,2 797.12).The highest number of DRGs group was from hospital B(661 groups),and the lowest from hospital G(43 groups).The highest value of CMI was from hospital F(2.091),and the lowest from hospital D(0.953).Hospitals B,I and P had wide disease type range,while hospitals F, B and I had higher overall technical level than the other hospitals.Of the service efficiency evaluation,hospital E had the lowest time consumption index(0.740),and hospital P had the lowest expenditure index(1.073).Of the service quality evaluation,hospitals F and G had the lowest risk of mortality and the lower risk of mortality(0.00%,0.00%).Hospital I had the highest total score (100.0 points), and hospital G had the lowest total score(51.1 points).Conclusions DRGs based evaluation on medical service quality and performance of medical institutions can ensure reliability and scientific adequacy of evaluation.It may contribute to the continuous improvement of medical quality, and provide data support and decision reference for medical service supervision.

In the present study, the complete genomes of four common (4/EV71/Wenzhou/CHN/2014, 15/ EV71/Wenzhou/CHN/2014, 116/EV71/Wenzhou/ CHN/2014, and 120/EV71/Wenzhou/CHN/2014) and two virulent (11/EV71/Wenzhou/CHN/2014 and 109/EV71/Wenzhou/CHN/2014) enterovirus 71 (EV71) isolates were sequenced and described. They are 7405 bp in length and belong to EV71 sub-genotype C4 (C4a cluster). Nucleotide sequence alignment revealed six nucleotide variations (GP151→TP151, GP199→AP199, GP261→TP261, AP328→CP328, GP422→AP422, and GP437→TP437) in the two virulent isolates within the 5'UTR of the IRES element. RNA secondary structure predictions of IRES and FCE indicated that the common isolates shared similar structures, which were different from those of the virulent isolates. Moreover, the GP114→CP114 and GP151→TP151 mutations in the virulent isolates contributed to the formation of the unique RNA secondary structures in SL II. Furthermore, nucleotide/amino acid sequence alignments of 82 EV71 isolates indicated that six sites (TP488 and CP577 in the 5'UTR; AsnP57 in 2A; IleP56 in 3C; CP10 and AP47 in the 3'UTR) are potentially associated with the neurovirulence of EV71. Finally, the 3D structures of 2A were analogous, whereas the structures of VP1 and 3C were variable.
Base Sequence ; Central Nervous System ; virology ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; pathogenicity ; Enterovirus Infections ; virology ; Genome, Viral ; Genomics ; Genotype ; Humans ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phylogeny ; RNA, Viral ; chemistry ; genetics ; Virulence