Objective:To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province.Methods:Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 software χ2 Inspection. Results:A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old ( χ2=146.59, P<0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) ( χ2=3.91, P=0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath ( χ2=259.15, 366.06, 12.48, P<0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old ( χ2=9.74, P<0.001), while RSV is more common in children under 1 year old ( χ2=178.63, P<0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old ( χ2=92.54, 12.90,22.21, P<0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak ( χ2=252.68, P<0.001). Conclusion:The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

Objective To observe the effects of Huatan Quyu Decoction on cognitive function and the expressions of GABA and VILIP-1 in brain tissue of rats with cerebral small vessel disease;To discuss its mechanism for treatment on cerebral small vessel disease.Methods Totally 48 male SD rats were randomly divided into blank group,model group,Huatan Quyu Decoction low-and high-dosage groups,with 12 rats in each group.Except for the blank group,a rat model of cerebral small vessel disease was prepared by in vitro injection of homologous microemboli.Huatan Quyu Decoction low-and high-dosage groups were given Huatan Quyu Decoction 1.25 and 2.5 g/kg by gavage,the blank group and model group were gavage with equal amounts of distilled water for 28 consecutive days.Morris water maze experiment was conducted on day 1,7,14,and 28 after administration to evaluate the learning and memory abilities of rats,HE staining was used to observe pathological changes in hippocampal tissue,and immunohistochemical staining was used to detect the expressions of GABA and VILIP-1 proteins in brain tissue.Results Compared with the blank group,the escape latency of Morris water maze experiment in model group significantly prolonged(P<0.05),and the number of crossing platforms was significantly reduced(P<0.05);the arrangement of hippocampal tissue cells was disordered,gaps widen,and nuclei atrophy and necrosis,the GABA expression in brain tissue significantly decreased(P<0.05),while the VILIP-1 expression significantly increased(P<0.05).Compared with the model group,the escape latency of Morris water maze experiment in the Huatan Quyu Decoction low-and high-dosage groups significantly shortened(P<0.05)on day 7,14,and 28 of administration,and the number of crossing platforms significantly increased(P<0.05),GABA expression significantly increased(P<0.05),while VILIP-1 expression significantly decreased(P<0.05).Compared with the Huatan Quyu Decoction low-dosage group,the escape latency of Morris water maze experiment in Huatan Quyu Decoction high-dosage group decreased at various time points,and the number of crossing platforms increase,the pathological damage of hippocampal tissue was reduced,the expression of GABA in brain tissue increased,and the expression of VILIP-1 decreased,with statistical significance(P<0.05).Conclusion Huatan Quyu Decoction can increase the expression of GABA in brain tissue and inhibit the expression of VILIP-1,thereby improve the cognitive function of rats with cerebrovascular disease.

Objective:To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province.Methods:Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 software χ2 Inspection. Results:A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old ( χ2=146.59, P<0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) ( χ2=3.91, P=0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath ( χ2=259.15, 366.06, 12.48, P<0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old ( χ2=9.74, P<0.001), while RSV is more common in children under 1 year old ( χ2=178.63, P<0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old ( χ2=92.54, 12.90,22.21, P<0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak ( χ2=252.68, P<0.001). Conclusion:The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

OBJECTIVE To investigate the improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steatohepatitis （NASH）. METHODS Normal human liver LO2 cells were induced to steatosis by free fatty acid， then were divided into normal group， model group， silybin group （100 μmol/mL）， T. yunnanensis ethanol extracts （TYS） group （50 μg/mL）， T. yunnanensis ethyl acetate extracts （TYSA） group （50 μg/mL）， and T. yunnanensis n-butanol extracts （TYSB） group （50 μg/mL）. After 24 hours of drug intervention， the deposition of lipid droplets was observed in LO2 cells in each group. The contents of total cholesterol （TC）， triacylglycerol （TG）， malondialdehyde （MDA） and glutathione （GSH）， the activities of aspartate transaminase （AST）， alanine transaminase （ALT） and superoxide dismutase （SOD）， the mRNA expressions of Kelch-like ECH-associated protein 1（ Keap1）， nuclear factor E2-related factor 2（ Nrf2） and heme oxygenase 1（ HO- 1） were detected. NASH rat model was induced by a high-fat diet， and then divided into normal group， model group， silybin group （12.6 mg/kg）， TYS group （80 mg/kg）， TYSA group （80 mg/kg） and TYSB group （80 mg/kg）， with six rats in each group. The liver indexes of rats in each group were calculated after 6 weeks of drug intervention. The liver histopathological changes were observed， and the contents of TC， TG， HDL-C and LDL-C， AST and ALT activities in serum， the contents of MDA and GSH， SOD activities in liver tissue were detected. RESULTS Compared with model group， TYS， TYSA and TYSB could reduce lipid droplet deposition， intracellular TC， TG and MDA contents， AST and ALT activities， and increase SOD activity， GSH content， and Keap1， Nrf2， HO-1 mRNA expression levels in LO2 cells after steatosis to varying degrees， with some differences being statistically significant （P＜0.05）. They also significantly improved liver injury in NASH model rats， reduced their liver indexes， TC， TG， LDL-C and MDA contents， AST and ALT 1-042） activities， and increased HDL-C （except for TYS and TYSB）， GSH contents and SOD activity， with TYSA having the most significant effect （P＜0.05）. CONCLUSIONS TYS， TYSA and TYSB have a certain improvement effect on NASH， among which TYSA has the most obvious effect. Its mechanism of action may be related to upregulating the Keap1/Nrf2/HO-1 signaling pathway and inhibiting oxidative stress

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

Objective:To investigate the changes in peripheral blood and liver-infiltrating natural killer-like B (NKB) cells in patients with primary hepatocellular carcinoma (HCC), and to assess the influence of IL-18 on NKB cells in vitro and the underlying mechanism. Methods:Forty-three HCC patients and 21 normal controls (NC) were enrolled in the study. Peripheral blood samples were collected to isolate plasma and peripheral blood mononuclear cells (PBMC). Intrahepatic lymphocytes (IHL) were isolated from tumor tissues and para-tumor tissues obtained from 16 HCC patients who received surgery. IL-12, IL-18 and IL-18 binding protein (IL-18BP) levels in plasma were measured by enzyme linked immunosorbent assay. The percentages of CD3 -NKp46 + CD19 + NKB cells and IL-18 + NKB cells in PBMC and IHL were analyzed by flow cytometry. Changes in the percentages of NKB cells and IL-18 + NKB cells were measured after stimulating PBMC and IHL with recombinant human IL-18 (1 ng/ml and 10 ng/ml). Changes in IL-18BP levels in the culture supernatants and phosphorylated nuclear factor-κB (NF-κB) in NKB cells were also assessed. Student′s t test, one-way analysis of variance or LSD-t test was used for statistical analysis. Results:There was no significant difference in plasma IL-12 level between HCC patients and NC ( P=0.245). Compared with NC, HCC patients had decreased IL-18 level in plasma [(224.3±58.89) pg/ml vs (327.0±52.27) pg/ml, P<0.000 1], but increased IL-18BP level [(4.421±0.97) ng/ml vs (0.92±0.18) ng/ml, P<0.000 1]. The percentages of peripheral blood NKB cells and IL-18 + NKB cells were lower in HCC patients than in NC [(2.68±1.23)% vs (8.88±2.95)% and (54.42±12.60)% vs (69.74±12.65)%, both P<0.000 1]. The percentage of NKB cells in IHL was reduced in tumor tissues as compared with that in para-tumor tissues [(2.89±0.86)% vs (4.66±1.17)%, P<0.000 1]. Moreover, the percentage of IL-18 + NKB cell was also down-regulated in tumor tissues as compared with that in para-tumor tissues [(51.50±13.18)% vs (62.13±9.24)%, P=0.013]. Recombinant human IL-18 stimulation reduced the IL-18BP level in the culture supernatants ( P<0.05). IL-18 stimulation at 1 ng/ml did not affect NKB cell percentage, IL-18 + NKB cell percentage or NF-κB phosphorylation in NKB cells from PBMC or IHL ( P>0.05), while 10 ng/ml of IL-18 not only elevated NKB cell percentage and IL-18+ NKB cell percentage, but also promoted NF-κB phosphorylation in NKB cells ( P<0.01). Conclusions:In vitro stimulation with high concentration of IL-18 might promote NF-κB phosphorylation by inhibition of IL-18BP expression. This process might play a positive feedback role to induce the activation of NKB cells and IL-18 secretion.

OBJECTIVE：To predict the active components and potential target of volatile oil of Citri reticulatae preventing and treating Alzheimer ’s disease （AD）. METHODS ：The volatile oil of C. reticulatae was determined by GC-MS ，and identified according to NIST 11.L database and manual data analysis. The active components and targets of volatile oil of C. reticulatae were predicted through TCMSP and PharmMapper database. The related targets of AD were obtained by using GeneCards and OMIM databases. Venny 2.1.0 software mapping was used to obtain the direct targets of volatile oil of C. reticulatae against AD. Core nodes were mined with STRING database and Cytoscape 7.2.1 software，and the indirect targets of volatile oil of C. reticulatae against AD were obtained by mapping and duplication coith Venny 2.1.0 software. With the help of DAVID 6.7 database，the above direct and indirect targets （i.e. action targets ）were used for gene ontology （GO）function enrichment analysis and KEGG pathway enrichment analysis. Using Cytoscape 7.2.1 software， topology analysis was conducted for the network of “active components-acting targets ”of volatile oil of C. reticulatae ，with node degree value ，betweenness centrality and closeness centrality as indexes ，then key components and key targets were mined. RESULTS & CONCLUSIONS ：A total of 40 chemical components in volatile oil were identified by GC-MS ，all of them were active components ，including D-limonene，γ-terpinene，etc. A total of 151 active components-corresponding targets and 1 291 AD-related targets were mined ，including 48 direct targets and 41 indirect targets. The above 89 targets were mainly concentrated in cell fraction ，axon，cytosol and other cell components ；intracellular signaling cascade ，response to organic substance and other biological processes ；protein kinase activity and amine receptor activity and other molecular functions ；as well as cancer pathway ，calcium signaling pathway and neurotrophin signaling pathway （P＜ 0.05）. A total of 10 key components including α-terpinene，β-elemen，thymol and （－）-4-terpineol，as well as 21 key targets such as androgen receptor ，prostaglandin G/H synthase 2，mitogen activated protein kinase 14，muscarinic acetylcholine receptor M 1 were excavated ，indicating the effect of volatile oil of C. reticulatae against AD had the characteristics of multi-component ， multi-target and multi-channel.

Neonatal infectious diseases (NIDs) are the main cause of neonatal death worldwide. Since the neonatal immune system is not fully developed, its pathogenic factors are more complex than adults and the clinical manifestations are more diverse. Early, rapid and comprehensive detection of infectious pathogens is of great significance for timely clinical treatment, and therefore can reduce mortality and complications. Traditional pathogen diagnosis methods are limited in small detection flux, long detection time and low screening efficiency. With the development of high-throughput sequencing technology, metagenomic next-generation sequencing (mNGS) is gradually widely applied in NIDs diagnosis. Not only can acquire the genetic information of pathogens in the samples, but also can be used to excavate the relationship between pathogens and host flora. In particular, mNGS has important reference value for the diagnosis of rare infectious diseases. In this study, the latest research progress and application of mNGS in detecting the pathogens of NIDs have been reviewed.

Objective To elevate the prevalence of fusion gene in children with acute lymphoblastic leukemia(ALL),and compare the difference in the clinical characteristics and prognosis of children with ALL carrying different fusion genes.Methods The results of fusion gene that detected by multiplex RT-PCR in children with 341 newly diagnosed ALL between July 2013 and December 2016 in West China Second University Hospital,Sichuan university were retrospectively reviewed.Date of clinical characteristics, morphology, immunophenotype, cytogenetic characteristics and event-free survival were collected and analyzed by χ2test and survival analysis in different groups according the results of fusion genes.Results The positive rate of fusion genes was 35.2%(120/341),including 69 cases with TEL-AML1,16 cases with E2A-PBX1,16 cases with BCR-ABL,10 cases with MLL gene rearrangement,5 cases with HOX11L2 and 4 cases with SIL-TAL1.There was statistical difference in age of different fusion gene groups(χ2=29.552, P<0.05),most of children carrying TEL-AML1,E2A-PBX1 were younger than 5 years,but carrying BCR-ABL,MLL gene rearrangement were opposite.The children with BCR-ABL,MLL gene rearrangement or SIL-TAL1 had higher WBC and severer enlarged liver, spleen and lymph node(χ2=27.657,45.822,P<0.05).There also had statistical difference in morphology and immunophenotype in fusion gene groups(χ2=31.333,P<0.05).TEL-AML1,E2A-PBX1 and BCR-ABL were mainly found in B-ALL,HOX11L2 and SIL-TAL1 were only found in T-ALL,but MLL gene rearrangement were found in both.The survival analysis showed that the event-free survival(EFS)in groups of BCR-ABL and MLL gene rearrangement were lower than other groups(χ2=15.368,P<0.05), but there was no significant difference in T-ALL(χ2=1.592, P>0.05).Conclusions Fusion gene detection is an important molecular marker in ALL of children.The ALL children with different fusion genes have different clinical features, immunophenotype and prognosis.

Objective To observe the efficacy of Metoclopramide Dihydrochloride Injection in the prevention of intra-and postoperative vomiting after emergency percutaneous coronary intervention (PCI) in patients with ST segment elevation myocardial infarction.Methods A total of 132 patients with ST segment elevation myocardial infarction and required treatment with PCI were selected from January 2014 to April 2016 and randomly divided into observation group and control group.The patients in observation group were treated with Metoclopramide Dihydrochloride Injection before PCI for preventive treatment,while those in control group were not,only if vomiting occurred,then corresponding symptomatic treatment was provided.The number of patients vomiting,frequency,duration and severity of vomiting during operation and within 24 h after operation were observed.Results The number of patients vomiting,the incidence rate of vomiting and vomiting duration during operation and within 24 h after operation in observation group were significantly lower than those in control group and the score of vomiting severity within 24 h after operation in observation group was significantly lower than that in control group,which indicated statistical differences (P ＜ 0.05).Conclusion Metoclopramide Dihydrochloride Injection is effective for significantly reducing the incidence of intra-and postoperative vomiting after emergency percutaneous coronary intervention (PCI) in patients with ST segment elevation myocardial infarction.