Objective To explore the effective substances that specifically bind to RSV-F protein in the water extract of Forsythia suspensa,and verify its effect.Methods Surface plasmon resonance(SPR)affinity fishing technology was used to enrich,regenerate and recover the active components that specifically bind to RSV-F protein in the water extract of Forsythia suspensa.The recovered samples were analyzed and identified by UHPLC-MS/MS,and the active components that stably bind to F protein were screened by molecular docking,molecular dynamics simulation and SPR affinity detection,and then returned to animal experiments for pharmacodynamics verification.BALB/c mice were randomly divided into normal group,model group,positive control group,protocatechuic acid group and verbascoside group.In the experimental group,RSV was dripped into the nose to make models.Each drug group began to be given intragastric intervention on the day of modeling,and samples were taken after 4 days.HE staining was used to observe the pathological changes of lung tissue,and ELISA was used to detect the changes of inflammatory factors in lung tissue.Results A variety of active components in the aqueous extract of Forsythia suspensa could bind to RSV-F protein,among which the results of verbascoside and protocatechuic acid were more stable.In vivo pharmacodynamics experiments showed that the lung tissue of the model group had obvious pathological changes and the level of inflammatory factors increased,and the pathological state was improved after the intervention of verbascoside and protocatechuic acid compared with the normal group.Conclusion Forsythia suspensa can interfere with the expression of RSV-F protein through many active components such as verbascoside and protocatechuic acid,which may be the material basis of its anti-RSV.

Objective In this preliminary survey,we sought to determine the composition of mosquito species inhabiting the Emeifeng Nature Reserve,Fujian Province,China.Methods Mosquito larvae were collected by straw and spoon trapping,and adult mosquitoes were collected by lamp trapping at selected breeding sites in the reserve.The specimens were initially identified based on morphology,with subsequent verification using molecular biology methods.Results A total of 34 mosquito species in 13 genera were collected,among which,there were 4 species of Anopheles(Genus Anopheles Meigen,1818),2 species of Lutzia(Genus Lutzia Theobald,1903),15 species of Culex(Genus Culex Linnaeus,1758),4 species of Stegomyia(Genus Stegomyia Theobald,1901),and single species of Hulecoeteomyia(Genus Hulecoeteomyia Theobald,1904),Luius(Genus Luius Reinert,Harbach et Kitching,2008),Aedes(Genus Aedes Meigen,1818),Downsiomyia(Genus Downsiomyia Vargas,1950),Collessius(Genus Collessius Reinert,Harbach et kitching,2006),Uranotaenia(Genus Uranotaenia Lynch 1891),Armigeres(Genus Armigeres Theobald,1901),Toxorhynchites(Genus Toxorhynchites Theobald,1901),and pestle mosquito(Genus Tripteroides Giles,1904).Conclusions The species composition of mosquitoes sampled in the Emeifeng Nature Reserve will provide a basis for further research on mosquito vectors and contribute to measures for local mosquito control.

Objective To explore the effective substances that specifically bind to RSV-F protein in the water extract of Forsythia suspensa,and verify its effect.Methods Surface plasmon resonance(SPR)affinity fishing technology was used to enrich,regenerate and recover the active components that specifically bind to RSV-F protein in the water extract of Forsythia suspensa.The recovered samples were analyzed and identified by UHPLC-MS/MS,and the active components that stably bind to F protein were screened by molecular docking,molecular dynamics simulation and SPR affinity detection,and then returned to animal experiments for pharmacodynamics verification.BALB/c mice were randomly divided into normal group,model group,positive control group,protocatechuic acid group and verbascoside group.In the experimental group,RSV was dripped into the nose to make models.Each drug group began to be given intragastric intervention on the day of modeling,and samples were taken after 4 days.HE staining was used to observe the pathological changes of lung tissue,and ELISA was used to detect the changes of inflammatory factors in lung tissue.Results A variety of active components in the aqueous extract of Forsythia suspensa could bind to RSV-F protein,among which the results of verbascoside and protocatechuic acid were more stable.In vivo pharmacodynamics experiments showed that the lung tissue of the model group had obvious pathological changes and the level of inflammatory factors increased,and the pathological state was improved after the intervention of verbascoside and protocatechuic acid compared with the normal group.Conclusion Forsythia suspensa can interfere with the expression of RSV-F protein through many active components such as verbascoside and protocatechuic acid,which may be the material basis of its anti-RSV.

Objective·To further clarify the mechanism of podocyte damage by studying the expression of cartilage oligomeric matrix protein(COMP)in glomerular podocytes and its relationship with podocyte autophagy under high glucose environment.Methods·The gene expression dataset GSE104948 was downloaded from the GENE EXPRESSION OMNIBUS(GEO)database,and differentially expressed genes(DEGs)were obtained via GEO2R.The molecular functions and signaling pathways related to differential genes were summarized.The most correlated key genes(hub genes)were acquired by Weighted Gene Co-Expression Network Analysis(WGCNA)and the protein-protein interaction network(PPI)of DEGs was constructed with STRING database.The enrichment analysis was performed again.Conditionally immortalized mouse podocyte cells were cultured in vitro.After being fully differentiated,they were stimulated with high glucose,and the expressions of COMP,mammalian target of rapamycin(mTOR),microtubule-associated protein 1 light chain3(LC3)and other proteins in podocytes were detected by Western blotting.The shRNA constructed by lentiviral vector was further used to infect podocytes to inhibit the expression of COMP,and the stable cell strains were screened by puromycin.The expression of COMP,mTOR,and LC3 of stable strains were detected by Western blotting,in order to observe the effect of COMP on autophagy.Results·A total of 362 DEGs were filtered for subsequent analysis.Among these DEGs,284 genes were up-regulated and 78 genes were down-regulated.The results of Gene Onotology(GO)term analysis showed that DEGs in diabetic nephropathy(DN)were mainly enriched in cell surface receptor signaling pathway,receptor binding,etc.The main enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways included phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway,extracellular matrix(ECM)-receptor interaction,etc.Sixty-four hub genes were refined through the intersection of WGCNA and PPI hub genes,and the hub genes with significantly increased or decreased expression were sifted.The hub genes were annotated with KEGG again,and it was found that most of the hub genes were enriched in"ECM-receptor interaction"and"PI3K/AKT signaling pathway".The PI3K/AKT/mTOR signaling pathway is a classic autophagy pathway,and COMP was absolutely overexpressed(logFC>2)in the 64 hub genes,suggesting that it may affect autophagy through this pathway.Western blotting showed that compared with the mannitol control group and the low glucose group,the expression of COMP in podocytes was significantly increased under high glucose stimulation.Compared with the control group,the expression of LC3-Ⅱ in the high glucose group was significantly decreased,indicating that the autophagy initiation of podocytes was inhibited under the high glucose environment.Compared with the negative control,the expression of LC3-Ⅱ in renal podocytes of mice with knockdown of COMP was significantly increased,and the mTOR decreased with the decrease of the expression of COMP,indicating that inhibiting COMP contributed to the recovery of autophagy in podocytes.Conclusion·COMP is highly expressed in DN patients and highly enriched in ECM receptor and PI3K/AKT signaling pathway.Autophagy in mouse renal podocytes is inhibited under high glucose conditions,and the high expression of COMP induced by high glucose may be a key factor in autophagy inhibition.Inhibiting COMP helps to restore autophagy in mouse renal podocytes.

Background::The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods::From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model. Results::A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A ( n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement. Conclusion::Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.

Objective:To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis.Methods:A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated.Results:The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant ( P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation ( P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P>0.05). Conclusions:The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective Observation of the response of Aedes albopictus to DEET and Dimefluthrin in the Three-Part Tube to evaluate the effectiveness of spatial repellency of dimefluthrin.Methods Referenced to the structure and principle of the HITTS device,the Three-Part Tube were designed to observe the behaviors and response of Ae.albopictus to dimefluthrin and deet in the Three-Part Tube.Results Aedes albopictus showed no repellent response in the blank condition of the Three-Part Tube(P>0.05).When tested with DEET in the Three-Part Tube,Aedes albopictus showed repellent effects at 1.0%to 50.0%(P<0.05).For dimefluthrin,repellency was observed at concentrations ranging from 0.0035%to 0.0050%(P<0.05).The repellent effect of 0.0050%dimefluthrin was comparable to that of 20%DEET,with no statistically significant difference(P>0.999).Conclusions Dimefluthrin at concentrations ranging from 0.0035%to 0.0050%had good spatial repellency against Ae.albopictus.

OBJECTIVE: To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITD^mut R/R AML) and analyze the molecular genetic characteristics of the patients. METHODS: Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITD^mut R/R AML were analyzed. RESULTS: 14.3% (1/7) of the patients in FLT3-ITD^mut group and 22.2% (2/9) of the patients in FLT3-ITD^wt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITD^mut group and FLT3-ITD^wt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITD^mut patients was significantly shorter than that of FLT3-ITD^wt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITD^mut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA. CONCLUSION VEN plus AZA showed a certain effect on patients with FLT3-ITD^mut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITD^mut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.
Humans ; Nucleophosmin ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Azacitidine/therapeutic use* ; fms-Like Tyrosine Kinase 3/genetics*