In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

OBJECTIVE: To explore the prenatal features and genetic etiology of a fetus with Short-rib cage dysplasia (SRTD) due to variants of DYNC2H1 gene. METHODS: A pregnant women presented at Xinxiang Central Hospital in June 2020 for abnormal prenatal ultrasound findings was selected as the study subject. With informed consent obtained, amniotic fluid sample was extracted from the woman, and clinical data of the fetus were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Xinxiang Central Hospital [Ethics No.: 2025-214-01(K)]. RESULTS: At 25⁺⁶ weeks gestation, genetic testing revealed that the fetus has harbored compound heterozygous variants of the DYNC2H1 gene, namely c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly), which were derived from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) variants were classified as pathogenic (PVS1+PM2_supporting+PM3+PP5) and likely pathogenic (PM1+PM2_supporting+PM3+PP3), respectively. Bioinformatics analysis suggested that both variants may affect the 3D structure of the DYNC2H1 protein. CONCLUSION The compound heterozygous variants of c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) of the DYNC2H1 gene probably underlay the pathogenesis of SRTD in the fetus. Above findings had facilitated prenatal diagnosis and genetic counseling for the couple.
Humans ; Female ; Pregnancy ; Cytoplasmic Dyneins/chemistry* ; Prenatal Diagnosis ; Adult ; Short Rib-Polydactyly Syndrome/diagnostic imaging* ; Mutation ; Exome Sequencing ; Fetus/abnormalities* ; Ultrasonography, Prenatal

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To evaluate the application of ELISA randomized quality control,and continuously improve the laboratory testing capacity and quality assurance,in order to gradually improve the application of randomized quality control to the daily testing of ELISA.Methods Collected the quality control data of KEHUA HBsAg,compared the difference between randomized quality control data and immobilized quality control data.Group comparison of randomization quality control between rows and columns.The randomized quality control data were analyzed retrospectively and the quality control chart was established by using the randomized quality control data.Analyzed and compared the lost-control situation of randomized quality control and immobilized quality control.Results Randomized quality control S/CO value(2.831±0.343)and immobilized quality control S/CO value(2.651±0.260)in the same microplate,the difference between two was statistically significant(t=5.970,P＜0.05).The differences between randomized quality control and immobilized quality control in columns 2 to 8 were statistically significant(t=2.285～5.536,all P<0.05).There were no statistically significant differences between randomized quality control and immobilized quality control in column 9 to 12(t=0.031～1.605,all P>0.05).There was no statistically significant difference in randomization quality control among all lines(F=0.858,P＞0.05).The randomized quality control data was used to establish a quality control chart.Within the time range of the collected data,the randomized quality control was out of control for 6 times,all were greater than+3s,and the loss of control rate was 4.72%(6/127).Fixed position quality control lost control 9 times during the same period,all of which were greater than+3s,with a loss of control rate of 0.61%(9/1 481).Conclusion The randomized quality control has a greater possibility to reflect the factors affecting all the samples on the microporous plate.Random quality control can be used to find possible systematic errors in testing.Randomized quality control can gradually be fully applied to daily indoor quality control,but the loss of control rate and coefficient of variation may increase.

Objective:To analyze the differentially expressed messenger RNA(mRNA), microRNA(miRNA), and long non-coding RNA(lncRNA)during the browning of mouse subcutaneous adipose tissue, construct a competitive endogenous RNA(ceRNA)network, and provide a theoretical basis for investigating the regulatory mechanisms of white adipose tissue browning.Methods:A cold-stimulated mouse model was established for transcriptome sequencing.Bioinformatics tools were employed to screen for differentially expressed mRNAs, miRNAs, and lncRNAs.An integrated mRNA-miRNA-lncRNA analysis was performed to construct a ceRNA network.Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and Gene Set Enrichment Analysis(GSEA)were conducted on the differentially expressed mRNAs and ceRNA networks to explore transcriptional regulation during the cold-induced browning of subcutaneous adipose tissue.Results:Transcriptomic analysis of the cold-stimulated model identified 4, 256 differentially expressed RNAs, which include 3, 600 mRNAs, 588 lncRNAs, and 68 miRNAs.GO and KEGG analyses revealed that the browning of white adipose tissue involves immune-related processes, such as immune system processes, immune responses, adaptive and innate immune responses, and the positive regulation of T-cell activation.A ceRNA network associated with browning regulation was constructed, comprising 233 nodes(188 mRNAs, 34 miRNAs, and 11 lncRNAs)and 351 edges.Protein-protein interaction(PPI)analysis of the mRNAs within the ceRNA network highlighted pathways including apoptosis, intracellular signaling transduction, hypoxia-inducible factor-1(HIF-1), AMP-activated protein kinase(AMPK), Janus kinase-signal transducer and activators of transcription(JAK-STAT)signaling, carbon metabolism, glycolysis, and thyroid hormone pathways, all of which regulate lipid metabolism, hypoxia, and glycolysis.Cytohubba analysis identified the top 10 hub genes: Bcl2, Src, Cebpb, Creb1, Runx1, Foxo3, Ets1, Socs3, Slc2 a4, and Pkm. Conclusions:The ceRNA network that regulates the browning of white adipose tissue is involved in various pathways, including carbon metabolism, glycolysis, thyroid hormone signaling, growth hormone signaling, prolactin signaling, as well as the HIF-1, AMPK, and JAK-STAT pathways.Key regulatory miRNAs in this context include miR-30e-5p, miR-182-5p, miR-20b-5p, miR-144-3p, miR-363-3p, miR-141-3p, miR-203-3p, and miR-107-3p.These miRNAs may serve as critical targets for inducing browning in response to cold exposure.

Objective To evaluate the application of ELISA randomized quality control,and continuously improve the laboratory testing capacity and quality assurance,in order to gradually improve the application of randomized quality control to the daily testing of ELISA.Methods Collected the quality control data of KEHUA HBsAg,compared the difference between randomized quality control data and immobilized quality control data.Group comparison of randomization quality control between rows and columns.The randomized quality control data were analyzed retrospectively and the quality control chart was established by using the randomized quality control data.Analyzed and compared the lost-control situation of randomized quality control and immobilized quality control.Results Randomized quality control S/CO value(2.831±0.343)and immobilized quality control S/CO value(2.651±0.260)in the same microplate,the difference between two was statistically significant(t=5.970,P＜0.05).The differences between randomized quality control and immobilized quality control in columns 2 to 8 were statistically significant(t=2.285～5.536,all P<0.05).There were no statistically significant differences between randomized quality control and immobilized quality control in column 9 to 12(t=0.031～1.605,all P>0.05).There was no statistically significant difference in randomization quality control among all lines(F=0.858,P＞0.05).The randomized quality control data was used to establish a quality control chart.Within the time range of the collected data,the randomized quality control was out of control for 6 times,all were greater than+3s,and the loss of control rate was 4.72%(6/127).Fixed position quality control lost control 9 times during the same period,all of which were greater than+3s,with a loss of control rate of 0.61%(9/1 481).Conclusion The randomized quality control has a greater possibility to reflect the factors affecting all the samples on the microporous plate.Random quality control can be used to find possible systematic errors in testing.Randomized quality control can gradually be fully applied to daily indoor quality control,but the loss of control rate and coefficient of variation may increase.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To analyze the differentially expressed messenger RNA(mRNA), microRNA(miRNA), and long non-coding RNA(lncRNA)during the browning of mouse subcutaneous adipose tissue, construct a competitive endogenous RNA(ceRNA)network, and provide a theoretical basis for investigating the regulatory mechanisms of white adipose tissue browning.Methods:A cold-stimulated mouse model was established for transcriptome sequencing.Bioinformatics tools were employed to screen for differentially expressed mRNAs, miRNAs, and lncRNAs.An integrated mRNA-miRNA-lncRNA analysis was performed to construct a ceRNA network.Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and Gene Set Enrichment Analysis(GSEA)were conducted on the differentially expressed mRNAs and ceRNA networks to explore transcriptional regulation during the cold-induced browning of subcutaneous adipose tissue.Results:Transcriptomic analysis of the cold-stimulated model identified 4, 256 differentially expressed RNAs, which include 3, 600 mRNAs, 588 lncRNAs, and 68 miRNAs.GO and KEGG analyses revealed that the browning of white adipose tissue involves immune-related processes, such as immune system processes, immune responses, adaptive and innate immune responses, and the positive regulation of T-cell activation.A ceRNA network associated with browning regulation was constructed, comprising 233 nodes(188 mRNAs, 34 miRNAs, and 11 lncRNAs)and 351 edges.Protein-protein interaction(PPI)analysis of the mRNAs within the ceRNA network highlighted pathways including apoptosis, intracellular signaling transduction, hypoxia-inducible factor-1(HIF-1), AMP-activated protein kinase(AMPK), Janus kinase-signal transducer and activators of transcription(JAK-STAT)signaling, carbon metabolism, glycolysis, and thyroid hormone pathways, all of which regulate lipid metabolism, hypoxia, and glycolysis.Cytohubba analysis identified the top 10 hub genes: Bcl2, Src, Cebpb, Creb1, Runx1, Foxo3, Ets1, Socs3, Slc2 a4, and Pkm. Conclusions:The ceRNA network that regulates the browning of white adipose tissue is involved in various pathways, including carbon metabolism, glycolysis, thyroid hormone signaling, growth hormone signaling, prolactin signaling, as well as the HIF-1, AMPK, and JAK-STAT pathways.Key regulatory miRNAs in this context include miR-30e-5p, miR-182-5p, miR-20b-5p, miR-144-3p, miR-363-3p, miR-141-3p, miR-203-3p, and miR-107-3p.These miRNAs may serve as critical targets for inducing browning in response to cold exposure.

Objective:To investigate the efficacy and safety of tocilizumab in the treatment of critically ill children with acute necrotizing encephalopathy (ANE).Methods:It is a retrospective cohort study. The children with ANE admitted to the pediatric intensive care unit of 4 Chinese tertiary hospitals from December 2022 to November 2023 were divided into conventional treatment group and tocilizumab group, and the comparison between groups was performed by using Mann ‐ Whitney U test or Chi-square test. Results:Among 21 cases of severe ANE, there were 11 males with the onset age of 65 (27, 113) months. The duration from onset to PICU admission was 2 (1, 2) days. There were 13 cases of ultra-high fever (greater than 40 ℃), including 18 cases of convulsions, and 19 cases with a GCS score of less than 8 points. The causative agent was novel coronavirus Omicron in 7 cases and influenza A in 14 cases. All cases had central respiratory failure requiring mechanical ventilation. Of the 21 cases, 18 were shock, 15 were coagulopathy, 10 were kidney injury and 13 were liver dysfunction. Of these hospitalized patients, 8 children with ANE were treated with tocilizumab. Eight cases received continuous blood purification (CBP) treatment, 5 of them were combined with plasmapheresis. Serum cytokine levels were elevated in 21 children with ANE, including (interleukin, IL)-6 and IL-8 (61 (22, 1 513) and 68 (5, 296) ng/L). There were 14 cases (67%) deaths, including 11 cases in the conventional treatment group and 3 cases in the tocilizumab group. There was no significant difference in the mortality rate between the two groups ( P=0.056). Tocilizumab-related rash or other adverse events were not observed. Conclusions:The motality of critically ill ANE patients was high. The combination of Tocilizumab with conventional treatment did not reduce the motality of severe ANE patients, and no adverse reactions of tocilizumab were observed.

Objective:To explore the prediction model of tissue chip technology for the chemotherapy response of patients with colorectal cancer.Methods:217 patients with colorectal cancer who had received standardized chemotherapy in the Affiliated People’s Hospital of Ningbo University from Jan. 2017 to Dec. 2019 were prospectively selected. The patients were randomly divided into training set (152 cases) and test set (65 cases) according to the ratio of 7:3, and were followed up for 6 months. The clinical data of the patients in the training set were compared, the expression levels of Ang-2, caspase-3 and CD147 in the patients were analyzed by tissue microarray technology, and the related factors affecting the responsiveness of colorectal cancer chemotherapy were analyzed by the Logistic regression model. R software was used based on the training set. A nomogram prediction model was built and model performance on the test set was evaluated.Results:One case was excluded from the training center, and 151 cases were finally included, including 93 cases in the chemotherapy response group and 58 cases in the chemotherapy response group. The tumor diameter, serum carcinoembryonic antigen, caspase3, Ang2 expression level, and the proportion of clinical stage IV in the poor chemotherapy group were significantly higher than those in the good chemotherapy group (all P<0.05) ; Logistic regression showed tumor diameter ( OR=2.394), serum carcinoembryonic antigen ( OR=1.878), caspase-3 ( OR=4.261), Ang-2 expression level ( OR=5.457), and clinical stage IV ( OR=5.954) were independent risk factors for adverse drug reactions in patients with colorectal cancer (all P<0.05). The consistency index (C-index) for predicting the factors related to adverse chemotherapy reactions in patients with colorectal cancer was 0.915. External verification showed that the sensitivity was 86.96%, the specificity was 92.50%, and the accuracy was 90.48% (42/65) . Conclusion:The expression levels of Ang-2 and caspase-3 are correlated with the responsiveness of colorectal cancer to chemotherapy, and can be used as predictive indicators to evaluate the responsiveness of colorectal cancer to chemotherapy.