Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Therefore,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. Methods PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and Clinicaltrial.gov were systematically searched from inception to July 2023.Randomized controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were included.Outcomes were computed as risk ratios(RR)using a fixed-effects model. Results Overall,39 RCTs with a total of 85,755 participants were included.Compared to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug subtypes.However,no significant associations were observed. Conclusion Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments.Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Objective:To explore the association between child abuse and suicidal ideation in patients with bi-polar disorder.The mediation of self-esteem and depression in this association was also investigated.Methods:A to-tal of 292 patients with bipolar disorder who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were enrolled.Their child abuse,suicidal ideation,self-esteem,depres-sion,and mania were assessed with the Childhood Trauma Questionnaire(CTQ),Beck Scale for Suicide Ideation-Chinese Version(BSICV),Self-Esteem Scale(SES),17-item Hamilton Depression Rating Scale(HAMD-17)and Young Mania Rating Scale(YMRS).The mediating effects were evaluated using PROCESS for SPSS.Results:The BSICV scores were positively associated with the scores of CTQ(r=0.37,P＜0.01)and HAMD-17(r=0.53,P＜0.01)and negatively associated with SES scores(r=-0.50,P＜0.01)in patients with bipolar disorder.Self-esteem and depression played mediating roles between child abuse and suicidal ideation,respectively(95％CI:0.01-0.09,0.01-0.10).Besides,self-esteem and depression sequentially mediated the relationship between child a-buse and suicidal ideation(95％CI:0.02-0.06).Conclusion:Child abuse,low self-esteem,and depression may be related factors of suicidal ideation in patients with bipolar disorder.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Objective:To screen and identify H-2 d-restricted T cell epitopes in fusion (F) and attachment (G) glycoproteins of Nipah virus (NiV) in mice. Methods:The complete peptides (single peptide contains 15 amino acids, and 10 amino acids were repeated in the front and back peptides) derived from F and G antigens were mixed into peptide libraries. BALB/c mice were immunized with DNA vaccines expressing NiV F and G proteins alone and in combination. The full sequence peptide libraries of F and G antigens were mixed into peptide pools by matrix design, and spleen cells of immunized mice were collected and analyzed by IFN-γ ELISPOT assay to detect the dominant H-2 d-restricted epitope peptides. Results:Twelve dominant H-2 d-restricted peptides were screened from the F protein-specific peptide library and the 56th peptide produced the strongest reaction. Four dominant peptides were screened from the G protein-specific peptide library and the 72nd peptide produced the strongest reaction. Conclusions:In this study, 12 F antigen-specific and 4 G antigen-specific H-2 d restricted dominant T cell epitopes of NiV were screened and identified by IFN-γ ELISPOT, which could provide reference for immunological analysis of NiV and vaccine research.

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) of aquaporin 7 ( AQP7) and aquaporin 9 ( AQP9) genes and type 2 diabetes mellitus (T2DM) among ethnic Han Chinese population. METHODS: A case-control study involving 1194 subjects with T2DM and 1274 non-diabetic mellitus (NDM) subjects were enrolled. Genotypes of three SNPs (rs3758269 of AQP7 gene, rs16939881 and rs57139208 of AQP9 gene) were determined by using a MassArray method. The association of the three SNPs with T2DM was assess, and the correlation of glucose and lipid metabolism parameters with various SNP genotypes in the NDM group was analyzed. RESULTS: The allelic and genotypic frequencies of the three SNPs did not differ significantly between the two groups (P>0.05). Nor was there significant difference between the two groups with different genetic models (P>0.05). No significant association of genotypes of AQP7 gene rs3758269, AQP9 gene rs16939881 and rs57139208 with glucose and lipid metabolism parameters were observed in the NDM group (P>0.05). CONCLUSION The rs3758269 in AQP7 gene and rs16939881 and rs57139208 in AQP9 gene are not associated with the genetic susceptibility of T2DM among ethnic Han Chinese population.
Aquaporins/genetics* ; Case-Control Studies ; China ; Diabetes Mellitus, Type 2/genetics* ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide

Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.
Core Binding Factor Alpha 2 Subunit/metabolism* ; DNA Methylation ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Promoter Regions, Genetic

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
Humans ; Lung Neoplasms/drug therapy* ; Treatment Outcome ; Neoplasm Recurrence, Local/chemically induced* ; Quinolines/adverse effects*

Objective:To explore the application of web problem-based learning (WPBL) + case-based learning (CBL) combined with clinical pathways in dermatological nursing teaching.Methods:A total of 120 nurses who practiced in the dermatology department of The First Affiliated Hospital of Air Force Medical University from July 2018 to June 2020 were selected as the research objects. According to the nurse practice period, they were divided into a control group and a study group, with 60 people in each group. The control group used traditional teaching, and the study group used WPBL+CBL combined with clinical pathways for teaching. After the teaching, the two groups of practical nurses were assessed for their theoretical and clinical operational abilities, and the comprehensive abilities of the two groups of practical nurses and their satisfaction with teaching were assessed through questionnaire surveys. SPSS 22.0 was used for t test and χ2 test. Results:The theoretical and clinical performance assessment results of the study group were better than those of the control group, and the difference was statistically significant ( P<0.001). The research group was better than the control group in assessment of improving clinical operation ability, independent problem-solving ability, cultivating teamwork ability, improving self-learning ability, improving ability of presenting and analyzing problems, improving comprehensive analysis ability, cultivating clinical thinking ability and comprehensive ability, with statistical significance ( P<0.001). The satisfaction rate of the trainee nurses in the study group was 93.33%, and the satisfaction rate of the trainee nurses in the control group was 31.67%, with statistically significant differences. Conclusion:WPBL+CBL combined with clinical pathways teaching can significantly improve the theoretical and clinical operation ability of dermatology practice nurses, and improve their comprehensive ability and clinical teaching satisfaction rate, which is worthy of application and promotion in clinical nursing teaching.

Objective:To investigate the discriminant function of optical coherence tomography angiography (OCTA) in the diagnosis of primary open angle glaucoma (POAG) and to evaluate the correlation between vessel density, as measured by OCTA, and visual field mean defect (MD) in patients with POAG.Methods:A case control study was designed.Ninety-five eyes of 54 patients with POAG and ninety-six eyes of 48 healthy subjects in Changsha Aier Eye Hospital were included in this study.The vessel density in the radial peripapillary capillary (RPC) network, the macular vessel density, the ganglion cell complex (GCC) layer thickness, the macular thickness, and the retinal nerve fiber layer thickness were tested for correlation with MD.The aera under the receiver operating characteristic (ROC) curves (AUC), as well as sensitivities at fixed vessel density specificities in the RPC network, and macular regions were analyzed.ROC regression was used to evaluate the effect of covariates on the diagnostic abilities.The study protocol was approved by the Ethics Committee of Changsha Aier Eye Hospital.Written informed consent was obtained from all subjects prior to entering the study cohort.Results:Compared with the normal control group, the macular area and vessel density in the RPC network were significantly decreased in the POAG group ( P<0.001). Also in the POAG group, except for the capillary density inside the disc, all other measurements including the density of superficial capillaries in the macula, the density of deep capillaries in the macula, the density of RPC layers around the optic disc, the average capillary density of the optic disc RPC layer, the capillary density of the optic disc RPC layer (above, below, nasal, and temporal), the thickness of the retinal nerve fiber layer, the thickness of the whole macular layer, and the thickness of the GCC layer of the macula area were positively correlated with the MD value ( r=0.586, 0.352, 0.610, 0.592, 0.598, 0.589, 0.445, 0.587, 0.578, 0.530, 0.609; all at P<0.01). The AUCs of vessel densities ranged from 0.623 to 0.927.The highest diagnostic efficiency was the RPC vessel density (whole image), the AUC value was 0.927. Conclusions:The OCTA parameters have a high diagnostic ability for POAG, except for the capillary density of inside the disc, all other vascular parameters are positively correlated with the MD value.

Objective To construct phage display antibody library of artificial mutation to compare with the sequence of the natural phage display antibody library. To scientifically evaluate the quality of the artificial mutation of phage display library, and provide some references for the further transformation of the nanobody. Methods Using random mutation method, NNY fixed-point santuration mutation was performed on combine the follicle-stimulating hormone receptor (FSHR) of human nanobody. The mutant DNA sequence was connected to the vector pMECS to construct the phage display library of VHH06-CDR3 random mutation. By sequencing and analysis of DNA sequences, the diversity of the library and the amino acid distribution of CDR3 were compared between mutation library and the immune library of FSHR. The degree of enrichment of cloning was determined by six rounds of affinity screening. Results According to the NNY mutation rule ,the CDR3 regions with 16 amino acids by random mutations was synthesized and the VHH-CDR3 random mutant phage display library was constructed . The phage display library of VHH06-CDR3 random mutant size was 7.36×108 cfu/ml. Polyclonal and monoclonal phage ELISA showed that after six rounds of screening, the output phage and the combination of FSHR showed obvious enrichment, but there was no clone combined with FSHR. Conclusions Although the VHH06-CDR3 mutant phage display library has sequence diversity, it is not conducive to obtaining target antibodies in affinity screening due to the lack of functional diversity of CDR3.