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 clinical efficacy of ceftazidime/avibactam(CZA)plus aztreonam(ATM)for New Delhi metallo-β-lactamase(NDM)carbapenem-resistant Klebsiella pneumoniae(CRKP)infection after kidney transplantation.Methods:Clinical data are retrospectively reviewed for 11 RT recipients infected with NDM metallo-β-lactamase CRKP admitted into First Affiliated Hospital of Xi 'an Jiaotong University and Affiliated Renji Hospital of Shanghai Jiao Tong University from November 2018 to December 2019.Based upon treatment protocol, they are divided into two groups of ceftazidime/avibactam plus aztreonam(CZA-ATM, 5 cases)and other effective antibiotics(OAA, 6 cases).Age, gender, infection type, drug resistance gene, changes in body temperature and leucocyte count, treatment course and prognosis are summarized.Results:A total of 11 patients with NDM-producing CRKP infection after RT are recruited.There are seven males and four females with an age range of(19~66)(38.9±14.4)years.There are mixed pulmonary and urinary tract infections(3 cases), urinary tract infection(2 cases), pulmonary infection(1 case)and perirenal infection(5 cases).All isolates harbore NDM carbapenemase gene, 5 isolates carry Klebsiella pneumoniae carbapenemase(KPC)gene and 1 isolate contained both imipenemase metallo-β-lactamase(IMP)and verona integron-encoded metallo-β-lactamase(VIM)gene concurrently.Ceftazidime-avibactam plus aztreonam(CZA-ATM)is prescribed in five patients while the remainders receive OAA.No adverse reactions occurred in individuals on CZA-ATM and 2 cases on OAA have adverse reactions with a poor appetite and diarrhea.After 30-day infection, the curative cases of CZA-ATM and OAAs groups reach 4 and 5 respectively.No death occurred in neither groups at Day 30.And 90-day mortality is 0 and 1 respectively.Conclusions:For RT patients infected with NDM-producing CRKP, CZA-ATM combination therapy may be another effective treatment.

Objective:To explore the correlation between post-transplant non-HLA antibodies and humoral rejection(HR)after kidney transplantation(KT).Methods:A retrospective study was conducted for KT recipients with non-HLA antibody level detected from September 2019 to January 2021.The recipients with biopsy confirmed HR and donor-specific HLA antibodies negative or feeble positive at the time of HR were designated as HR group while recipients with stable renal allograft function from 2 weeks post-KT to the time of detecting non-HLA antibody as stable group.The levels of HLA antibody, MHC classⅠchain-related gene A(MICA)antibody and 32 non-HLA antibodies were tested by Luminex single antigen bead and the levels of angiotensin Ⅱ type 1 receptor(AT1R)antibody quantified by enzyme-linked immunosorbent assay (ELISA). Inter-group differences in positive rate of non-HLA antibodies and number of positive non-HLA antibodies were analyzed.Results:Twenty-four recipients had positive non-HLA antibodies while the remainders had no positive non-HLA antibodies.Three HR recipients were positive for actin antibody, collagen Ⅲ antibody, glutathione S-transferase theta-1 antibody or IFN-γ antibody respectively.However, all four non-HLA antibodies of stable recipients were negative.There was significant inter-group difference( P=0.017). Four HR recipients were positive for collagenⅡantibody while only 1 stable recipient was positive for collagenⅡantibody.The positive rate of collagenⅡ antibody was significantly higher in HR recipients than that in stable recipients( P=0.023). HR recipients had an average of 2.36 positive non-HLA antibodies while stable recipients had an average of 0.90.There was significant inter-group difference ( P=0.008). Conclusions:A high level of non-HLA antibodies may elevate the risk of HR after KT.

Objective:To explore the protective effects of exosomes derived from bone marrow mesenchymal stem cells(BMSC)on ischemia-reperfusion injury(IRI)in mice.Methods:A total of 30 C57BL/6 mice were randomly grouped into 6 groups of control, Norm-BMSC-exo, Hypo-BMSC-exo, IRI, Norm-BMSC-exo+ IRI and Hypo-BMSC-exo+ IRI.The model for IRI(25 min)was constructed.The serum levels of creatinine(Cr)and blood urea nitrogen(BUN)and histomorphology were examined at 24 h post-reperfusion.The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β(IL-1β)monocyte chemoattractant protein-1(MCP-1)and interleukin-10 (IL-10)were measured.The survival rate was observed for 7 days post-IRI.We also detected macrophage polarization glycolysis and oxidative phosphorylation(OXPHOS).Results:Compared with IRI group, Norm-BMSC-exo+ IRI group showed low levels of creatinine(Cr)and blood urea nitrogen(BUN)and mild pathological injury.The protective effects were enhanced in Hypo-BMSC-exo+ IRI group.BMSC-exo pretreatment could significantly improve the survival rate of mice post-IRI.Reverse transcription-polymerase chain reaction(RT-PCR)revealed that BMSC-exo significantly lowered the levels of TNF-α, IL-1β, MCP-1 and elevated the level of IL-10.BMSC exosomes polarized macrophage toward an M2 phenotype.And Hypo-exo could reprogramme macrophages to undergo a metabolic switch toward OXPHOS and away from glycolysis.Conclusions:Hypo-BMSC-exo could improve kidney injury via inducing M2 polarization in macrophages through promoting OXPHOS and suppressing glycolysis.

【Objective】 To analyze the allele frequencies of the human platelet antigens 1-29 system (HPA-1-29bw) in Nanjing Han platelet donors, so as to provide references for compatible platelet transfusion. 【Methods】 HPA genotyping was performed by Sanger sequencing method in 900 Nanjing Han regular platelet donors who donated at Jiangsu Province Blood Center from February to September 2019. The frequencies of alleles and genotype were calculated using direct counting method. 【Results】 The HPA allele frequencies in Nanjing Han platelet donors were HPA-1a 0.9950, 1b 0.0050, 2a 0.9467, 2b 0.0533, 3a 0.5850, 3b 0.4150, 4a 0.9989, 4b 0.0011, 5a 0.9822, 5b 0.0178, 6a 0.9828, 6b 0.0172, 11a 0.9994, 11b 0.0006, 15a 0.5317, 15b 0.4683, 21a 0.9928 and 21b 0.0072, respectively. Only a allele was detected in HPA-7-10w, -12-14w, -16-20w and -22-29bw systems.The highest mismatch rate of HPA genes in 900 platelet donors was HPA-15 system, followed by HPA-3 system, with the rate of 37.40%(337/900) and 36.77%(331/900), respectively. One heterozygote was detected in HPA-11w system. 【Conclusion】 The chracteristics of HPA alleles frequencies in Nanjing Han platelet donors is that HPA-15 and HPA-3 are the most common heterozygotes, which should be paid attention to in local clinical transfusion.

Objective:To explorer the optimal method of detecting donor kidney carrier carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods:Clinical data were retrospectively analyzed for 1120 donation-after-circulatory-death (DCD) kidneys and bacterial detection of kidney perfusion fluid was performed from January 2015 to January 2019. A total of 1120 kidney perfusion fluid samples were collected with sterile tubes and submitted for culturing. And 451 specimens were delivered in sterile tubes and blood culture bottles simultaneously And 729 specimens assayed for carbapenemase genes with GeneXpert.Results:Among 1120 kidneys, CRKP was confirmed in 21 grafts with an infection rate of 1.87 %. The detection of carbapenemase genes with Genexpert showed that KPC was positive for 9/16 CRKP positive grafts. Sensitivity, specificity, false-positive rate, false-negative rate and ROC-AUC were calculated at 56.3 %, 100 %, 0, 43.7 % and 0.781 respectively. And 11 specimens delivered with sterile tube were culture positive for CRKP. Sensitivity, specificity, false-positive rate, false-negative rate and ROC-AUC were calculated at 52.3 %, 100 %, 0, 47.6 % and 0.762 respectively. Among 451 perfusion fluid samples collected with anaerobic blood culture bottle, 15 samples had a positive culture for CRKP. Sensitivity, specificity, false-positive rate, false-negative rate and ROC-AUC were calculated at 100 %, 100 %, 0, 0 and 1 respectively. In terms to anaerobic blood culture bottle, sensitivity, specificity, false-positive rate, false-negative rate and ROC-AUC were calculated at 60 %, 100 %, 0 , 40 % and 0.80 respectively.Conclusions:Genexpert assay is suitable for rapid and convenient detection of carbapenemase genes using kidney perfusion fluid. Culturing perfusion fluid samples collected with anaerobic blood culture bottle is clinically valuable diagnostic tool of CRKP. A combination of both methods is worthy of clinical promotion and application diagnosis of donor kidney derived CRKP in terms of greater accuracy and timeliness.

OBJECTIVE: To screen for Vel- rare blood type donors and determine the frequency of SMIM1 c.64_80del allele in Yili Prefecture of Xinjiang, China. METHODS: DNA pooling and PCR-sequence-specific primers (PCR-SSP) was conducted to screen individuals carrying the SMIM1 c.64_80del variant, and Sanger sequencing of SMIM1 exon 3 was carried out to verify the genotype of those with the variation. SMIM1 intron 2 was also sequenced to identify single nucleotide polymorphisms (SNPs) that may affect the expression of Vel antigen. RESULTS: Among 3328 blood donors, 14 were identified as heterozygotes for the SMIM1 c.64_80del allele, its allele frequency was 0.21%; no homozygous SMIM1 c.64_80 deletions was found. For SNP rs1175550, all of the 14 individuals had an AA genotype, among whom 5 carried heterozygous 7111ins GCA variant in intron 2. CONCLUSION The allelic frequency of SMIM1 c.64_80del in Yili area is approximately 0.21%, which is reported for the first time.
Alleles ; Blood Group Antigens/genetics* ; China ; Gene Frequency ; Genetic Variation/genetics* ; Genotype ; Humans ; Membrane Proteins/genetics* ; Polymorphism, Single Nucleotide/genetics*

Objective To explore the rapid diagnosis and clinic treatment of donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in renal transplant recipients .Methods Retrospective analysis was performed for clinical data and the diagnosis and treatment of 9 renal transplant recipients with donor-derived CRKP infection from March 2017 to May 2019 .Results Among 526 renal transplant recipients ,nine were diagnosed with donor-derived CRKP infection by bacterial culture or KPC enzyme gene test .The infection rate was 1 .71％ .One recipient receiving carbapenem and tigecycline died while the remainders survived after a treatment of ceftazidime-avibactam and carbapenem . One recipient underwent graft resection . Among 8 recipients on ceftazidime-avibactam ,5 cases received a standard dose of 3 .75 g/d while another 3 cases had a high dose of 7 .5 g/d .One patient in standard-dose group underwent graft resection due to an arteriorrhexis of artery anastomosis .After graft resection ,the patient received a high dose of ceftazidime-avibactam and survived to date .The grafts of three patients in high-dose treatment group survived .Conclusions KPC enzyme gene detection plus injecting lavage fluid into blood culture bottle for bacterial culture is rapid and accurate for diagnosing donor-derived CRKP infection . A combination of ceftazidime-avibactam plus carbapenem is effective for donor-derived CRKP infection .A high dose of ceftazidime-avibactam may improve the efficacy without obvious side effects .

OBJECTIVETo analyze a sample with ABO subgroup using serological and molecular methods.

METHODSThe ABO phenotype of the sample was determined with a tube method, and the activity of glycosyltransferases was determined with an uridine diphosphate galactose transferring method. The ABO gene of the propositus was identified by PCR with sequence-specific primers (PCR-SSP). In addition, exons 6 and 7 of the ABO gene were cloned and sequenced.

RESULTSNeither A nor B antigen was identified in the propositus, despite that its anti-B antibody was found to be attenuated. No activity of α -1, 3-D-galactosyltransferase was detected in the serum. The presence of B and O alleles were confirmed by PCR-SSP, and a novel mutation (562C to T) of the exon 7 was confirmed by sequencing, which has led to an amino acid substitution (Arg to Cys) at position 188. The genotype of the propositus was determined as Bnew/O.

CONCLUSIONA novel B allele has been identified, which was named as Bw39 by the Blood Group Antigen Gene Mutation Database (BGMUT).

ABO Blood-Group System ; genetics ; Adult ; Alleles ; Amino Acid Substitution ; Base Sequence ; Exons ; Galactosyltransferases ; genetics ; Humans ; Male ; Molecular Sequence Data ; Point Mutation

OBJECTIVETo analyze an individual with SMIM1 c.64_80 heterozygous deletional mutation and his family members.

METHODSBased on the molecular basis of Vel negative blood type, PCR primers specific for SMIM1 wild-type allele and c.64_80del allele were designed. PCR-sequence specific primer (PCR-SSP) and Sanger sequencing were employed to determine the genotype of all subjects. Inheritance of the Vel blood group system was investigated by pedigree analysis.

RESULTSPCR-SSP and DNA sequencing demonstrated that the proband was heterozygous for the SMIM1 c.64_80del allele. Pedigree investigation showed that his father had the same mutation, while his mother and elder sister were of wide type. No individual with homozygous c.64_80del allele was found.

CONCLUSIONPCR-SSP and DNA sequencing confirmed that the proband was heterozygous for the c.64_80del mutation. The mutation inherits form his father.

Adult ; Blood Group Antigens ; genetics ; Female ; Gene Deletion ; Genetic Testing ; Homozygote ; Humans ; Male ; Membrane Proteins ; genetics ; Pedigree ; Sequence Analysis, DNA