Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

Objective:To analyze the positive detection rate, main genotypes of β-thalassemia in western region of Guangxi Zhuang Autonomous Region (referred to as Guangxi).Methods:Retrospective analysis of 26 189 individuals who underwent gene testing for thalassemia at the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2013 to December 2019. Using the crossing breakpoint PCR (Gap-PCR) and reverse dot blot (RDB) techniques to detect Chinese common type of 7 kinds of α-thalassemia and 17 kinds of β-thalassemia genotypes, high-throughput sequencing(Sanger) was performed for suspected rare β-thalassemia. Gap-PCR was used for suspected deletion β-thalassemia types.Results:β-thalassemia was diagnosed in 4 495 (17.16%) of 26 189 samples. A total of 6 177 alleles of 20 types of β-thalassemia were detected, mainly CD17 (2 712 cases, 43.90%) and CD41-42 (2 240 cases, 36.26%), including 7 rare alleles: Gγ +( Aγδβ) 0, SEA-HPFH, Hb New York, Hb G-Taipei, Hb Hezhou, Hb G-Coushatta and IVS-Ⅱ-81. There were 3 903 case (86.83%) heterozygous, 273 case (6.07%) double heterozygous, and 319 case (7.10%) homozygous among 4 495 β-thalassaemia subjects. A total of 48 genotypes were detected. The two most common genotypes were CD17/β N (1 890 cases, 42.05%) and CD41-42/β N (1 212 cases, 26.96%), accounted for 69.01% (3 102/4 495). Seven rare genotypes were detected: Gγ +( Aγδβ) 0/β N in 3 cases, Hb New York/β N in 3 cases, Hb G-Taipei/β N in 2 cases, SEA-HPFH/β N, Hb Hezhou/β N, Hb G-Coushatta/β N and IVS-Ⅱ-81/β N in 1 case each. A total of 1 041 cases (3.97%, 1 041/26 189) of 116 types of αβ-thalassemia were detected, mainly -- SEA/αα composite CD17/β N (144 cases, 13.83%), followed by -α 3.7/αα composite CD17/β N (112 cases, 10.76%). Conclusions:Western region of Guangxi is a high prevalence area of β-thalassemia, CD17/β N and CD41-42/β N are the main genotypes. The variation spectrum of β-thalassemia is complex and diverse, with rich genotype.

Objective To investigate the characteristics of adverse drug event(ADE)related to tacrolimus(Tac)in pediatric solid organ transplant recipients.Methods The data were retrieved from the US Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the second quarter of 2023.The ADE data of pediatric organ transplant recipients with Tac as the primary suspected drug were extracted.The relationship between Tac and ADE was quantitatively analyzed by proportional imbalance method.Basic characteristics and signal strength of ADE related to Tac were analyzed.ADE related to Tac in children of different ages and different types of organ transplantation were analyzed.Results A total of 1 443 children's ADE reports involving Tac were screened,including 188 cases(13.0％)of heart transplantation,668 cases(46.3％)of liver transplantation,531 cases(36.8％)of kidney transplantation and 56 cases(3.9％)of lung transplantation.The median age of children was 10 years old.The top three countries with ADE reporting were the United States,France and the United Kingdom.China reported 26 cases,accounting for 1.8％.Infection and infectious diseases accounted for the highest proportion(20.96％)in ADE related to Tac,including EB virus and cytomegalovirus infection,etc.Infection and infectious diseases occupied the largest proportion of ADE related to Tac in children of different ages,whereas the pathogen types were different.Rejection,unstable immunosuppression level and renal function damage were also common ADE related to Tac in children of all ages.Nervous system disease was the main ADE in heart transplant recipients,while infection and infectious diseases were more common in liver and kidney transplant recipients.Rejection was the most common ADE in lung transplant recipients.Conclusions ADE related to Tac possess different distribution characteristics in different types of organ transplantation.Extensive attention should be paid to individualized drug monitoring and risk assessment in pediatric organ transplant recipients,thereby optimizing Tac treatment and reducing the risk of ADE.

Delayed graft function in kidney transplant recipients is one of the common early complications after kidney transplantation,which is an independent risk factor affecting the short-term and long-term survival of renal allografts.Branch of Organ Transplantation of Chinese Medical Association and Branch of Kidney Transplantation of China International Exchange and Promotive Association for Medical and Health Care organized well-known Chinese experts in organ transplantation and related disciplines to formulate and discuss the determination of the scope and clinical problems,evidence retrieval and screening,and the formation of recommendations based on"Technical Specification for the Diagnosis and Treatment on Delayed Graft Function After Renal Transplantation(2019 edition)".After two rounds of collective examination and approval by Chinese Medical Association and China International Exchange and Promotive Association for Medical and Health Care,"Guidelines for Clinical Diagnosis and Treatment of Delayed Graft Function in Kidney Transplant Recipients in China"was finally formulated.This guideline puts forward recommendations and explanations regarding 21 clinical problems including the concept,mechanism,risk factors,diagnosis,prevention,treatment and application of immunosuppressive drugs for delayed graft function in kidney transplant recipients,aiming to standardize the diagnosis,prevention and treatment of delayed graft function in kidney transplant recipients,enhance clinical efficacy of kidney transplantation,prolong short-term and long-term survival of kidney transplant recipients and renal allografts and promote the development of the discipline of transplantation.

Urinary tract infection is the most common infectious complication after kidney transplantation.To further reduce the incidence of urinary tract infection after kidney transplantation,improve the diagnosis and treatment level of urinary tract infection after kidney transplantation in China,prevent the development of bacterial drug resistance and ensure the safety and effectiveness of drug use,Branch of Organ Transplantation of Chinese Medical Association organized experts in the fields of kidney transplantation and infectious diseases to consider clinical status of urinary tract infection after kidney transplantation in China,refer to"Diagnosis and Treatment of Urological and Andrological Diseases in China(2022 edition)"and"Urinary Tract Infection in Solid Organ Transplant Recipients in American Society of Transplantation Practical Guidelines for Infectious Diseases(2019 edition)",and formulate"Guidelines for Clinical Diagnosis and Treatment of Urinary Tract Infection in Kidney Transplant Recipients in China"from the perspectives of clinical classification and definition,epidemiology and etiology,diagnosis and treatment of urinary tract infection after kidney transplantation,respectively.

Objective To explore the molecular mechanisms and cell-cell interactions in the injury process of pancreatic islet transplantation.Methods Single-cell transcriptome data from mouse islets treated with inflammatory factors were used,and data processing was performed using the Seurat package,with integrated data to remove batch effects.Cell subpopulations were annotated based on known markers.Cell-cell interactions in the inflammatory factor-treated group were analyzed using the CellChat package,and inferred based on the expression of cell surface receptors and ligands.Gene set enrichment analysis was used to clarify the biological processes enriched in β-cells after treatment with inflammatory factors.Finally,differentially expressed transcription factors were identified and verified using microarray datasets of donor islet ischemic injury and Western blotting.Results A total of 7 different cell subpopulations were found in mouse islets,with β-cells being the most abundant.Cell-cell interaction network analysis showed that the number and strength of interactions between ductal cells and other cells were the highest.Gene set enrichment analysis showed that after treatment with inflammatory factors,the immune response was positively enriched in β-cells,while peptide hormone metabolism,bile acid metabolism,and ion homeostasis were downregulated.The common differential transcription factors identified in the mouse single-cell transcriptome and the microarray dataset of donor islet ischemic injury were early growth response 1(EGR1),nuclear factor-κB inhibitor α(NFKBIA),and activating transcription factor 3(ATF3).Among them,NFKBIA and ATF3 were upregulated,while EGR1 was downregulated.The expression of EGR1 protein was downregulated after 24 h,48 h,and 72 h of cold ischemia.Conclusions EGR1 is a transcription factor closely related to islet cold ischemia,and future research should focus on the specific mechanisms of EGR1 and its downstream target genes,in order to provide more effective strategies for clinical treatment of islet transplantation.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b.Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases.It is involved in regulating the pathological process of myocardial infarction,myocardial ischemia/reperfusion injury,cardiac hypertrophy,atrial fibrillation,diabetic cardiomyopathy,atherosclerosis,pulmonary hyperten-sion,cerebral ischemia/reperfusion injury,Parkinson's disease,and Alzheimer's disease.Obviously,miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases.However,the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed.Therefore,in this review,we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases.Drugs targeting miR-135b for the treatment of diseases and related patents,highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases,have been discussed.

Kidney Transplantation/adverse effects* ; Magnetics ; Anastomosis, Surgical ; Magnetic Phenomena

Objective:To determine the accuracy and clinical application of donor HLA quartile genotyping based upon transplanted kidney biopsy.Methods:The clinical and follow-up data are retrospectively reviewed for 38 recipients of kidney transplantation(KT)at First Affiliated Hospital of Xi'an Jiaotong University from 2019 to 2022.They are suspected of rejection.HLA quartile genotyping of donor kidney is performed through puncture and DNA analysis by LABType SSO method.Known HLA genotypes of recipients are compared for predicting HLA genotypes of donors.Donor-specific antibody(DSA)is detected by Labscreen Single kit.And SPSS18.0 statistical software is employed for processing baseline data, donor/recipient HLA typing data, recipient DSA antibody data and transplant nephropathy parameters.Results:Among them, 12(31.58%)belonged to HLA-A, B, C, DR and DQ.Four loci are detected in 14 cases(36.84%). Three sites are detected in 10 cases(26.32%). Two sites are detected in 2 cases(5.26%)and a negative correlation exists between detected sites and transplantation time( rs=-0.707, P=0.001). The detection rate of HLA loci is 78.94%(30 cases). B: 65.78%(25 cases); C: 84.21%(32 cases); DR: 57.89%(22 cases); DQ: 100% (38 cases); HLA sites detected in puncture tissue are 89.47% consistent with the results of donor whole blood test, among which HLA-C and HLA-DQ sites are 100% consistent and HLA-A and HLA-B sites 87.50% and 90% consistent and HLA-DR sites 66.7% consistent( P<0.01). Spearman's rank correlation analysis indicated that pathological diagnosis of interstitial inflammation( rs=-0.432, P=0.017), renal tubule atrophy( rs=-0.587, P=0.001)and interstitial fibrosis( rs=-0.560, P=0.001)are correlated negatively with HLA detected sites in transplanted kidney puncture tissue.DSA is detected in 42.1% of recipients and 68.75% of recipients belonged to HLA-DQ. Conclusions:HLA typing results of puncture tissue are consistent with those of whole blood test.Time after transplantation, infiltration of transplanted nephritis cells and degree of fibrosis may influence the detection of HLA loci.Donor HLA quartile genotyping using transplanted kidney biopsy has some diagnostic values for detecting the presence of DSA.

On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Nirmatrelvir inhibits SARS-CoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression.The chiral structure of nirmatrelvir plays a key role in its antiviral activity.Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 expression and occupying the plasma protein binding sites.Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir.However,Paxlovid has many contraindications.Some patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after re-covery.Interestingly,the antiviral activity of nirmatrelvir metabolites,such as compounds 12-18,is similar to or higher than that of nirmatrelvir.Herein,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.