Efficient biosynthesis of γ-aminobutyric acid by rationally engineering the catalytic pH range of a glutamate decarboxylase from Lactobacillus plantarum / 生物工程学报

γ-aminobutyric acid can be produced by a one-step enzymatic reaction catalyzed by glutamic acid decarboxylase. The reaction system is simple and environmentally friendly. However, the majority of GAD enzymes catalyze the reaction under acidic pH at a relatively narrow range. Thus, inorganic salts are usually needed to maintain the optimal catalytic environment, which adds additional components to the reaction system. In addition, the pH of solution will gradually rise along with the production of γ-aminobutyric acid, which is not conducive for GAD to function continuously. In this study, we cloned the glutamate decarboxylase LpGAD from a Lactobacillus plantarum capable of efficiently producing γ-aminobutyric acid, and rationally engineered the catalytic pH range of LpGAD based on surface charge. A triple point mutant LpGADS24R/D88R/Y309K was obtained from different combinations of 9 point mutations. The enzyme activity at pH 6.0 was 1.68 times of that of the wild type, suggesting the catalytic pH range of the mutant was widened, and the possible mechanism underpinning this increase was discussed through kinetic simulation. Furthermore, we overexpressed the Lpgad and LpgadS24R/D88R/Y309K genes in Corynebacterium glutamicum E01 and optimized the transformation conditions. An optimized whole cell transformation process was conducted under 40 ℃, cell mass (OD600) 20, 100 g/L l-glutamic acid substrate and 100 μmol/L pyridoxal 5-phosphate. The γ-aminobutyric acid titer of the recombinant strain reached 402.8 g/L in a fed-batch reaction carried out in a 5 L fermenter without adjusting pH, which was 1.63 times higher than that of the control. This study expanded the catalytic pH range of and increased the enzyme activity of LpGAD. The improved production efficiency of γ-aminobutyric acid may facilitate its large-scale production.

Identification of M1 macrophage-related genes in rejection after kidney transplantation based on weighted gene co-expression network analysis / 器官移植

Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4+ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.

Identification and biological characterization of pathogen causing black spot of Pseudostellaria heterophylla in Fujian province / 中国中药杂志

In Zherong county, Fujian province, the black spot of Pseudostellaria heterophylla often breaks out in the rainy season from April to June every year. As one of the main leaf diseases of P. heterophylla, black spot seriously affects the yield and quality of the medicinal material. To identify and characterize the pathogens causing black spot, we isolated the pathogens, identified them as a species of Alternaria according to Koch's postulates, and then tested their pathogenicity and biological characteristics. The results showed that the pathogens causing P. heterophylla black spot were A. gaisen, as evidenced by the similar colony morphology, spore characteristics, sporulation phenotype, and the same clade with A. gaisen on the phylogenetic tree(the maximum likelihood support rate of 100% and the Bayesian posterior probability of 1.00) built based on the tandem sequences of ITS, tef1, gapdh, endoPG, Alta1, OPA10-2, and KOG1077. The optimum conditions for mycelial growth of the pathogen were 25 ℃, pH 5-8, and 24 h dark culture. The lethal conditions for mycelia and spores were both treatment at 50 ℃ for 10 min. We reported for the first time the A. gaisen-caused black spot of P. heterophylla. The results could provide a theoretical basis for the diagnosis and control of P. heterophylla leaf spot diseases.

Identification and biological characteristics of violet root rot pathogen of Pseudostellaria heterophylla in Fujian province / 中国中药杂志

Violet root rot is one of the main root diseases in the production process of Pseudostellaria heterophylla. To clarify the pathogenic species that cause the violet root rot of P. heterophylla in Fujian province, the roots and the sclerotia with violet root rot symptoms were collected from the main producing areas of P. heterophylla(Fujian province) from 2017 to 2021, and the pathogens were isolated by tissue separation method and identified by morphology and multi-gene phylogenetic analysis. Additionally, the biological characteristics of the pathogens were studied and the fungicides were determined. The results showed that 78 strains of violet root rot were isolated from the collected root samples, which belonged to one type after preliminary morphological identification. Two represen-tative strains were selected from the pathogens for multi-gene phylogenetic analysis, and they were clustered with Helicobasidium mompa together. The suitable culture conditions for the mycelium were OA medium, 25 ℃, pH 6, and ammonium oxalate as the nitrogen source. The lethal temperature of the mycelium was 50 ℃ for 10 minutes. Moreover, 99.1% propiconazole and 98.7% azoxystrobin had the optimal bacteriostatic effect, and the concentrations with the 50% bacteriostatic rate were 16.85 and 12.24 μg·mL~(-1), respectively. On the basis of the above results, the pathogen causing violet root rot of P. heterophylla in Fujian province was H. mompa. The medium type, growth temperature, pH value, nitrogen source, etc. had significant effect on the growth of mycelium.

Research progress on emerging biomarkers in kidney transplantation / 器官移植

The hosts could show complex and diverse immune responses to the allografts. Whether biomarkers can be employed to explain the complexity of graft immune responses and the degree of disease damage are of significance. Conventional biomarkers, such as estimated glomerular filtration rate and blood concenrtation of immunosuppressant, lack of sensitivity and specificity in accurately identifying between immune and non-immune renal allograft injuries. Although renal biopsy is the "gold standard" for the diagnosis of postoperative complications, it still has disadvantages, such as invasiveness and high price, etc. Emerging biomarkers have potential advantages in the non-invasive diagnosis of subclinical injury of renal allograft, prediction of treatment response and individualized adjustment of immunosuppressive regimen. In this article, emerging biomarkers including blood, urine and tissue biomarkers that have been applied and are expected to be applied in clinical practice in the field of kidney transplantation were reviewed, and the range of application and effect of these biomarkers were evaluated, aiming to promote appropriate and rational application of these promising emerging biomarkers in clinical practice.

Diagnosis and treatment strategies for solid organ transplant recipients with SARS-CoV-2 infection / 器官移植

Due to long-term use of immunosuppressive agents, solid organ transplant recipients (SOTR) belong to high-risk populations of multiple pathogenic infection, including SARS-CoV-2. In addition, SOTR are constantly complicated by chronic diseases, such as hypertension and diabetes mellitus, etc. After infected with SARS-CoV-2, the critically ill rate and fatality of SOTR are higher than those of the general population, which captivates widespread attention from experts in the field of organ transplantation. Omicrone variant is currently the significant pandemic strain worldwide, rapidly spreading to more than 100 countries worldwide and causing broad concern. According to the latest international guidelines on the diagnosis and treatment of SARS-CoV-2 infection and relevant expert consensus in China combined with current domestic situation of SARS-CoV-2 pandemic and China's "diagnosis and treatment regimen for SARS-CoV-2 infection (Trial Version 10)", the epidemiology, clinical manifestations and prognosis, diagnosis, clinical classification and treatment of SARS-CoV-2 infection were briefly reviewed.

Chinese expert consensus on clinical application of inhibitors of mammalian target of rapamycin in liver transplant recipients (2023 edition) / 器官移植

@#The long-term survival and quality of life of liver transplant recipients largely depend on long-term health management and immunosuppression regimen after surgery. Long-term use of immunosuppressants may lead to severe complications, such as kidney injury, metabolic diseases and new malignant tumors, and even increase the risk of liver cancer recurrence after liver transplantation. At present, common immunosuppressive regimens in liver transplant recipients are delivered based on calcineurin inhibitor (CNI). However, renal toxicity, neurotoxicity and increased tumor recurrence caused by CNI have significantly affected clinical prognosis of the recipients. In recent years, the dosage of CNI has been gradually reduced and alternative drugs have been explored. Recently, the use of immunosuppressive regimens based on mammalian target of rapamycin inhibitor (mTORi) has been gradually increased. Multiple domestic and international guidelines have provided guidance on the use of mTORi in liver transplant recipients. China Organ Transplantation Development Foundation organized experienced transplant experts in China, combined with published guidelines, consensus and research progress at home and abroad and solicited extensive opinions to jointly formulate this expert consensus, aiming to provide reference for liver transplant clinicians in China.

Clinical outcomes after treatment for NDM-producing Klebsiella pneumoniae infection after kidney transplantation / 中华器官移植杂志

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.

Development status of international transplantation pregnancy registration and its enlightenment for China / 中华器官移植杂志

With the continuous improvements of survival rate and quality-of-life for organ transplant recipients, the issue of pregnancy in organ transplant recipients is receiving greater attention from transplant specialists and obstetricians.Currently there are three major global registries related to transplant pregnancy, namely The United Kingdom Obstetric Surveillance System (UKOSS), The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) and The International Transplant Pregnancy Registry International (TPRI). Among them, TPRI is the most comprehensive and longest running system with a focus on the impact of pregnancy on transplant recipients and the impact of immunosuppressants on fertility and pregnancy outcomes.As the second largest organ transplant country in the world, China also has high expectations for pregnancy and fertility among transplant recipients.Therefore it is imperative to establish a pregnancy and childbirth registration office for organ transplantation in China, standardize the recording of relevant population data and conduct researches for formulating scientific guidance, providing reliable medical consultations and services for patients with pregnancy needs after organ transplantation in China.

The only way for the development of organ transplantation in China — Systematization of organ transplantation disciplines, specialization of organ donation and disciplinarization of OPO construction / 中华器官移植杂志

The problems that China's organ transplantation development facing are the disciplinary construction of Organ Procurement Organization (OPO), the cost of organ donation and financial management, and the construction of organ transplantation technology system under the "Chinese model". As long as we stick to the development path of specialization of organ donation, disciplinarization of OPO construction and systematization of organ transplantation, we will definitely be able to create Chinese technology, Chinese standards, Chinese team and Chinese system with Chinese characteristics and advancement.

Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection / 药物分析学报

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.

Association analysis of high level of BK virus viruria and HLA site after kidney transplantation / 中华器官移植杂志

Objective:To explore the temporal distribution of high level of BK virus(BKV) viruria after kidney transplantation(KT)and the association of high level of viruria with clinical factors and specific human leukocyte antigen(HLA)sites in donors and recipients.Methods:From January 1, 2017 to December 31, 2019, clinical data were retrospectively reviewed for 212 recipients of cadaveric KT.A high level of urinary BKV viruria was defined as urinary BKV-DNA quantification>10 7(copies/ml)after KT while 212 recipients with the same gender composition below the threshold during the same period were selected as low-level controls.Clinical data and HLA sites of two groups were statistically analyzed and risk factors for high level of viruria screened by univariate and multifactorial Logistic regressions. Results:The median time to initial high-level BKV infection in urine after RT was 125.5 days.Based upon univariate Logistic analysis, delayed graft function(DGF)and HLA-A24 of recipient were risk factors for high-level BKV infection in urine while HLA-DQ9 of donor acted as a protective factor.Through multivariate Logistic analysis, DGF( OR=2.18, 95% CI 1.18~4.01, P=0.012)and HLA-A24( OR=1.63, 95% CI 1.06~2.53, P=0.027)of recipient were independent risk factors for high-level BKV infection in urine.And HLA-DQ9 of donors( OR=0.58, 95% CI 0.36~0.91, P=0.019)was an independent protective factor. Conclusions:High level of BKV viruria after RT is associated with donor/recipient-specific HLA sites.Early risk factor stratification and protective factors of recipients can aid in tailoring postoperative immunosuppression and screening program and developing T cell-associated vaccines.

Efficacy and safety of basiliximab and antithymocyte globulin in immune induction in kidney transplantation: a Meta-analysis / 器官移植

Objective To evaluate the efficacy and safety of basiliximab (BAS) and antithymocyte globulin (ATG) in immune induction therapy in kidney transplantation by systematic review and Meta-analysis. Methods Prospective randomized controlled clinical trials screening and comparing BAS and ATG in immune induction therapy in kidney transplantation were systematically searched from global databases, screened and compared. The quality of clinical trials was evaluated by Jadad scoring system and data extraction was performed. The effects of BAS and ATG on the incidence of acute rejection, survival rate of kidney allografts, survival rate of recipients, incidence of delayed graft function, infection, cytomegalovirus infection, malignant tumor, leukopenia and thrombocytopenia at 1 year after kidney transplantation were analyzed. Results A total of 10 clinical trials in English consisting of 1 721 kidney transplant recipients were searched, including 883 cases in the ATG group and 838 cases in the BAS group. No significant differences were observed in the incidence of acute rejection, survival rate of kidney allografts, survival rate of recipients, incidence of delayed graft function, infection, cytomegalovirus infection and thrombocytopenia at postoperative 1 year between the ATG and BAS groups (all P > 0.05). The incidence of malignant tumor and leukopenia at postoperative 1 year in the ATG group were significantly higher than those in the BAS group (both P < 0.05). Conclusions The use of ATG and BAS for immune induction therapy in kidney transplantation yield equivalent efficacy at postoperative 1 year, but BAS is safer than ATG. Clinical trials related to stratified analyses of immune risk are urgently required to achieve individualized precision treatment.

Effects from Contact Area of the Instrument Causing Trauma on Skull Fracture in Rabbits / 医用生物力学

Objective To explore the effects from different contact areas of the instrument causing trauma on biomechanical response parameters of rabbit skull fractures under quasi-static compression conditions. Methods The rabbits were divided into the scalp preservation group and scalp removal group. Each group was subdivided into 3 mm group, 6 mm group, 9 mm group according to contact diameter of the instrument causing trauma. There were 9 rabbits in each group, 54 rabbits in total. All rabbits were put to death by over anesthesia and made into a skull compression model. An electronic universal material testing machine was used to perform quasi-static compression of rabbit skulls to fractures, and biomechanical response parameters such as ultimate load, deformation under ultimate load and compressive strength of rabbit skulls in each group were detected. Results The differences in ultimate load, deformation under ultimate load, and compressive strength of rabbit skulls in scalp preservation group and scalp removal group under different contact areas were statistically significant. The ultimate load was positively correlated with the contact area, and the compressive strength was negatively correlated with the contact area. No correlation was found between deformation under ultimate load and contact area. For scalp preservation group and scalp removal group, the difference in deformation under ultimate load was statistically significant in the 3 mm contact surface diameter group, and there was no statistical significance in the other groups. Conclusions The contact area is positively correlated with the ultimate load of rabbit skull fracture and negatively correlated with compressive strength, while it has no correlation with deformation under ultimate load and is unrelated to whether the scalp is removed.

Recommendations of severe acute respiratory syndrome coronavirus 2 vaccination in renal transplant recipients / 中华器官移植杂志

As novel coronavirus infection has become a major public health problem affecting human health, vaccination is the most effective means of preventing novel coronavirus infection.Therefore, besides implementing regular epidemic prevention and control, it has become the consensus of international community for effective prevention and control of novel coronavirus infection through accelerating the speed of novel coronavirus vaccination, expanding the scope of vaccination and improving public vaccination rate.Kidney transplant recipients are at an elevated risk of novel coronavirus infection.This population has been in a low immune state for a long time.Thus there are problems such as reduced immunogenicity of COVID-19 vaccine, selection and use of vaccine and breakthrough of infection.Based upon the published international and domestic data, this paper serves as a practical reference for clinicians and healthcare workers to provide consultations to kidney transplant recipients about the administration of novel coronavirus vaccine.

Analysis of clinical features and risk factors of systemic lupus erythematosus concomitant with interstitial lung disease in children / 中华实用儿科临床杂志

Objective:To explore the clinical features and risk factors of systemic lupus erythematosus(SLE) concomitant with interstitial lung disease(ILD) in children.Methods:A retrospective analysis was performed.A total of 111 hospitalized children diagnosed with SLE in the Department of Rheumatology and Immunology, Children′s Hospital of Soochow University from February 2016 to November 2018 were selected as the research subjects and divided into the SLE-ILD group(18 cases) and the SLE-non-ILD group(93 cases)according to the lung high-resolution CT manifestations. T-test and Wilcoxon rank sum test were used to compare and analyze the general situation, clinical manifestations and laboratory results.Multivariate Logistic regression was used to analyze the risk factors of SLE-ILD. Results:The prevalence of SLE-ILD was 16.2%(18/111 cases). There were significant differences between the SLE-ILD group and the SLE-non-ILD group in the course of disease [14.00 (12.00-24.25) months vs.1.00(1.00-2.00) months], the incidence of serositis [55.6%(10/18 cases) vs.8.6%(8/93 cases)], post-activity shortness of breath [83.3%(15/18 cases) vs.25.8%(24/93 cases)], nervous system damage [27.8%(5/18 cases) vs.6.5%(6/93 cases)], cardiovascular system damage [38.9%(7/18 cases) vs.9.7%(9/93 cases)], the occu-rrence of increased erythrocyte sedimentation rate [66.7%(12/18 cases) vs.31.2%(29/93 cases)], the decreased C 3[88.9%(16/18 cases) vs.62.4%(58/93 cases)], positive anti neutrophil cytoplasmic antibody (ANCA) [88.9%(16/18 cases) vs.18.3%(17/93 cases)], positive anti-Sm antibody [61.1%(11/18 cases) vs.15.1%(14/93 cases)] and anti ribonucleoprotein antibody (anti RNP antibody)[66.7%(12/18 cases) vs.16.1%(15/93 cases)](all P<0.05). Logistic regression analysis demonstrated that serositis( OR=30.535, 95% CI: 2.167-430.336, P=0.011), shortness of breath after exercise( OR=55.115, 95% CI: 1.117-2 579.852, P=0.041), positive ANCA( OR=65.090, 95% CI: 4.488-944.071, P=0.002) and positive anti-RNP antibody( OR=10.007, 95% CI: 1.362-73.500, P=0.024) were risk factors for SLE-ILD. Conclusions:The longer the course of SLE, the higher the incidence of ILD; serositis, shortness of breath after exercise, positive ANCA and positive anti RNP antibody may be risk factors for SLE-ILD.

Clinical characteristics and etiological changes of bronchiolitis before and after COVID-19 pandemic / 国际儿科学杂志

Objective:To compare the clinical characteristics and etiology changes of patients with bronchiolitis before the pandemic of coronavirus disease 2019(COVID-19)with those after the pandemic, and to provide a basis for the clinical diagnosis, treatment and prevention of bronchiolitis.Methods:Retrospective analysis were made on the clinical characteristics and etiological changes of patients who were hospitalized with bronchiolitis in the Department of Pulmonology, Children′s Hospital of Soochow University before COVID-19 pandemic(from February 1, 2019 to January 31, 2020, called as Group 2019-2020)and after COVID-19 pandemic(from February 1, 2020 to January 31, 2021, called as Group 2020-2021). Medical records were reviewed to compare general conditions, clinical manifestations, and laboratory tests.Nasopharyngeal secretion examination results were collected to compare the differences in pathogenic composition.Results:A total of 285 patients were enrolled in the Group 2019-2020, while 190 patients in the Group 2020-2021.There were no significant differences in gender, age, symptom duration prior to admission and length of stay between the two groups( P>0.05). The proportion of moderate/severe cases in the Group 2020-2021 was lower than that in the Group 2019-2020[10.53%(20/190)vs 21.75%(62/285)]and the difference was statistically significant( χ2=10.062, P<0.05). The proportion of stuffy nose rhinorrhea in the Group 2020-2021 was higher than that in the Group 2019-2020, while the proportion of gastrointestinal symptoms(vomiting and diarrhea)in the Group 2020-2021 was lower than that in the Group 2019-2020 [57.37%(109/190)vs 47.37%(135/285)and 15.79%(30/190)vs 24.56 %(70/285)]and the differences were statistically significant( χ2 were 4.563 and 5.278 respectively, all P<0.05). There were no significant differences in the proportions of fever, dyspnea, shortness of breath and cyanosis between the two groups(all P>0.05). The creatine kinase isoenzyme(CK-MB)in the Group 2020-2021 was lower than that in the Group 2019-2020[4.15(2.90~5.60)vs 6.70(4.20~22.10)]and the difference was statistically significant( Z=-8.757, P<0.05). There were no statistically significant differences in white blood cell count(WBC), percentage of neutrophil(N%), blood platelet count(PLT), percentage of eosinophil(EOS%), C-reactive protein(CRP), alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)between the two groups(all P>0.05). The total pathogen detection rate, positive rate of respiratory syncytial virus(RSV), positive rate of mycoplasma pneumoniae(MP)and mixed infection rate in the Group 2020-2021 were lower than those in the Group 2019-2020[65.26%(124/190)vs 75.09%(214/285), 14.21%(27/190)vs 30.18%(86/285), 6.32%(12/190)vs 15.09%(43/285), 16.84%(32/190)vs 25.61%(73/285)], with statistically significant differences( χ2 were 5.361, 16.026, 8.568 and 5.094 respectively, all P<0.05). The positive rate of rhinovirus in the Group 2020-2021 was higher than that in the Group 2019-2020[13.16%(25/190)vs 4.91%(14/285)]and the difference was statistically significant( χ2=10.285, P<0.05). There were no significant differences in the positive rates of human metapneumovirus, Boca virus and parainfluenza virus 3 between the two groups(all P>0.05). Conclusion:The clinical characteristics and etiology of patients with bronchiolitis have changed after the COVID-19 pandemic.The quarantine and protection measures reduce the transmission of associated pathogens and the severity of the disease.

Evaluating criteria of immune risk stratification for kidney transplant recipients / 中华器官移植杂志

Objective:To establish risk stratifying criteria for acute rejection(AR)after kidney transplantation(KT)through analyzing the preoperative risk factors of KT recipients from deceased donor(DD).Methods:A retrospective study is conducted for 1 382 KT recipients of DD kidney at First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2020.According to the presence or absence of AR within 1 year post-KT, they are divided into two groups of acute rejection(group AR, 115 cases)and non-rejection(group non-AR, 1 267 cases). Clinical data of two groups are examined by univariate and multivariate analyses for determining the risk factors of AR and a scoring standard is established on the basis of regression coefficients.They are divided into three groups of low-risk(907 cases), middle-risk(450 cases)and high-risk(25 cases)according to the scoring results and the incidence of AR is compared among different scoring groups.Results:Univariate analysis indicates that donor age(AR, 793 cases; non-AR, 474 cases, P=0.033), age difference between recipients and donors≥25 years(AR, 63 cases; non-AR; 315 cases; P<0.001), recipient panel-reactive antibodies(PRA)plus donor-specific antibody(DSA)(+ )(AR, 96 cases; non-AR, 1 169 cases, P=0.002), donor kidney cold ischemic time≥12h(AR, 81 cases; non-AR, 1 064 cases, P<0.001), donor/recipient HLA mismatch≥3(AR, 70 cases; non-AR, 984 cases, P<0.001)and expanded criteria donor(ECD)(AR, 50 cases; non-AR, 790 cases, P<0.001)are high risk factors for AR(all P<0.05). Variables with statistical significance during univariate analysis are included for multivariate analysis.Five variables are finally determined, including age difference between recipients and donors≥25 years(β=0.61, P=0.006), PRA+ DSA(+ )(β=0.74, P=0.008), donor kidney cold ischemic time≥12 h(β=0.74, P<0.001), HLA mismatch(≥3)(β=0.81, P<0.001)and ECD(β=0.82, P<0.001). Score for each risk factor is calculated according to the relevant regression coefficient and scoring standard formulate on the basis of the above five risk factors with a total score of 36.With an overall incidence of AR at 8.32%(115/1 382), the incidence of AR is 4.3%, 14.7% and 40.0% in low/middle/high-risk group and the difference is statistically significant.It hints that immune risk stratification can effectively determine the risk of postoperative AR for KT recipients.The incidence of AR is significantly higher in middle/high-risk group than that in low-risk group ( P<0.001). Conclusions:For recipients with middle/high immune risk, intensity and dose of immunosuppressants should be appropriately boosted during preoperative induction and maintenance period.And the occurrences of AR and infection should be dynamically monitored.

Assessment and monitoring of immune risk of kidney transplantation rejection / 器官移植

Kidney transplantation is the most efficacious treatment for end-stage renal failure. Although the shortterm survival and functional recovery of the kidney graft have been significantly improved, the long-term survival of the kidney graft remains to be enhanced. Antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR) caused by immune factors are still the most critical causes of kidney graft failure. In this article, the immune risk assessment and monitoring of kidney transplant recipients during the awaiting period, before and after kidney transplantation were reviewed. Through the evaluation of preexisting human leukocyte antigen (HLA) antibodies and non-HLA antibodies, HLA matching, lymphocytotoxicity cross-matching and immune memory cells in the recipients before kidney transplantation, programmed biopsy of the kidney graft of the recipients after kidney transplantation and monitoring of HLA antibodies, non-HLA antibodies and donor-derived cell-free DNA (dd-cfDNA), individualized immunosuppressive treatment and monitoring regimes could be established, and the incidence of rejection could be prevented, timely detected and diagnosed. According to the immune monitoring results, ineffective treatment or over-treatment could be avoided, thereby improving the long-term survival of kidney graft.

Predictive value of hypothermic machine perfusion parameters combined perfusate biomarkers in deceased donor kidney transplantation / 中华医学杂志(英文版)

BACKGROUND@#Delayed graft function (DGF) is the main cause of renal function failure after kidney transplantation. This study aims at investigating the value of hypothermic machine perfusion (HMP) parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor (DD) kidney transplantation.@*METHODS@#HMP parameters, perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1, 2019 to August 31, 2019 in the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.@*RESULTS@#In this study, the DGF incidence was 17.7% (20/113); The multivariate logistic regression results showed that terminal resistance (OR: 1.879, 95% CI 1.145-3.56) and glutathione S-transferase (GST)(OR = 1.62, 95% CI 1.23-2.46) were risk factors for DGF; The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time (HR = 0.823, 95% CI 0.735-0.981). The model combining terminal resistance and GST (AUC = 0.888, 95% CI: 0.842-0.933) significantly improved the DGF predictability compared with the use of terminal resistance (AUC = 0.756, 95% CI 0.693-0.818) or GST alone (AUC = 0.729, 95% CI 0.591-0.806).@*CONCLUSION@#According to the factors analyzed in this study, the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.