Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

Objective:To explore the clinical characteristics of pediatric kidney transplant recipients reinfected with SARS-CoV-2.Method:The relevant clinical data were retrospectively reviewed for 191 pediatric kidney transplant recipients at a single center. Based upon whether or not there was a reinfection of SARS-CoV-2, they were assigned into two groups of single infection (group A, 127 cases) and reinfection (group B, 64 cases). Baseline profiles, clinical symptoms, diagnostic and therapeutic strategies, markers of disease progression, immune status, respiratory support modalities, comorbidities and transplantation-related data were collected for comparing the inter-group differences during primary infection and between two infections in reinfected group.Result:As compared with group A, group B recipients had a higher proportion of age <12 years (71.9% vs 54.3%) ,unvaccinated (81.2% vs 66.1%) and such symptoms as high fever (34.4% vs 12.6% ), dry cough (43.8% vs 23.6% ) and chest tightness (14.1% vs 3.9 %) during primary infection (all P<0.05). During primary infection, the levels of IL-6 and CRP were higher in group B than in group A and inter-group difference was statistically significant (both P<0.01). The levels of IL-6 ( P<0.01), CRP ( P<0.01) and PCT ( P= 0.023) were lower in group B during reinfection than those during primary infection and the difference was statistically significant. During primary infection, the counts of CD3+, CD4+, CD8+, NK and B lymphocyte of group B were lower than those of group A. And inter-group differences were statistically significant (all P<0.01). During reinfection, the levels of CD3+, CD4+, CD8+, NK and B lymphocyte counts of group B spiked as compared with those of group A during primary infection and the differences were statistically significant (all P<0.01). The levels of SCr and UA in group B differed insignificantly before and after primary infection with SARS-CoV-2. However, the differences before and after reinfection were statistically significant (both P<0.01) . Conclusion:Symptomatic and immunocompromised pediatric KT recipients during primary infection with SARS-CoV-2 are more prone to reinfection during subsequent epidemics. Though mildly symptomatic, reinfection may exacerbate impairments of graft kidney function in pediatric KT recipients.

Objective:Currently,patients with pre-exsiting donor-specific antibody(DSA)are prone to antibody-mediated rejection(AMR)after surgery and are at a relatively high risk of postoperative complications and graft failure.The risk of postoperative complications and graft failure is relatively high.This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation,providing single-center treatment experience for DSA-positive kidney transplantation. Methods:We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022.Eight cases were organ donation after citizen's death(DCD)kidney transplant recipients,of which 3 cases in the early stage were not treated with preoperative desensitisation therapy(DCD untreated group,n=3),and 5 recipients were treated with preoperative rituximab desensitisation(DCD preprocessing group,n=5).The remaining 7 cases were living related donors recipients(LRD)who received preoperative desensitisation treatment with rituximab and plasma exchange(LRD preprocessing group,n=7).We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1,3 and 5 years,and to compare the differences in recovery and postoperative complications between 3 groups. Results:All 15 recipients were positive for preoperative panel reactive antibody(PRA)and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation.DCD untreated group all suffered from DSA level rebound,delayed renal graft function(DGF)and rejection reaction after surgery.After the combined treatment,DSA level was reduced and the graft renal function returned to normal.The DCD preprocessing group were all without antibody rebound,1 recipient developed DGF and the renal function returned to normal after plasmapheresis,and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation.In the LRD preprocessing group,2 cases had antibody rebound and 1 case had rejection,but all of them recovered to normal after treatment,and DSA was maintained at a low level or even disappeared.The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group;and there were no significant difference in the incidence of postoperative haematuria,proteinuria,bacterial and fungal infections,and BK virus infection between the 3 groups(all P>0.05).A total of 11 of the 15 recipients were followed up for more than 1 year,6 for more than 3 years,and 1 for more than 5 years,and the survival rates of both the recipients and the transplanted kidneys were 100%. Conclusion:Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.

Objective:To explore the efficacy and safety of low-dose rabbit anti-human thymocyte globulin (rATG) for induction therapy of kidney transplantation (KT) in children.Methods:From October 2018 to May 2021, clinical data were reviewed retrospectively for 77 pediatric KT recipients on a low-dose rATG induction protocol.Recipient/graft survival rate, renal function recovery, acute rejection (AR) and adverse reactions were observed at 1 year post-operation.The postoperative changes of renal function were examined by Friedman’s test; According to the preoperative baseline data, Pearson’s Chi-square or Fisher's exact test was utilized for examining the influencing factors of postoperative AR.Results:A total of 16(20.78%) recipients had AR within the first 6 months post-operation.The incidence of delayed graft function (DGF) was 14.29%(11/77); The incidence of severe infection post-transplantation 18.18%(14/77), the infection rate of BK virus 25.97%(20/77) and the incidence of neutropenia 32.47%(25/77).The recipient/graft survival rate at 1 year post-operation was 97.40%(75/77) and 94.81%(73/77) respectively.Chi-square test indicated that the incidence of postoperative infection in children with body weight ≤30 kg and height ≤138 cm was 28.95%(11/38) and 27.50%(11/40) respectively, Both were higher than 7.69%(3/39) and 8.11%(3/37) of children with body weight >30 kg and height>138 cm.The difference between groups was statistically significant ( P=0.016 and 0.028). Conclusions:Low-dose rATG is generally excellent in preventing AR in pediatric KT recipients.And the risk of related AR may be lower.The infection rate of recipients with decent preoperative development is low.

Objective:To explore the clinical efficacy of vascular interventional therapy in children with transplantation renal artery stenosis(TRAS).Methods:From January 2013 to September 2021, retrospective analysis was performed for clinical data of 238 TRAS children.Peak systolic velocity(PSV)of transplant renal artery, interlobular artery PSV, transplant renal artery PSV/ interlobular artery PSV(post PSV ratio)and serum creatinine level before and after vascular interventional therapy and at the last follow-up were compared.Results:Six pediatric kidney transplantation recipients were diagnosed as TRAS.The median operative age was 12(9-17)years, the median postoperative time to diagnosing TRAS 4(1.7-18.0)months and the median follow-up period 6.6(2.5-8.0)years.All of them received vascular interventional therapy of percutaneous transluminal angioplasty(PTA, n=5)and stent angioplasty( n=1). The serum creatinine pre-treatment with vascular interventional therapy was significantly higher than baseline serum creatinine level at discharge(200.8±88.5)vs(75.2±27.9)μmol/L, P=0.025 and decreased to(103.8±44.7)μmol/L at Month 1 post-treatment( P=0.196)and(98.7±30.2)μmol/L at the last follow-up( P=0.115). Comparing with internal diameter of grafted renal artery anastomosis site(2.6±0.6 mm)pre-treatment with vascular interventional therapy, significant changes occurred at 24 h post-treatment(3.8±0.5 mm)and at the last follow-up(4.1±0.8 mm)(all P=0.027). In addition, PSV and post PSV ratio of transplanted renal artery at 24 h post-treatment(163±45.0 cm/s, 6.5±2.2)and at the last follow-up(184.7±80.8 cm/s, 5.4±2.0)were significantly lower than that before vascular interventional therapy(356.5±77.9 cm/s, 18.0±5.8)and interlobular artery PSV was significantly higher than that before vascular interventional therapy( P=0.024, P=0.032, respectively). During follow-ups, no restenosis or thrombosis occurred in transplanted renal arteries. Conclusions:PTA or stent angioplasty for TRAS children is technically feasible with low restenosis rate and relatively satisfactory mid/long-term outcomes.

Objective To investigate the exposure difference of different dosage forms of mycophenolic acid (MPA) between children aged ≤12 and > 12 years old after kidney transplantation. Methods Clinical data of 73 children undergoing kidney transplantation from donation after cardiac death (DCD) were retrospectively analyzed. Postoperative immunosuppressive regimen was MPA+ tacrolimus+glucocorticoid. According to different dosage forms of MPA, all recipients were divided into group A (n=37, mycophenolate mofetil capsules), group B (n=28, enteric-coated mycophenolate sodium) and group C (n=8, mycophenolate mofetil dispersible tablets). All children were divided into ≤12 and > 12 years old groups according to the age of kidney transplantation. The daily dosage of different dosage forms was calculated. The blood concentration (C) of MPA and the area under the curve (AUC) were detected by enzyme-multiplied immunoassay technique. The MPA blood concentration was statistically compared between two age groups at different time points. The recovery of renal function and postoperative complications were assessed. Results No significant differences were observed in the dosage and blood concentration of drug at different time points among groups A, B and C (all P > 0.05). The MPA-C_{4 h} and AUC in the ≤12 years old group were significantly higher than those in the > 12 years old group (both P < 0.05). In group B, the MPA-C_{4 h} of children aged ≤12 years old was significantly higher compared with that in those aged > 12 years old (P=0.016). The MPA-C_{4 h} of children aged ≤12 years old in group B was higher than those in group A and group C, but the differences were not statistically significant (P=0.080). There was no significant difference in the incidence of acute rejection and infection among three groups (both P > 0.05). Conclusions Children of different ages who are given with different dosage forms of MPA after kidney transplantation obtain different exposure rates. The exposure rate of kidney transplant recipients aged ≤12 years old tends to be higher than that of their counterparts aged > 12 years old, mainly seen in the recipients treated with enteric-coated mycophenolate sodium. Therefore, it is necessary to monitor the exposure level of MPA, which provides significant guidance for adjusting the drug dosage of different dosage forms.

Objective:To compare the efficacy of single kidney transplantation for children from pediatric donors between body weight ≤15 kg and >15 kg.Methods:A retrospective review in 156 children with single donor kidney transplantation from August 2010 to December 2019 in the Kidney Transplantation Department of the First Affiliated Hospital of Zhengzhou University was conducted. The patients were classified into the small kidney group (pediatric donor body weight ≤15 kg) and the big kidney group (pediatric donor body weight >15 kg). In this study, 89 cases were concluded in the small kidney group and 67 cases were concluded in the big kidney group. The donor kidneys were obtained from 46 cases of small weight (≤15 kg) pediatric donors and 48 cases of large weight (>15 kg) pediatric donors. There were significant differences in age [1.00 (0.02 - 4.00) years vs. 10.00 (3.00-18.00) years], body weight [10.0 (3.4 - 15.0) kg vs. 35.0 (16.2- 35.0) kg], height [76 (50- 113) cm vs. 144 (67-172) cm], GFR [(31.50±7.46)ml/min vs. (36.79±7.00) ml/min], and renal length to diameter [(5.91±0.48) cm vs. (8.71±1.88) cm] between the small kidney group and the big kidney group ( P < 0.01). There was no significant difference between the two groups of donors in gender, cold/warm ischemia time and cause of death ( P>0.05). There were significant differences in age [(11.28±3.89) years vs. (13.86±3.56) years], body weight [(31.83±10.45)kg vs. (35.13±9.15) kg], and height [(130.02±28.56) cm vs. (143.97±16.59) cm] between recipients of the small kidney group and big kidney group ( P < 0.05). While there were no significant differences in preoperative serum creatinine level [(822.65 ± 135.04) μmol/L vs. (777.31 ± 165.40) μmol/L], HLA mismatch [(3.4 ± 1.4) site vs. (3.2±1.3) site], and primary disease between the two groups ( P > 0.05). The recovery of renal function, postoperative adverse events, postoperative children, and graft survival were compared between the two groups. Results:The renal function of the two groups of recipients returned to normal 3 months after operation. The perioperative complications in the small kidney group and the big kidney group mainly included renal delayed recovery [5.6% (5/89) vs. 7.5% (5/67), P=0.89], renal vascular embolization [3.4% (3/89) vs. 0, P=0.35], and acute rejection [2.2% (2/89) vs. 4.3% (3/67) , P=0.75]. The main cause of recipient death during the follow-up period was pulmonary infection [4.5% (4/89) vs. 6.0% (4/67) , P=0.68]. The postoperative small kidney group was followed up for an average of 30 (3-74) months. The survival rates of children in the small kidney group at the 1, 3 and 5 years after surgery were 96.6% (86/89), 91.0% (81/89) and 91.0%(81/89), while the transplanted renal survival rates were 92.1% (82/89), 86.5% (77/89) and 84.2% (75/89), respectively. The postoperative big kidney group was followed up for an average of 32 (4-89 ) months. The survival rates of children in the big kidney group were 95.5% (64/67), 94.0% (63/67) and 91.0%(61/67) in the first 1, 3 and 5 years postoperatively, while the graft survival rates were 92.5% (62/67), 83.6% (56/67) and 83.6% (56/67), respectively. The postoperative kidneys of two groups were fast-growing, and there was no significant difference between the small kidney group and the big kidney group in graft length to diameter [(9.63±0.31) cm vs. (9.75±0.71) cm] after 1 year ( P>0.05). Conclusions:The effect of single pediatric kidney transplantation for pediatric donor with body weight ≤15 kg is equivalent to that for pediatric donor with body weight >15 kg , which can be carried out clinically.

Objective:To evaluate the effect of unilateral pediatric kidney donation for adult kidney transplantation.Methods:Retrospective analysis was conducted on the cases of children who donated unilateral donor kidney for adult kidney transplantation recipients in our hospital, and those who were followed up for more than three years were included in this study. The body weight of the recipients in group A was ≤50 kg, and the body weight of the recipients in group B was ≤70 kg.The recipients were divided into 0-5 year old donor group (group A) and 6-17 year old donor group (B group). Clinical data, recipient/kidney survival, graft function and growth, and complications of the recipient were analyzed.Results:A total of 45 adult recipients were enrolled, including 12 in group A and 33 in group B. The renal survival rate at 3 years after operation was (100%, 96.9%)/(91.6%, 93.9%). One week after the operation, the early postoperative recovery of renal function in group B was better than that in group A, and the difference of serum creatinine was statistically significant ( P<0.05), while the difference of serum creatinine in other postoperative follow-up time points was not statistically significant ( P>0.05). Within a year, both groups of grafts continued to grow, reaching adult levels in one year. There was no statistical significance in the incidence of complications between the two groups ( P>0.05). The incidence of protein in the two groups was 33.3% and 6.1%, respectively, 1 case in each group still had proteinuria at 1 year after surgery, and only 1 case in the infant donor kidney recipient in group A had proteinuria at 3 years after surgery. Conclusions:Unilateral donor kidney transplantation from children can provide good results for adult patients with uremia by selecting suitable donors according to the weight of the recipient.

Objective:To explore whether hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) preconditioning can relieve inflammation, reduce cell apoptosis and alleviate renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly divided into three groups of sham operation (sham), ischemia reperfusion injury (IRI) and IRI+ HIF-PHI ( n=6 each). In IRI+ HIF-PHI group, mice received an intragastric dose of roxadustat (20 mg/kg) every other day one week before. After renal IRI modeling, serum creatinine (SCr) level was monitored and hematoxylin-eosin (HE) staining employed for observing the pathological changes of renal tissue and scoring injury degree. Apoptosis of renal tubular epithelial cells was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mRNA expressions of HIF-1α, TNF-α and IL-1β in renal tissues. Immunofluorescence and immunohistochemistry were employed for detecting the expressions of hypoxia-inducing factor 1α (HIF-1α), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results:As compared with IRI group, SCr level declined markedly in IRI+ HIF-PHI group ( P<0.01), renal tissue injury improved markedly, semi-quantitative score of renal tubule injury dropped ( P<0.01), apoptotic cells decreased ( P<0.01) and the expression levels of TNF-α and IL-1β declined ( P<0.05). Compared with sham group, the mRNA expression of HIF-1α was not significantly elevated in IRI group ( P>0.05). Immunofluorescence showed that the expression of HIF-1α in medulla of renal tissues was up-regulated in IRI group, but not markedly in cortex. While the mRNA expression of HIF-1α was markedly up-regulated after a pretreatment of HIF-PHI ( P<0.05), the expression spiked markedly in renal cortex, but was weaker in medulla than that in IRI group. Conclusions:HIF-PHI can boost the expression level of HIF-1α, reduce the expression of inflammatory factors, relieve the inflammatory response, reduce cell apoptosis, improve renal function and alleviate renal ischemia reperfusion injury.