This study aimed to evaluate the efficacy and preliminary safety of preheated colistimethate sodium (CMS) in reducing the load of multidrug-resistant and extensively drug-resistant (MDR/XDR) Gram-negative bacilli in preservation fluid (PF) under simulated static cold storage (SCS) conditions in vitro. CMS was preheated at 37–60 °C for 5 ~ 30 min. The antibacterial effects of preheated CMS were evaluated against five MDR/XDR strains: carbapenem-resistant Pseudomonas aeruginosa (CRPA), Klebsiella pneumoniae (CRKP), Escherichia coli (CREC), Acinetobacter baumannii (CRAB), and methicillin-resistant Staphylococcus aureus (MRSA). Bacterial counts were assessed after 3 h of SCS, and the average inhibition rate (AIR) was calculated. The safety experiment was performed to evaluate the nephrotoxicity of preheated CMS under hypothermic condition. Preheating CMS at 60 °C for 15 ~ 30 min significantly reduced bacterial loads of CRPA, CRKP, CREC, and CRAB, with average inhibition rates (AIR) up to 100%, 96.91%, 98.36%, and 85.06%, respectively. At 37 °C, extended heating (30 min) was required for partial efficacy against CRKP and CRAB, while CREC remained largely unaffected. MRSA showed no susceptibility to preheated CMS. Preheated CMS did not cause significant morphological alterations or reduction in HK-2 cell viability within 3 ~ 6 h of SCS. Thermal pretreatment of CMS at 60 °C represents a novel, practical, and safe strategy for PF decontamination, providing rapid bactericidal activity against frequently encountered MDR/XDR Gram-negative bacilli during the SCS process.
AIMS:The present study aims to investigate the role and mechanism of lactate-induced histone lactylation in regulating cuproptosis during renal IRI. MATERIALS AND METHODS:We employed both in vivo (mouse IRI) and in vitro (HK-2 cell oxygen-glucose deprivation/reperfusion, OGD/R) models. Multi-omics analyses (proteomics, CUT&Tag, RNA-seq) were integrated with molecular techniques (Western blot, transmission electron microscopy, biochemical assays, ChIP-qPCR, RT-qPCR) to examine histone lactylation and cuproptosis. KEY FINDINGS:Renal IRI led to significant lactate accumulation and a global increase in histone lactylation, with the H3K18 site being most prominently modified. Proteomics indicated significant enrichment of cuproptosis-related pathways, alongside copper dysmetabolism, mitochondrial damage, and elevated oxidative stress. Inhibition of lactate dehydrogenase (LDHA) reduced H3K18la levels and alleviated cuproptosis. Integrated multi-omics analysis identified HSPA6 (heat shock protein family A member 6) as a direct downstream target of H3K18la, linked to MAPK (mitogen-activated protein kinase) signaling. Lactate stimulation or inhibition reciprocally regulated HSPA6 expression via H3K18la, confirmed by ChIP-qPCR. Knockdown of HSPA6 effectively suppressed OGD/R-induced cuproptosis. SIGNIFICANCE:The present study unveils a previously unidentified epigenetic pathway in AKI, whereby lactate-driven H3K18 lactylation transcriptionally activates HSPA6, consequently promoting cuproptosis and exacerbating renal damage. The "lactate-H3K18la-HSPA6" axis has been identified as a promising new target for therapeutic intervention in AKI.
BackgroundHigh intra-patient variability (IPV) in tacrolimus exposure is a known risk factor for poor long-term kidney transplant outcomes. However, significant heterogeneity exists regarding the optimal post-transplant period for its assessment. This study aimed to identify the earliest predictive time window for tacrolimus IPV and to evaluate its association with de novo donor-specific antibody (dnDSA) development and rejection, while also examining the impact of CYP3A5*3 and CYP3A4*1G polymorphisms on IPV.MethodsIn a single-center retrospective study (2016-2021) of Chinese kidney transplant recipients, tacrolimus IPV (coefficient of variation) was calculated across consecutive intervals from transplantation to month 24, using all available whole blood drug trough concentration measurements within each window. The primary analysis assessed the association between time-window-specific IPV and the cumulative 7-year incidence of dnDSA, antibody-mediated rejection (ABMR), and T-cell-mediated rejection (TCMR). The influence of dnDSA on rejection and of genetic polymorphisms on IPV was also analyzed.ResultsA total of 446 kidney transplant recipients were included in the analysis. The cumulative incidences of dnDSA and overall rejection were 16.37% (73/446) and 17.04% (76/446), respectively, comprising ABMR (n=49, 64.47%), TCMR (n=21, 27.63%), and mixed ABMR + TCMR (n=6, 7.89%). Tacrolimus IPV calculated over the first 7 postoperative months emerged as the earliest significant predictor for dnDSA development (P = 0.0048). IPV from month 13 onward significantly correlated with overall rejection risk (P = 0.014). No association was found between CYP3A5*3 or CYP3A4*1G polymorphisms and IPV. Furthermore, dnDSA-positive patients had significantly higher risks of overall rejection (34.25% vs. 10.99%, P = 0.022) and ABMR (26.03% vs. 8.04%, P = 0.0049) compared to dnDSA-negative patients.ConclusionTacrolimus IPV during the initial 7 post-transplant months serves as the earliest predictive window for dnDSA, a key risk factor for subsequent ABMR. These findings advocate for a dual strategy integrating early IPV-guided tacrolimus monitoring and systematic dnDSA surveillance to improve long-term graft outcomes.
Tacrolimus is a critical immunosuppressive agent in kidney transplantation, but its pharmacokinetic variability, especially intra-patient variability (IPV), can lead to suboptimal outcomes. Genetic polymorphisms in CYP3A5 and ABCC2 may influence tacrolimus metabolism and transport, affecting dosing requirements and IPV. However, their combined impact during the first year after kidney transplantation remains insufficiently characterized. This study aimed to evaluate the influence of CYP3A5*3 (rs776746) and ABCC2 (rs3740066, rs2273697) polymorphisms on tacrolimus exposure, IPV (C0-IPV and C0/D-IPV), and short-term renal allograft function in kidney transplant recipients, with a focus on the first post-transplant year. A prospective cohort of 60 kidney transplant recipients was followed for one year. Tacrolimus trough concentrations (C0) were measured on postoperative Day 7, Day 14, Month 1, Month 3, Month 6, and Year 1. IPV was assessed using C0-IPV and dose-adjusted C0/D-IPV. Genotyping was performed using the SNaPshot platform. Multivariable regression models identified predictors of IPV and renal allograft function was evaluated by estimated glomerular filtration rate (eGFR) at Year 1. CYP3A5*3 expressers required significantly higher tacrolimus doses than non-expressers from Day 7 through Month 3 (P < 0.05) and showed correspondingly lower C0/D values during this period (P < 0.01). ABCC2 rs3740066 was associated with C0/D at Month 6 (P = 0.037) and with the daily dose at Year 1 (P = 0.045). In the multivariable analysis, the ABCC2 rs2273697 variant (β = 8.429, 95
The recurrence rate of IgA nephropathy (IgAN) in transplanted kidneys ranges from 30% to 58%, posing a significant threat to the long-term survival of transplant recipients. Early detection of recurrence allows timely and targeted intervention, thus may significantly improve graft survival outcomes. To date, prediction of IgAN recurrence remains challenging. Repeated kidney biopsies, while critical for monitoring disease progression, are highly invasive and carry inherent risks. This underscores the urgent need for an early, reliable and non-invasive strategy to monitor the IgAN recurrence and optimize recipient outcomes. In this study, we introduce an ultrasensitive and tractable diagnostic approach that can interrogate urine samples from IgAN patients at a molecular level through the combination of deep learning with surface-enhanced Raman spectroscopy (SERS). Flexible composite films of MXene and Au nanocubes (AuNCs) with high sensitivity and excellent biocompatibility are developed as SERS substrates to achieve molecular spectral fingerprints of urinary components, that can be utilized to reflect the physiological characteristics caused by IgAN. The spectral fingerprint differences of urine components are successfully profiled through a deep learning model, showing a diagnosis accuracy of 98% for recurrent IgAN. Meanwhile, for those patients with recurrent IgAN, the model predicted them with early recurrence through quantitative assessment of the similarity between spectral datasets. Additionally, we successfully conducted quantitative profiling of three proteins including CD89, CD71 and ASGP-R in urine samples from patients with recurrent IgAN, which present significant difference between early recurrence and severe recurrence. This analysis highlighted the clinical significance of these proteins as biomarkers for current IgAN diagnosis and monitoring. Thus, the integration of SERS with explainable deep learning established a novel method for recurrent IgAN diagnosis, not only achieving exceptional diagnostic performance but also significantly advancing model interpretability through SERS spectral analysis.
Introduction: Recurrent Ig A nephropathy (IgAN; rIgAN) after kidney transplantation is heterogeneous and lacks a guideline or a standard treatment. We evaluated the efficacy and safety of telitacicept as an add-on therapy for rIgAN with persistent proteinuria in kidney recipients. Methods: In this prospective, single-center, single-arm cohort study, 25 kidney transplant recipients with biopsy-confirmed rIgAN received add-on telitacicept 240 mg subcutaneously weekly for 12 weeks, then every 2 weeks until week 28. Primary end points were 24-hour urinary protein (24h-UP) and urine albumin-to-creatinine ratio (UACR). Secondary assessments included remission, kidney function, laboratory parameters, and mechanistic biomarkers. Results: Twenty-two participants completed the follow-up. At week 28, 24h-UP and UACR decreased by 51.6% and 62.7% (both P < 0.001), respectively. Complete and partial remission rates were achieved in 47.6% and 57.1% of patients, respectively. Serum albumin increased significantly, whereas serum creatinine (SCr), estimated glomerular filtration rate, and hemoglobin remained stable. Circulating galactose-deficient IgA1 (Gd-IgA1) and asialoglycoprotein receptor (ASGPR) levels declined; Ig levels also decreased, in line with B-cell inhibition and on-target pathways suppression. No treatment-related severe adverse events were reported. The most common adverse events were mild injection site reactions and transient infections. Conclusion: Add-on telitacicept was associated with marked proteinuria reduction and a favorable safety profile in kidney transplant recipients with rIgAN and persistent proteinuria, supporting its potential as a therapeutic option.
Organ preservation solutions (PS) contaminated with multidrug-resistant bacteria (MDRB) risk donor-derived infections in transplantation. Eravacycline (ERV), a novel tetracycline antibiotic, shows potent activity against MDRB, but its efficacy in hypothermic PS (0°C-4°C) is unverified. In this study, six multidrug-resistant bacterial strains-including carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, VIM-positive Pseudomonas aeruginosa, carbapenemase-negative P. aeruginosa, and methicillin-resistant Staphylococcus aureus-were exposed to eravacycline diluted in preservation solution at concentrations of 25, 50, 100, and 200 mg/L for three hours at 0-4°C. Bacterial viability was assessed by colony-forming unit counts after incubation. Results showed that eravacycline at 25 mg/L inhibited methicillin-resistant S. aureus and carbapenem-resistant A. baumannii, while 50 mg/L suppressed carbapenem-resistant K. pneumoniae, E. coli, and VIM-positive P. aeruginosa. Carbapenemase-negative P. aeruginosa required 200 mg/L for inhibition. These findings indicate that eravacycline exhibits strain-dependent antibacterial activity in hypothermic preservation solution, with 50 mg/L being effective against most tested multidrug-resistant organisms except carbapenemase-negative P. aeruginosa. Further clinical studies are warranted to evaluate its potential application in transplantation settings.
Accurate therapeutic drug monitoring (TDM) of antibiotics including ceftriaxone, ampicillin, and vancomycin plays an important role in the treatment of neonatal sepsis, a common and life-threatening disease in neonates. A highly sensitive surface-enhanced Raman spectroscopy (SERS) method using tungsten disulfide/gold and silver core-shell (WS2/Au@Ag) nanocomposites was developed for the rapid detection of the three antibiotics, with a wide response range (0.5-1000 mu g/mL). A twodimensional convolutional neural network (2D-CNN) regression model was proposed to predict antibiotic concentrations in complex mixed serum solutions, simulating various drug use scenarios. The model achieved excellent regression results for ceftriaxone and ampicillin simultaneously, with R-squared (R2) values of 0.9993 and 0.9997. The integration of ultra-sensitive SERS with the 2D-CNN based deep learning model provides a promising approach for rapid TDM and personalized patient treatment.
BackgroundKidney transplantation is recognized as the optimal treatment for end-stage kidney disease (ESKD) in children, which significantly improves growth delay, pubertal development, and social prognosis in pediatric patients. This study analyzed the long-term prognosis and influencing factors following pediatric kidney transplantation at our center.MethodsA total of 101 pediatric recipients who underwent kidney transplantation at our center were enrolled in this study. Post-transplant outcomes, including renal function, height development, pubertal progression, and social adaptation, were systematically analyzed.ResultsThe height-for-age Z-score (HAZ) significantly improved from −2.27 ± 1.64 at transplantation to −0.76 ± 1.13 after achieving post-transplant stability. The graft survival rates were 100% and 93.4% at 5 and 10 years post-transplantation, respectively, while patient survival rates remained 100% at both 5 and 10 years. At the last follow-up, the mean serum creatinine level was 83.85 ± 38.34 μmol/L, with an estimated glomerular filtration rate (eGFR) of 79.49 ± 27.25 ml/min/1.73 m2. Among school-aged recipients, 93.75% successfully returned to school, while only 33.3% of those who completed their education achieved employment. Among male adolescents (13 years, n = 43), 37 cases (86.0%) experienced spermarche, with a mean age of 14.5 years in prepubertal transplant recipients. In the female cohort (n = 45), 42 patients (12 years) reached puberty, demonstrating a mean menarche age of 12.5 years in prepubertal recipients vs. 13.2 years in postpubertal transplants (P > 0.05). Menstrual irregularities were observed in 8 cases, accounting for 19.51% of menstruating females.ConclusionThis study demonstrates significant improvements in height development, pubertal progression, and social adaptation following kidney transplantation in pediatric recipients. While recipient gender, pre-transplant dialysis modality, and dialysis duration showed no significant impact on near-final height (NFH), both transplantation age and height at transplantation significantly influenced NFH attainment. These findings emphasize that early transplantation and maintaining optimal graft function are crucial for ameliorating growth delay and pubertal development, while also positively influencing long-term social outcomes in pediatric transplant recipients.
BACKGROUND:The use of antimicrobial agents in the preservation solution (PS) could prevent the bacterial transmission to recipients in organ transplantation. However, antibiotics may exhibit different decontamination efficacy in the hypothermic PS. This study aimed to evaluate the antibacterial activity of ceftazidime-avibactam (CAZ-AVI) combined with aztreonam (ATM) against multidrug-resistant bacteria (MDRB) at varying ratios and concentrations during 3 h, 0°C-4°C PS decontamination. METHODS:An in vitro model simulating PS decontamination was established. Five MDRB isolates were collected and tested (CRKP, CRPA, CREC, CRAB, and MRSA). CAZ-AVI and ATM were prepared at different ratios (1:1, 1:2, 1:4, 2:1) and concentration gradients (0.5×, 1×, 2×, 4× the baseline). Antibacterial efficacy was recorded and analyzed. RESULTS:For CRKP and CREC, the 2:1 ratio at 0.5× concentration (250 mg/L CAZ-AVI + 0.5 g/L ATM) showed significant antibacterial effects (p = 0.002 and p < 0.001, respectively). For CRPA, efficacy was observed at the 1× concentration with a 2:1 ratio (500 mg/L CAZ-AVI + 1.0 g/L ATM; p = 0.022), while for CRAB, the 1:1 ratio at 0.5× concentration (125 mg/L CAZ-AVI + 0.5 g/L ATM; p < 0.001) was effective. The combination was only effective against MRSA at high concentrations (1000 mg/L CAZ-AVI + 2.0 g/L ATM; p < 0.001). CONCLUSIONS:The combination of CAZ-AVI and ATM effectively decontaminates MDR Gram-negative bacteria in PS. The 2:1 ratio at baseline concentration is recommended for clinical use, with potential escalation of CAZ-AVI concentration if needed.
BackgroundDonation-related infections (DRIs), particularly those caused by carbapenem-resistant gram-negative bacteria (CRGNB), can have disastrous consequences because of their extensive drug resistance. Contamination during graft acquisition and transport can lead to DRIs, and the use of antibiotics in preservation fluid (PF) before organ transplantation can reduce the incidence of DRIs. This study was to determine and compare the effectiveness of different PF decontamination regimens to prevent CRGNB related DRIs.MethodsTwelve CRGNB strains were chosen to be the targets of decontamination, and a drug concentration gradient was established for each test drug based on the previous clinical research. In addition the standard decontamination procedures were performed to evaluate the antimicrobial effectiveness of polymyxin B (PB), colistin sulfate (CS), colistimethate sodium (CMS) and amikacin (AK) in the 0~4°C PF, and to explore the antimicrobial effects of CMS after different preprocessing methods.ResultsPB and CS exhibited significantly better antimicrobial effectiveness against CRGNB than AK and CMS in the 0~4°C PF, and the antimicrobial effects on CRGNB increased with the increasing concentration of drugs. Notably, CMS after pretreatment (CMS-AP), its antibacterial was significantly enhanced at 4°C.ConclusionsThe PF decontamination is important in preventing the DRIs caused by CRGNB, and the decontamination regimens based on PB or CS were confirmed effective. Notably, CMS could even achieve a better decontamination effect than PB after a simple and fast pretreatment.
Several diseases affect the female reproductive system, and both disease factors and treatments impact its integrity and function. Consequently, understanding the mechanisms of disease occurrence and exploring treatment methods are key research focuses in obstetrics and gynecology. However, constructing accurate disease models requires a microenvironment closely resembling the human body, and current animal models and 2D in vitro cell models fall short in this regard. Thus, innovative in vitro female reproductive system models are urgently needed. Additionally, female reproductive system diseases often cause tissue loss, yet effective tissue repair and regeneration have long been a bottleneck in the medical field. 3D bioprinting offers a solution by enabling the construction of implants with tissue repair and regeneration capabilities, promoting cell adhesion, extension, and proliferation. This helps maintain the long-term efficacy of bioactive implants and achieves both structural and functional repair of the reproductive system. By combining live cells with biomaterials, 3D bioprinting can create in vitro 3D biomimetic cellular models, facilitating in-depth studies of cell-cell and cell-extracellular microenvironment interactions, which enhances our understanding of reproductive system diseases and supports disease-specific drug screening. This article reviews 3D bioprinting methods and materials applicable to the female reproductive system, discussing their advantages and limitations to aid in selecting optimal 3D bioprinting strategies. We also summarize and critically evaluate recent advancements in 3D bioprinting applications for tissue regeneration and in vitro disease models and address the prospects and challenges for translating 3D bioprinting technology into clinical applications within the female reproductive system.
The kidney allograft has been under continuous attack from diverse injuries since the very beginning of organ procurement, leading to a gradual decline in function, chronic fibrosis, and allograft loss. It is vital to routinely and precisely monitor the risk of injuries after renal transplantation, which is difficult to achieve because the traditional laboratory tests lack sensitivity and specificity, and graft biopsies are invasive with the risk of many complications and time-consuming. Herein, a novel method for the diagnosis of graft injury is demonstrated, using deep learning-assisted surface-enhanced Raman spectroscopy (SERS) of the urine analysis. Specifically, we developed a hybrid SERS substrate composed of gold and silver with high sensitivity to the urine composition under test, eliminating the need for labels, which makes measurements easy to perform and meanwhile results in extremely abundant and complex Raman vibrational bands. Deep learning algorithms were then developed to improve the interpretation of the SERS spectral fingerprints. The deep learning model was trained with SERS signals of urine samples of recipients with different injury types including delayed graft function (DGF), calcineurin-inhibitor toxicity (CNIT), T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), and BK virus nephropathy (BKVN), which explored the features of these types and achieved the injury differentiation with an overall accuracy of 93.03%. The results highlight the potential of combining label-free SERS spectroscopy with deep learning as a method for liquid biopsy of kidney allograft injuries, which can provide great potential to diagnose and evaluate allograft injuries, and thus extend the life of kidney allografts.
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis -Specific Protein Y -encoded -Like 2 (TSPYL2) plays a fibrogenic role in diabetes -associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress in vitro and in vivo . Further investigation showed that TSPYL2 regulated SREBP-2 acetylation by inhibiting SIRT1 and promoting p300 activity, thereby promoting the transcriptional activity of ACMSD. In conclusion, TSPYL2 was identified as a pivotal regulator of IRI-induced kidney damage by activating ACMSD, which may lead to NAD+ content and the damaging response in the kidney.
目的 分析肾移植围术期两种不同补液方案对护士工作状态及人性化护理能力的影响.方法 采用回顾性分析的方法,将2020年6月至2020年12月上海3家三级甲等综合医院器官移植科的100名护士,参与实施传统补液方案肾移植患者护理的50名纳入对照组,参与实施单一品种连续补液方案(复方果糖电解质注射液)肾移植患者护理的50名纳入试验组,采用简易应对方式量表、工作投入量表和护士人性化护理能力量表对两组护士分别进行调查.结果 试验组积极应对维度为(25.32±4.30)分,对照组为(23.10±4.63)分,试验组得分情况高于对照组,且差异有统计学意义(P=0.003).两组消极应对维度得分差异无统计学意义(P>0.05).试验组工作投入得分及人性化护理能力得分均高于对照组且有统计学意义(P<0.05).结论 单一品种连续补液方案可有效缓解护士应对临床护理工作的压力,提高其工作积极性,激发护士主动增加工作投入度,并促进其人性化护理能力的成长.
Background Islet transplantation is used therapeutically in a minority of patients with type 1 diabetes (T1D). However, successful outcomes are hampered by early islet β-cell loss caused by immune rejection and autoimmunity. Recent studies have demonstrated that mesenchymal stromal cells can enhance islet function both in vitro and in vivo by secreting ligands that activate islet G-protein coupled receptors (GPCRs). Stromal cell-derived factor 1 (SDF-1) is an MSC-secreted GPCR ligand, whereas the suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of STAT3-activating cytokines. Here, we determined whether improvement in islet function mediated by exogenous SDF-1 is impaired by SOCS3 in experimental models of T1D. Methods Isolated islets were cultured for 48 h with SDF-1. Cytokine-induced apoptosis was measured immediately. Islets from Socs3 −/− mice were pre-cultured with exogenous SDF-1 and transplanted underneath the kidney capsule of C57BL/6 mice with streptozotocin-induced diabetes. Blood glucose levels were monitored for 28 days. AMD3100, an antagonist of the SDF-1 ligand CXCR4, was administered subcutaneously to islet transplanted mice to inhibit CXCR4 before and after transplantation. Results SDF-1 protected islet cells from cytokine-induced apoptosis in vitro. SOCS3-knockout (KO) islets pretreated with SDF-1 were effective in reducing blood glucose in non-obese diabetic mice in vivo. We found that SDF-1 elicits localized immunosuppression in transplanted SOCS3-KO islets. Immunomodulation was observed when SOCS-KO islets were preconditioned with SDF-1. Gene expression and flow cytometric analyses revealed significantly decreased immune cell infiltration, inflammatory cytokines, and concomitant increases in FOXP3 + regulatory T cells, alternatively activated M2 macrophages, and dendritic cell phenotypes. Administration of AMD3100 impaired the SDF-1-mediated improvement in SOCS3-KO islet function and local immune suppression. Conclusion SDF-1 improves the function of islet grafts in autoimmune diabetes through regulation by CXCR4; however, the presence of SOCS3 reverses the protective effect of SDF-1 on islet grafts. These data reveal a molecular pathway that can elicit localized immunosuppression and delay graft destruction in transplanted islets.
Chitinase 3-like 1 (CH3L1) and liver fatty acid binding protein (L-FABP) are promising biomarkers for the early diagnosis of acute kidney injury (AKI). Here, a highly sensitive method for the quantitative detection of CH3L1 and L-FABP by surface-enhanced Raman spectroscopy (SERS) based on graphene oxide/gold and silver core-shell nanoparticles (GO/Au@Ag NPs) was proposed. The results showed that such GO/Au@Ag substrate can achieve rapid sensing of CH3L1 and L-FABP with a wide response range (2 x 10-1 to 2 x 10-8 mg/mL and 1.2 x 10-1 to 1.2 x 10-8 mg/mL, respectively) and high sensitivity. The detection limits of CH3L1 and L-FABP were 1.21 x 10-8 mg/mL and 0.62 x 10-8 mg/mL, respectively. In addition, the simultaneous detection of the two biomarkers in serum was demonstrated, showing the feasibility of this method in the complex biological environment. The detection of CH3L1 and L-FABP will greatly improve the early diagnosis and intervention of AKI.
海上发生落水事件时,快速组织有效的搜救和航空救治转运对于落水的舰船员和飞行人员具有重要的意义。随着我国远海编队落水飞行员搜救体系的建设,直升机航空救治和转运的重要性逐渐凸显,但目前其治疗要点和对策研究较少。本研究讨论了在搜救落水人员后进行航空救治以及转运的训练中,伤情拟定、人员和器械配备以及技能培训中存在的问题和训练心得,为完善直升机海上救助及卫勤保障提供借鉴。
Objective:To explore the risk factors related to acute rejection (AR) after pediatric kidney transplantation (KT).Methods:Retrospective analysis was performed for 189 pediatric KT recipients from September 2011 to August 2022.They were divided into two groups of AR (n=33) and non-AR (n=156).Univariate and multivariate Logistic regression analyses were performed for identifying potential risk factors of AR.And the effects of AR on graft function and survival were also examined.Results:During follow-ups, a total of 33(17.5%) patients developed AR with a 1-year cumulative incidence of AR of 16.9%(32/189).Univariate analysis revealed that median time on dialysis was longer in AR group than that in non-AR group (19 vs. 11 months, P=0.034).Median age of donors (12 vs. 24 months, P=0.033), median weight of donors (9.5 vs. 12 kg, P=0.025) and median donor/recipient body weight ratio (0.36 vs. 0.50, P=0.005) were lower in AR group than those in non-AR group.And the proportion of subtherapeutic tacrolimus (TAC) trough level was higher in AR group than that in non-AR group (45.5% vs. 21.2%, P=0.004).Multivariate regression analysis indicated that subtherapeutic TAC trough level was an independent risk factor for AR ( OR=2.977, 95% CI: 1.314-6.743, P=0.009).At the last follow-up, serum creatinine and eGFR were (78.4±24.3) vs. (74.6±24.7) μmol/L and (85.3±26.3) vs. (89.5±24.2) ml·min -1·1.73 m -2 in AR and non-AR groups respectively.There were no significant differences.1/5-year patient survival rate was both 97% in AR group and both 99.4% in non-AR group; 1/5-year graft survival rate both 90.9% in AR group and was 98.1% and 97.4% in non-AR group.No significant inter-group differences existed in patient and graft survival. Conclusions:Although an occurrence of early AR does not negatively impact graft outcomes, the incidence of AR remains high after pediatric KT.Therefore prompt diagnosis and treatment of AR should be strengthened.
In kidney transplantation, the donor kidney inevitably undergoes ischemia-reperfusion injury. It is of great importance to study the pathogenesis of ischemia-reperfusion injury and find effective measures to attenuate acute injury of renal tubules after ischemia-reperfusion. We systematically analyzed differences in the expression profiles of three SHP-1 (encoded by Ptpn6)-insufficient mice and three wild-type mice and achieved the expression data of 21367 genes by RNA-sequencing.TopHat v2.1.0 was used with the default parameters to generate acceptable alignments for Cufflinks, which was used to align the RNA sequencing paired-end reads against the reference genome, Ensembl release 90 GRCm38.p5. The expression of the annotated genes in the RNA-seq data was evaluated in fragments per kilobase million (FPKM) using Cufflinks. The following formula was used to calculate the FPKM value: FPKM = (number of mapped fragments) × 103 × 106/ [(length of transcript) × (total number of fragments)]. Log transformation and zero-mean normalization were used to normalize the expression data for comparisons. The false discovery rate (FDR) of <0.05, after applying Benjamini-Hochberg correction, was chosen for determining significant differentially expressed genes.Data sheet name: allsymbol.genes.expressionThis data sheet include the whole expression data of 21367 genes in three SHP-1 (encoded by Ptpn6)-insufficient mice and three wild-type mice.Data sheet name: WT-vs-HE.genes.annotThis data sheet include the comparasion of expression data of 21367 genes in three SHP-1 (encoded by Ptpn6)-insufficient mice and three wild-type mice.Data sheet name: WT-vs-HE.genes.filter.annotThis data sheet include the comparasion of expression data of 161 significant differentially expressed genes in three SHP-1 (encoded by Ptpn6)-insufficient mice and three wild-type mice.