Objective:To explore the impact of early and late antibody-mediated rejection (AMR) on treatment options and allograft outcomes after kidney transplantation (KT).Methods:From January 2013 to December 2022, the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria. Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group (n=19) while the remainders assigned as late AMR group (n=122). The outcome endpoints included recipient survival rate, death-censored graft survival rate, follow-up estimated glomerular filtration rate (eGFR) and immunodominant donor-specific antibody (DSA) intensity. Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact. Treatment regimens for AMR were collected and categorized.Results:The median follow-up duration was 2.6(1.2, 5.2) year. No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure, with 34 cases (77.2%) due to AMR progression. The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group [100% vs 60.1%(50.5%, 71.6%), P=0.002]. The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group [19.3(-2.6, 38.1) vs -3.3(-14.0, 5.4), P=0.001]. One-year mean fluorescent intensity (MFI) of early AMR group was 1 158(401.5, 3 126.5). It was significantly lower than that when diagnosed with early AMR [3 120.5(2 392.8, 9 340.0)] and one-year MFI of late AMR group [8 094(2 251.5, 13 560.5)] ( P=0.005, P<0.001). Early AMR group primarily received standard treatment (3/19, 15.8%) and regimens centered on rituximab and/or bortezomib (7/19, 43.8%). Late AMR group mainly received standard (16/122, 13.1%) or intensified regimens (9/122, 7.4%) and regimens focused upon rituximab and/or bortezomib (32/122, 26.2%) and MP monotherapy (21/122, 17.2%). Conclusion:The outcome for early AMR is significantly better than that for late AMR. For early AMR, early and robust immunosuppression is recommended. For late AMR, early detection and timely treatment are crucial and individualized strategies should be implemented.

This report described one patient of giant polycystic liver and polycystic kidney involving iliac fossa. Preoperative computed tomography (CT) revealed a large polycystic kidney occupying partially iliac fossa space. A decompression of lower pole of original kidney was planned for placing transplanted kidney. During total liver resection plus orthotopic liver transplantation, right polycystic kidney could move up on its own and iliac fossa space was released for placing transplanted kidney smoothly. Polycystic kidney shrunk markedly post-operation. It provided references for surgical planning of combined liver-kidney transplantation for this type of disease.

Objective:To explore the morbidity features and therapeutic outcomes of rejections in pediatric kidney transplantation (KT) recipients.Methods:Between January 2013 and June 2022, 360 children undergoing KT were recruited.The relevant clinical data were collected for examining the morbidity features and therapeutic outcomes of rejections.The serum levels of creatinine were compared among groups by non-parametric rank test.And Kaplan-Meier and Log-rank methods were employed for examining the incidence of rejection and comparing mortality-censored graft survival rates among patients with different times of rejection.Results:A total of 58 recipients had 82 incidents of rejection with a cumulative incidence of 6.3%, 9.2% and 11.3% at 3/6/12 months respectively.Among 50 incidents of biopsy-proved rejections, the types were T cell-mediated rejection [TCMR, 42.0%(21/50)], antibody-mediated rejection [20.0%(10/50), ABMR] and mixed rejection [38.0%(19/50)].Among 58 incidents of initial rejection, 69% had maintained graft function (MGF) and 31% impaired graft function (IGF) after anti-rejection regimens.Among 80.8%, 85.7% and 75% of recipients with clinical rejection, ABMR or borderline rejection while 36.4% in TCMR patients had MGF.Fifteen kidney allografts lost function in 58 recipients with rejection.Five-year death-censored graft survival was significantly lower in patients with two or more incidents of rejection (30.5%, 95% CI: 12.3%-75.4%) than in those without rejection (92.9%, 95% CI: 89.3%-96.6%) ( P<0.000 1) or with only one rejection (82.9%, 95% CI: 65.9%-100%)( P<0.001). Conclusions:The rejection rate remains high in KT children and it affects graft survival.And TCMR is more likely to cause impaired graft function.Recurrent rejections have a more pronounced impact upon graft survival.

ObjectiveTo investigate the effect of Zhizi Dahuang decoction （ZZDHT） in the treatment of alcoholic liver disease （ALD） by improving oxidative stress in hepatic neutrophils. MethodsNetwork pharmacology was used to obtain the chemical components of ZZDHT and their corresponding action targets and analyze the potential targets and functional pathways of ZZDHT in the treatment of ALD. The non-target metabolomics technology was used to observe the changes in the metabolites of ZZDHT in mouse serum and liver. The mice were given ZZDHT at a dose twice as much as the middle dose concentration by gavage， and serum and liver samples were collected at six time points after gavage （10 minutes， 30 minutes， 1 hour， 2 hours， 4 hours， and 6 hours） and were then mixed for mass spectrometry （administration group with 18 mice）， while the 18 mice in the control group were given an equal volume of normal saline by gavage. Ultra-performance liquid chromatography was used for rapid isolation and identification of the metabolites of ZZDHT in serum and liver tissue， and the effective constituents of ZZDHT were validated. Male C57BL/6J mice， aged 8 weeks， were randomly and equally divided into control group， model group， and low-， middle-， and high-dose ZZDHT groups， with 10 mice in each group. All mice except those in the control group were used to establish a mouse model of ALD （NIAAA model mice）， and at the same time， the mice in the administration groups were given low-， middle-， and high-dose ZZDHT by gavage， while those in the control group and the model group were given an equal volume of normal saline by gavage. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and triglyceride （TG） were measured； PCR was used to measure the gene expression levels of related inflammation， oxidative stress， and neutrophil indicators in the liver； ELISA was used to measure the levels of related inflammation and oxidative stress indicators in serum； superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured to observe the level of oxidative stress in the liver； HE staining， myeloperoxidase staining， and oil red staining were used to observe liver injury， neutrophil infiltration， and lipid deposition. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsA total of 53 active components and 227 target genes were obtained for ZZDHT， and there were 8685 target genes of ALD， resulting in 222 common target genes between these two groups of genes. Core pathways included the interleukin-6 signaling pathway and the TNF signaling pathway. The non-targeted metabolic analysis of ZZDHT obtained 225 metabolites in mouse liver and 227 metabolites in serum， among which there were 126 common metabolites. The core pathways of liver metabolites included glycerolipid metabolism and inflammatory mediator regulation of TRP channels， and the core pathways of serum metabolites included the AMPK signaling pathway and oxidative phosphorylation， all of which were associated with oxidative stress- and inflammation-related pathways. Compared with the model group， the low-， middle-， and high-dose ZZDHT groups had significant reductions in the serum levels of ALT， AST， and TG （all P<0.05）， and the middle-dose ZZDHT group had significant reductions in the levels of Ly6g， Ncf1， Ncf2， IL-6， TNF-α， IL-1β， MDA， 4-HNE， Gp91， and P22 in the liver （all P<0.05）， a significant increase in the level of SOD （P<0.05）， a significant reduction in the serum level of 4-HNE （P<0.05）， and a significant increase in the level of GSH-Px （P<0.05）. There were significant improvements in fat deposition and neutrophil infiltration in the liver of mice in the middle-dose ZZDHT group （both P<0.05）. ConclusionZZDHT significantly reduces oxidative stress and inflammatory response in NIAAA model mice.

Heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria are aerobic microorganisms that can remove nitrogen under high-salt conditions, but their performance in practical applications are not satisfactory. As a compatible solute, trehalose helps microorganisms to cope with high salt stress by participating in the regulation of cellular osmotic pressure, and plays an important role in promoting the nitrogen removal efficiency of microbial populations in the high-salt environment. We investigated the mechanism of exogenous-trehalose-enhanced metabolism of HN-AD community under high-salt stress by starting up a membrane aerobic biofilm reactor (MABR) to enrich HN-AD bacteria, and designed a C₁₅₀ experimental group with 150 μmol/L trehalose addition and a C₀ control group without trehalose. The reactor performance and the community structure showed that NH₄⁺-N, total nitrogen (TN) and chemical oxygen demand (COD) removal efficiency were increased by 29.7%, 28.0% and 29.1%, respectively. The total relative abundance of salt-tolerant HN-AD bacteria (with Acinetobacter and Pseudofulvimonas as the dominant genus) in the C₁₅₀ group reached 66.8%, an 18.2% increase compared with that of the C₀ group. This demonstrated that trehalose addition promoted the enrichment of salt-tolerant HN-AD bacteria in the high-salt environment to enhance the nitrogen removal performance of the system. In-depth metabolomics analysis showed that the exogenous trehalose was utilized by microorganisms to improve proline synthesis to increase resistance to high-salt stress. By regulating the activity of cell proliferation signaling pathways (cGMP-PKG, PI3K-Akt), phospholipid metabolism pathway and aminoacyl-tRNA synthesis pathway, the abundances of phosphoethanolamine, which was one of the glycerophospholipid metabolites, and purine and pyrimidine were up-regulated to stimulate bacterial aggregation and cell proliferation to promote the growth of HN-AD bacteria in the high-salt environment. Meanwhile, the addition of trehalose accelerated the tricarboxylic acid (TCA) cycle, which might provide more electron donors and energy to the carbon and nitrogen metabolisms of HN-AD bacteria and promote the nitrogen removal performance of the system. These results may facilitate using HN-AD bacteria in the treatment of high-salt and high-nitrogen wastewater.
Nitrification ; Denitrification ; Trehalose ; Phosphatidylinositol 3-Kinases/metabolism* ; Heterotrophic Processes ; Salt Stress ; Nitrogen/metabolism* ; Aerobiosis ; Bioreactors/microbiology*

Objective:To explore the diagnosis and treatment of transplanted renal artery stenosis(TRAS)in children.Methods:From January 2016 to August 2021, clinical data of 7 TRAS patients were collected.A definite diagnosis was confirmed by Doppler ultrasound and computed tomography angiography.Results:Patient age was significantly higher than donor age(11.9±3.7 vs 1.0±0.5 years, P<0.001); 5 patients had a widened diameter at stenotic grafted renal artery after intervention(1.98±0.47 vs 4.64±1.19 mm, P=0.002). A reduction in peak systolic flow velocity in stenotic segment of artery(463.3±90.6 vs 183.6±58.9 cm/s, P<0.001)and lower systolic blood pressure(137.2±15.5 vs 129.7±12.3 mmHg, P=0.029)were observed.Resistance index rose(0.38±0.22 vs 0.60±0.03, P=0.063). Significant difference of estimated glomerular filtration rate was observed at Week 4 post-operation as compared with pre-intervention.Two patients developed complications after intervention, including perirenal hematoma and stent-attached thrombus.Two patients were treated conservatively with a gradual increase in blood pressure and three antihypertensive drugs prescribed. Conclusions:Doppler ultrasound should be performed regularly after renal transplantation for detecting TRAS at an early stage in children.Interventional treatment is ideal for severe TRAS to improve perfusion and renal function.Clinicians should pay more attention to complications.

Objective:To conduct a retrospective analysis of efficacy and safety of different conversion schemes of tacrolimus to slow-release dosage forms for recipients in stable phase after renal transplantation to provide rationales for the conversion strategy of tacrolimus.Methods:From January 2020 to June 2020, clinical data were reviewed for 101 kidney transplant recipients converting from common tacrolimus dosage form to tacrolimus sustained-release dosage form during postoperative stable period.There were 62 males and 49 females with an age range of 19 to 69 years.They were divided into two groups according to iso-dose and incremental-dose switching schemes.The common dosage form of tacrolimus was converted into a sustained-release dosage form with different conversion doses, They were divided into two groups of 1∶1 conversion( n=55)and >1∶1 conversion( n=46). The clinical parameters of serum creatinine(Scr), blood urea nitrogen(BUN), alanine aminotransferase(ALT)and aspartate aminotransferase(AST), alkaline phosphatase(ALP), serum albumin(ALB), white blood cell count(WBC), urinary white blood cell(UWBC), hemoglobin(Hb)and fasting blood glucose(Glu)were compared between two groups after conversion. Results:Regarding numerical change trend after switching to tacrolimus sustained-release dosage form, drug dose/variation trend was smaller and blood drug concentration more stabilized.In two subgroups converted by 1∶1 and 1>1 initial dose, change trend of dose/blood concentration in 1∶1 conversion group appeared to be more stable.However, no inter-group difference existed in long-term parameters.Scr was lower at 1 week and 3 months after switching to extended-release dosage form( P<0.05)and BUN was lower at 2 weeks( P<0.05). In addition, at 5 months after conversion, ALT and AST significantly improved as compared with common dosage form( P<0.05). Significant differences existed in urinary WBC(UWBC)at 2/3 weeks( P<0.05). After switching for 2 weeks, hemoglobin significantly improved compared with common dosage form( P<0.05). No significant differences existed in ALP, ALB or Glu at other timepoints and pre-conversion( P>0.05). In 1∶1 switch group, renal function tended to improve.At 2 weeks, BUN was lower than pre-conversion; at 1/3 weeks, Scr was lower than pre-conversion( P<0.05). In addition, there was also a trend of improvement in liver function in 1∶1 conversion group.At 1 week and 5 months, ALT was lower than pre-conversion( P<0.05). However, no significant differences existed in AST, ALB, ALP, Glu, UWBC and serum WBC count at each timepoint between two different dose conversion groups( P>0.05). After conversion, intra-individual variability of tacrolimus trough concentration significantly improved( P<0.05). Conclusions:With the same safety and efficacy as common dosage form, sustained-release dosage form of tacrolimus may improve drug variability of individuals.When converting common dosage form into sustained-release dosage form, individual differences should be considered.While monitoring trough concentrations, proper doses should be adjusted on the basis of various clinical parameters.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and metabolic stress-induced liver injury. There are currently no approved effective pharmacological treatments for NAFLD. Traditional Chinese medicine (TCM) has been used for centuries to treat patients with chronic liver diseases without clear disease types and mechanisms. More recently, TCM has been shown to have unique advantages in the treatment of NAFLD. We performed a systematic review of the medical literature published over the last two decades and found that many TCM formulas have been reported to be beneficial for the treatment of metabolic dysfunctions, including Potentilla discolor Bunge (PDB). PDB has a variety of active compounds, including flavonoids, terpenoids, organic acids, steroids and tannins. Many compounds have been shown to exhibit a series of beneficial effects for the treatment of NAFLD, including anti-oxidative and anti-inflammatory functions, improvement of lipid metabolism and reversal of insulin resistance. In this review, we summarize potential therapeutic effects of TCM formulas for the treatment of NAFLD, focusing on the medicinal properties of natural active compounds from PDB and their underlying mechanisms. We point out that PDB can be classified as a novel candidate for the treatment and prevention of NAFLD.

Objective:To explore the clinical efficacy of dual-kidney transplantation from infant donors to adult recipients.Methods:From December 2012 to November 2020 in Organ Transplant Center First Affiliated Hospital Sun Yat-sen University, rertrospective reviews were conducted for clinical data of 25 pairs of infant donors and adult recipients. The survival rates were calculated for both recipients and transplanted kidneys at Year 1/3/5 post-transplantation. And the postoperative recovery status and the postoperative incidence of adverse events of recipients were observed.Results:The survival rates of recipients were all 95.8% at Year 1/3/5 and those of transplanted kidney and dealth-cancelling transplanted kidney all 87.2%. One case died due to acute inferior-wall cardiac infarction while three others lost renal functions for vascular thrombosis, ureteral stenosis and urinary fistula. Except for loss of renal function and death, the postoperative estimated golmerular fitration rate was (99.35±21.78), (103.11±29.20) and (114.99±28.55) ml/(min·1.73 m 2) at Year 1/2/3 respectively. Conclusions:Selecting proper recipients, standardizing donor acquisition and surgical procedures and strengthening perioperative managements may expand the donor pool. The overall outcomes are excellent for adult recipients with dual-kidney transplantation from donations after infants' death.

Objective:To explore the application value of modified technique of ureter implantation in murine renal transplantation.Methods:Thirty left donor kidneys from BALB/c mice was transplanted into syngeneic mice. Cuff technique was applied for anastomosing kidney artery and vein. The procedure of ureter-bladder anastomoses shifted from implication-fixation-embedding to fixation-implication-embedding. Operative duration, recipient survival rate and complications were recorded.Results:Time for separating vessels, perfusion and excision of donor graft was (25±3) min, (10±6) s for warm ischemia and (25±5) min for cold ischemia. Time for separating recipient vessels was (12±5) min, (7±1) min for arterial anastomosis, (7±1) min for venous anastomosis, (13±2) min for ureter-bladder anastomosis, (5±1) min for right kidney excision and (5±1) min for abdominal closure. Operative duration was(77±3)min. Twenty-six recipients survived over 3 months. The successful operative rate was 86.7%.Conclusions:With a shorter learning curve, modified technique of ureter implantation is easier and faster so as to reduce the postoperative incidence of urinary tract complications during murine renal transplantation.