Enhanced recovery after surgery in percutaneous transhepatic cholangioscopic lithotripsy for patients with hepatolithiasis and choledocholithiasis.

Background: Percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) provides an effective alternative procedure for the management of complex hepatolithiasis and choledocholithiasis. Enhanced recovery after surgery (ERAS) program is an evidence-based approach that was developed to reduce surgical stress and accelerate postoperative recovery. However, little is known regarding PTCSL in the context of ERAS. The aim of this study was to evaluate the efficacy and safety of PTCSL within ERAS programs. Patient and methods: The clinical data of patients who underwent PTCSL within ERAS programs consulted at our hospital between November 2017 and November 2022 was retrospectively reviewed. Individualized perioperative ERAS items were evaluated for all patients. The demographics, intraoperative variables, and postoperative outcomes were analyzed. Results: A total of 43 patients who underwent PTCSL were included in the study. There were 13 men and 30 women aged between 39 and 89 years with an average age of 60 years (60.49 ± 12.37). The stone clearance rate was 77 % after the first operation, and the final clearance rate was 95 %. The incidence of complications in this study is 18.6 % (8/43), including 6 patients with Clavien-Dindo I-II, and 2 patients with Clavien-Dindo III. Pleural effusion, abdominal effusion, infection, bile leakage, and biliary bleeding are the most common complications, however, all patients recovered after aggressive treatment. Conclusion: PTCSL is a relatively safe, feasible, and efficient method for treating complex hepatolithiasis and choledocholithiasis within ERAS programs. Individualized ERAS entries and precise disease management are required to minimize the occurrence of complications and to provide effective treatment.

Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study.

BACKGROUND: Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHODS: Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. CONCLUSIONS: The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.

Knowledge Mapping of Immunotherapy for Hepatocellular Carcinoma: A Bibliometric Study.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and many patients are diagnosed with advanced disease. The treatment of advanced liver cancer has made significant strides in recent years, owing to the practice of immunotherapy drugs. Numerous studies have been published on immunotherapy for HCC; however, no relevant bibliometric study has been published. This study aims to gain a better understanding of the current situation and to identify potential new research directions by conducting a bibliometric analysis on immunotherapy for HCC. Methods: We searched the Web of Science Core Collection (WoSCC) for articles related to immunotherapy for HCC. Three software (VOSviewer, CiteSpace, and python) were primarily used to assess the contribution and co-occurrence relationships of various countries/regions, institutes, journals, and, authors as well as to identify research hotspots and promising future trends in this research field. Results: A total of 1,641 English articles published between 2011 and 2020 were collected, with the number of articles increasing nearly every year. The majority of publications originated from China (n = 893, 54.42%), followed by the United States and Japan. The Sun Yat-sen University contributed the most publications (n = 97, 5.91%). Nakatsura Tetsuya (n = 26) and Llovet JM (n = 366) were ranked first in the top ten authors and co-cited authors. Cancer Immunology Immunotherapy was the most productive academic journal on immunotherapy for HCC [n = 46, 2.80%; impact factor (IF) 2020 = 6.9679]. Aggregation and identification of critical nodes in the co-cited network demonstrated a shift in the field of HCC immunotherapy. Initially, the hotspots were predominantly "glypican-3", "cytokine-induced killer cells", and "ny-eso-1", while the emphasis has shifted in recent years to "landscape", "camrelizumab", "combination therapy", and "immune score". Conclusion: Increased attention has been paid to HCC with the advancement of immunotherapy. At the moment, the most active frontiers are focused on better understanding the immunological landscape of liver cancer, screening the population that can benefit from immunotherapy, and the clinical application of immune checkpoint inhibitors, particularly in combination with other therapeutic options (such as local therapy and targeted therapy).

Abnormal bile acid-microbiota crosstalk promotes the development of hepatocellular carcinoma.

BACKGROUND: Gut microbiota and microbe-derived metabolites are involved in the development of HCC. Bile acids (BAs) are the most important gut microbiota-modulated endogenous signaling molecules. METHODS: We tested serum bile acid levels and gut microbiome compositions in patients with HCC, chemical-induced HCC mouse models (DEN-HCC mice) and mouse orthotopic implanted liver tumor models with vancomycin treatment (vancomycin-treated mice). Then, we screened an important kind of HCC-related BAs, and verified its effect on the growth of HCC in vivo and in vitro. RESULTS: We found that the remarkably decreasing percentages of serum secondary BAs in the total bile acids of patients and DEN-HCC mice, especially, conjugated deoxycholic acids (DCA). The relative abundance of the bile salt hydrolase (BSH)-rich bacteria (Bifidobacteriales, Lactobacillales, Bacteroidales, and Clostridiales) was decreased in the feces of patients and DEN-HCC mice. Then, in vancomycin-treated mice, vancomycin treatment induced a reduction in the BSH-rich bacteria and promoted the growth of liver tumors. Similarly, the percentage of conjugated DCA after vancomycin treatment was significantly declined. We used a kind of conjugated DCA, Glyco-deoxycholic acid (GDCA), and found that GDCA remarkably inhibited the growth of HCC in vivo and in vitro. CONCLUSIONS: We conclude that the remarkably decreasing percentages of serum conjugated DCA may be closely associated with HCC, which may be induced by the reducing gut BSH-rich bacteria. The mechanisms may be correlated with conjugated DCA directly inhibiting the growth and migration of HCC cells.

Diversity and composition of microbiota during fermentation of traditional Nuodeng ham.

The microbial community is one of the most important factors in shaping the characteristics of fermented food. Nuodeng ham, traditionally produced and subjected to 1-4 years of fermentation, is a dry fermented food product with cultural and economic significance to locals in southwestern China. In this study, we aimed to characterize the microbiota and physicochemical profiles of Nuodeng ham across different stages of fermentation. Ham samples from each of the four years were analyzed by sequencing bacterial 16S rRNA gene and fungal internal transcribed spacer sequence, in order to characterize the diversity and composition of their microflora. A total of 2,679,483 bacterial and 2,983,234 fungal sequences of high quality were obtained and assigned to 514 and 57 genera, respectively. Among these microbes, Staphylococcus and Candida were the most abundant genera observed in the ham samples, though samples from different years showed differences in their microbial abundance. Results of physicochemical properties (pH, water, amino acid, NaCl, nitrate and nitrite contents, and the composition of volatile compounds) revealed differences among the ham samples in the composition of volatile compounds, especially in the third year samples, in which no nitrite was detected. These results suggest that the structure and diversity of microbial communities significantly differed across different stages of fermentation. Moreover, the third year hams exhibits a unique and balanced microbial community, which might contribute to the special flavor in the green and safe food products. Thus, our study lends insights into the production of high quality Nuodeng ham.

[Screening and Identification of Blood Group Alloantibody by Surface Plasmon Resonance Technique and Its Preliminary Application].

OBJECTIVE: To investigate the feasibilily of screening and identifying the red blood cell type alloantibodies by means of surface plasman resonance(SPR) technique so as to provide a new method for detecting the transfusion compatibility of red blood cells. METHODS: The RBC antigens for screening the alloantibody were fixed on the SPR chip surface by means of amino coupling method; the analysis conditions of SPR chip were optimized and then the control serum with RBC blood group antibody positive was detected; the performance of SPR chip for detection of serum was analysed; the consistance of rusults detected by SPR technique and microcolum agglutination for clinieal samples of 129 thalasstmia patients with history of lone-term blood transfusion were compared; at the same time, the blood group amtibodies in 7 patients with blood group antibody positive were identified before blood transfusion by using SPR chip so as to select the RBC antigen compatible blood for transfusion; and the efficacy of RBC transfusion was followed up and evaluated. RESULTS: The repeatability, sensitivity and specificity of SPR chip technique for detecting the blood group alloantibodies all were better. The SPR technique and microcolumn agglutination method were not significant different for screening blood group alloantibodies (χ2 = 0.333, P＞0.05), and the overall consistency was 97.2%; the results of SPR technique in 7 patients with positive blood group antibodies were as follows: 3 cases with anti-E, 1 case anti-M, 1 case anti-C, 1 case anti-Jka and 1 case autoantibody, which were consistent with the results of microcolumn agglutination tests, and the compatible red blood cells were selected for transfusion, of which the infusion of 6 cases was effective. In only 1 case the infusion was ineffective because of autoantibody. CONCLUSION: For screening and identification of blood group alloantibodies, the performance of SPR chip technique is equivalent to the micro-column agglutination, but the procedure of SPR technique is simpler, faster and high-throughput and label-free, which can meet the basic requirements for rapid screening and identification of blood group alloantibodies before transfusion of red blood cells.

Usefulness of mizoribine administration in children with frequently relapsing nephrotic syndrome, and the relationship between pharmacokinetic parameters and efficacy: a multicenter prospective cohort study in China.

BACKGROUND: Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy. There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS). We investigated the efficacy and safety for treating MZR with FRNS. Furthermore, the relationship between efficacy and serum concentration was investigated. METHODS: A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS. Serum MZR concentration was measured, and the relationships between pharmacokinetic parameters (Cmax, AUC), number of relapses, and urinary protein were evaluated. RESULTS: Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone. MZR treatment significantly reduced the number of relapses and steroid doses. A correlation between pharmacokinetic parameters and relapses was observed, which fits well with the sigmoidal Emax model. Even in the relationship between pharmacokinetic parameters and urinary proteins, it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model. Eleven patients (13.4%) experienced mild adverse events. CONCLUSIONS: MZR therapy was effective in reducing the number of relapses and steroid doses. No severe adverse reactions were observed. Therapeutically effective serum concentrations were estimated to be Cmax ≥ about 2 µg/mL or AUC ≥ about 10 µg h/mL. MZR and steroid treatment were effective and safe for pediatric FRNS.

Effect of Salt Intake on Plasma and Urinary Uric Acid Levels in Chinese Adults: An Interventional Trial.

Uric acid (UA) has been proposed as an important risk factor for cardiovascular and renal morbidity. We conducted an interventional trial to assess effects of altered salt intake on plasma and urine UA levels and the relationship between UA levels and salt sensitivity in humans. Ninety subjects (18-65 years old) were sequentially maintained on a normal diet for 3 days at baseline, a low-salt diet for 7 days (3.0 g/day, NaCl), and a high-salt diet for an additional 7 days (18.0 g/day of NaCl). Plasma UA levels significantly increased from baseline to low-salt diet and decreased from low-salt to high-salt diet. By contrast, daily urinary levels of UA significantly decreased from baseline to low-salt diet and increased from low-salt to high-salt diet. The 24 h urinary sodium excretions showed inverse correlation with plasma UA and positive correlation with urinary UA excretions. Additionally, salt-sensitive subjects presented significantly higher plasma UA changes in comparison to salt-resistant subjects, and a negative correlation was observed between degree of salt sensitivity and plasma UA difference. The present study indicates that variations in dietary salt intake affect plasma and urine UA levels, and plasma UA may be involved in pathophysiological process of salt sensitivity.

Effect of Salt Intake on Serum Glucagon-Like Peptide-1 Levels in Normotensive Salt-Sensitive Subjects.

BACKGROUND/AIMS: Excess dietary salt is a critical risk factor of salt-sensitive hypertension. Glucagon-like peptide-1 (GLP-1) , a gut incretin hormone, conferring benefits for blood pressure by natriuresis and diuresis. We implemented a randomized trial to verify the effect of altered salt intake on serum GLP-1 level in human beings. METHODS: The 38 subjects were recruited from a rural community of Northern China. All subjects were sequentially maintained a baseline diet period for 3 days, a low-salt diet period for 7 days (3.0g/day of NaCl) , and a high-salt diet period for additional 7 days (18.0g/day of NaCl). RESULTS: Serum GLP-1 level increased significantly with the change from the baseline period to the low-salt diet period and decreased with the change from the low-salt to high-salt diet in normotensive salt-sensitive (SS) but not salt-resistant (SR) individuals. There was a significant inverse correlation between the serum GLP-1 level and the MAP in SS subjects. Inverse correlation between the serum GLP-1 level and 24-h urinary sodium excretion was also found among different dietary interventions in SS subjects. CONCLUSIONS: Our study indicates that variations in dietary salt intake affect the serum GLP-1 level in normotensive salt-sensitive Chinese adults.

Lupus glomerulonephritis in 788 Chinese children: a multi-centre clinical and histopathological analysis based on 549 renal biopsies.

BACKGROUND: System lupus erythematosus (SLE) is a severe multisystem autoimmune disease. OBJECTIVE: To describe the clinical and pathological features, treatment, and renal outcome in children under 18 years with lupus nephritis (LN). METHODS: The study was undertaken by a questionnaire completed in 26 Grade 3A hospitals' paediatric renal units in China. The study comprised 788 children (619 girls, 169 boys) diagnosed with SLE by the American College of Rheumatology criteria (1997) during 2005-2010. Results of renal biopsies were classified according to the guidelines of The International Association of Nephrology and the Renal Pathology Society (2003). Guidelines by the Chinese Society of Paediatric Nephrology were applied for the diagnosis and treatment (for trial implementation) in 2010 to determine inclusion. The data included the prevalence of acute kidney injury (AKI), SLE disease activity index (SLEDAI), renal histopathology and the induction of therapy mode. RESULTS: The mean (SD) age of onset of SLE was 10.9 (2.90) years (range 1-18) and at diagnosis was 11.3 (2.9) years. The mean (SD) SLEDAI score was 13.5 (5.53). The clinical classification was as follows: about 36 (4.6%) patients had isolated haematuria, 99 (12.6%) isolated proteinuria, 60 (7.6%) isolated haematuria and proteinuria, 157 (19.9%) acute glomerulonephritis, 392 (49.7%) nephrotic syndrome, 20 (2.5%) rapidly progressive glomerulonephritis, 15 (1.9%) chronic nephritis, 2 (0.3%) tubule-interstitial damage and 7 (0.9%) subclinical LN. A total of 549 children (69.7%) underwent renal biopsy. The most frequent renal histopathological findings of LN were Class IV, followed by Class II and Class V + IV. There were no significant differences between the age groups in either renal pathological types or prognosis. In 242 (30.7%) patients, LN was complicated by AKI. Those with AKI had an older mean (SD) age at onset than the non-AKI patients [11.5 (2.8) years vs 10.7 (2.9) years, respectively, p < 0.0001] and a higher SLEDAI score [14.3 (5.8) vs 13.1 (5.4), respectively, p = 0.003]. In the induction phase, cyclophosphamide (CTX) and mycophenolate mofetil (MMF) were equally effective in the patients with the same pathological type. Follow-up records were only available for 482 (61.2%) patients, with a mean (SD) follow-up time of 21.5 (18.4) months. Six of the 35 patients who deteriorated required dialysis and seven died. CONCLUSION: In LN, AKI is a risk factor for poor outcome. Owing to different times of onset and remission, the pathological types of LN cannot be estimated by clinical manifestation alone, and therefore renal biopsy should be undertaken in all LN children with AKI. In the induction phase, there was no significant difference in efficacy between CTX and MMF. Follow-up of children with LN in China needs to be improved.

Roles of 1,25(OH)2D3 and Vitamin D Receptor in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus by Regulating the Activation of CD4+ T Cells and the PKCδ/ERK Signaling Pathway.

BACKGROUND/AIMS: The study aims to elucidate the roles of 1,25(OH)2D3 and vitamin D receptor (VDR) in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by regulating the activation of CD4+ T cells and the PKCδ/ERK signaling pathway. METHODS: From January 2013 to December 2015, a total of 130 SLE patients, 137 RA patients and 130 healthy controls were selected in this study. Serum levels of 1,25(OH)2D3 and VDR mRNA expression were detected by ELISA and real-time fluorescence quantitative PCR (RT-qPCR). Density gradient centrifugation was performed to separate peripheral blood mononuclear cells (PBMCs). CD4+ T cells were separated using magnetic activated cell sorting (MACS). CD4+T cells in logarithmic growth phase were collected and assigned into 9 groups: the normal control group, the normal negative control (NC) group, the VDR siRNA group, the RA control group, the RA NC group, the VDR over-expressed RA group, the SLE control group, the SLE NC group, and the VDR over-expressed SLE group. The mRNA and protein expressions of VDR, PKCδ, ERK1/2, CD11a, CD70 and CD40L were detected by RT-qPCR and Western blotting. Bisulfite genomic sequencing was conducted to monitor the methylation status of CD11a, CD70 and CD40L. RESULTS: Compared with healthy controls, serum 1,25(OH)2D3 level and VDR mRNA expression in peripheral blood were decreased in SLE patients and RA patients. With the increase of concentrations of 1,25(OH)2D3 treatment, the VDR mRNA expression and DNA methylation levels of CD11a, CD70 and CD40L were declined, while the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L were elevated in SLE, RA and normal CD4+T cells. Compared with the SLE contro, RA control, SLE NC and RA NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L decreased but DNA methylation levels of CD11a, CD70 and CD40L increased in the VDR over-expressed SLE group and VDR over-expressed RA group. However, compared with the normal control and normal NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L increased, but DNA methylation levels of CD11a, CD70 and CD40L decreased in the VDR siRNA group. Compared with the normal control group, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L increased, but DNA methylation levels of CD11a, CD70 and CD40L decreased in the SLE control and RA control groups. CONCLUSION: Our study provide evidence that 1,25(OH)2D3 and VDR could inhibit the activation of CD4+ T cells and suppress the immune response of SLE and RA through inhibiting PKCδ/ERK pathway and promoting DNA methylation of CD11a, CD70 and CD40L.

Intravenous transfusion of endothelial progenitor cells that overexpress vitamin D receptor inhibits atherosclerosis in apoE-deficient mice.

Endothelial progenitor cells (EPCs) are widely used for angiogenic therapies, as well as predictive biomarkers to assess cardiovascular disease risk. However, it is unknown that whether overexpressed vitamin D receptor (VDR) in EPCs could help EPCs counteracting atherosclerotic risks. Here, we study intravenous transplantation of genetically modified EPCs over-expressing VDR in regulating endothelial dysfunction and spontaneously arising atherosclerotic plaques of ApoE-deficient mice. Firstly, we found that over-expression of VDR in EPCs could reduce atherosclerotic plaque formation in transplanted ApoE-/- mice. In addition, the concentration of serum HDL-C in ovVDR-EPCs group was much higher than that in control groups (ApoE-/- mice without injection or injected with fresh medium or adenovirus vector). While concentrations of serum total cholesterol, LDL-C, apoB and Lp (a) were negatively correlated with the expression level of VDR. What's more, improved serum concentration of NO and elevated serum and vessel wall expression of eNOS were observed in ovVDR-EPCs group. Furthermore, reduced expression and activity of MMP2, and elevated expression and activity of TIMP2 were detected in ovVDR-EPCs group. Taken together, intravenous transfusion of EPCs that overexpress VDR significantly inhibited atherosclerosis in ApoE-deficient mice and could be used as a potential method for angiogenic therapy.

Etiology and outcomes of acute kidney injury in Chinese children: a prospective multicentre investigation.

BACKGROUND: The incidence of AKI appears to have increasing trend. Up to now, prospective, multi-center, large-sample epidemiological study done on pediatric AKI on aspects of epidemiological characteristics, causes and outcomes have not reported. It is necessary to develop prospective, multi-center, large-sample epidemiological study in our country on pediatric AKI. The aim of this study was to determine the clinical features, etiology, and outcomes of acute kidney injury (AKI) in Chinese children. METHOD: Paediatric patients (≤18 years old) admitted to 27 hospitals (14 children's hospitals and 13 general hospitals) affiliated with the Medical University were investigated. AKI was defined using the 2005 Acute Kidney Injury Network criteria. RESULTS: During the study period, 388,736 paediatric patients were admitted. From this total, AKI was diagnosed in 1,257 patients, 43 of whom died. The incidence and mortality of AKI was 0.32% and 3.4% respectively. The mean (± SD) age of patients was 48.4 ± 50.4 months. Among the 1,257 AKI paediatric patients, 632 were less than one year old. Among the AKI paediatric patients, 615 (48.9%) were in stage 1, 277 (22.0%) in stage 2, and 365 (29.0%) in stage 3. The most common causes of AKI were renal causes (57.52%), whereas postrenal (25.69%) and prerenal (14.96%) causes were the least common. The three most common causes of AKI according to individual etiological disease were urolithiasis (22.35%), of which exposure to melamine-contaminated milk accounted for the highest incidence (63.7%); acute glomerulonephritis (10.10%); and severe dehydration (7.48%). A total of 43 AKI patients (3.4%) died during their hospital stay; 15 (34.9%) of the 43 died as a result of sepsis. CONCLUSION: Primary renal diseases are a major risk factor for paediatric AKI in China. In terms of specific etiological disease, urolithiasis (postrenal disease) was the leading cause of paediatric AKI in 2008, when the disease was linked to exposure to melamine-contaminated milk. Sepsis is the leading cause of death in Chinese paediatric AKI patients. Future studies should focus on effective ways of controlling renal disorders and sepsis to improve the clinical management of paediatric AKI in China.

Number and function of peripheral blood endothelial progenitor cells in Henoch-Schönlein purpura nephritis children with different degrees of renal vascular lesions.

The aim of this study was to explore the correlation between different degrees of renal vascular lesions in children with Henoch-Schönlein purpura nephritis (HSPN) and changes in progenitor cell number and function in peripheral blood. Forty-eight HSPN patients were divided into three groups, mild, moderate and severe, according to the degree of renal vascular lesions. Peripheral blood mononuclear cells were isolated and cultured. Endothelial progenitor cells (EPCs) were identified by immunofluorescence assay. The number of EPCs and the migration and adhesion of EPCs were detected by flow cytometry. The numbers of peripheral blood CD34(+), kinase insert domain receptor(+) (KDR(+)) and CD133(+) cells were lower in the severe and moderate vascular lesion groups compared with the mild vascular lesion group (all P<0.05) and were also lower in the severe vascular lesion group compared with the mild and moderate vascular lesion groups (all P<0.05). The adhesion and migration of EPCs were reduced in turn in the mild, moderate and severe groups. There were significant differences between the severe group and the mild and moderate groups (all P<0.05). Renal vascular lesions are involved in the occurrence and development of HSPN, while the number of EPCs, migration and adhesion of EPCs are important factors in renal vascular lesions.

Nephroprotective effects of subcapsular transplantation of metanephric mesenchymal cells on gentamicin-induced acute tubular necrosis in rats.

BACKGROUND: The subcapsular transplantation of metanephric mesenchymal cells (MMCs) may be a new therapeutic approach for the treatment of acute tubular necrosis (ATN). To investigate this hypothesis and provide evidence for its possible use in the clinic, we evaluated the nephroprotective effects of transplanting MMCs into the renal subcaspsule of rats with ATN induced by gentamicin. METHODS: MMCs were expanded in culture. After gentamicin-induced ATN was established, fluorescently-labeled cells were transplanted and traced in kidney tissues by fluorescence microscopy. Serum creatinine (Cr), urea nitrogen (BUN), and N-acetyl-b-D-glucosaminidase (NAG) levels were determined at different time points. Kidney pathology was studied by hematoxylin-eosin staining. Apoptosis was examined by the TUNEL assay. RESULTS: In the MMCs-treated group, the mortality rate decreased; BUN, Cr, and NAG levels peaked at 8 days, and were significantly lower than those in the other groups at 11 and 14 days. RIMM-18 cells locally recruited through precise tropism to sites of injury had the ability to migrate into the tubuli from the renal subcapsule. Damage to the cell-treated kidneys was reduced. The pathologic lesion scores of tubular damage reached the highest values at 8 days in the treated kidneys and 11 days in the untreated ones. The apoptotic index showed that the peaks of apoptosis occurred at earlier stages of the injury process in cell-treated than in untreated kidney and thereafter declined in a time-dependent manner. CONCLUSION: The subcapsular transplantation of MMCs could ameliorate renal function and repair kidney injury.

[Relationship between renal Th1/Th2 ratio and renal microvascular injury in children with Henoch-Sch-nlein purpura nephritis].

OBJECTIVE: To explore possible correlations between renal Th1/Th2 ratio and renal microvascular injury in children with Henoch-Sch-nlein purpura nephritis (HSPN). METHODS: Thirty-two children with HSPN were enrolled. They were classified into four groups by renal pathology: HSPN class II (n=8), HSPN class IIIa (n=7), HSPN class IIIb (n=10) and HSPN class IV/V (n=7). Five patients undergoing nephrectomy due to trauma were used as the controls. INFγ, IL-4 and CD34 in the renal tissues were measured by immunohistochemical analysis. INFγ was used as a marker of Th1, IL-4 was used as a marker of Th2 and CD34 was used as a marker of microvessel. The renal microvessel density was evaluated according to the Weidner standard. The relationships among the local Th1/Th2 ratio, renal pathological grade, microvessel score and microvessel density were studied. RESULTS: Immunohistochemical analysis showed a lower expression of INFγ and a higher expression of IL-4 in the HSPN groups than in the control group. The local Th1/Th2 ratio in the HSPN groups decreased and correlated significantly with the renal pathological grade. There were significant differences among four HSPN subgroups (P<0.05). Compared with the control group, the renal microvessel density in the HSPN class II and class IIIa groups increased significantly (P<0.05), but it decreased in the HSPN class IV/V group (P<0.05). The renal microvessel scores in the HSPN class IIIa, class IIIb and class IV/V groups increased significantly compared with those in the control and the HSPN classⅡ. The increased renal microvessel scores were associated with more severe renal pathological changes. A negative correlation was found between the local Th1/Th2 ratio and the microvessel density in kidneys (r=-0.921, P<0.01). CONCLUSIONS: The decrease of Th1/Th2 ratio in kidneys might be responsible for renal microvascular injury in children with HSPN.

[Relationship of 24-hour ambulatory blood pressure and rennin-angiotensin-aldosterone system in children with primary nephrotic syndrome].

OBJECTIVE: To investigate the changes of blood pressure by 24-hour ambulatory blood pressure (ABP) monitoring in children with primary nephrotic syndrome (PNS) and explore the relationship of the changes in blood pressure with rennin-angiotensin-aldosterone system (RAAS) in these children. METHODS: ABP and casual blood pressure (CBP) monitoring were performed in 114 children with PNS. Plasma levels of rennin activity (PRA), angiotensin II (AngII) and aldosterone (ALD) were measured. The correlation of plasma levels of PRA, AngII and ALD with ABP was evaluated. RESULTS: Of the 114 children with PNS, 101 (88.6%) presented elevated blood pressure. Mild or severe masked hypertension was found in 45 children (39.5%). Eighty (70.2%) children showed non-dipper blood pressure. The index and load of systolic blood pressure were higher than those of diastolic blood pressure. The blood pressure index and blood pressure load during sleep were higher than those during wakefulness. The boy presented higher diastolic blood pressure index and load than girls. Decubitus blood PRA, AngII and ALD levels in children with PNS were significantly higher than normal controls. The group with elevated blood pressure presented significantly higher decubitus blood PRA, AngII and ALD levels than the group with normal blood pressure. AngII level was significantly positively correlated with the index and load of both systolic blood pressure and diastolic blood pressure. CONCLUSIONS: The children with PNS present a high incidence of hypertension, with a large percentage of masked hypertension and non-dipper blood pressure. Systolic blood pressure increases more significantly than diastolic blood pressure. Blood pressure during sleep increases more significantly than that during wakefulness. Diastolic blood pressure increases more significantly in boys than in girls. RAAS activity is elevated and the elevated RAAS activity might increase the blood pressure mainly by AngII in children with PNS.