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Erdheim–Chester disease is a rare form of non-Langerhans histiocytosis. A 40-year-old woman was diagnosed as Erdheim-Chester disease based on typical bone scintigraphy, symmetric osteosclerosis and findings of foamy, non-Langerhans histiocytes in bone marrow. BRAFV600E mutation was detected in a bone biopsy. Treatment with IFN-α showed significant improvement. The BRAFV600E mutant was detected in plasma cell-free DNA (cfDNA) by a droplet-digital PCR assay. Longitudinal analysis of BRAFV600E in plasma cfDNA showed a decreasing trend during treatment. We could not detect the mutant in urinary cfDNA. While, similar studies have detected the BRAFV600E mutant in urine, but not in plasma. A combination of allele burden assessments in plasma and urine may be helpful for detecting the residual mutant burden and monitoring therapeutic response.

BackgroundLipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai.MethodMale ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (−/−) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the humanApoE SendaiandApoE Kyoto,apoE3, andeGFPgenes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin–creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed.ResultsAfter virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4–6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin–creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (−/−) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation.ConclusionsIn this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.

Background and purpose Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA-based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation. Experimental approach Two murine models of hyperoxic lung injury (with or without miR-342-5p or Sprouty-related, EVH1 domain-containing protein 3 [Spred3] modulation) were employed: a hyperoxia-induced acute lung injury model (100% O2 on postnatal days 1-7) and the BPD model (100% O2 on postnatal days 1-4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR-342-5p analysis. Key results Hyperoxia decreased miR-342-5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR-342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD-associated pulmonary arterial hypertension (PAH). T2AEC-specific miR-342 transgenic overexpression, as well as miR-342-5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR-342-5p targets the 3'UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR-342-5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR-342-5p levels relative to healthy control pellets. Conclusion and implications These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD.

Rationale: Mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene result in a very variable presentation, including maturity onset diabetes of the young (MODY), renal cysts, renal dysplasia, and autosomal dominant tubulointerstitial kidney disease (ADTKD), which is characterized by tubular damage, renal fibrosis, and progressive renal dysfunction. Patient concerns: A 22-year-old man came to the hospital presenting with hyperglycemia, hyperuricemia and elevated serum creatinine. His urine protein was within the normal range. The ultrasound examination revealed shrunken kidneys with renal cysts. The patient's mother was diagnosed with diabetes mellitus when she was 25 years old. Her laboratory results showed elevated serum creatinine. Her ultrasonography revealed shrunken kidneys with renal cysts and hydronephrosis without kidney stones. The next-generation sequencing revealed that the proband and his mother held the same heterozygous missense mutation (c.530G>A, NM_000458, p.R177Q) in the HNF1B gene. Bioinformatic analyses predicted that the mutation was likely pathogenic. Diagnosis: The patient and his mother were diagnosed as ADTKD and MODY5 due to HNF1B mutation. Intervention: The proband was administered metformin at a dose of 500 mg/day. Outcomes: The patient had well-controlled blood glucose levels and a stable renal function at his 12-month follow-up. Lessons: We should take into account the diagnoses of ADTKD and MODY5 if patients present with early onset diabetes and multiple renal cysts or evidence of renal tubulointerstitial dysplasia, especially those with negative proteinuria results. Genetic testing helps detect the HNF1B gene mutations.

Background C3 glomerulopathy (C3G) is a recent disease classification that is characterized by the presence of glomerular deposits (composed of C3) in the absence of significant amounts of immunoglobulin and comprises dense deposit disease and C3 glomerulonephritis (C3GN). Most C3GN manifests as membranoproliferative, mesangial proliferative glomerulonephritis patterns via light microscopy. Pure membranous nephropathy (MN)-like glomerular lesions are rare manifestations of C3GN. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also seldomly reported to be positive in C3GN. Herein, we report the case of a C3GN patient presenting with an MN-like glomerular pattern with ANCA positivity. Case presentation A 68-year-old woman was admitted to a local hospital with elevated serum creatinine for two weeks. Laboratory tests showed a hemoglobin level of 85 g/L. Urinalysis was positive for 2 + protein and 360 RBCs/HPF. Blood biochemistry analysis revealed the following concentrations: albumin, 30.3 g/L; globulin, 46.2 g/L; blood urea nitrogen, 19.9 mmol/L; and serum creatinine, 234 µmol/L. The serum C3 level was 0.4950 g/L, and the serum C4 level was 0.1050 g/L. The direct Coombs test was positive. Serologic testing for ANCA revealed the presence of p-ANCA (1:10) by indirect immunofluorescence microscopy assay, as well as the presence of PR3 1.2 (normal range Conclusions We present the rare case of a patient with MN-like C3GN with ANCA positivity. C3GN with ANCA positivity may be represented by more crescents, severe renal dysfunction and more extrarenal manifestations. More cases are needed to elucidate the clinicopathologic features and optimal treatments of these patients.

The pathogenesis of idiopathic membranous nephropathy is associated with autoantibodies, most often against the phospholipase A2 receptor (PLA2R) and with genetic factors, especially those involving human leukocyte antigen (HLA) genes. Idiopathic membranous nephropathy is not a typical inherited Mendelian disorder. Reports of idiopathic membranous nephropathy in twins are rare. Herein, we report on two twin sisters diagnosed with PLA2R-associated idiopathic membranous nephropathy. We identified the HLA-DRB1*0301, HLA-DRB1*1501, and HLA-DQB1*0602 alleles in the twin sisters, which were reported as independent risk alleles for idiopathic membranous nephropathy in the Asian population. This case report provides novel evidence for the role of predisposing HLA alleles in the pathogenesis of idiopathic membranous nephropathy.

Aims Lipoprotein glomerulopathy (LPG) is a rare inherited renal disease. Several apolipoprotein E (apoE) mutations have been reported to be related to LPG. Herein, we report a case of a LPG patient with a novel apoE mutation. Methods A 45-year-old Chinese female was diagnosed as LPG by renal biopsy. APOE gene was sequenced. Clinical and genetic studies were conducted. Results The patient presented with nephrotic syndrome and hypertension. A fasting lipid panel showed mild hyperlipidemia and elevated serum apoE (5.6 mg/dL). Renal biopsy revealed typical LPG lesions with whorled, mesh-like material in dilated glomerular capillary lumens that stained positive for Sudan Ⅲ and apoE. apoE gene analysis revealed a T-to-C point mutation at amino acid 173 that caused a substitution of a proline residue for a leucine residue, which has not been reported previously. We named this mutation apoE Chengdu (c.518T＞C, p.L173P). Two of five of the family members carried this mutation, including the patient's brother who was receiving hemodialysis, and her sister, whose urine protein levels were normal. All mutation carriers were heterozygotes with the apoE genotype e3/e3. This mutation was not found among 200 of the local people. Fenofibrate treatment for one year induced clinical improvement. Conclusions ApoE Chengdu (p.L173P) is a novel mutation causing LPG. This case supports the hypothesis that the substitution of proline in or near the LDL receptor-binding area contributes to the development of LPG. The detailed mechanism of action of this variant remains to be elucidated.

Background Understanding the uncommon association of IgG4-related disease with other disorders is essential for the accurate diagnosis and effective treatment of patients. To the best of our knowledge, there have been only few reports of patients with IgG4-related kidney disease coexisting with metastasis of malignancy. Here, we report a rare case of simultaneous occurring IgG4-related tubulointerstitial nephritis and colon adenocarcinoma with hepatic metastasis. Case presentation A 71-year-old Chinese man presented with dysuria and was initially diagnosed as benign prostatic hyperplasia for one year. He was admitted to the hospital for surgery. After admission, the renal function tests revealed a rapid increase of serum creatinine from 291.0 μmol/L to 415 μmol/L. The hemoglobin level was 89 g/L. Fecal occult blood testing was positive. Urinalysis revealed mild proteinuria. The serum IgG4 level was 13.9 g/L. The abdominal imaging examination revealed multiple solid nodules in the liver. The gastrointestinal endoscopy combined with the biopsy revealed colon adenocarcinoma. Kidney biopsy showed massive IgG4-positive plasma cells and storiform fibrosis infiltration in the tubulointerstitial area, thus establishing the diagnosis of IgG4-related tubulointerstitial nephritis. Corticosteroid therapy was initiated, and subsequently, the renal function dramatically improved without the diminution of the liver nodules. The liver biopsy was performed and a diagnosis of metastatic colon adenocarcinoma was confirmed. Conclusions We here reported a rare case of simultaneous occurring of IgG4-related tubulointerstitial nephritis, colon adenocarcinoma with hepatic metastasis. The case highlights the importance of screening for malignancy in patients with IgG4-related disease, and the nature of the mass in other organs of patients with coexisting IgG4-related disease and malignancy should be carefully checked.

Rationale Membranous glomerulonephritis (MN) is the leading cause of nephrotic syndrome in adults and is classified as primary or secondary. Secondary MN accounts for 20% to 30% of all MN cases and can arise from a number of conditions, including autoimmune diseases. Recently exostosin 1/exostosin 2 (EXT1/EXT2) have been identified as the common antigens in secondary autoimmune MN and are present in cases of pure membranous lupus nephritis (LN). The treatment of EXT1/EXT2-associated MN remains elusive. Patient concerns We present the case of a 15-year-old female who presented with nephrotic syndrome, positive ANA and dsDNA, and low serum complements. A renal biopsy revealed pure membranous nephritis with IgG and C3 deposition. EXT1 was found along the glomerular capillary walls and stained positive, while phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were negative. Diagnosis The patient was diagnosed with ETX1-associated membranous LN. Interventions She was treated with prednisone and multiple low-dose rituximab (4 200 mg doses, approximately every 2 months, based on CD19+ cells counts). Outcomes The patient had complete remission within 8 months later, and she remained in remission for the 16-month period of follow-up. Lessons To our knowledge, this is the first case of EXT1-associated MN that has been successfully treated by multiple low-dose rituximab. Further studies can investigate the optimal dosage and treatment protocol.

AarF domain-containing kinase 4 (ADCK4)-associated glomerulopathy (ADCK4-GN) is an inherited mitochondrial nephropathy caused by mutations in the ADCK4 gene. Herein, we report a case of ADCK4-GN. The patient, a 14-year-old Chinese male, presented with asymptomatic proteinuria and steroid resistance. A renal biopsy showed focal segmental glomerulosclerosis (FSGS) and dysmorphic mitochondria in podocytes. Coenzyme Q10 treatment was partially effective. No adverse events were observed. Next generation and Sanger sequencing analyses revealed compound heterozygous mutations (c.625C > G, p.D209H and c.918G > T, p.C306X). Both inherited mutations are located in the highly conserved ABC1 domain. The unreported nonsense mutation causes a loss of 197 amino acids from the C-terminal portion of ADCK4, suggesting a deleterious effect of the truncating mutation by abolishing ADCK4 function. In conclusion, we identified a novel ABC1 domain-localized pathogenic mutation responsible for ADCK4-GN, further supporting the importance of the C-terminal portion of ADCK4. Next generation sequencing facilitated the early diagnosis. CoQ10 treatment may reduce proteinuria and postpone ADCK4-GN progression.

Podocytes play a key role in the formation of cellular crescents in experimental and human diseases. However, the underlying mechanisms for podocytes in promoting crescent formation need further investigation. Here, we demonstrated that mammalian target of rapamycin complex 1 (mTORC1) signaling was remarkably activated and hypoxia-inducible factor (HIF) 1α expression was largely induced in cellular crescents from patients with crescentic glomerular diseases. Specific deletion of Tsc1 in podocytes led to mTORC1 activation in podocytes and kidney dysfunction in mice. Interestingly, 33 of 36 knockouts developed cellular or mixed cellular and fibrous crescents at 7 wk of age (14.19 ± 3.86% of total glomeruli in knockouts vs. 0% in control littermates, n = 12–36, P = 0.04). All of the seven knockouts developed crescents at 12 wk of age (30.92 ± 11.961% of total glomeruli in knockouts vs. 0% in control littermates, n = 4–7, P = 0.002). Most notably, bridging cells between the glomerular tuft and the parietal basement membrane as well as the cellular crescents were immunostaining positive for WT1, p-S6, HIF1α, and Cxcr4. Furthermore, continuously administrating rapamycin starting at 7 wk of age for 5 wk abolished crescents as well as the induction of p-S6, HIF1α, and Cxcr4 in the glomeruli from the knockouts. Together, it is concluded that mTORC1 activation in podocytes promotes cellular crescent formation, and targeting this signaling may shed new light on the treatment of patients with crescentic glomerular diseases.

Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation of the APOE gene, characterized by proteinuria and nephrotic syndrome with elevated serum apoE. Since its treatment and outcome are unknown, we retrospectively studied 35 patients within 31 unrelated Han families with biopsy-proven lipoprotein glomerulopathy residing in the same county in southwest China. DNA sequencing detected the APOE Kyoto mutation (p. Arg25Cys) in all patients and 28 asymptomatic relatives. All shared the same e3 allele. The patients presented with proteinuria, higher total triglyceride, and serum apoE levels relative to non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers were between those of the patients and non-carriers. Sixteen patients received fenofibrate treatment for over 12 months. Six reached complete remission (proteinuria under 0.3g/day with stable serum creatinine) with intensive control of their lipid profile (normalized serum apoE and triglycerides under 100mg/dl). Eight reached partial remission. At 3 years of follow-up, patients treated with fenofibrate had superior survival and stable renal function. Thus, fenofibrate can induce lipoprotein glomerulopathy remission and the fibrate effects depend on the degree of lipid control and baseline proteinuria. Moreover, normalization of serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering treatment.

To compare the efficacy and safety of Nasal intermittent positive pressure ventilation (NIPPV) and Nasal continuous positive airway pressure (nCPAP) in neonates.Standard search strategy for the Cochrane Neonatal Review Group was performed. The participants were both preterm and term infants suffering from neonatal respiratory distress syndrome or experiencing apnea of prematurity.14 eligible andomized controlled trials involving 1052 newborn infants were included. The study quality and evidence validity was defined as moderate. As compared with nCPAP, NIPPV significantly reduced the incidence of endotracheal ventilation OR 0.44, 95%CI 0.31 - 0.63, increased the successful rate of extubation (OR 0.15, 95%CI:0.08 - 0.31), and had a better outcome indicated by decreased death and/or bronchopulmonary dysplasia (OR 0.57, 95% CI:0.37 - 0.88). Moreover, NIPPV decreased the number of apneic episodes of prematurity (WMD-0.48, 95%CI 0.58 - 0.37), and marginally decreased the incidence of bronchopulmonary dysplasia (OR 0.63, 95%CI 0.39 - 1.00). No side effects specifically associated with NIPPV were reported.NIPPV could be used to reduce endotracheal ventilation, increase successful extubation, decrease the rate of apnea of prematurity, and have better outcome indicated by fewer death and/or bronchopulmonary dysplasia in preterm and term newborn infants.

Little is known about the frequency features of spontaneous neural activity in the brains of moderate and late preterm (MLPT) newborns. We used resting-state functional magnetic resonance imaging (rs-fMRI) and the amplitude of low-frequency fluctuation (ALFF) method to investigate the frequency properties of spontaneous blood oxygen level-dependent (BOLD) signals in 26 MLPT and 35 term newborns. Two frequency bands, slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz), were analyzed. Our results showed widespread differences in ALFF between the two bands; differences occurred mainly in the primary sensory and motor cortices and to a lesser extent in association cortices and subcortical areas. Compared with term newborns, MLPT newborns showed significantly altered neural activity predominantly in the primary sensory and motor cortices and in the posterior cingulate gyrus/precuneus. In addition, a significant interaction between frequency bands and groups was observed in the primary somatosensory cortex. Intriguingly, these primary sensory and motor regions have been proven to be the major cortical hubs during the neonatal period. Our results revealed the frequency of spontaneous BOLD signal differences between MLPT and term newborns, which contribute to the understanding of regional development of spontaneous brain rhythms of MLPT newborns.

INTRODUCTION: The Sichuan earthquake caused a large number of crush injuries and many of them developed acute renal failure (ARF). A retrospective study was performed on victims with crush injuries of West China Hospital to investigate the predictive factors for acute renal failure (ARF) in crush injuries. PATIENTS AND METHODS: Medical records of injured victims treated in West China Hospital within the first week after the Sichuan earthquake were retrospectively reviewed and 101 patients with crush injury were enrolled in the study. We divided them into an ARF group and a non-ARF group. The clinical data of included patients were extracted and analysed. RESULTS: Patients with ARF accounted for 42% of the included population. Patients younger than 20 made up the biggest age category (45%), and the entrapped time under the debris (22 [IQR 3.5-38]h) was longer than previous reports. In univariate analysis, male gender, multiple crush injuries, medical comorbidities, surgical interventions and infections were more frequent in patients with ARF than in those without ARF. Mean arterial pressure was higher in the ARF group. Besides, the risk of ARF was increased by creatine kinase >14,494.5IU/L most significantly, followed by time under the rubble >4h, aspartate transaminase >453.5IU/L, albumin 11.8×10(9)/L. In multivariate analysis, male gender, time under the rubble, multiple crush injuries, surgical interventions, infections and creatine kinase level were independently associated with ARF in crush injuries. CONCLUSIONS: The entrapped time under the debris, multiple crush injuries, male gender, infections, and creatine kinase level are predictive factors for ARF in crush injuries. Language: en

Cerebral glucose metabolism was measured by (18)F-fluorodeoxyglucose position emission tomography in infants at different gestational ages and with neonatal hypoxic-ischemic encephalopathy. Thirty-six preterm and term infants at different gestational ages without brain injury were divided into four subgroups: ≤32 weeks (n = 4), 33-34 weeks (n = 5), 35-36 weeks (n = 12), and ≥37 weeks (n = 15). Twenty-four newborn infants with hypoxic-ischemic encephalopathy were divided into three subgroups: mild (n = 13), moderate (n = 7), and severe (n = 4). Cerebral glucose metabolism manifested a trend toward increase, and the structure of cranial (18)F-fluorodeoxyglucose positron emission tomography images became clear with increased gestational age, especially at ≥37 weeks. Uptakes of (18)F-fluorodeoxyglucose in the ≥37-week group were significantly higher than in the ≤32-week group (P < 0.01). Cerebral glucose metabolism changed significantly in neonatal hypoxic-ischemic encephalopathy, and was either unbalanced bilaterally or relatively low at all sites. Moreover, uptakes of (18)F-fluorodeoxyglucose were significantly lower in severe than in mild and medium hypoxic-ischemic encephalopathy (P < 0.05). Cerebral glucose metabolism, as measured by (18)F-fluorodeoxyglucose positron emission tomography, may prove useful for estimating brain development and injury in newborn infants, and its clinical values need further investigation.

Background: Seventeen cases of Acinetobacter baumannii infection in a neonatal intensive care unit (NICU) were evaluated. The strains were characterized as resistant to carbapenems. The aim of the present study was therefore to investigate the clinical and molecular epidemiological characteristics of the 17 carbapenem-resistant A. baumannii strains. Methods: Samples were isolated from blood or sputum from the patients in the NICU, cultured using conventional techniques and an automated system. Multiplex polymerase chain reaction (PCR) was used to detect blaOXA-51-like, blaOXA-23-like, OXA-24, OXA-58 and Ambler class B carbapenemases. The genotype of the strains was identified on pulsed-field gel electrophoresis (PFGE). Results: BlaOXA-23 was detected in all of the isolates. PFGE genotype analysis suggested three clones among the 17 strains. Two clones were isolated from other wards of the hospital including the adult ICU and Department of Pulmonology. The other clone was proved to be the first appearance in the hospital as genotype analysis. Conclusion: BlaOXA-23 was the drug-resistant gene that made A. baumannii resistant to carbepenem. The source of blaOXA-23 in the 17 isolates was different.

Objective: An 8.0-magnitude earthquake struck Sichuan province of China on May 12, 2008. Over the next 10 days, the firstly arrived uniformed pediatricians in the epicenter zone took part in emergency relief care for children. The investigations of major injuries and diseases in children were taken. Methods: Demographic data collected included (if possible) age, date of presentation, injury, disease, and surgery performed. Results: Total casualties were estimated to be more than 80,000, and much more were injured. Eight hundred eighty-two inpatients were treated by the relief team during the first 10 days. Of 882 inpatients, 192 (21.8%) were younger than 18 years. Children's ages were not evenly distributed. Twenty-seven patients were neonates, infants, and toddlers (14%), 105 were school-aged (55%), and were 60 adolescents (31%). The admitted children had 256 injuries. Limb (106 cases, 55.2%) and body surface (67 cases, 34.9%) were the majorly injured locations. One hundred twenty-seven cases (66.2%) had simple open injuries, and 106 (55.2% had fractures. The children's conditions were evaluated as mild (121 cases, 63.0%), moderate (56 cases, 29.7%), severe (8 cases, 4.2%), and fatal (7 cases, 3.7%). Conclusions: More than 20% of patients requiring hospitalization were children. School-aged children were heavily injured. The increase in infectious diseases followed on. The data show that there is an immediate need for orthopedic and general surgery skills, and pediatricians should play an important role in early rescue and subsequent control of infectious diseases in a huge earthquake hazard.

Rationale Fibromuscular dysplasia (FMD) is a rare vascular disorder that causes abnormal cell growth in arterial walls. The classic "string of beads" sign has been reported in many cases, whereas the appearance of tubular stenosis and distal tapering of renal arteries with multiple renal infarctions, as well as left kidney atrophy occurring in one patient, has not been precisely described. Patient concerns A 19-year-old woman presented to us with a history of elevated blood pressure without any symptoms for the past 1 month. Routine laboratory tests indicated a moderately impaired renal function, and ultrasound examination demonstrated a small-sized left kidney and seriously decreased blood flow of the left renal artery and its branches. Diagnosis Subsequent contrast-enhanced computed tomographic angiography (CTA) demonstrated multiple ischemic infarctions in the bilateral kidneys, and FMD was suggested at that time. Thereafter, we performed selective reno-angiography, which confirmed that the all left renal arteries had tubular stenosis and that right renal arterial branches presented distal tapering. Intervention Antihypertensive drugs were prescribed conservatively, including nifedipine 60 mg/d and prazosin 4 mg/d, to lower the patient's blood pressure. Outcomes The patient had a well-controlled blood pressure and an improved renal function at her 6-month follow-up. Lessons We should take the diagnosis of FMD into account if young women develop asymptomatic hypertension. To our knowledge, this is the first case that exhibited renal artery FMD manifesting as tubular stenosis and distal tapering, especially followed by bilateral renal infarctions and significant atrophy of the left kidney. In addition, CTA combined with digital subtraction angiography (DSA) may be more sensitive than other tests with respect to the detection of intrarenal infarctions and arterial variants of FMD.

Recent evidence suggested that angiogenesis played a pivotal role in the development of hepatocellular carcinoma cells (HCC), thus the therapy strategy targeting antiangiogenesis has been regarded as promising method for HCC therapy. Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. However, the antiangiogenesis therapy of HCC based on TEM8 has not been reported. In this study, the recombinant adenovirus encoding TEM8 was constructed, and the DCs were transduced with the Ad-TEM8. In addition, the modified DCs were transferred into the BALB/c mice to determine whether DCs transduced with TEM8 could elicit a potent antitumor immunogenic response in vivo. The results demonstrated that DCs transduced with Ad-TEM8 induced specific CTLs effectively, which could secrete IFN-γ and lyse HCC. Furthermore, the modified DCs could effectively protect BALB/c mice from lethal challenges against HCC, reduce tumor growth and increase the mice life span by decreasing tumor vasculature density. These data suggest that the Ad-TEM8 modified DCs may induce antitumor immunity by disrupting tumor vasculature and may thus be used as an efficient therapy strategy to influence tumor development in clinical applications.

Autosomal dominant polycystic kidney disease (ADPKD) is a common and severe renal disease. Mutations of PKD1 and PKD2 genes are responsible for approximately 85% and 15% of ADPKD cases, respectively. In the present study, PKD1 and PKD2 genes were analyzed in a large Chinese family with ADPKD using denaturing high-performance liquid chromatography and DNA sequencing. A novel mutation, c.3623-3624insGTGT in exon 15 of the PKD1 gene, was identified in all nine affected family members, but not in any unaffected consanguineous relatives or 100 unrelated controls. These findings suggest that the unique 4 bp insertion, c.3623-3624insGTGT, in the PKD1 gene might be the pathogenic mutation responsible for the disease in this family.

Objective: The purpose of this study was to find whether Cardiac Magnetic Resonance (CMR) could assess the myocardial interstitium in patients suffering from systemic amyloidosis with normal left ventricular ejection fraction. Methods: Twenty Six patients in whom systemic amyloidosis was confirmed by kidney biopsy were investigated. Five patients with normal left ventricular ejection fraction were selected. The heart function of the patients was diagnosed by two-dimensional transthoracic echocardiography. The main MR sequences include an inversion recovery prepared echo planar imaging perfusion sequence, inversion recovery TrueFISP sequence (delayed enhancement) and TrueFISP cine sequence for heart function measurement (including ejection fraction (EF), end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and cardiac output (CO)). Results : Perfusion defects were seen in three patients. In these patients, myocardial enhancement was visible on late gadolinium enhancement images. The enhancement pattern was diffuse in three patients and focal in two patients. Heart dysfunction was mild, as follows: EF normal (range, 56-75%; mean, 69.4%), ESV normal (range, 15.7-30.0; mean, 23.0), EDV decreased (range, 42.1-96.6; mean, 72.7), SV decreased (range, 23.7-68.6; mean, 49.6) and CO normal (range, 2.6-5.9; mean, 3.9). Hematoxylin and eosin stain and Congo red stain demonstrated typical amyloid deposits. Amyloidosis was classified as amyloid light chain by kappa and lambda stain. Conclusions: Cardiac Magnetic Resonance could detect abnormal myocardial interstitium in systemic amyloidosis patients with normal left ventricular ejection fraction.

Cholesteryl ester transfer protein (CETP) inhibitors are gaining substantial research interest for raising high density lipoprotein cholesterol levels. The aim of the research was to estimate the efficacy and safety of cholesteryl ester transfer protein inhibitors as novel lipid modifying drugs. Systematic searches of English literature for randomized controlled trials (RCT) were collected from MEDLINE, EBASE, CENTRAL and references listed in eligible studies. Two independent authors assessed the search results and only included the double-blind RCTs by using cholesteryl ester transfer protein inhibitors as exclusively or co-administrated with statin therapy irrespective of gender in enrolled adult subjects. Two independent authors extracted the data by using predefined data fields. Of 503 studies identified, 14 studies met the inclusion criteria, and 12 studies were included into the final meta-analysis. Our meta-analysis revealed that CETP inhibitors increased the HDL-c levels (n = 2826, p

Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease with an incidence of 1 in 400 to 1000. The disease is genetically heterogeneous, with two genes identified: PKD1 (16p13.3) and PKD2 (4q21). Molecular diagnosis of the disease in at-risk individuals is complicated due to the structural complexity of PKD1 gene and the high diversity of the mutations. This study is the first systematic ADPKD mutation analysis of both PKD1 and PKD2 genes in Chinese patients using denaturing high-performance liquid chromatography (DHPLC). Methods Both PKD1 and PKD2 genes were mutation screened in each proband from 65 families using DHPLC followed by DNA sequencing. Novel variations found in the probands were checked in their family members available and 100 unrelated normal controls. Then the pathogenic potential of the variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice site alterations using online mutation prediction resources. Results A total of 92 variations were identified, including 27 reported previously. Definitely pathogenic mutations (ten frameshift, ten nonsense, two splicing defects and one duplication) were identified in 28 families, and probably pathogenic mutations were found in an additional six families, giving a total detection level of 52.3% (34/65). About 69% (20/29) of the mutations are first reported with a recurrent mutation rate of 31%. Conclusions Mutation study of PKD1 and PKD2 genes in Chinese Hans with ADPKD may contribute to a better understanding of the genetic diversity between different ethnic groups and enrich the mutation database. Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease.

The Oxford classification of immunoglobulin A (IgA) nephropathy (IgAN) provides a histopathologic grading system that is associated with kidney disease outcomes independent of clinical features. We evaluated the Oxford IgAN classification in a large cohort of patients from China.Retrospective study.1,026 adults with IgAN from 18 referral centers in China. Inclusion criteria and statistical analysis were similar to the Oxford study.Histologic findings of mesangial hypercellularity score, endocapillary proliferation, segmental sclerosis or adhesion, crescents, necrosis, and tubular atrophy/interstitial fibrosis. Clinical features, blood pressure, estimated glomerular filtration rate (eGFR), proteinuria, and treatment modalities.Time to a 50% reduction in eGFR or end-stage renal disease (the combined event); the rate of eGFR decline (slope of eGFR); proteinuria during follow-up.Compared with the Oxford cohort, the Chinese cohort had a lower proportion of patients with mesangial hypercellularity (43%) and endocapillary proliferation (11%), higher proportion with segmental sclerosis or adhesion (83%) and necrosis (15%), and similar proportion with crescents (48%) and tubular atrophy/interstitial fibrosis (moderate, 24%; severe, 3.3%). During a median follow-up of 53 (25th-75th percentile, 36-67) months, 159 (15.5%) patients reached the combined event. Our study showed that patients with a mesangial hypercellularity score higher than 0.5 were associated with a 2.0-fold (95% CI, 1.5-2.8; P0.001) higher risk of the combined event than patients with a score of 0.5 or lower. Patients with tubular atrophy/interstitial fibrosis of 25%-50% and50% versus25% were associated with a 3.7-fold (95% CI, 2.6-5.1; P0.001) and 15.1-fold (95% CI, 9.5-24.2; P0.001) higher risk of the combined event, respectively. Endocapillary proliferation, glomerular crescents, and necrosis were not significant.Retrospective study; the therapeutic interventions were miscellaneous.We confirmed the associations of mesangial hypercellularity and tubular atrophy/interstitial fibrosis with kidney disease outcomes.

Background Lipoprotein glomerulopathy (LPG) is a rare inherited renal disease characterized by intraglomerular lipoprotein within the lumina of severely dilated glomerular capillaries. The common clinical presentation of LPG includes proteinuria or nephrotic syndrome. Hypertension and anemia were thought to be mild in LPG. Thrombotic microangiopathy (TMA) in LPG has not been previously reported. In this report, we present a patient with LPG that developed TMA. To the best of our knowledge, this is the first report of TMA in LPG. Case presentation Four years ago (2005), a 19-year-old Chinese woman was diagnosed with nephrotic syndrome and provided prednisone treatment. A combination of prednisone and cyclophosphamide did not have any effect and was discontinued after six months. Although she was steroid-resistant, over the next subsequent three years, she maintained normal renal function without anemia and thrombocytopenia. In February 2009, she had a severe headache and blurry vision and presented at a local hospital with severe hypertension. Blood pressure was 220/160 mmHg. Laboratory data showed hemoglobin 3.8 g/dL; platelet counts 29×109/L; urinary protein 7.90 g/d; total bilirubin 29.9 umol/L; indirect bilirubin 28.2 umol/L; LDH 1172 U/L; ALB 2.66 g/dL; urea nitrogen 52 mg/dL; serum creatinine 3.2 mg/dL; triglyceride 253 mg/dL; total cholesterol 273 mg/dL. ANA, ds-DNA, ANCA, anti-GBM antibody and anticardiolipin were all negative. A renal biopsy revealed LPG with TMA. Genetic evaluation showed the patient carried the APOE Kyoto mutation. Adequate control of blood pressure improved microangiopathic anemia and thrombocytopenia, however, renal function did not improve and she eventually developed uremia and became hemodialysis dependent. Conclusion We report on a rare case of TMA probably due to malignant hypertension in LPG. Early lipid-lowering and antihypertensive treatment may improve outcome. The pathophysiologic relationship between LPG and TMA should be investigated further.

730 Sichuan Earthquake and Emergency Relief Care for Children: Report From the Firstly Arrived Pediatricians in the Epicenter Zone

Background Anti-glomerular basement membrane (GBM) glomerulonephritis and systemic lupus erythematosus (SLE) are both disorders of the immune system; however, they are known as distinct diseases. Till now no clinical evidence suggests the genetic relationship between these two diseases. Herein, we present two identical twins; one was diagnosed as anti-GBM glomerulonephritis, the other SLE. This is the first clinical report on the genetic relationship between these two diseases. Case presentation A 25-year-old female was admitted complaining of intermittent gross hematuria for 6 months and elevated serum creatinine for 1 month. She denied hemoptysis. Laboratory examinations showed hemoglobin 7.4 g/dL, serum creatinine 7.15 mg/dL and albumin 2.8 g/dL. Urinalysis showed hematuria (484 RBCs per high-power field) and proteinuria 4+. Antinuclear antibody, complement levels and ANCAs were all normal. Renal ultrasound showed normal-sized kidneys without obstruction or masses. Serum anti-GBM antibody assay showed 119.70 RU/mL (normal range, Conclusion The presence of identical twins having anti-GBM nephritis and SLE respectively provides clinical evidence to support that anti-GBM nephritis and lupus may share a common genetic background to some extent, while environment may contribute to disease evolution in part.