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ObjectiveThis study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS. Methods① The sera of primary FSGS patients （17 cases） were collected. Healthy volunteers （10 cases） and patients with other types of primary nephrotic syndrome （10 cases） were set as normal and disease controls. SuPAR levels were detected by ELISA； ② Podocytes were stimulated by suPAR in vitro， and cells were collected to analyze apoptosis by flow cytometry and for RNAseq analysis； ③ Differentially expressed genes （DEGs） were screened from RNAseq data. Both up-regulated and down-regulated genes were analyzed by KEGG and GO enrichment analysis. Heat map was used to show expression of genes related to podocyte focal adhesion， slit diaphragm and actin dynamics and endocytosis. Differentially expressed genes were verified by qPCR. Results① The level of suPAR in FSGS patients was significantly increased， and that in other nephrotic syndrome（NS） patients was also significantly increased； ② suPAR stimulation significantly altered the transcriptome pattern of human podocytes. A total of 272 up-regulated genes and 288 down-regulated genes were screened； ③ KEGG and GO enrichment analysis of up-regulated and down-regulated genes showed that Focal adhesion and DNA replication and DNA repair related pathways were significantly down-regulated； ④ suPAR did not increase podocyte apoptosis. ConclusionThe level of suPAR is significantly increased in patients with primary FSGS. SuPAR may promote podocyte injury by interfering with genomic homeostasis and disrupting focal adhesion， slit diaphragm， actin dynamics and endocytosis-related functional molecules of podocytes.
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Objective To explore the therapeutic advantages of suprapatellar nailing for treatment of segmental tibial fractures. Methods Twenty-one tibial segmental fractures were managed and followed-up regularly in our hospital from March 2012 to August 2018. They were 15 males and 6 females, with an average age of 46.0 years (range, from 26 to 71 years). There were 13 cases of type Ⅰ,4 cases of type Ⅱ, 2 cases of typeⅢand 2 cases of typeⅣ, according to Melis classification. There were totally 10 open fractures (5 cases of type Ⅰ, 2 cases of type Ⅱ, one case of type ⅢA and 2 cases of type ⅢB, according to Gustilo classification). All the cases received closed reduction and internal fixation with suprapatellar locked tibial nailing of the third generation. Non-weight-bearing exercises of the knee and ankle and muscular strength training for the low ex-tremity commenced 3 days after internal fixation. The knee functions were evaluated postoperatively using the Lysholm knee scoring. Results All the 21 cases were followed up for 10 to 36 months (average, 17.8 months; more than 3 times during at least 10 months). X-ray revealed occurrence of the callus from 2 to 11 months (average, 7.1 months) after operation. One case of nonunion occurred at the tibial mid-shaft. There was no wound infection, soft tissue necrosis or osteomyelitis. Two cases complained of knee pain and 5 cases of ankle pain, with VAS scores ranging from 2 to 3. After symptomatic management, the knee pain was relieved in 2 cases after 5 months and the ankle pain was relieved in 3 cases. The average Lysholm score 10 months after surgery was 95 points (range, from 87 to 99 points). Conclusion Suprapatellar nailing is an effective treatment for segmental tibial shaft fractures, especially for those involving injuries to the metaphyseal region and peripatellar soft tissue, because it can provide effective fixation of the multiple metaphyseal fractures and avoid disadvantages of conventional intramedullary nailing, leading to limited postoperative knee pain.
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Focal segmental glomerulosclerosis (FSGS) in children, which is a kind of nephrotic syndrome showing steroid resistance, usually progresses to a substantial number of end stage renal disease (ESRD). Although the pathogenesis of primary FSGS is unclear, several recent studies have reported that FSGS is associated with circulating immune factors such as soluble urokinase-type plasminogen activator receptor (suPAR) or anti-CD40 autoantibody. We report a successfully treated case of a 19-year-old female patient who experienced a recurrence of primary FSGS. After the diagnosis of FSGS, the patient progressed to ESRD and received a kidney transplantation (KT). Three days later, recurrence was suspected through proteinuria and hypoalbuminemia. She has been performed plasmapheresis and high dose methylprednisolone pulse therapy and shown remission status without increasing proteinuria for four years after KT. In conclusion, strong immunosuppressive therapy may be helpful for a good prognosis of recurrent FSGS, suppressing several immunologic circulating factors related disease pathogenesis.
Subject(s)
Child , Female , Humans , Young Adult , Diagnosis , Glomerulosclerosis, Focal Segmental , Hypoalbuminemia , Immunologic Factors , Kidney Failure, Chronic , Kidney Transplantation , Methylprednisolone , Nephrotic Syndrome , Plasmapheresis , Prognosis , Proteinuria , Recurrence , Urokinase-Type Plasminogen ActivatorABSTRACT
Objective To determine the diagnostic and assessment value of soluble urokinase plasminogen activator receptor (suPAR) level in septic patients.Methods Totally 82 septic patients in the Department of Intensive Care Unit of The First Affiliated Hospital,Sun Yat-Sen University were prospectively analyzed from June 2013 to March 2014.Another 29 patients with systemic inflammatory response syndrome (SIRS) and 15 healthy subjects served as controls.Septic patients were divided into sepsis group (n =27),severe sepsis group (n =27) and septic shock group (n =28) according to the severity,and there was no significant difference in age and sex among these groups.Measurement of plasma suPAR,serum procalcitonin (PCT) and C-reactive protein (CRP) levels,and calculation of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were performed.Comparison of group differences for continuous variables was done by oneway ANOVA or nonparametric Kruskal-Wallis test.Spearman rank correlation analysis was applied to establish the relation between variables.Receiver operating characteristics (ROC) curve was created and area under curve (AUC) was calculated to determine the diagnostic value of these variables in sepsis.Results The levels of plasma suPAR in SIRS group,sepsis group,severe sepsis group,septic shock group,and healthy control group were (8.22±0.61),(11.45±1.12),(12.99±1.28),(15.75± 1.23) and (4.65 ±0.30) ng/mL,respectively.Plasma suPAR levels in SIRS group and sepsis group were higher than that in healthy control group (P ＜ 0.01),and elevated plasma suPAR was accompanied by increased severity of sepsis (P ＜ 0.05).PCT levels of sepsis group (17.66 ± 8.42) ng/mL,severe sepsis group (9.67 ±3.56) ng/mL and septic shock group (29.19 ± 10.78) ng/mL were greater than that in SIRS group (1.10 ± 0.78) ng/mL,P ＜ 0.01.CRP levels elevated in all groups,but there were no significant differences among them.When suPAR and CRP were applied to distinguishing sepsis from SIRS,the AUC values from suPAR and combination of suPAR and PCT were 0.817 (P ＜ 0.01,95 ％ CI:0.714-0.921) and 0.927 (P＜0.01,95％ CI:0.870-0.985),respectively.Using9.52 ng/mL suPAR as the best cut-off to distinguish sepsis from SIRS,there were 71.93％ sensitivity and 95.46％ specificity.The levels of plasma suPAR positively correlated with PCT levels (r =0.326),APACHE Ⅱ score (r =0.492) and SOFA score (r =0.386),P ＜ 0.01.Conclusions Plasma suPAR levels significantly elevated in septic patients and correlated with the severity of sepsis.Sepsis and SIRS may be discerned by plasma suPAR levels.Joint use of suPAR and PCT could greatly increase the specificity of diagnosis of sepsis.
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Objective To evaluate the value of plasma soluble urokinase plasminogen activator receptor (suPAR) and serum pmcalcitonin (PCT) to investigate their assessment of disease severity and prognosis in patients with sepsis.Methods The levels of plasma suPAR and serum PCT were monitored in 77 patients with sepsis.The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded.According to the disease severity and their prognosis,the value of plasma suPAR,serum PCT,APACHE Ⅱ and SOFA score on predict the disease severity and prognosis of septic patients were compared.Results The levels of plasma suPAR in septic patients [(7.9 ±6.5) ng/mL] were lower than severe sepsis patients [(8.4 ±4.5) ng/mL] and septic shock patients [(13.9 ± 8.0) ng/mL],allP ＜ 0.05.The levels of serum PCT in septic patients (6.3 ± 3.5) ng/mLwere lower than severe sepsis patients [(23.7 ± 3.9) ng/mL] and septic shock patients [(25.7 ±4.3) ng/mL],allP ＜0.05.But there was no significant difference in the levels of serum PCT between the severe sepsis group and the septic shock group.Receiver operator characteristic curve (ROC)of the level of plasma suPAR could distinguish survivors from non-survivors in septic patients,maximal area under curve (AUC) of plasma suPAR was 0.803.The best cut-off value of plasma suPAR to distinguish survivors from non-survivors was 9.905 ng/mL.And the AUC of serum PCT was 0.61 (P ＞ 0.05) ; the AUCofAPACHEⅡ score was 0.832 (P＜0.05); the AUC of SOFA score was 0.767 (P＜0.05).Conclusion Monitoring of the levels of plasma suPAR and the APACHE Ⅱ score can help to assess the severity and the prognosis of sepsis in the early stage.
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La esclerosis focal y segmentaria glomerular primaria es una causa frecuente de sindrome nefrótico con alta morbilidad que con frecuencia lleva a la insuficiencia renal terminal debido a que sus esquemas terapeúticos no son exitosos, ya que sus mecanismos fisiopatológicos a la actualidad han sido parcialmente descifrados. Éstos son heterogéneos, complejos de integrar, y además el término agrupa bajo la misma denominación -la cual evoca una descripción histológica- a un variado número de causas moleculares con distinta fisiopatogenia. En esta revisión se describen los últimos adelantos respecto a la fisiopatología de esta compleja entidad y los últimos adelantos en su terapéutica.
Primary focal and segmental glomerulosclerosis is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure as the different available therapeutic approaches are unsuccessful, due in part to the fact that the pathophysiological mechanisms have not been fully deciphered, are heterogeneous and complex to integrate, and more important, the denomination employed evokes a histological description shared by a number of different causes with different molecular pathogenesis. This review describes the latest developments regarding the pathophysiology of this complexentity and describes recent advances in therapy.
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Glomerulosclerosis, Focal Segmental , Urokinase-Type Plasminogen Activator , Podocytes , ProteinuriaABSTRACT
Objective To explore the relationship of serum level of Cystatin C and suPAR with tumor infiltration, metastasis, and treatment of patients with malignant tumor. Methods: The serum levels of Cystatin C was detected by particle enhanced nephelometic immunoassay (PENIA) by 7600-010 full-automatic biochemical analyzer made in Japan. The level of suPAR was detected by ELISA. The serum levels of Cystatin C and suPARof 82 normal adults and 172 patients with malignant tumor were measured and compared. Results: The serum level of Cystatin C and suPAR in patients with malignant tumor was significantly increased compared with that of normal adults (P＜0.01 and P＜0.01). The level of Cystatin C and suPAR in terminally ill patients or patients with metastasis was significantly higher than that in the control group. The levels of the two indices in postoperative patients were lower than those in preoperative patients. No significant difference was found in the levels of the two indicies before chemotherapy or radiotherapy and after therapy. Conclusion: The serum levels of Cystatin C and suPARin patients with malignant tumor are correlated with tumor invasion, metastasis and surgical intervention. Detection of Cystatin C and suPAR levels in patients with malignant tumor is valuable for disease monitoring and treatment evaluation.
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Objective:To investigate the quality of Naosaitong Tablets by determing of the dissolution rates of different batches of tablets. Methods: The rotatory-basket method was used. The cumulative dissolution percentage was determined by UV. The dissolution parameters were got and their correlation was studied. Results: Statistics indicated there was a significant difference in dissolution parameter (T 50) between film-coated tablets and sugar-coated tablets. The dissolution percentage of film-coated tablets in 45 minutes was over 90%, whereas sugar-coated tablets was only 49-78%. Conclusion: Niaosaitong Film-coated Tablets in superior to its sugar-coated tablets in dissolution rate. It is necessary to improve the quality of Niaosationg Sugar-coated Tablets.