This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Objective:To analyze the long-term prognosis of IgA nephropathy (IgAN) with focal segmental glomerulosclerosis (FSGS) and the risk factors related to renal prognosis in children with IgAN-FSGS.Methods:A retrospective study was concluded in IgAN-FSGS children who were followed up for more than 5 years and diagnosed by renal biopsy for the first time in the Eastern Theater General Hospital from January, 2004 to December, 2018. The end-point events of the study were entering end-stage kidney disease (ESKD) or estimated glomerular filtration rate (eGFR) decreased by ≥50% from baseline, which were defined as poor renal prognosis. Baseline clinicopathologic data of IgAN-FSGS children were compared between the end-point event group and the non-end-point event group. The cumulative renal survival rate of IgAN-FSGS children was calculated by Kaplan-Meier survival analysis. The influencing factors of poor renal prognosis in IgAN-FSGS children were analyzed by Cox proportional hazards model, and the diagnostic value was evaluated by the receiver operating characteristic curve (ROC curve) and area under the curve (AUC). The diagnostic value was verified by time dependent-ROC and time dependent-AUC.Results:A total of 204 IgAN-FSGS children were enrolled in this study, of whom 132 cases were males (64.7%). The median age of renal biopsy was 16 (14, 17) years old. During a median follow-up time of 90.7 (71.7, 114.8) months, 57 cases (27.9%) reached the end-point events. Compared with the non-end-point event group ( n=147), the end-point event group ( n=57) had higher proportions of males and hypertension, higher levels of 24-hour urinary protein, serum creatinine, serum uric acid, urinary N-acetyl-β- D-glucosaminidase, urinary retinol binding protein, higher proportions of glomerular segmental sclerosis (S1) ≥25% and tubular atrophy/interstitial fibrosis (T1/T2), and lower levels of serum albumin, serum IgA, and serum IgG (all P<0.05). There was no statistical difference between the two groups in treatment (all P>0.05). Kaplan-Meier survival analysis showed that with entry of ESKD or eGFR decreased by ≥50% from baseline as the end-point events, the 5-year, 10-year, and 15-year cumulative renal survival rates in IgAN-FSGS children were 88.7%, 67.6%, and 50.7%, respectively. Multivariate Cox regression analysis showed that proteinuria >1 g/24 h ( HR=3.702, 95% CI 1.657-8.272, P=0.001), hyperuricemia ( HR=3.066, 95% CI 1.793-5.245, P<0.001), S1≥25% ( HR=2.017, 95% CI 1.050-3.874, P=0.035), T1/T2 ( HR=1.863, 95% CI 1.021-3.158, P=0.016) were the independent related factors for poor renal prognosis. ROC curve analysis showed that S1≥25% ( AUC=0.605, P=0.021, sensitivity 26.3%, specificity 94.6%), T1/T2 ( AUC=0.624, P=0.006, sensitivity 43.9%, specificity 81.0%), hyperuricemia ( AUC=0.658, P<0.001, sensitivity 52.6%, specificity 78.9%), proteinuria>1 g/24 h ( AUC=0.670, P<0.001, sensitivity 87.7%, specificity 46.3%) could accurately predict the renal outcome of IgAN-FSGS. Time dependent-ROC curve validation showed that the combined diagnosis of S1≥25%, T1/T2, hyperuricemia and proteinuria>1 g/24 h had a good predictive value for renal prognosis (3-year AUC=0.846 and 5-year AUC=0.777, respectively). Conclusions:During a median follow-up of 90.7 months, 27.9% of IgAN-FSGS children have poor renal prognosis, and the 5-year, 10-year, and 15-year cumulative renal survival rates are 88.7%, 67.6%, and 50.7%, respectively. Urinary protein >1 g/24 h, hyperuricemia, T1/T2, and S1 ≥25% are the risk factors for renal prognosis in IgAN-FSGS children.

Objective:To analyze the clinical and pathological characteristics in children diagnosed with primary focal segmental glomerulosclerosis (FSGS) after repeated renal biopsy.Methods:The clinicopathological data of children who ever experienced renal biopsy in Jinling Hospital from January 1, 2000 to December 31, 2020 were retrospectively reviewed. Clinical manifestations, pathological characteristics and treatment responses were analyzed.Results:Of the 34 enrolled patients, there were 22 males and 12 females. The median age of the first renal biopsy was 14 years old (1-18 years old), and the median interval between repeat renal biopsy and first renal biopsy was 6 months (1-151 months). Thirty-one showed nephrotic syndrome, of which 22 had microscopic hematuria, and 4 had elevated serum creatinine. Among the other 3 patients, 2 had hematuria and proteinuria, and 1 had proteinuria. In the first renal biopsy, 16 cases were diagnosed as minimal change disease, 14 cases were diagnosed as mesangial proliferative glomerulonephritis, 2 cases were diagnosed as IgA nephropathy, and 2 cases were diagnosed as IgM nephropathy. All 34 children showed poor responses to hormone and immunosuppressive therapies. The pathological features of the first renal biopsy in some patients were adhesion (2/34), decreased loop podocyte attachment (2/34), peripheral loop extension to the urinary pole (2/34), renal tubular reflux (4/34), capillary thrombosis (2/34) and IgM deposition (12/34).Conclusions:The initial diagnosis of FSGS is difficult, and the lesions are atypical and easily misdiagnosed. The patients have poor responses to hormone and immunosuppressive therapies. For patients with the pathological changes of adhesion, decreased loop podocyte attachment, peripheral loop extension to the urinary pole, renal tubular reflux, capillary thrombosis and IgM deposition, follow-up is required, and if necessary, repeat renal biopsy needs be performed to determine whether it is FSGS.

Objective:To investigate the effect of tonsillectomy combined with glucocorticoids therapy on long-term clinical remission and renal prognosis in IgA nephropathy (IgAN) children with recurrent acute onset history of tonsillitis.Methods:The clinical data of children who were diagnosed with primary IgAN from January 2000 to December 2017 in Jinling Hospital were retrospectively analyzed. All participants were treated with long course therapy of glucocorticoids. The children with recurrent acute onset history of tonsillitis were divided into tonsillectomy group and non-tonsillectomy group according to whether to perform tonsillectomy, followed up until the patients' serum creatinine doubled, the estimated glomerular filtration rate decreased by more than 50%, progression to end-stage renal disease, renal replacement therapy or death. The renal survival rate was calculated and compared by Kaplan-Meier method. Univariate and multivariate Cox regression models were used to analyze the effect of tonsillectomy on the renal prognosis of IgAN children.Results:A total of 120 children with IgAN were enrolled in this study, including 40 cases in tonsillectomy group and 80 cases in non-tonsillectomy group. The median follow-up time was 97.5(57.3, 132.0) months. The clinical remission rate in the tonsillectomy group was higher than that in the non-tonsillectomy group (72.5% vs 45.0%, χ2=8.123, P=0.004). The Kaplan-Meier survival curve showed that there was no significant difference in renal survival rate between the two groups (Log-rank test χ2=0.070, P=0.791). Multivariate Cox regression analysis showed that tonsillectomy was not an independent risk factor affecting renal end-point events in IgAN children ( HR=0.986, 95% CI 0.499-1.948, P=0.967). Conclusions:The clinical remission rate of IgAN children undergoing tonsillectomy is higher than that of children without tonsillectomy. Tonsillectomy is not an independent factor affecting renal end-point events in IgAN children. Tonsillectomy does not delay the time of entry into end-stage renal disease for children with IgAN.

Focal segmental glomerulosclerosis (FSGS) is characterized by the fusion of foot processes of podocytes, and can lead to end-stage kidney disease in children.The pathogenesis of FSGS has not been fully clarified, but more than 30 pathogenic genes have been identified in FSGS patients in recent years with the development of molecular genetics.These findings prove that the destruction of the structure and function of podocytes plays a role in the pathogenesis of FSGS.In this paper, the research progress of common pathogenic genes of FSGS was reviewed.

Objective To investigate the renoprotective effect of aspirin-triggered lipoxins(ATL)on kidney of mice with acute kidney injury(AKI).Methods Eighty-eight male specific pathogen-free(SPF)C57BL/6J mice were randomly divided into lipopolysaccharide(LPS)groups(including 2 h group,4 h group,8 h group,12 h group, 24 h group),ATL+LPS(including 2 h group,4 h group,8 h group,12 h group,24 h group)and normal control group according to random numble table,and each group had 8 mice.The mice in LPS groups were given LPS intraperitoneal injection to establish AKI animal models,while the mice in ATL+LPS groups were given ATL intraperitoneal injection 30 minutes before LPS intraperitoneal injection.The enzyme linked immunosorbent assay was used to test the serum creatinine(Scr),serum urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and urine neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),cysteine-rich protein-61 (Cyr61)and netrin-1 levels of mice.Results The kidney tissue injury scores of mice of ATL+LPS group[4 h:(22.32 ± 1.04)scores,8 h:(31.11 ± 1.86)scores,12 h:(18.22 ± 0.92)scores,24 h:(20.87 ± 3.18)scores] were lower than those of LPS group at the corresponding time points[4 h:(35.47 ± 2.27)scores,8 h:(52.28 ± 2.82) scores,12 h:(54.99 ± 4.56)scores,24 h:(53.41 ± 4.76)scores],and the differences were statistically significant(all P<0.01).The values of Scr,BUN,TNF-α and IL-1β in ATL+LPS group[Scr 8 h:(143.07 ± 5.02)μmol/L, BUN 12 h:(33.07 ± 3.52)mmol/L,TNF-α 4 h:(196.33 ± 14.181)ng/L and 8 h:(221.77 ± 10.11)ng/L,IL-1β 4 h:(50.25 ± 2.67 ng/L)]were lower than those in LPS group at the corresponding time points[Scr 8 h:(227.43 ± 11.17)μmol/L,BUN 12 h:(59.68 ± 3.84)mmol/L,TNF-α 4 h:(267.87 ± 26.48)ng/L and 8 h:(334.78 ± 21.08)ng/L,IL-1β 4 h:(89.45 ± 5.87)ng/L],and the differences were statistically significant(all P<0.01). The urine NGAL[4 h:(56.76 ± 4.01)μg/L,8 h:(65.44 ± 7.81)μg/L],KIM-1[8 h:(78.19 ± 9.48)μg/L] and netrin-1[8 h:(40.12 ± 2.01)ng/L,12 h:(36.87 ± 2.87)ng/L]of mice in ATL+LPS group were lower than those in LPS group at the corresponding time points[NGAL 4 h:(168.77 ± 10.77)μg/L,8 h:(155.33 ± 8.26) μg/L;KIM-1 8 h:(124.73 ± 13.47)μg/L;netrin-1 8 h:(89.17 ± 2.74)ng/L,12 h:(81.11 ± 3.88)ng/L],and the differences were statistically significant(all P<0.01).Conclusions ATL can treat LPS-induced AKI and play a renoprotective role in the kidney.

Objective To evaluate the value of low-dose spectral CT imaging combined with ASIR recon-struction in differenting peripheral lung cancer from inflammatory mass. Methods We retrospectively analyzed the imaging data of 147 cases with 165 pulmonary nodules or masses underwent enhanced CT scans with spectral imag-ing mode from June 2015 to May 2016. Spectral curves,normalized slope rates,iodine-water concentration were measured on the lesions in arteral phase images. The differences of the spectral characteristic parameters were eval-uated statistically by indepengdent samples t test. Results Among 165 pulmonary nodules or masses,including 68 inflammatory mass and 97 peripheral lung cancer. In the arterial phase,the iodine concentration,water concentra-tion and normalized spectral curves rates of peripheral lung cancer were 10.93 ± 5.12,1033.96 ± 9.74,0.998 ± 0.66,which was obviously higher than those in inflammatory mass in 5.29 ± 0.96,1028.85 ± 9.31,0.620 ± 0.16. There were significant difference between peripheral lung cancer and inflammatory mass(0.000 ,0.008 ,0.001 in P values). Conclusion The iodine concentration,water concentration and normalized spectral curves rates has high value for differential diagnosis of peripheral pung cancer and pneumonia mass in the arterial phase using low-dose spectral CT imaging combined with ASIR reconstruction.

Lipoxins are metabolic products of arachidonic acid,which possess a wide spectrum of adjustment function for various inflammatory cell function and the expression of inflammatory related genes.It is known asstop signals or braking signals of inflammatory response,which can promote the regression of inflammation through regulating a variety of inflammatory signaling pathway.Now,the progress in the regulation of multiple signal pathways by lipoxins and its anti-inflammatory mechanism are reviewed.