Objective To investigate clinical and pathological features of idiopathic membranous nephropathy (IMN) accompanied by mesangial dense deposit.Methods Clinical data of 46 patients who were diagnosed as IMN accompanied by mesangial dense deposit admitted to Zhejiang Provincial People's Hospital from January 2013 to December 2014 were retrospectively analyzed.They were compared with those of 29 patients who were diagnosed as IMN without mesangial dense deposit during the same period in the hospital.Analysis of their clinical and pathological features was conducted.Results The IMN accompanied by mesangial dense deposit accounted for IMN 61.3％,and had more hyaline changes of arteriole (43.5％ vs 6.9％,P=0.001) and more obvious arteriolar wall thickening (78.2％ vs 51.7％,P=0.016) than IMN without mesangial dense deposit.Furthermore,the positive rate of IgA deposition in IMN accompanied by mesangial dense deposit was greatly higher than that in IMN without mesangial dense deposit (21.7％ vs 0,P=0.007).In other index,such as serum biochemical parameters,urine protein,glomerular lesion,tubulointerstitium pathological damage and other immunopathologic changes,no statistically significant differences were found between these two groups.Conclusions IMN patients accompanied by mesangial dense deposit have severe intrarenal artery lesions,and high positive rate of IgA deposition.

Objective To investigate the clinical and pathological features of idiopathic membranous nephropathy (IMN) in young patients.Methods Clinical data of 20 young patients, 16 to 44 years, who were diagnosed as IMN admitted to the Zhejiang Provincial People's Hospital from January 2013 to December 2014 were retrospectively analyzed, comparing to 55 mid-aged patients who were diagnosed as IMN during the same period in the hospital.Clinical and pathological features of above mentioned patients were analyzed.Results Young patients with IMN accounted for 26.7％ of IMN patients.Compared to mid-aged patients, young patients with IMN had lower proportion of hypertension (P=0.003), lower blood glucose level (P=0.010), higher estimated glomerular filtration rate (eGFR) and low-density lipoprotein (LDL) (P=0.012, P=0.038), and lower levels of T3 and T4 (P=0.030, P=0.034).Furthermore, there were less sclerosis glomeruli (P＜ 0.001), hyaline change of arteriole (P=0.040) and arteriolar wall thickening (P ＜ 0.0001), lower positive ratios of IgA (P=0.008),and more without renal tubulointerstitial lesions (P=0.018) in young patients.There were no statistically significant differences between these two groups in other index.Conclusions Compared to mid-aged patients, young patients with IMN have better blood pressure and blood glucose level, higher glomerular filtration rate and LDL.Moreover, thyroid function is significantly affected, meanwhile the lesions of glomerular, interstitial and vascular are mild in young patients.

Objective To investigate the keratin 9 gene mutation in epidermolytic palmoplantar keratoderma (EPPK) and its relationship with clinical manifestations. Methods Three Chinese pedigrees with EPPK were studied. Polymerase chain reaction (PCR) was performed to amplify the seven exons encoded by keratin 9. Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific PCR were used to reveal the sequence variation in the PCR products. Results An insertion-deletion mutation in the exon 1 of keratin 9 497delAinsGGCT, was revealed in all 3 EPPK families, resulting in the keratin 9 change from tyrosine166 to tryptophan and leucine (Y166delinsWL). Allele-specific PCR confirmed that the mutation was not a commonly seen polymorphism, but a novel mutation which has not been reported in The Human Intermediate Filament Mutation Database (http://www.interfil.org). Conclusions A new keratin 9 gene mutation, 497delAinsGGCT, is found in these Chinese EPPK pedigrees, which may be the genetic basis of EPPK.

Objective To study As2O3toxicity on rat liver in a retrograde isolated hepatic perfusion model. Methods In this study 104 male Sprague-Dawley rats weighing between 300 and 400 g were used. Eight male SD rats were used for preoperatively normal control and the remaining rats were randomly divided into 4 subgroups receiving As2O3at dosage of 0 mg/kg,0.75 mg/kg, 1.5 mg/kg, 3 mg/kg respectively. Modified RIHP was used in which As2O3was infused through hepatic artery. Ringer's lactate was retrogradly infused through hepatic veins and the portal vein was used as the outflow tract. Hepatic function, pathology and liver enzymes were assessed at different time points. As2O3concentration was monitered during the perfusion in rats of subgroup C. Results Serum ALT and AST rose to the peak on the first day, returning to normal after 3 or 7 days in all four subgroups. There was no difference between the peak levels of serum ALT and AST between subgroup A and B. Differences in serum ALT、AST level between subgroup A and C, A and D, B and C, B and D, C and D were all statistically significant (FALT=40.811,P<0.01;FAST= 48.212,P <0.01). On day 7, ALT and AST in subgroup D were still statistically higher when compared with that of other subgroups and normal control (FALT=13.928, P<0.01;FAST=17.942, P<0.01), and the hepatic pathology showed necrosis of the hepatocyte. The peak levels of As2O3were 13.21±0.82(μg/ ml) and 0.09±0.008 (μg/ml)in rats liver and systemic circulation in subgroup C during isolated perfuision. There were significant differences between the peak levels of concentration of As2O3in rats liver and systemic circulation (t=35.758,P<0.01). Conclusions The hepatic toxicity is reversible caused by As2O3when given at a dosage of 1.5 mg/kg of As2O3in a murine model of RIHP.

Objective To study the change of CD4+ CD25+ Foxp3high regulatory T cells (Treg cells) and the molecules associated with Treg cells in different immune status in infant with sepsis, and to further clarity the pathogenesis of disturbed immune function in infant with sepsis. Method Totally 36 sepsis infants admitted in In-tensive Care Unit of Shenzhen Children' s Hospital from May 2007 to November 2007 and 16 age-matched healthy infants were collected for prospective study, after excluding autoimmune disease, immunodeficiency, inherited metabolic disorders, tumor, and drug-treatment that could affect immune function during lately 6 months. The study was approved by Ethics Committee of Shenzhen Children's Hospital. The 36 infants with sepsis were divided into two groups according to expression levels of HLA-DR in CD14-positive cells: DR-H group was defined as patients with HLA-DR > 30%, while DR-L group was defined as patients with HLA-DR < 30%. Expression levels of HLA-DR in CD14-positive cells and the proportion of Treg cells were analyzed by flow cytometry. Real-time PCR were used to evaluate the mRNA levels of Foxp3, CTLA-4,GITR, and IL-10 in CD4-posidve ceils. Statistical analysis was performed by one-way Anova. There was statistical difference with P < 0.05. Results The proportion of Treg cells in DR-L group was found to be significantly higher than that in healthy control or DR-H group (P <0.05).Compared with healthy control group or DR-H group, transcriptional levels of Foxp3, CTLA-4 and IL-10were significantly increased in DR-L group (P <0.05). The levels of GITR mRNA in DR-L group were detected to be higher than those in DR-H group (P < 0.05). Conclusions Aberrant increased proportion of Treg cells may be associated with suppressed immune status in infant with sepsis.

Angiofibroma ; pathology ; Humans ; Soft Tissue Neoplasms ; pathology

Adult ; Carcinoma, Renal Cell ; diagnosis ; Diagnosis, Differential ; Humans ; Kidney ; pathology ; Kidney Neoplasms ; diagnosis

Objective: To investigate the clinicopathologic and molecular characteristics, diagnostic, differential diagnostic and prognostic features of malignant gastrointestinal neuroectodermal tumor. Methods: Two cases of malignant gastrointestinal neuroectodermal tumor were retrieved; the clinical and radiologic features, histomorphology, immunophenotype, molecular genetics and prognosis were analyzed and the relevant literature reviewed. Results: Case 1 was a 57-year-old male, presented with recurrent abdominal pain and melena. Pelvic imaging showed a circumscribed thickening of the wall of a small intestinal segment, and a malignant lymphoma was favored. Case 2 was a 24-year-old male, presented with recurrent small intestinal malignancy. Imaging demonstrated multiple masses in the peritoneal and pelvic cavities, and a malignant gastrointestinal stromal tumor with multiple metastases was suspected. Grossly both tumors were located mainly in the muscularis propria of small intestine. Case 1 showed a single 5.5 cm tumor; and case 2 consisted of two tumors measuring 4 cm and 6 cm respectively. Microscopic examination of both tumors showed small round blue, but focally spindled or clear tumor cells in solid pattern. The tumor cells had scanty cytoplasm, indistinctive nucleoli and brisk mitoses. Osteoclast-like giant cells were dispersed within the stroma. In case 1 rosette-like and pseudo-papillary growth patterns were noted, and in case 2 there were variable-sized hemorrhagic cysts. By immunohistochemistry, both tumors showed strong and diffuse expression of SOX10 and S-100, and focal to diffuse expression of neuroendocrine markers (CD56 or synaptophysin). Case 2 exhibited focal reactivity to pan-cytokeratin. Both tumors lacked expression of markers associated with gastrointestinal stromal tumor, smooth muscle tumor, melanoma (HMB45 or Melan A), dendritic cell tumor and Ewing sarcoma. Fluorescence in situ hybridization analysis demonstrated EWSR1 rearrangement in both tumors and the next generation sequencing confirmed EWSR1-ATF1 gene fusion in case 2. At follow-up of 16 months, case 1 was recurrence or metastasis free; whereas case 2 showed multiple recurrences and metastases within 19 months although stable disease was transiently achieved when treated with combinations of multidrug and targeted chemotherapy. Conclusions Malignant gastrointestinal neuroectodermal tumor is a rare and aggressive soft tissue sarcoma with a predilection for small intestine. It has distinctive morphologic, immunohistochemical and molecular characteristics and needs to be distinguished from other small blue round and spindle cell tumors that occur in the gut. Careful attentions to its characteristic histomorphology with the judicious use of immunohistochemistry and molecular genetics can help to distinguish this tumor from its many mimickers.

Objective: To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Methods: Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People′s Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. Results: All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, β-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. Conclusions ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.