Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective To explore the relevant factors of functionally healing the basic type of intermittent exotropia.Methods A prospective observation study was designed.One hundred and thirty-two cases with basic type of intermittent exotropia in Tianjin Eye Hospital from August 2015 to March 2016.Pre-and post-operation examinations to each patient,including the tests of ocular alignment,Worth four-dot test at 2 m and 33 cm,Titmus,functional visual analyzer (FVA),Frisby Davis distance (FD2) were used to explore the influencing factors of postoperative eye position and stereoscopic reconstruction,and to find the cutoff point of surgery.This study followed the Declaration of Helsinki.This study protocol was approved by Ethic Committee of Tianjin Eye Hospital (No.YKLL-2015-8-21).Written informed consent was obtained from each patient or guardian prior to entering study cohort.Results At 6 months postoperatively,there were 84 cases of orthopedic position,4 cases of overcorrection and 44 cases of undercorrection.The success rate was 63.6％.The deviation at day 1 and peripheral fusion function were statistically significant to postoperative eye position (b =-0.093,P =0.037;b =0.725,P =0.017).The area under the receiver operating characteristic (ROC) curve was 0.645,which showed that the result of Worth four-dot test at 33 cm had lower diagnostic value.Seventy-two cases with eye position between 0 and +10 PD at 1 day postoperatively were all successful in eye position at 6 months postoperatively.The postoperative eye position was the influencing factor for postoperative distance stereo with FVA (x2 =4.036,P =0.045).The age of onset and the preoperative distance stereoacuity with FD2 were the influencing factors of postoperative distance stereo reconstruction (b =-0.213,P =0.023;b =0.021,P =0.036).The area under the ROC curve of the age of onset and the preoperative distance stereoacuity with FD2 was 0.257 and 0.752,respectively.The former had no diagnostic value,and the latter had a medium diagnostic value.The best cutoff point was 22.5" with FD2 at 6 m.Conclusions Success rate of postoperative eye position is affected by the postoperative deviation at day 1.The optimal deviation at post-operation day 1 is 0-10 PD.Postoperative distance stereopsis is improved well and the surgery should be done before the distance stereoacuity is decreased to 22.5" with FD2 at 6 m.

Objective To explore the condition of MYC/BCL2 protein coexpression in 245 patients with diffuse large B-cell lymphoma (DLBCL)and to find the correlations among MYC/BCL2 protein coexpres-sion,the germinal center B-cell-like (GCB)subtype and non-GCB subtype.Methods Paraffin-embedded lymphoma samples from 245 patients with DLBCL were studied using immunohistochemistry for MYC,BCL2, CD10,BCL6,MUM1 and KI67.And the protein expressions of them were analyzed.Results In the speci-mens of 245 patients with DLBCL,the patients with non-GCB were 163 (66.5%),and the patients with GCB were 82 (33.5%).The group of MYC/BCL2 protein coexpression comprised 35.9% (88/246)of the all patients.Non-GCB subtype group had a significantly higher frequency of MYC/BCL2 protein coexpression than the GCB subtype group (41.7%∶24.4%;χ2 =7.116,P=0.008).Conclusion The data shows that MYC/BCL2 protein coexpression occurs significantly more commonly in the non-GCB subtype.We can predict prog-nosis and choose therapeutic regimen base on the assessment for MYC and BCL2 protein expression.

Aim To establish a model of focal cerebral ischemic tissue of rat brain and explore the injury mechanism of focal cerebral ischemia reperfusion in whole level of proteins.Method The model was established with suture method by reperfusion 24 h after ischemic 2 h according to Koizumi′s method,total brain tissue proteins were extracted with Lysis buffer,proteins were separated by two-dimensional electrophoresis(2-DE),stained by Coomassie brilliant blue,the patterns were gotten,differential proteins were found out,PMS was obtained by MALDI-TOF-MS,and related information of proteins was gained by MS-Fit database.Results A comparative proteomic study of model and normal group was performed.Compared with model group,the normal group gained 23 differential protein spots,13 spots expressed lowly,and 10 spots high,6 protein spots were identified,the relative cerebral ischemic proteins such as Leukotriene A-4 hydrolase,Thyrotropin-releasing hormone-degrading ectoenzyme etc were found out.Conclusions Establishing a 2-DE technology is applied to protein analysis of brain tissue,and the relative proteins of cerebral ischemia are found from proteome aspect.This will contribute to the research on the injury mechanism of cerebral ischemic tissues.

Objective To investigate the relationships of peroxisome proliferators activated receptor ?(PPAR?) and matrix metallo protease-7 ( MMP-7) with gastric cancer ( including low and high grade atypical hyperplasia). Methods One hundred and twenty gastric tissue specimens (four groups) were collected by gastroscopy or surgical operation, including 31 patients with chronic gastritis, 25 patients with low-grade atypical hyperplasia, 27 patients with high-grade atypical hyperplasia, and 28 patients with gastric cancer. The expression of PPAR? and MMP-7 were observed by immunohistochemical technique and analyzed by statistic methods. Results Both of them have high expression in the groups of gastric cancer respectively, and the high combined expressions of them were found in gastric cancer and high-grade atypical hyperplasia. Conclusion PPAR? and MMP-7 were the important differential signs of the gastric cancer and precancer by inference, the combined expression of PPAR? and MMP-7 was the evidences in differential diagnosis among gastric cancer, high and low grade atypical hyperplasia and gastritis.

Aim To explore the mechanism of neuro-protecting effects of TGRP on ischemic cerebral injury.Methods The middle cerebral artery was occluded for 2 h to produce focal ischemic followed by 24 h reperfusion.HE staining,TUNEL labeling and immunohistochemical methods were used to investigate changes of neuronal apoptosis and expression of the apoptosis-related proteins after administration of TGRP.Result TGRP decreased the pathologic changes significantly.The apoptosis of neural cells and the expression of Bax positive cells in the TGRP groups significantly decreased compared with the control group(P

Aim To screen alteration in protein level in brain tissue between middle cererbral artery occlusion(MCAO) and the total saponins of Rubus Parviflolius L(TSRP) treated rats and to learn the mechanism of nerve-protecting effects of TSRP after focal cerebral ischemia-reperfusion.Methods The MCAO 2 h reperfusion of 24 h model was established in rats,2-DE was applied to preparein step 1 for the separation of protein,and imaging analysis of gels was done with Image-Master 2D software.Different protein spots expressing between cerebral ischemic reperfusion(CIR) model and TSRP group were cut from the gels for the MS analysis,Different protein spots expressing between cerebral ischemic tissue administered with or without TSRP were also cut from the gels for the MS analysis.MALDI-TOF-MS and database search: protein spots from step 2 were subject to in-gel digestion and MALDI-TOF-MS analysis,which resulted in the peptide mass fingerprint spectra(PMF).PMF were search against swiss-prot database using search program of Ms-Fit.Results By comparative proteome analysis,29 expression-altered spots were excised for MS and informatics analysis,comparing to the CIR model,18 proteins up-regulated in the TSRP group,11 proteins down-regulated,7 spots of them were identified and characterized.Conclusion The protective effect of TSRP on cerebral ischemia-reperfusion is the result of the participation of a number of proteins.