1.The relationship between subclassification and prognosis of patients with gastrointestinal diffuse large B-cell lymphoma
Zizhen ZHANG ; Xingzhi NI ; Xiaolu YIN ; Danping SHEN ; Yanying SHEN
Chinese Journal of General Surgery 2008;23(12):946-949
Objective To investigate the relationship between tumor subclassifieation and the clinicopathologic features and prognosis of patients with gastrointestinal diffuse large B-cell lymphoma (DLBCL). Method From June 2000 to June 2007, 63 gastrointestinal DLBCL cases were enrolled. Immunohistochemical staining was performed to detect CDIO, Bcl-6 and MUM1 expression. Tumors were subclassified according to CDIO, Bcl-6 and MUM1 expression. Results CD10 expression was positive in 13 cases. Bcl-6 expression was positive in 53 cases. MUM1 expression was positive in 52 cases. According to the expression of CD10, Bcl-6 and MUM1, 17 cases(27%) were of germinal center B cell-like (GCB) DLBCL and 46 cases (73%) were of non-GCB. There was a significant difference in local lymph node metastasis between GCB group and non-GCB group, but there was no significant difference in terms of tumor size and infiltrate depth between the two subgroups. The survival time of patients in GCB group(76 months) was significantly longer than that of non-GCB group (28 months). Among cases receiving postoperative chemotherapy (CHOP), the survival of GCB group (76 months) was longer than non-GCB group (24 months). All 4 GCB cases and 4 non-GCB cases under R-CHOP chemotherapy are alive (22 ~ 47 months). Conclusion Gastrointestinal DLBCL subclassification is closely correlated with local lymph node metastasis, and this in combination with the expression of CD10 could be used to predict the prognosis of patients with gastrointestinal DLBCL.
2.Evaluation of different histopathological classification in cases of gastrointestinal stromal tumor
Danping SHEN ; Xingzhi NI ; Xiaolu YIN ; Yanying SHEN
Chinese Journal of General Surgery 2010;25(5):349-352
Objective To evaluate two different histopathological classification systems (Fletcher and Miettinen) for the risk in cases of gastrointestinal stromal tumors (GIST). Methods One hundred and sixty-five GIST cases with complete clinicopathologic and follow-up data were evaluated for their biologic potential by the histopathological classification systems of Fletcher, and among those, 164 cases GIST were evaluated by the histopathological classification systems of Miettinen. The implication of two classification systems were compared by survival analysis. Results Evaluated by Fletcher histopathological classification system, 59 cases (35. 8%) were graded as high risk, 49 cases (29. 7%) as intermediate risk, 43 cases (26. 1%) as low risk and 14 cases (8. 5%) were very-low risk. Evaluated by Miettinen's system, 68 cases (41.5%) were as high risk, 23 cases (14. 0%) were intermedatie risk, 60 cases (36. 6%) were low risk and 13 cases (7. 9%) were very-low risk. Evaluated by both two systems, the survival time and disease-free survival time of high risk GIST were lower than those of very-low, low and intermediate risk GIST(P <0. 05), the survival time and disease-free survival time of intermediate risk GIST were lower than those of low risk GIST(P<0. 05). According to Fletcher's system, in the high risk GIST, the disease-free survival time of small intestinal, colonic and rectal GIST was lower than that of gastric GIST(P = 0. 022), and in the intermediate risk GIST, the survival time of small intestinal, colonic and rectal GIST was lower than that of gastric GIST(P =0. 032). According to Miettinen's system, in the risk subgroup of GIST, the survival time and disease-free survival time of gastric, small intestinal, colonic and rectal GIST has no statistical difference(P > 0. 05). Conclusions Fletcher histopathological classification system is simple and easy to use, while Miettinen's system for evaluating biological potential by anatomic site is more accurate and predictive in the selection of high risk patients for target adjuvant treatment.
3.Clinical obser ration of interferon α-2b on the treatment of viral keratitis:476 cases study
Yan LIU ; Xiaolu SHEN ; Xiaodong SUN ; Xun XU
Chinese Journal of Primary Medicine and Pharmacy 2009;16(9):1578-1579
Objective To observe the clinical effect of interferon on the treatment of virus keratitis. Meth-ods Review and analysis was made of 476 patients with virus keratitis who was treated with high concentration of an-ti-virus eyedrops and one million unit of α-2b interferon, the clinical safety and effect was evaluated. Result The total cure rate was 59. 1%, and the type from high to low is interstitial、endothelial、epithelial and the total cornea. The total recurrence rate is 23.5% ,and the type from high to low is epithelial,the total cornea,endothelial and inter-stitial. The incidence rate of the adverse effect is 10. 7%. Condusion Systemic administration of interferon has a direct anti-virus effect, and it can raise the cure rate of virus keratitis as well as decrease recurrencerate. One million unit of interferon has a high clinical safety and effect.
5.Initial exploration on clinical application of resting-state functional magnetic resonance imaging amplitude of low-frequency fluctuation method on cognitive impairment in amyotrophic lateral sclerosis
Pan PENG ; Xiaolu LI ; Liying CUI ; Bo HOU ; Feng FENG ; Dongchao SHEN
Chinese Journal of Neurology 2017;50(1):28-33
Objective To explore diagnostic value of amplitude of low-frequency fluctuation ( ALFF) on cognitive impairment in amyotrophic lateral sclerosis ( ALS ) using resting-state functional magnetic resonance imaging ( MRI ) .Methods Sixteen ALS patients from neurological clinic in Peking Union Medical College Hospital were enrolled between November 2013 and April 2015.The patients were divided into two groups by the presence (ALSi, n=7) or absence (ALSu, n=9) of cognitive impairment. Routine MRI structural images and resting-state functional MRI were collected for comparison between groups through voxel-based morphometry ( VBM ) and ALFF.Results ( 1 ) Neuropsychological analysis showed significant differences in Montreal Cognitive Assessment score (22.9 ±2.0 vs 25.8 ±2.3, t=2.622, P=0.020), Frontal Assessment Battery score (12.4 ±1.6 vs 15.1 ±1.4, t=3.600, P=0.003), animal listing test (13.6 ±1.8 vs 16.7 ±2.9, t=2.482, P=0.026), naming test (2(1) vs 0(1), Z=-2.746, P=0.006), similarity test (7.9 ±3.7 vs 17.3 ±2.8, t=5.846, P=0.000) and clock drawing test (2(2) vs 3(0), Z=2.516, P=0.012).(2) VBM analysis showed no significant differences in both gray matter and white matter density between the two groups .(3) ALFF analysis showed significantly increased signals in widespread areas of bilateral cerebrum and cerebellum in ALSi group compared to ALSu group . Conclusion ALFF value has the potential to provide more valuable imaging basis for early diagnosis on cognitive impairment in ALS.
6.Association between the C46T polymorphism of coagulation factor Ⅻgene and the involvement of ;factor Ⅻ activity in patients with unexplained recurrent spontaneous abortion
Yanhui JIN ; Xiaolu SHEN ; Mingshan WANG ; Xiaomin XU ; Meina LIU ; Zhangsheng ZHAO ; Jiayong ZHENG
Chinese Journal of Obstetrics and Gynecology 2016;51(8):597-601
Objective To explore the association between the C46T polymorphism of coagulation factor Ⅻ (FⅫ) gene and the involvement of FⅫ activity (FⅫ:C) in patients with unexplained recurrent spontaneous abortion (URSA), and to elucidate its role in the pathogenesis of URSA. Methods This study included 203 patients with URSA (URSA group) and 171 healthy women with at least one child and no history of infertility or miscarriage (control group) in the southern area of Zhejiang Province. The C 46T polymorphism of the FⅫ gene was analyzed with matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS) in all subjects. The values of prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, FⅫ:C and other coagulant parameters were determined. The frequency distribution of the wild-type (CC), heterozygote (CT), homozygote (TT) genotypes and C and T alleles were compared between the patients and controls. A comprehensive analysis of association was conducted between C46T genotypes and the FⅫ:C levels in URSA patients. Results The CC, CT, TT genotypes of the FⅫgene were observed in 7 (3.4%, 7/203), 83 (40.9%, 83/203) and 113 (55.7%, 113/203) patients with URSA versus 7 (4.1%, 7/171), 46 (26.9%, 46/171) and 118 (69.0%, 118/171) controls. The frequency of CT in the patients with URSA was significantly higher than that in controls, but the frequency of TT in the patients was lower than that in controls (χ2=7.939, OR=1.884, 95%CI:1.210-2.935, P<0.05). The frequencies of allele C and allele T were observed in 97 (23.9%, 97/406) and 309 (76.1%, 309/406) patients with URSA versus 60 (17.5%, 60/342) and 282 (82.5%, 282/342) controls. The distribution frequency of allele T in URSA group was lower than that in control group (χ2=4.510, OR=1.475, 95%CI:1.029-2.115, P<0.05). The FⅫ:C levels in the patients were (102±13)%in CC genotype, (78±11)%in CT genotype and (59± 9)%in TT genotype, respectively. The differences of the FⅫ:C levels between the CC and CT, CT and TT, CC and TT genotypes in the patients were significant (all P<0.05). Conclusions The low level of FⅫ:C maybe result from the T allele of the FⅫgene in URSA patients. The CT genotype might be relative to the pathogenesis of URSA in a Chinese Han female population from the southern area of Zhejiang province.
7.Bcl-2 Gene Amplification and Protein Expression and Their Relationship with Clinicopathological Characteristics and Immunophenotype of Primary Gastrointestinal Diffuse Large B-cell Lymphoma
Qi HAN ; Shuqiong FAN ; Zizhen ZHANG ; Danping SHEN ; Jiahua LIU ; Yikuan CHEN ; Hulin HAN ; Haihua FU ; Xinying SU ; Xiaolu YIN ; Xingzhi NI
Chinese Journal of Gastroenterology 2017;22(5):266-271
Background: Aberrant Bcl-2 transcription is closely related with nodal diffuse large B-cell lymphoma (DLBCL), however, the relationship between Bcl-2 and primary gastrointestinal DLBCL (PGI-DLBCL) was not fully studied.Aims: To investigate the relationship between Bcl-2 gene amplification and protein expression and clinicopathological characteristics, immunophenotype and prognosis of PGI-DLBCL.Methods: Clinical data was collected from 136 PGI-DLBCL patients receiving surgical treatment, and a telephone interview was conducted for survival information.Bcl-2 gene amplification and protein expression in tumor tissue were determined by fluorescence in situ hybridization and immuno-histochemistry, respectively, and relationships between Bcl-2 and clinicopathological characteristics, immunophenotype and prognosis of PGI-DLBCL were analyzed.Results: Among 136 PGI-DLBCL patients, 33 (24.3%) showing gene amplification and 90 (66.2%) showing protein expression of Bcl-2;gene amplification was correlated with primary tumor location, Ann Arbor stage, serum lactate dehydrogenase level, B symptom and International Prognostic Index (IPI) score (P<0.05), while protein expression was correlated with primary tumor location and immunophenotype (P<0.05).5-year overall survival (OS) in patients positive for Bcl-2 gene amplification and patients with non-GCB immunophenotype and positive for Bcl-2 protein expression were inferior to those negative ones (41.5%vs.71.5%, P<0.05;54.6% vs.84.6%, P<0.05).In Bcl-2 gene amplification or protein expression positive patients, 5-year OS of CHOP chemotherapy was inferior to that of rituximab combined with CHOP chemotherapy (48.6%vs.80.3%, P<0.05;66.4%vs.83.4%, P<0.05).Conclusions: Detection of Bcl-2 gene amplification is useful for prediction of prognosis in PGI-DLBCL.Both patients with Bcl-2 gene amplification and non-GCB patients with Bcl-2 protein expression have a poorer prognosis.Rituximab may improve the prognosis in patients with Bcl-2 gene amplification or protein expression.
8.MiR-181a and miR-181b influence proliferation, migration, invasion and angiogenesis via targeting FUT1 in colorectal cancer
Jie ZHOU ; Yuanming ZHENG ; Zongkun SHEN ; Xiaolu MA ; Yanju LI
Chinese Journal of Laboratory Medicine 2018;41(11):841-846
Objective To investigate the correlation of miR-181a and miR-181b with fucosyltransferase FUT1, the functional mechanism was elucidated in a colorectal cancer ( CRC).Methods It collected 32 pairs of tissue samples , 18 males and 14 females in the first affiliated hospital of Dalian Medicinal University, from March 2014 to January 2016.The expression of miR-181a and miR-181b was detected by RT-PCR in CRC tissues , adjacent tissues , serum of colorectal cancer patients and healthy people, and CRC cell lines SW620 and SW480 with differently metastatic ability.The relationship of FUT1 and miR-181a, miR-181b expression were verificated by Pearson's correlation curve.FUT1 was identified the target of miR-181a and miR-181b by Network prediction softwares ( TargetScan Human 7.1, microRNA.org and Starbase v2.0) and luciferase assay.The effects of miR-181a and miR-181b expression on the proliferation, migration, invasion and angiogenesis of SW 480 and SW620 cells were further detected by CCK8, wound healing, transwell and tube foramtion assays.T-test was used for comparison between two independent samples , and one-way anova was used for comparison between multiple samples . Pearson correlation coefficient was used for correlation analysis .Results The levels of miR-181a and 181b in CRC tissues were much lower than in tumor-adjacent tissues (3.12 ±1.88 vs 6.44 ±2.32, t=11.74;3.16 ± 1.77 vs 5.52 ±2.45, t=3.24 ;P<0.05).The levels of miR-181a and 181b in serum of colorectal cancer patients were much lower than in healthy people (1.32 ±0.25,2.57 ±0.48,t=10.26;0.91 ±0.14,1.63 ± 0.29,t=5.19;P<0.05 ) .The levels of miR-181a and miR-181b in SW620, SW480 CRC cells were detected to be much lower than in normal colorectal epithelial cells [(0.65 ±0.10, 0.50 ±0.09) vs 1.0;(0.60 ±0.12,0.42 ±0.03)vs 1.0;t=3.08, P<0.05].FUT1 was highly expressed in CRC tissues and SW620 (t=5.23, P<0.05).Based on the network prediction softwares and luciferase assays , FUT1 was the common target of miR-181a and miR-181b.Over expression of miR-181a or miR-181b inhibited FUT1 level and attenuated the capacity of cell migration , invasion and proliferation in SW 620.Down-regulation of miRNAs in SW480 increased FUT1 expression and promoted the capability of cell migration , invasion and proliferation.Downregulation of the two miRNAs attenuated the capability of cell invasion in SW 480, which was blocked by the reductive FUT1.Conclusion MiR-181a and miR-181b mediated the progression of CRC cells by targeting FUT1.
9.Age-dependent application of high-risk HPV E6/E7mRNA test in triage of ASC-US
Qiangwei PAN ; Xiaodong ZHENG ; Xiaolu SHEN ; Jie YANG ; Yuehui ZHANG ; Lixiao SHA ; Jieqiang LYU
Chinese Journal of Experimental and Clinical Virology 2016;(1):45-49
Objective To evaluate the clinical performance of high-risk human papillomavirus ( HR-HPV) E6/E7 mRNA test in female in different groups with atypical squamous cell of undetermined significance ( ASC-US) cytology.Methods 320 samples from female patients with ASC-US were detected with HR-HPV E6/E7 mRNA test and HR-HPV DNA test simultaneously, patients were examined with colposcopy and cervical biopsy.They were divided into two groups:younger than 30 years and 30 years and older.The statistical analysis were performed.Results There were no statistically significance in the positive rate of HR-HPV E6/E7 mRNA between two groups ( P>0.05) .In the group aged younger than 30 years, the positive rate of HR-HPV DNA was significantly higher than the group aged 30 years and older ( P<0.05),but the prevalence of CINⅡor greater was significantly lower than the other group (P<0.05).In the group aged younger than 30 years, the specificity of HR-HPV E6/E7 mRNA test for detection of CINⅡor greater was 68.0%,which was significantly higher (P<0.05) than that of HR-HPV DNA test 38.7%, meanwhile, the specificity of HR-HPV E6/E7mRNA test for detection of CINⅡor greater was significantly higher ( P<0.05) than that of HR-HPV DNA test ( 76.5% vs 69.4%) in the group aged 30 years and older.There were no statistically significance (P>0.05) in sensitivity, positive predictive value(PPV) and negative predictive value( NPV) between the two tests in each group.Conclusion Comparing to HR-HPV DNA test, HR-HPV E6/E7mRNA test is more suitable for triage of ASC-US including female patients who were younger than 30 years.
10.Role and mechanisms of disulfiram in improving cardiac function and re-ducing myocardial inflammation in HFpEF rats based on NLRP3/cas-pase-1/GSDMD signaling pathway
Xuanyang SHEN ; Weidong LI ; Xiaolu JIANG ; Meiqi ZHANG ; Wentao TAN ; Yuan SHEN ; Hongfu WEN
Chinese Journal of Pathophysiology 2024;40(10):1891-1897
AIM:To investigate the role and possible mechanisms of disulfiram(DSF)in a rat model of heart failure with preserved ejection fraction(HFpEF)induced by high-fat diet(HFD)and nitric oxide blocker Nω-nitro-L-argi-nine methyl ester(L-NAME).METHODS:The HFpEF rat model was constructed using HFD and L-NAME.Sprague-Dawley rats were randomly divided into 3 groups:control group(fed with a normal diet and water),HFpEF group(fed with HFD and drinking water containing 0.5 g/L L-NAME),and DSF+HFpEF group(treated with DSF in addition to HFD and L-NAME).After 5 weeks,cardiac function of the rats was examined using echocardiography and exercise test.Myo-cardial pathological changes were detected using hematoxylin-eosin and wheat germ agglutinin staining,the degree of car-diac fibrosis was assessed using Masson staining,and apoptosis levels were observed using TUNEL staining.Western blot was performed to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),cleaved caspase-1,gasdermin D N-terminal fragment(GSDMD-N)in the myocardium,and serum level of N-terminal pro-brain natriuretic peptide(NT-proBNP),and interleukin(IL)-1β and IL-18 in the myocardium were detected by ELISA.RESULTS:Compared with control group,the rats in HFpEF group showed increased body weight,systolic blood pres-sure,diastolic blood pressure,E/E′ ratio,left ventricular anterior wall thickness at diastole and serum NT-proBNP level(P<0.05),and decreased E/A ratio and absolute value of global longitudinal strain(GLS;P<0.05).In contrast,the rats in DSF+HFpEF group showed decreased body weight,E/E′ ratio,diastolic blood pressure and serum NT-proBNP level(P<0.05),and increased E/A ratio and absolute value of GLS(P<0.05),with no significant changes in systolic blood pressure,left ventricular posterior wall thickness at diastole and left ventricular ejection fraction(P>0.05).The rats in HFpEF group had increased myocardial fibrosis area,cardiomyocyte cross-sectional area,and apoptotic rate compared with control group(P<0.05),while these indexes were reduced in DSF+HFpEF group(P<0.05).The results of Western blot and ELISA showed that the levels of NLRP3,cleaved caspase-1,GSDMD-N,IL-1β and IL-18 were increased in the myocardium of rats in HFpEF group compared with control group(P<0.05),but decreased in DSF+HFpEF group com-pared with HFpEF group(P<0.05).CONCLUSION:Disulfiram improves cardiac function and attenuates myocardial remodeling in HFpEF rats.The mechanism may be related to the modulation of NLRP3/caspase-1/GSDMD signaling path-way and the reduction of myocardial inflammatory response.