Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesio...Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.展开更多
BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal ...BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal biopsies is challenging due to histomorphological overlaps,variability in pathological diagnosis consistency,and limited reproducibility.AIM To evaluate the diagnostic utility of P53,Ki67,P504S,and IMP3 in gastric cancer and its precancerous lesions,focusing on their effectiveness in distinguishing AH,LGD,HGD,and AC.METHODS From January 2018 to September 2020,a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors(2019).The specimens were categorized into four groups:AH,LGD,HGD,and AC.Immunohistochemistry was employed to assess the expression status of P53,Ki67,P504S,and IMP3.Intergroup comparisons were performed using theχ^(2)test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.RESULTS The expression rate of P504S was highest in the LGD group(53.3%,16/30),while IMP3 expression was highest in the AC group(41.9%,26/62),followed by the HGD group(33.3%).Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups(P<0.001).Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD,HGD,and AC groups(P<0.001),as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups,and between the LGD group and the HGD and AC groups(P<0.001).Additionally,significant correlations were found between P504S and the polarity expression pattern of Ki67,and between IMP3 and the mutation expression pattern of P53(P<0.001).The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67“polarity”expression pattern.IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern.The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.The rational use of P504S,Ki67,IMP3,and p53 can help distinguish gastric cancer and precancerous lesions,improving the early cancer diagnosis rate.展开更多
BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate de...BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.展开更多
目的:探索表观弥散系数(apparent diffusion coefficient,ADC)在前列腺影像报告和数据系统(prostate imaging-reporting and data system,PI-RADS)3分且前列腺特异性抗原(prostate specific antigen,PSA)灰区患者中对减少非必要前列腺...目的:探索表观弥散系数(apparent diffusion coefficient,ADC)在前列腺影像报告和数据系统(prostate imaging-reporting and data system,PI-RADS)3分且前列腺特异性抗原(prostate specific antigen,PSA)灰区患者中对减少非必要前列腺穿刺活检的应用价值。方法:回顾性收集2019年1月—2023年12月在中国科学技术大学附属第一医院(安徽省立医院)泌尿外科接受经会阴前列腺穿刺活检患者的临床资料。对于PI-RADS 3分病灶ADC值的计算,由1位泌尿外科医生只选择病灶上最可疑的区域,即在ADC图像上最可疑区域依次绘制2个圆形感兴趣区(region of interest,ROI)(大小为10~20 mm~(-2)),影像系统将自动计算ADC值,最终的ADC值取2次绘制的ROI所对应ADC值的平均值,记为ADC_(min)。采用Mann-Whitney U检验比较各临床变量在良、恶性组的组间差异,使用受试者工作特征(receiver operating characteristic,ROC)曲线及其曲线下面积(area under curve,AUC)、灵敏度和特异度来评价各临床变量的诊断价值。结果:本研究共纳入121例患者,其中88例患者术后病理为良性、33例患者为前列腺癌(prostate cancer,PCa)(包括16例临床有意义前列腺癌患者)。前列腺体积(prostate volume,PV)、前列腺特异性抗原密度(prostate specific antigen density,PSAD)和ADC_(min)在组间比较时差异均有统计学意义。在诊断效能方面,ADC_(min)(AUC=0.810,95%CI:0.729~0.876)明显优于前列腺特异性抗原(PSA)(AUC=0.593,95%CI:0.446~0.630)、PV(AUC=0.691,95%CI:0.600~0.772)、PSAD(AUC=0.683,95%CI:0.592~0.765)。当ADC_(min)<600μm^(2)/s时,93.33%(14/15)的患者术后病理为PCa;当ADC_(min)>750μm^(2)/s时,仅有13.33%(10/75)的患者术后病理为PCa。结论:对于PI-RADS 3分且PSA灰区患者而言,ADC_(min)在区分前列腺穿刺活检术后病理良恶性中有很好的应用价值,ADC_(min)越小,患者患PCa的风险就越大。展开更多
AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical ...AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.展开更多
AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in the formation of gastric tumors induced by drinking water con...AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in Wistar rats. METHODS: One hundred and twenty Wistar rats were randomly divided into two groups (60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups (20 in each group): C/M15, C/M25 and C/M40 (15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/mL MNNG. Stomach tissues were collected at the end of the 15<sup>th</sup>, 25<sup>th</sup> and 40<sup>th</sup> week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS: (1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group (2.5 ± 1.0, 2.75 ± 0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy (6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different (P > 0.05); (2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy (10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different (P > 0.05); and (3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.展开更多
Systemic lupus erythematosus（SLE） is a multiple organ autoimmune disorder,including the liver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcripti...Systemic lupus erythematosus（SLE） is a multiple organ autoimmune disorder,including the liver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcription factor Foxp3＋ regulatory T cells（Tregs） and several other immune molecules [programmed cell death 1 and its ligand（PD1 and PD-L1）,and interleukin 10（IL-10） and transform growth factor β（TGF-β）] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry,real-time quantitative reverse transcription PCR,and enzyme-linked immunosorbent assay.Results showed that both frequency and number of Foxp3＋ Tregs were dramatically reduced in the thymus,spleen and kidney of the BXSB mice（P0.05）,but those in the liver were kept in nearly normal range,when compared to negative control C57BL/6 mice.In comparison to control mice,the mRNA levels of Foxp3,PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice（P0.05）,but there was no significant difference in the livers of the BXSB mice（P0.05）.Protein levels of IL-10 and TGF-β in serum showed no significant difference between BXSB and C57BL/6 mice,but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice（P0.05）.These results suggest that reduced Foxp3＋ Tregs are involved in the pathogenesis of SLE in BXSB mice,and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice,which may provide insights into development of new therapeutic approaches in SLE patients.展开更多
Since its emergence in 2000, small bowel capsule endoscopy(SBCE) has assumed a pivotal role as an investigation method for small bowel diseases. The PillCam SB2-ex offers 12 h of battery time, 4 more than the previous...Since its emergence in 2000, small bowel capsule endoscopy(SBCE) has assumed a pivotal role as an investigation method for small bowel diseases. The PillCam SB2-ex offers 12 h of battery time, 4 more than the previous version(SB2). Rahman et al recently found that the PillCam SB2-ex has a significantly increased completion rate, although without higher diagnostic yield, compared with the SB2. We would like to discuss these somewhat surprising results and the new potentialities of the PillCam SB3 regarding the diagnostic yield of small bowel studies. PillCam SB3 offers improved image resolution and faster adaptable frame rate over previous versions of SBCE. We recently compared the major duodenal papilla detection rate obtained with PillCam SB3 and SB2 as a surrogate indicator of diagnostic yield in the proximal small bowel. The PillCam SB3 had a significantly higher major duodenal papilla detection rate than the PillCam SB2(42.7% vs 24%, P = 0.015). Thus, the most recent version of the PillCam capsule, SB3, may increase diagnostic yield, particularly in the proximal segments of the small bowel.展开更多
Objective： We investigated the relationship between the expression of Caspase-3, cell proliferation and apoptosis in gastric cancer and their precancerous lesions, to explore the tumorigenesis of the stomach mucosa. ...Objective： We investigated the relationship between the expression of Caspase-3, cell proliferation and apoptosis in gastric cancer and their precancerous lesions, to explore the tumorigenesis of the stomach mucosa. Methods： Caspase- 3 expression in 13 normal gastric mucosa, 6 chronic atrophic gastritis （CAG）, 31 intestinal metaplasia （IM）, 114 dysplasia （DYS） and 20 gastric carcinomas were investigated immunohistochemically. Cell proliferation was evaluated with anti-Ki-67 immunostaining and apoptosis was evaluated using DNA fragmentation in situ by TdT-mediated dUTP biotin nick end labeling （TUNEL） method. Results： Caspase-3 mild-moderately positive expression was observed in most of normal superficial epithelia, its positively polar distribution in normal mucosa, CAG, IM, DYS and gastric carcinomas changed as seen in TU- NEL, and so did the positive rate. Caspase-3 protein expression showed significantly positive correlation with the number of apoptotic cells labeled with TUNEL （correlation coefficient r = 0,94; P 〈 0101）. Ki-67 expression showed a negative but not significant correlation trend with Caspase-3 （correlation coefficient r = -0.23; P 〉 0.05）. Conclusion： Caspase-3 protein expression was up-regulated from CAG to IM and mild-moderate atypical dysplasia, but down-regulated in severe dysplasia and gastric carcinoma, indicating that inactivity or reduced expression of Caspase-3 is closely correlated with carcinogenesis of the stomach mucosa.展开更多
Pathological mineralizations in breast lesions are closely associated with disease progression and serves as a critical diagnostic indicator.However,systematic understanding remains lacking regarding the phase categor...Pathological mineralizations in breast lesions are closely associated with disease progression and serves as a critical diagnostic indicator.However,systematic understanding remains lacking regarding the phase categories,distribution patterns,and proportional occurrences of mineral phases across different breast lesion types.The diagnostic implications of specific phases,such as calcium oxalate,for distinguishing benign and malignant lesions remain controversial.This study employed polarizing microscopy,environmental scanning electron microscopy(SEM)with energy dispersive spectroscopy(EDS),transmission electron microscopy(TEM),Fourier transform infrared spectroscopy(FTIR),and Raman spectroscopy to analyze the phase composition of 61 mineralized samples from three lesion types:Invasive carcinoma,carcinoma in situ and benign lesions.Results demonstrate that breast lesion mineralizations predominantly comprise calcium phosphates,including hydroxyapatite(HA),amorphous calcium phosphate(ACP),and whitlockite,occasionally accompanied by calcium oxalate(monohydrate or dihydrate).Distinct distribution patterns and proportional occurrences of minerals were observed among the three types of lesion mineralizations.HA,as the predominant phase,was ubiquitously present across all three lesion categories.ACP,a mineralization precursor phase,emerged during early mineralization stages across all lesion types.Notably,whitlockite exclusively occurred in benign lesions and carcinoma in situ,with higher prevalence in benign cases,suggesting a progressive decline in Mg^(2+)concentration within the lesion microenvironment as malignancy advances.Calcium oxalate coexisted with HA in mineralized regions across all lesion types,and its presence in invasive carcinoma specimens warrants heightened clinical attention.展开更多
OBJECTIVE: To investigate the mechanism underlying the action of Weipixiao(WPX) in a rat's model with ameliorating gastric precancerous lesions(GPL).METHODS: HPLC analysis was performed to identify the chemical co...OBJECTIVE: To investigate the mechanism underlying the action of Weipixiao(WPX) in a rat's model with ameliorating gastric precancerous lesions(GPL).METHODS: HPLC analysis was performed to identify the chemical constituents of WPX preparation.Sprague-Dawley rats were randomly assigned into control group, model group, vitacoenzyme group,high-dose WPX group(H-WPX), medium-dose WPX group(M-WPX) and low-dose WPX group(L-WPX).After modeling, the treated rats were administrated WPX or vitacoenzyme intragastrically for consecutive 10 weeks. Gene and protein expressions ofGSK3β, C-myc, Cylin E were evaluated by quantitative real-time reverse transcription-polymerase chain reaction(RT-qPCR) and immunohistochemistry, respectively.RESULTS: WPX could efficiently attenuate the pathological alterations of "non-progressive GPL" in rats.As expected, mRNA and protein levels of C-myc and Cylin E were up-regulated in model rats, while GSK3β expression down-regulated(P < 0.01). WPX treatment, especially at low dose, could significantly down-regulate the m RNA as well as protein levels of C-myc, and could lead to remarkable up-regulation of mRNA and protein levels of GSK3β in GPL rats(P < 0.05). However, no significant changes were observed in WPX-treated rats.CONCLUSION: Our findings suggested that WPX-mediated attenuation of GPL pathological alterations might be due to its regulatory effect on the expressions of GSK3β and C-myc, and on the dysregulation of Wnt/GSK3β pathway.展开更多
Objective: to investigate whether MR 3D-FSE Cube sequence imaging is superior to traditional 2 D-FSE sequence imaging in the diagnosis of space occupying lesions in saddle area. Methods: From January 2018 to January 2...Objective: to investigate whether MR 3D-FSE Cube sequence imaging is superior to traditional 2 D-FSE sequence imaging in the diagnosis of space occupying lesions in saddle area. Methods: From January 2018 to January 2020, data of 106 patients with space-occupying lesions in saddle area confirmed by surgery and pathology were collected, Routine 2 D-FSE sequence and 3 D-FSE Cube sequence scans were performed in all patients before operation. Analysis of MRI images by two radiologists over 10 years of service, and the two sequences were independently diagnosed, based on surgical and pathological findings, the diagnostic results were statistically analyzed. Results: according to conventional 2 D-FSE sequence images and 3 D-FSE Cube sequence images, the diagnostic accuracy was 70.7%(75/106) and 84.9%(90/106), difference was statistically significant (P<0.05). Conclusion: MR 3D-FSE Cube sequence imaging is superior to traditional 2 D-FSE in the qualitative diagnosis of space occupying lesions in saddle area, it is worth popularizing in clinical application.展开更多
基金supported by the Qingdao Medical Health Research Project,No.2023-WJZD212(to XX)。
文摘Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.
基金Supported by The Science and Technology Research Project of Anyang,No.2022C01SF074。
文摘BACKGROUND Differential diagnosis among atypical hyperplasia(AH)(including reparative hyperplasia and intestinal metaplasia),low-grade dysplasia(LGD),high-grade dysplasia(HGD),and adenocarcinoma(AC)in gastric mucosal biopsies is challenging due to histomorphological overlaps,variability in pathological diagnosis consistency,and limited reproducibility.AIM To evaluate the diagnostic utility of P53,Ki67,P504S,and IMP3 in gastric cancer and its precancerous lesions,focusing on their effectiveness in distinguishing AH,LGD,HGD,and AC.METHODS From January 2018 to September 2020,a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors(2019).The specimens were categorized into four groups:AH,LGD,HGD,and AC.Immunohistochemistry was employed to assess the expression status of P53,Ki67,P504S,and IMP3.Intergroup comparisons were performed using theχ^(2)test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.RESULTS The expression rate of P504S was highest in the LGD group(53.3%,16/30),while IMP3 expression was highest in the AC group(41.9%,26/62),followed by the HGD group(33.3%).Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups(P<0.001).Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD,HGD,and AC groups(P<0.001),as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups,and between the LGD group and the HGD and AC groups(P<0.001).Additionally,significant correlations were found between P504S and the polarity expression pattern of Ki67,and between IMP3 and the mutation expression pattern of P53(P<0.001).The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67“polarity”expression pattern.IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern.The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC,respectively.The rational use of P504S,Ki67,IMP3,and p53 can help distinguish gastric cancer and precancerous lesions,improving the early cancer diagnosis rate.
基金Supported by the National Natural Science Foundation of China,No.81070319the Beijing Natural Science Foundation of China,No.7102013the Beijing Municipal Education Commission Research Program,China,No.KM201610025004
文摘BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.
文摘目的:探索表观弥散系数(apparent diffusion coefficient,ADC)在前列腺影像报告和数据系统(prostate imaging-reporting and data system,PI-RADS)3分且前列腺特异性抗原(prostate specific antigen,PSA)灰区患者中对减少非必要前列腺穿刺活检的应用价值。方法:回顾性收集2019年1月—2023年12月在中国科学技术大学附属第一医院(安徽省立医院)泌尿外科接受经会阴前列腺穿刺活检患者的临床资料。对于PI-RADS 3分病灶ADC值的计算,由1位泌尿外科医生只选择病灶上最可疑的区域,即在ADC图像上最可疑区域依次绘制2个圆形感兴趣区(region of interest,ROI)(大小为10~20 mm~(-2)),影像系统将自动计算ADC值,最终的ADC值取2次绘制的ROI所对应ADC值的平均值,记为ADC_(min)。采用Mann-Whitney U检验比较各临床变量在良、恶性组的组间差异,使用受试者工作特征(receiver operating characteristic,ROC)曲线及其曲线下面积(area under curve,AUC)、灵敏度和特异度来评价各临床变量的诊断价值。结果:本研究共纳入121例患者,其中88例患者术后病理为良性、33例患者为前列腺癌(prostate cancer,PCa)(包括16例临床有意义前列腺癌患者)。前列腺体积(prostate volume,PV)、前列腺特异性抗原密度(prostate specific antigen density,PSAD)和ADC_(min)在组间比较时差异均有统计学意义。在诊断效能方面,ADC_(min)(AUC=0.810,95%CI:0.729~0.876)明显优于前列腺特异性抗原(PSA)(AUC=0.593,95%CI:0.446~0.630)、PV(AUC=0.691,95%CI:0.600~0.772)、PSAD(AUC=0.683,95%CI:0.592~0.765)。当ADC_(min)<600μm^(2)/s时,93.33%(14/15)的患者术后病理为PCa;当ADC_(min)>750μm^(2)/s时,仅有13.33%(10/75)的患者术后病理为PCa。结论:对于PI-RADS 3分且PSA灰区患者而言,ADC_(min)在区分前列腺穿刺活检术后病理良恶性中有很好的应用价值,ADC_(min)越小,患者患PCa的风险就越大。
基金Supported by National Natural Science Foundation of China, No.30973503Special Fund for Climbing Scholars of Universities in Liaoning Province, China, 2009-2010
文摘AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.
文摘AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in Wistar rats. METHODS: One hundred and twenty Wistar rats were randomly divided into two groups (60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups (20 in each group): C/M15, C/M25 and C/M40 (15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/mL MNNG. Stomach tissues were collected at the end of the 15<sup>th</sup>, 25<sup>th</sup> and 40<sup>th</sup> week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS: (1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group (2.5 ± 1.0, 2.75 ± 0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy (6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different (P > 0.05); (2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy (10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different (P > 0.05); and (3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.
文摘Systemic lupus erythematosus（SLE） is a multiple organ autoimmune disorder,including the liver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcription factor Foxp3＋ regulatory T cells（Tregs） and several other immune molecules [programmed cell death 1 and its ligand（PD1 and PD-L1）,and interleukin 10（IL-10） and transform growth factor β（TGF-β）] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry,real-time quantitative reverse transcription PCR,and enzyme-linked immunosorbent assay.Results showed that both frequency and number of Foxp3＋ Tregs were dramatically reduced in the thymus,spleen and kidney of the BXSB mice（P0.05）,but those in the liver were kept in nearly normal range,when compared to negative control C57BL/6 mice.In comparison to control mice,the mRNA levels of Foxp3,PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice（P0.05）,but there was no significant difference in the livers of the BXSB mice（P0.05）.Protein levels of IL-10 and TGF-β in serum showed no significant difference between BXSB and C57BL/6 mice,but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice（P0.05）.These results suggest that reduced Foxp3＋ Tregs are involved in the pathogenesis of SLE in BXSB mice,and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice,which may provide insights into development of new therapeutic approaches in SLE patients.
文摘Since its emergence in 2000, small bowel capsule endoscopy(SBCE) has assumed a pivotal role as an investigation method for small bowel diseases. The PillCam SB2-ex offers 12 h of battery time, 4 more than the previous version(SB2). Rahman et al recently found that the PillCam SB2-ex has a significantly increased completion rate, although without higher diagnostic yield, compared with the SB2. We would like to discuss these somewhat surprising results and the new potentialities of the PillCam SB3 regarding the diagnostic yield of small bowel studies. PillCam SB3 offers improved image resolution and faster adaptable frame rate over previous versions of SBCE. We recently compared the major duodenal papilla detection rate obtained with PillCam SB3 and SB2 as a surrogate indicator of diagnostic yield in the proximal small bowel. The PillCam SB3 had a significantly higher major duodenal papilla detection rate than the PillCam SB2(42.7% vs 24%, P = 0.015). Thus, the most recent version of the PillCam capsule, SB3, may increase diagnostic yield, particularly in the proximal segments of the small bowel.
基金Supported by grants from the National Natural Science Foundation of China (No. 30070845, 30271607, 30600286)Climbing Scholars of the Universities in Liaoning Province (2009–2011)
文摘Objective： We investigated the relationship between the expression of Caspase-3, cell proliferation and apoptosis in gastric cancer and their precancerous lesions, to explore the tumorigenesis of the stomach mucosa. Methods： Caspase- 3 expression in 13 normal gastric mucosa, 6 chronic atrophic gastritis （CAG）, 31 intestinal metaplasia （IM）, 114 dysplasia （DYS） and 20 gastric carcinomas were investigated immunohistochemically. Cell proliferation was evaluated with anti-Ki-67 immunostaining and apoptosis was evaluated using DNA fragmentation in situ by TdT-mediated dUTP biotin nick end labeling （TUNEL） method. Results： Caspase-3 mild-moderately positive expression was observed in most of normal superficial epithelia, its positively polar distribution in normal mucosa, CAG, IM, DYS and gastric carcinomas changed as seen in TU- NEL, and so did the positive rate. Caspase-3 protein expression showed significantly positive correlation with the number of apoptotic cells labeled with TUNEL （correlation coefficient r = 0,94; P 〈 0101）. Ki-67 expression showed a negative but not significant correlation trend with Caspase-3 （correlation coefficient r = -0.23; P 〉 0.05）. Conclusion： Caspase-3 protein expression was up-regulated from CAG to IM and mild-moderate atypical dysplasia, but down-regulated in severe dysplasia and gastric carcinoma, indicating that inactivity or reduced expression of Caspase-3 is closely correlated with carcinogenesis of the stomach mucosa.
基金financially supported by the National Natural Science Foundation of China(41772033,41272048).
文摘Pathological mineralizations in breast lesions are closely associated with disease progression and serves as a critical diagnostic indicator.However,systematic understanding remains lacking regarding the phase categories,distribution patterns,and proportional occurrences of mineral phases across different breast lesion types.The diagnostic implications of specific phases,such as calcium oxalate,for distinguishing benign and malignant lesions remain controversial.This study employed polarizing microscopy,environmental scanning electron microscopy(SEM)with energy dispersive spectroscopy(EDS),transmission electron microscopy(TEM),Fourier transform infrared spectroscopy(FTIR),and Raman spectroscopy to analyze the phase composition of 61 mineralized samples from three lesion types:Invasive carcinoma,carcinoma in situ and benign lesions.Results demonstrate that breast lesion mineralizations predominantly comprise calcium phosphates,including hydroxyapatite(HA),amorphous calcium phosphate(ACP),and whitlockite,occasionally accompanied by calcium oxalate(monohydrate or dihydrate).Distinct distribution patterns and proportional occurrences of minerals were observed among the three types of lesion mineralizations.HA,as the predominant phase,was ubiquitously present across all three lesion categories.ACP,a mineralization precursor phase,emerged during early mineralization stages across all lesion types.Notably,whitlockite exclusively occurred in benign lesions and carcinoma in situ,with higher prevalence in benign cases,suggesting a progressive decline in Mg^(2+)concentration within the lesion microenvironment as malignancy advances.Calcium oxalate coexisted with HA in mineralized regions across all lesion types,and its presence in invasive carcinoma specimens warrants heightened clinical attention.
基金Supportted by the National Natural Science Foundation of China(No.81804066 No.81273739+1 种基金 No.81473620)the Research Project of Sichuan Provincial Administration of TCM(No.2018QN022)
文摘OBJECTIVE: To investigate the mechanism underlying the action of Weipixiao(WPX) in a rat's model with ameliorating gastric precancerous lesions(GPL).METHODS: HPLC analysis was performed to identify the chemical constituents of WPX preparation.Sprague-Dawley rats were randomly assigned into control group, model group, vitacoenzyme group,high-dose WPX group(H-WPX), medium-dose WPX group(M-WPX) and low-dose WPX group(L-WPX).After modeling, the treated rats were administrated WPX or vitacoenzyme intragastrically for consecutive 10 weeks. Gene and protein expressions ofGSK3β, C-myc, Cylin E were evaluated by quantitative real-time reverse transcription-polymerase chain reaction(RT-qPCR) and immunohistochemistry, respectively.RESULTS: WPX could efficiently attenuate the pathological alterations of "non-progressive GPL" in rats.As expected, mRNA and protein levels of C-myc and Cylin E were up-regulated in model rats, while GSK3β expression down-regulated(P < 0.01). WPX treatment, especially at low dose, could significantly down-regulate the m RNA as well as protein levels of C-myc, and could lead to remarkable up-regulation of mRNA and protein levels of GSK3β in GPL rats(P < 0.05). However, no significant changes were observed in WPX-treated rats.CONCLUSION: Our findings suggested that WPX-mediated attenuation of GPL pathological alterations might be due to its regulatory effect on the expressions of GSK3β and C-myc, and on the dysregulation of Wnt/GSK3β pathway.
文摘Objective: to investigate whether MR 3D-FSE Cube sequence imaging is superior to traditional 2 D-FSE sequence imaging in the diagnosis of space occupying lesions in saddle area. Methods: From January 2018 to January 2020, data of 106 patients with space-occupying lesions in saddle area confirmed by surgery and pathology were collected, Routine 2 D-FSE sequence and 3 D-FSE Cube sequence scans were performed in all patients before operation. Analysis of MRI images by two radiologists over 10 years of service, and the two sequences were independently diagnosed, based on surgical and pathological findings, the diagnostic results were statistically analyzed. Results: according to conventional 2 D-FSE sequence images and 3 D-FSE Cube sequence images, the diagnostic accuracy was 70.7%(75/106) and 84.9%(90/106), difference was statistically significant (P<0.05). Conclusion: MR 3D-FSE Cube sequence imaging is superior to traditional 2 D-FSE in the qualitative diagnosis of space occupying lesions in saddle area, it is worth popularizing in clinical application.
