AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected...AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.展开更多
Single zircons from two trondhjemitic gneisses and two clastic metasedimentary rocks without Eu anomaly of the Kongling high-grade metamorphic terrain are dated by the in situ SHRIMP U-Pb method. The results show that...Single zircons from two trondhjemitic gneisses and two clastic metasedimentary rocks without Eu anomaly of the Kongling high-grade metamorphic terrain are dated by the in situ SHRIMP U-Pb method. The results show that the trondhjemitic magma emplaced at 2947-2903 Ma. Concordant age of as old as 3.3 Ga is present in the detrital zircons from the clastic metasedimentary rocks. Together with the depleted mantle Nd model age (TDM =3.2-3.3 Ga) of the clastic metasedimentary rocks, this documents the presence of Paleoarchean continental crust in the Yangtze craton.展开更多
Some 1.95 Ga metamorphism of high-grade Ar-chean rocks in Kongling terrain, continental nucleus of Yangtze Block, South China, are recognized by Sm-Nd dating. This event is further confirmed by the ages of single zirc...Some 1.95 Ga metamorphism of high-grade Ar-chean rocks in Kongling terrain, continental nucleus of Yangtze Block, South China, are recognized by Sm-Nd dating. This event is further confirmed by the ages of single zircon SHRIMP U-Pb and K-Ar analyses of TTG and (or) paragneisses, and intrusions of potassic-granitic batholith in the region. The coincidence in period between the high-grade metamorphism in the Kongling area and the creation of major basement rocks of its neighborhoods of the Yangtze Block around the Kongling Archean nucleus makes it a favorable explanation for their tectonic connections that, in the whole Yangtze Block there was some tectono-thermal event of ca. 2.0-1.8 Ga, which resulted in the formation of unitive Yangtze basement.展开更多
The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of...The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.展开更多
The early Precambrian high-grade metamorphosed basement in the Xi Ulanbulang area, central Inner Mongolia of China, is composed mainly of intermediate granulites and charnockitic gneisses. Both types of the rocks are ...The early Precambrian high-grade metamorphosed basement in the Xi Ulanbulang area, central Inner Mongolia of China, is composed mainly of intermediate granulites and charnockitic gneisses. Both types of the rocks are closely associated spatially and temporally, with a gradual variation between them. In order to understand timing of the high-grade metamorphism, we carried out SHRIMP U-Pb dating of zircons of the rocks. Zircons from the granulites and charnockitic gneisses are similar in structure and age. Zircon cores show magmatic zoning and have ages of 2507-2545 Ma. The ages are interpreted as the forming time of protolith of the granulites and charnockitic gneisses, indicating that a strong magmatism existed at that time in the Yinshan Block. The zircon mantles and rims show homogeneous structures and record a strong granulite facies metamorphism event around 2500 Ma, with a time interval between the metamorphism and magamatism being less than 50 Ma. These suggest that the Western Block was similar to the Eastern Block in tectono-thermal timing at the end of the Neoarchean.展开更多
Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and t...Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.展开更多
The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion （HSIL） patients with positive margin by conization. Clinico-pathological data of HSIL patien...The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion （HSIL） patients with positive margin by conization. Clinico-pathological data of HSIL patients with positive margin by conization were retrospectively collected from January 2009 to December 2014. All patients underwent secondary conization or hysterectomy within 6 months. The rate of residual lesion was calculated, and the factors associated with residual lesion were analyzed by univariate and multivariate analyses. Among a total of 119 patients, 56 （47.06%） patients presented residual HSIL in their subsequent surgical specimens, including 4 cases of invasive cervical carcinoma （3 stage IA1 and 1 stage IA2 patients）. Univariate analysis showed that patient age 〉 35 years （P = 0.005）, menopausal period 〉 5 years （P = 0.0035）, and multiple- quadrant involvement （P=0.001） were significantly correlated with residual disease; however, multivariate analysis revealed that multiple-quadrant involvement （P=0.001; OR, 3.701; 95%CI, 1.496-9.154） was an independent risk factor for residua! disease. Nearly half of HSIL patients with positive margin by conization were disease-free in subsequent surgical specimens, and those with multiple positive margins may consider re- conization or re-assessment.展开更多
Cytology triage has been generally recommended for human papillomavirus （HPV）-positive women, but is highly dependent on well-trained cytologists. The present study was designed to explore whether HPV E6/E7 mRNA det...Cytology triage has been generally recommended for human papillomavirus （HPV）-positive women, but is highly dependent on well-trained cytologists. The present study was designed to explore whether HPV E6/E7 mRNA detection in cervical exfoliated cells can be a potential triage for HPV-positive women from a clinic-based population. Both the primary HPV testing and Papanicolaou （Pap） test were performed on all eligible HPV-positive women. HPV E6/E7 mRNA was detected by QuantiVirus HPV E6/E7 mRNA assay in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. The data were assessed by Pearson＇s Chi-squared test and the receiver operating characteristic curve. A total of 404 eligible HPV-positive women were enrolled. Positive rate of E6/E7 mRNA in high-grade squamous intraepithelial lesion （HSIL） cases was higher than that in low-grade squamous intraepithelial lesion （LSIL） or normal cases. There was no statistical difference found between mRNA and cytological testing with sensitivity （89.52% vs. 86.67%, P=0.671）, specificity （48.96% vs. 48.96%, P=1.000）, positive predictive value （39.00% vs. 38.24%, P=1.000）, and negative predictive value （92.76% vs. 90.97%, P=-0.678） for detecting ≥HSIL. HPV E6/E7 mRNA detection in cervical exfoliated cells shows the same performance as Pap triage for HSIL identification for HPV-positive women. Detection of HPV E6/E7 mRNA may be used as a new triage option for HPV-positive women.展开更多
The predominant types of high-grade iron deposits in China include skarn,sedimentary metamorphic(banded ironformation,BIF-type),continental/submarine volcanic-hosted and magmatic Fe-Ti-Voxide deposits.Based on a compr...The predominant types of high-grade iron deposits in China include skarn,sedimentary metamorphic(banded ironformation,BIF-type),continental/submarine volcanic-hosted and magmatic Fe-Ti-Voxide deposits.Based on a comprehensive review of current studies on these deposits,this paper suggests that the oxygen concentration in atmosphere played an important role for the formation of BIFs,whereas the tectonic setting and deep magmatic differentiation processes are more important for the other types.Notably,both high temperature and high pressure experiments and melt inclusion studies indicate that during the differentiation,high temperature magmas could develop iron-rich magma via liquid immiscibility but not pure oxide melt("iron ore magma").Fe-P melt could be generated directly by liquid immiscibility under hydrous and oxidized condition.The formation of high-grade iron deposits is mostly associated with the processes related to multiple stages of superimposition,e.g.,desiliconization and iron enrichment,removal of impurity,and remobilization and re-precipitation of iron.According to the temporal evolution,the high-grade iron deposit could be divided into multi-episode superimposition type(temporally discontinuous mineralization)and multi-stage superimposition type(temporally continuous mineralization).The former is represented by the sedimentary metamorphic iron deposit,and the latter includes those related to magmatic-hydrothermal fluids(e.g.,skarn,volcanic-hosted and magmatic types).展开更多
Little is known about how chronic inflammation contributes to the progression of hepatoceUular carcinoma （HCC）, especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HC...Little is known about how chronic inflammation contributes to the progression of hepatoceUular carcinoma （HCC）, especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HCC and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c.myc mice and age-matched wt-C57BL/6 mice using our dynamical network biomarker （DNB） model. DNB analysis indicated that the 5th month after birth of transgenic mice was the critical period of cancer initiation, just before the critical transition, which is consistent with clinical symptoms. Meanwhile, the DNB-associated network showed a drastic inversion of protein expression and coexpression levels before and after the critical transition. Two members of DNB, PLA2G6 and CYP2C44, along with their associated differentially expressed proteins, were found to induce dysfunction of arachidonic acid metabolism, further activate inflammatory responses through inflammatory mediator regulation of transient receptor potential channels, and finally lead to impairments of liver detoxification and malignant transition to cancer. As a c-Myc target, PLA2G6 positively correlated with c-Myc in expression, showing a trend from decreasing to increasing during carcinogenesis, with the minimal point at the critical transition or tipping point. Such trend of homologous PLA2G6 and c-Myc was also observed during human hepatocarcinogenesis, with the minimal point at high-grade dysplastic nodules （a stage just before the carcinogenesis）. Our study implies that PLA2G6 might function as an oncogene like famous c-Myc during hepatocar- cinogenesis, while downregulation of PLA2G6 and c-Myc could be a warning signal indicating imminent carcinogenesis.展开更多
文摘AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.
基金Ministry of Science and Technology of China (Grant No.1999043202), the National Natural Science Foundation of China (Grant Nos. 49625305, 49573183, 49673184, 49794043), the Northwest University, the Ministry of Education of China and the Australian Res
文摘Single zircons from two trondhjemitic gneisses and two clastic metasedimentary rocks without Eu anomaly of the Kongling high-grade metamorphic terrain are dated by the in situ SHRIMP U-Pb method. The results show that the trondhjemitic magma emplaced at 2947-2903 Ma. Concordant age of as old as 3.3 Ga is present in the detrital zircons from the clastic metasedimentary rocks. Together with the depleted mantle Nd model age (TDM =3.2-3.3 Ga) of the clastic metasedimentary rocks, this documents the presence of Paleoarchean continental crust in the Yangtze craton.
基金the National Natural Science Foundation of China (Grant Nos. 49603044, 49625305, 49873010 and 49794043) the Project of the Open Laboratory of Consitution, Interaction and Dynamics of Crust-Mantle System, the Ministry of Land and Resources of China.
文摘Some 1.95 Ga metamorphism of high-grade Ar-chean rocks in Kongling terrain, continental nucleus of Yangtze Block, South China, are recognized by Sm-Nd dating. This event is further confirmed by the ages of single zircon SHRIMP U-Pb and K-Ar analyses of TTG and (or) paragneisses, and intrusions of potassic-granitic batholith in the region. The coincidence in period between the high-grade metamorphism in the Kongling area and the creation of major basement rocks of its neighborhoods of the Yangtze Block around the Kongling Archean nucleus makes it a favorable explanation for their tectonic connections that, in the whole Yangtze Block there was some tectono-thermal event of ca. 2.0-1.8 Ga, which resulted in the formation of unitive Yangtze basement.
文摘The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.
基金supported by National Natural Science Foundation of China (Grant Nos. 90814006, 40972135)Geological Survey of China (Grant No. 1212010510515)
文摘The early Precambrian high-grade metamorphosed basement in the Xi Ulanbulang area, central Inner Mongolia of China, is composed mainly of intermediate granulites and charnockitic gneisses. Both types of the rocks are closely associated spatially and temporally, with a gradual variation between them. In order to understand timing of the high-grade metamorphism, we carried out SHRIMP U-Pb dating of zircons of the rocks. Zircons from the granulites and charnockitic gneisses are similar in structure and age. Zircon cores show magmatic zoning and have ages of 2507-2545 Ma. The ages are interpreted as the forming time of protolith of the granulites and charnockitic gneisses, indicating that a strong magmatism existed at that time in the Yinshan Block. The zircon mantles and rims show homogeneous structures and record a strong granulite facies metamorphism event around 2500 Ma, with a time interval between the metamorphism and magamatism being less than 50 Ma. These suggest that the Western Block was similar to the Eastern Block in tectono-thermal timing at the end of the Neoarchean.
文摘Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.
文摘The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion （HSIL） patients with positive margin by conization. Clinico-pathological data of HSIL patients with positive margin by conization were retrospectively collected from January 2009 to December 2014. All patients underwent secondary conization or hysterectomy within 6 months. The rate of residual lesion was calculated, and the factors associated with residual lesion were analyzed by univariate and multivariate analyses. Among a total of 119 patients, 56 （47.06%） patients presented residual HSIL in their subsequent surgical specimens, including 4 cases of invasive cervical carcinoma （3 stage IA1 and 1 stage IA2 patients）. Univariate analysis showed that patient age 〉 35 years （P = 0.005）, menopausal period 〉 5 years （P = 0.0035）, and multiple- quadrant involvement （P=0.001） were significantly correlated with residual disease; however, multivariate analysis revealed that multiple-quadrant involvement （P=0.001; OR, 3.701; 95%CI, 1.496-9.154） was an independent risk factor for residua! disease. Nearly half of HSIL patients with positive margin by conization were disease-free in subsequent surgical specimens, and those with multiple positive margins may consider re- conization or re-assessment.
基金Project supported by the Special Fund for Scientific Research in the Public Interest from the National Health and Family Planning Commission of the People’s Republic of China(No.201402010)the National Key Technology R&D Program of China(No.2016YFC1302900)+2 种基金the Zhejiang Provincial Educational Project(No.Y201328819)the Zhejiang Provincial Medical & Hygienic Science and Technology Project(Nos.2013KYB147 and 2013KYA104)the Zhejiang Provincial Natural Science Foundation(No.LQ14H160007),China
文摘Cytology triage has been generally recommended for human papillomavirus （HPV）-positive women, but is highly dependent on well-trained cytologists. The present study was designed to explore whether HPV E6/E7 mRNA detection in cervical exfoliated cells can be a potential triage for HPV-positive women from a clinic-based population. Both the primary HPV testing and Papanicolaou （Pap） test were performed on all eligible HPV-positive women. HPV E6/E7 mRNA was detected by QuantiVirus HPV E6/E7 mRNA assay in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. The data were assessed by Pearson＇s Chi-squared test and the receiver operating characteristic curve. A total of 404 eligible HPV-positive women were enrolled. Positive rate of E6/E7 mRNA in high-grade squamous intraepithelial lesion （HSIL） cases was higher than that in low-grade squamous intraepithelial lesion （LSIL） or normal cases. There was no statistical difference found between mRNA and cytological testing with sensitivity （89.52% vs. 86.67%, P=0.671）, specificity （48.96% vs. 48.96%, P=1.000）, positive predictive value （39.00% vs. 38.24%, P=1.000）, and negative predictive value （92.76% vs. 90.97%, P=-0.678） for detecting ≥HSIL. HPV E6/E7 mRNA detection in cervical exfoliated cells shows the same performance as Pap triage for HSIL identification for HPV-positive women. Detection of HPV E6/E7 mRNA may be used as a new triage option for HPV-positive women.
基金supported by the National Basic Research Program of China(Grant No.2012CB416800)。
文摘The predominant types of high-grade iron deposits in China include skarn,sedimentary metamorphic(banded ironformation,BIF-type),continental/submarine volcanic-hosted and magmatic Fe-Ti-Voxide deposits.Based on a comprehensive review of current studies on these deposits,this paper suggests that the oxygen concentration in atmosphere played an important role for the formation of BIFs,whereas the tectonic setting and deep magmatic differentiation processes are more important for the other types.Notably,both high temperature and high pressure experiments and melt inclusion studies indicate that during the differentiation,high temperature magmas could develop iron-rich magma via liquid immiscibility but not pure oxide melt("iron ore magma").Fe-P melt could be generated directly by liquid immiscibility under hydrous and oxidized condition.The formation of high-grade iron deposits is mostly associated with the processes related to multiple stages of superimposition,e.g.,desiliconization and iron enrichment,removal of impurity,and remobilization and re-precipitation of iron.According to the temporal evolution,the high-grade iron deposit could be divided into multi-episode superimposition type(temporally discontinuous mineralization)and multi-stage superimposition type(temporally continuous mineralization).The former is represented by the sedimentary metamorphic iron deposit,and the latter includes those related to magmatic-hydrothermal fluids(e.g.,skarn,volcanic-hosted and magmatic types).
文摘Little is known about how chronic inflammation contributes to the progression of hepatoceUular carcinoma （HCC）, especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HCC and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c.myc mice and age-matched wt-C57BL/6 mice using our dynamical network biomarker （DNB） model. DNB analysis indicated that the 5th month after birth of transgenic mice was the critical period of cancer initiation, just before the critical transition, which is consistent with clinical symptoms. Meanwhile, the DNB-associated network showed a drastic inversion of protein expression and coexpression levels before and after the critical transition. Two members of DNB, PLA2G6 and CYP2C44, along with their associated differentially expressed proteins, were found to induce dysfunction of arachidonic acid metabolism, further activate inflammatory responses through inflammatory mediator regulation of transient receptor potential channels, and finally lead to impairments of liver detoxification and malignant transition to cancer. As a c-Myc target, PLA2G6 positively correlated with c-Myc in expression, showing a trend from decreasing to increasing during carcinogenesis, with the minimal point at the critical transition or tipping point. Such trend of homologous PLA2G6 and c-Myc was also observed during human hepatocarcinogenesis, with the minimal point at high-grade dysplastic nodules （a stage just before the carcinogenesis）. Our study implies that PLA2G6 might function as an oncogene like famous c-Myc during hepatocar- cinogenesis, while downregulation of PLA2G6 and c-Myc could be a warning signal indicating imminent carcinogenesis.
