BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after curative resection remains a major cause of treatment failure and tumor-related death.Patterns of HCC recurrence can be categorized into early recurrence an...BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after curative resection remains a major cause of treatment failure and tumor-related death.Patterns of HCC recurrence can be categorized into early recurrence and late recurrence which have different underlying mechanisms.In this study,we investigated if simple inflammation-based clinical markers can distinguish patterns of recurrence after curative resection of HCC.METHODS:A retrospective analysis of 223 patients who underwent curative hepatectomy for HCC was performed.Preoperative inflammation-based factors including neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio,γ-glutamyl transferase/alanine aminotransferase ratio,aspartate aminotransferase/platelet ratio index(APRI) and prognostic nutritional index together with other clinicopathologic parameters were evaluated by univariate analysis and multivariate analysis to identify independent prognostic factors.By combining risk factors,predictive models were established to distinguish populations at high risk of early or late recurrence.RESULTS:Age ≤50 years,resection margin ≤1 cm,TNM stage III-IV,NLR>2.75,APRI>0.23 and positive alpha-fetoprotein were independent adverse prognostic factors for early recurrence.Patients with three or more risk factors were at significant higher risk of early recurrence.APRI>0.23 and positive hepatitis B e antigen(HBe Ag) were independent risk factors of late recurrence,the coexistence of high APRI and positive HBe Ag increased the risk of late recurrence.CONCLUSIONS:Preoperative inflammation-based prognostic factors predict early and late recurrence of HCC after curative resection.Different prognostic factor combinations distinguish high-risk populations of early or late HCC recurrence.展开更多
BACKGROUND:Early recurrence of hepatocellular carcinoma(HCC)is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early re...BACKGROUND:Early recurrence of hepatocellular carcinoma(HCC)is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early recurrence after cu rative hepatectomy and to establish a simple predictive model for HCC early recurrence.展开更多
Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in m...Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in multiple bioactive processes. However, little is known about the role of Sph K1 in hepatic I/R injury. This study aimed to investigate the effect of Sph K1 knockout on liver I/R injury and to explore underlying mechanisms. Methods: Sph K1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3(STAT3). Western blotting was used to determine the expression of S1 P receptor 1(S1 PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. Results: Sph K1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in Sph K1 knockout mice as demonstrated by attenuated expression of S1 PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1 β, interleukin-6 and tumor necrosis factor-α were also inhibited by Sph K1 genetic deletion. The oxidative stress markers were lower in Sph K1 knockout mice after I/R injury than wild type mice. Conclusions: Knockout of Sph K1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. Sph K1 may be a novel and potent target in clinical practice in I/R-related liver injury.展开更多
AIM:To characterize the two components of theory of mind(ToM) in patients with esophageal cancer combined with depression.METHODS:Sixty-five patients with esophageal cancer combined with depression(depressed group) an...AIM:To characterize the two components of theory of mind(ToM) in patients with esophageal cancer combined with depression.METHODS:Sixty-five patients with esophageal cancer combined with depression(depressed group) and 62 normal controls(control group) were assessed using reading the mind in the eyes test,faux pas task,verbal fluency test,digit span test and WAIS IQ test.The depressed group was divided into two subgroups including psychotic depressed(PD) group(32 cases) and nonpsychotic depressed(NPD) group(33 cases).The clinical symptoms of patients were assessed using Beck depression inventory version Ⅱ and brief psychiatric reacting scale(BPRS).RESULTS:There was a significant difference between the depressed group and the control group on tasks involving ToM social perceptual components(mind reading:t = 7.39,P < 0.01) and tests involving ToM social cognitive components(faux pas questions:t = 13.75,P < 0.01),respectively.A significant difference was also found among the PD group,the NPD group and the control group on mind reading(F = 32.98,P < 0.01) and faux pas questions(χ 2 = 78.15,P < 0.01),respectively.The PD group and NPD group performed worse than normal group controls both on mind reading and faux pas questions(P < 0.05).The PD group performed significantly worse than the NPD group on tasks involving ToM(mind reading:F = 18.99,P < 0.01;faux pas questions:F = 36.01,P < 0.01).In the depressed group,there was a negative correlation between ToM performances and BPRS total score(mind reading:r =-0.35,P < 0.01;faux pas questions:r =-0.51,P < 0.01),and between ToM performances and hostile suspiciousness factor score(mind reading:r =-0.75,P < 0.01;faux pas questions:r =-0.73,P < 0.01),respectively.CONCLUSION:The two components of ToM are both impaired in patients with esophageal cancer combined with depression.This indicates that there may be an association between ToM deficits and psychotic symptoms in clinical depression.展开更多
Cyclin-dependent kinases(CDKs) have become potential targets for treating various diseases, especially cancer. Compound i CDK9 is an excellent and selective CDK9 inhibitor, but its major limitation is the potential to...Cyclin-dependent kinases(CDKs) have become potential targets for treating various diseases, especially cancer. Compound i CDK9 is an excellent and selective CDK9 inhibitor, but its major limitation is the potential toxicity and poor understanding of the underlying mechanism. The PROTAC(proteolysis targeting chimera) degraders of bioactive molecules can significantly induce in vitro and in vivo degradation of their target protein with high selectivity and effectively reduce the dose-limiting toxicity of small molecule drugs. Therefore, we designed and synthesized the bifunctional PROTAC molecules of i CDK9, being used for identifying its previously unknown target and revealing the underlying pharmacological mechanism.The PROTAC bifunctional molecule CD-5 could selectively and significantly degrade CDK9 with low cell toxicity. Therefore, we selected CD-5 as a chemical prober in the SILAC quantitative proteomic analysis, which disclosed that CD-5 could enormously lessen the lysine acetyltransferase KAT6A. Furthermore,KAT6A degradation induced by CD-5 repressed the levels of H3K14Ac and H3K23Ac. Lastly, the streptavidin immunoprecipitation(IP) assay confirmed a direct interaction between KAT6A and i CDK9. Collectively, our results uncover that KAT6A is a potential non-kinase target of i CDK9. Notably, this study also demonstrates that the PROTAC-SILAC strategy is an alternative approach for cellular target identification of bioactive molecules.展开更多
Phosphate residue is a kind of hazardous solid waste and if not properly disposed of, could cause serious environmental contaminations. The abundant iron salt available in phosphate residue can be used to prepare phot...Phosphate residue is a kind of hazardous solid waste and if not properly disposed of, could cause serious environmental contaminations. The abundant iron salt available in phosphate residue can be used to prepare photo-Fenton catalytic reagent for wastewater treatment. In this study, the phosphate residue was effectively purified by a hydrothermal recrystallization method, reaching an iron phosphate purity of 94.2%. The particles of iron phosphate were further processed with ball milling with their average size reduced from 19.4 to 1.6 μm. By hydrothermal crystallization of iron phosphate and thermal decomposition of oxalate precursor, porous iron hydroxy phosphate was prepared. The modified porous iron hydroxy phosphate(m-PIHP) of higher surface area with iron oxalate on its surface can degrade 98.87% of Rhodamine B in 15 min. Cyclic experiment showed that the catalyst still had a good catalytic activity after six cycles( > 40%). The X-ray photoelectron spectroscopy results showed that the iron oxalate complex on the catalyst surface decomposed to produce ferrous ions and accelerated the rate of · OH production. The current work demonstrated that the m-PIHP synthesized from phosphate residue and modified with iron oxalate can be used as an effective dye wastewater treatment agent.展开更多
The existing depth video coding algorithms are generally based on in-loop depth filters, whose performance are unstable and easily affected by the outliers. In this paper, we design a joint weighted sparse representat...The existing depth video coding algorithms are generally based on in-loop depth filters, whose performance are unstable and easily affected by the outliers. In this paper, we design a joint weighted sparse representation-based median filter as the in-loop filter in depth video codec. It constructs depth candidate set which contains relevant neighboring depth pixel based on depth and intensity similarity weighted sparse coding, then the median operation is performed on this set to select a neighboring depth pixel as the result of the filtering. The experimental results indicate that the depth bitrate is reduced by about 9% compared with anchor method. It is confirmed that the proposed method is more effective in reducing the required depth bitrates for a given synthesis quality level.展开更多
基金supported by grants from the National Natural Science Foundation of China(81572393)Key Project of Medical Science and Technology Development Foundation,Nanjing Department of Health(ZKX15020)+1 种基金Jiangsu Province Innovation for Ph.D.Candidate(KYLX_0058)Scientific Research Foundation of Graduate School of Nanjing University(2013CL14)
文摘BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after curative resection remains a major cause of treatment failure and tumor-related death.Patterns of HCC recurrence can be categorized into early recurrence and late recurrence which have different underlying mechanisms.In this study,we investigated if simple inflammation-based clinical markers can distinguish patterns of recurrence after curative resection of HCC.METHODS:A retrospective analysis of 223 patients who underwent curative hepatectomy for HCC was performed.Preoperative inflammation-based factors including neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio,γ-glutamyl transferase/alanine aminotransferase ratio,aspartate aminotransferase/platelet ratio index(APRI) and prognostic nutritional index together with other clinicopathologic parameters were evaluated by univariate analysis and multivariate analysis to identify independent prognostic factors.By combining risk factors,predictive models were established to distinguish populations at high risk of early or late recurrence.RESULTS:Age ≤50 years,resection margin ≤1 cm,TNM stage III-IV,NLR>2.75,APRI>0.23 and positive alpha-fetoprotein were independent adverse prognostic factors for early recurrence.Patients with three or more risk factors were at significant higher risk of early recurrence.APRI>0.23 and positive hepatitis B e antigen(HBe Ag) were independent risk factors of late recurrence,the coexistence of high APRI and positive HBe Ag increased the risk of late recurrence.CONCLUSIONS:Preoperative inflammation-based prognostic factors predict early and late recurrence of HCC after curative resection.Different prognostic factor combinations distinguish high-risk populations of early or late HCC recurrence.
基金supported by grants from the Key Project of Medical Science and Technology Development FoundationNanjing Municipality Health Bureau(ZKX12011)+1 种基金Jiangsu Provincial Innovation Program for Ph D Candidates(KYLX_0058)Scientific Research Foundation of Graduate School of Nanjing University(2013CL14)
文摘BACKGROUND:Early recurrence of hepatocellular carcinoma(HCC)is associated with worse prognosis after liver resection This study aimed to investigate the prognostic value of com mon liver enzyme markers in HCC early recurrence after cu rative hepatectomy and to establish a simple predictive model for HCC early recurrence.
基金supported by grants from the National Natural Science Foundation of China(81572393 and 81602093)the Natural Science Foundation of Jiangsu Province(BK20160118)+1 种基金the Key Projects supported by Medical Science and Technology Develop-ment Foundation,Nanjing Municipality Health Bureau(ZKX15020 and ZKX17022)Fundamental Research Funds for the Central Universities(021414380215,020414380080 and 021414380329)
文摘Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in multiple bioactive processes. However, little is known about the role of Sph K1 in hepatic I/R injury. This study aimed to investigate the effect of Sph K1 knockout on liver I/R injury and to explore underlying mechanisms. Methods: Sph K1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3(STAT3). Western blotting was used to determine the expression of S1 P receptor 1(S1 PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. Results: Sph K1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in Sph K1 knockout mice as demonstrated by attenuated expression of S1 PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1 β, interleukin-6 and tumor necrosis factor-α were also inhibited by Sph K1 genetic deletion. The oxidative stress markers were lower in Sph K1 knockout mice after I/R injury than wild type mice. Conclusions: Knockout of Sph K1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. Sph K1 may be a novel and potent target in clinical practice in I/R-related liver injury.
文摘AIM:To characterize the two components of theory of mind(ToM) in patients with esophageal cancer combined with depression.METHODS:Sixty-five patients with esophageal cancer combined with depression(depressed group) and 62 normal controls(control group) were assessed using reading the mind in the eyes test,faux pas task,verbal fluency test,digit span test and WAIS IQ test.The depressed group was divided into two subgroups including psychotic depressed(PD) group(32 cases) and nonpsychotic depressed(NPD) group(33 cases).The clinical symptoms of patients were assessed using Beck depression inventory version Ⅱ and brief psychiatric reacting scale(BPRS).RESULTS:There was a significant difference between the depressed group and the control group on tasks involving ToM social perceptual components(mind reading:t = 7.39,P < 0.01) and tests involving ToM social cognitive components(faux pas questions:t = 13.75,P < 0.01),respectively.A significant difference was also found among the PD group,the NPD group and the control group on mind reading(F = 32.98,P < 0.01) and faux pas questions(χ 2 = 78.15,P < 0.01),respectively.The PD group and NPD group performed worse than normal group controls both on mind reading and faux pas questions(P < 0.05).The PD group performed significantly worse than the NPD group on tasks involving ToM(mind reading:F = 18.99,P < 0.01;faux pas questions:F = 36.01,P < 0.01).In the depressed group,there was a negative correlation between ToM performances and BPRS total score(mind reading:r =-0.35,P < 0.01;faux pas questions:r =-0.51,P < 0.01),and between ToM performances and hostile suspiciousness factor score(mind reading:r =-0.75,P < 0.01;faux pas questions:r =-0.73,P < 0.01),respectively.CONCLUSION:The two components of ToM are both impaired in patients with esophageal cancer combined with depression.This indicates that there may be an association between ToM deficits and psychotic symptoms in clinical depression.
基金supported by grants from the National Key R&D Program of China (Nos. 2018YFA0107303 and 2020YFA0908100)the National Natural Science Foundation of China (Nos. 81773600and 82102746)+1 种基金the China Postdoctoral Science Foundation (No.2021M690095)the Fundamental Research Funds for the Central Universities (No. 20720180051)。
文摘Cyclin-dependent kinases(CDKs) have become potential targets for treating various diseases, especially cancer. Compound i CDK9 is an excellent and selective CDK9 inhibitor, but its major limitation is the potential toxicity and poor understanding of the underlying mechanism. The PROTAC(proteolysis targeting chimera) degraders of bioactive molecules can significantly induce in vitro and in vivo degradation of their target protein with high selectivity and effectively reduce the dose-limiting toxicity of small molecule drugs. Therefore, we designed and synthesized the bifunctional PROTAC molecules of i CDK9, being used for identifying its previously unknown target and revealing the underlying pharmacological mechanism.The PROTAC bifunctional molecule CD-5 could selectively and significantly degrade CDK9 with low cell toxicity. Therefore, we selected CD-5 as a chemical prober in the SILAC quantitative proteomic analysis, which disclosed that CD-5 could enormously lessen the lysine acetyltransferase KAT6A. Furthermore,KAT6A degradation induced by CD-5 repressed the levels of H3K14Ac and H3K23Ac. Lastly, the streptavidin immunoprecipitation(IP) assay confirmed a direct interaction between KAT6A and i CDK9. Collectively, our results uncover that KAT6A is a potential non-kinase target of i CDK9. Notably, this study also demonstrates that the PROTAC-SILAC strategy is an alternative approach for cellular target identification of bioactive molecules.
基金supported by the Science and Technology Development Foundation of Pudong New Area (No. PKJ2014-Z03)Dawn Program of Shanghai (No. 09SG54 )Material Science and Engineering Key Subject of Shanghai Polytechnic University (No. XXKZD1601)。
文摘Phosphate residue is a kind of hazardous solid waste and if not properly disposed of, could cause serious environmental contaminations. The abundant iron salt available in phosphate residue can be used to prepare photo-Fenton catalytic reagent for wastewater treatment. In this study, the phosphate residue was effectively purified by a hydrothermal recrystallization method, reaching an iron phosphate purity of 94.2%. The particles of iron phosphate were further processed with ball milling with their average size reduced from 19.4 to 1.6 μm. By hydrothermal crystallization of iron phosphate and thermal decomposition of oxalate precursor, porous iron hydroxy phosphate was prepared. The modified porous iron hydroxy phosphate(m-PIHP) of higher surface area with iron oxalate on its surface can degrade 98.87% of Rhodamine B in 15 min. Cyclic experiment showed that the catalyst still had a good catalytic activity after six cycles( > 40%). The X-ray photoelectron spectroscopy results showed that the iron oxalate complex on the catalyst surface decomposed to produce ferrous ions and accelerated the rate of · OH production. The current work demonstrated that the m-PIHP synthesized from phosphate residue and modified with iron oxalate can be used as an effective dye wastewater treatment agent.
基金Supported by the National Natural Science Foundation of China(61462048)
文摘The existing depth video coding algorithms are generally based on in-loop depth filters, whose performance are unstable and easily affected by the outliers. In this paper, we design a joint weighted sparse representation-based median filter as the in-loop filter in depth video codec. It constructs depth candidate set which contains relevant neighboring depth pixel based on depth and intensity similarity weighted sparse coding, then the median operation is performed on this set to select a neighboring depth pixel as the result of the filtering. The experimental results indicate that the depth bitrate is reduced by about 9% compared with anchor method. It is confirmed that the proposed method is more effective in reducing the required depth bitrates for a given synthesis quality level.
