AIM： To study the relationship between Survivin and PTEN expression and lymph node metastasis, depth of invasion and prognosis of gastric cancer patients in China.METHODS： Specimens of gastric cancer tissue were col...AIM： To study the relationship between Survivin and PTEN expression and lymph node metastasis, depth of invasion and prognosis of gastric cancer patients in China.METHODS： Specimens of gastric cancer tissue were collected from the Affiliated Hospital of Jianghan University. All the 140 patients had complete examination data. All lymph nodes were found by the fat-clearing method. The interrupted serial 4-micron sections, routine hematoxylin and eosin staining and immunohistochemical methods were used to detect the lymph node metastases. Gastric cancer tissue microarray was performed to test the expression of Survivin and PTEN （17A） in gastric cancer by immunohistochemical method. All data were processed using X^2 test, Fisher＇s exact test, Kaplan-Meyer Log-rank method and Cox multivariate analysis （SPSS 12.0 software）.RESULTS： One hundred and eighteen specimens were used in our tissue microarray （utilization rate was 82.4%）. A total of 7580 lymph nodes were found. Metastases were found in 90 specimens and 1618 lymph nodes were detected. The positive rate of Survivin and PTEN expression was 52.5% （62/118） and 76.2% （90/118）, respectively. A highly positive correlation was found between Survivin and PTEN expression （X^2=4.17, P=0.04）. Survivin expression was positively correlated with UICC N stage （X^2=8.69, P=0.03） and histological classification （X^2=4.41, P=0.04） by X^2 tests. PTEN expression was positively correlated with depth of invasion （P=0.02） and histological classification （X^2=5.47, P=0.02）. But Survivin and PTEN expressions were not related with prognosis of gastric cancer patients. A significant correlation between lymph node metastasis and prognosis was demonstrated by Cox multivariate analysis （X^2=4.85, P=0.028）.CONCLUSION： Survivin is positively correlated with PTEN expression in gastric cancer and is a molecular marker of lymph node metastasis while PTEN expression is a molecular marker of advanced gastric cancer. UICC N stage is the most important prognostic factor of gastric cancer in China.展开更多
AIM： To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS： Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematic...AIM： To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS： Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three （41%） of the 106 patients were staged as pT1/2, 63 （59%） as pT3/4, 51 （48%） as pNo, and 55 （52%） as pN1. The study population included 59 （56%） patients exhibiting G1/2, and 47 （44%） patients with G3 tumors. Patients received no adjuvant chemoor radiation therapy and were followed up for a median of 12 （range： 3.5 to 139） mo.RESULTS： Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as ＂tumor free＂ by conventional histopathology in 73 （69%） out of the 106 patients. Twenty-nine （57%） of 51 patients staged histopathologically as pNo had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free （relative risk 2.92, P = 0.005） and overall （relative risk 2.49, P = 0.009） survival. CONCLUSION： The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports stratification of patients with may help to improve risk pancreatic cancer.展开更多
Liver carcinoma has been one of themalignant tumors of common occurrenceand high mortality in China,and cases ofmiddle and late period are very difficult tobe treated.However,the present authorshave improved the condi...Liver carcinoma has been one of themalignant tumors of common occurrenceand high mortality in China,and cases ofmiddle and late period are very difficult tobe treated.However,the present authorshave improved the condition of patientswith liver carcinoma and prolonged theirsurvival period by a topical adhesive methodas the chief therapeutic means.The展开更多
Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC...Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.展开更多
Eomesodermin(Eomes)is a critical factor in the development of natural killer(NK)cells,but its precise role in temporal and spatial coordination during this process remains unclear.Our study revealed that Eomes plays d...Eomesodermin(Eomes)is a critical factor in the development of natural killer(NK)cells,but its precise role in temporal and spatial coordination during this process remains unclear.Our study revealed that Eomes plays distinct roles during the early and late stages of NK cell development.Specifically,the early deletion of Eomes via the CD122-Cre transgene resulted in significant blockade at the progenitor stage due to the downregulation of KLF2,another important transcription factor.ChIP-seq revealed direct binding of Eomes to the conserved noncoding sequence(CNS)of Klf2.Utilizing the CHimeric IMmune Editing(CHIME)technique,we found that deletion of the CNS region of Klf2 via CRISPRi led to a reduction in the NK cell population and developmental arrest.Moreover,constitutive activation of this specific CNS region through CRISPRa significantly reversed the severe defects in NK cell development caused by Eomes deficiency.Conversely,Ncr1-Cre-mediated terminal deletion of Eomes expedited the transition of NK cell subsets from the CD27+CD11b+phenotype to the CD27−CD11b+phenotype.Late-stage deficiency of Eomes led to a significant increase in T-bet expression,which subsequently increased the expression of the transcription factor Zeb2.Genetic deletion of one allele of Tbx21,encoding T-bet,effectively reversed the aberrant differentiation of Eomes-deficient NK cells.In summary,we utilized two innovative genetic models to elucidate the intricate mechanisms underlying Eomes-mediated NK cell commitment and differentiation.展开更多
The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impai...The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stressevoked tumor susceptibility, and the stress hormone glucocorticoid(GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor(low-density lipoprotein receptor-related protein-1, LRP1) and the "don’t eat me" signal receptor(signal regulatory protein alpha, SIRPa). Further analysis revealed that GC led to a direct, glucocorticoid receptor(GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevatedgene level of SIRPa by down-regulating mi RNA-4695-3 p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPa axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPa axis may serve as a potential therapeutic strategy for tumor treatment.展开更多
Objective： To characterize the relationship between STAT1 and Survivin expression, and the relationship between them and lymph node metastasis, depth of invasion and prognosis in full lymph node examined gastric canc...Objective： To characterize the relationship between STAT1 and Survivin expression, and the relationship between them and lymph node metastasis, depth of invasion and prognosis in full lymph node examined gastric cancer patients of China. Methods： Specimens of curative dissection between 1988 and 2003 were collected from the affiliated hospital of Jianghan University. All 140 patients had complete examination data. All lymph nodes were found by clearing fat method. The interrupted serial 4 μm sections, routine hematoxylin and eosin staining and immunohistochemical methods were used to detect the lymph node metastases. Gastric cancer tissue microarray was formed and the expression of survivin and STAT1 in gastric cancer was detected by immunohistochemical method. All data were processed using Spearman rank correlation analysis, Kaplan-Meyer Log-rank method and Cox multivariate analysis （SPSS 12.0 software）. Results： Among 140 gastric cancer tissue microarrays constructed, 110 could be used （utilization rate was 78.6%）. 7079 lymph nodes were found in 110 cases （64.4/case）. Metastases were found in 89 cases and 1679 lymph nodes. Positive expression rate of survivin and STAT1 was 52.7% （58/110） and 40% （44/110） respectively. There was a significant negative correlation between STAT1 expression and survivin expression （r=-0.19, P=0.04）. STAT1 expression had a negative correlation with depth of invasion （r=0.21, P=0.04）. Survivin expression had a negative correlation with UICC N stage （r=-0.24, P=0.01） and histological classification （r=-0.21, P=0.03） by Spearman rank correlation analysis. But survivin and STAT1 expression was not related with prognosis. A significant correlation between lymph node metastasis and prognosis was demonstrated by Cox multivariate analysis （X^2=4.85, P=0.028）. Conclusion： STAT1 has a negative correlation with survivin expression in gastric cancer. Both of them have no correlation with prognosis in gastric cancer. STAT1 expression can be a molecular marker to predict advanced gastric cancer and survivin a molecular marker of lymph node metastasis in gastric cancer. UICC N stage is the most important prognostic factor in gastric caner in China.展开更多
AIM: To determine the growth rule and tendency of retinoblastoma (Rb) literature, and to provide the basis for research of diagnosis, treatment and on Rb. METHODS: Bibliometric analyses were carried out on Rb literatu...AIM: To determine the growth rule and tendency of retinoblastoma (Rb) literature, and to provide the basis for research of diagnosis, treatment and on Rb. METHODS: Bibliometric analyses were carried out on Rb literatures which contain the descriptors of Rb in their titles or texts from 1929 to 2010 in PubMed database (www.ncbi.nlm. nih.gov/Pubmed). The biomedical journals referring to Rb by using bibliometric indicators were calculated. The principal bibliometric indicators, i.e, Price's and Bradford's laws to the increase or distribution of scientific literature, the participation index of languages and the journals were applied. By means of manual coding, Rb documents were classified according to documents studied and to statistical analysis. RESULTS: During 1929-2010, there were 16162 literatures in the PubMed database including the word Rb. According to the literature type, it includes Review (n=2026), Randomized Controlled Trial (n = 7), Practice guideline (n = 3), meta-analysis (n = 4), letter (n = 215), editorial (n = 98), clinical trial (n = 115) and others (n = 13694). By the statistical analysis, its equation is near power index (y = 3.0477 x(2.6088), R(2) = 0.9666). From 1929 to 2010, Rb literatures in English were primarily dominant (90.71%) and the amount of the literature in Chinese ranked the fourth (1.37%). By searching PubMed, 1420 (8.8%) literatures covered were from 41 of 48 ophthalmological, and 406 (2.5%) literatures from 44 of 86 pediatrics journals that correlated with retinoblastoma (SCI-indexed). The data showed that the literatures of Rb were gradually increasing year by year and were approximate near power index during 1929-2010, and the document publishes published mainly in ophthalmological journals, and in English (90.71%), and showing that the study on Rb is a popular subject in the last half century. CONCLUSION: The literatures of Rb are gradually increasing, mainly English in ophthalmologic journals.展开更多
Dear editor,Primary pulmonary artery sarcoma(PPAS)is an uncommon neoplastic disease that can masquerade as pulmonary thromboembolism(PE).The nonspecific symptoms of this condition generally vary from mild dyspnea to s...Dear editor,Primary pulmonary artery sarcoma(PPAS)is an uncommon neoplastic disease that can masquerade as pulmonary thromboembolism(PE).The nonspecific symptoms of this condition generally vary from mild dyspnea to severe respiratory distress and right heart failure.A male patient is discussed in this report who presented with fever,cough,and shortness of breath.An enhanced contrast computed tomography(EC-CT)scan revealed an intraluminal hypoattenuated area originating from the main pulmonary artery and extending further into the left pulmonary artery and the bilateral lobar pulmonary arteries,evidence for multiple lesions in both lungs.The spindle cell tumor,positive for smooth muscle actin,was pathologically diagnosed as PPAS using a needle biopsy of the lower lobe of the left lung.展开更多
Background Nitric oxide （NO） is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm （AAA） formation is unclear. The aim of th...Background Nitric oxide （NO） is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm （AAA） formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase （iNOS）, and their possible role in AAA. Methods A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells （SMCs）. Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-HaenszelX^2 test and Kendall＇ Tau correlation. Results Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls （P〈0.05） and the patients with occlusive arteries （P〈0.05）. iNOS protein and media NOx （nitrite＋nitrate） also increased in cultured SMCs from human AAA （n=4, P〈0.05）, while plasma NOx decreased in patients with AAA （n=25） compared to the healthy controls （n=20）. There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall （Kendall coefficient=0.5032, P=0.0029） Conclusions SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.展开更多
Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mort...Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung inflammation.Corticosterone(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed mice.We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice.Mechanistically,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in vitro.Furthermore,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this process.Gain-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS.Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.展开更多
Colonization is believed a rate-limiting step of metastasis cascade.However,its underlying mechanism is not well understood.Uveal melanoma(UM),which is featured with single organ liver metastasis,may provide a simplif...Colonization is believed a rate-limiting step of metastasis cascade.However,its underlying mechanism is not well understood.Uveal melanoma(UM),which is featured with single organ liver metastasis,may provide a simplified model for realizing the complicated colonization process.Because DDR1 was identified to be overexpressed in UM cell lines and specimens,and abundant pathological deposition of extracellular matrix collagen,a type of DDR1 ligand,was noted in the microenvironment of liver in metastatic patients with UM,we postulated the hypothesis that DDR1 and its ligand might ignite the interaction between UM cells and their surrounding niche of liver thereby conferring strengthened survival,proliferation,sternness and eventually promoting metastatic colonization in liver.We tested this hypothesis and found that DDR1 promoted these malignant cellular phenotypes and facilitated metastatic colonization of UM in liver.Mechanistically,UM cells secreted TGF-β1 which induced quiescent hepatic stellate cells(qHSCs)into activated HSCs(aHSCs)which secreted collagen type I.Such a remodeling of extracellular matrix,in turn,activated DDR1,strengthening survival through upregulating STAT3-dependent Mcl-1 expression,enhancing sternness via upregulating STAT3-dependent S0X2,and promoting clonogenicity in cancer cells.Targeting DDR1 by using 7rh,a specific inhibitor,repressed proliferation and survival in vitro and in vivo outgrowth.More importantly,targeting cancer cells by pharmacological inactivation of DDR1 or targeting microenvironmental TGF-β1-collagen I loop exhibited a prominent anti-metastasis effect in mice.In conclusion,targeting DDR1 signaling and TGF-β1 signaling may be a novel approach to diminish hepatic metastasis in UM.展开更多
Three new chromone derivatives, phomochromenones A-C （1-3）, and one known chaetocyclinone B （4） were obtained from the cultures ofPhomopsis sp. HNY29-2B isolated from the mangrove Acanthus ilicifolius Linn., which...Three new chromone derivatives, phomochromenones A-C （1-3）, and one known chaetocyclinone B （4） were obtained from the cultures ofPhomopsis sp. HNY29-2B isolated from the mangrove Acanthus ilicifolius Linn., which was collected from the South China Sea. Their structures were determined by the analysis of 1D NMR and 2D NMR as well as mass spectroscopic data. The absolute configurations of I and 2 were assigned by quantum chemi- cal calculations of the electronic circular dichroism （ECD） spectra. Compound 3 is the third example of alkaloids possessing the unique chromeno [3,2-c] pyridine nucleus. In the bioactivity assay, compound 4 showed cytotoxicity against human prostate cancer cell lines （PC-3 and DU145 cells） with the IC50 values of 8.13 and 3.59 μmol/L, respectively.展开更多
基金Supported by The Key Science and Technolog Fund of Wuhan,No.30224801Chenguang Youth Fund of Wuhan,No.20045006071-7
文摘AIM： To study the relationship between Survivin and PTEN expression and lymph node metastasis, depth of invasion and prognosis of gastric cancer patients in China.METHODS： Specimens of gastric cancer tissue were collected from the Affiliated Hospital of Jianghan University. All the 140 patients had complete examination data. All lymph nodes were found by the fat-clearing method. The interrupted serial 4-micron sections, routine hematoxylin and eosin staining and immunohistochemical methods were used to detect the lymph node metastases. Gastric cancer tissue microarray was performed to test the expression of Survivin and PTEN （17A） in gastric cancer by immunohistochemical method. All data were processed using X^2 test, Fisher＇s exact test, Kaplan-Meyer Log-rank method and Cox multivariate analysis （SPSS 12.0 software）.RESULTS： One hundred and eighteen specimens were used in our tissue microarray （utilization rate was 82.4%）. A total of 7580 lymph nodes were found. Metastases were found in 90 specimens and 1618 lymph nodes were detected. The positive rate of Survivin and PTEN expression was 52.5% （62/118） and 76.2% （90/118）, respectively. A highly positive correlation was found between Survivin and PTEN expression （X^2=4.17, P=0.04）. Survivin expression was positively correlated with UICC N stage （X^2=8.69, P=0.03） and histological classification （X^2=4.41, P=0.04） by X^2 tests. PTEN expression was positively correlated with depth of invasion （P=0.02） and histological classification （X^2=5.47, P=0.02）. But Survivin and PTEN expressions were not related with prognosis of gastric cancer patients. A significant correlation between lymph node metastasis and prognosis was demonstrated by Cox multivariate analysis （X^2=4.85, P=0.028）.CONCLUSION： Survivin is positively correlated with PTEN expression in gastric cancer and is a molecular marker of lymph node metastasis while PTEN expression is a molecular marker of advanced gastric cancer. UICC N stage is the most important prognostic factor of gastric cancer in China.
基金Supported by the "Hamburger Krebsgesellschaft e. V."(06-04-2004) , the Roggenbuck-Stiftung, Hamburg (05-07-2004), and the Deutsche Forschungsgemeinschaft, Bonn, Germany
文摘AIM： To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS： Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three （41%） of the 106 patients were staged as pT1/2, 63 （59%） as pT3/4, 51 （48%） as pNo, and 55 （52%） as pN1. The study population included 59 （56%） patients exhibiting G1/2, and 47 （44%） patients with G3 tumors. Patients received no adjuvant chemoor radiation therapy and were followed up for a median of 12 （range： 3.5 to 139） mo.RESULTS： Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as ＂tumor free＂ by conventional histopathology in 73 （69%） out of the 106 patients. Twenty-nine （57%） of 51 patients staged histopathologically as pNo had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free （relative risk 2.92, P = 0.005） and overall （relative risk 2.49, P = 0.009） survival. CONCLUSION： The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports stratification of patients with may help to improve risk pancreatic cancer.
文摘Liver carcinoma has been one of themalignant tumors of common occurrenceand high mortality in China,and cases ofmiddle and late period are very difficult tobe treated.However,the present authorshave improved the condition of patientswith liver carcinoma and prolonged theirsurvival period by a topical adhesive methodas the chief therapeutic means.The
基金supported by the grants from the Beijing Hope Run Special Fund(#LC2012YF44)National Natural Science Foundation of China(No.81402740)+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education(No.20131106120014)The National Health and Family Planning Committee of P.R.China
文摘Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.
基金supported by the Natural Science Foundation of China(32330034,31830027,31821003,82271754 and 82071737)the National Key Research&Developmental Program of China(2022YFF0710602)+1 种基金the Excellent Research and Innovation Team in Anhui Province’s Universities(2023AH010085)the China Postdoctoral Science Foundation(2020M670296 and 2021T140372).
文摘Eomesodermin(Eomes)is a critical factor in the development of natural killer(NK)cells,but its precise role in temporal and spatial coordination during this process remains unclear.Our study revealed that Eomes plays distinct roles during the early and late stages of NK cell development.Specifically,the early deletion of Eomes via the CD122-Cre transgene resulted in significant blockade at the progenitor stage due to the downregulation of KLF2,another important transcription factor.ChIP-seq revealed direct binding of Eomes to the conserved noncoding sequence(CNS)of Klf2.Utilizing the CHimeric IMmune Editing(CHIME)technique,we found that deletion of the CNS region of Klf2 via CRISPRi led to a reduction in the NK cell population and developmental arrest.Moreover,constitutive activation of this specific CNS region through CRISPRa significantly reversed the severe defects in NK cell development caused by Eomes deficiency.Conversely,Ncr1-Cre-mediated terminal deletion of Eomes expedited the transition of NK cell subsets from the CD27+CD11b+phenotype to the CD27−CD11b+phenotype.Late-stage deficiency of Eomes led to a significant increase in T-bet expression,which subsequently increased the expression of the transcription factor Zeb2.Genetic deletion of one allele of Tbx21,encoding T-bet,effectively reversed the aberrant differentiation of Eomes-deficient NK cells.In summary,we utilized two innovative genetic models to elucidate the intricate mechanisms underlying Eomes-mediated NK cell commitment and differentiation.
基金supported,in part,by National Natural Science Foundation of China(grant numbers 81673709,82004231,U1801284 and 81873209)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(grant number 2017BT01Y036,China)and GDUPS(2019,China)+5 种基金Guangdong Science and Technology Foundation for Distinguished Young Scholars(grant number 2017A030306004,China)Science and Technology Program of Guangzhou(grant numbers 201903010062 and 202102010116,China)Fellowship of China Postdoctoral Science Foundation(grant number 2020M683204,China)Guangdong Basic and Applied Basic Research Fund(grant number 2020A1515110388,China)Fundamental Research Funds for the Central Universities(grant number 21620448,China)support of K.C.Wong Education Foundation。
文摘The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stressevoked tumor susceptibility, and the stress hormone glucocorticoid(GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor(low-density lipoprotein receptor-related protein-1, LRP1) and the "don’t eat me" signal receptor(signal regulatory protein alpha, SIRPa). Further analysis revealed that GC led to a direct, glucocorticoid receptor(GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevatedgene level of SIRPa by down-regulating mi RNA-4695-3 p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPa axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPa axis may serve as a potential therapeutic strategy for tumor treatment.
文摘Objective： To characterize the relationship between STAT1 and Survivin expression, and the relationship between them and lymph node metastasis, depth of invasion and prognosis in full lymph node examined gastric cancer patients of China. Methods： Specimens of curative dissection between 1988 and 2003 were collected from the affiliated hospital of Jianghan University. All 140 patients had complete examination data. All lymph nodes were found by clearing fat method. The interrupted serial 4 μm sections, routine hematoxylin and eosin staining and immunohistochemical methods were used to detect the lymph node metastases. Gastric cancer tissue microarray was formed and the expression of survivin and STAT1 in gastric cancer was detected by immunohistochemical method. All data were processed using Spearman rank correlation analysis, Kaplan-Meyer Log-rank method and Cox multivariate analysis （SPSS 12.0 software）. Results： Among 140 gastric cancer tissue microarrays constructed, 110 could be used （utilization rate was 78.6%）. 7079 lymph nodes were found in 110 cases （64.4/case）. Metastases were found in 89 cases and 1679 lymph nodes. Positive expression rate of survivin and STAT1 was 52.7% （58/110） and 40% （44/110） respectively. There was a significant negative correlation between STAT1 expression and survivin expression （r=-0.19, P=0.04）. STAT1 expression had a negative correlation with depth of invasion （r=0.21, P=0.04）. Survivin expression had a negative correlation with UICC N stage （r=-0.24, P=0.01） and histological classification （r=-0.21, P=0.03） by Spearman rank correlation analysis. But survivin and STAT1 expression was not related with prognosis. A significant correlation between lymph node metastasis and prognosis was demonstrated by Cox multivariate analysis （X^2=4.85, P=0.028）. Conclusion： STAT1 has a negative correlation with survivin expression in gastric cancer. Both of them have no correlation with prognosis in gastric cancer. STAT1 expression can be a molecular marker to predict advanced gastric cancer and survivin a molecular marker of lymph node metastasis in gastric cancer. UICC N stage is the most important prognostic factor in gastric caner in China.
基金National Natural Science Foundation of China (No. 39580683)
文摘AIM: To determine the growth rule and tendency of retinoblastoma (Rb) literature, and to provide the basis for research of diagnosis, treatment and on Rb. METHODS: Bibliometric analyses were carried out on Rb literatures which contain the descriptors of Rb in their titles or texts from 1929 to 2010 in PubMed database (www.ncbi.nlm. nih.gov/Pubmed). The biomedical journals referring to Rb by using bibliometric indicators were calculated. The principal bibliometric indicators, i.e, Price's and Bradford's laws to the increase or distribution of scientific literature, the participation index of languages and the journals were applied. By means of manual coding, Rb documents were classified according to documents studied and to statistical analysis. RESULTS: During 1929-2010, there were 16162 literatures in the PubMed database including the word Rb. According to the literature type, it includes Review (n=2026), Randomized Controlled Trial (n = 7), Practice guideline (n = 3), meta-analysis (n = 4), letter (n = 215), editorial (n = 98), clinical trial (n = 115) and others (n = 13694). By the statistical analysis, its equation is near power index (y = 3.0477 x(2.6088), R(2) = 0.9666). From 1929 to 2010, Rb literatures in English were primarily dominant (90.71%) and the amount of the literature in Chinese ranked the fourth (1.37%). By searching PubMed, 1420 (8.8%) literatures covered were from 41 of 48 ophthalmological, and 406 (2.5%) literatures from 44 of 86 pediatrics journals that correlated with retinoblastoma (SCI-indexed). The data showed that the literatures of Rb were gradually increasing year by year and were approximate near power index during 1929-2010, and the document publishes published mainly in ophthalmological journals, and in English (90.71%), and showing that the study on Rb is a popular subject in the last half century. CONCLUSION: The literatures of Rb are gradually increasing, mainly English in ophthalmologic journals.
文摘Dear editor,Primary pulmonary artery sarcoma(PPAS)is an uncommon neoplastic disease that can masquerade as pulmonary thromboembolism(PE).The nonspecific symptoms of this condition generally vary from mild dyspnea to severe respiratory distress and right heart failure.A male patient is discussed in this report who presented with fever,cough,and shortness of breath.An enhanced contrast computed tomography(EC-CT)scan revealed an intraluminal hypoattenuated area originating from the main pulmonary artery and extending further into the left pulmonary artery and the bilateral lobar pulmonary arteries,evidence for multiple lesions in both lungs.The spindle cell tumor,positive for smooth muscle actin,was pathologically diagnosed as PPAS using a needle biopsy of the lower lobe of the left lung.
基金This study was supported by a grant from Clinical Medical Center of Vascular Surgery in Shanghai (NO. ZX03B1).
文摘Background Nitric oxide （NO） is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm （AAA） formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase （iNOS）, and their possible role in AAA. Methods A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells （SMCs）. Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-HaenszelX^2 test and Kendall＇ Tau correlation. Results Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls （P〈0.05） and the patients with occlusive arteries （P〈0.05）. iNOS protein and media NOx （nitrite＋nitrate） also increased in cultured SMCs from human AAA （n=4, P〈0.05）, while plasma NOx decreased in patients with AAA （n=25） compared to the healthy controls （n=20）. There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall （Kendall coefficient=0.5032, P=0.0029） Conclusions SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.
基金supported,in part,by Natural Science Foundation of China(grant numbers 81622050,81573675,U1801284,81673709,81873209)National Key Research and Development Program of China(grant number 2017YFC1700404)+4 种基金the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(grant number 2017BT01Y036)and GDUPS(2019)the Guangdong Science and Technology Foundation for Distinguished Young Scholars(grant number 2017A030306004)the Youth Top-notch Talent Support Program of Guangdong Province(2016TQ03R586)the Program of Hong Kong Scholar(XJ2016017)the Science and Technology Program of Guangzhou(grant number 201903010062).
文摘Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung inflammation.Corticosterone(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed mice.We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice.Mechanistically,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in vitro.Furthermore,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this process.Gain-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS.Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.
基金supported by National Key Research and Development Program of China(2020YFA0509400 to J.Pan)Natural Science Foundation of China(Key Program Project 81930101 to J.Pan,Youth Project 82003797 to W.D.)the Research Foundation of Guangzhou Municipal Science and Technology Bureau(Key Program project 201904020003 to J.Pan).
文摘Colonization is believed a rate-limiting step of metastasis cascade.However,its underlying mechanism is not well understood.Uveal melanoma(UM),which is featured with single organ liver metastasis,may provide a simplified model for realizing the complicated colonization process.Because DDR1 was identified to be overexpressed in UM cell lines and specimens,and abundant pathological deposition of extracellular matrix collagen,a type of DDR1 ligand,was noted in the microenvironment of liver in metastatic patients with UM,we postulated the hypothesis that DDR1 and its ligand might ignite the interaction between UM cells and their surrounding niche of liver thereby conferring strengthened survival,proliferation,sternness and eventually promoting metastatic colonization in liver.We tested this hypothesis and found that DDR1 promoted these malignant cellular phenotypes and facilitated metastatic colonization of UM in liver.Mechanistically,UM cells secreted TGF-β1 which induced quiescent hepatic stellate cells(qHSCs)into activated HSCs(aHSCs)which secreted collagen type I.Such a remodeling of extracellular matrix,in turn,activated DDR1,strengthening survival through upregulating STAT3-dependent Mcl-1 expression,enhancing sternness via upregulating STAT3-dependent S0X2,and promoting clonogenicity in cancer cells.Targeting DDR1 by using 7rh,a specific inhibitor,repressed proliferation and survival in vitro and in vivo outgrowth.More importantly,targeting cancer cells by pharmacological inactivation of DDR1 or targeting microenvironmental TGF-β1-collagen I loop exhibited a prominent anti-metastasis effect in mice.In conclusion,targeting DDR1 signaling and TGF-β1 signaling may be a novel approach to diminish hepatic metastasis in UM.
基金Supporting information for this article is available on the WWW under http：//dx.doi.org/10.1002/cjoc.201700375 or from the author.Acknowledgement We thank the National Natural Science Foundation of China （Nos. 21472251, 41276146）, the Key Project of Natural Science Foundation of Guangdong Province （No. 2016A030311026）, the Science ＆ Technology Plan Project of Guangdong Province of China （Nos. 2013B021100011, 2016A040403091）, the Special Financial Fund of Innovative Development of Marine Economic Demonstration Project （No. GD2012-D01- 001）, the China＇s Marine Commonweal Research Project （No. 201305017）, the Guangzhou Project of Science ＆ Technology Planning （No. 201300000062）, the Fundamental Research Funds for the Central Universities （No. 141gjc16） and the Supercomputing Center of Chinese Academy of Sciences （SCCAS） for generous support.
文摘Three new chromone derivatives, phomochromenones A-C （1-3）, and one known chaetocyclinone B （4） were obtained from the cultures ofPhomopsis sp. HNY29-2B isolated from the mangrove Acanthus ilicifolius Linn., which was collected from the South China Sea. Their structures were determined by the analysis of 1D NMR and 2D NMR as well as mass spectroscopic data. The absolute configurations of I and 2 were assigned by quantum chemi- cal calculations of the electronic circular dichroism （ECD） spectra. Compound 3 is the third example of alkaloids possessing the unique chromeno [3,2-c] pyridine nucleus. In the bioactivity assay, compound 4 showed cytotoxicity against human prostate cancer cell lines （PC-3 and DU145 cells） with the IC50 values of 8.13 and 3.59 μmol/L, respectively.
