BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recomm...BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.展开更多
Gene therapy offers potentially transformative strategies for major human diseases.However,one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissu...Gene therapy offers potentially transformative strategies for major human diseases.However,one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue.Here,we report a novel virus-like nanoparticle,the bioorthgonal engineered viruslike recombinant biosome(reBiosome),for efficient gene therapies of cancer and inflammatory diseases.The mutant virus-like biosome(mBiosome)is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site,and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry.The results show that the reBiosome exhibits reduced virus-like immunogenicity,prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci(like tumor and arthritic tissue).Furthermore,reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems,respectively.In conclusion,this study develops a universal,safe and efficient platform for gene therapies for cancer and inflammatory diseases.展开更多
The HY-2A satellite,which is equipped with a radar altimeter and was launched on August 16,2011,is the first Chinese marine dynamic environmental monitoring satellite.Extracting ocean tides is one of the important app...The HY-2A satellite,which is equipped with a radar altimeter and was launched on August 16,2011,is the first Chinese marine dynamic environmental monitoring satellite.Extracting ocean tides is one of the important applications of the radar altimeter data.The radar altimeter data of the HY-2A satellite from November 1,2011 to August 16,2014 are used herein to extract global ocean tides.The constants representing the tidal constituents are extracted by HY-2A RA data with harmonic analysis based on the least squares method.Considering tide aliasing issues,the analysis of the alias periods and alias synodic periods of different tidal constituents shows that only the tidal constituents M_(2),N_(2),and K_(2)are retrieved precisely by the HY-2A RA data.The derived tidal constants of the tidal constituents M_(2),N_(2)and K_(2)are compared to those of tidal gauge data and the TPXO tide model results.The comparison between the derived results and the tidal gauge data shows that the RMSEs of the tidal amplitude and phase lag are 9.6 cm and 13.34°,2.4 cm and 10.47°,and 8.1 cm and 14.19°for tidal constituents M_(2),N_(2),and K_(2),respectively.The comparisons of the semidiurnal tides with the TPXO model results show that tidal constituents have good consistency with the TPXO model results.These findings confirm the good performance of HY-2A RA for retrieving semidiurnal tides in the global ocean.展开更多
Purpose:Exploring a dimensionality reduction model that can adeptly eliminate outliers and select the appropriate number of clusters is of profound theoretical and practical importance.Additionally,the interpretabilit...Purpose:Exploring a dimensionality reduction model that can adeptly eliminate outliers and select the appropriate number of clusters is of profound theoretical and practical importance.Additionally,the interpretability of these models presents a persistent challenge.Design/methodology/approach:This paper proposes two innovative dimensionality reduction models based on integer programming(DRMBIP).These models assess compactness through the correlation of each indicator with its class center,while separation is evaluated by the correlation between different class centers.In contrast to DRMBIP-p,the DRMBIP-v considers the threshold parameter as a variable aiming to optimally balances both compactness and separation.Findings:This study,getting data from the Global Health Observatory(GHO),investigates 141 indicators that influence life expectancy.The findings reveal that DRMBIP-p effectively reduces the dimensionality of data,ensuring compactness.It also maintains compatibility with other models.Additionally,DRMBIP-v finds the optimal result,showing exceptional separation.Visualization of the results reveals that all classes have a high compactness.Research limitations:The DRMBIP-p requires the input of the correlation threshold parameter,which plays a pivotal role in the effectiveness of the final dimensionality reduction results.In the DRMBIP-v,modifying the threshold parameter to variable potentially emphasizes either separation or compactness.This necessitates an artificial adjustment to the overflow component within the objective function.Practical implications:The DRMBIP presented in this paper is adept at uncovering the primary geometric structures within high-dimensional indicators.Validated by life expectancy data,this paper demonstrates potential to assist data miners with the reduction of data dimensions.Originality/value:To our knowledge,this is the first time that integer programming has been used to build a dimensionality reduction model with indicator filtering.It not only has applications in life expectancy,but also has obvious advantages in data mining work that requires precise class centers.展开更多
BACKGROUND Umbilical cord(UC)mesenchymal stem cell(MSC)transplantation is a potential therapeutic intervention for atherosclerotic vascular disease.Integrin beta 3(ITGB3)promotes cell migration in several cell types.H...BACKGROUND Umbilical cord(UC)mesenchymal stem cell(MSC)transplantation is a potential therapeutic intervention for atherosclerotic vascular disease.Integrin beta 3(ITGB3)promotes cell migration in several cell types.However,whether ITGBmodified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear.AIM To investigate whether ITGB3-overexpressing MSCs(MSCs^(ITGB3))would exhibit improved homing efficacy in atherosclerosis.METHODS UC MSCs were isolated and expanded.Lentiviral vectors encoding ITGB3 or green fluorescent protein(GFP)as control were transfected into MSCs.Sixty male apolipoprotein E-/-mice were acquired from Beijing Vital River Lab Animal Technology Co.,Ltd and fed with a high-fat diet(HFD)for 12 wk to induce the formation of atherosclerotic lesions.These HFD-fed mice were randomly separated into three clusters.GFP-labeled MSCs(MSCs^(GFP))or MSCs^(ITGB3)were transplanted into the mice intravenously via the tail vein.Immunofluorescence staining,Oil red O staining,histological analyses,western blotting,enzymelinked immunosorbent assay,and quantitative real-time polymerase chain reaction were used for the analyses.RESULTS ITGB3 modified MSCs successfully differentiated into the“osteocyte”and“adipocyte”phenotypes and were characterized by positive expression(>91.3%)of CD29,CD73,and CD105 and negative expression(<1.35%)of CD34 and Human Leukocyte Antigen-DR.In a transwell assay,MSCs^(ITGB3)showed significantly faster migration than MSCsGFP.ITGB3 overexpression had no effects on MSC viability,differentiation,and secretion.Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites.Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCs^(ITGB3),significantly reducing the plaque area.Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSC^(ITGB3)transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro-and anti-inflammatory cytokines.CONCLUSION These results showed that ITGB3 overexpression enhanced the MSC homing ability,providing a potential approach for MSC delivery to plaque sites,thereby optimizing their therapeutic effects.展开更多
At present,methods for treating tertiary oil recovery wastewater via electro-coagulation are still in their early stage of development.In this study,a device for electro-coagulation wastewater treatment was built and ...At present,methods for treating tertiary oil recovery wastewater via electro-coagulation are still in their early stage of development.In this study,a device for electro-coagulation wastewater treatment was built and tested in an oil field.The effects that the initial pH value,electrode type,and connection mode have on the coagulation and separation effect were assessed by measuring the mass fraction and turbidity of oil.The results have shown that when the electro-coagulation method is used,the effectiveness of the treatment can be significantly increased in neutral pH conditions(pH=7),in acidic conditions,and in alkaline conditions.Compared to an Al electrode,the floc that is produced by an Fe electrode is smaller;thus,it does not easily coagulate and settle in a short time.Using the oil removal rate,turbidity removal rate and energy consumption as a basis to assess the performances,the results have demonstrated that the combined aluminum alloy iron composite electrode should be used as electrolytic electrode.展开更多
With the development of deep sequencing and bioinformatics technology, a large number of products produced by abnormal RNA splicing, such as chimeric RNA and chimeric/fusion proteins, have been discovered. Natural chi...With the development of deep sequencing and bioinformatics technology, a large number of products produced by abnormal RNA splicing, such as chimeric RNA and chimeric/fusion proteins, have been discovered. Natural chimeric/fusion genes are new genes formed by natural fusion of two or more independent genes. Chimeric RNAs can be transcribed by natural chimeric genes, and can also be formed by cis-splicing or trans-splicing of two or more precursor mRNAs. Unlike fusion genes, the production of chimeric RNAs does not involve changes in the DNA level of chromosomes. At first, chimeric RNAs were found as tumor markers. With the deepening of research, researchers also found a large number of chimeric RNAs in normal tissues. From the perspective of biological function, chimeric RNAs can play a biological role in regulating the expression of corresponding maternal genes, translating into chimeric proteins, and forming long non-coding RNAs. The objective of the present study focused on the frontiers of chimeric RNA and reviewed its role in health and tumor study to reveal research progress of chimeric RNA and health and provide a new sight of relative disease treatment. The main conclusion of this review is that chimeric RNA may serve as a biomarker for specific tumor diagnose and treatment while its role in normal physiology needs to be revealed.展开更多
基金National Natural Science Foundation of China,No.82170618.
文摘BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.
基金supported by the National Natural Science Foundation of China(Grant No.81874303 and No.82173752 W.L.Lu).
文摘Gene therapy offers potentially transformative strategies for major human diseases.However,one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue.Here,we report a novel virus-like nanoparticle,the bioorthgonal engineered viruslike recombinant biosome(reBiosome),for efficient gene therapies of cancer and inflammatory diseases.The mutant virus-like biosome(mBiosome)is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site,and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry.The results show that the reBiosome exhibits reduced virus-like immunogenicity,prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci(like tumor and arthritic tissue).Furthermore,reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems,respectively.In conclusion,this study develops a universal,safe and efficient platform for gene therapies for cancer and inflammatory diseases.
基金The National Key Research and Development Program of China under contract No.2016YFC1401801.
文摘The HY-2A satellite,which is equipped with a radar altimeter and was launched on August 16,2011,is the first Chinese marine dynamic environmental monitoring satellite.Extracting ocean tides is one of the important applications of the radar altimeter data.The radar altimeter data of the HY-2A satellite from November 1,2011 to August 16,2014 are used herein to extract global ocean tides.The constants representing the tidal constituents are extracted by HY-2A RA data with harmonic analysis based on the least squares method.Considering tide aliasing issues,the analysis of the alias periods and alias synodic periods of different tidal constituents shows that only the tidal constituents M_(2),N_(2),and K_(2)are retrieved precisely by the HY-2A RA data.The derived tidal constants of the tidal constituents M_(2),N_(2)and K_(2)are compared to those of tidal gauge data and the TPXO tide model results.The comparison between the derived results and the tidal gauge data shows that the RMSEs of the tidal amplitude and phase lag are 9.6 cm and 13.34°,2.4 cm and 10.47°,and 8.1 cm and 14.19°for tidal constituents M_(2),N_(2),and K_(2),respectively.The comparisons of the semidiurnal tides with the TPXO model results show that tidal constituents have good consistency with the TPXO model results.These findings confirm the good performance of HY-2A RA for retrieving semidiurnal tides in the global ocean.
基金supported by the National Natural Science Foundation of China (Nos.72371115)the Natural Science Foundation of Jilin,China (No.20230101184JC)。
文摘Purpose:Exploring a dimensionality reduction model that can adeptly eliminate outliers and select the appropriate number of clusters is of profound theoretical and practical importance.Additionally,the interpretability of these models presents a persistent challenge.Design/methodology/approach:This paper proposes two innovative dimensionality reduction models based on integer programming(DRMBIP).These models assess compactness through the correlation of each indicator with its class center,while separation is evaluated by the correlation between different class centers.In contrast to DRMBIP-p,the DRMBIP-v considers the threshold parameter as a variable aiming to optimally balances both compactness and separation.Findings:This study,getting data from the Global Health Observatory(GHO),investigates 141 indicators that influence life expectancy.The findings reveal that DRMBIP-p effectively reduces the dimensionality of data,ensuring compactness.It also maintains compatibility with other models.Additionally,DRMBIP-v finds the optimal result,showing exceptional separation.Visualization of the results reveals that all classes have a high compactness.Research limitations:The DRMBIP-p requires the input of the correlation threshold parameter,which plays a pivotal role in the effectiveness of the final dimensionality reduction results.In the DRMBIP-v,modifying the threshold parameter to variable potentially emphasizes either separation or compactness.This necessitates an artificial adjustment to the overflow component within the objective function.Practical implications:The DRMBIP presented in this paper is adept at uncovering the primary geometric structures within high-dimensional indicators.Validated by life expectancy data,this paper demonstrates potential to assist data miners with the reduction of data dimensions.Originality/value:To our knowledge,this is the first time that integer programming has been used to build a dimensionality reduction model with indicator filtering.It not only has applications in life expectancy,but also has obvious advantages in data mining work that requires precise class centers.
基金National Natural Science Foundation of China,No.82100301Key Science and Technology Research Program of Hebei Provincial Department of Health,No,20221014.
文摘BACKGROUND Umbilical cord(UC)mesenchymal stem cell(MSC)transplantation is a potential therapeutic intervention for atherosclerotic vascular disease.Integrin beta 3(ITGB3)promotes cell migration in several cell types.However,whether ITGBmodified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear.AIM To investigate whether ITGB3-overexpressing MSCs(MSCs^(ITGB3))would exhibit improved homing efficacy in atherosclerosis.METHODS UC MSCs were isolated and expanded.Lentiviral vectors encoding ITGB3 or green fluorescent protein(GFP)as control were transfected into MSCs.Sixty male apolipoprotein E-/-mice were acquired from Beijing Vital River Lab Animal Technology Co.,Ltd and fed with a high-fat diet(HFD)for 12 wk to induce the formation of atherosclerotic lesions.These HFD-fed mice were randomly separated into three clusters.GFP-labeled MSCs(MSCs^(GFP))or MSCs^(ITGB3)were transplanted into the mice intravenously via the tail vein.Immunofluorescence staining,Oil red O staining,histological analyses,western blotting,enzymelinked immunosorbent assay,and quantitative real-time polymerase chain reaction were used for the analyses.RESULTS ITGB3 modified MSCs successfully differentiated into the“osteocyte”and“adipocyte”phenotypes and were characterized by positive expression(>91.3%)of CD29,CD73,and CD105 and negative expression(<1.35%)of CD34 and Human Leukocyte Antigen-DR.In a transwell assay,MSCs^(ITGB3)showed significantly faster migration than MSCsGFP.ITGB3 overexpression had no effects on MSC viability,differentiation,and secretion.Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites.Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCs^(ITGB3),significantly reducing the plaque area.Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSC^(ITGB3)transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro-and anti-inflammatory cytokines.CONCLUSION These results showed that ITGB3 overexpression enhanced the MSC homing ability,providing a potential approach for MSC delivery to plaque sites,thereby optimizing their therapeutic effects.
文摘At present,methods for treating tertiary oil recovery wastewater via electro-coagulation are still in their early stage of development.In this study,a device for electro-coagulation wastewater treatment was built and tested in an oil field.The effects that the initial pH value,electrode type,and connection mode have on the coagulation and separation effect were assessed by measuring the mass fraction and turbidity of oil.The results have shown that when the electro-coagulation method is used,the effectiveness of the treatment can be significantly increased in neutral pH conditions(pH=7),in acidic conditions,and in alkaline conditions.Compared to an Al electrode,the floc that is produced by an Fe electrode is smaller;thus,it does not easily coagulate and settle in a short time.Using the oil removal rate,turbidity removal rate and energy consumption as a basis to assess the performances,the results have demonstrated that the combined aluminum alloy iron composite electrode should be used as electrolytic electrode.
文摘With the development of deep sequencing and bioinformatics technology, a large number of products produced by abnormal RNA splicing, such as chimeric RNA and chimeric/fusion proteins, have been discovered. Natural chimeric/fusion genes are new genes formed by natural fusion of two or more independent genes. Chimeric RNAs can be transcribed by natural chimeric genes, and can also be formed by cis-splicing or trans-splicing of two or more precursor mRNAs. Unlike fusion genes, the production of chimeric RNAs does not involve changes in the DNA level of chromosomes. At first, chimeric RNAs were found as tumor markers. With the deepening of research, researchers also found a large number of chimeric RNAs in normal tissues. From the perspective of biological function, chimeric RNAs can play a biological role in regulating the expression of corresponding maternal genes, translating into chimeric proteins, and forming long non-coding RNAs. The objective of the present study focused on the frontiers of chimeric RNA and reviewed its role in health and tumor study to reveal research progress of chimeric RNA and health and provide a new sight of relative disease treatment. The main conclusion of this review is that chimeric RNA may serve as a biomarker for specific tumor diagnose and treatment while its role in normal physiology needs to be revealed.
