Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrat...Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.展开更多
Objective:Hepatocellular carcinoma(HCC)is the most common pathological subtype of primary liver cancer and is associated with high incidence and mortality.External beam radiation therapy(EBRT)is a widely used local tr...Objective:Hepatocellular carcinoma(HCC)is the most common pathological subtype of primary liver cancer and is associated with high incidence and mortality.External beam radiation therapy(EBRT)is a widely used local treatment modality for HCC across different disease stages.In the era of precision radiotherapy,standardized safety evaluation indicators for HCC radiotherapy remain lacking.Normal liver tissue surrounding the tumor may lose hepatic function after high-dose irradiation.In this study,remnant functional liver volume(RFLV)was defined as the volume of liver tissue that retains normal function after irradiation,and the residual remnant functional liver volume after x Gy irradiation(rRFLV_(x))was defined as the absolute liver volume receiving less than a given dose threshold(x Gy),and plans to explore the performance of rRFLV_(x) as a radiotherapy safety dose indicator based on real-world data,as well as to explore the safety and efficacy of EBRT in HCC.Methods:A total of 113 HCC patients who received stereotactic body radiotherapy(a SBRT group,n=35)or intensity-modulated radiation therapy(a IMRT group,n=78)for liver lesions at the Third Xiangya Hospital of Central South University between 2015 and 2023 were prospectively collected and selected.The occurrence of radiation-induced liver diseases(RILDs)was recorded.Dosimetric parameters potentially associated with RILDs were analyzed using binary logistic regression with Hosmer-Lemeshow test,mainly including mean liver dose(MLD),remnant liver volume(RLV),standard liver volume(SLV),and rRFLV_(x).Radiotherapy-related hepatitis virus reactivation and other radiotherapy-related toxicities were also observed.Progression-free survival(PFS)and overall survival(OS)were used to evaluate the efficacy of EBRT in HCC.Results:Among the 113 HCC patients,12 were diagnosed with RILDs,including 11 in the IMRT group and only 1 in the SBRT group.Binary logistic regression with Hosmer-Lemeshow test results suggested that rRFLV_(25),rRFLV_(20),rRFLV_(15),rRFLV_(25)/SLV,rRFLV_(20)/SLV,and rRFLV_(15)/SLV were significantly associated with the occurrence of RILDs in HCC patients in the IMRT group(all P<0.05),while MLD and RLV were not associated with the occurrence of RILDs(P=0.88).One patient without regular anti-hepatitis viral treatment was diagnosed with radiotherapy-related HBV clinical reactivation,and one patient was diagnosed with immunotherapy-related HBV clinical reactivation.The median PFS was 5.6 months in the IMRT group and 16.4 months in the SBRT group,and the best local control rates were 98.6%and 100.0%,respectively.The median OS was 12.2 months in the IMRT group and 33.5 months in the SBRT group.The 6-month,1-year,and 2-year OS rates in the IMRT group were 77.1%,52.6%,and 18.6%,respectively.The 1-year,2-year,3-year,4-year,and 5-year OS rates in the SBRT group were 86.1%,61.7%,39.2%,25.7%,and 18.3%,respectively.Conclusion:EBRT is safe and effective for HCC patients at different stages.Compared with MLD and RLV,rRFLV_(x) and rRFLV_(x)/SLV may be more reliable for evaluating the occurrence of RILDs after IMRT treatment.For patients with hepatitis background,concurrent antiviral therapy during radiotherapy is relatively safe,but serum viral load should be closely monitored.Further research is needed to explore the efficacy and safety of radiotherapy combined with targeted and immunotherapy.展开更多
OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,tradit...OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The primary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were laboratory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic regressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ^(2)=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital preparation group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.展开更多
Thermally activated delayed fluorescence(TADF)molecules have outstanding potential for applications in organic light-emitting diodes(OLEDs).Due to the lack of systematic studies on the correlation between molecular st...Thermally activated delayed fluorescence(TADF)molecules have outstanding potential for applications in organic light-emitting diodes(OLEDs).Due to the lack of systematic studies on the correlation between molecular structure and luminescence properties,TADF molecules are far from meeting the needs of practical applications in terms of variety and number.In this paper,three twisted TADF molecules are studied and their photophysical properties are theoretically predicted based on the thermal vibrational correlation function method combined with multiscale calculations.The results show that all the molecules exhibit fast reverse intersystem crossing(RISC)rates(kRISC),predicting their TADF luminescence properties.In addition,the binding of DHPAzSi as the donor unit with different acceptors can change the dihedral angle between the ground and excited states,and the planarity of the acceptors is positively correlated with the reorganization energy,a property that has a strong influence on the non-radiative process.Furthermore,a decrease in the energy of the molecular charge transfer state and an increase in the kRISC were observed in the films.This study not only provides a reliable explanation for the observed experimental results,but also offers valuable insights that can guide the design of future TADF molecules.展开更多
Hanyu Xu 1,Xuedan Song 1,*,Qing Zhang 1,Chang Yu 1,Jieshan Qiu 1,2,*1 Liaoning Key Lab for Energy Materials and Chemical Engineering,State Key Laboratory of Fine Chemicals,School of Chemical Engineering,Dalian Univers...Hanyu Xu 1,Xuedan Song 1,*,Qing Zhang 1,Chang Yu 1,Jieshan Qiu 1,2,*1 Liaoning Key Lab for Energy Materials and Chemical Engineering,State Key Laboratory of Fine Chemicals,School of Chemical Engineering,Dalian University of Technology,Dalian 116024,Liaoning Province,China.展开更多
中国糖尿病患病率不断攀升,患者超2.33亿,然而,针对心血管疾病和癌症等糖尿病并发症的本土研究缺失。中国心血管代谢与恶性肿瘤队列研究[China Cardiometabolic Disease and Cancer Cohort(4C)Study](基线调查于2011—2012年开展,最新...中国糖尿病患病率不断攀升,患者超2.33亿,然而,针对心血管疾病和癌症等糖尿病并发症的本土研究缺失。中国心血管代谢与恶性肿瘤队列研究[China Cardiometabolic Disease and Cancer Cohort(4C)Study](基线调查于2011—2012年开展,最新随访至2024年)首次系统揭示中国糖尿病患者多种糖尿病并发症结局规律,填补循证空白。本文综述了4C研究的背景、研究方法、研究结果、学术影响和争议,指出了未来的挑战和策略。展开更多
基金supported by the Natural Science Foundation of Hunan Province (2022JJ30987)the Key Research and Development Project of Hunan Province (2024JK2107),China。
文摘Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.
基金supported by the National Natural Science Foundation(81872473)the Chen Xiaoping Foundation for the Development of Science and Technology of Hubei Province(CXPJJH12000001-2020216)the Wu Jieping Medical Foundation(320.6750.19094-30),China。
文摘Objective:Hepatocellular carcinoma(HCC)is the most common pathological subtype of primary liver cancer and is associated with high incidence and mortality.External beam radiation therapy(EBRT)is a widely used local treatment modality for HCC across different disease stages.In the era of precision radiotherapy,standardized safety evaluation indicators for HCC radiotherapy remain lacking.Normal liver tissue surrounding the tumor may lose hepatic function after high-dose irradiation.In this study,remnant functional liver volume(RFLV)was defined as the volume of liver tissue that retains normal function after irradiation,and the residual remnant functional liver volume after x Gy irradiation(rRFLV_(x))was defined as the absolute liver volume receiving less than a given dose threshold(x Gy),and plans to explore the performance of rRFLV_(x) as a radiotherapy safety dose indicator based on real-world data,as well as to explore the safety and efficacy of EBRT in HCC.Methods:A total of 113 HCC patients who received stereotactic body radiotherapy(a SBRT group,n=35)or intensity-modulated radiation therapy(a IMRT group,n=78)for liver lesions at the Third Xiangya Hospital of Central South University between 2015 and 2023 were prospectively collected and selected.The occurrence of radiation-induced liver diseases(RILDs)was recorded.Dosimetric parameters potentially associated with RILDs were analyzed using binary logistic regression with Hosmer-Lemeshow test,mainly including mean liver dose(MLD),remnant liver volume(RLV),standard liver volume(SLV),and rRFLV_(x).Radiotherapy-related hepatitis virus reactivation and other radiotherapy-related toxicities were also observed.Progression-free survival(PFS)and overall survival(OS)were used to evaluate the efficacy of EBRT in HCC.Results:Among the 113 HCC patients,12 were diagnosed with RILDs,including 11 in the IMRT group and only 1 in the SBRT group.Binary logistic regression with Hosmer-Lemeshow test results suggested that rRFLV_(25),rRFLV_(20),rRFLV_(15),rRFLV_(25)/SLV,rRFLV_(20)/SLV,and rRFLV_(15)/SLV were significantly associated with the occurrence of RILDs in HCC patients in the IMRT group(all P<0.05),while MLD and RLV were not associated with the occurrence of RILDs(P=0.88).One patient without regular anti-hepatitis viral treatment was diagnosed with radiotherapy-related HBV clinical reactivation,and one patient was diagnosed with immunotherapy-related HBV clinical reactivation.The median PFS was 5.6 months in the IMRT group and 16.4 months in the SBRT group,and the best local control rates were 98.6%and 100.0%,respectively.The median OS was 12.2 months in the IMRT group and 33.5 months in the SBRT group.The 6-month,1-year,and 2-year OS rates in the IMRT group were 77.1%,52.6%,and 18.6%,respectively.The 1-year,2-year,3-year,4-year,and 5-year OS rates in the SBRT group were 86.1%,61.7%,39.2%,25.7%,and 18.3%,respectively.Conclusion:EBRT is safe and effective for HCC patients at different stages.Compared with MLD and RLV,rRFLV_(x) and rRFLV_(x)/SLV may be more reliable for evaluating the occurrence of RILDs after IMRT treatment.For patients with hepatitis background,concurrent antiviral therapy during radiotherapy is relatively safe,but serum viral load should be closely monitored.Further research is needed to explore the efficacy and safety of radiotherapy combined with targeted and immunotherapy.
文摘OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The primary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were laboratory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic regressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ^(2)=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital preparation group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.
文摘Thermally activated delayed fluorescence(TADF)molecules have outstanding potential for applications in organic light-emitting diodes(OLEDs).Due to the lack of systematic studies on the correlation between molecular structure and luminescence properties,TADF molecules are far from meeting the needs of practical applications in terms of variety and number.In this paper,three twisted TADF molecules are studied and their photophysical properties are theoretically predicted based on the thermal vibrational correlation function method combined with multiscale calculations.The results show that all the molecules exhibit fast reverse intersystem crossing(RISC)rates(kRISC),predicting their TADF luminescence properties.In addition,the binding of DHPAzSi as the donor unit with different acceptors can change the dihedral angle between the ground and excited states,and the planarity of the acceptors is positively correlated with the reorganization energy,a property that has a strong influence on the non-radiative process.Furthermore,a decrease in the energy of the molecular charge transfer state and an increase in the kRISC were observed in the films.This study not only provides a reliable explanation for the observed experimental results,but also offers valuable insights that can guide the design of future TADF molecules.
文摘Hanyu Xu 1,Xuedan Song 1,*,Qing Zhang 1,Chang Yu 1,Jieshan Qiu 1,2,*1 Liaoning Key Lab for Energy Materials and Chemical Engineering,State Key Laboratory of Fine Chemicals,School of Chemical Engineering,Dalian University of Technology,Dalian 116024,Liaoning Province,China.
文摘中国糖尿病患病率不断攀升,患者超2.33亿,然而,针对心血管疾病和癌症等糖尿病并发症的本土研究缺失。中国心血管代谢与恶性肿瘤队列研究[China Cardiometabolic Disease and Cancer Cohort(4C)Study](基线调查于2011—2012年开展,最新随访至2024年)首次系统揭示中国糖尿病患者多种糖尿病并发症结局规律,填补循证空白。本文综述了4C研究的背景、研究方法、研究结果、学术影响和争议,指出了未来的挑战和策略。
