Objective： To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors （RFs, including nulliparity, mean number of children, age at first birth and breastf...Objective： To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors （RFs, including nulliparity, mean number of children, age at first birth and breastfeeding）, use of oral contraceptives （OCs, restricted to the age group of 15-49 years）, and hormone replacement therapy （HRT）, as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005. Methods： We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure. Results： Exposure of RFs in 2002 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer （712 cases, 294 deaths）. The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction （PAF） of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths. Conclusion： RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.展开更多
目的探讨超声定位下颈丛神经阻滞联合帕瑞昔布钠对老年甲状腺癌切除术患者氧化应激、疼痛介质及术后认知功能障碍(POCD)的影响。方法选取2018年2月—2021年3月行老年甲状腺癌切除术112例,根据麻醉镇痛方法分为观察组和对照组各56例。对...目的探讨超声定位下颈丛神经阻滞联合帕瑞昔布钠对老年甲状腺癌切除术患者氧化应激、疼痛介质及术后认知功能障碍(POCD)的影响。方法选取2018年2月—2021年3月行老年甲状腺癌切除术112例,根据麻醉镇痛方法分为观察组和对照组各56例。对照组于麻醉诱导前予以超声定位下颈丛神经阻滞,观察组在对照组基础上联合帕瑞昔布钠。比较2组阻滞前(T0)、手术切皮时(T1)、切除甲状腺时(T2)、术毕时(T3)血流动力学指标,T0、术后12 h(T4)、术后24 h(T5)、术后48 h(T6)氧化应激指标及疼痛介质,观察T4、T5、T6疼痛情况及T0、T5、T6、术后7 d简易智能精神状态检查量表(MMSE)评分,并统计不良反应发生情况与术后7 d POCD发生率。结果观察组T1、T2、T3时心率、平均动脉压低于对照组(P<0.05);观察组T4、T5、T6时血清超氧化物歧化酶水平高于对照组,丙二醛、血清前列腺素E_(2)、P物质、神经肽Y水平及视觉模拟评分法评分低于对照组(P<0.05)。观察组T5、T6、术后7 d时MMSE评分高于对照组(P<0.05);观察组术后7 d POCD发生率低于对照组(P<0.05)。结论超声定位下颈丛神经阻滞联合帕瑞昔布钠能有效稳定老年甲状腺癌切除术患者术中血流动力学,减轻机体氧化应激及疼痛程度,减少术后POCD。展开更多
Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is ef...Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.展开更多
基金supported by International Agency for Research on Cancer (Lyon, France) (No. CRA No GEE/08/19)supported in part by the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988)
文摘Objective： To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors （RFs, including nulliparity, mean number of children, age at first birth and breastfeeding）, use of oral contraceptives （OCs, restricted to the age group of 15-49 years）, and hormone replacement therapy （HRT）, as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005. Methods： We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure. Results： Exposure of RFs in 2002 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer （712 cases, 294 deaths）. The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction （PAF） of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths. Conclusion： RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.
文摘目的探讨超声定位下颈丛神经阻滞联合帕瑞昔布钠对老年甲状腺癌切除术患者氧化应激、疼痛介质及术后认知功能障碍(POCD)的影响。方法选取2018年2月—2021年3月行老年甲状腺癌切除术112例,根据麻醉镇痛方法分为观察组和对照组各56例。对照组于麻醉诱导前予以超声定位下颈丛神经阻滞,观察组在对照组基础上联合帕瑞昔布钠。比较2组阻滞前(T0)、手术切皮时(T1)、切除甲状腺时(T2)、术毕时(T3)血流动力学指标,T0、术后12 h(T4)、术后24 h(T5)、术后48 h(T6)氧化应激指标及疼痛介质,观察T4、T5、T6疼痛情况及T0、T5、T6、术后7 d简易智能精神状态检查量表(MMSE)评分,并统计不良反应发生情况与术后7 d POCD发生率。结果观察组T1、T2、T3时心率、平均动脉压低于对照组(P<0.05);观察组T4、T5、T6时血清超氧化物歧化酶水平高于对照组,丙二醛、血清前列腺素E_(2)、P物质、神经肽Y水平及视觉模拟评分法评分低于对照组(P<0.05)。观察组T5、T6、术后7 d时MMSE评分高于对照组(P<0.05);观察组术后7 d POCD发生率低于对照组(P<0.05)。结论超声定位下颈丛神经阻滞联合帕瑞昔布钠能有效稳定老年甲状腺癌切除术患者术中血流动力学,减轻机体氧化应激及疼痛程度,减少术后POCD。
基金supported by the Natural Science Foundation of Shanghai (21ZR1475600)Science and Technology Commission of Shanghai Municipality (20431900100)+4 种基金Shanghai Science and Technology Committee (19430750100)National Key R&D Program of China (2016YFA0502301 and 2021YFC2301204)Drug development for the newly emerging viral infectious diseases (SIMM010107)Fundamental Research Funds for the Central Universities (2022ZFJH003)Zhejiang Provincial Key Research&Development Program of China (2021C03043 and No.2021C03039).
文摘Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.
