In the present study, we described a novel, simple, and scalable method for isolating and purifying natural mangiferin from fresh mango leaves. An ultrasonic-assisted method was used to extract mangiferin from mango l...In the present study, we described a novel, simple, and scalable method for isolating and purifying natural mangiferin from fresh mango leaves. An ultrasonic-assisted method was used to extract mangiferin from mango leaves using methanol as the solvent. The yields of the mangiferin crude extract and purified mangiferin recrystallized from a mixture of methanol and trichloromethane(10:1, v/v) were 1.41%(purity 86.5%) and 0.75%(purity > 99.6%), respectively. The purity of mangiferin was assessed by UV spectroscopy and HPLC. The structure of the purified compound was confirmed spectroscopically by UV, IR, Q-TOF/MS,;H NMR, and;C NMR. The method described herein to isolate mangiferin was simple, inexpensive, rapid, and efficient. Moreover, we, for the first time, obtained mangiferin with a purity of more than 99.6% using this method.展开更多
Concurrent inhibition of angiogenesis and immune checkpoints represents a potent therapeutic approach.We conducted a phase 2,multicenter,basket study to assess the efficacy and safety of combination therapy of famitin...Concurrent inhibition of angiogenesis and immune checkpoints represents a potent therapeutic approach.We conducted a phase 2,multicenter,basket study to assess the efficacy and safety of combination therapy of famitinib(anti-angiogenic agent)plus camrelizumab(PD-1 antagonist)in patients with metastatic solid tumors across 11 cohorts(this study was registered at Clinicaltrials.gov[NCT04346381]).This report focuses on the cohort of patients with metastatic or advanced colorectal cancer.Eligible patients,who had previously received R2 lines of systemic treatments for their metastatic disease,were treated with famitinib(20 mg once daily)in combination with camrelizumab(200 mg intravenously every 3 weeks).The primary endpoint was the objective response rate,with secondary endpoints encompassing progressionfree survival,overall survival,duration of response,safety and exploratory biomarkers.A total of 44 patients were enrolled and treated.With a median follow-up time of 9.46 months(range 2.0-22.5 months),objective responses were observed in 6 patients(13.6%;95%confidence interval[CI],5.2%-27.4%),all of whom had rectal cancer.The median duration of response is 6.2 months(95%CI,2.3-10.6 months).Median progression-free survival was 3.3 months(95%CI,2.1-4.1 months),and median overall survival was 10.9 months(95%CI,7.6-15.2 months).Among the 44 patients,29(65.9%)experienced grade 3 or 4 treatment-related adverse events,predominantly hypertension and proteinuria.In conclusion,the combination of famitinib and camrelizumab demonstrates promising antitumor activity with a manageable safety profile in metastatic colorectal cancer patients.Further research is warranted to confirm and extend these findings.展开更多
The randomized phase 3 CHART trial(NCT03520478)revealed that rezvilutamide(REZ)plus androgen deprivation therapy(ADT)in high-volume,metastatic,hormone-sensitive prostate cancer(mHSPC)significantly enhanced radiographi...The randomized phase 3 CHART trial(NCT03520478)revealed that rezvilutamide(REZ)plus androgen deprivation therapy(ADT)in high-volume,metastatic,hormone-sensitive prostate cancer(mHSPC)significantly enhanced radiographic progression-free and overall survival than bicalutamide(BIC)-ADT.Accordingly,we examined patient-reported outcomes(PROs)results,which were exploratory endpoints in the CHART trial.The patients were randomly allocated to receive REZ-ADT or BIC-ADT in a 1:1 ratio.The PROs were evaluated with the Brief Pain Inventory-Short Form(BPI-SF)and the Functional Assessment of Cancer Therapy-Prostate(FACT-P)questionnaires.Both study groups displayed comparable baseline pain scores and functional status.Patients administered REZ-ADT had an extended time to progression of worst pain intensity in comparison to those treated with BIC-ADT(25th percentile,9.2[95%CI 7.4-16.6]vs.6.4 months[95%CI 5.5-8.3];HR 0.75[95%CI 0.57-0.97];p=0.026).Similarly,patients received REZ-ADT exhibited a delayed time to progression of pain interference in comparison to those receiving BIC-ADT(25th percentile,20.2[95%CI 12.9-31.3]vs.10.2 months[95%CI 7.4-11.1];HR 0.70[95%CI 0.52-0.93];p=0.015).Additionally,the REZ-ADT group demonstrated a prolonged delay in the deterioration of the total score on the FACT-P questionnaire(25th percentile,12.8[95%CI 7.4-20.3]vs.6.0 months[95%CI 4.6-9.2];HR 0.66[95%CI 0.50-0.86];p=0.002),as well as most of the FACT-P subscale scores,in comparison to the BIC-ADT group.In conclusion,REZ-ADT is superior to BIC-ADT regarding the pain alleviation and enhancement of functional scales for high-volume mHSPC.展开更多
Distribution and removal of chemicals in wastewater treatment plants(WWTPs)have mainly relied on mathematical models.Existing exposure assessment models such as SimpleTreat,STPWIN are based on conventional activated s...Distribution and removal of chemicals in wastewater treatment plants(WWTPs)have mainly relied on mathematical models.Existing exposure assessment models such as SimpleTreat,STPWIN are based on conventional activated sludge processes.There is an urgent need to develop an A^(2)/O-based WWTPs exposure assessment model.Organophosphates(OPEs)have different physical and chemical properties and potential environmental risks.The fate and biodegradation kinetics of three types of OPEs,including alkyl OPEs,chlorinated OPEs and triphenyl ester OPEs,were studied in a laboratory-scale anaerobic/anoxic/aerobic(A^(2)/O)sewage treatment system and batch reactors.The three types of OPEs had different anaerobic,anoxic,and aerobic removal characteristics.A compensation mechanism was found between anaerobic and anoxic/aerobic removal.When the hydraulic retention time decreased from 82 to 20.5 h,the removal efficiencies in the anaerobic unit decreased,while those in the anoxic unit increased;as a result,the total removal efficiencies remained high(>80%)for all OPEs except triphenyl phosphate(65.5%-75.1%).The concept of effective sludge concentration(MLSS eff)was proposed to illustrate the compensation mechanism and calibrate the second-order kinetic equation for predicting pollutant removal in the A^(2)/O system:MLSS eff=k_(en)×MLSS,where ken is a constant related to the influent total organic carbon content(TOC).The influent TOC contents of the anoxic and aerobic units affected the value of MLSS_(eff)and OPEs removal.The results are of great significance for assessing OPEs exposure and predicting exposure to emerging micropollutants in sewage treatment systems.展开更多
基金The Key R&D projects in Hainan Province (Grant No. ZDYF2020160)the National Key Research and Development Project of China (Grant No. 2017YFF0207800)Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences (Grant No. 1630082017001)。
文摘In the present study, we described a novel, simple, and scalable method for isolating and purifying natural mangiferin from fresh mango leaves. An ultrasonic-assisted method was used to extract mangiferin from mango leaves using methanol as the solvent. The yields of the mangiferin crude extract and purified mangiferin recrystallized from a mixture of methanol and trichloromethane(10:1, v/v) were 1.41%(purity 86.5%) and 0.75%(purity > 99.6%), respectively. The purity of mangiferin was assessed by UV spectroscopy and HPLC. The structure of the purified compound was confirmed spectroscopically by UV, IR, Q-TOF/MS,;H NMR, and;C NMR. The method described herein to isolate mangiferin was simple, inexpensive, rapid, and efficient. Moreover, we, for the first time, obtained mangiferin with a purity of more than 99.6% using this method.
基金supported by Jiangsu Hengrui Pharmaceuticals Co.,Ltd.,National Natural Science Foundation of China(82373402,82272775)Shanghai Shen-kang Hospital Development Center(SHDC2022CRT001)+1 种基金Shanghai Rising-Star Program(21QA1401600)the Cancer Center,Zhongshan Hospital(2023XKPT19-RC1).
文摘Concurrent inhibition of angiogenesis and immune checkpoints represents a potent therapeutic approach.We conducted a phase 2,multicenter,basket study to assess the efficacy and safety of combination therapy of famitinib(anti-angiogenic agent)plus camrelizumab(PD-1 antagonist)in patients with metastatic solid tumors across 11 cohorts(this study was registered at Clinicaltrials.gov[NCT04346381]).This report focuses on the cohort of patients with metastatic or advanced colorectal cancer.Eligible patients,who had previously received R2 lines of systemic treatments for their metastatic disease,were treated with famitinib(20 mg once daily)in combination with camrelizumab(200 mg intravenously every 3 weeks).The primary endpoint was the objective response rate,with secondary endpoints encompassing progressionfree survival,overall survival,duration of response,safety and exploratory biomarkers.A total of 44 patients were enrolled and treated.With a median follow-up time of 9.46 months(range 2.0-22.5 months),objective responses were observed in 6 patients(13.6%;95%confidence interval[CI],5.2%-27.4%),all of whom had rectal cancer.The median duration of response is 6.2 months(95%CI,2.3-10.6 months).Median progression-free survival was 3.3 months(95%CI,2.1-4.1 months),and median overall survival was 10.9 months(95%CI,7.6-15.2 months).Among the 44 patients,29(65.9%)experienced grade 3 or 4 treatment-related adverse events,predominantly hypertension and proteinuria.In conclusion,the combination of famitinib and camrelizumab demonstrates promising antitumor activity with a manageable safety profile in metastatic colorectal cancer patients.Further research is warranted to confirm and extend these findings.
文摘The randomized phase 3 CHART trial(NCT03520478)revealed that rezvilutamide(REZ)plus androgen deprivation therapy(ADT)in high-volume,metastatic,hormone-sensitive prostate cancer(mHSPC)significantly enhanced radiographic progression-free and overall survival than bicalutamide(BIC)-ADT.Accordingly,we examined patient-reported outcomes(PROs)results,which were exploratory endpoints in the CHART trial.The patients were randomly allocated to receive REZ-ADT or BIC-ADT in a 1:1 ratio.The PROs were evaluated with the Brief Pain Inventory-Short Form(BPI-SF)and the Functional Assessment of Cancer Therapy-Prostate(FACT-P)questionnaires.Both study groups displayed comparable baseline pain scores and functional status.Patients administered REZ-ADT had an extended time to progression of worst pain intensity in comparison to those treated with BIC-ADT(25th percentile,9.2[95%CI 7.4-16.6]vs.6.4 months[95%CI 5.5-8.3];HR 0.75[95%CI 0.57-0.97];p=0.026).Similarly,patients received REZ-ADT exhibited a delayed time to progression of pain interference in comparison to those receiving BIC-ADT(25th percentile,20.2[95%CI 12.9-31.3]vs.10.2 months[95%CI 7.4-11.1];HR 0.70[95%CI 0.52-0.93];p=0.015).Additionally,the REZ-ADT group demonstrated a prolonged delay in the deterioration of the total score on the FACT-P questionnaire(25th percentile,12.8[95%CI 7.4-20.3]vs.6.0 months[95%CI 4.6-9.2];HR 0.66[95%CI 0.50-0.86];p=0.002),as well as most of the FACT-P subscale scores,in comparison to the BIC-ADT group.In conclusion,REZ-ADT is superior to BIC-ADT regarding the pain alleviation and enhancement of functional scales for high-volume mHSPC.
基金supported by the Research Beidou Plan(Version 2.0)(Talent Project)of Nanjing Polytechnic Institute(NJPI-RC-2022-03)the Central Scientific Research Projects for Public Welfare Research Institutes(ZX2023QT003)the National Key R and D Program of China(2018YFC1801504).
文摘Distribution and removal of chemicals in wastewater treatment plants(WWTPs)have mainly relied on mathematical models.Existing exposure assessment models such as SimpleTreat,STPWIN are based on conventional activated sludge processes.There is an urgent need to develop an A^(2)/O-based WWTPs exposure assessment model.Organophosphates(OPEs)have different physical and chemical properties and potential environmental risks.The fate and biodegradation kinetics of three types of OPEs,including alkyl OPEs,chlorinated OPEs and triphenyl ester OPEs,were studied in a laboratory-scale anaerobic/anoxic/aerobic(A^(2)/O)sewage treatment system and batch reactors.The three types of OPEs had different anaerobic,anoxic,and aerobic removal characteristics.A compensation mechanism was found between anaerobic and anoxic/aerobic removal.When the hydraulic retention time decreased from 82 to 20.5 h,the removal efficiencies in the anaerobic unit decreased,while those in the anoxic unit increased;as a result,the total removal efficiencies remained high(>80%)for all OPEs except triphenyl phosphate(65.5%-75.1%).The concept of effective sludge concentration(MLSS eff)was proposed to illustrate the compensation mechanism and calibrate the second-order kinetic equation for predicting pollutant removal in the A^(2)/O system:MLSS eff=k_(en)×MLSS,where ken is a constant related to the influent total organic carbon content(TOC).The influent TOC contents of the anoxic and aerobic units affected the value of MLSS_(eff)and OPEs removal.The results are of great significance for assessing OPEs exposure and predicting exposure to emerging micropollutants in sewage treatment systems.
