Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
The next generation of very long baseline interferometry(VLBI)is stepping into the era of microarcsecond(μas)astronomy,and pushing astronomy,especially astrometry,to new heights.VLBI with the Square Kilometre Array(S...The next generation of very long baseline interferometry(VLBI)is stepping into the era of microarcsecond(μas)astronomy,and pushing astronomy,especially astrometry,to new heights.VLBI with the Square Kilometre Array(SKA),SKA-VLBI,will increase current sensitivity by an order of magnitude,and reach astrometric precision routinely below 10μas,even challenging 1μas.This advancement allows precise parallax and proper motion measurements of various celestial objects.Such improvements can be used to study objects(including isolated objects,and binary or multiple systems)in different stellar stages(such as star formation,main-sequence stars,asymptotic giant branch stars,pulsars,black holes,white dwarfs,etc.),unveil the structure and evolution of complex systems(such as the Milky Way),benchmark the international celestial reference frame,and reveal cosmic expansion.Furthermore,the theory of general relativity can also be tested with SKA-VLBI using precise measurements of light deflection under the gravitational fields of different solar system objects and the perihelion precession of solar system objects.展开更多
Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts ...Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.展开更多
Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide1.Surgical radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative sur...Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide1.Surgical radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of surgery2.Fortunately,the transformation of high-throughput sequencing has accelerated the development of precision medicine.For example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in CRC3.Furthermore,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.展开更多
Objective:To analyze the effects of repetitive transcranial magnetic stimulation combined with motor control training on the treatment of stroke-induced hemiplegia,specifically focusing on the impact on patients’bala...Objective:To analyze the effects of repetitive transcranial magnetic stimulation combined with motor control training on the treatment of stroke-induced hemiplegia,specifically focusing on the impact on patients’balance function and gait.Methods:Fifty-two cases of hemiplegic stroke patients were randomly divided into two groups,26 in the control group and 26 in the observation group,using computer-generated random grouping.All participants underwent conventional treatment and rehabilitation training.In addition to these,the control group received repetitive transcranial magnetic pseudo-stimulation therapy+motor control training,while the observation group received repetitive transcranial magnetic stimulation therapy+motor control training.The balance function and gait parameters of both groups were compared before and after the interventions and assessed the satisfaction of the interventions in both groups.Results:Before the invention,there were no significant differences in balance function scores and each gait parameter between the two groups(P>0.05).However,after the intervention,the observation group showed higher balance function scores compared to the control group(P<0.05).The observation group also exhibited higher step speed and step frequency,longer step length,and a higher overall satisfaction level with the intervention compared to the control group(P<0.05).Conclusion:The combination of repetitive transcranial magnetic stimulation and motor control training in the treatment of stroke-induced hemiplegia has demonstrated positive effects.It not only improves the patient’s balance function and gait but also contributes to overall physical rehabilitation.展开更多
Objective:To study the effect of repetitive peripheral magnetic stimulation(rPMS)combined with conventional rehabilitation measures on shoulder dysfunction in early stroke.Methods:60 patients with shoulder dysfunction...Objective:To study the effect of repetitive peripheral magnetic stimulation(rPMS)combined with conventional rehabilitation measures on shoulder dysfunction in early stroke.Methods:60 patients with shoulder dysfunction in early stroke were selected,and all of them were admitted to our hospital from August 2021 to August 2023.The patients were randomly grouped into a control group(conventional rehabilitation measures intervention,30 cases)and an intervention group(rPMS and conventional rehabilitation measures intervention,30 cases)according to the lottery method.The pain scores,shoulder mobility,and motor function scores of the two groups were compared.Results:The pain score was lower in the intervention group,and the shoulder mobility and motor function scores were higher in the intervention group(P<0.05)as compared to that of the control group.Conclusion:The effect of combining rPMS and conventional rehabilitation measures in treating shoulder dysfunction in early stroke was remarkable and should be popularized.展开更多
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
基金funded by the National Natural Science Foundation of China(NSFC,Grant Nos.12203104 and 11933011)the Natural Science Foundation of Jiangsu Province(grants No.BK20210999)+2 种基金the National SKA Program of China(grant No.2022SKA0120103)the Entrepreneurship and Innovation Program of Jiangsu Provincethe Key Laboratory for Radio Astronomy,CAS。
文摘The next generation of very long baseline interferometry(VLBI)is stepping into the era of microarcsecond(μas)astronomy,and pushing astronomy,especially astrometry,to new heights.VLBI with the Square Kilometre Array(SKA),SKA-VLBI,will increase current sensitivity by an order of magnitude,and reach astrometric precision routinely below 10μas,even challenging 1μas.This advancement allows precise parallax and proper motion measurements of various celestial objects.Such improvements can be used to study objects(including isolated objects,and binary or multiple systems)in different stellar stages(such as star formation,main-sequence stars,asymptotic giant branch stars,pulsars,black holes,white dwarfs,etc.),unveil the structure and evolution of complex systems(such as the Milky Way),benchmark the international celestial reference frame,and reveal cosmic expansion.Furthermore,the theory of general relativity can also be tested with SKA-VLBI using precise measurements of light deflection under the gravitational fields of different solar system objects and the perihelion precession of solar system objects.
基金supported by the Science and Technology project of Henan Province(202102310142)the National Natural Science Foundation of China(32001806)。
文摘Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.
基金the Ministry of Science and Technology of China(Grant No.2018YFE0201604)the National Natural Science Foundation of China(Grant No.81872137 and 82072917)the Science and Technology Commission of Shanghai Municipality(Grant No.20DZ1100100)。
文摘Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide1.Surgical radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of surgery2.Fortunately,the transformation of high-throughput sequencing has accelerated the development of precision medicine.For example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in CRC3.Furthermore,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.
基金supported by National Nature Science Foundation of China(30973290,81172559,881172302)Key Research Program from Science and Technology Department of Hunan Province,China(2010FJ2009)Nature Science Foundation of Hunan Province,China(11JJ2045)
文摘Objective:To analyze the effects of repetitive transcranial magnetic stimulation combined with motor control training on the treatment of stroke-induced hemiplegia,specifically focusing on the impact on patients’balance function and gait.Methods:Fifty-two cases of hemiplegic stroke patients were randomly divided into two groups,26 in the control group and 26 in the observation group,using computer-generated random grouping.All participants underwent conventional treatment and rehabilitation training.In addition to these,the control group received repetitive transcranial magnetic pseudo-stimulation therapy+motor control training,while the observation group received repetitive transcranial magnetic stimulation therapy+motor control training.The balance function and gait parameters of both groups were compared before and after the interventions and assessed the satisfaction of the interventions in both groups.Results:Before the invention,there were no significant differences in balance function scores and each gait parameter between the two groups(P>0.05).However,after the intervention,the observation group showed higher balance function scores compared to the control group(P<0.05).The observation group also exhibited higher step speed and step frequency,longer step length,and a higher overall satisfaction level with the intervention compared to the control group(P<0.05).Conclusion:The combination of repetitive transcranial magnetic stimulation and motor control training in the treatment of stroke-induced hemiplegia has demonstrated positive effects.It not only improves the patient’s balance function and gait but also contributes to overall physical rehabilitation.
文摘Objective:To study the effect of repetitive peripheral magnetic stimulation(rPMS)combined with conventional rehabilitation measures on shoulder dysfunction in early stroke.Methods:60 patients with shoulder dysfunction in early stroke were selected,and all of them were admitted to our hospital from August 2021 to August 2023.The patients were randomly grouped into a control group(conventional rehabilitation measures intervention,30 cases)and an intervention group(rPMS and conventional rehabilitation measures intervention,30 cases)according to the lottery method.The pain scores,shoulder mobility,and motor function scores of the two groups were compared.Results:The pain score was lower in the intervention group,and the shoulder mobility and motor function scores were higher in the intervention group(P<0.05)as compared to that of the control group.Conclusion:The effect of combining rPMS and conventional rehabilitation measures in treating shoulder dysfunction in early stroke was remarkable and should be popularized.
