Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refine...Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC.Methods:Data were collected from the China Pancreas Data Center(CPDC)for patients with resected PDAC in 2016 and 2017,and cancer-specific survival(CSS)was evaluated using the Kaplan-Meier method and log-rank test.Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors.The recursive partitioning analysis(RPA),Kaplan-Meier method,and log-rank test were performed on the training dataset to generate a proposed modification for the 8 th TNM staging system utilizing the preoperative carbohydrate antigen(CA)19-9 level.Validation was performed for both staging systems in the validation cohort.Results:A total of 1,676 PDAC patients were retrieved,and the median CSS was significantly different between the 8 th TNM groupings,with no significant difference in survival between stage IB and IIA.The analysis of T and N stages demonstrated a better prognostic value in the N category.Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors.All patients with CA19-9>500 U/mL had similar survival,and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III.The modified staging system had a better performance for predicting CSS than the 8 th AJCC staging scheme.Conclusions:The 8 th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients,and the N category has a better prognostic value than the T category.Our modified staging system has superior accuracy in predicting survival than the 8 th AJCC TNM staging system.展开更多
Auxin polar transport genes PIN(PINFORMED)determine the concentration gradient of auxin in plants.To understand the relationship between the development of different tissues in Betula pendula‘Dalecartica’,BpPIN gene...Auxin polar transport genes PIN(PINFORMED)determine the concentration gradient of auxin in plants.To understand the relationship between the development of different tissues in Betula pendula‘Dalecartica’,BpPIN gene expression and indole-3-acetic acid(IAA)content were analyzed using qRT-PCR,ELISA,and GUS staining.Gene expression of BpPIN genes and IAA levels in the leaves,buds,stems,xylem,and roots of B.pendula‘Dalecartica’and B.pendula as a control were measured.BpPIN1,BpPIN5 and BpPIN6 were upregulated during development in both species,suggesting a dominant role in the development of B.pendula‘Dalecartica’leaves.Moreover,BpPIN1 gene expression was positively associated with IAA levels during leaf,vein and petiole development in B.pendula‘Dalecartica’only.The correlation coefficient of the first three leaves was 0.69(P=0.04),while that of the first three petioles was 0.85(P=0.001).In addition,GUS staining of the pro-DR5::GUS transgenic line of cultivar was correlated with the results of BpPIN1 expression.Overall,these findings suggest that BpPIN1 is associated with the formation of lobed leaves in B.pendula‘Dalecartica’.展开更多
Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metaboli...Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD pathology.In this study,the cognitive function and gut microbiota of TgCRND8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,respectively.Young pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of neuropathology.Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions.Our results showed that gut dysbiosis,neuroinflammation response,Ab deposition,tau hyperphosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice age-dependently.Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the brains.On the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuroinflammation,Ab deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice.Moreover,excessive choline treatment was also shown to aggravate the cognitive deficits,Ab deposition,neuroinflammation and CDK5/STAT3 pathway activation.These findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.展开更多
Breast cancer is a malignant disease that seriously threatens women's health.Studying the mechanism of cancer occurrence and development is an urgent problem to be solved.In this paper,the eigen-microstate method ...Breast cancer is a malignant disease that seriously threatens women's health.Studying the mechanism of cancer occurrence and development is an urgent problem to be solved.In this paper,the eigen-microstate method was used to study conversion of normal breast cells into breast cancer cells and the reason.The main conclusions are as follows:the microstates of normal breast cell and breast cancer cell are different.There is a state conversion when a normal breast cell transforms into a breast cancer cell.The main reason for this state conversion is the combined effect of tumor suppressor genes and oncogenes.By analyzing the function of key genes,it was found that these genes do play an important role in the development of breast cancer.The findings contribute to understanding the mechanism by which breast cancer occurs and progresses,and key genes can serve as potential biomarkers or target genes for breast cancer treatment.展开更多
The increased coronavirus disease 2019(COVID-19)breakthrough cases pose the need of booster vaccination.We conducted a randomised,double-blinded,controlled,phase 2 trial to assess the immunogenicity and safety of the ...The increased coronavirus disease 2019(COVID-19)breakthrough cases pose the need of booster vaccination.We conducted a randomised,double-blinded,controlled,phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine(BBIBP-CorV)followed by a recombinant protein-based vaccine(NVSI-06-07),using homologous boost with BBIBP-CorV as control.Three groups of healthy adults(600 individuals per group)who had completed two-dose BBIBP-CorV vaccinations 1–3 months,4–6 months and≥6 months earlier,respectively,were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost.Immunogenicity assays showed that in NVSI-06-07 groups,neutralizing antibody geometric mean titers(GMTs)against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination,whereas only 4.20–16.78 folds of increases were observed in control groups.For Omicron variant,the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14,however,a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster.Similar results were obtained for other SARS-CoV-2 variants of concerns(VOCs),including Alpha,Beta and Delta.Both heterologous and homologous boosters have a good safety profile.Local and systemic adverse reactions were absent,mild or moderate in most participants,and the overall safety was quite similar between two booster schemes.Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs,including Omicron.展开更多
Human cancers typically express a high level of tumor-promoting mutant p53 protein(Mutp53)with a minimal level of tumor-suppressing wild-type p53 protein(WTp53).In this regard,inducing Mutp53 degradation while activat...Human cancers typically express a high level of tumor-promoting mutant p53 protein(Mutp53)with a minimal level of tumor-suppressing wild-type p53 protein(WTp53).In this regard,inducing Mutp53 degradation while activating WTp53 is a viable strategy for precise anti-tumor therapy.Herein,a new carrier-free nanoprodrug(i.e.,Mn-ZnO_(2)nanoparticles)was developed for concurrent delivery of dual Zn-Mn ions and reactive oxygen species(ROS)within tumor to regulate the p53 protein for high anti-tumor efficacy.In response to the mild tumor acidic environment,the released Zn^(2+)and H_(2)O_(2)from Mn-ZnO_(2)NPs induced ubiquitination-mediated proteasomal degradation of Mutp53,while the liberative Mn^(2+)and increased ROS level activated the ATM-p53-Bax pathway to elevate WTp53 level.Both in vitro and in vivo results demonstrated that pH-responsive decomposition of Mn-ZnO2 NPs could effectively elevate the intracellular dual Zn-Mn ions and ROS level and subsequently generate the cytotoxic hydroxyl radical(·OH)through the Fenton-like reaction.With the integration of multiple functions(i.e.,carrier-free ion and ROS delivery,tumor accumulation,p53 protein modulation,toxic·OH generation,and pH-activated MRI contrast)in a single nanosystem,Mn-ZnO_(2)NPs demonstrate its superiority as a promising nanotherapeutics for p53-mutated tumor therapy.展开更多
Objective:The objective of this study was to investigate whether 70%aqueous ethanol extract of San-Jia-Fu-Mai decoction extract(SJFMDE)could protect against 1-methyl-4-phenylpyridinium(MPP+)-induced oxidative stress i...Objective:The objective of this study was to investigate whether 70%aqueous ethanol extract of San-Jia-Fu-Mai decoction extract(SJFMDE)could protect against 1-methyl-4-phenylpyridinium(MPP+)-induced oxidative stress in PC12 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced motor function deficits in mice.Materials and Methods:The cell viability,the levels of intracellular reactive oxygen species(ROS),malondialdehyde(MDA),and glutathione(GSH)in the MPP+-treated PC12 cells were measured.Motor function deficits and dopamine(DA)level in the brain striatum and tyrosine hydroxylase(TH)-positive cells in substantia nigra pars compacta(SNc)of the MPTP-treated mice were determined.Results:The results showed that SJFMDE could reduce cell death and the levels of ROS and MDA while increase the level of GSH in the MPP+-treated PC12 cells.In addition,in vivo studies showed that oral administration of SJFMDE(3,6,and 12 g/kg)significantly improved the motor function deficits induced by MPTP and enhanced the DA level in the striatum and TH-positive neuronal cells in SNc of the MPTP-treated mice.Conclusions:Our results revealed that SJFMDE possessed neuroprotective effects against neurotoxicity induced by MPP+and motor function deficits induced by MPTP via suppressing oxidative stress and increasing the levels of DA and TH,indicating that SJFMDE might be a promising Chinese medicine formula for the treatment of Parkinson’s disease.展开更多
As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability o...As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine(TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials.展开更多
An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18...An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18 years and older from the United Arab Emirates(UAE),who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment.The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV.The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant,and the exploratory outcome was cross-immunogenicity against other circulating strains.Between May 25 and 30,2022,516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group.Interim results showed a similar safety profile between two booster groups,with low incidence of adverse reactions of grade 1 or 2.For immunogenicity,by day 14 post-booster,the fold rises in neutralizing antibody geometric mean titers(GMTs)from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain(19.67 vs 4.47-fold),Omicron BA.1.1(42.35 vs 3.78-fold),BA.2(25.09 vs 2.91-fold),BA.4(22.42 vs 2.69-fold),and BA.5 variants(27.06 vs 4.73-fold).Similarly,the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV.Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants,including Omicron and its sub-lineages.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81672353 and 81871954)。
文摘Objective:To validate the 8 th edition of the American Joint Committee on Cancer(AJCC)staging system for pancreatic ductal adenocarcinoma(PDAC)in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC.Methods:Data were collected from the China Pancreas Data Center(CPDC)for patients with resected PDAC in 2016 and 2017,and cancer-specific survival(CSS)was evaluated using the Kaplan-Meier method and log-rank test.Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors.The recursive partitioning analysis(RPA),Kaplan-Meier method,and log-rank test were performed on the training dataset to generate a proposed modification for the 8 th TNM staging system utilizing the preoperative carbohydrate antigen(CA)19-9 level.Validation was performed for both staging systems in the validation cohort.Results:A total of 1,676 PDAC patients were retrieved,and the median CSS was significantly different between the 8 th TNM groupings,with no significant difference in survival between stage IB and IIA.The analysis of T and N stages demonstrated a better prognostic value in the N category.Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors.All patients with CA19-9>500 U/mL had similar survival,and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III.The modified staging system had a better performance for predicting CSS than the 8 th AJCC staging scheme.Conclusions:The 8 th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients,and the N category has a better prognostic value than the T category.Our modified staging system has superior accuracy in predicting survival than the 8 th AJCC TNM staging system.
基金supported by the National Natural Science Foundation of China(NSFCGrant No.31670673)the 111 Project of China(Grant No.B16010)
文摘Auxin polar transport genes PIN(PINFORMED)determine the concentration gradient of auxin in plants.To understand the relationship between the development of different tissues in Betula pendula‘Dalecartica’,BpPIN gene expression and indole-3-acetic acid(IAA)content were analyzed using qRT-PCR,ELISA,and GUS staining.Gene expression of BpPIN genes and IAA levels in the leaves,buds,stems,xylem,and roots of B.pendula‘Dalecartica’and B.pendula as a control were measured.BpPIN1,BpPIN5 and BpPIN6 were upregulated during development in both species,suggesting a dominant role in the development of B.pendula‘Dalecartica’leaves.Moreover,BpPIN1 gene expression was positively associated with IAA levels during leaf,vein and petiole development in B.pendula‘Dalecartica’only.The correlation coefficient of the first three leaves was 0.69(P=0.04),while that of the first three petioles was 0.85(P=0.001).In addition,GUS staining of the pro-DR5::GUS transgenic line of cultivar was correlated with the results of BpPIN1 expression.Overall,these findings suggest that BpPIN1 is associated with the formation of lobed leaves in B.pendula‘Dalecartica’.
基金This work was partially supported by National Natural Science Foundation of China(Project No.:82104414)Natural Science Foundation of Guangdong Province of China(Project No.:2022A1515011682)a direct grant from The Chinese University of Hong Kong(Project No.:2021.071).
文摘Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD pathology.In this study,the cognitive function and gut microbiota of TgCRND8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,respectively.Young pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of neuropathology.Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions.Our results showed that gut dysbiosis,neuroinflammation response,Ab deposition,tau hyperphosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice age-dependently.Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the brains.On the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuroinflammation,Ab deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice.Moreover,excessive choline treatment was also shown to aggravate the cognitive deficits,Ab deposition,neuroinflammation and CDK5/STAT3 pathway activation.These findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.
基金the National Natural Science Foundation of China(Grant No.11735006)。
文摘Breast cancer is a malignant disease that seriously threatens women's health.Studying the mechanism of cancer occurrence and development is an urgent problem to be solved.In this paper,the eigen-microstate method was used to study conversion of normal breast cells into breast cancer cells and the reason.The main conclusions are as follows:the microstates of normal breast cell and breast cancer cell are different.There is a state conversion when a normal breast cell transforms into a breast cancer cell.The main reason for this state conversion is the combined effect of tumor suppressor genes and oncogenes.By analyzing the function of key genes,it was found that these genes do play an important role in the development of breast cancer.The findings contribute to understanding the mechanism by which breast cancer occurs and progresses,and key genes can serve as potential biomarkers or target genes for breast cancer treatment.
基金supported by the National Science Fund for Distinguished Young Scholars(52025034)the National Key Research and Development Program of China(2022YFB3807100 and 2022YFB3807101)+2 种基金the National Natural Science Foundation of China(21875190 and 52203101)the National Science and Technology Major Project of China(J2019-VI-0017-0132)the Innovation Team of Shaanxi Sanqin Scholars。
基金funded by Lanzhou Institute of Biological Products Company Limited.We would like to thank Prof.Guoyong Yuan from the University of Hong Kong for providing SARS-CoV-2 Omicron virus applied in live-virus neutralization assay。
文摘The increased coronavirus disease 2019(COVID-19)breakthrough cases pose the need of booster vaccination.We conducted a randomised,double-blinded,controlled,phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine(BBIBP-CorV)followed by a recombinant protein-based vaccine(NVSI-06-07),using homologous boost with BBIBP-CorV as control.Three groups of healthy adults(600 individuals per group)who had completed two-dose BBIBP-CorV vaccinations 1–3 months,4–6 months and≥6 months earlier,respectively,were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost.Immunogenicity assays showed that in NVSI-06-07 groups,neutralizing antibody geometric mean titers(GMTs)against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination,whereas only 4.20–16.78 folds of increases were observed in control groups.For Omicron variant,the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14,however,a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster.Similar results were obtained for other SARS-CoV-2 variants of concerns(VOCs),including Alpha,Beta and Delta.Both heterologous and homologous boosters have a good safety profile.Local and systemic adverse reactions were absent,mild or moderate in most participants,and the overall safety was quite similar between two booster schemes.Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs,including Omicron.
基金supported by the NIAMS award number 1R01AR067859National Natural Science Foundation of China(82102208,81830061)+2 种基金Program for Excellent Innovative Talents in Universities of Hebei Province(BJ2021019)Natural Science Foundation of Hebei Province(H2021202002,H2020202005)the Natural Science Foundation of Tianjin(19JCYBJC28300).
文摘Human cancers typically express a high level of tumor-promoting mutant p53 protein(Mutp53)with a minimal level of tumor-suppressing wild-type p53 protein(WTp53).In this regard,inducing Mutp53 degradation while activating WTp53 is a viable strategy for precise anti-tumor therapy.Herein,a new carrier-free nanoprodrug(i.e.,Mn-ZnO_(2)nanoparticles)was developed for concurrent delivery of dual Zn-Mn ions and reactive oxygen species(ROS)within tumor to regulate the p53 protein for high anti-tumor efficacy.In response to the mild tumor acidic environment,the released Zn^(2+)and H_(2)O_(2)from Mn-ZnO_(2)NPs induced ubiquitination-mediated proteasomal degradation of Mutp53,while the liberative Mn^(2+)and increased ROS level activated the ATM-p53-Bax pathway to elevate WTp53 level.Both in vitro and in vivo results demonstrated that pH-responsive decomposition of Mn-ZnO2 NPs could effectively elevate the intracellular dual Zn-Mn ions and ROS level and subsequently generate the cytotoxic hydroxyl radical(·OH)through the Fenton-like reaction.With the integration of multiple functions(i.e.,carrier-free ion and ROS delivery,tumor accumulation,p53 protein modulation,toxic·OH generation,and pH-activated MRI contrast)in a single nanosystem,Mn-ZnO_(2)NPs demonstrate its superiority as a promising nanotherapeutics for p53-mutated tumor therapy.
基金supported by the Innovation and Technology Commission Funding Administrative System of Hong Kong(Project No.:ITS/122/19FP)the Natural Science Fund of Guangdong(project no.2019A1515011257)
文摘Objective:The objective of this study was to investigate whether 70%aqueous ethanol extract of San-Jia-Fu-Mai decoction extract(SJFMDE)could protect against 1-methyl-4-phenylpyridinium(MPP+)-induced oxidative stress in PC12 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced motor function deficits in mice.Materials and Methods:The cell viability,the levels of intracellular reactive oxygen species(ROS),malondialdehyde(MDA),and glutathione(GSH)in the MPP+-treated PC12 cells were measured.Motor function deficits and dopamine(DA)level in the brain striatum and tyrosine hydroxylase(TH)-positive cells in substantia nigra pars compacta(SNc)of the MPTP-treated mice were determined.Results:The results showed that SJFMDE could reduce cell death and the levels of ROS and MDA while increase the level of GSH in the MPP+-treated PC12 cells.In addition,in vivo studies showed that oral administration of SJFMDE(3,6,and 12 g/kg)significantly improved the motor function deficits induced by MPTP and enhanced the DA level in the striatum and TH-positive neuronal cells in SNc of the MPTP-treated mice.Conclusions:Our results revealed that SJFMDE possessed neuroprotective effects against neurotoxicity induced by MPP+and motor function deficits induced by MPTP via suppressing oxidative stress and increasing the levels of DA and TH,indicating that SJFMDE might be a promising Chinese medicine formula for the treatment of Parkinson’s disease.
基金supported by the National Natural Science Foundation of China(No.82174530).
文摘As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine(TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials.
基金The study was funded by Lanzhou Institute of Biological Products Co.,Ltd(LIBP)of Sinopharm,and Beijing Institute of Biological Products Co.,Ltd(BIBP)of Sinopharm.X.J.G.,X.Y.M.,H.W.,and J.Zhang are employees of the funders.The funders did not participate in design of the trial,analysis of the data,or writing of the manuscript.
文摘An ongoing randomized,double-blind,controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate,named NVSI-06-09,as a booster dose in subjects aged 18 years and older from the United Arab Emirates(UAE),who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment.The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV.The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant,and the exploratory outcome was cross-immunogenicity against other circulating strains.Between May 25 and 30,2022,516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group.Interim results showed a similar safety profile between two booster groups,with low incidence of adverse reactions of grade 1 or 2.For immunogenicity,by day 14 post-booster,the fold rises in neutralizing antibody geometric mean titers(GMTs)from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain(19.67 vs 4.47-fold),Omicron BA.1.1(42.35 vs 3.78-fold),BA.2(25.09 vs 2.91-fold),BA.4(22.42 vs 2.69-fold),and BA.5 variants(27.06 vs 4.73-fold).Similarly,the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV.Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants,including Omicron and its sub-lineages.
