Objective: To obtain epidemiological data on Traditional Chinese Medicine (TCM) therapeutic status of acute myocardial infarction (AMI) and to determine TCM characteristics and advantages to improve the level of TCM p...Objective: To obtain epidemiological data on Traditional Chinese Medicine (TCM) therapeutic status of acute myocardial infarction (AMI) and to determine TCM characteristics and advantages to improve the level of TCM prevention and treatment of AMI. Methods: Clinical epidemiology methods were used to register and survey the TCM therapeutic status of hospitalized AMI patients. In 2001, the Chinese Association of Integrative Medicine surveyed the therapeutic status of 3308 AMI patients hospitalized in 30 hospitals in Beijing and Shanghai from 2000-2001. The Beijing Collaborative Study Group on Therapeutic Status of Acute Myocardial Infarction (the Study Group) then conducted a 10-year-long register survey on hospitalized AMI patients in Third-grade A-Level TCM hospitals in Beijing. After 2002, the Study Group further surveyed the treatment conditions of AMI-hospitalized patients in 10 Second-grade A-Level TCM hospitals. The therapeutic status in 8 Third-grade A-Level Western medicine hospitals was surveyed in 2001 and 2005 as a control. In 2008, in cooperation with the China Association of Chinese Medicine, the Study Group further performed a survey at 26 Third-grade A-Level TCM hospitals nation-wide. Approximately 5000 cases were investigated to obtain authoritative data on the therapeutic status of AMI patients in TCM hospitals in China. Results: We found that Chinese herbal intravenous preparations may be beneficial in reducing the mortality of AMI. Major complications of AMI, such as heart failure and arrhythmia, were significantly less during the 10-year survey period. The mortality of hospitalized AMI patients showed a decline. TCM treatment was helpful for AMI patients in improving their quality of life. Ten-year dynamic monitoring showed that the ability to perform reperfusion and to use drugs appropriately, as well as an effort to carry out the Clinical Guidelines has made great progress in TCM hospitals. However, TCM hospitals still have some problems in treating AMI, including a lack of standardized TCM syndrome diagnosis, the need for syndrome differentiation and treatment standardization, and clinical skills in reperfusion and standardized drug treatment still need to be further improved. Compared with AMI patients in Western medicine hospitals during the same period, those in TCM hospitals had the following characteristics: they were admitted to hospital later; they were older when they had a heart attack; there were more females, they had more problems in their medical history, and they had more concomitant illnesses and complications. Therefore, the demographic baseline data were significantly different between AMI patients in TCM hospitals and those in Western medicine hospitals. This indicated that patients in TCM hospitals were more critical than those in Western medicine hospitals. Conclusions: TCM has special advantages in treating AMI. TCM hospitals are making continuous progress in standardized treatment of AMI, but further improvement is still required. AMI patients in TCM hospitals have some special characteristics, and their condition may be more critical. Further clinical research on TCM treatment of AMI is required.展开更多
Inflammatory arthritis refers to the migration of inflammatory cells(such as monocytes/macrophages,lymphocytes,and granulocytes)from the blood to the synovium or synovial fluid,causing joint pain and swelling.It is of...Inflammatory arthritis refers to the migration of inflammatory cells(such as monocytes/macrophages,lymphocytes,and granulocytes)from the blood to the synovium or synovial fluid,causing joint pain and swelling.It is often associated with decreased joint mobility and functional damage.Some diseases lead to cartilage and skeletal damage,resulting in joint destruction.Common inflammatory arthritis includes rheumatoid arthritis,ankylosing spondylitis,and gout.展开更多
Objective:Aerva lanata (Linn) Juss ex Schult,family Amaranthaceae,is a common wayside weed.The herb is accepted by the Ayurvedic Formulary of India.This study was undertaken to establish morphoanatomic and physiochemi...Objective:Aerva lanata (Linn) Juss ex Schult,family Amaranthaceae,is a common wayside weed.The herb is accepted by the Ayurvedic Formulary of India.This study was undertaken to establish morphoanatomic and physiochemical standards of A.lanata.Methods:Leaf constants and high-performance thin layer chromatography fingerprint profiles of A.lanata were performed.Results and conclusion:The physico-chemical,morphologic,and histologic parameters presented in this paper may be proposed as standards to establish the authenticity of A.lanata and help differentiate it from other species such as Aerva tomentosa.展开更多
[Objectives] To study the effects of Tiaomaiyin and its disassembled prescription on expression of L-type calcium channel β2 subunit in rat model of tachyarrhythmia. [Methods] Sixty Wistar rats were randomly divided ...[Objectives] To study the effects of Tiaomaiyin and its disassembled prescription on expression of L-type calcium channel β2 subunit in rat model of tachyarrhythmia. [Methods] Sixty Wistar rats were randomly divided into model group,Tiaomaiyin prescription group( whole prescription group),main efficacy group of removing heat to cool blood( blood cooling group),and auxiliary drug efficacy group of benefiting qi and nourishing heart( qi benefiting group),auxiliary efficacy group of promoting flow of qi and blood circulation( qi flow promoting group),and amiodarone group( western medicine group). Aconitine was given 7 d after the intragastric administration of the corresponding drugs,and the time of occurrence of arrhythmia in each group was observed. The left ventricular myocardium was subjected to reverse transcription-polymerase chain reaction and Western blotting. [Results] The ventricular premature beats( VPB) time in the whole prescription group and western medicine group was significantly longer than that in the model group. Ventricular tachycardia( VT),ventricular fibrillation( VF),and cardiac arrest( CA) were longer in the whole prescription group,blood cooling group,and western medicine group. The mRNA and protein expression of L-type calcium channel β2 subunit in the whole prescription group,blood cooling group and western medicine group were significantly decreased. [Conclusions] Tiaomaiyin whole prescription group and blood cooling group can reduce the occurrence time of tachyarrhythmia and reduce the expression of LTCC β2 in myocardium.展开更多
OBJECTIVE:To update the current characteristics about the scope and quality of mixed methods research(MMR)in complementary and alternative medicine(CAM)after nearly 10 years.METHODS:A 5-stage approach for conducting a...OBJECTIVE:To update the current characteristics about the scope and quality of mixed methods research(MMR)in complementary and alternative medicine(CAM)after nearly 10 years.METHODS:A 5-stage approach for conducting a scoping review was adopted.Articles published on the top 10 journals in CAM with the highest impact factor in 2020 were screened for MMR.Information of included articles were extracted,and then synthesized to illustrate the current state.Methodological quality was evaluated according to the Mixed Method Appraisal Tool(MMAT)2018 version.RESULTS:A total of 55(55/2991,2%)articles using mixed methods were retrieved,including 17 medical studies and 38 ethnobotanical studies.We performed an in-depth analysis on the 17 medical studies,which studied cancer,stress,pain,fatigue,exercises,mindfulness intervention,herbal medicine use,art and acupuncture.Thirteen pilot studies applied MMR to evaluate the feasibility of interventions or programs(13/17,76%);phenomenology was inferred as the most common philosophical assumptions(13/17,76%);the most applied type of MMR was convergent design(16/17,94%);integration often took place at integration(12/17,71%).Among the 16 eligible studies for quality appraisal,majority were rated as good(14/16,88%),whereas two studies were rated as poorly described.Primarily,a poor rating was due to incomplete reporting of data analysis and citations in qualitative components;lack of confounder controlling and the sampling strategy in quantitative components;poor description of integration and justification for mixed methods.Comparing with the previous review,fewer MMR were published in 2020 in CAM,but the proportion of studies that clearly reported MMR has increased by 4 times(4%→15%).CONCLUSION:CAM researchers need to realize the benefits that MMR can have on conducting further health care research.Our findings highlight that applying MMR will be helpful to understand the complex dynamics and interdisciplinary nature of complex intervention.In addition,addressing a standardized reporting criteria for MMR is recommended.展开更多
OBJECTIVE: A systematic review of the literature was conducted to evaluate the curative effect and safety of Duhuojisheng Tang on prolapse of the lumbar intervertebral disc. METHODS: The databases of PubMed, China N...OBJECTIVE: A systematic review of the literature was conducted to evaluate the curative effect and safety of Duhuojisheng Tang on prolapse of the lumbar intervertebral disc. METHODS: The databases of PubMed, China Na- tional Knowledge Infrastructure (CNKI), Chinese Sci- entific Journals Database (VlP), Chinese Biomedical Literature Database (CBM) and Chinese Medical Ci- tation Index (CMCl) were searched up to January 30, 2012. Randomized controlled trials were select- ed to compare Duhuojisheng Tang with one ormore of the following treatments: traction, acu- puncture, massage, cupping and Western medical treatment. The quality-evaluating standard and the software RevMan 5.1 in Cochrane coordinative net were used to analyze the data. The effective index- es of the results were clinical curative rate, effective- ness of alleviating clinical symptoms and adverse reaction. RESULTS: Thirty-one randomized controlled trials of low quality, involving 3915 patients were system- atically evaluated. Statistical analyses showed that good curative effect was achieved in both the group using Duhuojisheng Tang alone and with combined therapies. CONCLUSION: Using Duhuojisheng Tang alone or combined with other therapies can effectively im- prove pain, leg-raising height and other clinical symptoms of patients with prolapse of lumbar in- tervertebral disc. Due to low methodological quali- ty of the articles, no exact recommendations can be made.展开更多
A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV, This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarit...A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV, This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarithromycin. A simple one-step deproteinization procedure was used to prepare plasma samples. Separation was achieved on a CAPCELL CORE ADME CI8 column with a gradient mobile phase consisting of solution A (water containing 0.1% formic acid) and solution B (acetonitrile) at a flow rate of 0.3 mL/min. Multiple reaction monitoring (MRM) was used with an electrospray ionization source (ESI) in positive mode. A good linear response was observed within the ranges of 0.01 to 5.00 ~g/mL for paeoniflorin and 0.000l to 0.05 ~tg/mL for astragaloside IV. The accuracy (RE) was within the range of-3.5% to 6.3%, and the intra- and inter-day precisions (RSD) were within 14.2%. The extraction recoveries were all above 78.9%. The pharmacokinetic study of the two analytes in rats after oral administration of Huangqi Guizhi Wuwu Decoction (HGWD) was successfully completed through this method. The method develooed in this studv will fill a gap in oharmacokinetic studies of HGWD.展开更多
In the present study, we aimed to investigate the frequency of CYP3 A4*18 B genetic polymorphism in Han Chinese populations, and to assess the effect of the CYP3 A4*18 B genetic polymorphism on the pharmacokinetics of...In the present study, we aimed to investigate the frequency of CYP3 A4*18 B genetic polymorphism in Han Chinese populations, and to assess the effect of the CYP3 A4*18 B genetic polymorphism on the pharmacokinetics of tinidazole. A total of 100 healthy volunteers from Han nationalities in China were recruited. DNA was extracted from peripheral leukocytes using a standard protocol. A PCR-RFLP method was developed to detect the alleles of CYP3 A4*18 B. A pharmacokinetic study of tinidazole was then carried out in two groups with CYP3 A4*1/*1(n = 10) and CYP3 A4*1/*18 B(n = 9) genotypes. Concentrations of tinidazole were determined using high-performance liquid chromatography in plasma samples that were collected up to 72 h after drug intake. In this study, 88 healthy volunteers were found with CYP3 A4*1/*1 genotype, and 12 were found with CYP3 A4*1/*18 B genotype. CYP3 A4*18 B/*18 B were absent from all subjects. The allele frequencies of CYP3 A4*18 B were 6%. The pharmacokinetic parameters of CYP3 A4*1/*1 genotype and CYP3 A4*1/*18 B genotype in healthy subjects were as follows: t1/2:(15.92±1.62),(15.77±1.67) h;Cmax:(18.72±3.10),(20.25±3.42) mg/L;tmax:(1.50±0.66),(1.45±0.69) h;Vd/F:(55.73±10.66),(51.30±7.75) L;CL/F:(2.44±0.47),(2.26±0.30) L·h;AUC0–∞:(424.40±82.38),(450.53±69.48) mg·h/L. Collectively, the CYP3 A4*18 B genetic polymorphism did not affect pharmacokinetics of tinidazolein healthy volunteers.展开更多
基金supported by the Capital Research Foundation for Medical Development, Beijing Medicine & Health Science Collaborative Research Project (Grant No. 2001-I-04)Beijing Administration of Traditional Chinese Medicine Professional Ethics 51510 Projects (Grant Nos. JJ-2006-56, JJ2007-031)
文摘Objective: To obtain epidemiological data on Traditional Chinese Medicine (TCM) therapeutic status of acute myocardial infarction (AMI) and to determine TCM characteristics and advantages to improve the level of TCM prevention and treatment of AMI. Methods: Clinical epidemiology methods were used to register and survey the TCM therapeutic status of hospitalized AMI patients. In 2001, the Chinese Association of Integrative Medicine surveyed the therapeutic status of 3308 AMI patients hospitalized in 30 hospitals in Beijing and Shanghai from 2000-2001. The Beijing Collaborative Study Group on Therapeutic Status of Acute Myocardial Infarction (the Study Group) then conducted a 10-year-long register survey on hospitalized AMI patients in Third-grade A-Level TCM hospitals in Beijing. After 2002, the Study Group further surveyed the treatment conditions of AMI-hospitalized patients in 10 Second-grade A-Level TCM hospitals. The therapeutic status in 8 Third-grade A-Level Western medicine hospitals was surveyed in 2001 and 2005 as a control. In 2008, in cooperation with the China Association of Chinese Medicine, the Study Group further performed a survey at 26 Third-grade A-Level TCM hospitals nation-wide. Approximately 5000 cases were investigated to obtain authoritative data on the therapeutic status of AMI patients in TCM hospitals in China. Results: We found that Chinese herbal intravenous preparations may be beneficial in reducing the mortality of AMI. Major complications of AMI, such as heart failure and arrhythmia, were significantly less during the 10-year survey period. The mortality of hospitalized AMI patients showed a decline. TCM treatment was helpful for AMI patients in improving their quality of life. Ten-year dynamic monitoring showed that the ability to perform reperfusion and to use drugs appropriately, as well as an effort to carry out the Clinical Guidelines has made great progress in TCM hospitals. However, TCM hospitals still have some problems in treating AMI, including a lack of standardized TCM syndrome diagnosis, the need for syndrome differentiation and treatment standardization, and clinical skills in reperfusion and standardized drug treatment still need to be further improved. Compared with AMI patients in Western medicine hospitals during the same period, those in TCM hospitals had the following characteristics: they were admitted to hospital later; they were older when they had a heart attack; there were more females, they had more problems in their medical history, and they had more concomitant illnesses and complications. Therefore, the demographic baseline data were significantly different between AMI patients in TCM hospitals and those in Western medicine hospitals. This indicated that patients in TCM hospitals were more critical than those in Western medicine hospitals. Conclusions: TCM has special advantages in treating AMI. TCM hospitals are making continuous progress in standardized treatment of AMI, but further improvement is still required. AMI patients in TCM hospitals have some special characteristics, and their condition may be more critical. Further clinical research on TCM treatment of AMI is required.
文摘Inflammatory arthritis refers to the migration of inflammatory cells(such as monocytes/macrophages,lymphocytes,and granulocytes)from the blood to the synovium or synovial fluid,causing joint pain and swelling.It is often associated with decreased joint mobility and functional damage.Some diseases lead to cartilage and skeletal damage,resulting in joint destruction.Common inflammatory arthritis includes rheumatoid arthritis,ankylosing spondylitis,and gout.
基金The authors thank the Principal of Shivalik College of Pharmacy,Nangal and BITS,Ranchi for providing the facilities for this research work.Support was also provided by Capital Application Project on Clinical Characteristics of Science and Technology Commission of Beijing Municipality(No.Z111107058811056)by the Planned Project on Beijing Traditional Chinese Medicine“Inheritance of 3 t 3 Program”of the Beijing Chinese Medicine Administration Bureau.
文摘Objective:Aerva lanata (Linn) Juss ex Schult,family Amaranthaceae,is a common wayside weed.The herb is accepted by the Ayurvedic Formulary of India.This study was undertaken to establish morphoanatomic and physiochemical standards of A.lanata.Methods:Leaf constants and high-performance thin layer chromatography fingerprint profiles of A.lanata were performed.Results and conclusion:The physico-chemical,morphologic,and histologic parameters presented in this paper may be proposed as standards to establish the authenticity of A.lanata and help differentiate it from other species such as Aerva tomentosa.
基金Supported by the Project of Beijing Municipal Natural Science Foundation(7173261)
文摘[Objectives] To study the effects of Tiaomaiyin and its disassembled prescription on expression of L-type calcium channel β2 subunit in rat model of tachyarrhythmia. [Methods] Sixty Wistar rats were randomly divided into model group,Tiaomaiyin prescription group( whole prescription group),main efficacy group of removing heat to cool blood( blood cooling group),and auxiliary drug efficacy group of benefiting qi and nourishing heart( qi benefiting group),auxiliary efficacy group of promoting flow of qi and blood circulation( qi flow promoting group),and amiodarone group( western medicine group). Aconitine was given 7 d after the intragastric administration of the corresponding drugs,and the time of occurrence of arrhythmia in each group was observed. The left ventricular myocardium was subjected to reverse transcription-polymerase chain reaction and Western blotting. [Results] The ventricular premature beats( VPB) time in the whole prescription group and western medicine group was significantly longer than that in the model group. Ventricular tachycardia( VT),ventricular fibrillation( VF),and cardiac arrest( CA) were longer in the whole prescription group,blood cooling group,and western medicine group. The mRNA and protein expression of L-type calcium channel β2 subunit in the whole prescription group,blood cooling group and western medicine group were significantly decreased. [Conclusions] Tiaomaiyin whole prescription group and blood cooling group can reduce the occurrence time of tachyarrhythmia and reduce the expression of LTCC β2 in myocardium.
基金Supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences:Design and Application of Mixed Method Research in Traditional Chinese Medicine(No.CI2021B003)Special Project of China Center for Evidence Based Traditional Chinese Medicine:Integrated Innovation and Application of Traditional Trial and Real-World Study of Chinese Medicine in Integrated Chinese and Western Medicine Setting(No.2020YJSZX-3)the Fundamental Research Funds for the Central Public Welfare Research Institutes:the Optimal Subject Setting and Design of Evidence-Based Research Implementation in the Area of Brain Diseases of Traditional Chinese Medicine(No.ZZ13-024-3)
文摘OBJECTIVE:To update the current characteristics about the scope and quality of mixed methods research(MMR)in complementary and alternative medicine(CAM)after nearly 10 years.METHODS:A 5-stage approach for conducting a scoping review was adopted.Articles published on the top 10 journals in CAM with the highest impact factor in 2020 were screened for MMR.Information of included articles were extracted,and then synthesized to illustrate the current state.Methodological quality was evaluated according to the Mixed Method Appraisal Tool(MMAT)2018 version.RESULTS:A total of 55(55/2991,2%)articles using mixed methods were retrieved,including 17 medical studies and 38 ethnobotanical studies.We performed an in-depth analysis on the 17 medical studies,which studied cancer,stress,pain,fatigue,exercises,mindfulness intervention,herbal medicine use,art and acupuncture.Thirteen pilot studies applied MMR to evaluate the feasibility of interventions or programs(13/17,76%);phenomenology was inferred as the most common philosophical assumptions(13/17,76%);the most applied type of MMR was convergent design(16/17,94%);integration often took place at integration(12/17,71%).Among the 16 eligible studies for quality appraisal,majority were rated as good(14/16,88%),whereas two studies were rated as poorly described.Primarily,a poor rating was due to incomplete reporting of data analysis and citations in qualitative components;lack of confounder controlling and the sampling strategy in quantitative components;poor description of integration and justification for mixed methods.Comparing with the previous review,fewer MMR were published in 2020 in CAM,but the proportion of studies that clearly reported MMR has increased by 4 times(4%→15%).CONCLUSION:CAM researchers need to realize the benefits that MMR can have on conducting further health care research.Our findings highlight that applying MMR will be helpful to understand the complex dynamics and interdisciplinary nature of complex intervention.In addition,addressing a standardized reporting criteria for MMR is recommended.
基金Supported by Capital Application Project on Clinical Characteristics of Science and Technology Commission of Beijing Municipalit (No. Z111107058811056)Planned Project on Beijing Traditional Chinese Medicine "inheritance of 3 + 3 programme" of Beijing Chinese Medicine Administration Bureau (2011-SZ-C-34)
文摘OBJECTIVE: A systematic review of the literature was conducted to evaluate the curative effect and safety of Duhuojisheng Tang on prolapse of the lumbar intervertebral disc. METHODS: The databases of PubMed, China Na- tional Knowledge Infrastructure (CNKI), Chinese Sci- entific Journals Database (VlP), Chinese Biomedical Literature Database (CBM) and Chinese Medical Ci- tation Index (CMCl) were searched up to January 30, 2012. Randomized controlled trials were select- ed to compare Duhuojisheng Tang with one ormore of the following treatments: traction, acu- puncture, massage, cupping and Western medical treatment. The quality-evaluating standard and the software RevMan 5.1 in Cochrane coordinative net were used to analyze the data. The effective index- es of the results were clinical curative rate, effective- ness of alleviating clinical symptoms and adverse reaction. RESULTS: Thirty-one randomized controlled trials of low quality, involving 3915 patients were system- atically evaluated. Statistical analyses showed that good curative effect was achieved in both the group using Duhuojisheng Tang alone and with combined therapies. CONCLUSION: Using Duhuojisheng Tang alone or combined with other therapies can effectively im- prove pain, leg-raising height and other clinical symptoms of patients with prolapse of lumbar in- tervertebral disc. Due to low methodological quali- ty of the articles, no exact recommendations can be made.
文摘A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV, This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarithromycin. A simple one-step deproteinization procedure was used to prepare plasma samples. Separation was achieved on a CAPCELL CORE ADME CI8 column with a gradient mobile phase consisting of solution A (water containing 0.1% formic acid) and solution B (acetonitrile) at a flow rate of 0.3 mL/min. Multiple reaction monitoring (MRM) was used with an electrospray ionization source (ESI) in positive mode. A good linear response was observed within the ranges of 0.01 to 5.00 ~g/mL for paeoniflorin and 0.000l to 0.05 ~tg/mL for astragaloside IV. The accuracy (RE) was within the range of-3.5% to 6.3%, and the intra- and inter-day precisions (RSD) were within 14.2%. The extraction recoveries were all above 78.9%. The pharmacokinetic study of the two analytes in rats after oral administration of Huangqi Guizhi Wuwu Decoction (HGWD) was successfully completed through this method. The method develooed in this studv will fill a gap in oharmacokinetic studies of HGWD.
基金The Research Grant from the 115 Project of Legionary Medical Treatment and Public Health(Grant No.06G023).
文摘In the present study, we aimed to investigate the frequency of CYP3 A4*18 B genetic polymorphism in Han Chinese populations, and to assess the effect of the CYP3 A4*18 B genetic polymorphism on the pharmacokinetics of tinidazole. A total of 100 healthy volunteers from Han nationalities in China were recruited. DNA was extracted from peripheral leukocytes using a standard protocol. A PCR-RFLP method was developed to detect the alleles of CYP3 A4*18 B. A pharmacokinetic study of tinidazole was then carried out in two groups with CYP3 A4*1/*1(n = 10) and CYP3 A4*1/*18 B(n = 9) genotypes. Concentrations of tinidazole were determined using high-performance liquid chromatography in plasma samples that were collected up to 72 h after drug intake. In this study, 88 healthy volunteers were found with CYP3 A4*1/*1 genotype, and 12 were found with CYP3 A4*1/*18 B genotype. CYP3 A4*18 B/*18 B were absent from all subjects. The allele frequencies of CYP3 A4*18 B were 6%. The pharmacokinetic parameters of CYP3 A4*1/*1 genotype and CYP3 A4*1/*18 B genotype in healthy subjects were as follows: t1/2:(15.92±1.62),(15.77±1.67) h;Cmax:(18.72±3.10),(20.25±3.42) mg/L;tmax:(1.50±0.66),(1.45±0.69) h;Vd/F:(55.73±10.66),(51.30±7.75) L;CL/F:(2.44±0.47),(2.26±0.30) L·h;AUC0–∞:(424.40±82.38),(450.53±69.48) mg·h/L. Collectively, the CYP3 A4*18 B genetic polymorphism did not affect pharmacokinetics of tinidazolein healthy volunteers.