Jing Si Herbal Tea Liquid Packet in the Treatment of Dyspeptic Symptoms and Psychophysical Burden in Patients With Disorders of Long-Coronavirus Disease(COVID) Gut-brain Interaction --a Double-blind, Randomized, Placebo Controlled Study
Phase: NA
Conditions: Healthy Subjects, COVID-19 Pneumonia, Irritable Bowel Syndrome, Functional Gastrointestinal Disorders
Sponsor: Buddhist Tzu Chi General Hospital

Version date：(Version 3, 11/10/2022) 
Application Form of Buddhist Tzu Chi Medical Foundation 
"Clinical Research on Jingsi Bencao Decoction" 
Application number：________________ 
A. Basic information 
Plan 
name 
Chinese 
淨斯本草飲濃縮液對長新冠症狀-腸腦軸失調之身心症狀療效-隨機雙盲臨床試驗 
English 
Jing Si Herbal Tea Liquid Packet in the treatment of dyspeptic symptoms and 
psychophysical burden in patients with disorders of long-COVID gut-brain interaction --a 
double-blind, randomized, placebo-controlled study 
Principal 
Investigator 
Name 
Chen, 
Chien-Lin 
Job 
title 
Director of 
Gastroenterology Campus Hualien Tzu 
Chi Hospital 
unit 
or 
department 
Gastroenterology 
Plan execution 
period 
■One year 
   From January 1, 2012 to December 31, 2012, a total of 1 year. 
This year, apply to host various research projects (including pre-approval cases) in the hospital, a total of 1 
case. (Co-hosted projects will not be counted) 
■ Yes, project name: Exploring the relationship between supragastric belching, physical and mental symptoms, 
and esophageal acid reflux: clinical application of treatment optimization for gastroesophageal reflux disease. 
□ No. 
Whether the project has carried out the following related experiments: [If you tick any of the following items, 
you need to attach the relevant experiment/research consent documents] 
□ No. 
■ Human experiments/human specimens (including human embryos/human embryonic stem cells).          
A total of 1 document must be attached. 
Program Contact 姓名：Chen, Chien-Lin _ Tel: (public) (03)8561825#13224  (mobile) 0988-282055 
E-MAIL：harry.clchen@msa.hinet.net 
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of the host of the 
total 
plan (please sign in 
person) 
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the project (please 
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the project (please 
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the project (please 
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Version date：(Version 3, 11/10/2022) 
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the project (please 
sign in person) 
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the project (please 
sign in person) 
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the project (please 
sign in person) 
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Dean's signature 
(personal signature 
or seal) 
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 Remarks: If there are more than one co-hosts of the plan, please add the column by yourself to 
facilitate signature 
 
B. Personnel participating in the plan 
Category 
(moderator, co-host, 
co-host, researcher, etc.) 
Name 
Current position 
The specific nature, project and scope of work 
undertaken in this research project 
Moderator 
Chen, 
Chien-Lin 
Director of 
Gastroenterology 
Project progress supervision, research conduct and 
research plan formulation, data analysis analysis and 
report writing. 
Co-host 
Wong, 
Ming-Wun 
Attending Physician 
of Gastroenterology 
Actual case acceptance, case processing, and data 
collation in the plan. 
Co-host 
Liu, Tso-Tsai 
Director of 
Endoscopy 
Department 
Actual case acceptance, case processing, and data 
collation in the plan. 
Co-host 
Yi, 
Chih-Hsun 
Attending Physician 
of Gastroenterology 
Actual case acceptance, case processing, and data 
collation in the plan. 
Co-host 
Lei, Wei-Yi 
Attending Physician 
of Gastroenterology 
Actual case acceptance, case processing, and data 
collation in the plan. 
Co-host 
Hung, 
Jui-Sheng 
Attending Physician 
of Gastroenterology 
Actual case acceptance, case processing, and data 
collation in the plan. 
Co-host 
Liang, 
Shu-Wei 
Attending Physician 
of Gastroenterology 
Actual case acceptance, case processing, and data 
collation in the plan. 
Co-host 
Liu,     
Chin-Hung 
Associate Professor Specimen analysis, data analysis and statistics in the 
plan. 
Co-host 
Chen, 
Chun-Yao  
Assistant professor Specimen analysis, data analysis and statistics in the 
plan. 

Version date：(Version 3, 11/10/2022) 
Research assistant 
Jian, 
Yu-Xhuan 
Research assistant Organize data, data analysis and statistics and handle 
administrative affairs. 
※If there are not enough fields, please copy by yourself. 
C. Implementation of other research projects 
In the past three years, the project host, co-hosts, and other research team members must fill in the 
details of the implementation of the research plan. 
Category 
(moderator, 
co-host, co-host, 
researcher, etc.) 
Name 
Project name 
Jobs 
within the 
plan 
from year to 
month 
Grant 
agencies 
Host 
Chen, 
Chien-Lin 
To explore the pathophysiological 
effects of esophageal contraction, 
mucosal integrity and acid 
sensitivity on gastroesophageal 
reflux disease and the basis for 
treatment strategies 
Host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Host 
Chen, 
Chien-Lin 
Efficacy of Jingsi Bencao 
Decoction on physical and mental 
symptoms of functional 
dyspepsia-a randomized 
double-blind clinical trial 
Host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Host 
Chen, 
Chien-Lin 
Discuss the pathophysiological 
mechanism of gastroesophageal 
reflux disease and establish the 
basis for accurate diagnosis and 
treatment based on esophageal 
reflux clearance ability, mucosal 
integrity and physical and mental 
characteristics 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Chen, 
Chien-Lin 
Discussion on the 
Pathophysiological Mechanism of 
Laryngopharyngeal Reflux 
Disease: Clinical Application of 
Artificial Intelligence Assisted 
and Accurate Diagnosis and 
Personalized Treatment Strategies 
Co-host 
2022/8/1~ 
2025/07/31 
Ministry of 
Science and 
Technology 
Host 
Chen, 
Chien-Lin 
Discuss the pathophysiological 
mechanism and treatment strategy 
of afferent nerve distribution, 
esophageal peristalsis and drug 
regulation in gastroesophageal 
reflux disease 
Co-host 
2022/8/1~ 
2025/07/31 
Ministry of 
Science and 
Technology 
Host 
Chen, 
Chien-Lin 
To explore the influence and 
clinical application of opioid 
analgesics on the 
pathophysiological mechanism of 
esophageal contraction and reflux 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Chen, 
Chien-Lin 
Analysis of 24-hour esophageal 
acid-base impedance 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
examination-technical 
performance and clinical 
application of gastroesophageal 
reflux disease diagnosis with 
artificial intelligence of 
supervised learning 
Host 
Chen, 
Chien-Lin 
Application of high-resolution 
impedance pharyngeal function 
test and Sydney swallowing 
questionnaire in oropharyngeal 
dysphagia and voice disorders 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Chen, 
Chien-Lin 
Application of artificial 
intelligence in high-resolution 
esophageal function examination 
- research on unsupervised 
algorithm model based on deep 
learning 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Chen, 
Chien-Lin 
To explore the influence of 
clinical characteristics and 
intestinal flora in patients with 
metabolism-related fatty liver 
under the regulation of diet and 
exercise 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Chen, 
Chien-Lin 
To explore the role of esophageal 
microbiota in novel impedance 
parameters, clinical classification 
and hypersensitivity in 
gastroesophageal reflux disease 
Host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Chen, 
Chien-Lin 
Clinical application of new 
esophageal impedance basic 
value supplemented with risk 
assessment to predict treatment 
response and recurrence of 
gastroesophageal reflux disease 
Host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Chen, 
Chien-Lin 
To explore the relationship 
between esophageal acid 
sensitivity, second-degree 
contraction of esophagus and 
subtypes of gastroesophageal 
reflux and the pathogenic 
mechanism 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Chen, 
Chien-Lin 
Clinical Application of 
High-resolution Impedance 
Pharyngeal Function Examination 
in Investigating Pharyngeal 
Dysphagia and Drug Response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Chen, 
Chien-Lin 
Can a cure for hepatitis C 
improve quality of life? 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Chen, 
Chien-Lin 
Improving the quality of fatty 
liver treatment with cross-group 
care 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Chen, 
Chien-Lin 
Discussion of differences in drug 
therapy in patients with sensitive 
esophagus and the role of 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
mucosal afferent innervation in 
this disease 
Co-host 
Chen, 
Chien-Lin 
To explore the pathophysiological 
role of esophageal mucosal 
afferent nerve distribution in 
gastroesophageal reflux disease 
complicated with esophageal 
motility dysfunction 
Co-host 
2020/8/1~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Chen, 
Chien-Lin 
Improve the diagnosis of 
laryngopharyngeal reflux disease 
and establish the indication of 
hydrogen ion pump blocker by 
using the average basic mucosal 
impedance value of the proximal 
esophagus at night 
Co-host 
2020/8/1~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Host 
Wong, 
Ming-Wun 
Discussion on the 
Pathophysiological Mechanism of 
Laryngopharyngeal Reflux 
Disease: Clinical Application of 
Artificial Intelligence Assisted 
and Accurate Diagnosis and 
Personalized Treatment Strategies 
Host 
2022/8/1~ 
2025/07/31 
Ministry of 
Science and 
Technology 
Host 
Wong, 
Ming-Wun 
Analysis of 24-hour esophageal 
acid-base impedance 
examination-technical 
performance and clinical 
application of gastroesophageal 
reflux disease diagnosis with 
artificial intelligence of 
supervised learning 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
Discuss the pathophysiological 
mechanism of gastroesophageal 
reflux disease and establish the 
basis for accurate diagnosis and 
treatment based on esophageal 
reflux clearance ability, mucosal 
integrity and physical and mental 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
To explore the influence and 
clinical application of opioid 
analgesics on the 
pathophysiological mechanism of 
esophageal contraction and reflux 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
Application of high-resolution 
impedance pharyngeal function 
test and Sydney swallowing 
questionnaire in oropharyngeal 
dysphagia and voice disorders 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
Application of artificial 
intelligence in high-resolution 
esophageal function examination 
- research on unsupervised 
algorithm model based on deep 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
learning 
Host 
Wong, 
Ming-Wun 
To explore the influence of 
clinical characteristics and 
intestinal flora in patients with 
metabolism-related fatty liver 
under the regulation of diet and 
exercise 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
Efficacy of Jingsi Bencao 
Decoction on physical and mental 
symptoms of functional 
dyspepsia-a randomized 
double-blind clinical trial 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Host 
Wong, 
Ming-Wun 
Improve the diagnosis of 
laryngopharyngeal reflux disease 
and establish the indication of 
hydrogen ion pump blocker by 
using the average basic mucosal 
impedance value of the proximal 
esophagus at night 
Host 
2020/8/1~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Host 
Wong, 
Ming-Wun 
To explore the role of esophageal 
microbiota in novel impedance 
parameters, clinical classification 
and hypersensitivity in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
To explore the relationship 
between esophageal acid 
sensitivity, second-degree 
contraction of esophagus and 
subtypes of gastroesophageal 
reflux and the pathogenic 
mechanism 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
Clinical Application of 
High-resolution Impedance 
Pharyngeal Function Examination 
in Investigating Pharyngeal 
Dysphagia and Drug Response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
To explore the pathophysiological 
effects of esophageal contraction, 
mucosal integrity and acid 
sensitivity on gastroesophageal 
reflux disease and the basis for 
treatment strategies 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Host 
Wong, 
Ming-Wun 
Can a cure for hepatitis C 
improve quality of life? 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
Improving the quality of fatty 
liver treatment with cross-group 
care 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Host 
Wong, 
Ming-Wun 
Clinical application of new 
esophageal impedance basic 
value supplemented with risk 
assessment to predict treatment 
response and recurrence of 
gastroesophageal reflux disease 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
Host 
Wong, 
Ming-Wun 
Discussion of differences in drug 
therapy in patients with sensitive 
esophagus and the role of 
mucosal afferent innervation in 
this disease 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Yi, 
Chih-Hsun 
Exploring the relationship 
between esophageal contraction, 
esophageal mucosal integrity and 
esophageal mucosal afferent 
nerves: the mechanism of 
influence on esophageal 
dysfunction and gastroesophageal 
reflux 
Co-host 
  2017/8/1~ 
2020/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Liu, 
Tso-Tsai 
To explore the influence of 
clinical characteristics and 
intestinal flora in patients with 
metabolism-related fatty liver 
under the regulation of diet and 
exercise 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Discuss the pathophysiological 
mechanism of gastroesophageal 
reflux disease and establish the 
basis for accurate diagnosis and 
treatment based on esophageal 
reflux clearance ability, mucosal 
integrity and physical and mental 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
To explore the influence and 
clinical application of opioid 
analgesics on the 
pathophysiological mechanism of 
esophageal contraction and reflux 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Application of high-resolution 
impedance pharyngeal function 
test and Sydney swallowing 
questionnaire in oropharyngeal 
dysphagia and voice disorders 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Analysis of 24-hour esophageal 
acid-base impedance 
examination-technical 
performance and clinical 
application of gastroesophageal 
reflux disease diagnosis with 
artificial intelligence of 
supervised learning 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Application of artificial 
intelligence in high-resolution 
esophageal function examination 
- research on unsupervised 
algorithm model based on deep 
learning 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Efficacy of Jingsi Bencao 
Decoction on physical and mental 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 

Version date：(Version 3, 11/10/2022) 
symptoms of functional 
dyspepsia-a randomized 
double-blind clinical trial 
Corporation 
Co-host 
Liu, 
Tso-Tsai 
To explore the role of esophageal 
microbiota in novel impedance 
parameters, clinical classification 
and hypersensitivity in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
To explore the relationship 
between esophageal acid 
sensitivity, second-degree 
contraction of esophagus and 
subtypes of gastroesophageal 
reflux and the pathogenic 
mechanism 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Clinical Application of 
High-resolution Impedance 
Pharyngeal Function Examination 
in Investigating Pharyngeal 
Dysphagia and Drug Response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Improving the quality of fatty 
liver treatment with cross-group 
care 
Host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Can a cure for hepatitis C 
improve quality of life? 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Clinical application of new 
esophageal impedance basic 
value supplemented with risk 
assessment to predict treatment 
response and recurrence of 
gastroesophageal reflux disease 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
Discussion of differences in drug 
therapy in patients with sensitive 
esophagus and the role of 
mucosal afferent innervation in 
this disease 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu, 
Tso-Tsai 
To explore the pathophysiological 
effects of esophageal contraction, 
mucosal integrity and acid 
sensitivity on gastroesophageal 
reflux disease and the basis for 
treatment strategies 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Lei, Wei-Yi 
Discuss the pathophysiological 
mechanism and treatment strategy 
of afferent nerve distribution, 
esophageal peristalsis and drug 
regulation in gastroesophageal 
reflux disease 
Host 
2022/8/1~ 
2025/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Lei, Wei-Yi 
To explore the influence and 
clinical application of opioid 
analgesics on the 
pathophysiological mechanism of 
esophageal contraction and reflux 
characteristics 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
Co-host 
Lei, Wei-Yi 
Discuss the pathophysiological 
mechanism of gastroesophageal 
reflux disease and establish the 
basis for accurate diagnosis and 
treatment based on esophageal 
reflux clearance ability, mucosal 
integrity and physical and mental 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
Application of high-resolution 
impedance pharyngeal function 
test and Sydney swallowing 
questionnaire in oropharyngeal 
dysphagia and voice disorders 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
Application of artificial 
intelligence in high-resolution 
esophageal function examination 
- research on unsupervised 
algorithm model based on deep 
learning 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
Analysis of 24-hour esophageal 
acid-base impedance 
examination-technical 
performance and clinical 
application of gastroesophageal 
reflux disease diagnosis with 
artificial intelligence of 
supervised learning 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
To explore the influence of 
clinical characteristics and 
intestinal flora in patients with 
metabolism-related fatty liver 
under the regulation of diet and 
exercise 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
Efficacy of Jingsi Bencao 
Decoction on physical and mental 
symptoms of functional 
dyspepsia-a randomized 
double-blind clinical trial 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Co-host 
Lei, Wei-Yi 
To explore the pathophysiological 
role of esophageal mucosal 
afferent nerve distribution in 
gastroesophageal reflux disease 
complicated with esophageal 
motility dysfunction 
Host 
2020/8/1~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Lei, Wei-Yi 
To explore the role of esophageal 
microbiota in novel impedance 
parameters, clinical classification 
and hypersensitivity in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
To explore the relationship 
between esophageal acid 
sensitivity, second-degree 
contraction of esophagus and 
subtypes of gastroesophageal 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
reflux and the pathogenic 
mechanism 
Co-host 
Lei, Wei-Yi 
Clinical Application of 
High-resolution Impedance 
Pharyngeal Function Examination 
in Investigating Pharyngeal 
Dysphagia and Drug Response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
Can a cure for hepatitis C 
improve quality of life? 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
Improving the quality of fatty 
liver treatment with cross-group 
care 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
Clinical application of new 
esophageal impedance basic 
value supplemented with risk 
assessment to predict treatment 
response and recurrence of 
gastroesophageal reflux disease 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
Discussion of differences in drug 
therapy in patients with sensitive 
esophagus and the role of 
mucosal afferent innervation in 
this disease 
Host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Lei, Wei-Yi 
To explore the pathophysiological 
effects of esophageal contraction, 
mucosal integrity and acid 
sensitivity on gastroesophageal 
reflux disease and the basis for 
treatment strategies 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Lei, Wei-Yi 
Exploring the relationship 
between esophageal contraction, 
esophageal mucosal integrity and 
esophageal mucosal afferent 
nerves: the mechanism of 
influence on esophageal 
dysfunction and gastroesophageal 
reflux 
Co-host 
2017/8/1~ 
2020/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Hung, 
Jui-Sheng 
Application of high-resolution 
impedance pharyngeal function 
test and Sydney swallowing 
questionnaire in oropharyngeal 
dysphagia and voice disorders 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
Discuss the pathophysiological 
mechanism of gastroesophageal 
reflux disease and establish the 
basis for accurate diagnosis and 
treatment based on esophageal 
reflux clearance ability, mucosal 
integrity and physical and mental 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
To explore the influence and 
clinical application of opioid 
analgesics on the 
pathophysiological mechanism of 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
esophageal contraction and reflux 
characteristics 
Co-host 
Hung, 
Jui-Sheng 
Analysis of 24-hour esophageal 
acid-base impedance 
examination-technical 
performance and clinical 
application of gastroesophageal 
reflux disease diagnosis with 
artificial intelligence of 
supervised learning 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
Application of artificial 
intelligence in high-resolution 
esophageal function examination 
- research on unsupervised 
algorithm model based on deep 
learning 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
To explore the influence of 
clinical characteristics and 
intestinal flora in patients with 
metabolism-related fatty liver 
under the regulation of diet and 
exercise 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
Efficacy of Jingsi Bencao 
Decoction on physical and mental 
symptoms of functional 
dyspepsia-a randomized 
double-blind clinical trial 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Co-host 
Hung, 
Jui-Sheng 
Clinical Application of 
High-resolution Impedance 
Pharyngeal Function Examination 
in Investigating Pharyngeal 
Dysphagia and Drug Response 
Host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
To explore the role of esophageal 
microbiota in novel impedance 
parameters, clinical classification 
and hypersensitivity in 
gastroesophageal reflux disease 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
To explore the relationship 
between esophageal acid 
sensitivity, second-degree 
contraction of esophagus and 
subtypes of gastroesophageal 
reflux and the pathogenic 
mechanism 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
Can a cure for hepatitis C 
improve quality of life? 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
Improving the quality of fatty 
liver treatment with cross-group 
care 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
Clinical application of new 
esophageal impedance basic 
value supplemented with risk 
assessment to predict treatment 
response and recurrence of 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
gastroesophageal reflux disease 
Co-host 
Hung, 
Jui-Sheng 
Discussion of differences in drug 
therapy in patients with sensitive 
esophagus and the role of 
mucosal afferent innervation in 
this disease 
Co-host 
2020/1/1~ 
2020/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Hung, 
Jui-Sheng 
Discussion of differences in drug 
therapy in patients with sensitive 
esophagus and the role of 
mucosal afferent innervation in 
this disease 
Co-host 
2020/8/1~ 
2023/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Liang, 
Shu-Wei 
Application of artificial 
intelligence in high-resolution 
esophageal function examination 
- research on unsupervised 
algorithm model based on deep 
learning 
Host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liang, 
Shu-Wei 
Analysis of 24-hour esophageal 
acid-base impedance 
examination-technical 
performance and clinical 
application of gastroesophageal 
reflux disease diagnosis with 
artificial intelligence of 
supervised learning 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liang, 
Shu-Wei 
Discuss the pathophysiological 
mechanism of gastroesophageal 
reflux disease and establish the 
basis for accurate diagnosis and 
treatment based on esophageal 
reflux clearance ability, mucosal 
integrity and physical and mental 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liang, 
Shu-Wei 
To explore the influence and 
clinical application of opioid 
analgesics on the 
pathophysiological mechanism of 
esophageal contraction and reflux 
characteristics 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liang, 
Shu-Wei 
To explore the influence of 
clinical characteristics and 
intestinal flora in patients with 
metabolism-related fatty liver 
under the regulation of diet and 
exercise 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liang, 
Shu-Wei 
Efficacy of Jingsi Bencao 
Decoction on physical and mental 
symptoms of functional 
dyspepsia-a randomized 
double-blind clinical trial 
Co-host 
2022/1/1~ 
2022/12/31 
Tzu Chi 
Medical 
Corporation 
Co-host 
Liang, 
Shu-Wei 
To explore the role of esophageal 
microbiota in novel impedance 
parameters, clinical classification 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 

Version date：(Version 3, 11/10/2022) 
and hypersensitivity in 
gastroesophageal reflux disease 
Co-host 
Liang, 
Shu-Wei 
To explore the relationship 
between esophageal acid 
sensitivity, second-degree 
contraction of esophagus and 
subtypes of gastroesophageal 
reflux and the pathogenic 
mechanism 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liang, 
Shu-Wei 
Clinical Application of 
High-resolution Impedance 
Pharyngeal Function Examination 
in Investigating Pharyngeal 
Dysphagia and Drug Response 
Co-host 
2021/1/1~ 
2021/12/31 
Hualien Tzu 
Chi Hospital 
Co-host 
Liu,    
Chin-Hung 
Using bee indicators and 
geographic information system to 
assess pesticide exposure in 
different crops 
MOST109-2314-B-320-002-MY2 
Co-host 
2020/08/01~ 
2022/07/31 
Ministry of 
Science and 
Technology 
Co-host 
Liu,    
Chin-Hung 
Exploring the relationship 
between cholesterol metabolism 
pathway and drug insensitivity in 
oral squamous cell carcinoma 
TCMRC-P-110011 
Host 
2022/01/01~ 
2022/12/31 
慈濟大學 
Co-host 
Liu,    
Chin-Hung 
Synergistic antitumor effects of 
statins and SREBP2 inhibitors in 
oral squamous cell carcinoma: the 
role of the mevalonate pathway 
and statin-insensitive features 
TCMRC-P-109009 
Host 
2021/01/01~ 
2021/12/31 
慈濟大學 
Co-host 
Liu,    
Chin-Hung 
Molecular mechanisms of statins 
inhibiting the growth of oral 
squamous cell carcinoma: the role 
of DNA methyltransferases and 
the regulation of tumor 
suppressor gene epigenetics 
TCMRC-P-108003 
Host 
2019/10/01~ 
2020/09/30 
慈濟大學 
Co-host 
Chen, 
Chun-Yao 
To explore the influence of 
clinical characteristics and 
intestinal flora in patients with 
metabolism-related fatty liver 
under the regulation of diet and 
exercise 
Co-host 
2022/1/1~ 
2022/12/31 
Hualien 
Tzu 
Chi Hospital 
※If there are not enough fields, please copy by yourself. 
 
 
 
 
 
 
 

Version date：(Version 3, 11/10/2022) 
 
 
 
 
D. Instructions for Expected Use of Funds(Funding will be included in the review 
and scoring items, please do not make up) 
1. 
Please provide a detailed description of the purpose and annual amount of each expense (including 
research labor costs, consumables, etc.), if the column is insufficient, please add it yourself. 
2. 
Research manpower expenses shall not be diverted to other business expenses.                       
[Funds for the first year] (Please copy the form yourself and list the estimated funds year by year) 
(New Taiwan dollars) 
project name 
illustrate 
unit price 
quantity 
total price 
1. Research manpower 
■Full-time 
□ concurrently 
(Please refer to the regulations 
in the Medical Special 
Management Measures for 
relevant insurance premiums) 
Full-time staff: (the second year of 
full-time assistant at the bachelor level) 
The highest rank of personnel is limited to the ninth 
level of master's degree, and the items included in the 
work remuneration, labor and health insurance 
employer-borne 
expenses, 
labor 
retirement 
employer-borne expenses and year-end bonuses are 
handled in accordance with the regulations of the 
implementing agency (up to 1.5 months as the upper 
limit). 
32,240 
2,689 
37 
1,632 
1,998 
13 
12 
12 
12 
12 
419,120 
32,268 
444 
19,584 
23,976 
Subtotal 
 
 
495,392 
2. Consumables, items 
and miscellaneous 
expenses 
Computer peripheral consumables: printer 
ribbon, toner cartridge, ink cartridge, 
printer photosensitive drum/roller, special 
printing paper, etc. 
 
Miscellaneous: postage and 
telecommunications fees, printing fees, 
photocopying paper, photocopying fees, 
binding fees, stationery fees, poster 
production fees, computer data statistics 
fees, computer data analysis fees, paper 
submission fees, paper publication fees, 
etc. 
14,608 
 
 
10,000 
 
14,608 
 
 
10,000 
Subtotal 
 
 
24,608 
3. Medicine expenses 
(Jingsi herbal drink 
concentrate, please fill 
in the quantity) 
Jingsi herbal drink concentrate (2 packs*30 
days*150 people) 
Placebo (2 packs*30 days*150 people) 
0 
0 
9,000 
9,000 
0 
0 
Subtotal 
 
 
0 
4. Subject subsidy 
Subject allowance (subsidy) 
1,200 
150 
180,000 
Subtotal 
 
 
180,000 
5. Inspection fee 
(Please fill in the 
inspection items and 
fees) 
LC-MS sample processing and analysis, 
intestinal bacteria analysis 
5,000 
150 
750,000 
Subtotal 
 
 
750,000 
total 1,450,000 

Version date：(Version 3, 11/10/2022) 
= 
E. Summary of the plan in Chinese 
Please give an overview of the main points of this project within 500 words, and customize keywords 
according to the nature of this project, and please write in Chinese. 
    新冠肺炎患者在痊癒後，約10%患者產生長新冠症狀，長新冠症狀中的腹痛、腹脹、腹瀉及便祕
源自於腸腦軸失調，腸腦軸失調包含功能性消化不良和腸躁症，常規檢查無明顯異常，由於原因不明
但盛行率高，往往對患者的身心健康影響甚鉅。即使腸腦軸失調目前被認為和胃腸道局部發炎和微生
物菌相改變有關，但目前西醫治療療效不佳。有鑑於此，許多研究應用中草藥在功能性消化不良，並
且達到不錯的療效。淨斯本草飲濃縮液為取得衛福部外銷專用許可證之食品，其成分為艾葉、魚針草、
麥門冬、魚腥草、桔梗、甘草、紫蘇葉、菊花等臺灣本土八種能清潤、散寒、宣肺化痰、利濕清熱的
中藥草，在臨床試驗登記立案作為輔助新冠肺炎的治療，目前初步發現亦可改善患者腸胃症狀以及憂
焦慮程度。故本研究採雙盲隨機試驗，以淨斯本草飲濃縮液用於客觀檢查皆正常之長新冠症狀-腸腦軸
失調患者，評估其治療前後之身心症狀以及腸道菌代謝產物之變化。 
 
關鍵詞：長新冠症狀、腸腦軸失調、淨斯本草飲濃縮液、身心症狀 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
※If there are not enough fields, please copy by yourself. 
計畫概述：請概述執行本計畫之目的及可能產生對社會、經濟、學術發展等
面向的預期影響性(三百字以內)。 
 
腸腦軸失調(DGBI)包含功能性消化不良和腸躁症為新冠肺炎感染後的腸胃
道問題，也是傳統西醫療效值得改善的疾病，淨斯本草飲濃縮液為東部地區
研發之中草藥食品，期待淨斯本草飲濃縮液在感染新冠肺炎病毒後改善腸胃
道功能以及憂鬱情況的發現能夠用於改善腸腦軸失調(DGBI)之身心症狀。 
 
※此部分內容於獲核定補助後將逕予公開 

Version date：(Version 3, 11/10/2022) 
F. Summary of the plan in English 
Please provide an overview of the main points of this project within 500 words, and customize keywords 
according to the nature of this project, and please write in English. 
Dyspepsia refers to chronic or recurrent upper gastrointestinal symptoms. According to the Rome IV 
criteria, functional dyspepsia (FD) symptoms included meal-related fullness, early satiation, epigastric pain 
or burning which are unexplained after routine investigation. FD causes substantial psychophysical burden 
because of its unknown etiology and high prevalence. Although FD is currently associated with local 
inflammation of the gastrointestinal tract and microbiota alteration, current available treatments for FD are of 
limited effectiveness. In view of this, many studies have applied Chinese herbal medicine in FD and 
achieved some therapeutic benefit. The Jing Si Herbal Tea Liquid Packet composed of eight native 
Taiwanese herbs (wormwood, hickory grass, Ophiopogon japonicus, houttuynia cordata, platycodon, 
licorice, perilla leaves, chrysanthemum) has obtained a special export license from the Ministry of Health 
and Welfare. The Jing Si Herbal Tea Liquid Packet also has been registered in clinical trials as a 
complementary treatment for COVID-19. The preliminary data demonstrated that the Jing Si Herbal Tea 
Liquid Packet may improve gastrointestinal symptoms and anxiety in patients with COVID-19. Therefore, 
this study aims to investigate the impact of the Jing Si Herbal Tea Liquid Packet on psychophysical burden 
and metabolites of microbiota in patients with FD through a double-blind randomized manner. 
 
關鍵詞：functional dyspepsia; Jing Si Herbal Tea Liquid Packet; psychophysical burden 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
※If there are not enough fields, please copy by yourself. 

Version date：(Version 3, 11/10/2022) 
G. Background and purpose of the research project 
Please describe in detail the background, purpose, importance of this research project and the research 
situation related to this project at home and abroad, 
Comments on important references, etc., please write in Chinese format. 
Background 
Symptoms of the new crown-gut-brain axis disorder (disorders of gut-brain interaction, DGBI) 
    COVID-19 is raging all over the world. The novel coronavirus recognizes type 2 angiotensin-converting 
enzyme and infects various cells in the body, including cells in the gastrointestinal tract. About 12%–20% of 
patients are infected and develop gastrointestinal symptoms. (1, 2) About 10% of patients with COVID-19 
will develop symptoms of COVID-19 after recovery, (3) Abdominal pain, bloating, diarrhea and constipation 
in symptoms of COVID-19 originate from disorders of gut-brain interaction , DGBI). (4) In the upper 
gastrointestinal tract (upper abdominal pain, abdominal distension), it is called functional dyspepsia, and in 
the lower gastrointestinal tract (abdominal pain, diarrhea, constipation), it is called irritable bowel syndrome. 
(5) In a large-scale survey in the United States (more than 100,000 people), it was found that after the 
COVID-19 epidemic, the incidence of gut-brain axis disorder (DGBI) increased by 75% compared with 
before the epidemic. (6) Disorders of the gut-brain axis (DGBI) include functional dyspepsia and irritable 
bowel disorder. At present, there is no clear pathogenesis and standard treatment. The consensus is to use the 
Roman diagnostic criteria, evaluate by questionnaire, and exclude other organic diseases. disease to 
diagnose. (5) The possible mechanisms of gut-brain axis disorder (DGBI) include local inflammation of the 
gastrointestinal tract, infiltration and activation of allergic cells, mucosal defects, changes in microbial flora, 
and hypersensitivity of viscera. (7) In terms of the microbial flora of the brain-gut axis, the metabolites of 
intestinal bacteria are regarded as the key to influence, among which short-chain fatty acids (SCFA) are 
regarded as good metabolizers As a product, when carbohydrates are fermented, anaerobic bacteria will 
produce many short-chain fatty acids (SCFA) in the distal small intestine and colon, which are composed of 
1-6 carbon atoms, and the main three metabolic compounds are acetic acid ( Acetate), Propionate and 
Butyrate. Short-chain fatty acids (SCFA) have been shown in research to have anti-inflammatory, 
anti-oxidant, anti-diabetic, anti-cancer and antibacterial effects. When the bacterial phase changes, the 
concentration of short-chain fatty acids may change accordingly and affect human physiological responses. 
When the intestinal flora is out of balance, a variety of bad metabolites will be produced: Trimethylamine 
N-oxide, TMAO (derived from L-Carnitine or Choline), indoxyl sulfate (derived from Tryptophan) and 
p-cresyl sulfate (derived from Tyrosine), etc. (8) 
Changes in the bacterial phase of the new crown symptoms 
SARS-CoV-2 infection caused significant changes in the intestinal flora of patients. The number of 

Version date：(Version 3, 11/10/2022) 
potential pathogens in the patient's body increases, and the antibiotic treatment also reduces the beneficial 
bacteria. 9 Hazan et al. (2022) showed reduced gut bacterial diversity in infected individuals, with reduced 
numbers of Bifidobacterium, Faecalibacterium, and Roseburium. 10 At six months post-infection, the 
intestinal bacterial diversity of the patients was still significantly low. 11 In addition to reduced diversity, 
these symptomatic patients had lower numbers of anti-inflammatory bacteria such as Faecalibacterium 
prausnitzii, Eubacterium rectale, Bifidobacterium adolescentis, and potential pathogens such as Rothia, 
Erysipelatoclostridium, Ruminococcus gnavus in the gut three months after infection. , Ruminococcus 
torques, and Bacteroides dorei are more. 12 Su et al. (2022) studied the dysbiosis caused by post-acute 
COVID-19 syndrome and found that there were more potential pathogens such as Erysipelatoclostridium 
ramosum and Ruminococcus gnavus, and beneficial bacteria Bifidobacterium adolescentis, B. 
pseudocatenulatum) decreased. 13 These evidences show that the intestinal flora has not fully recovered from 
the imbalance during infection, and is still in a state of low diversity and favorable pathogens, which can 
continue to cause immune responses in the intestine. Functional dyspepsia is also thought to be caused by 
increased permeability of the intestinal wall of the small intestine, allowing intestinal microbial metabolites 
to infiltrate the tissues and activate the immune system. 14 
In both functional dyspepsia and irritable bowel disorder, there is marked dysbiosis in the gut. Bacterial 
changes in patients with functional dyspepsia include decreased numbers of Bacteroidetes (Prevotellaceae) 
and increased numbers of Proteobacteria, Firmicutes (Streptococcus and Clostridia) and Bifidobacteria. 15 
Bacterial changes in IBD included increased Clostridia (increased Ruminococcus but decreased 
Faecalibacterium), increased Lactobacillus and Streptococcus within the phylum Firmicutes, increased 
Bacteroides, and decreased Bifidobacteria. 16 After synthesis, it can be seen that the changes in the gut-brain 
axis disorder are mainly due to the replacement of Bacteroidetes by Firmicutes, while the changes in the 
number of Proteobacteria and Bifidobacteria are inconsistent. 
Jing Si Herbal Tea Liquid Packet 
    The ingredients of Jing Si Herbal Tea Liquid Packet are mugwort leaves, houttuynia cordata, 
Ophiopogon japonicus, Houttuynia cordata, Campanulaceae, licorice, perilla leaves, chrysanthemum and 
other eight native Taiwanese herbs that can clear away moisture, dispel cold, relieve lungs and resolve 
phlegm, and clear away dampness and heat. Chinese medicinal herb, current research has found that it can 
block the combination of the new coronavirus and cells, and can also reduce cell penetration and block the 
virus from penetrating cells, while targeting wild-type and mutant viruses D614G, B.1.1.7, 501Y.V2 Carrying 
out animal studies, it was found that Jing Si Herbal Tea Liquid Packet can reduce the ability of 60 to 70% of 
the virus to infect the upper respiratory tract, lung, heart, and intestine of mice and reduce the expression of 
FKBP51, a protein related to depression, by 40%. The effect of using Jing Si Herbal Tea Liquid Packet to 
help reduce the amount of virus and systemic anti-inflammatory effect in patients with COVID-19. (9) In our 

Version date：(Version 3, 11/10/2022) 
ongoing clinical study, for functional dyspepsia (FD) patients, Jing Si Herbal Tea Liquid Packet can improve 
symptoms in 75% of patients, compared with only 33% of placebo. 
Purpose 
A double-blind randomized trial was conducted to investigate the improvement of Jingsi Bencao 
decoction concentrate on the physical and mental symptoms of gut-brain axis disorder (DGBI) and the 
changes in intestinal flora after COVID-19. 
Importance 
Gut-brain axis disorders (DGBI), including functional dyspepsia and irritable bowel syndrome, 
are gastrointestinal problems after COVID-19 infection. They are also diseases that are worthy of 
improvement in the efficacy of traditional Western medicine. The discovery that Jingsi Bencao Drink 
Concentrate improves gastrointestinal function and depression after infection with the new coronavirus can 
be used to improve the physical and mental symptoms of gut-brain axis disorder (DGBI). 
 
※If there are not enough fields, please copy by yourself. 
 

Version date：(Version 3, 11/10/2022) 
H. Research methods, steps and implementation progress 
1. Please describe in detail the research methods and reasons used in this project. 
2. Estimated possible difficulties and solutions. 
3. If it is a continuous plan, the research progress report or primary data of the previous year 
should be attached at the same time. 
4. Please write in Chinese format. 
1. Subject acceptance and exclusion conditions 
This study is a prospective study, which is expected to last for one year. It is planned to recruit 150 
subjects with gut-brain axis disorder (DGBI) three months after being infected with new coronary 
pneumonia: 75 of them Functional dyspepsia (FD) subjects and 75 irritable bowel syndrome (IBS) 
subjects. 
Subject inclusion conditions (Inclusion criteria) 
1. Age between 20-70 years old. 
2. Those who meet the definition of functional dyspepsia (FD). 
(Functional dyspepsia (FD) is chronic (once a week, lasting at least three months, at least six 
months before the first symptom) upper gastrointestinal symptoms (any of the following): 
postprandial abdominal distension, easy to feel full, Epigastric pain or burning sensation in the 
upper abdomen, and no symptoms of gastrointestinal bleeding or significant weight loss, no 
abnormality after upper gastrointestinal endoscopy). 
3. Those who meet the definition of irritable bowel syndrome (IBS). 
(Irritable bowel syndrome (IBS) is chronic (once a week, lasting for at least three months) lower 
gastrointestinal symptoms: abdominal pain combined with diarrhea or constipation, and no 
symptoms of gastrointestinal bleeding or significant weight loss, no abnormalities after 
colonoscopy) . 
4.Be conscious and willing to sign the subject's consent form. 
Subject Exclusions (Exclusion criteria) 
1. Abnormal liver and kidney function; 
2. Abnormal blood tests and thyroid abnormalities; 
3. Have received surgery on the digestive tract; 
4. Abnormal upper gastrointestinal endoscopy; 
5. Abnormal colonoscopy; 
6. Antibiotics are being used for infectious diseases; 
7. Pregnant or breastfeeding women; 
8. Suffering from heart, liver, or kidney failure; 
9. Physical weakness, allergies, asthenia and cold constitution and chronic diseases. 
2. Experimental process 
150 subjects with gut-brain axis disorder (DGBI) three months after being infected with new coronary 

Version date：(Version 3, 11/10/2022) 
pneumonia will be recruited in the outpatient department of gastroenterology, including 75 subjects with 
functional dyspepsia (FD) and 75 subjects with irritable bowel syndrome (IBS) ) subjects; qualified subjects 
will receive blood and feces sampling and complete physical and mental symptom assessment (sleep habits 
questionnaire, anxiety questionnaire, stress questionnaire, gastrointestinal symptoms questionnaire, and 
irritable bowel syndrome questionnaire) before treatment , and then according to the double-blind random 
allocation method, the computer generated garbled characters, and assigned Jing Si Herbal Tea Liquid Packet 
or placebo according to the coding sequence, and the research assistant gave Jing Si Herbal Tea Liquid 
Packet or placebo, Host and recipients None of the subjects knew what the content of the assignment was. 
The experimenters took Jing Si Herbal Tea Liquid Packet or placebo in the first month, and after the end of 
the month, they received blood and stool tests and complete physical and mental symptom assessment (sleep 
habits questionnaire, anxiety questionnaire, stress questionnaire) , gastrointestinal symptom questionnaire, 
and irritable bowel syndrome questionnaire), the laboratory will conduct pre- and post-test analysis of 
LC-MS and intestinal bacteria, and then conduct a cross-test. The original placebo will take Jing Si Herbal 
Tea Liquid Packet in the second month, previously taking Jing Si Herbal Tea Liquid Packet will take a 
placebo in the second month, after the end of the second month, do the third complete physical and mental 
symptom assessment (sleep habits questionnaire, anxiety questionnaire, stress questionnaire, digestive tract 
Symptom Questionnaire, Irritable Bowel Disorder Questionnaire), the test is completed. 
Research flow chart 
 

Version date：(Version 3, 11/10/2022) 
3. Questionnaire 
The questionnaire items included sleep habits questionnaire, anxiety questionnaire, stress questionnaire, 
gastrointestinal symptoms questionnaire, and irritable bowel syndrome questionnaire. The details of the 
questionnaire are attached. 
4.Collection, preservation, transportation and DNA extraction of feces 
Fix the collection box on the toilet lid, discharge fresh feces into the collection box, then screw the lid 
tightly and place it in a zipper bag within 4 hours or in a -4°C refrigerator within 24-48 hours Sent to the 
laboratory for sub-packaging, and then refrigerated in a -80°C refrigerator. Thaw when the DNA is extracted, 
the extraction process includes the following steps sample homogenization, cell lysis, non-DNA material 
removal and DNA purification. 
5.Gut micrtobiota sequencing and community analysis 
In this study, 16S rDNA massively parallel sequencing will be used to analyze the composition of gut 
bacteria. 0.25 g of stool samples were pooled for DNA extraction with the QIAmp PowerFecal Kit (Qiagen, 
Hilden, Germany). The purified DNA was PCRed with primers for 341F and 805R to amplify the V3-V4 
fragments of the 16S rRNA gene, and the barcode was sent to the manufacturer for library building. The 
Illumina MiSeq platform was used for next-generation pair-end sequencing. Sample 30000 reads. After the 
sequence obtained by the manufacturer was screened for high-quality fragments by Mothur and Usearch 
software, the bacterial phase composition and taxonomic status of each sample were calculated. The 
taxonomic status of each sequence was determined by comparing the Mothur software with the SILVA 
sequence database. The investigators will use Microbiome Analyst R and other suitable R programming 
language packages to perform cluster analysis and network analysis of bacterial composition. 
6.Stool and Blood LC-MS Analysis 
I. Plasma sample collection and preparation： 
    Whole blood was collected in Vacutainer K2E-EDTA (BD Diagnostics, Franklin Lakes, NJ, USA) blood 
collection tubes. The collected whole blood samples were then transferred to 15 mL containing Ficoll-paque 
PLUS medium [whole blood (hall blood)/ Ficoll-paque PLUS medium = 4/3 (volume ratio v/v)] (GE 
Healthcare Life Sciences, Pittsburgh, PA, USA) and centrifuge (3000 rpm, 30 min) at room temperature. 
After centrifugation, the plasma (plasma) supernatant that was successfully layered was collected and 
distributed into sterilized 1.5 mL microcentrifuge tubes (eppendorf), and glacial acetic acid with a 
concentration of 1 N and a volume of 1% was added. ) aqueous solution to prevent the degradation of the 
analyte in plasma. Plasma is stored in a freezer at -80oC, and the storage period does not exceed 1 year. 
II. Previous processing method of Lipophilic Substances： 

Version date：(Version 3, 11/10/2022) 
    Thaw the plasma sample at room temperature for 10-20 minutes, then transfer 100 µL of plasma to a 
new 1.5 mL microcentrifuge tube. Add the internal standard (internal control, 13C-PA) first, then add 
methanol 3 times the volume of plasma for deproteinization, and let it stand at room temperature for about 
15-20 minutes. Then centrifuge the rested microcentrifuge tube (3,000 rpm, 10 min, 4 °C), and transfer the 
supernatant to the corresponding small glass test tube. Move the glass test tubes to a nitrogen blowing 
system, dry the samples through a nitrogen flow, and then add 100 µL of chloroform (Chloroform) to each 
sample for redissolution. A filtration extraction system was set up, and solid phase extraction columns [Solid 
phase extraction (SPE) columns (Strata-X-C 33 µm polymeric strong cation 60 mg/3 mL, Phenomenex, 
Torrance, CA, USA)] were used for extraction. Add 1.0-1.5 mL of n-hexane (hexane) solution to the erected 
column to activate the column, and use a vacuum pump to pump positive pressure for about 20-30 seconds. 
Replace the glass test tubes that have been filled with n-hexane solution under the filter extraction system, 
and then add the samples to the activated column in sequence. Add 1.0-1.5 mL of ethyl acetate (ethyl acetate) 
for vacuum extraction for about 30-45 seconds, and transfer the sample extracted with ethyl acetate to a 
nitrogen blowing system to dry it. Redissolve the sample with 100 µL of methanol, and finally transfer the 
reconstituted sample to a liquid chromatography-mass spectrometer (LC-MS) vial equipped with insert, and 
prepare for analysis on the machine with an injection volume of 30 µL per needle . 
III. Hydrophilic Substances before the processing method： 
    There are two extraction methods for such compounds, namely traditional methanol extraction (Traditional 
deproteinized extraction) and SLE column extraction (SLE column extraction). First, place the plasma sample at 
room temperature to thaw for about 10-20 minutes. After the thawing is complete, take 100 µL to a new 1.5 mL 
microcentrifuge tube (two tubes of 100 µL are required for each sample). Plasma samples were deproteinized by 
adding methanol at a volume ratio of 3 times or adding an equal volume of 50 mM sodium phosphate dibasic 
heptahydrate (Sodium phosphate dibasic heptahydrate) and evenly mixed. Set up the SLE column filtration 
system and sample test tube, put the sample mixed with 50 mM disodium hydrogen phosphate hydrate into the 
column, turn on the vacuum pump to filter and extract, wait for about 3 minutes, then add 1.2-1.5 mL of acetic 
acid Ethyl esters are used for dike flushing. In addition, for the methanol deproteinized group, after waiting for 
about 20 minutes, they were centrifuged (3,000 rpm, 10 min, 4 °C), and then the supernatant was taken out into 
the corresponding glass test tube. The samples with two different treatment methods were put into the nitrogen 
blowing system for drying and concentration. For the group undergoing deproteinization, add 300 µL of methanol 
to redissolve, and filter with MILLEX GP 0.45 µM PVDF filter (Millipore), and discharge the liquid into the 
LC-MS special sample bottle loaded with insert; For the group extracted by the column, 100 µL of methanol was 
added for back-dissolution and reconstitution, and it was put into the LC-MS special sample bottle loaded with 
insert, ready for analysis on the machine. 
d. LC-MS Analysis Conditions (Liquid Chromatography Mass Spectrometer)： 
 LC-MS condition I：Used to analyze Lipophilic Substances 
 LC-MS condition II：Used to analyze Hydrophilic Substances Substances) 

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Table 1. LC-MS analysis conditions: 
LC conditions 
HPLC system 
Waters Alliance e2695 
Injection volume 
30 µL 
Runtime 
60.0 min (I) 
18.0 min (II)  
Column 
Phenomenex Luna 
C18(2) 
(250 x 4.6 mm, 5 µm) 
Flow rate 
0.6 mL/min (I) 
0.8 mL/min (II) 
Column temp 
35℃ (I) 
40℃ (I) 
Condiction I (Lipophilic Substances) 
Mobile phase A 
Mobile phase B 
60:40 Acetonitrile:ddH2O with 9.2 mM 
Ammonium acetate (NH4CH3CO2) (pH 8.85) 
90:10 Isopropanol:Acetonitrile with 9.2 mM 
Ammonium acetate (NH4CH3CO2) 
Time (min) 
%A 
%B 
Curve 
Initial 
85 
15 
6 
8.0 
70 
30 
6 
10.0 
52 
48 
6 
44.0 
18 
82 
6 
46.0 
1 
99 
6 
48.0 
1 
99 
6 
48.4 
85 
15 
6 
60.0 
85 
15 
6 
Condiction II (Hydrophilic Substances) 
Mobile phase A 
Mobile phase B 
0.1% Formic acid in 99.9% ddH2O 
0.1% Formic acid in 99.9% MeOH 
Time (min) 
%A 
%B 
Curve 
0 
95 
5 
6 
14 
30 
70 
6 
16 
30 
70 
6 
18 
50 
50 
6 
MS conditions 
Detector 
Waters ACQUITY QDa (Performance) 
Ionization mode 
ESI Negative (I); ESI Negative and Positive (II) 
Capillary voltage 
Default (0.8 kV) 
Probe temp 
Default (600℃) 
Cone voltage 
20V(I); 15V(II) 
Sampling rate 
8 Hz 
Full scan 
250-600 m/z for Negative (I); 70-600 m/z for Negative or Positive 
SIR 
See Table 2 - "Molecular Ions (m/z)" 
 
e. Method validation： 
    Including Limits of detection, LOD and Limits of quantitation, LOQ, Calibration curve, Recovery, 
accuracy and precision, Intra-assay, accuracy and precision and Inter-assay precision and accuracy of each 
test substance. 
 
Table 2. LC-MS analysis Standard List: 
 
Molecular ion 
(m/z) 
Ion source 
mode 

Version date：(Version 3, 11/10/2022) 
Lipophilic Substances 
Short Chain Fatty 
acids (SCFAs) 
Acetate (2:0) 
42.0+153 (3NPH) 
ESI Negative 
Propionate (3:0) 
57+153 (3NPH) 
ESI Negative 
Butyrate (4:0) 
72+153 (3NPH) 
ESI Negative 
Long Chain 
Fatty acids 
Palmitic acid, PA (16:0) 
255.1 
ESI Negative 
Stearic Acid, SA (18:0) 
283.2 
ESI Negative 
Palmitoleic Acid, POA (16:1) 
253.2 
ESI Negative 
Oleic Acid, OA (18:1) 
281.2 
ESI Negative 
Fatty acid esters of 
hydroxy fatty acids 
(FAHFAs) 
Palmitoleic Acid Ester of 
9-Hydroxystearic Acid (9-POHSA) 
535.5 
ESI Negative 
Oleic Acid Ester of 
9-Hydroxystearic Acid (9-OAHSA) 
563.5 
ESI Negative 
Internal standards 
[13C16]- Palmitic acid (IS1) 
271.4 
ESI Negative 
Hydrophilic Substances 
Methionine cycle 
L-Methionine (L-Met) 
150.1 
ESI Positive 
S-adenosyl-L-methionine (SAM) 
399.0 
ESI Positive 
S-adenosyl-L-homocysteine (SAH) 
385.0 
ESI Positive 
L-Homocysteine (L-Hcy) 
136.1 
ESI Positive 
Methylmalonic acid (MMA) 
117.1 
ESI Negative 
Antioxidants 
Ascorbic acid (AA) 
174.9 
ESI Negative 
Nutrition index 
3-Methyl-L-histidine (3-MH) 
170.0 
ESI Negative 
Fatty acids carrier 
L-Carnitine (L-Car) 
162.1 
ESI Positive 
Acetyl-L-Carnitine (ALC) 
204.0 
ESI Positive 
Propionyl-L-Carnitine (PLC) 
218.0 
ESI Positive 
Nephrotoxin 
Trimethylamine N-oxide (TMAO) 
76.0 
ESI Positive 
Indoxyl Sulfate (InS) 
211.9 
ESI Negative 
p-Cresyl sulfate (pCS) 
187.0 
ESI Negative 
Internal standards 
d3-L-Methionine (d3-L-Met) (IS2) 
153.1 
ESI Positive 
d9-Trimethylamine N-oxide (d9-TMAO) (IS3) 
85.0 
ESI Positive 
7.Jing Si Herbal Tea Liquid Packet 
In this experiment, Jing Si Herbal Tea Liquid Packet was used. Its ingredients are eight kinds of native 
Taiwan species, such as mugwort leaves, hinoki, Ophiopogon japonicus, Houttuynia cordata, bellflower, 
licorice, perilla leaves, and chrysanthemum. , Dampness-clearing and heat-clearing herbs, take Jing Si Herbal 
Tea Liquid Packet 15 ml once a day in the morning and evening. 

Version date：(Version 3, 11/10/2022) 
 
8.Statistical Analysis 
Continuous variables were expressed as mean and standard deviation if they were normally distributed; 
if they were not normally distributed, they were expressed as median and interquartile range. The treatment 
effect is presented by the improvement percentage of the sleep habits questionnaire, depression 
questionnaire, anxiety questionnaire, stress questionnaire, gastrointestinal symptoms questionnaire, and 
irritable bowel syndrome questionnaire before and after treatment, and the curative effect of Jingsi Bencao 
Drink Concentrate and placebo is expressed as the chi-square by the improvement percentage Chi-squared 
test comparison, P value less than 0.05 was considered statistically significant difference, the statistical 
analysis software used was SPSS 19 for Windows (SPSS, Inc, Chicago, IL, USA). 
9. Sample Size Estimation 
According to our ongoing research, it is estimated that the efficacy of Jing Si Herbal Tea Liquid Packet 
for functional dyspepsia (FD) is 75%, while the efficacy of placebo is 33.3%. It is estimated by α-error 0.05; 
β-error 0.20, at least 100 subjects are required to be admitted, and taking into account that the subjects may 
withdraw and fail to complete the trial successfully, the estimated number of subjects admitted in this study 
is 150. 
10. Possible difficulties and solutions 
Possible difficulties: According to our current research, the effect of placebo on functional dyspepsia (FD) 
can reach 33.3%, so if the investigators want to prove that Jing Si Herbal Tea Liquid Packet has a positive 
effect on patients with new coronary pneumonia three months after infection Gut-brain axis dysregulation 
(DGBI) had to be statistically significantly greater than placebo to have a significant effect. 

Version date：(Version 3, 11/10/2022) 
Solution: This trial adopts a multi-faceted whole-person care model to evaluate the curative effect, not only 
the symptoms of gut-brain axis disorder (DGBI) three months after being infected with new coronary 
pneumonia, but also the assessment of physical and mental symptoms, stress, and intestinal flora. Confirm 
the effect of Jing Si Herbal Tea Liquid Packet on various aspects of gut-brain axis disorder (DGBI). 
 
11. References 
1. 
Mao R, Qiu Y, He JS, et al. Manifestations and prognosis of gastrointestinal and liver involvement in 
1. Mao R, Qiu Y, He JS, et al. Manifestations and prognosis of gastrointestinal and liver involvement 
in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 
2020;5:667-678. 
2. 
Cheung KS, Hung IFN, Chan PPY, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection 
and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. 
Gastroenterology 2020;159:81-95. 
3. 
Golla R, Vuyyuru SK, Kante B, et al. Disorders of gut-brain interaction in post-acute COVID-19 
syndrome. Postgrad Med J 2022. 
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Schmulson M, Ghoshal UC, Barbara G. Managing the Inevitable Surge of Post-COVID-19 Functional 
Gastrointestinal Disorders. Am J Gastroenterol 2021;116:4-7. 
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Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features 
and Rome IV. Gastroenterology 2016:1262-1279. 
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Aloysius MM, Goyal H, Ali A, et al. S220 Cancer-Specific 5-Year Survival Following Endoscopic 
Polypectomy versus Surgery for Malignant Colorectal Polyps.  2021;116:S97-S98. 
7. 
Margolis KG, Cryan JF, Mayer EA. The Microbiota-Gut-Brain Axis: From Motility to Mood. 
Gastroenterology 2021;160:1486-1501. 
8. 
Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 
2021;19:55-71. 
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Zuo T, Wu X, Wen W, et al. Gut Microbiome Alterations in COVID-19. Genomics Proteomics 
Bioinformatics 2021;19:679-688. 
10. 
Hazan S, Stollman N, Bozkurt HS, et al. Lost microbes of COVID-19: Bifidobacterium, 
Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 
infection severity. BMJ Open Gastroenterol 2022;9. 
11. 
Chen Y, Gu S, Chen Y, et al. Six-month follow-up of gut microbiota richness in patients with 
COVID-19. Gut 2022;71:222-225. 
12. 
Tian Y, Sun KY, Meng TQ, et al. Gut Microbiota May Not Be Fully Restored in Recovered 
COVID-19 Patients After 3-Month Recovery. Front Nutr 2021;8:638825. 
13. 
Su Q, Lau RI, Liu Q, et al. Post-acute COVID-19 syndrome and gut dysbiosis linger beyond 1 year 
after SARS-CoV-2 clearance. Gut 2022:gutjnl-2022-328319. 
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Wauters L, Ceulemans M, Schol J, et al. The Role of Leaky Gut in Functional Dyspepsia. Front 
Neurosci 2022;16:851012. 
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Zhou L, Zeng Y, Zhang H, et al. The Role of Gastrointestinal Microbiota in Functional Dyspepsia: A 
Review. Front Physiol 2022;13:910568. 
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Mazzawi T. Gut Microbiota Manipulation in Irritable Bowel Syndrome. Microorganisms 2022;10. 
17. 
Hsieh PC, Chao YC, Tsai KW, et al. Efficacy and Safety of Complementary Therapy With Jing Si 
Herbal Tea in Patients With Mild-To-Moderate COVID-19: A Prospective Cohort Study. Front Nutr 
2022;9:832321. 
 
 
 
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