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\begin{document}

\title{Combinatorial biomedicine: A novel discipline}



\author[1]{Chunsong Hu}%
\affil[1]{Nanchang University}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Based on the author's previous work, this article proposed a novel
discipline-- combinatorial biomedicine. Currently, there are several
classical examples. One is a magic ``polypill'' covering the ``Health
Essential (HE) 5'', that is, ``environment-sleep-emotion-exercise-diet''
intervention {[}E(e)SEEDi{]} lifestyle; Another is an innovative
``traditional Chinese medicine (TCM) Hot Pot''. In addition, the
iRT-ABCDEFG program is indeed suitable for better management of human
diseases. In fact, combinatorial biomedicine is pivotal in the
development of life science, biology and medicine, in particular the
pandemic and post-COVID-19 era, and has obvious advantages in screening,
diagnosis, treatments, prevention and rehabilitation of both major
non-communicable diseases (such as cardiovascular disease, diabetes,
cancer, stroke, and neurodegenerative diseases) and major infectious
diseases (such as AIDS, Helicobacter pylori infection, and COVID-19). As
a novel discipline, combinatorial biomedicine plays a crucial role in
combating human diseases and improving population health. It is about
time to propose and establish this novel discipline.%
\end{abstract}%



\sloppy


Review or Mini-Review

\textbf{Combinatorial biomedicine: A novel discipline}

Running title: CBM

Chunsong Hu

\emph{Department of Cardiovascular Medicine, Nanchang University,
Hospital of Nanchang University, Jiangxi Academy of Medical Science,
Nanchang 330006, Jiangxi, China}

From: Department of Cardiovascular Medicine, Nanchang University,
Hospital of Nanchang University, Jiangxi Academy of Medical Science, No.
461 Bayi Ave, Nanchang 330006, Jiangxi, China. Tel: (+86) 189 70816800;
Email: cnhucs@ncu.edu.cn or cnhucs@163.com

Word count: 2,436 (Main text) + 150 (Abstract)

References: 47

Table: 1

Figure: 1 Total pages: 17

Corresponding author.

\emph{E-mail address:} cnhucs@ncu.edu.cn or cnhucs@163.com (C. Hu).

ABSTRACT

Based on the author's previous work, this article proposed a novel
discipline-- combinatorial biomedicine. Currently, there are several
classical examples. One is a magic ``polypill'' covering the ``Health
Essential (HE) 5'', that is, ``environment-sleep-emotion-exercise-diet''
intervention {[}E(e)SEEDi{]} lifestyle; Another is an innovative
``traditional Chinese medicine (TCM) Hot Pot''. In addition, the
iRT-ABCDEFG program is indeed suitable for better management of human
diseases. In fact, combinatorial biomedicine is pivotal in the
development of life science, biology and medicine, in particular the
pandemic and post-COVID-19 era, and has obvious advantages in screening,
diagnosis, treatments, prevention and rehabilitation of both major
non-communicable diseases (such as cardiovascular disease, diabetes,
cancer, stroke, and neurodegenerative diseases) and major infectious
diseases (such as AIDS, Helicobacter pylori infection, and COVID-19). As
a novel discipline, combinatorial biomedicine plays a crucial role in
combating human diseases and improving population health. It is about
time to propose and establish this novel discipline.

\emph{Keywords:} \textbf{}

Combinatorial biomedicine

Infectious diseases

Innovation

Non-communicable diseases

Translational medicine

\textbf{1. Introduction}

With the rapid development of modern science and technology, various new
disciplines are constantly emerging in various fields. After returned to
China from the United States in 2001 as a visiting scholar sponsored by
China Scholarship Council, I has developed a unique way and devoted
myself to combinatorial biology and medicine innovation for decades
without the support of state funding. So far, as a Chinese scholar, I
made a series of achievements and fruits in China, such as from the
RT-ABCDE to the iRT-ABCDEF(G) strategies, obesity-OSA-hypertension
syndrome (OOHS) \& non-obesity-OSA-hypertension syndrome (NOOHS),
cardiovascular, diabetes, and cancer (CDC) strips, ``Level 210'' of
comprehensive prevention, and
SEEDi\textsuperscript{1.0-3.0}technologies. Some are the first in the
world, for example, ``a magic polypill'' {[}1{]}, that is the E(e)SEEDi
covering ``the Essential 5''
(``environment-sleep-emotion-exercise-diet'' intervention). In fact,
these innovations are not only helpful in both healthy China and global
health, but also gave birth to a new discipline--~combinatorial
biomedicine (Table 1).

\textbf{2. Scientific combination is vital and beneficial}

Currently, a new paradigm~of self-help traditional Chinese medicine
(TCM) prescription was created during the early COVID-19 pandemic
(2020), and the novel theory and fresh program of ``TCM Hot Pot''
consists of ``Bark-Flower-Fruit-Grass-Leaf-Nucleolus(seed)-Root''
{[}BFFGLNR{]} {[}2{]}. Due to the characteristic advantages, more easy
to learn and use, this discovery has won wide recognition and praise
from medical peers.~In fact, the innovative ``TCM Hot Pot'' has become a
new milestone in the medical field, and will better serve global
health.~Moreover, when a combination of ``TCM Hot Pot'' with ``the magic
polypill'', it will become all-round prescription, and people will no
longer be afraid of the COVID-19 pandemic and SARS-CoV-2 infection.~At
the same time, based on this new combination, novel treatment programs
and agents could be developed for cardiovascular diseases (CVD), such as
``Fuya Keli'' or ``Fuya Decoration'' for hypertension, which is relative
to Shensong~Yangxin~Capsule or ``Wenxin Keli'' for arrhythmia {[}3,4{]},
``Tongxinluo Capsule'' for coronary heart disease {[}5{]}, and ``Qili
Qiangxin Capsule'' for chronic heart failure {[}6{]}.

Generally speaking, on the one hand, the TCM prescription itself is
composed of several to dozens of herbs, and the names of many famous
clinical trials were combined, such as the CAST trial {[}7{]}, the
SPRINT trial {[}8{]}, and the HOPE-3 trial {[}9{]}. On the other hand,
many novel technologies and therapies in the biomedical field are also
combined, and there are some classical examples in both major
non-communicable diseases (mNCDs) including CVD, diabetes, and cancer,
and major infectious diseases (mIDs) including Helicobacter pylori (HP),
tuberculosis (TB), ~human immunodeficiency virus-1~(HIV), and COVID
infection. For example, new ``four-combined~treatment, FCT'' or
``quadruple treatment'' for chronic heart failure, ``triple-combination
therapy, TCT'' for eradicating Hp infection in~chronic~gastritis and
peptic~ulcer as well as the famous ``cocktail therapy'' for
AIDS.~Therefore, scientific combinations are vital and beneficial to
better efficacy in clinical medicine.

\textbf{3. Scientific combination originates from evidence-based
studies}

In fact, there are a series of clinical combinations for improvement of
efficacy. For example, there is common single-pill combination (SPC)
therapy or free-equivalent combination (FEC) therapy in hypertension
{[}10{]}, and there is often TB-HIV coinfection, which definitely needs
combinatorial treatment. To date, since faecal microbiota transplants
are effective for infection and recurrent infections, biotherapies by
combinations of vital gut microbiota are a promising choice {[}11{]}.
Studies in recent years found that antivirulence-antibiotic
combinatorial treatments {[}12{]} are effective strategies in treating
infections and limiting the spread of antibiotic resistance, and the
combination of PBT2 + polymyxin (colistin or FADDI-287) may improve
survival and reduce bacterial dissemination to other organs {[}13{]}.
With the rapid development of artificial intelligence (AI) and
machine-learning, their applications to the self-help prescription of
``TCM Hot Pot'' and deep development will surely usher in a brand-new
development of TCM.~As a typical example of combinatorial biomedicine,
``TCM Hot Pot'' will bring more benefits to human beings. Indeed, in
current field of translational medicine, there is an arising need for
combining and integrating computational or AI technologies with
experimental and clinical medicine across academia, industry, and
healthcare settings {[}14{]}.

However, only scientific and evidence-based combinations are vital and
beneficial in clinical practice. For example, the use of high-flow nasal
oxygen with noninvasive ventilation immediately after extubation
significantly decreased the risk of reintubation compared with high-flow
nasal oxygen alone {[}15{]}. A combination of medications with intensive
weight management using a low-carbohydrate diet showed better outcomes
and advantages {[}16{]}. Higher adherence to the Plant-Based Portfolio
Diet was associated with a reduction in CVD risk due to lower LDL-C
{[}17,18{]}. However, clinical trials may also help to confirm that some
combinations did not improve, and sometime likely worsened, clinical
outcomes {[}19{]}. A combination of electronic reminders, lottery-based
incentives, and social support did not significantly improve medication
adherence or outcomes for acute myocardial infarction survivors
{[}20{]}.

\textbf{4. Combinatorial biomedicine has obvious advantages}

Totally, combinatorial biomedicine has a lot of obvious advantages, in
particular screening, diagnosis, and treatments of both mNCDs (such as
CVD, diabetes, and cancer) as well as mIDs (such as AIDS, Helicobacter
pylori infection, and COVID-19).~For example, combination therapy with
intravenous doxycycline and azithromycin is a better option for severe
infection {[}21{]}, a combination treatment (Cabozantinib plus Nivolumab
and Ipilimumab) of cancer has significantly longer progression-free
survival {[}22{]}, and venetoclax-obinutuzumab with or without ibrutinib
is better than chemoimmunotherapy as first-line treatment in chronic
lymphocytic leukemia {[}23{]}. Recent studies in \emph{Nature
Cancer}supported that combinatorial treatment led to a significant
increase in survival and could further improve the therapeutic outcome
in a syngeneic model of pancreatic ductal adenocarcinoma {[}24{]}.

Of course, we should know the concept of the right combination of drugs
or agents and therapeutic programs, for example, combined~PD-1, BRAF and
MEK inhibition in colorectal~cancer {[}25{]}, and the optimal sequence
of several combination therapies is indeed pivotal to improve the
outcomes in the treatment of cancer {[}26{]}. For example, combination
chemotherapy for cancer cases by integrating the clinical and molecular
features of the cancer is helpful to precise medicine and personalized
and targeting treatment. Since there are multi-pathways of mechanisms
and multi-factors of etiology, both mNCDs and mIDs need combinatorial
treatment. Moreover, combinatorial biomedicine has resulted in newer
concepts and better solutions, such as CDCs, OOHS,
SEEDi\textsuperscript{1.0-3.0} technologies, and the iRT-ABCDEFG
strategy, as well higher efficacy (1+1\textgreater{}2,
1+1+1\textgreater{}3) and less adverse events.

As we know, combinatorial immunotherapy for cancer is a promising
approach {[}27{]}. Previous study showed that the chemotherapeutic
effects of EGCG in combination with p53siRNA therapy induced a synergic
pro-apoptotic effect {[}28{]}, in fact, combinatorial~treatments
{[}29{]} in cancer are common, for example, triple-combination
nanovesicles for cancer {[}30{]}, Atezolizumab plus nab-Paclitaxel for
metastatic triple-negative breast cancer {[}31{]}.
Triple-drug combination against cervical cancer is a promising
antineoplastic therapy since it inhibits the mTOR pathway leading to
cell death by apoptosis {[}32{]}. Obviously, optimal patient-specific
cancer targeted treatments need possible combinations, and there is a
large drug combination dataset in AstraZeneca {[}33{]}. However, tumors'
resistance may reduce or combat some drug combinations. Hence, we need
an effective platform for combinatorial drug screening {[}34{]}.
Moreover, we need to know how combination therapies may become the
preferable approach over monotherapy for cancer {[}35{]}. Moreover,
combining~a machine-learning molecular method with biomarkers may help
predict early recurrence of some cancers {[}36{]}. As new personalized
combinatorial treatments {[}37{]}, combination of microfluidic
experiments and mathematical model can be a novel tool toward cancer
precision medicine. Therefore, as a new strategy, a fresh combination of
therapeutic agents is efficacy for cancer in preclinical and clinical
investigation {[}38{]}.

In addition, there are combinatorial~drug screening, diagnosis, and
prediction of clinical outcomes and analysis of biological structure and
molecular mechanisms. Herein, just as synthetic biology is popular, it
is believed that combinatorial biomedicine, like click chemistry
{[}39-41{]}, will become a new discipline with great prospect and
potential growth in the future. All in all, combination is always
present and ubiquitous. As is well known, a house is composed of several
building materials, and a car is composed of several parts. The classic
biological example is that the double helix structure of deoxypentose
nucleic acids (DNA) molecules {[}42-44{]} is composed of four
complementary pairs of A, C, G, and T bases. Currently, synergistic
molecular targeting therapy with the combination of all-trans-retinoic
acid and arsenic trioxide for acute promyelocytic leukaemia is a
valuable translational model {[}45{]}. Adeno-associated virus-delivered
gene therapy of hemophilia A with a human/rat hybrid FVIII has an
enhanced therapeutic effect {[}46{]}. In addition, a combination of
elexacaftor/tezacaftor/ivacaftor may restore renal transmembrane
conductance regulator function in patients with cystic fibrosis
{[}47{]}, and decrease risk for electrolyte disorders and metabolic
alkalosis. No doubt, these are also classical examples of combinatorial
biomedicine.

\textbf{5. Conclusions and outlook}

As a new discipline, what people need to understand about combinatorial
biomedicine is ``5W1H'', that is, ``What combination? When to combine?
Where to combine? Who will combine? Why combination? And how to combine
it?'' For example, here is \emph{The Book of Health} in the new era, the
author's updated working fruit (Figure 1). In fact, not only social
sciences need to be combined, but also natural sciences need to be
combined even more. In real world, people are intentionally or
unintentionally doing related combinatorial works. Thus, it is time to
propose and establish this novel discipline due to obvious advantages in
screening, diagnosis, treatments, prevention and rehabilitation of both
mNCDs and infectious diseases. And the author's innovative ``TCM Hot
Pot'' theory is a classical hallmark of combinatorial biomedicine.

Based on the previous works in the last decades, the author has already
developed and proposed in time a novel discipline -- combinatorial
biomedicine. A series of classical examples confirmed that combinatorial
biomedicine has a number of obvious advantages in screening, diagnosis,
treatments, prevention and rehabilitation of both mNCDs (such as
cardiovascular disease, diabetes, cancer, stroke, and neurodegenerative
diseases) and mIDs (such as AIDS, Helicobacter pylori infection, and
COVID-19), and will be helpful in the development of life science,
biology and medicine, in particular the pandemic and post-COVID-19 era.

\textbf{Table 1}

Combinatorial biomedicine -- Dr. Chunsong Hu developed and proposed a
novel discipline\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Authors \& Published Time\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Main Contents\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Journals or Other Platforms\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2023 Hu C.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
``Traditional Chinese Medicine (TCM) Hot Pot'' consisting of
``Bark-Flower-Fruit-Grass-Leaf-Nucleolus(seed)-Root''
{[}BFFGLNR{]}\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Clin Complement Med Pharmacol\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2022-2023 Hu C. or Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
``ISISI'' barriers and strategies for COVID-19 infection \&
``Brain-heart-gut'' axis-- a novel theory and mechanisms for future
cardiovascular disease (fCVD) \& iRT-ABCDEFG for T2D\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Preprints at Authorea\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2022 Hu C.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
iRT-ABCDEF for human diseases\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
J Evid Based Med\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2021 Hu C.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
A novel classification of clinical risk factors based on unhealthy
E(e)SEEDi lifestyle in acute myocardial infarction (AMI)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Abstract for 2021 Annual Conference of China Society of Cardiology\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2021 Hu C.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
A novel scoring system based on healthy E(e)SEEDi lifestyle for aging
and longevity\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Abstract for 2021 China Heart Congress\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2020 Hu CS.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
E(e)SEEDi for improving human immunity\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
SN Compr Clin Med\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2020 Hu CS.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
iRT-ABCDEF for arrhythmogenic right ventricular cardiomyopathy
(ARVC)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Turk Kardiyol Dern Ars\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2019 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
iRT-ABCDEF for acute myocardial infarction (AMI)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Eur Heart J\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2019 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
iRT-ABCDEF for major viral infectious diseases (mVIDs)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Asia Pacific J Trop Med\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2019 Hu CS.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
iRT-ABCDEF for cancer\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Croat Med J\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2018 Hu C.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
E(e)SEEDi: a magic ``polypill''\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Eur Heart J\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2018 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
iRT-ABCDEF for chronic heart failure (CHF)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Chronic Dis Transl Med\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2017 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Novel strategies (SEEDi, E(e)SEEDi, HHLi) for cardiovascular, diabetes,
and cancer (CDC) strips, C-type hypertension (CtH), and
obesity-OSA-hypertension syndrome (OOHS)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Chronic Dis Transl Med\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2017 Hu C.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
``S-E-E-D'' for prevention of ASCVD\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Zhong Nan Da Xue Xue Bao Yi Xue Ban\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2017 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
SEEDi\textsuperscript{1.0-3.0} technologies for major non-communicable
diseases (mNCDs)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
J Intergr Med\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2016 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
``Level 210'' of comprehensive prevention\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Front Med\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2016 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
An equation=RT-ABCDEF + E(e)SEED-BasED + 210 (Management of major
chronic diseases and Health \& Longevity)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Chin Med J (Engl)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2015 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
A novel management program for hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Cardiovasc Diagn Ther\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2014 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Cardiovascular, diabetes, and cancer (CDC) strips\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
J Thorac Dis\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2011 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
E(e)SEED-BasED lifestyle (Hu's healthy lifestyle)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Qing Chun Shi Yu (A poem book in Chinese)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2008 Hu CS.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
RT-ABCDE strategies for control of human diseases\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Chin J Intergr Med\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2007 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Obesity OSA hypertension syndrome (OOHS) \& Non-Obesity OSA hypertension
syndrome (NOOHS)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Health News in Chinese\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2005 Hu C, et al.\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
``S-E-E-D'' for healthcare\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
In Chinese\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2003 Hu CS.\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
``3Y'' (safety, efficacy, and stability) in gene therapy\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Yichuan\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Fig. 1. \emph{The Book of Health} in the new era.} This figure
shows the relationship among ``Healthy Essential 5''
(Environment-Sleep-Emotion-Exercise-Diet), ``The Five Elements'' (Metal
or Gold, Wood, Water, Fire, and Earth), and ``The Five Viscera'' (Lung,
Kidney, Liver, Heart, and Spleen) of traditional Chinese medicine (TCM).
They interact and influence each other, and highly link to infectious
diseases (IDs) due to changing human immunity and major non-communicable
diseases (mNCDs), such as cardiovascular disease (CVD), diabetes,
cancer, depression and anxiety, stroke, dementia or Alzheimer's disease
(AD). Therefore, we can easily develop a novel treatment for both IDs
and mNCDs by modification of lifestyle and these Essentials or Elements.
For example, due to improvement of human immunity, the magic
``polypill'', that is E(e)SEEDi, is just like ``a dual-effects vaccine''
for treatment and prevention of human disease, including IDs and mNCDs.
It can also help the recovery of patients with COVID-19 or individuals
with the infection of SARS-CoV-2, control and prevent CVD, type 2
diabetes (T2D), and cancer, depression and anxiety, stroke, dementia or
AD by healthy E(e)SEEDi lifestyle. Another example, we can control and
prevent abnormal emotion (depression and anxiety) and neurodegenerative
diseases (AD and Parkinson's disease) by changing external environment
and optimizing internal environment, better sleep, more and active
exercise, and specific or balancing diet. In fact, it would be a whole
new kind of therapy for depression and anxiety according to the novel
theory of The Book of Health in the new era. Moreover, when combining
with specific vaccinations for individual prevention and screening
(VIPs), such as cancer or COVID-19 vaccines, that is E(e)SEEDi + VIPs,
it would be a very strong ``weapon'' for combating human disease. Here
in this figure, IDs: infectious diseases; NCDs: non-communicable
diseases.

\textbf{Funding}

No funding from this study was received.

\textbf{Declaration of competing interest}

The author declares that he has no conflicts of interest in this work.

\textbf{Acknowledgments}

The reviewers and editors are gratefully acknowledged for critical
review.

\textbf{Author contributions}

CH contributed to manuscript conceptualization and design, literature
review, table and figure production, wrote and edited the manuscript,
and read and approved the final manuscript.

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