"Wugeng" (??)—literally meaning "free of obstruction/infarction for stroke and dementia" represents a transformative national health goal for China: the annual elimination or near-zero incidence of lethal stroke, dementia, and heart attack through systematic preservation of the muscle-vascular-brain axis. These three conditions collectively account for over 70% of cardiovascular-cerebrovascular mortality in China [1].

The COVID-19 pandemic has amplified this urgency. SARS-CoV-2 infects host cells via ACE2 receptors abundantly expressed on vascular endothelium, causing direct endothelial injury and persistent dysfunction in long COVID affecting ~400 million globally [2–4]. The Wugeng China framework addresses this through an innovative 4S (Systemic, Standardized, Sustainable, Scalable) automobile maintenance model:

The 4s core principle

In the future, over 90% of people will be expected to achieve health through 4S, with less than 10% requiring medical intervention in China. People need annual maintenance when healthy, like automobile maintenance, one service cannot last years.

We propose that progressive microcirculatory endothelial dysfunction (MED) driven by sarcopenia (age-related muscle loss), myokine deficiency, and accelerated by COVID-19-induced ACE2 downregulation represents the universal pre-disease state underlying lethal stroke, dementia, and heart attack.

Skeletal muscle as the microcirculatory engine

Skeletal muscle comprises around 40% of body mass and houses the body's largest microvascular bed, functioning as a critical endocrine organ secreting 600+ myokines that regulate systemic vascular function [5,6]. Key myokines include:

Sarcopenia-microcirculatory decline

Age-related muscle loss reduces microcirculatory reserve by:

• Capillary rarefaction: Reduced muscle VEGF/angiopoietin signaling decreases systemic microvascular density [14]
• Myokine deficiency: Loss of irisin, IL-6, and FGF21 impairs endothelial protection and angiogenesis [5,7,11]
• Endothelial dysfunction: Reduced IGF-1 signaling in aging muscle disrupts muscle-endothelial crosstalk, accelerating microvascular senescence [15]

Post-COVID amplification

SARS-CoV-2 infection accelerates attrition through ACE2 downregulation, reduced NO bioavailability, and persistent pro-thrombotic endothelial phenotype [2–4].

Dual-strategy approach

We further propose that "Activating Blood Circulation to Remove Stasis" (????, Huó Xuè Huà Y?) package that we practice synergizes with muscle-targeted interventions by improving muscle perfusion, enhancing myokine delivery, and addressing hemorheological disturbances whenever necessary [16–18].

The annual attrition law

Microcirculatory density declines ~1% annually after age 30, driven by sarcopenia-related myokine deficiency and capillary rarefaction [14,19]. Without annual 4S maintenance, this crosses the Wugeng Threshold (30% residual function), triggering stroke, dementia, or myocardial infarction [14,19].

Endothelial-to-mesenchymal transition (EndMT)

EndMT represents the fundamental mechanism wherein endothelial cells transform into mesenchymal cells [20]:

• Stroke: Cerebral microvascular EndMT reduces collateral circulation [20, 21].
• Dementia: Hippocampal microvascular EndMT causes chronic hypoperfusion; irisin deficiency impairs neurogenesis [22].
• Heart attack: Coronary microcirculatory EndMT precipitates plaque instability; FGF21 deficiency impairs cardiac protection [11,20].

Defining microcirculatory environment cleansing (???????)

Strategy A: Muscle-targeted MVAR (modern precision medicine)

Primary interventions

• Myokine-enhancing exercise: Resistance training to increase muscle capillarization by 20-40% and boost irisin/FGF21 secretion [5,7,11].
• ACE2 pathway restoration: Counter COVID-induced downregulation [2,3].
• TGF-β modulation: Suppress EndMT to preserve muscle-vascular coupling [20].
• Glycocalyx regeneration: Sulodexide for endothelial barrier repair [23].

Strategy B: TCM Huó Xuè Huà Y? (????) package mechanisms

• Huó Xuè (Activating Blood): Improves muscle capillary perfusion, enhancing myokine delivery to brain and heart [16–18].
• Huà Y? (Resolving Stasis): Fibrinolytic activation, anti-thrombotic effects, addressing post-COVID microthrombosis [16–18].

Evidence base

• Meta-analysis (Chen et al., 2018): the RCTs (n>1,500) demonstrated Huoxue Huayu therapy reduced in-stent restenosis by 43% (RR=0.57) [16,17].
• Systematic review (Gao et al., 2025): the RCTs (n>3000) confirmed TCM formulas improved microcirculation (D-dimer, fibrinogen, endothelin) [18].
• Xuefu Zhuyu Tang: Improves hemorheology, enhances muscle pump efficiency [24–26].

So far, we formalize the 4S maintenance schedule through the AI-aided articulate Wugeng Muscle-Vascular Reserve Index (WMVRI):

Post-COVID adjustment

LC patients automatically classified as Yellow Status for 12 months.

4s station service integration

4s station core services:

1. Screening: Annual DEXA muscle mass, serum irisin/FGF21, capillary imaging, sarcopenia index, post-COVID ACE2 autoantibodies.
2. Muscle index: Personalized exercise (irisin-boosting HIIT, resistance training for capillarization), myokine modulation.
3. TCM evaluation: Constitution identification; Huó Xuè Huà Y? package for Status muscle-perfusion optimization.
4. Integrated monitoring: tracking with muscle strength, gait speed, hemorheology.

Phase I: Green status maintenance (ages 20–30)

• Muscle Target: Maintain lean mass >90th percentile; serum irisin >15 ng/mL.
• Exercise: Combined aerobic + resistance to maximize myokine diversity [5,7].
• Post-COVID: 6-month enhanced monitoring.
• TCM option: Preventive Qi and Blood regulation.

Phase II: Yellow status restoration (ages 30–50, including all post-covid)

• Muscle Target: Reverse early sarcopenia; restore capillary density.
• Exercise: High-load resistance training (3×/week) to increase muscle capillarization by 25% [14].
• TCM Primary: Huó Xuè Huà Y? therapy (Xuefu Zhuyu Tang) for muscle microcirculation and myokine transport [16–18].

Phase III: Red status intervention (ages 50+, severe lc, advanced sarcopenia)

• Interventions: Myokine replacement (irisin analogs), intensive exercise rehabilitation.
• TCM Adjunct: Intensive muscle perfusion support, and beyond.

The FDA Modernization Act 2.0 and NIH PAR-25-198 enable regulatory-qualified testing [27–29]. However, in near future, Wugeng Muscle-Vascular Digital Twins will need to integrate:

• Muscle fiber-ECM-vascular units: Patient-derived myocytes with endothelial co-culture to test myokine secretion.
• Sarcopenia modeling: Age-related muscle atrophy MPS to optimize MVAR protocols [30].
• Post-COVID modeling: ACE2-downregulated vasculature to test EER strategies [31].
• TCM validation: Huó Xuè Huà Y? compound testing for muscle perfusion enhancement.

Infrastructure:

Towards 10 thousand nationwide Wugeng 4S Muscle Stations

Workforce:

• Exercise myokine specialists: Certified in irisin-boosting protocols, sarcopenia assessment, resistance training prescription.
• Modern EER specialists: Post-COVID cardiovascular rehabilitation, ACE2 pathway expertise.
• TCM muscle practitioners: Huó Xuè Huà Y? for muscle-perfusion optimization.

Computed economic model:

• Green Status: ¥500/year (muscle maintenance, exercise prescription).
• Yellow Status (including all LC): ¥1,000/year (resistance training + Huó Xuè Huà Y? therapy + myokine monitoring).
• Red Status: Intensive intervention (vs. stroke/dementia/LC costs: ¥100,000–600,000).

1. 90/10 prediction: Expect Annual 4S muscle maintenance achieves >90% Green/Yellow Status with <10% medical intervention in China.
2. Sarcopenia reversal: estimate that 12-week resistance training restores muscle capillarization and reduces arterial stiffness, preventing progression to Red Status [14].
3. Myokine efficacy: Theoretically Irisin-boosting exercise increases cerebral microcirculatory density by 15-20%, delaying dementia onset by 5-10 years [7,9]
4. TCM-muscle synergy: Yellow Status patients receiving resistance training + Huó Xuè Huà Y? show 30% faster WMVRI improvement than exercise alone (enhanced muscle perfusion → increased myokine delivery).

The Wugeng China initiative establishes skeletal muscle as the command center of microcirculatory health, expecting to integrate modern myokine science (irisin, FGF21, IL-6, resistance training) with TCM Huó Xuè Huà Y? (muscle perfusion optimization). By targeting sarcopenia reversal, myokine signaling restoration, and post-COVID endothelial repair, we may create a resilient dual-strategy framework.

The 4S model treats muscle as the "engine" requiring annual maintenance with 90% achieving health through muscle preservation, <10% requiring medical intervention in China. This muscle-centric approach honors both biomedical rigor and cultural medical heritage in the service of a singular goal: so far, what successfully hundreds of cases have been treated successfully is a promising signal towards a China free of lethal stroke, dementia, and heart attack.