The Simultaneous Treatment of Pulse and Syndrome of Water Qi Disease chapter of Synopsis of Golden Chamber is regarded as one of its most challenging sections. Although nominally focused on water qi disease, this chapter also discusses yellowish sweating disease, qifen disease, and other diseases. This multiplicity of topics led to the misconception that all these diseases are water qi diseases, complicating the diagnosis and treatment strategies. By distinguishing water qi as both a pathogenic factor and a disease entity, this paper redefines the concept, linking it to the abnormal accumulation of liquid and gaseous water in the body, akin to the disrupted water cycle of the nature. It demonstrates that ZHANG Zhongjing recognizes the primary syndrome, pathogenesis, and therapeutic principles of water qi disease from the generation, aggregation, and dissipation of vaporous water. The study further differentiates water qi disease, yellowish sweating disease, and qifen disease as distinct entities. An analysis of their etiology, pathogenesis, syndromes, and treatment approaches establishes their independence while exploring their interrelations. Moreover, the relationships among the qifen, xuefen, and water phase diseases are clarified. ZHANG Zhongjing′s discussion in the Simultaneous Treatment of Pulse and Syndrome of Water Qi Disease identifies the three diseases around the three " disease of water phase." The clarification of the concepts and relationships of the diseases in the Simultaneous Treatment of Pulse and Syndrome of Water Qi Disease will help to systematically and thoroughly elucidate ZHANG Zhongjing′s principles and thoughts on identifying and treating water qi disease.

Houshiheisan, a classic prescription for stroke treatment, originates from Chapter 5 on Pulse Syndrome Complex and Treatment of Apoplexy and Acute Arthritis of Synopsis of Golden Chamber, which discusses pulse syndrome complex and apoplexy and acute arthritis treatment. Renowned as a primary prescription for stroke, it exemplifies the therapeutic principle of tonifying deficiencies while reducing excesses. This study showed that Houshiheisan improves hemorheology, reduces oxidative damage, protects neurovascular units after cerebral ischemic injury, promotes neovascularization maturation, and maintains cerebrovascular endothelial barrier integrity. Based on the pathogenesis theory of stroke, which is the cause of internal deficiency and pathogenic factor invasion, studies on Houshiheisan disassembling were conducted. The herbs in the prescription were divided into wind-dispelling herbs such as Flos Chrysanthemi, Radix Saposhnikoviae, and Ramulus Cinnamomi and deficiency-tonifying herbs such as Radix Ginseng, Radix Angelicae Sinensis, and Rhizoma Atractylodis Macrocephalae. Wind-dispelling herbs primarily reduced cerebral ischemia injury by downregulating Caspase-3 expression, an apoptotic protein, and deficiency-tonifying herbs reduced cerebral ischemia by upregulating poly ADP-ribose polymerase expression, a DNA repair protein. Wind-dispelling herbs exhibited a rapid yet short-lived effect by significantly downregulating aquaporin-4 (AQP4) expression in the lateral ventricle six hours after cerebral ischemia. In contrast, deficiency-tonifying herbs showed a delayed but sustained regulatory impact on AQP4 expression. These complementary time-dependent effects reflect the dual function of the prescription of dispelling wind and tonifying deficiencies, aligning well with the early pathogenesis of cerebral small vessel disease, which is characterized by wind-phlegm and blood stasis obstructing the brain collaterals. Additionally, Houshiheisan reduces blood pressure and blood lipids, improves patients′ hemorheology, and alleviates vascular endothelial cell dysfunction. Therefore, Houshiheisan is a safe and effective classic prescription for preventing and treating early cerebral small vessel disease. Future research should focus on exploring its molecular mechanisms in treating cerebral small vessel diseases.

" Lijie and yellowish sweating" originates from the chapter on stroke and arthralgia diseases in Synopsis of Golden Chamber. Later generations typically interpret it as yellow fluid oozing from painful joints, a characteristic manifestation of arthralgia. In Western medicine, Lijie corresponds to diseases such as gouty arthritis, with its primary clinical manifestations being redness, swelling, heat, and painful joints, most often without yellow fluid discharge. Therefore, the interpretation of " Lijie and yellowish sweating" contradicts the clinical manifestations often observed in this disease. Thus, this article reinterprets the meaning of " Lijie and yellowish sweating" from the pathogenesis of " sweat exposure to water, as if water harms the heart" , combined with the viewpoints of other medical practitioners. Determining the meaning of " yellowish sweating" is crucial for understanding the pathogenesis of arthralgia and clarifying the relationship between arthralgia and yellowish sweating. ZHANG Zhongjing mentioned arthralgia and " yellowish sweating" together, not to differentiate between the two diseases but to emphasize the common pathogenesis of the two, namely, the cold and dampness injuring the heart, blood, and vessels. This paper proposes a new explanation of " Lijie and yellowish sweating" , which suggests that " yellowish sweating" is not confined to the joints but can be found all over the body. The pathogenesis of " Lijie and yellowish sweating" lies in the insufficiency of the liver and kidney and exogenous water dampness, leading to disharmony between nutrient qi and defensive qi and between yin and yang. Primary treatment should harmonize yingfen and weifen, as well as tonify and replenish the liver and kidney. The clinical selection of medicines can be considered Guizhi Decotion, a type of formula. The pathogenesis of " Lijie and yellowish sweating" is complex, and clinical treatment should be comprehensively considered to achieve the best therapeutic effect.

Defensive qi is a core concept of qi theory in the Huangdi Neijing. Some chapters of the Huangdi Neijing and later physicians often refer to both nutrient qi and defensive qi as ying-wei qi, viewing them as interdependent; however, the status and role of defensive qi far exceed that of nutrient qi. According to the Huangdi Neijing, defensive qi plays a crucial role in life activities, disease occurrence, and acupuncture treatment. However, the text also presents various descriptions of the circulation and distribution of defensive qi, with conceptual overlaps and interconnections with yang and genuine qi, resulting in a somewhat unsystematic understanding of defensive qi theory in later generations. This study elucidates the formation and foundation theories of defensive qi based on records from pre-Qin literature and the Huangdi Neijing. The background of the emergence of defensive qi lies in ancient moxa-wool moxibustion therapy, used to treat diseases caused by cold pathogens, which embodies the nurturing and therapeutic effects on human health and represents a concretization of the abstract philosophical concept of qi. The circulation of defensive qi exists in three patterns: from the extremities to the head and face, from the head and face to the hands and feet, and circularly through the twelve meridians originating from the middle jiao. These patterns reflect the integration of medical practice and philosophical thought. In the Huangdi Neijing, the concept of defensive qi is a medical term closely related to somatological medicine, rooted in acupuncture and moxibustion practices. Defensive qi circulates between the muscles and within the fascia and is closely associated with the therapeutic effects of acupuncture. Defensive qi holds great theoretical and clinical value in modern acupuncture treatment and life science research.

By analyzing the meridian related diseases of the heart in the Lingshu · Meridians chapter, this study summarizes the characteristics of heart diseases caused by the Heart Channel of Hand-Shaoyin, Pericardium Channel of Hand-Jueyin, and other meridians from the perspectives of pathogenic meridians, lesion sites, and disease nature. The pathogenesis and connotation of these diseases are analyzed, providing new ideas for the prevention and treatment of heart related diseases. Among the twelve meridians, besides the Heart Channel of Hand-Shaoyin and Pericardium Channel of Hand-Jueyin, there are five meridians that cause heart diseases, namely the Lung Channel of Hand-Taiyin, Stomach Channel of Foot-Yangming, Spleen Channel of Foot-Taiyin, Kidney Channel of Foot-Shaoyin, and Gallbladder Channel of Foot-Shaoyang. Diseases are more common in the yin meridian, with pain and heat as the main symptoms. They are related to the fact that the heart is a yang zang-organ, and evil qi is easily converted from yang to heat, causing diseases through the transmission of heart fire. There are three mechanisms by which other meridians can affect the Heart Channel of Hand-Shaoyin and Pericardium Channel of Hand-Jueyin, leading to symptoms such as heart pain and palpitations. Firstly, pathogenic factors can be transmitted along the meridians, causing discomfort and heartache to the heart; secondly, due to the abnormal pathogenic behavior of the Five Elements, where the gallbladder wood do not generate heart fire, and the heart yang is weak and painful; kidney water does not control heart fire, and the heat disturbs the mind and causes palpitations; thirdly, qi function is abnormal, which leads to abnormal opening and closing of the Yangming and Shaoyang channels, causing palpitations due to insufficient yin qi in the pericardium meridian or pain due to yang deficiency in the heart channel. External pathogens enter the lung through the channels, causing obstacles in the generation and distribution of pectoral qi, affecting the qi function of the heart channel and causing distress. The three mechanisms can exist independently or simultaneously as diseases.

The theory of " heart governing the exterior" derives from Prohibition of Pricking in Suwen, which has an important position in the clinical practice of traditional Chinese medicine. This article sorts out the interpretation of " heart governing the exterior" of physicians in the past dynasties, and summarizes the clinical application of " heart governing the exterior" in chest painful impediment, warm disease, dermatosis, allergic rhinitis, tic disorder, and diabetic neuropathy. It is found that the theory of " heart governing the exterior" is widely used in clinical practice and has good effects. This paper further expands and enhances its theoretical connotation, that is, the physiological and pathological connection and clinical application of the three dimensions of heart yang, heart blood, and heart spirit with the life and mental activities dominated by it, as well as the overall external performance. In addition, by exploring the relationship between " heart governing the exterior" and " brain-heart axis" , " brain-skin axis" in Western medicine, it indirectly confirms the rationality of " heart governing the exterior" in Western medicine, and lays the foundation for the further development and application of the theory of " heart governing the exterior" .

Yin-yang, visceral manifestation, and ti-yong theories are the core theories of traditional Chinese medicine (TCM) and play a crucial role in its formation and development. With the continuous evolution of Chinese philosophy, TCM philosophy and theories have undergone significant influence, resulting in differing interpretations of the visceral manifestation of liver and mingmen across various historical periods by different medical practitioners. This paper focuses on the different understandings of the position of liver and mingmen, combining relevant philosophical images and TCM anatomical illustrations to deeply explore ancient medical theorists′ concepts regarding the four spatial directions of left, right, up, and down. The research reveals that ancient medical theorists′ conceptualization of spatial theory transitioned from an initial circular motion to a vertical movement, with the focus shifting from the upper part to the lower part. The primary reasons for these differences and changes could be explained by the varying emphasis on the ti-yong theory and differing focal points within the yin-yang theory. This study systematically examines the evolution of visceral manifestation theories related to liver and mingmen, highlights the shifts in physicians′ perspectives on spatial theory, and analyzes the influence of the ti-yong theory and yin-yang theory on these changes. The findings aim to provide a theoretical guide for advancing research and clinical application of spatial theory in TCM, thereby fostering the integration of TCM philosophy with medical theory.

Objective: To investigate the regulatory effect of Jieduan Niwan Formula (JDNWF) drug-containing serum on AMPK-mediated mitochondrial quality control in D-GalN-induced HepG2 cells. Methods: Twenty male Wistar rats were randomly divided into blank control and JDNWF-containing serum groups, 10 rats per group. The JDNWF-containing serum group was gavaged with JDNWF (21.7 g/kg), whereas the blank control group was gavaged with saline. Blood was collected to prepare JDNWF-containing and blank control serum. Cell viability, mitochondrial damage indicators, and MQC pathway protein expression levels were evaluated to determine the optimal volume fraction of JDNWF. HepG2 cells were divided into control, D-GalN, DMSO, AMPK inhibitor, JDNWF drug-containing serum, and JDNWF drug-containing serum plus AMPK inhibitor groups, and corresponding drug interventions were administered to each group. Cells were collected after the interventions, and the CCK-8 assay was used to measure cell viability, the 2′-7′-dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) levels, JC-1 was used to detect mitochondrial membrane potential, thiobarbituric acid was used to measure malondialdehyde (MDA) levels, WST-8 was used to measure superoxide dismutase (SOD) activity, and western blotting was used to detect the expression levels of mitochondrial quality control-related proteins, including p-AMPK, AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1. Results: 5% JDNWF drug-containing serum most significantly restored cell viability, mitochondrial damage markers, and MQC pathway protein expression in the model group. Therefore, it was chosen for intervention in subsequent experiments. Compared to the control group, the cell viability of the D-GalN, DMSO, and AMPK inhibitor groups was significantly reduced (P<0.01). In contrast, the heterogeneity of mitochondrial membrane potential, ROS, and MDA levels was significantly increased (P<0.01), and SOD activity was significantly decreased (P<0.01). The p-AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1 protein expression levels were significantly decreased (P<0.01). After JDNWF drug-containing serum intervention, compared to the DMSO group, cell viability significantly increased (P<0.01), mitochondrial membrane potential heterogeneity, ROS, and MDA levels significantly decreased (P<0.01), SOD activity significantly increased (P<0.01), and p-AMPK, PGC-1α, NRF1, TFAM, and MFN2 protein expression levels significantly increased (P<0.01), whereas DRP1 protein expression significantly decreased (P<0.01). Compared to the JDNWF drug-containing serum group, the cell viability in the JDNWF plus AMPK inhibitor group significantly decreased (P<0.01), mitochondrial membrane potential heterogeneity and ROS levels significantly increased (P<0.01), MDA levels significantly increased (P<0.05), SOD activity significantly decreased (P<0.05), p-AMPK, PGC-1α, NRF1, and TFAM protein expression levels significantly decreased (P<0.01), MFN2 protein expression significantly decreased (P<0.05), and DRP1 protein expression significantly increased (P<0.01). Conclusion JDNWF drug-containing serum may restore mitochondrial function and improve D-GalN-induced HepG2 cell injury by regulating AMPK-mediated mitochondrial quality control.

Objective: We aimed to explore the mechanism of Pizhan Powder in regulating the Wnt4/β-catenin signaling pathway to promote wound healing in mice with chronic skin ulcer. Methods: Male BALB/c mice were divided into blank, model, Pizhan Powder, Pizhan powder removed bark medications, bark medications, inhibitor, and Pizhan Powder + inhibitor groups using the random number table method, with six mice per group. Except for the blank group, chronic skin ulcer wound models were prepared in the other groups by implanting foreign bodies. The blank control group received no treatment, whereas the wounds of the model group were cleaned with furacilin solution. The Pizhan Powder, Pizhan Powder removed bark medications, and bark medications groups were each administered 0.1 g of the corresponding medication on the skin wounds. The inhibitor group received an intraperitoneal injection of 3-(4-methylphenylsulfonamido) benzoic acid methyl ester (MSAB) at a dosage of 10 mg/kg. The Pizhan Powder + inhibitor group was administered 0.1 g of Pizhan Powder on the skin wound, and an intraperitoneal injection of MSAB was also administered (10 mg/kg). These treatments were administered once a day for 14 consecutive days. Wound healing was observed on the first, third, seventh, and 14th day of treatment; hematoxylin and eosin staining was used to observe the pathological changes of ulcerated skin; keratin 10 (CK10), keratin 14 (CK14), cell proliferation nuclear antigen (Ki-67), α-smooth muscle actin (α-SMA), and β-catenin expression in wounds was observed through immunofluorescence; Western blotting was used to detect the expression of signaling pathway-related proteins (Wnt4 and β-catenin). Results: Compared to the model group, the Pizhan Powder group showed a reduced wound area and an increased wound healing rate (P<0.05) and elevated CK10, CK14, Ki-67, α-SMA, β-catenin, and Wnt4 protein expressions (P<0.05). Compared to the Pizhan Powder group, the wound healing rate of the bark medications and Pizhan Powder removed bark medications groups was reduced (P<0.05). The wound healing rate and the fluorescence expression of CK10, CK14, Ki-67, and α-SMA in the Pizhan Powder removed bark medications group were lower than that in the bark medications group (P<0.05). Compared to the Pizhan Powder group, the wound healing rate of the Pizhan Powder + inhibitor group was reduced, and CK10, CK14, Ki-67, α-SMA, β-catenin and Wnt4 protein expression were lower (P<0.05). Conclusion Pizhan Powder promotes wound healing in chronic skin ulcers of mice by regulating the Wnt4/β-catenin signaling pathway. The bark medications (buffalo hide, white mulberry root-bark, and Chinese wolfberry root-bark) play a crucial role, representing a concrete application of the traditional Chinese medicine theory of " treating skin with skin.

The " liver disease affecting to the spleen" theory first appeared in Nanjing and was further elaborated in Jingui Yaolue. This theory encapsulates the traditional Chinese medicine principles of the " unity of the five viscera" and the " preventive treatment of disease" . The theory emphasizes that the spleen is the pivotal point where depression may progress from a functional disorder to an organic disease. The liver governs the emotions and qi flow, whereas the spleen is responsible for qi, blood, and body. In the early stages of the disease, emotional disorders and qi flow disorders primarily affect the liver, manifesting as depression or low mood. As the condition progresses, the liver (Wood) overacts on the spleen (Earth), disrupting liver and spleen functions and causing qi and blood disharmony. This stage is marked by fatigue and psychomotor retardation. Prolonged illness depletes qi and blood, eventually involving all five viscera, disrupting the harmony of the five spirits, and affecting both body and spirit. At this advanced phase, intense emotional distress or agitation often arises, accompanied by a heightened risk of suicide. The disease progression follows a dynamic " qi-blood-spirit" pattern, in which depression begins in the liver, characterized by qi stagnation, then affects the spleen, involving blood disharmony. In later stages, the disease eventually affects all viscera, with profound effects on both physical and mental health. Treatment strategies should align with the disease stage. Early intervention should focus on regulating the flow of qi, treating the liver, and strengthening the spleen. In the middle stages, qi and blood should be harmonized while promoting the harmonized functions of the liver and spleen. In the later stages, treatment should harmonize the five viscera to restore balance between body and spirit. Guided by this theory, integrating modern medical understanding of the progression of depression from emotional to somatic symptoms and adopting a stage-based approach to treatment in clinical practice can yield effective therapeutic outcomes for managing depression and related disorders.