🌿 Folk Prescriptions

Differentiation and treatment based on syndrome is a hallmark distinguishing TCM from modern and other traditional medicine. “Syndrome” is the foundation of TCM differentiation and the essence of TCM. Modernization research in TCM inevitably involves investigating the essence of “syndrome.” What is the essence of TCM syndromes? How can TCM syndromes be objectified? Academician Shen Ziyin, following the intrinsic developmental logic of TCM, conducted nearly half a century of research on kidney yang deficiency syndrome. He became the first to internationally confirm that kidney yang deficiency syndrome has a specific material basis, locating the primary regulatory hub in the hypothalamus—making a significant contribution to TCM’s modernization. His research methodology and findings may offer valuable insights.
Academician Shen Ziyin graduated from the Medical Department of Shanghai First Medical College in 1952. In 1955, he studied under renowned Shanghai physician Jiang Chunhua, systematically learning classical TCM texts and clinical practice. His experience in “learning Chinese medicine from Western medicine” enabled him to integrate both TCM and modern medical research perspectives in studying “syndrome.” He believed that due to historical differences in TCM diagnostic methods, interpretations of “syndrome” vary across different angles—essentially different ways of perceiving syndrome. Zang-fu differentiation originated from the *Huangdi Neijing*, based on the principle that “internal organs reside within, external manifestations reveal their state.” By observing external signs, one infers internal conditions. Since the *Huangdi Neijing* emerged during the era of Zhou and Qin dynasties, when yin-yang and Wu Xing theories were dominant, zang-fu differentiation carries distinct philosophical characteristics. Later, Zhang Zhongjing applied these philosophical ideas clinically, “drawing extensively from various formulas” to prioritize efficacy. Each formula corresponds to a specific syndrome—“if the syndrome exists, use the formula”—commonly referred to as “formula-syndrome.” Using formulas to identify syndromes falls within the scope of syndrome differentiation, hence called “formula-based differentiation.” Academician Shen Ziyin built his research on these two approaches, taking kidney yang deficiency syndrome as a starting point, progressing from organ essence research to syndrome essence research.
Phase I: Research on Zang-Fu Differentiation
In the 1950s, Academician Shen Ziyin began studying syndromes through the lens of zang-fu differentiation—inferring internal organ essence from external manifestations (“form reveals inner reality”). He established uniform diagnostic criteria, selecting typical patients with clear kidney yang deficiency syndrome and no overlapping syndromes, then screened specific indicators reflecting internal organ function. Although no unique “gold-standard” indicator for kidney yang deficiency was found, he discovered that kidney yang deficiency involves functional disturbances at multiple levels of the hypothalamic-pituitary-adrenal (HPA) axis, representing latent changes—indicating that “syndrome” has a material basis. If a syndrome has a material basis, scientifically speaking, it can be quantitatively and qualitatively studied. In the late 1970s, Shen further added thyroid and gonadal axis function studies and included comparative groups with different syndromes for the same disease to avoid confounding effects of disease itself. He also compared kidney yang deficiency patients with those aged 65 and above. Results showed that kidney yang deficiency involves multi-glandular (three-axis) functional disturbance, with no evidence of cross-axis influence observed in parallel. From the zang-fu differentiation perspective, the primary pathogenic site of kidney yang deficiency may lie in hypothalamic (or higher central) regulatory dysfunction. Since elderly subjects showed similar abnormalities in two axes, kidney yang deficiency externally presents as premature aging of the hypothalamus-pituitary and certain target glands. Human growth, development, and aging are determined by the abundance or depletion of kidney essence and qi. Aging thus equates to physiological kidney deficiency.
From this phase, we understand: ① Studying TCM syndromes should not blindly pursue a single specific indicator. If a syndrome can be defined by one such indicator, it would meet disease diagnostic criteria and enter the “disease” category. ② Syndrome is a composite functional state—dynamic, capable of evolution and transformation. The human body possesses powerful regulatory capacity, constantly restoring homeostasis via feedback mechanisms. Pathological manifestations arise when regulatory control fails. ③ While zang-fu differentiation leads to inference about the pathological origin, it still cannot pinpoint the exact entity corresponding to the syndrome or its regulatory center.
Phase II: Research on Formula-Based Differentiation
Traditional TCM emphasizes judging the correctness of syndrome differentiation through treatment efficacy. Zhang Zhongjing’s “use the formula if the syndrome exists” demonstrates that syndrome existence can be verified by drug response. Zang-fu differentiation starts from observable external signs, so research subjects are always human. However, due to limitations in human sampling, the earlier conclusion that kidney yang deficiency originates in the hypothalamus remained speculative. To verify whether the regulatory center is truly located in the hypothalamus, the second phase required animal models for drug testing—specifically, samples from the hypothalamus. Starting in the mid-1980s, Academician Shen Ziyin adopted the formula-based differentiation approach, using two models: aged rats exhibiting physiological kidney deficiency, and rats induced with exogenous glucocorticoids (corticosterone) to suppress the hypothalamic-pituitary-adrenal cortex axis, mimicking kidney yang deficiency. These models allowed verification of whether the regulatory center lies in the hypothalamus. Because animal models provide clear etiology, controllable conditions, easy sample collection, and compatibility with comparative studies using different classic formulas, they offered ideal conditions to clarify disease localization and identify the regulatory centers of drugs acting on kidney yang deficiency syndrome.
In 1986, Shen observed that Bushen Yishou Pills significantly increased serum testosterone in elderly individuals, whereas Sijunzi Tang had no effect. He then divided 24-month-old aged rats into Bushen (treated with Bushen Yishou Pills) and control groups, comparing them with 4-month-old adult rats. Specimens were specifically collected from the hypothalamus. Results showed significantly reduced affinity of dihydrotestosterone receptors in the hypothalamus of aged rats compared to adults. Bushen herbal formulations effectively improved receptor affinity in aged rats, indicating that kidney-nourishing drugs directly act on the hypothalamus—providing one piece of evidence for the localization of kidney yang deficiency syndrome.
In 1990, in a comparative study of kidney-nourishing versus spleen-strengthening drugs, Shen demonstrated that kidney-nourishing drugs improved age-related deterioration of catecholamine neurons in the hypothalamus, whereas spleen-strengthening drugs did not—second evidence for the localization of kidney yang deficiency syndrome.
In 1995, Shen investigated the regulatory effects of warm-kidney-replenishing decoctions Yougui Yin and his self-designed Mingmen Heji in corticosterone-treated rats (a model of suppressed hypothalamic-pituitary-adrenal-thymus [HPAT] axis, essentially a neural-endocrine-immune [NEI] network suppression model). Both formulas effectively improved disrupted monoamine neurotransmitter levels in the hypothalamus, normalized HPAT axis morphology and function, and reversed widespread suppression of cellular immunity—indicating an intrinsic link between kidney yang deficiency syndrome and the NEI network. Warm-kidney replenishment proved effective in regulating the hypothalamus, NEI network, and HPAT axis—third evidence for syndrome localization.
In 1996, Shen examined the effects of aconitine, the main component of aconite (a representative warm-kidney-replenishing herb), on the morphology and function of CRH in normal rats’ hypothalamus. Results further confirmed the specific regulatory action of warm-kidney-replenishing drugs on the hypothalamus—fourth evidence for localization.
In 1997, using RT-PCR chemiluminescence quantitative methods, Shen compared the effects of kidney-nourishing, spleen-strengthening, and blood-activating formulas on CRF mRNA expression and HPAT axis function in corticosterone-treated rats. Results showed that only warm-kidney-replenishing formulas significantly enhanced CRF mRNA expression, thereby reversing the suppressed state of the HPAT axis—fifth evidence for localization in the hypothalamus.
Thus, multiple lines of evidence collectively indicate that the regulatory center of kidney yang deficiency syndrome is located in the hypothalamus. Of course, the hypothalamus is also regulated by higher central regions and other brain areas, and kidney-nourishing drugs also exert broad regulatory effects on peripheral effector organs.
Academician Shen Ziyin, starting from zang-fu differentiation, inferred the pathogenic site of kidney yang deficiency syndrome in the hypothalamus based on dysfunction across three axes. From formula-based differentiation, he concluded that kidney yang deficiency syndrome encompasses the NEI network, with its regulatory center in the hypothalamus. Therefore, we may speculate that for syndrome essence research, if kidney yang deficiency syndrome serves as a model, the approach might be generalized to other syndromes: a syndrome is a composite functional state with a specific functional network and regulatory center.
Since kidney-nourishing drugs can specifically enhance the expression of the critical functional gene—CRF gene—in the hypothalamus, thereby enabling the hypothalamus to regulate the NEI functional network, modern science, though pioneering the NEI network theory, lacks means for balancing regulation. Though gene therapy offers unique, targeted solutions for monogenic diseases (disease or mutated genes), it lacks holistic regulatory tools for polygenic diseases involving functional genes. From Shen Ziyin’s research on kidney yang deficiency syndrome, we can confidently affirm and take pride in the fact that TCM can fill gaps left by modern medicine. The future advantage of TCM lies precisely in its ability to regulate functional networks and functional genes.