Zhishi Shaoyaosan is the 34^th prescription in the Catalogue of Ancient Classic Formulas （Second Batch） published by the National Administration of Traditional Chinese Medicine in 2023. It is widely used in clinical practice and has a definite curative effect. However， there is currently a lack of its ancient literature analysis and textual research， and there is no corresponding Chinese patent medicine preparation. By consulting and combing the relevant ancient books of traditional Chinese medicine， this paper analyzes and conducts textual research of the origin， composition， measurement， administration， and efficacy of Zhishi Shaoyaosan. The results show that Zhishi Shaoyaosan is derived from Essentials from the Golden Cabinet written by Zhang Zhongjing in the Eastern Han Dynasty. It is mainly recorded in the name of Zhishi Shaoyaosan in the literature of the past dynasties. The prescription is composed of Aurantii Fructus Immaturus and Paeoniae Radix Alba. The processing method is stir-frying Aurantii Fructus Immaturus to scorch and using raw Paeoniae Radix Alba. The dose of the prescription recorded in the ancient books is mainly an equal amount of Aurantii Fructus Immaturus and Paeoniae Radix Alba in one square-cun spoon， taken three times a day， which is converted into a modern dose of 1.5 g each time （0.75 g Aurantii Fructus Immaturus and 0.75 g Paeoniae Radix Alba each time）. The components of the prescription are ground into powder and taken with barley porridge， three times a day. The efficacy is to break stagnated Qi， harmonize blood， and relieve restlessness and pain. It is mainly used to treat postpartum abdominal pain， acute pelvic inflammatory disease， acute cholecystitis and intestinal diseases， stroke sequelae， and other diseases. This study combs and analyzes the ancient literature recording Zhishi Shaoyaosan and clarifies the key information of the prescription， which provides a basis for promoting the research and development of its patent medicine.

Diabetic retinopathy（DR）， as one of the most common and serious microvascular complications of diabetes mellitus， seriously threatens human health， and belongs to "Xiaoke eye diseases" in traditional Chinese medicine（TCM）， which has been richly experienced by medical practitioners through the ages， but is mostly recorded in a piecemeal manner and has not been systematically researched. This disease is featured by long course and repeated attack， and is refractory， which belongs to the research category of "persistent illness entering collaterals". Systematic establishment of TCM collateral disease theory for guiding prevention and treatment of DR has important clinical value. On the basis of close correlation between tertiary collaterals at the terminal of collaterals and capillaries and microcirculation， the concept of "tertiary collaterals-microvascular" is proposed. It is pointed out that DR falls within the scope of "tertiary collaterals-microvascular" diseases， and presents four types of micro-pathological characteristics， including stasis， insufficiency， growth and bleeding of tertiary collaterals. It is concluded that "deficiency of both Qi and Yin" is the basic pathogenesis of DR， and "blood stasis and collateral obstruction" is the important pathogenesis and key factor. Thus， the treatment method of "dispersing blood stasis， dredging collateral， tonifying Qi and Yin， stopping hemorrhage and improving eyesight" is determined， and the formula of Tongluo Mingmu capsules is developed. The article tightly focuses on the pathological changes such as stasis， growth， insufficiency and bleeding of collaterals， addresses both symptoms and root causes， and plays a synergistic role of both dispersing stasis and stopping bleeding. In this way， it can realize the purpose of tonifying Qi and Yin to replenish the essence， dispersing stasis and dredging collaterals to meet the requirement， as well as stopping hemorrhage and improving eyesight to deal with changes. Fundamental researches demonstrate that Tongluo Mingmu capsules has synergy effects of protecting both retinal capillaries and retinal cells. Phase-Ⅲ clinical trial of new drug has proven definite clinical efficacy and good safety， which provides a new drug choice for enhancing clinical effect of DR， and further supports the scientific value of Luobing theory in preventing and treating DR and other clinically significant diseases.

The theoretical basis of premature aging originates from The Yellow Emperor's Inner Classic. The etiology of premature aging is complex， and the disease mechanism is based on deficiency. The treatment for premature aging is based on tonicity. The essence-Qi-spirit theory of Qiluo doctrine summarizes that "essence is the origin of life， Qi is the driving force of life， and spirit is the embodiment of life"， which is the law of life. The theory puts forward the core disease mechanism of aging， which states that "deficiency of kidney essence is the root of aging， deficiency of primordial Qi is the key to aging， impairment of soma and spirit is the manifestation of aging". The theory also proposes the treatment of "tonifying kidney and supplementing essence， harmonizing Yin and Yang， warming and supporting primordial Qi， and nourishing soma and spirit" and the representative anti-aging drugs. The article unfolds from the perspective of the concepts of natural life span， premature senility before fifty， decline， and aging and also explains the origins and connotations of premature aging. The article explains the disease mechanism of premature aging under the guidance of the essence-Qi-spirit theory of Qiluo doctrine， which is "early deprivation of kidney essence， deficiency of primordial Qi， accumulation of deficiencies into impairment， and decline and impairment of soma and spirit"， summarizes the progress of modern medical research on the treatment of premature aging and representative drugs， and finds that Bazi Bushen capsules have a precise therapeutic effect on the overall premature aging， systematic functional decline， and related diseases. The study provides theoretical basis and new ideas to solve the problems of premature aging and geriatric diseases.

The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.

ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

OBJECTIVE To investigate the effect and potential mechanism of astilbin （AST） on renal injury in chronic renal failure （CRF） rats based on the Jagged-1/Notch-1 signaling pathway. METHODS CRF model was constructed by 5/6 nephrotomy. The successfully modeled rats were randomly separated into Model group， AST low-dose group （AST-L group）， AST high-dose group （AST-H group）， high-dose of AST+Notch pathway activator （Jagged-1/FC chimerin， referred to as “JFC”） group （AST-H+ JFC group）， and control group （CK group） for open surgery without resection was set up， with 10 rats in each group. The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST， respectively； the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC， and the rats in the CK group and Model group were given an equal volume of normal saline， once a day， for 4 weeks. After the last administration， the serum levels of blood urea nitrogen （BUN）， serum creatinine （SCr）， and the level of 24 h urinary protein （UP） in urine， as well as the serum levels of lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in each group were detected. The morphology and fibrosis of renal tissue were observed. The content of adenosine triphosphate （ATP） and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected. The protein expressions of transforming growth factor- β （TGF- β）， hypoxia-inducible factor-1α （HIF-1α）， α-smooth muscle actin （α-SMA）， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were also observed. RESULTS Compared with CK group， the renal tissue of rats in the Model group was obviously damaged， renal tissue fibrosis was severe； the serum BUN and SCr levels， urine UP level， serum 4 LDH， TNF-α and IL-6 levels， as well as the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were significantly increased， while the serum IL-10 level， ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were significantly decreased （P＜0.05）. Compared with Model group， the renal tissue damage and fibrosis in the AST groups were reduced， the serum BUN and SCr levels， urine UP level， serum LDH， TNF-α and IL-6 levels， and the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 were significantly decreased， while the serum IL-10 level， ATP content and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria were significantly increased； the changes in the aforementioned indicators in AST- H group were more significant than those in the AST-L group（P＜0.05）. JFC could significantly reverse the improvement effect of high dose of AST on renal injury in CRF rats （P＜0.05）. CONCLUSIONS AST can reduce inflammation in CRF rats， alleviate renal tissue damage and fibrosis， and improve renal mitochondrial capacity metabolism， possibly by inhibiting the Jagged-1/Notch-1 signaling pathway.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.