Evolution and Information Analysis of Classical Formulas Guizhi Shaoyao Zhimutang / 中国实验方剂学杂志

The classic formula Guizhi Shaoyao Zhimutang, listed as the 15th formula in the Catalog of Ancient Classic Formulas (First Batch) published in 2018, originated from Synopsis of the Golden Chamber （《金匮要略》） written by ZHANG Zhongjing in the Eastern Han Dynasty. It consists of Cinnamomi Ramulus, Ephedrae Herba, Aconiti Lateralis Radix Praeparata, Anemarrhenae Rhizoma, Paeoniae Radix Alba, Atractylodis Macrocephalae Rhizoma, Saposhnikoviae Radix, Zingiberis Rhizoma Recens, and Glycyrrhizae Radix et Rhizoma, and is effective in dispelling wind, eliminating dampness, dispersing cold, relieving impediment, nourishing Yin, and clearing heat. It is mainly used to treat diseases characterized by wind, cold, and dampness invading the body, combined with heat damaging Yin, such as joint disorders, rheumatism, gout, and knee osteoarthritis. Based on the call for "inheritance of essence and application of ancient knowledge for modern use", this study conducted a comprehensive analysis of historical evolution, composition, formulation principles, processing, dosage, decocting methods, and indications of Guizhi Shaoyao Zhimutang using textual research on ancient and modern literature. When analyzing modern literature, it has been found that this formula is widely used in the treatment of various diseases. It is mainly applied to rheumatic diseases such as rheumatism, rheumatoid arthritis, gout, gouty arthritis, and psoriatic arthritis, as well as orthopedic diseases like knee osteoarthritis, ankylosing spondylitis, sciatica, and knee joint effusion. It can also be used for diseases in other systems, including the endocrine system, gynecology, respiratory system, and circulatory system. The pathological mechanisms involve the invasion of wind, cold, and dampness accompanied by heat pathogens, reflecting the concept of treating different diseases with the same principles in traditional Chinese medicine (TCM). Through the analysis of ancient and modern literature on Guizhi Shaoyao Zhimutang using a literature statistical method, the historical evolution and key formula and syndrome information were clarified to provide a theoretical basis for the development and further research of Guizhi Shaoyao Zhimutang in terms of its formulation and subsequent in-depth studies.

Clinical Efficacy of Guizhi Shaoyao Zhimutang Combined with Fire Needling in Treatment of Periarthritis of Shoulder with Wind-cold-dampness Impediment Syndrome by Stimulating Pain Points and "Shoulder Three Acupoints" / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Guizhi Shaoyao Zhimutang （GZSYZM） combined with fire needling in the treatment of periarthritis of shoulder with wind-cold-dampness impediment syndrome by stimulating pain points and "shoulder three acupoints". MethodA total of 120 patients with periarthritis of shoulder with wind-cold-dampness impediment syndrome， admitted to Hainan General Hospital from August 2020 to August 2022， were randomly divided into two groups using a random number table. The control group （60 cases） received treatment with GZSYZM for two weeks， while the observation group （60 cases） received treatment with GZSYZM combined with fire needling at pain points and "shoulder three acupoints" for two weeks. The clinical efficacy， adverse reactions， shoulder pain intensity， shoulder joint function， and levels of calcitonin gene-related peptide （CGRP）， cyclooxygenase-2 （COX-2）， interleukin （IL）-2， and IL-17 before and after treatment were compared between the two groups. ResultThe total effective rate in the observation group was 88.33% （53/60）， significantly higher than 68.33% （41/60） of the control group （χ²=7.070， P<0.01）. Compared with the results before treatment， both groups showed significant reductions in pain rating index （PRI）， visual analog scale （VAS） scores， present pain intensity （PPI）， and Simplified McGill Pain Questionnaire （SF-MPQ） total scores， as well as serum levels of CGRP， COX-2， IL-2， and IL-17 after treatment （P<0.01）， and improved pain intensity， daily life abilities， joint mobility， muscle strength， and Constant-Murley score （P<0.01）. Compared with the control group after treatment， the observation group showed significantly reduced PRI， VAS score， PPI， SF-MPQ total score， as well as serum levels of CGRP， COX-2， IL-2， and IL-17 （P<0.01）， and increased pain intensity， daily life abilities， joint mobility， muscle strength， and Constant-Murley score （P<0.01）. There was no significant difference in the incidence of adverse reactions between the two groups. ConclusionGZSYZM combined with fire needling at pain points and "shoulder three acupoints" can effectively reduce the levels of serum inflammatory factors and pain mediators， alleviate pain， and improve shoulder joint function in patients with periarthritis of shoulder with wind-cold-dampness impediment syndrome.

Therapeutic Effect of Guizhi Shaoyao Zhimutang on Osteoporosis in Rats Based on RANKL/OPG / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect of Guizhi Shaoyao Zhimutang （GSZT） on the osteoporosis （OP） in SD female rats induced by ovariectomy （OVX） combined with glucocorticoid injection and its related mechanisms. Method:The rats were divided into a sham operation group and an experimental group for OVX. One week later， the experimental rats were divided into an OP model group， a calciferol （positive control， 0.1 mg·kg^-1） group， and low（0.8 g·kg^-1）， medium（1.6 g·kg^-1）， and high-dose （3.2 g·kg^-1） GSZT groups. Except for those in the sham operation group， the rats received an intramuscular injection of dexamethasone （1 mg·kg^-1） twice per week for six weeks. After the rats were treated correspondingly for eight weeks， the rats were sacrificed for thighbone sample collection. The computer microtomography （Micro CT） was used to analyze the parameters of bone mineral density （BMD）， bone volume （BV）， tissue volume （TV）， structure model index （SMI）， connectivity density （Conn.D）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， trabecular pattern factor （Tb.Pf）， and trabecular separation （Tb.Sp）. In addition， hematoxylin-eosin （HE） and Masson staining was used for the histopathological examination of the thighbone. Tartrate-resistant acid phosphatase （TRAP） staining was used to analyze osteoclasts in bone tissues. The enzyme-linked immunosorbent assay （ELISA） was used to determine matrix metalloproteinase-9 （MMP-9）， cathepsin K （CTSK）， and TRAP5b in bone tissues， and Western blot was carried out to determine receptor activator of NF-kappaB ligand （RANKL）， osteoprotegerin （OPG）， alkaline phosphatase （ALP） in bone tissues. Result:Compared with normal group， the number of bone trabeculae in cancellous part of OP model rats decreased significantly， the spacing widened， the thickness became thinner， and the continuity was poor. Compared with model group， GZST medium and high-dose groups could improve the changes of femoral bone trabecular cancellous bone. Masson staining showed that compared with the normal group， the growth plate thickness of the distal femur epiphysis was thinner and the area of new bone was smaller in the OP model group， while the reduction of new bone was inhibited in the high dose group of calcitol and GZST. TRAP staining results showed that the number of osteoclasts in OP group was significantly increased compared with the normal group， and the number of osteoclasts in medium-high dose GZST group was reduced. Micro CT results showed that compared with normal group， BMD， BV， Tb.N， Tb.Th and Conn.D of OP rats were decreased， SMI and Tb.Sp were significantly increased（<italic>P</italic><0.01）. Compared with model group， medium and high dose of GZST could improve the degree of osteoporosis in OP rats， BV， Tb.N were significantly increased， SMI， Tb.Sp were significantly decreased （<italic>P</italic><0.01）. ELISA results revealed that compared with the sham operation group， the OP model group showed decreased ALP content （<italic>P</italic><0.01） and increased MMP-9， TRAP5b， and CTSK （<italic>P</italic><0.01）. Compared with the OP model group， the high-dose GSZT group showed increased ALP content （<italic>P</italic><0.01） and decreased MMP-9， TRAP5b， and CTSK （<italic>P</italic><0.01）. Western blot results demonstrated that compared with the OP model group， the calciferol group and the high-dose GSZT group showed inhibited expression of the RANKL protein （<italic>P</italic><0.05）， and increased OPG expression （<italic>P</italic><0.05）. Conclusion:The findings suggest that GZST has a potential therapeutic effect on OP caused by OVX combined with glucocorticoids in rats， and the underlying mechanism is associated with the regulation of RANKL/OPG in bone tissues. This study is expected to lay a preliminary foundation for its clinical application and modern preparation development.