The Essential Role of Traditional Chinese Medicine Compounds in Regulating Recurrent Spontaneous Abortion by Inhibiting Oxidative Stress.

Due to the lack of accurate registration of RSA and miscarriages, many early miscarriages are overlooked and not diagnosed or treated promptly in hospitals. This uncertainty in pathogenesis prevents clinicians from taking targeted therapeutic measures, leading to unsatisfactory treatment outcomes and placing a heavy burden on the patient's family and the healthcare system. Oxidative stress is present in embryonic development and affects the regulation of oxidative stress in pregnancy and the reproductive endocrine system. Oxidative stress injury is a significant pathogenesis of RSA, so improving the body's ability to resist oxidative stress injury is crucial in treating RSA. For patients with RSA, there is an urgent need for safe, efficient, and cost-effective anti-oxidative stress drugs, and there is growing evidence that treatment with Traditional Chinese medicine (TCM) can improve pregnancy success with fewer adverse effects. Many active ingredients for treating RSA are mainly derived from certain components of TCM, including flavonoids, phenols, and other compounds, which have been shown to treat RSA directly or indirectly by targeting anti-oxidative stress-related pathways. This article summarizes the experimental and clinical evidence of several common TCM compounds for treating RSA. It provides ideas and perspectives for further exploring the pathogenesis of RSA and TCM compounds for treating RSA.

[Discussion on reference sample research of traditional Chinese medicine compound preparations developed from catalogued ancient classical prescriptions].

The concept of reference sample was put forward in the Guidance on CMC of Traditional Chinese Medicine Compound Preparations Developed from Catalogued Ancient Classical Prescriptions(Interim). The research on reference sample is a key link in the research and development of traditional Chinese medicine(TCM) compound prescriptions from catalogued ancient classical prescriptions(known as Category 3.1 TCM). This paper discusses the content of research on reference sample by analyzing the characteristics of Category 3.1 TCM and the purpose of research on reference sample. Furthermore, suggestions on the research of reference sample are proposed according to the development and evaluation practice of Category 3.1 TCM and research achievements of TCM regulatory science, aiming to provide reference for colleagues in this industry.

Therapeutic effect and mechanisms of traditional Chinese medicine compound (Qilong capsule) in the treatment of ischemic stroke.

Background Qilong capsule (QLC) is a well-known traditional Chinese medicine compound extensively used in clinical practice. It has been approved by the China's FDA for the treatment of ischemic stroke (IS). In our clinical trial involving QLC (ClinicalTrials.gov identifier: NCT03174535), we observed the potential of QLC to improve neurological function in IS patients at the 24th week, while ensuring their safety. However, the effectiveness of QLC beyond the initial 12-week period remains uncertain, and the precise mechanisms underlying its action in IS have not been fully elucidated. Purpose In order to further explore the clinical efficacy of QLC in treating IS beyond the initial 12-week period and systematically elucidate its underlying mechanisms. Study Design This study employed an interdisciplinary integration strategy that combines post hoc analysis of clinical trials, transcriptome sequencing, integrated bioinformatics analysis, and animal experiments. Methods In this study, we conducted a post-hoc analysis with 2302 participants to evaluate the effectiveness of QLC at the 12th week. The primary outcome was the proportion of patients achieving functional independence at the 12th week, defined as a score of 0-2 on the modified Rankin Scale (mRS), which ranges from 0 (no symptoms) to 6 (death). Subsequently, we employed RNA sequencing (RNA-Seq) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) techniques in the QLC trial to investigate the potential molecular mechanisms underlying the therapeutic effect of QLC in IS. Simultaneously, we utilized integrated bioinformatics analyses driven by external multi-source data and algorithms to further supplement the exploration and validation of QLC's therapeutic mechanism in treating IS. This encompassed network pharmacology analysis and analyses at the mRNA, cellular, and pathway levels focusing on core targets. Additionally, we developed a disease risk prediction model using machine learning. By identifying differentially expressed core genes (DECGs) between the normal and IS groups, we quantitatively predicted IS occurrence. Furthermore, to assess its protective effects and determine the key regulated pathway, we conducted experiments using a middle cerebral artery occlusion and reperfusion (MACO/R) rat model. Results Our findings demonstrated that the combination of QLC and conventional treatment (CT) significantly improved the proportion of patients achieving functional independence (mRS score 0-2) at the 12th week compared to CT alone (n = 2,302, 88.65 % vs 87.33 %, p = 0.3337; n = 600, 91.33 % vs 84.67 %, p = 0.0165). Transcriptome data revealed that the potential underlying mechanism of QLC for IS is related to the regulation of the NF-κB inflammatory pathway. The RT-qPCR results demonstrated that the regulatory trends of key genes, such as MD-2, were consistent with those observed in the RNA-Seq analysis. Integrated bioinformatics analysis elucidated that QLC regulates the NF-κB signaling pathway by identifying core targets, and machine learning was utilized to forecast the risk of IS onset. The MACO/R rat model experiment confirmed that QLC exerts its anti-CIRI effects by inhibiting the MD-2/TLR-4/NF-κB signaling axis. Conclusion: Our interdisciplinary integration study has demonstrated that the combination of QLC with CT exhibits significant superiority over CT alone in improving functional independence in patients at the 12th week. The potential mechanism underlying QLC's therapeutic effect in IS involves the inhibition of the MD-2/TLR4/NF-κB inflammatory signaling pathway, thereby attenuating cerebral ischemia/reperfusion inflammatory injury and facilitating neurofunctional recovery. The novelty and innovative potential of this study primarily lie in the novel finding that QLC significantly enhances the proportion of patients achieving functional independence (mRS score 0-2) at the 12th week. Furthermore, employing a "multilevel-multimethod" integrated research approach, we elucidated the potential mechanism underlying QLC's therapeutic effect in IS.

Application of network pharmacology in synergistic action of Chinese herbal compounds.

Herbal medicines are frequently blended in the form of multi-drug combinations primarily based on the precept of medicinal compatibility, to achieve the purpose of treating diseases. However, due to the lack of appropriate techniques and the multi-component and multi-target nature of Chinese medicine compounding, it is tough to explain how the drugs interact with each other. As a rising discipline, cyber pharmacology has formed a new approach characterized by using holistic and systematic "network targets" via the cross-fertilization of computer technology, bioinformatics, and different multidisciplinary disciplines. It can broadly screen the active ingredients of traditional Chinese medicine, enhance the effective utilization of drugs, and elucidate the mechanism of drug action. We will overview the principles of Chinese medicine compounding and dispensing, the research methods of network pharmacology, and the software of network pharmacology in the lookup of compounded Chinese medicines, aiming to supply thoughts for the better application of network pharmacology in the research of Chinese medicines.

Network Pharmacology in Research on Efficacy of Traditional Chinese Medicine and Compound Prescriptions / 中国实验方剂学杂志

The efficacy of traditional Chinese medicine （TCM） and compound prescriptions is confirmed based on practical experience. It is a highly generalized expression of the clinical characteristics and scope of prescriptions and a unique expression of the medical effects of TCM. Network pharmacology， as a cross-disciplinary field based on the theory of systems biology and multi-level analysis of biological systems， has become a common virtual screening tool in TCM research and gradually developed with the progress in big data and artificial intelligence. In the context of modern medicine， the efficacy of TCM compound prescriptions has a vague concept and lacks scientific evidence. Elucidating the connotation of TCM efficacy and guiding TCM theoretical research has become one of the hotspots and difficulties in TCM research. This article explores the feasibility of using network pharmacology for the research on the efficacy of TCM compound prescriptions and investigates whether the research results can represent part of the efficacy of prescriptions. Furthermore， the research platforms and algorithms in this field are summarized. The research ideas and existing problems in this field are proposed from the aspects of efficacy concept embodiment， target screening， result verification， efficacy network building， and homogenization avoiding of network pharmacology research results. Finally， the future development directions are prospected. This article is expected to provide a reference for exploring the modern biological basis of the efficacy of TCM and compound prescriptions and for the clinical application and theoretical research of TCM.

Research progress of traditional Chinese medicine monomer and compound intervention on the Wnt signaling pathway in regulating bone metabolism / 中国药房

Bone metabolism refers to the decomposition and anabolism occurring during bone remodeling， and its balance is regulated by bone resorption and bone formation. A slight deviation of this balance causes various skeletal diseases， such as osteoporosis and renal osteodystrophy. Traditional Chinese medicine （TCM） monomers and compounds have certain advantages in treating bone metabolism diseases. The Wnt signaling pathway includes the canonical Wnt signaling pathway， dependent on β-catenin， and the non-canonical Wnt signaling pathway， independent of β-catenin. Both types of pathways can maintain bone metabolism balance by regulating bone formation and bone resorption and are essential for bone development， bone mass maintenance， and bone remodeling. A variety of TCM monomers （albiflorin， catalpol and icariin） and formulas （Zuogui pill， Yishen gugu prescription， Duzhong jiangu prescription， etc.） have been confirmed to promote differentiation of bone marrow mesenchymal stem cells， proliferation and differentiation of osteoblasts， bone injury repair， and osteoporosis improvement by activating the Wnt signaling pathway in recent years. Here， this article summarizes the research progress in the Wnt signaling pathway regulation of bone metabolism by TCM monomers and compounds to provide ideas for the clinical application of TCM and the research and development of new drugs for the prevention and treatment of bone metabolism diseases.

Efficacy of traditional Chinese medicine compound on amenorrhea in female patients with schizophrenia caused by antipsychotic drugs： a Meta-analysis / 四川精神卫生

BackgroundThe incidence of mental disorders is steadily increasing. However， antipsychotic medications， commonly used in treatment， can lead to drug-induced amenorrhea in female patients. This side effect significantly reduces medication adherence and increases the risk of disease recurrence. Therefore， addressing drug-induced amenorrhea in female patients has become an urgent problem requiring effective solutions. ObjectiveTo explore the efficacy and safety of traditional Chinese medicine compound in treating antipsychotic-induced amenorrhea， so as to provide guidance for the treatment of this condition using traditional Chinese medicine compound. MethodsOn September 4， 2022， a computerized search was conducted on across multiple databases， including China National Knowledge Infrastructure， VIP Database， Wanfang Database， China Biomedical Literature Database， PubMed， Cochrane Library and Embase， and randomized controlled trials （RCT） of traditional Chinese medicine compound in treating antipsychotic-induced amenorrhea were collected. The quality of the included literature was assessed using Cochrane 5.3 bias risk assessment tool. Meta-analysis was performed to assess the total effective rate， cure rate， incidence of adverse reactions and recurrence rate using RevMan 5.3. ResultsUltimately， 22 RCT involving 1 879 patients were included. Meta-analysis results showed that the total effective rate （RR=1.29， 95% CI： 1.16~1.44） and cure rate （RR=1.62， 95% CI： 1.45~1.80） of traditional Chinese medicine compound or its combination with western medicine in treating antipsychotic-induced amenorrhea were significantly higher compared to western medicine alone. Moreover， the incidence of adverse reactions （RR=0.56， 95% CI： 0.41~0.76） and recurrence rate （RR=0.16， 95% CI： 0.06~0.42） were significantly lower than those of western medicine alone. ConclusionTraditional Chinese medicine compound may offer benefits in ameliorating antipsychotic-induced amenorrhea and its safety is better than simple western medicine treatment.

Discussion on the Antipruritic Mechanism of Qiwei Antipruritic Based on Network Pharmacology and Molecular Docking Technology.

Objective: To explore the mechanism of Qiwei antipruritic by using network pharmacology and molecular docking technology. Methods: The components and related targets of Qiwei antipruritic were screened by using the traditional Chinese medicine system pharmacology database (TCMSP and symmap databases). GeneCards and OMIM databases were used to screen itch-related targets. The protein-protein interaction (PPI) network between active ingredient targets and pruritus disease targets was constructed using STRING database. Cytoscape 3.8.0 software was used to draw the visualization network of "drug-component-target-signaling pathway" and screen the core targets. Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R software. AutoDock vina software was used to perform molecular docking of key targets and their corresponding key components. Results: There were 44 main components of Qiwei antipruritic compound, 118 corresponding targets and 3869 itch-related genes. A total of 82 predicted targets of Qiwei antipruritic in the treatment of pruritus were obtained. Eleven key targets were screened. Among the 23 KEGG enriched pathways, 12 signaling pathways were related to skin pruritus. Molecular docking results showed that the core components of Qiwei antipruritic, including quercetin, kaempferol, ß-sitosterol, stigmasterol, luteolin, and preskimmianine, had good binding ability with ESR1, PPARG, IL6, TP53, and EGFR, and the docking scores were all less than -4. Conclusion: The mechanism of Qiwei antipruritic may be related to histamine activation mechanism, calcium channel mechanism, inhibition of inflammatory signaling pathway, inhibition of neurotransmitters, and regulation of immune pathways. The traditional Chinese medicine compound Qiwei antipruritic can treat clinical pruritus through multiple targets and pathways.

[Role of TGF-ß/Smad signaling pathway in diabetic kidney disease and research progress of traditional Chinese medicine intervention].

Diabetic kidney disease is an important microvascular complication of diabetes and the leading cause of end-stage renal disease. Its pathological characteristics mainly include epithelial mesenchymal transition(EMT) in glomerulus, podocyte apoptosis and autophagy, and damage of glomerular filtration barrier. Transforming growth factor-ß(TGF-ß)/Smad signaling pathway is specifically regulated by a variety of mechanisms, and is a classic pathway involved in physiological activities such as apoptosis, proliferation and differentiation. At present, many studies have found that TGF-ß/Smad signaling pathway plays a key role in the pathogenesis of diabetic kidney disease. Traditional Chinese medicine has significant advantages in the treatment of diabetic kidney disease for its multi-component, multi-target and multi-pathway characteristics, and some traditional Chinese medicine extracts, traditional Chinese medicines and traditional Chinese medicine compound prescription improve the renal injury of diabetic kidney disease by regulating TGF-ß/Smad signaling pathway. This study clarified the mechanism of TGF-ß/Smad signaling pathway in diabetic kidney disease by expounding the relationship between the key targets of the pathway and diabetic kidney disease, and summarized the research progress of traditional Chinese medicine in the treatment of diabetic kidney disease by interfering with TGF-ß/Smad signaling pathway in recent years, to provide reference for drug research and clinical treatment of diabetic kidney disease in the future.

Interaction of Bmal1 and eIF2α/ATF4 pathway was involved in Shuxie compound alleviation of circadian rhythm disturbance-induced hepatic endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuxie Compound (SX) combines the composition and efficacy of Suanzaoren decoction and Huanglian Wendan decoction. It can soothe the liver, regulate the qi, nourish the blood and calm the mind. It is used in the clinical treatment of sleep disorder with liver stagnation. Modern studies have proved that circadian rhythm disorder (CRD) can cause sleep deprivation and liver damage, which can be effectively ameliorated by traditional Chinese medicine to soothe the liver stagnation. However, the mechanism of SX is unclear. AIM OF THE STUDY: This study was designed to demonstrate the impact of SX on CRD in vivo, and confirm the molecular mechanisms of SX in vitro. MATERIALS AND METHODS: The quality of SX and drug-containing serum was controlled by UPLC-Q-TOF/MS, which were used in vivo and in vitro experiments, respectively. In vivo, a light deprivation mouse model was used. In vitro, a stable knockdown Bmal1 cell line was used to explore SX mechanism. RESULTS: Low-dose SX (SXL) could restore (1) circadian activity pattern, (2) 24-h basal metabolic pattern, (3) liver injury, and (4) Endoplasmic reticulum (ER) stress in CRD mice. CRD decreased the liver Bmal1 protein at ZT15, which was reversed by SXL treatment. Besides, SXL decreased the mRNA expression of Grp78/ATF4/Chop and the protein expression of ATF4/Chop at ZT11. In vitro experiments, SX reduced the protein expression of thapsigargin (tg)-induced p-eIF2α/ATF4 pathway and increase the viability of AML12 cells by increasing the expression of Bmal1 protein. CONCLUSIONS: SXL relieved CRD-induced ER stress and improve cell viability by up-regulating the expression of Bmal1 protein in the liver and then inhibiting the protein expression of p-eIF2α/ATF4.

Role of TGF-β/Smad signaling pathway in diabetic kidney disease and research progress of traditional Chinese medicine intervention / 中国中药杂志

Diabetic kidney disease is an important microvascular complication of diabetes and the leading cause of end-stage renal disease. Its pathological characteristics mainly include epithelial mesenchymal transition(EMT) in glomerulus, podocyte apoptosis and autophagy, and damage of glomerular filtration barrier. Transforming growth factor-β(TGF-β)/Smad signaling pathway is specifically regulated by a variety of mechanisms, and is a classic pathway involved in physiological activities such as apoptosis, proliferation and differentiation. At present, many studies have found that TGF-β/Smad signaling pathway plays a key role in the pathogenesis of diabetic kidney disease. Traditional Chinese medicine has significant advantages in the treatment of diabetic kidney disease for its multi-component, multi-target and multi-pathway characteristics, and some traditional Chinese medicine extracts, traditional Chinese medicines and traditional Chinese medicine compound prescription improve the renal injury of diabetic kidney disease by regulating TGF-β/Smad signaling pathway. This study clarified the mechanism of TGF-β/Smad signaling pathway in diabetic kidney disease by expounding the relationship between the key targets of the pathway and diabetic kidney disease, and summarized the research progress of traditional Chinese medicine in the treatment of diabetic kidney disease by interfering with TGF-β/Smad signaling pathway in recent years, to provide reference for drug research and clinical treatment of diabetic kidney disease in the future.

Traditional Chinese Medicine Treats Chronic Atrophic Gastritis via Multiple Pathways / 中国实验方剂学杂志

ObjectiveTo mine the compatibility rules of patented traditional Chinese medicine (TCM) compound prescriptions for treating chronic atrophic gastritis (CAG) by systems pharmacology and molecular docking methods, and predict the targets and molecular mechanisms of Chinese medicinals with different efficacy in the treatment of CAG. MethodThe TCM compound prescriptions for treating CAG were extracted from the patent system of the China National Intellectual Property Administration. The active components and targets of the prescriptions were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrative Database (TCMID), and UniProt. The candidate targets and pathways of CAG were obtained from GeneCards, DisGeNet, Online Mendelian Inheritance in Man (OMIM), MalaCards, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome. The gene ontology (GO) functional annotation and KEGG pathway enrichment were realized by R Studio 4.1.2. STRING11.0 was employed to build the protein-protein interaction (PPI) network, and AutoDock Vina 4.2.6 was used for the docking between key targets and components. ResultA total of 228 TCM compound prescriptions for treating CAG were extracted. The medicinals used in these prescriptions mainly had warm or cold nature, bitter or sweet taste, tropism to the spleen, stomach, and liver meridians, and the efficacy of tonifying Qi, regulating Qi movement, clearing heat, and activating and toniying blood. The prescriptions mainly treated CAG via p53, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), forkhead box protein O (FoxO), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1 (HIF-1) signaling pathways. Molecular docking results confirmed that the active components in the prescriptions had docking activities with key receptor proteins. ConclusionThis study preliminarily analyzed the compatibility rules of TCM compound prescriptions in the treatment of CAG. The medicinals with different efficacy treat CAG by regulating cell proliferation, apoptosis, and oxidative stress response, preventing carcinogen production, promoting gastric acid secretion, and improving local microcirculation in a multi-target, multi-pathway, multi-link manner. The findings facilitate the research on the TCM treatment of CAG.

Study on the Medication Rule of the National Patent of Traditional Chinese Medicine Compound Formula in the Treatment of Depression / 中医杂志

ObjectiveTo explore the medication rules of traditional Chinese medicine compounds for depression in the National Patent Database using data mining， and to provide ideas for the clinical treatment and the development of new drugs for depression. MethodsThe patent data of traditional Chinese medicine compounds for the treatment of depression were searched from inception to July 1st， 2022 on the Patent Publication Announcement website of China National Intellectual Property Administration. The selected traditional Chinese medicine compounds were analyzed by using the data mining section of the ancient and modern medical record cloud platform （V2.3.5） for drug frequency， and based on this， the nature， flavor， channel entry and function of the medicinals were analyzed. Representative high-frequency herbal combinations were obtained through correlation analysis， while the classification of Chinese medicine compounds for depression was analyzed by cluster analysis， and the core combinations of herbs for the treatment of depression were screened out using complex network analysis. ResultsA total of 325 Chinese medicine compounds were included， involving 452 herbs， with a total frequency of 3532 times. The top 10 mostly used herbs were Yujin （Radix Curcumae， 122 times）， Chaihu （Radix Bupleuri， 122 times）， Baishao （Radix Paeoniae Alba， 109 times）， Suanzaoren （Spina Date Seed， 95 times）， Fuling （Poria， 94 times）， Danggui （Radix Angelicae Sinensis， 94 times）， Yuanzhi （Radix Polygalae， 84 times）， Baizhu （Rhizoma Atractylodis Macrocephalae， 72 times）， Shichangpu （Rhizoma Acori Graminei， 71 times）， and Danshen （Salvia Miltiorrhiza， 61 times）. The natures of the herbs were mainly warm （998 times）， neutral （944 times）， slightly cold （596 times） and cold （497 times）； the flavors were mainly sweet （1648 times）， acrid （1392 times）， and bitter （1337 times）； the channels of entry were mainly liver （1695 times）， heart （1521 times）， spleen （1326 times） and lung （1268 times）. The medicinals with the function of soothing liver to relieve constraint， moistening the intestines to promote defecation， calming the heart and the mind， moving qi to relieve constraint were used more frequently. The high frequency herbal combinations by association analysis included “Chaihu （Radix Bupleuri）→ Baishao （Radix Paeoniae Alba）”， “Danggui （Radix Angelicae Sinensis）→Chaihu （Radix Bupleuri）” and “Baishao （Radix Paeoniae Alba）→ Yujin （Radix Curcumae）”. The 22 high frequency medicinals used more than 40 times could be clustered into six categories. Complex network analysis found the core herbal combination for the treatment of depression was the formula of Chaihu （Radix Bupleuri）， Yujin （Radix Curcumae）， Baishao （Radix Paeoniae Alba）， Danggui （Radix Angelicae Sinensis）， Fuling （Poria）， Suanzaoren （Spina Date Seed）， and Xiangfu （Cyperi Rhizoma）. ConclusionTraditional Chinese medicine compounds for the treatment of depression is mainly based on the pathogenesis of constraint， stasis and deficiency， focusing on the liver， heart， spleen and lung， commonly using medicinals with the function of soothing liver to relieve constraint， fortifying spleen and nourishing heart， regulating qi and invigorating blood， and moistening the intestines to promote defecation， which can provide a reference for the clinical treatment and new drug research and development for depression.

Traditional Chinese medicine compounds ameliorating glomerular diseases via autophagy: A mechanism review.

Glomerular diseases are major components of kidney disease, mainly manifested as podocyte disease, immune complex-associated glomerulonephritis, and renal autoimmune disease. They are the third leading cause of end-stage renal disease, especially in younger populations. Podocyte death or shedding is a key factor in the progression of glomerular diseases, and autophagy plays an important role in maintaining podocyte homeostasis. Dysfunction of autophagy has been associated with the progression of various glomerular diseases. Modulation of autophagy has been shown to play a protective role in experimental models of glomerular diseases, suggesting that autophagy is a potential therapeutic target for glomerular diseases. Traditional Chinese medicine (TCM) has unique advantages in the treatment of kidney disease. In vivo and in vitro studies have shown that TCM compounds can reduce podocyte apoptosis, inhibit inflammation, improve endoplasmic reticulum stress and oxidative stress responses, and play an active role via autophagy. This review summarizes the roles of autophagy in glomerular diseases and provides evidence that TCM compounds can regulate autophagy through different signaling pathways to ameliorate glomerular diseases.

Value and influencing factors of valid Traditional Chinese Medicine compound prescription patents for mammary gland hyperplasia.

OBJECTIVE: To explore the value and factors influencing the maintenance of valid Traditional Chinese Medicine compound prescription patents for the management of mammary gland hyperplasia. METHODS: The State Intellectual Property Office Patents Database, China Patent Information Center Patents Database, Soopat Patent Search Platform, and CNIPR Search Platform of Chinese and Foreign Patent Database were searched to identify Traditional Chinese Medicine compound prescription patents for mammary gland hyperplasia that had been maintained for at least 5 years. Logistic regression analysis was used to detect the factors influencing the maintenance of valid patents. RESULTS: From 1 January 1993 to 31 December 2019, a total of 1228, Traditional Chinese Medicine compound prescription patents for mammary gland hyperplasia were authorized. Of these applications, 381 patents were granted and only 176 patents were maintained for more than 5 years. The five independent variables assessed in this study all had significant explanatory functions. CONCLUSIONS: The maintenance of valid patents for Traditional Chinese Medicine compound prescriptions for treating mammary gland hyperplasia is of great importance. The maintenance of such patents depends on many factors, such as the concentration of effective herbs, number of dependent claims, provision of new dosage forms and detailed experimental data, and transfer of patent rights.

Phase Difference of Traditional Chinese Medicine Compound Decoction： A Review / 中国实验方剂学杂志

Decoction is a traditional clinical way of traditional Chinese medicine （TCM） compound. A series of complex physical and chemical changes are often involved in the process of decoction， which presents a mixed-phase system. In most studies on the TCM compound decoction， it has always focused on the amounts of chemical substances in decoction， while the phase properties and existence forms of these components are neglected. Most of the chemical components exist in the mixed-phase system as molecules， ions or other particles. According to the particle size of the contained particles， the differences among the phases， including true solution phase， colloidal phase， suspended phase and precipitated phase， lead to their differences in pharmaceutical and biological effects. Based on the above research background， this paper takes the phase state differences of decoction as the breakthrough point， and systematically reviews the physicochemical properties， the physical structures of the active components and the biological effects of the decoction caused by the phase state differences. The phase state differences of TCM compound decoction have been found to be closely related to their efficacy， which might be a good perspective to investigate the possible mechanism. It might provide a beneficial reference for the exploration of related basic research on TCM compounds.

[Construction of "2R network pharmacology" research method for effective components of traditional Chinese medicine based on "prediction of dominant components-screening of potential targets"].

Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a "double reduction network pharmacology"(2 R network pharmacology) research method based on "prediction of dominant components-potential target selection". Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is "reducing constituents"; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is "reducing targets". To improve the efficiency and accuracy of effective component screening, the network relationship of "component target" was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.

Chinese Herbal Medicines for Promoting Blood Circulation and Removing Blood Stasis for Preventing Deep Venous Thrombosis after Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

AIM AND OBJECTIVE: To evaluate the efficacy and safety of Chinese herbal medicines for promoting blood circulation and removing blood stasis (PBCRBSM) for preventing deep venous thrombosis (DVT) after total hip arthroplasty (THA). MATERIALS AND METHODS: The databases were searched for studies comparing the preventive abilities of PBCRBSM and Western medicine, such as low molecular weight heparin (LMWH), rivaroxaban, and aspirin, as well as for randomized controlled trials on DVT after THA. Data were analyzed using RevMan 5.3 software. RESULTS: A total of 3254 randomized controlled trials were included, including 1630 cases in the experimental group and 1624 cases in the control group. Meta-analysis showed that compared with Western medicine, PBCRBSM reduced the incidence of DVT (OR=0.38, 95% CI [0.30, 0.48], P < 0.001); prolonged activated partial thromboplastin time (APTT) (SMD=0.44, 95% CI [0.35, 0.53], P < 0.001); reduced D-dimer (SMD=-0.75, 95% CI [-0.84,-0.65], P < 0.001), FIB (SMD=-0.61, 95% CI [-0.72, -0.50], P < 0.001), blood viscosity (P<0.01), circumference difference in lower extremities (P<0.01), venous blood flow velocity (SMD=0.97, 95% CI [0.77, 1.16], P < 0.001), and drainage volume (SMD=-1.53, 95% CI [-1.71, -1.35], P < 0.001); and reduced adverse reactions (OR = 0.32, 95% CI [0.19, 0.56], P < 0.001). There was no significant difference in prolonging prothrombin time (PT) between traditional Chinese medicine and Western medicine (SMD = 0.07, 95% CI [-0.0.01). 3, 0.16], P > 0.05. CONCLUSION: PBCRBSM is an effective method for preventing DVT after THA and has fewer adverse effects.

Construction of "2R network pharmacology" research method for effective components of traditional Chinese medicine based on "prediction of dominant components-screening of potential targets" / 中国中药杂志

Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a "double reduction network pharmacology"(2 R network pharmacology) research method based on "prediction of dominant components-potential target selection". Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is "reducing constituents"; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is "reducing targets". To improve the efficiency and accuracy of effective component screening, the network relationship of "component target" was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.

Study on the Plasma Protein Binding Rate and Compatibility Regularity of the Constituents Migrating to Blood of Simiao Yong'an Decoction.

OBJECTIVE: To study the compatibility regularity of Simiao Yong'an decoction by determining the plasma protein binding rate with the constituents in Simiao Yong'an decoction and to preliminarily clarify the effects of the compatibility on the plasma protein binding rate of different components. METHODS: Based on the equilibrium dialysis method, high-performance liquid chromatography was used to determine the contents of six constituents, which were divided into a single group and combination groups, in Simiao Yong'an decoction in the internal and external dialysis solutions. The obtained plasma protein binding rate through calculations was an index to evaluate the binding of the above components to plasma protein in different conditions. RESULTS: Harpagide, harpagoside, sweroside and loganin showed low plasma protein binding rates, ferulic acid exhibited a moderate plasma protein binding rate, and glycyrrhizic acid showed a high plasma protein binding rate. The compatibility study showed that glycyrrhizic acid promoted the binding of ferulic acid to plasma protein. Glycyrrhizic acid and ferulic acid were the key compounds to promote the binding of harpagide to plasma protein. Glycyrrhizic acid, harpagide, harpagoside and loganin had a significant inhibitory effects on the binding of sweroside to plasma protein. The plasma protein binding capacities of harpagoside and loganin were reduced by the other five constituents. Glycyrrhizic acid had the strongest plasma protein binding effect, and the binding effect was not affected by other components. CONCLUSION: This study explores the effects of compound compatibility on effective components from the perspective of plasma protein binding by high-performance liquid chromatography combined with the equilibrium dialysis method, and lays a foundation for clarifying the compatibility rule of Simiao Yong'an decoction and also provides a new idea for the study of the compatibility of traditional Chinese medicine formulas.