1.Research progress of nano drug delivery system based on metal-polyphenol network for the diagnosis and treatment of inflammatory diseases
Meng-jie ZHAO ; Xia-li ZHU ; Yi-jing LI ; Zi-ang WANG ; Yun-long ZHAO ; Gao-jian WEI ; Yu CHEN ; Sheng-nan HUANG
Acta Pharmaceutica Sinica 2025;60(2):323-336
Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.
2.Advances in oral distant targeted nanodelivery systems
Min SUN ; Chuan-sheng HUANG ; Li-ping WANG ; Xu-li RUAN ; Yun-li ZHAO ; Xin-chun WANG
Acta Pharmaceutica Sinica 2025;60(1):72-81
Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.
3.Role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 and effect of Bushen Jianpi Huoxue Decoction.
Tong-Ying CHEN ; Sai FU ; Xiao-Yun LI ; Shu-Hua LIU ; Yi-Fu YANG ; Dong-Sheng YANG ; Yun-Jie ZENG ; Yang-Bo LI ; Dan LUO ; Hong-Xing HUANG ; Lei WAN
China Journal of Chinese Materia Medica 2025;50(3):583-589
Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism*
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Autophagy/drug effects*
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Apoptosis/drug effects*
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Humans
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Drugs, Chinese Herbal/administration & dosage*
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Animals
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Cell Line
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bcl-X Protein/metabolism*
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Osteoblasts/metabolism*
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Rats
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Osteoporosis/physiopathology*
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Male
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Rats, Sprague-Dawley
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Osteogenesis/drug effects*
4.Tanshinone II A Facilitates Chemosensitivity of Osteosarcoma Cells to Cisplatin via Activation of p38 MAPK Pathway.
Da-Ming XIE ; Zhi-Yun LI ; Bing-Kai REN ; Rui GONG ; Dong YANG ; Sheng HUANG
Chinese journal of integrative medicine 2025;31(4):326-335
OBJECTIVE:
To examine the mechanism of action of tanshinone II A (Tan II A) in promoting chemosensitization of osteosarcoma cells to cisplatin (DDP).
METHODS:
The effects of different concentrations of Tan II A (0-80 µ mol/L) and DDP (0-2 µ mol/L) on the proliferation of osteosarcoma cell lines (U2R, U2OS, 143B, and HOS) at different times were examined using the cell counting kit-8 and colony formation assays. Migration and invasion of U2R and U2OS cells were detected after 24 h treatment with 30 µ mol/L Tan II A, 0.5 µ mol/L DDP alone, and a combination of 10 µ mol/L Tan II A and 0.25 µ mol/L DDP using the transwell assay. After 48 h of treatment of U2R and U2OS cells with predetermined concentrations of each group of drugs, the cell cycle was analyzed using a cell cycle detection kit and flow cytometry. After 48 h treatment, apoptosis of U2R and U2OS cells was detected using annexin V-FITC apoptosis detection kit and flow cytometry. U2R cells were inoculated into the unilateral axilla of nude mice and then the mice were randomly divided into 4 groups of 6 nude mice each. The 4 groups were treated with equal volume of Tan II A (15 mg/kg), DDP (3 mg/kg), Tan II A (7.5 mg/kg) + DDP (1.5 mg/kg), and normal saline, respectively. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell-related gene and signaling pathway expression were detected by RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis. p38 MAPK signaling pathway proteins and apoptotic protein expressions were detected by Western blot.
RESULTS:
In vitro studies have shown that Tan II A, DDP and the combination of Tan II A and DDP inhibit the proliferation, migration and invasion of osteosarcoma cells. The inhibitory effect was more pronounced in the Tan II A and DDP combined treatment group (P<0.05 or P<0.01). Osteosarcoma cells underwent significantly cell-cycle arrest and cell apoptosis by Tan II A-DDP combination treatment (P<0.05 or P<0.01). In vivo studies demonstrated that the Tan II A-DD combination treatment group significantly inhibited tumor growth compared to the Tan II A and DDP single drug group (P<0.01). Additionally, we found that the combination of Tan II A and DDP treatment enhanced the p38 MAPK signaling pathway. Western blot assays showed higher p-p38, cleaved caspase-3, and Bax and lower caspase-3, and Bcl-2 expressions with the combination of Tan II A and DDP treatment compared to the single drug treatment (P<0.01).
CONCLUSION
Tan II A synergizes with DDP by activating the p38/MAPK pathway to upregulate cleaved caspase-3 and Bax pro-apoptotic gene expressions, and downregulate caspase-3 and Bcl-2 inhibitory apoptotic gene expressions, thereby enhancing the chemosensitivity of osteosarcoma cells to DDP.
Abietanes/therapeutic use*
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Osteosarcoma/enzymology*
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Cisplatin/therapeutic use*
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Humans
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Cell Line, Tumor
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Animals
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Apoptosis/drug effects*
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Mice, Nude
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Cell Proliferation/drug effects*
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Cell Movement/drug effects*
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p38 Mitogen-Activated Protein Kinases/metabolism*
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MAP Kinase Signaling System/drug effects*
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Bone Neoplasms/enzymology*
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Cell Cycle/drug effects*
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Xenograft Model Antitumor Assays
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Mice
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Drug Resistance, Neoplasm/drug effects*
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Neoplasm Invasiveness
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Mice, Inbred BALB C
5.Zheng Gan Decoction inhibits diethylnitrosamine-induced hepatocellular carcinoma in rats by activating the Hippo/YAP signaling pathway.
Tianli SONG ; Yimin WANG ; Tong SUN ; Xu LIU ; Sheng HUANG ; Yun RAN
Journal of Southern Medical University 2025;45(4):799-809
OBJECTIVES:
To investigate the inhibitory effect of Zheng GanDecoction (ZGF) on tumor progression in a rat model of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and explore the possible mechanism.
METHODS:
Seventy SD rats were subjected to regular intraperitoneal injections of DEN (50 mg/kg) for 12 weeks to induce HCC tumorigenesis, with another 10 rats receiving saline injections as the normal control. After successful modeling, the rats were randomized into 5 groups (n=10) for daily treatment with distilled water ( model group), Huaier Granules (4 g/kg; positive control group), or ZGF at low, medium, and high doses (2, 4, and 8 g/kg, respectively) via gavage for 17 weeks. Body weight changes of the rats were monitored, and after completion of the treatments, the rats were euthanized for measurement of liver, spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining. The expressions of YAP, p-YAP, MST1, LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting.
RESULTS:
Compared with the normal control rats, the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate, increased body weight and liver and spleen indices, and a lowered thymus index. ZGF treatment obviously reduced liver and spleen indices, increased the thymus index, and improved pathologies of the liver tissues of the rat models. Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats, which also exhibited significantly upregulated hepatic expressions of MST1, LATS1 and p-LATS1.
CONCLUSIONS
ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression, which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.
Animals
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Drugs, Chinese Herbal/pharmacology*
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Diethylnitrosamine
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Rats, Sprague-Dawley
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Rats
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Signal Transduction/drug effects*
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Protein Serine-Threonine Kinases/metabolism*
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Carcinoma, Hepatocellular/drug therapy*
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YAP-Signaling Proteins
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Liver Neoplasms/drug therapy*
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Hippo Signaling Pathway
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Male
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Liver Neoplasms, Experimental/metabolism*
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Transcription Factors/metabolism*
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Adaptor Proteins, Signal Transducing/metabolism*
6.Effect of total flavonoids of Dracocephalum moldavica on TMAO-mediated JAK/STAT axis against atherosclerosis in rats and inflammation in RAW264.7 cells
Wen-Jiang CAO ; Chun-Yan DU ; Chuan-Sheng HUANG ; Yun-Li ZHAO ; Xiao-Li MA ; Yong YUAN ; Xin-Chun WANG
Chinese Pharmacological Bulletin 2024;40(9):1766-1772
Aim To investigate the protective effect of total flavonoids of Dracocephalum moldavica(TFDM)on atherosclerosis in rats and the inflammation of mouse macrophage RAW264.7 aggravated by trimeth-ylamine N-oxide(TMAO)and its possible mecha-nism.Methods The AS model of SD rats was estab-lished by high-fat diet feeding combined with intraper-itoneal injection of vitamin D3.The rats were divided into control group,model group,simvastatin group(15 mg·kg-1)and TFDM group(60,30,15 mg·kg-1).Biochemical method was used to detect the levels of se-rum total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C).HE staining was used to detect the pathological changes of aortic tissue.ELISA kit was used to detect the expression of TMAO,IL-1β,IL-6 in serum and TNF-α in liver tis-sue.Western blot was used to detect the expression of JAK,STAT and TNF-α protein in aorta.In addition,RAW264.7 macrophages were cultured in vitro,and LPS+TMAO was used to establish a macrophage in-flammation model,which was intervened by TFDM(100,50,25 mg·L-1).CCK-8 was used to determine cell viability and proliferation,and RT-qPCR was used to detect the expression of TNF-α,IL-6,JAK and STAT mRNA in cells.Results TFDM could significantly down-regulate the levels of serum TC,TG,LDL-C,ser-um TMAO,IL-1β,IL-6 and liver TNF-α,reduce aortic plaque deposition,and down-regulate the protein ex-pression of TNF-α,JAK and STAT in aorta.In addi-tion,TFDM intervention can significantly down-regulate the expression of TNF-α,IL-6,JAK,STAT mRNA and the expression of JAK,STAT protein.Conclusion TFDM can reduce the content of TMAO in serum,in-hibit JAK/STAT inflammatory signaling pathway and slow down the occurrence of inflammation,playing an anti-AS role.
7.The origin and development of history of Xiangya public health discipline(1911-2023)
Shan-Qi HUANG ; Zhi-Sheng LIU ; Guo DING ; Yun WANG
Chinese Journal of Infection Control 2024;23(11):1333-1343
Public health is a public service that is related to the health of the general public in a country or region.This article traces back to 1911-2023 and summarizes the major public health events during multiple periods,inclu-ding the beginning of public health during the Yale period,the initial establishment of Xiangya,and the establish-ment of the Faculty of Health of Hunan Medical College.It is the first systematic compilation of the history of Xiangya public health discipline.The milestones in the history of Xiangya public health discipline are as follows:(1)Dr.Yan Fuqing was the founder of health and public health around the establishment of Xiangya,and is the first person to propose the term'public health'.(2)The course of Health and Public Health in Xiangya began in 1916 and was offered in the academic year of 1918-1919.(3)Until the establishment of the Faculty of Health in 1975,the course of Health and Public Health was compulsory for Xiangya students.(4)In 1988,the Faculty of Health was renamed as the Faculty of Preventive Medicine,and the Institute of Preventive Medicine was established;In 1995,it was renamed as the School of Public Health of Hunan Medical University.In April 2000,after the merger and es-tablishment of Central South University,it was renamed as the School of Public Health of Central South University;In 2015,it was renamed as Xiangya School of Public Health of Central South University.Xiangya Public Health has been involved in almost all major public health work in China since its beginning,adhering to the principle of preven-tion first,promoting and serving people's health.
8.Discussion on the Pathogenesis Evolution of Chronic Obstructive Pulmonary Disease and Its Complications Based on the Theory of Five-Viscera Correlation
Yun-Sheng XU ; Chu-Shuan HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1335-1340
Based on Professor DENG Tie-Tao's five-viscera correlation theory and the achievements of modern medical research,the pathogenesis evolution of chronic obstructive pulmonary disease(COPD)and its complications was analyzed.It is believed that COPD mainly involves the lung,and is also closely related to the spleen,kidney,heart and liver,which can affect each other and cause the disease of other organs.After repeated exogenous attack of pathogens,COPD patients usually have lung qi deficiency and internal retention of phlegm-damp.Phlegm retention in the lungs induces the self-transmission and change of the viscera which causes the development of bronchiectasis and lung cancer;qi deficiency fails in helping the heart to promote the movement of blood,and then the heart blood stasis and obstruction occurs which can cause cardiovascular diseases such as hypertension and cardiac insufficiency.For the child-organ disease affects its mother-organ,lung qi deficiency can induce the transportation and transformation disorders of the spleen and stomach and internal retention of phlegm-damp,which causes gastroesophageal reflux disease.Lung qi stagnation and liver failing in maintaining free movement of qi dysfunction can lead to the emotional diseases such as anxiety and depression.Lung deficiency affects the kidney,and then the depletion of kidney essence and deficiency of bones occur which can cause osteoporosis.The deficiency of lung,spleen and kidney results in the impairment of breathing and the malnutrition of airway muscle which causes obstructive sleep apnea-hypopnea syndrome.The prolonged lung distension results in the insufficiency of the lung,spleen and kidney yin and fluid and the internal abundance of dry heat which causes diabetes.During the clinical treatment of COPD,its complications should be identified firstly,and comprehensive regulation of the zang-fu organs based on five-viscera correlation theory should be performed for the prevention of the COPD complications,thus to enhance the clinical efficacy.
9.Clinical Study on Yiqi Huatan Tongluo Prescription Combined with Drug-Coated Balloon in the Treatment of Coronary Heart Disease of Qi Deficiency and Phlegm Stasis Obstructing Collateral Type
Mei-Chun HUANG ; Yu-Peng LIANG ; Pei-Zhong LIU ; Sheng-Yun ZHANG ; Se PENG ; Chuang-Peng LI ; He-Zhen ZHANG ; Tian-Wei LAI ; Chang-Jiang AI ; Qing LIU ; Ai-Meng ZHANG ; Shao-Hui LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2656-2662
Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68%(47/53),and that of the control group was 75.47%(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P<0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P>0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P<0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P<0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87%(10/53),and that in the control group was 20.75%(11/53).There was no significant difference between the two groups(P>0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.
10.Clinical Study on Bazhen Decoction Combined with Traumatic Medicated Gauze in the Treatment of Diabetic Foot Ulcer of Qi-Blood Deficiency Syndrome
Sheng-Han HUANG ; Guang-Li LI ; Si-Yun LI ; Jue ZHANG ; Ai-Sheng WEI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(11):2943-2948
Objective To observe the clinical efficacy of Bazhen Decoction combined with traumatic medicated gauze(prepared mainly with the herbs of Scutellariae Radix,Phellodendri Chinensis Cortex and Sanguisorbae Radix)in the treatment of patients with diabetic foot ulcer(DFU)of qi-blood deficiency syndrome.Methods A total of 42 cases of DFU patients with qi-blood deficiency syndrome were randomly divided into a control group and an observation group,with 21 cases in each group.The control group was given basic western medicine treatment combined with external application of traumatic medicated gauze on wound surface,while the observation group was treated with Bazhen Decoction orally on the basis of treatment for the control group,and the treatment course of both groups covered four weeks.The changes of wound area,traditional Chinese medicine(TCM)syndrome scores,ankle-brachial index(ABI),and serum levels of fibrinogen(FIB),C-reactive protein(CRP),tumor necrosis factor α(TNF-α)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety in the two groups were compared.Results(1)After four weeks of treatment,the total effective rate in the observation group was 95.24%(20/21)and that in the control group was 85.71%(18/21),and the intergroup comparison(by rank sum test)showed that the clinical efficacy in the observation group was significantly superior to that in the control group(P<0.05).(2)After treatment,the wound area and TCM syndrome scores in the two groups were significantly improved compared with those before treatment(P<0.05),and the improvement of the wound area and TCM syndrome score in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,ABI in the two groups was increased when compared with that before treatment(P<0.05),and the improvement of ABI in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the levels of serum CRP,TNF-α and FIB in the two groups were all decreased compared with those before treatment(P<0.05),and the improvement of the serum levels in the observation group was significantly superior to that in the control group(P<0.05).(5)During the treatment,there were no significant adverse reactions occurring in the two groups,with high safety.Conclusion Bazhen Decoction combined with traumatic medicated gauze exerts certain effect in the treatment of DFU patients with qi-blood deficiency syndrome.The combined therapy is effective on improving the coagulation function and lower limb ischemia,reducing the levels of inflammatory factors,and relieving the inflammatory reaction,without obvious adverse reactions.

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