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      Vol. 29 ， Issue 6 ， 2023

        Original Article

      • HAN Guan-ya,WU Xiao-li,LI Dong-mei,CAI Hai-rui,ZHOU Jun-jun,HE Xiao-bo
        Vol. 29, Issue 6, Pages: 483-489(2023) DOI: 10.1007/s11655-023-3730-0
        Abstract：Objective:To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial.Methods:This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments.Results:During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P <0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P <0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49±2.68 days vs. 8.96±2.35 days, P <0.01). The rate of postoperative C-reactive protein elevation (100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P <0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group.Conclusions:CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626)  
        Keywords：Chinese medicine plaster;rhubarb and mirabilite;surgical site infection;cesarean delivery;randomized controlled trial   
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        Published：2023-05-25
      • LIU Ya-lin,XU Jian-jun,HAN Lin-ran,LIU Xiang-fei,LIN Mu-hai,WANG Yun,XIAO Zhe,HUANG Yun-ke,REN Ping,HUANG Xi
        Vol. 29, Issue 6, Pages: 490-499(2023) DOI: 10.1007/s11655-022-3308-2
        Abstract：Objective:To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.Methods:Totally 120 Spraque-Dawley rats were randomly divided into 5–8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).Results:MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus–thalamus–basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.Conclusions:MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.  
        Keywords：Chinese medicine;Gan (Liver) governing free flow of qi;comorbidity;depression;hypomotility;ghrelin;blood oxygen level-dependent   
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        Published：2023-05-25
      • FENG Fu-zhen,GONG Wen-yan,LI Si-yun,DENG Yan-hui
        Vol. 29, Issue 6, Pages: 500-507(2023) DOI: 10.1007/s11655-022-3530-y
        Abstract：Objective:To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-β1 (TGF-β1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs).Methods:The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 μmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-Ⅱ) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-β1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016.Results:LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-Ⅱ (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of –8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1.Conclusion:RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.  
        Keywords：resveratrol;glomerular mesangial cells proliferation;sphingosine kinase 1 pathway;transformation growth factor-β1;molecular docking   
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        Published：2023-05-25
      • DING Dou,ZHANG Qi,ZENG Fu-jia,CAI Ming-xing,GAN Yuan,DONG Xiao-jun
        Vol. 29, Issue 6, Pages: 508-516(2023) DOI: 10.1007/s11655-022-3723-4
        Abstract：Objective:To investigate the therapeutic effect of gentisic acid (GA) on rheumatoid arthritis (RA) based on the miR-19b-3p/RAF1 axis.Methods:The cell counting kit-8 method was used to detect the growth inhibitory effect of different concentrations of GA on MH7A cells, and the drug concentration of GA was determined in the experiment. The quantificational real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-19b-3p and RAF1. RAF1, extracellular regulated protein kinases1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) were examined by Western blotting. Three methods (dual-luciferase assay, qRT-PCR and Western blot analysis) were used to verify miR-19b-3p targeting RAF1. Flow cytometry was performed to detect MH7A cell apoptosis. Transwell and wound healing assays were used to determine the invasion and migration capacities of MH7A cells.Results:The growth of MH7A cells was gradually inhibited with increasing GA concentration. When the GA concentration exceeded 80 mmol/L, GA was significantly cytotoxic to MH7A cells, so the half maximal inhibitory concentration of GA for MH7A cells was calculated as 67.019 mmol/L. GA upregulated miR-19b-3p expression, downregulated RAF1 expression, inhibited ERK1/2 phosphorylation, induced MH7A cell apoptosis and suppressed MH7A cell invasion and migration (P<0.05 or P<0.01). RAF1 was identified as the target of miR-19b-3p and reversed inhibitory effects on miR-19b-3p expression (P<0.05 or P <0.01). The miR-19b-3p inhibitor upregulated RAF1 expression and ERK1/2 phosphorylation, suppressed MH7A cell apoptosis and induced MH7A cell invasion and migration (P<0.01).Conclusion:GA regulated miR-19b-3p/RAF1 axis to mediate ERK pathway and inhibit the development of RA.  
        Keywords：gentisic acid;rheumatoid arthritis;miR-19b-3p;RAF1;MAPK/ERK   
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        Published：2023-05-25
      • LEI Ming-jun,BAI Fan,ZHANG Qing-yun,YANG Qing-qing,TIAN Zan
        Vol. 29, Issue 6, Pages: 517-525(2023) DOI: 10.1007/s11655-023-3737-y
        Abstract：Objective:To investigate the therapeutic effects of total glucosides of paeony (TGP) on psoriasis based on the immunomodulatory effect of dermal mesenchymal stem cells (DMSCs).Methods:A total of 30 male BALB/c mice were divided into 6 groups (n=5 in each) by a random number table method, including control, psoriasis model (model, 5% imiquimod cream 42 mg/d), low-, medium- and high-dose TGP (50, 100, and 200 mg/kg, L, M-, and H-TGP, respectively), and positive control group (2.5 mg/kg acitretin). After 14 days of continuous administration, the skin's histopathological changes, apoptosis, secretion of inflammatory cytokines, and proportion of regulatory T cells (Treg) and T helper cell 17 (Th17) were evaluated using hematoxylin-eosin (HE) staining, TdT-mediated dUTP nick end labeling staining, enzyme-linked immunosorbent assay, and flow cytometry, respectively. DMSCs were further isolated from the skin tissues of normal and psoriatic mice, and the cell morphology, phenotype, and cycle were observed. Furthermore, TGP was used to treat psoriatic DMSCs to analyze the effects on the DMSCs immune regulation.Results:TGP alleviated skin pathological injury, reduced epidermis layer thickness, inhibited apoptosis, and regulated the secretion of inflammatory cytokines and the proportion of Treg and Th17 in the skin tissues of psoriatic mice (P<0.05 or P<0.01). There was no significant difference in cell morphology and phenotype between control and psoriatic DMSCs (P>0.05), however, more psoriatic DMSCs remained in G0/G1 phase compared with the normal DMSCs (P<0.01). TGP treatment of psoriatic DMSCs significantly increased cell viability, decreased apoptosis, relieved inflammatory response, and inhibited the expression of toll-like receptor 4 and P65 (P<0.05 or P<0.01).Conclusion:TGP may exert a good therapeutic effect on psoriasis by regulating the immune imbalance of DMSCs.  
        Keywords：total glucosides of paeony;psoriasis;dermal mesenchymal stem cells;inflammatory response;immune imbalance   
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        Published：2023-05-25
      • GE Xiao-fen,LI Sha-sha,LIU Yan-hua,LU Mei-qiu,SU Hui-na,YANG Xin,SUN Xiao-wan
        Vol. 29, Issue 6, Pages: 526-533(2023) DOI: 10.1007/s11655-022-3514-3
        Abstract：Objective:To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin Ⅱ (AngⅡ)-induced hypertension in ovariectomized (OVX) rats.Methods:Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+AngⅡ, OVX, OVX+AngⅡ, OVX+AngⅡ+E2, and OVX+AngⅡ+KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg•d) and 17-β-estradiol (E2, 1.2 mg/(kg•d)] respectively, AngⅡ was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+AngⅡ+KT, OVX+AngⅡ+E2) and the negative control group (OVX+AngⅡ). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3Ⅱ/Ⅰ ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting.Results:Compared with the OVX+AngⅡ group, the systolic blood pressure of OVX+AngⅡ+KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+AngⅡ+KT group compared with the OVX+AngⅡ group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+AngⅡ+KT group, respectively (P<0.05). Compared with OVX+AngⅡ group, the levels of cardiac proteins beclin-1 and LC3Ⅱ/LC3Ⅰ in OVX+AngⅡ+KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05).Conclusion:KT could protect blood pressure of AngⅡ-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.  
        Keywords：Kuntai Capsule;Chinese medicine;perimenopausal hypertension;angiotensin Ⅱ   
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        Published：2023-05-25

        Acupuncture Research

      • LU Chao,LI Guang-liang,DENG De-hou,BAO Wen-long,WANG Yan,ZHANG Ai-qin
        Vol. 29, Issue 6, Pages: 534-539(2023) DOI: 10.1007/s11655-022-3684-7
        Abstract：Objective:To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL).Methods:This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded.Results:The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group.Conclusions:TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075)  
        Keywords：transcutaneous electrical acupoint stimulation;warm acupuncture;breast cancer related upper limb lymphedema;comprehensive detumescence treatment;clinical efficacy   
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        Published：2023-05-25

        Regulation and Guideline

      • YANG Jing-yi,SANG Zhen,WANG Rui,SHI Yan-hong,HUANG Yi-ran
        Vol. 29, Issue 6, Pages: 540-548(2023) DOI: 10.1007/s11655-022-3526-7
        Abstract：Medicinal plants or Chinese materia medica (CMM) are now attracting worldwide attention as they have increasingly prominent advantages over chemical drugs in disease treatment and healthcare. Since the 1990s, World Health Organization (WHO) and International Organization for Standardization established the Technical Committee of Traditional Chinese Medicine (ISO/TC 249) have carried out the development of quality standards on medicinal plants or CMMs respectively, and a considerable number of monographs and international standards have been published. Since the two international organizations adhere to different principles, the standards they develop naturally have different emphasis. Driven by market demand and international trade, ISO mainly takes quality, efficacy and safety into consideration when developing standards, while WHO pays more attention to clinical practice, quality control and medication guidance. Up to now, there is a lack of comparative analysis on the records, background, principles, basic content, and main requirements of quality standards on medicinal plants or CMMs respectively published by WHO and ISO. Therefore, based on international standards of CMM developed by ISO/TC 249 platform and WHO Monographs on Selected Medicinal Plants, this paper systematically compares the purposes, selected principles, standard-developing process, basic content, and main quality requirements to summarize their similarities and differences, and find their merits, aiming to serve as a reference to the development of international standards for CMMs that helps them go global.  
        Keywords：Chinese materia medica;medicinal plants;international standards;International Organization for Standardization;Technical Committee of Traditional Chinese Medicine;World Health Organization   
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        Published：2023-05-25

        Herbal and Botanical Review

      • Rabiya Ahsan,Anuradha Mishra,Badruddeen Badar,Mohammad Owais,Vijayshwari Mishra
        Vol. 29, Issue 6, Pages: 549-555(2023) DOI: 10.1007/s11655-023-3733-2
        Abstract：Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.  
        Keywords：Tinospora cordifolia;Guduchi;menispermaceae;pharmacology   
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        Published：2023-05-25

        Review

      • WANG Ya-li,ZHANG Hui-xiang,CHEN Yan-qi,YANG Li-li,LI Zheng-jun,ZHAO Min,LI Wen-lin,BIAN Yao-yao,ZENG Li
        Vol. 29, Issue 6, Pages: 556-565(2023) DOI: 10.1007/s11655-023-3735-0
        Abstract：Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.  
        Keywords：postoperative adhesion;Chinese medicine;prevention;treatment;review   
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        Published：2023-05-25
      • WANG Chang-lin,GAO Ming-zhou,GAO Xiang-ju,MU Xiang-yu,WANG Jie-qiong,GAO Dong-mei,QIAO Ming-qi
        Vol. 29, Issue 6, Pages: 566-576(2023) DOI: 10.1007/s11655-022-3724-3
        Abstract：Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the risk of progression to thyroid cancer. This review aims to provide a comprehensive summary of the mechanisms underlying the therapeutic effect of Chinese medicine (CM) in nodular goiter. Articles were systematically retrieved from databases, including PubMed, Web of Science and China National Knowledge Infrastructure. New evidence showed that CM exhibited multi-pathway and multi-target characteristics in the treatment of nodular goiter, involving hypothalamus-pituitary-thyroid axis, oxidative stress, blood rheology, cell proliferation, apoptosis, and autophagy, especially inhibition of cell proliferation and promotion of cell apoptosis, involving multiple signal pathways and a variety of cytokines. This review provides a scientific basis for the therapeutic use of CM against nodular goiter. Nonetheless, future studies are warranted to identify more regulatory genes and pathways to provide new approaches for the treatment of nodular goiter.  
        Keywords：nodular goiter;Chinese medicine;mechanism;pharmacology;review   
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