Latest Issue
      2019 Year 25 Vol. 1 Issue

        Feature Article

      • Si-ming LI,Jin-gen LI,Hao XU
        2019, 25(1): 3-8. DOI: 10.1007/s11655-018-2995-1
        Abstract：Inflammation, which plays a critical role in atherosclerosis and the occurrence of acute cardiovascular events, may be a new target for treatment of coronary artery disease (CAD) to reduce residual cardiovascular risk. Recently, Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS), the largest scale clinical trial that targeted inflammation but not lipids, has affirmed for the first time the inflammatory hypothesis of artherosclerosis and marked the advent of an exciting era of targeting inflammation for the prevention and treatment of cardiovascular diseases. Chinese medicine (CM) is a promising adjuvant therapy for CAD in light of its safety and pleiotropic effect of anti-inflammation, anti-platelet, lipid-regulating, endothelium-protection, microcirculation-improving, etc. In recent years, exploration of anti-inflammatory treatment of CAD with CM has been going on from theory to practice. Taking CANTOS as an example, the design strategy to combine CM and Western medicine to inhibit inflammation were discussed in this paper, which might provide a new perspective for CM intervention on CAD.  
        Keywords：coronary artery disease;inflammation;Chinese medicine   
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        Original Article

      • Kang ZHAO,Jin-fan TIAN,Cong ZHAO,Fei YUAN,Zhu-ye GAO,Li-zhi LI,Hong-xu LIU,Xian WANG,Chang-jiang GE,Shu-zheng LU
        2019, 25(1): 9-15. DOI: 10.1007/s11655-016-2454-9
        Abstract：Objective:To evaluate the effectiveness of integrative medicine (IM) on patients with coronary artery disease (CAD) and investigate the prognostic factors of CAD in a real-world setting.Methods:A total of 1,087 hospitalized patients with CAD from four hospitals in Beijing, China were consecutively selected between August 2011 and February 2012. The patients were assigned to two groups based on the treatment: Chinese medicine (CM) plus conventional treatment, i.e., IM therapy (IM group); or conventional treatment alone (CT group). The endpoint was major adverse cardiac events [MACE; including cardiac death, myocardial infarction (MI), and revascularization].Results:A total of 1,040 patients finished the 2-year follow-up. Of them, 49.4% (514/1,040) received IM therapy. During the 2-year follow-up, the total incidence of MACE was 11.3%. Most of the events involved revascularization (9.3%). Cardiac death/MI occurred in 3.0% of cases. For revascularization, logistic stepwise regression analysis revealed that age ≥ 65 years [odds ratio (OR), 2.224], MI (OR, 2.561), diabetes mellitus (OR, 1.650), multi-vessel lesions (OR, 2.554), baseline high sensitivity C-reactive protein level ≥ 3 mg/L (OR, 1.678), and moderate or severe anxiety/depression (OR, 1.849) were negative predictors (P<0.05); while anti-platelet agents (OR, 0.422), β-blockers (OR, 0.626), statins (OR, 0.318), and IM therapy (OR, 0.583) were protective predictors (P<0.05). For cardiac death/MI, age ≥ 65 years (OR, 6.389) and heart failure (OR, 7.969) were negative predictors (P<0.05), while statin use (OR, 0.323) was a protective predictor (P<0.05) and IM therapy showed a beneficial tendency (OR, 0.587), although the difference was not statistically significant (P=0.218).Conclusion:In a real-world setting, for patients with CAD, IM therapy was associated with a decreased incidence of revascularization and showed a potential benefit in reducing the incidence of cardiac death or MI.  
        Keywords：coronary artery disease;Chinese medicine;integrative medicine;effectiveness;real-world study   
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        Published：2021-08-27
      • Shi-wei LIU,Jie GUO,Wei-kang WU,Ze-liang CHEN,Ning ZHANG
        2019, 25(1): 16-22. DOI: 10.1007/s11655-017-2960-4
        Abstract：Objective:To evaluate Chinese medicine (CM) formula Bazheng Powder (八正散) as an alternative therapeutic option for female patients with recurrent urinary tract infection (RUTI).Methods:A randomized double-blinded trial was performed. Eligible female patients with RUTI were recruited from one hospital and two community health centers. By using a blocked randomization scheme, participants were randomized to receive a CM formula (10 herbs) and antibiotics placebo for 4 weeks, or antibiotics for 1 week followed by 3 weeks of placebo and CM formula placebo. Clinical cure rate and microbiological cure and recurrence after treatment were evaluated.Results:A total 122 eligible patients were enrolled, with 61 cases in each group. The clinical cure rate by the intent-to-treatment approach was 90.2% for the CM group and 82.0% for the antibiotics group (P>0.05). Bacteria were cleared from 88.5% (54/61) of patients in the CM group and 82.0% (50/61) in the antibiotics group. The recurrence rate in recovered patients at the 6-month follow-up was 9.1% (5/61) and 14.0 (7/61) in the CM and antibiotics groups, respectively (P>0.05).Conclusion:CM formula Bazheng Powder is a good alternative option for RUTI treatment. (Registration No. NCT01745328)  
        Keywords：Chinese medicine;recurrent urinary tract infection;randomized control trial   
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        Published：2021-08-27
      • Xue-li LI,Ji-ping FAN,Jian-xun LIU,Li-na LIANG
        2019, 25(1): 23-30. DOI: 10.1007/s11655-016-2747-z
        Abstract：Objective:To investigate the effects of salvianolic acid A (SAA) on cardiomyocyte apoptosis and mitochondrial dysfunction in response to hypoxia/reoxygenation (H/R) injury and to determine whether the Akt signaling pathway might play a role.Methods:An in vitro model of H/R injury was used to study outcomes on primary cultured neonatal rat cardiomyocytes. The cardiomyocytes were treated with 12.5, 25, 50 μg/mL SAA at the beginning of hypoxia and reoxygenation, respectively. Adenosine triphospate (ATP) and reactive oxygen species (ROS) levels were assayed. Cell apoptosis was evaluated by flow cytometry and the expression of cleavedcaspase 3, Bax and Bcl-2 were detected by Western blotting. The effects of SAA on mitochondrial dysfunction were examined by determining the mitochondrial membrane potential (△Ψm) and mitochondrial permeability transition pore (mPTP), followed by the phosphorylation of Akt (p-Akt) and GSK-3β (p-GSK-3β), which were measured by Western blotting.Results:SAA significantly preserved ATP levels and reduced ROS production. Importantly, SAA markedly reduced the number of apoptotic cells and decreased cleaved-caspase 3 expression levels, while also reducing the ratio of Bax/Bcl-2. Furthermore, SAA prevented the loss of △Ψm and inhibited the activation of mPTP. Western blotting experiments further revealed that SAA significantly increased the expression of p-Akt and p-GSK-3β, and the increase in p-GSK-3β expression was attenuated after inhibition of the Akt signaling pathway with LY294002.Conclusion:SAA has a protective effect on cardiomyocyte H/R injury; the underlying mechanism may be related to the preservation of mitochondrial function and the activation of the Akt/GSK-3β signaling pathway.  
        Keywords：salvianolic acid A;cardiomyocyte;hypoxia/reoxygenation injury;mitochondria;Akt/GSK-3β   
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        Published：2021-08-27
      • Peng YANG,Jia-hui LI,Ai-li LI,Jing LI,Yong WANG,Shi-yan REN,Xian-lun LI
        2019, 25(1): 31-36. DOI: 10.1007/s11655-017-2757-5
        Abstract：Objective:To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction (AMI) by affecting adhesion molecules integrin β1/CD29 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31).Methods:Twenty-two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in the model and garlicin groups. AMI porcine model was established in the model and garlicin groups. The distal parts of the left anterior descending coronary artery in the animals of the model and garlicin groups were occluded by dilated balloon for 2 h, followed by reperfusion for 3 h. Garlicin (1.88 mg/kg) was injected over a period of 1 h, beginning just before reperfusion, in the garlicin group. Real-time polymerase chain reaction, immunohistochemistry and Western blot were carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after reperfusion.Results:Hematoxylin-eosin staining showed a better myocardial structure in the garlicin group after reperfusion. Compared to the model group, garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in reperfusion area and no-reflow area (both P<0.05).Conclusions:Garlicin post-conditioning induced cardio-protection against myocardial ischemia-reperfusion injury in this catheter-based porcine model of AMI. The cardio-protective effect of garlicin is possibly owing to suppression of production of CD29 and CD31, by inhibition of the mRNA expression of CD29 and CD31.  
        Keywords：garlicin;reperfusion injury;myocardial infarction;CD29;CD31   
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        Published：2021-08-27
      • Qing-ping LI,Ri-bao WEI,Xi YANG,Xiao-yong ZHENG,Ting-yu SU,Meng-jie HUANG,Zhong YIN,Xiang-mei CHEN
        2019, 25(1): 37-44. DOI: 10.1007/s11655-017-2756-6
        Abstract：Objective:To investigate the protective effects and potential mechanisms of Shenhua Tablet (肾华片, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI).Methods:Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside (150 mg•kg-1•d-1), low- and high-dose SHT (1.5 and 3.0 g•kg-1•d-1, repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling, serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed; pathological damage were scored after periodic acid-Schiff staining. TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) protein and mRNA expressions were detected by inmmunohistochemistry, Western blot and qPCR. Tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) protein expressions were detected by enzyme linked immunosorbent assay.Results:Compared with the sham group, the model group exhibited severe change in renal function (Scr: 189.42±21.50, P<0.05), pathological damage (damage score: 4.50±0.55, P<0.05), and the expression levels of TLR2, TLR4, MyD88, TNF-α, IL-6 were significantly higher than other groups. Meanwhile, the levels of TLRs in model group showed upward tendency from 24 to 72 h, unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent, and, in addition to TLRs, presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model (P<0.05); in particular, the most significant mitigation of these changes was observed in the SHT-H group (P<0.05).Conclusions:TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the MyD88-dependent signaling pathway and exhibit some dose dependence.  
        Keywords：Shenhua Tablet;Chinese medicine;kidney injury;toll-like receptors;myeloid differentiation factor 88;ischemia-reperfusion injury   
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        Published：2021-08-27
      • Cheng-yin LI,Su-ling WU,Li-xia SUN,Ting-ting YAN,Yue WANG
        2019, 25(1): 45-50. DOI: 10.1007/s11655-014-1981-5
        Abstract：Objective:To investigate the protective effect of Zengye Decoction (增液汤, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice.Methods:Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by realtime polymerase chain reaction.Results:Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05).Conclusions:ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.  
        Keywords：Sjögren's syndrome;Th1/Th2;vasoactive intestinal peptide;Zengye Decoction;Chinese medicine   
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        Published：2021-08-27
      • Yan-min LIU,Hong-bo SHI,Yi-rong LIU,Hong-lin SHI,Feng REN,Yu CHEN,De-xi CHEN,Jin-li LOU,Zhong-ping DUAN
        2019, 25(1): 51-58. DOI: 10.1007/s11655-015-2430-9
        Abstract：Objective:To investigate the potential antifibrotic mechanisms of Chinese medicine Ganshuang Granules (肝爽颗粒, GSG) and to provide clinical therapeutic evidence of its effects.Methods:A cirrhotic mouse model was established by intraperitoneally injecting a mixture of CCl4 (40%) and oil (60%) at 0.2 mL per 100 g of body weight twice a week for 12 weeks. After 12-week modeling, GSG was intragastric administrated to the mice for 2 weeks, and the mice were divided into low-, medium- and high-dose groups at doses of 1, 2 and 4 g/(kg•day), respectively. Liver morphology changes were observed using Masson's trichrome staining and B-ultrasound. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hyaluronic acid (HA) in serum were detected using an automatic biochemistry analyzer. The expressions of desmin, smooth muscle actin (SMA) and Foxp3 in liver were detected by immunofluorescence. The regulatory T cell (Treg) frequency was determined through flow cytometry analysis. Collagen-Ⅰ, SMA, IL-6, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and transforming growth factor β1 (TGF-β1) expression levels were measured using quantitative polymerase chain reaction (qPCR).Results:Masson's staining result showed fewer pseudolobule structures and fibrous connective tissue in the GSG-treatment groups than in the spontaneous recovery group. Ultrasonography showed that GSG treatment reduced the number of punctate hyperechoic lesions in mice cirrhotic livers. The serum ALT, AST, HA levels were significantly ameliorated by GSG treatment (ALT: F=8.104, P=0.000; AST: F=7.078, P=0.002; and HA: F=7.621, P=0.001). The expression levels of collagen-Ⅰ and SMA in the cirrhotic livers were also attenuated by GSG treatment (collagen-Ⅰ: F=3.938, P=0.011; SMA: F=4.115, P=0.009). Tregs, which were elevated in the fibrotic livers, were suppressed by GSG treatment (F=8.268, P=0.001). The expressions of IL-6, TNF-α and IL-1β increased, and TGF-β levels decreased in the cirrhotic livers after GSG treatment (IL-6: F=5.457, P=0.004; TNF-α: F=6.023, P=0.002; IL-1β: F=6.658, P=0.001; and TGF-β1: F=11.239, P=0.000).Conclusions:GSG promoted the resolution/regression of cirrhosis and restored liver functions in part by suppressing Treg cell differentiation, which may be mediated by hepatic stellate cells.  
        Keywords：Ganshuang Granules;liver cirrhosis;regulatory T cell;hepatic stellate cell;Chinese medicine   
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        Published：2021-08-27

        Clinical Experience

      • Kai-liang FAN,Jun-hui WANG,Li KONG,Fei-hu ZHANG,Hao HAO,Hao ZHAO,Zheng-yun TIAN,Ming-xin YIN,Hua FANG,Hui-hui YANG,Yang LIU
        2019, 25(1): 59-63. DOI: 10.1007/s11655-017-2965-z
        Abstract：Objective:To investigate the hemodynamic effect of Shen-Fu Injection (参附注射液, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output (PICCO).Methods:All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1st, 2014 to December 31th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group (33 cases) and control group (32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation.Results:The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h (P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group (P<0.05), including cardiac index (CI), global end diastolic volume index (GEDI), mean arterial pressure (MAP) and heart rate (HR). In addition, there was no significant change of extra-vascular lung water index between the two groups (P>0.05).Conclusion:SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.  
        Keywords：septic shock;hemodynamic;Shen-Fu Injection;Chinese medicine;pulse indicator continuous cardiac output   
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        Academic Exploration

      • Yan-bo REN,Jian-hua HUANG,Wai-jiao CAI,Zi-yin SHEN
        2019, 25(1): 64-70. DOI: 10.1007/s11655-015-2136-z
        Abstract：As the epitome of the modern regenerative medicine, stem cells were proposed in the basic sense no more than 200 years ago. However, the concept of "stem cells" existed long before the modern medical description. The hypothesis that all things, including our sentient body, were generated from a small origin was shared between Western and Chinese people. The ancient Chinese philosophers considered Jing (also known as essence) as the origin of life. In Chinese medicine (CM), Jing is mainly stored in Kidney (Shen) and the so-called Shen-Jing (Kidney essence). Here, we propose that Shen-Jing is the CM term used to express the meaning of "origin and regeneration". This theoretical discovery has at least two applications. First, the actions underlying causing Shen-Jing deficiency, such as excess sexual intercourse, chronic diseases, and aging, might damage the function of stem cells. Second, a large number of Chinese herbs with Shen-Jing-nourishing efficacy had been proven to affect stem cell proliferation and differentiation. Therefore, if Shen-Jing in CM is equivalent with stem cells in regenerative medicine, higher effective modulators for regulating stem-cell behaviors from Kidney-tonifying herbs would be expected.  
        Keywords：Shen-Jing;Kidney essence;Kidney tonifying herbs;regenerative medicine;stem cells   
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        Published：2021-08-27

        Regulation and Guideline

      • Liang DAI,Chung-wah CHENG,Ran TIAN,Linda LD ZHONG,You-ping LI,Ai-ping LYU,An-wen CHAN,Hong-cai SHANG,Zhao-xiang BIAN,Zhao-xiang BIAN
        2019, 25(1): 71-79. DOI: 10.1007/s11655-018-2999-x
        Abstract：Traditional Chinese Medicine (TCM) is one of the oldest systems of medicine. More and more attention has been paid to TCM application, but the variable quality of clinical trials with TCM impedes its widespread acceptance. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement has established guidelines for designing clinical trials to ensure that the trial results are accurate and reliable. However, there are difficulties when applying SPIRIT 2013 Statement to trials with TCM, due to the unique theory and the characteristic of TCM intervention. An Extension to the original SPIRIT was developed to ensure the quality of trial design with TCM. As Chinese herbal formulae, acupuncture and moxibustion are common and representative interventions in TCM practice, the executive working group determined that the SPIRIT-TCM Extension focus on these three interventions. Extension was developed through initiation, 3 rounds of Delphi consensus survey, and finalizing expert meeting. Seven items from the SPIRIT 2013 Statement were modified, namely, "title", "background and rationale", "objectives", "eligibility criteria", "interventions", "outcomes", and "data collection methods". The Extension includes the introduction of the concept of TCM pattern and 3 major TCM interventions, with examples and explanations. The SPIRIT-TCM Extension 2018 provides suggestion for investigators in designing high quality TCM clinical trials. It is expected that wide dissemination and application of this extension ensure continuous improvement of TCM trial quality throughout the world.  
        Keywords：SPIRIT;traditional Chinese medicine;clinical trial;extension;recommendation   
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