Latest Issue

    2020 Year 26 Vol. 2 Issue

      Hot Topic

    • Xue-zhong GONG
      2020, 26(2): 83-87. DOI: 10.1007/s11655-019-3210-8
      Abstract:Arsenic from environmental contamination is a risk factor for kidney disease, and the clinical use of arsenic also triggers a new concern that the potential kidney damage caused by exposure to clinical doses of arsenic trivalent. So far, the undergoing mechanisms contributing to arsenic nephrotoxicity mostly remain unclear, and universally accepted methods for preventing this complication are limited too. Ancient Chinese medical scientists recognized the toxicity of arsenic long ago, and there were some records of Chinese herbs against arsenic poisoning in ancient books of Chinese medicine. In the past decade, several herbal formulations, as well as some potentially active compounds extracted from Chinese herbs, have been employed to prevent arsenic nephrotoxicity both in vivo and in vitro and showed better therapeutic effects. The present paper thus summarizes and discusses these Chinese medicine methods in preventing such a public health problem. In addition, we call for large, well-designed, randomized, and controlled clinical trials to be performed to further assess the efficacy and safety of these potential methods of Chinese medicine against arsenic nephrotoxicity.  
      Keywords:arsenic;nephrotoxicity;Chinese medicine;therapy;acute kidney injury   
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      Commentary

    • Rui-hua ZHAO,Wei-wei SUN,Yong LIU,Ze-qi DAI
      2020, 26(2): 88-91. DOI: 10.1007/s11655-018-2937-3
      Abstract:Endometriosis (EM), a refractory, highly recurrent and life-threatening chronic disease, requires long-term management and long-term drug treatment. Our previous studies showed that Chinese medicine (CM) can inhibit the postoperative recurrence of EM, improve quality of life, shorten the time to conception and increase pregnancy rates. CM produces few adverse reactions with high safety. These characteristics might be associated with the mechanism of CM's inhibition of recurrence. Therefore, we believe that CM may represent a good choice for long-term drug treatment and is worthy of clinical application.  
      Keywords:endometriosis;Chinese medicine;long-term management;individualized treatment   
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      Original Article

    • Rui-hua ZHAO,Yong LIU,Dan LU,Ying WU,Xiao-yun WANG,Wei-li LI,Cheng ZENG,Qing-wei MENG,Feng-mei LIAN,Jun ZHOU,Yun SHI,Wei-wei SUN,Qian HAN,Yi TANG,Guang SHI
      2020, 26(2): 92-99. DOI: 10.1007/s11655-019-3208-2
      Abstract:Objective:To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility.Methods:A multicenter, randomized, doubleblind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1–5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (活血消异颗粒); after ovulation, Bushen Zhuyun Granule (补肾助孕颗粒) was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment.Results:(1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05).Conclusion:Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713)  
      Keywords:endometriosis;infertility;Huoxue Xiaoyi Granule;Bushen Zhuyun Granule;pregnancy rate;randomized controlled clinical trial;Chinese medicine   
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      Published:2021-08-23
    • Seyedeh-Fatemeh Hekmatzadeh,Fatemeh Bazarganipour,Helen Allan,Shahintaj Aramesh,Jamshid Mohammadi
      2020, 26(2): 100-105. DOI: 10.1007/s11655-019-3222-4
      Abstract:Objective:To evaluate the effect of boiled dill seed (Anethum graveolens) on anxiety during childbirth compared with oxytocin.Methods:This study was a randomized controlled trial with 100 pregnant women who were assigned to the oxytocin (50 cases) and the boiled dill seed (50 cases) group by a table of random number. In the boiled dill seed group, 10 g of dill seed was boiled in 100 mL for 10 min and was given to women after filtration once orally at the beginning of active phase. In the oxytocin group, 10 IU of oxytocin in 1000 mL of Ringer solution was prescribed according to the clinical routine. The State-Trait Anxiety Inventory (STAI) in both groups before (at the beginning of the active phase) and after (6 h after the delivery) was completed. Meanwhile, pain intensity and duration of labor, dilatation and effacement scores, Apgar score of newborns, and FHR were measured and evaluated.Results:No statistically significant differences were shown in obvious anxiety scores between the two groups at baseline (P>0.05). After the delivery, in the boiled dill seed group, the number of women with severe [0 vs. 8.0% (4/50)] and almost severe [0 vs. 14.0% (7/50)] trait and almost severe [0 vs. 14.0% (7/50)] state anxiety was lower than those in the control group (P=0.050, P=0.041, respectively). Moreover, labor was shorter in the 1st (P<0.01), 2nd (P=0.78) and 3rd (P=0.10) stages in the boiled dill seed group compared to the control group.Conclusions:Dill seed could be used as an effective treatment to reduce anxiety during labor. Dill seed can be effective in reducing the length of labor. Due to lack of maternal and fetal complications, the boiled dill seed could also be used to reduce cesarean section rates in women who are fearful and anxious of delivery. (RCT Code: IRCT201607177065N2)  
      Keywords:dill seed;Anethum graveolens oxytocine;anxiety;delivery;pain   
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      Published:2021-08-23
    • Bo DU,Li-hong LIU,Yu-juan LV,Hao AI
      2020, 26(2): 106-113. DOI: 10.1007/s11655-019-3201-9
      Abstract:Objective:To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction (二仙汤, EXD) as a treatment for premature ovarian failure (POF) using a systems pharmacology approach.Methods:The compounds present in EXD were obtained from three databases. The active ingredient was identified by analyzing the values of oral bioavailability (OB), drug-likeness (DL), and Lipinski's rule (LR). The active ingredients were further searched in research articles, drug targets in the DrugBank database, and the C-T and T-P networks, as well as by pathway analysis using the Cytoscape platform.Results:A total of 728 compounds were identified in EXD. Of these, 59 were identified as active compounds that conformed to the criteria with OB≥30% and DL≥0.18. By further searches in the literature, 126 related targets were identified that could interact with the active compounds. Additionally, it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immune system, modulation of estrogen levels, and anti-oxidative activities, and that it may act in a synergistic or cooperative manner with other therapeutic agents.Conclusions:The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF. The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.  
      Keywords:premature ovarian failure;Chinese medicine;Erxian Decoction;systems pharmacology;pharmacological mechanism   
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      Published:2021-08-23
    • Shan-shan LI,Hui CAO,Ding-zhu SHEN,Chuan CHEN,San-li XING,Fang-fang DOU,Qing-ling JIA
      2020, 26(2): 114-121. DOI: 10.1007/s11655-019-2942-9
      Abstract:Objective:To investigate the effect of quercetin on ATP binding cassette transporter A1 (ABCA1), liver X receptor (LXR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) expressions in apoE-knockout (ApoE-/-) mice.Methods:The high-fat diet-induced atherosclerosis (AS) in ApoE-/- mice was established. Thirtysix mice were divided into 3 groups using random number table method: model group (n=12), quercetin group (n=12), and atorvastatin group (n=12), with C57BL/6J mice of the same strain and age as the control group (n=12). Quercetin group and atorvastatin group were administrated with quercetin and atorvastatin by oral gavage, with doses of 12.5 and 4 mg/(kg•d), respectively. Animals in the control and model groups were given an equal volume of distilled water by oral gavage once per day for a total of 12 weeks. Western blot and immunohistochemical methods were employed to determine the aortic ABCA1, LXR-α and PCSK9 protein expression. Enzyme linked immunosorbent assay method was used to detect the expression of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoproteincholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10, combined with tissue pathological examination.Results:ApoE-/- mice fed with a high-fat diet had notable atherosclerosis lesions, with reduced ABCA1, LXR-α and IL-10 levels (all P<0.01), elevated PCSK9, TNF-α and IL-6 expression, and increased TC and LDL-C contents (all P<0.01). After quercetin intervention, the areas of AS plaques and the expressions of PCSK9, TNF-α and IL-6 were significantly reduced (all P<0.01), while the expressions of ABCA1 and LXR-α were increased significantly (all P<0.01).Conclusion:Quercetin effectively interfered with AS development by regulating the expressions of ABCA1, LXR-α and PCSK9 in ApoE-/- mice.  
      Keywords:quercetin;atherosclerosis;ATP binding cassette transporter A1;liver X receptor;proprotein convertase subtilisin/kexin type 9   
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    • Hai-feng JIN,Jin-feng DAI,Li-na MENG,Bin LU
      2020, 26(2): 122-129. DOI: 10.1007/s11655-017-2958-y
      Abstract:Objective:To investigate the effects and possible mechanisms of action of Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl alcohol extract (CWNAE) on repression of human gastric cancer (GC) AGS cell invasion induced by co-culturing with Helicobacter pylori (HP).Methods:AGS cells were cultured with HP of positive or negative cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) expression (CagA+/- or VacA+/-) and divided into 5 group. Group A was cultured without HP as a control, Group B with HPCagA+VacA+, Group C with HPCagA-VacA-, Group D with HPCagA+VacA+ and CWNAE, and Group E with HPCagA-VacA and CWNAE. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and tumor invasion assays, examinations of morphology and ultramicroscopic structures, quantitative real-time polymerase chain reaction and Western blots were performed to measure the effects and uncover the mechanisms behind these effects of HPCagA+VacA+ and CWNAE on the epithelial-mesenchymal transition (EMT) of AGS cells.Results:The 10% inhibitory concentration of CWNAE against AGS cells after a 48 h incubation was 19.73±1.30 μg/mL. More AGS cells were elongated after co-culturing with HPCagA+VacA+ than after culturing with HPCagA-VacA-. In tumor invasion assays, HPCagA+VacA+ significantly enhanced the invasiveness of AGS cells compared to the other experimental groups (all P value <0.05), and this effect was inhibited by CWNAE. Treatment with CWNAE normalized tight junctions and reduced the number of pseudopodia of AGS cells co-cultured with HPCagA+VacA+. HPCagA+VacA+ up-regulated zincfinger ebox binding homeobox 1 (ZEB1) in AGS cells after co-culturing for 24 h. Expression of caudal type homeobox transcription factor (CDX-2) and claudin-2 was significantly increased by HPCagA+VacA+ (P<0.05), but not by HPCagA-VacA-.Conclusions:HPCagA+VacA+ promoted the invasiveness of AGS cells through up-regulation of ZEB1 transcription and claudin-2 and CDX-2 expression. CWNAE inhibited these effects of HPCagA+VacA+ on AGS cells by down-regulating ZEB1 transcription, and CDX-2 and claudin-2 expression.  
      Keywords:Helicobacter pylori;gastric cancer;AGS;zincfinger ebox binding homeobox 1;caudal type homeobox transcription factor;claudin-2;Chinese medicine   
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    • Junyoung Oh,Dong Hyun Kim,Gi-young Kim,Eun-Jin Park,Jong Hoon Ryu,Ji Wook Jung,Se Jin Park,Gwang-Woo Kim,Seungheon Lee
      2020, 26(2): 130-137. DOI: 10.1007/s11655-019-3204-6
      Abstract:Objective:To determine the effects of Hydrangeae Dulcis Folium (EHDF) on physical stress, changes in the whole-body cortisol level and behaviour in zebrafish (Danio rerio).Methods:One hundred and seventy-four fish were randomly divided into 4 [adrenocorticotropin hormone (ACTH) challenge test: 4 fish per group] or 6 groups (behavioural test: 10–12 fish per group, whole-body cortisol: 4 fish per group). Net handling stress (NHS) was used to induce physical stress. Fish were treated with vehicle or EHDF (5–20 mg/L) for 6 min before they were exposed to stress. And then, fish were sacrificed for collecting body fluid from whole-body or conducted behavioural tests, including novel tank test and open field test, and were evaluated to observe anxiety-like behaviours and locomotion. In addition, to elucidate the mode of action of the anti-stress effects of EHDF, ACTH (0.2 IU/g, i.p.) challenge test was performed.Results:The increased anxiety-like behaviours in novel tank test and open field test under stress were prevented by treatment with EHDF at 5–20 mg/L (P<0.05). Moreover, compared with the unstressed group, which was not treated with NHS, the whole-body cortisol level was significantly increased by treatment with NHS (P<0.05). Compared with the NHS-treated stressed control group, pre-treatment with EHDF at concentrations of 5–20 mg/L for 6 min significantly prevented the NHS-increased whole-body cortisol level (P<0.05). In addition, ACTH challenge test showed that EHDF completely blocked the effects of ACTH on cortisol secretion (P<0.05).Conclusion:EHDF may be a good antistress candidate and its mechanism of action may be related to its positive effects on cortisol release.  
      Keywords:net handling stress;zebrafish;Hydrangeae Dulcis Folium;whole-body cortisol;behavioural tests   
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    • Chu-xin DENG,Zhi-bing WU,Yi CHEN,Zheng-miao YU
      2020, 26(2): 138-145. DOI: 10.1007/s11655-019-2944-7
      Abstract:Objective:To investigate the neuromodulatory effect of pinellia total alkaloids (PTA) on the gamma-aminobutyric acidergic (GABAergic) system in epileptic rats, and preliminarily evaluate the anti-epileptic effect of PTA.Methods:Ninety-one male Sprague-Dawley rats were randomized to a control group (n=17) or an epileptic group (n=74) using computer-generated random numbers. Status epilepticus (SE) was induced with pilocarpine in the epileptic group. Epileptic rats that survived SE were randomly divided into 4 groups, namely an epilepsy group (n=13), a topiramate (TPM, 60 mg/kg) group (n=12), a high-dose PTA (800 mg/kg) group (n=12), and a low-dose PTA (400 mg/kg) group (n=10). Treatments were given intragastrically once daily for 14 days. The control group and epilepsy group received normal saline. Spontaneous recurrent seizures (SRSs) were monitored 8-h daily for 7 days after treatment. Then, the hippocampal formation tissues were collected. GABA level was measured using enzyme-linked immunosorbent assay. Protein and mRNA expression levels of glutamate decarboxylase 65 (GAD65), GABA transporter-1 (GAT-1), GABA transaminase (GABA-T), and GABAA receptor (GABAAR) α4, α5, γ2 and δ subunits were measured using Western-blotting analysis and quantitative polymerase chain reaction.Results:PTA lowered the incidence and frequency of SRS (both doses vs. the TPM group, P>0.05). Compared with the epilepsy group, PTA increased the levels of GABA (both doses P<0.01) and GAD65 (mRNA, 800 mg/kg, P<0.01), and suppressed the levels of GAT-1 (mRNA, 800 mg/kg, P<0.01; 400 mg/kg, P<0.05), GABA-T (mRNA, both doses P<0.01), and GABAAR δ subunit (protein, 800 mg/kg, P<0.05) and γ2 subunit (protein, both doses P<0.01). PTA upregulated the low-expressed mRNA levels of GABAAR α5 subunit (400 mg/kg, P<0.01), δ subunit (800 mg/kg, P<0.05), and γ2 subunit (400 mg/kg, P<0.05).Conclusions:PTA regulated the GABAergic system through modulating GABA levels and the expression levels of GAD65, GAT-1, GABA-T, and GABAAR α4, α5, γ2 and δ subunits. PTA may exert antiepileptic effects on the pilocarpine-induced epilepsy model.  
      Keywords:Pinellia total alkaloids;Pinellia ternata;gamma-aminobutyric acidergic agents;seizure;epilepsy   
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      Clinical Experience

    • Fu WANG,Qing-he GAO,Qiang GENG,Qiang HAN,Jia-you ZHAO,Guo-jin YU,Ji-wei ZHANG,Bin YAN,Jun GUO,Chun-sheng SONG
      2020, 26(2): 146-151. DOI: 10.1007/s11655-020-3211-7
      Abstract:Objective:To evaluate the clinical effectiveness and safety of the Chinese medicine (CM) Qixiong Zhongzi Decoction (芪芎种子汤, QZD) in the treatment of patients with idiopathic asthenozoospermia.Methods:A total number of 66 patients with idiopathic asthenozoospermia were included and randomly divided into treatment and control groups by SAS-generated code from January 2015 to August 2016, 33 patients in each group. Patients in the treatment group were administered with 150 mL of QZD twice a day, whereas those in the control group were given 1 g of levocarnitine oral liquid twice a day. The two groups received the indicated medication for 12 weeks and were then followed up for 4 weeks. The primary outcome was sperm motility, and the secondary therapeutic indices were sperm volume, density, pregnancy probability, and CM syndrome score. The comparison between groups was carried out at 4, 8 and 12 weeks, respectively. The safety was determined before and after treatment.Results:(1) Drop-off: 5 cases (7.58%) were lost after treatment (2 from the treatment group and 3 from the control group). (2) Primary outcomes: after 8- and 12-week treatment, the progressive sperms in the two groups were significantly higher than the baseline (all P<0.05); however, the treatment group showed greater improvement compared with the control group at 12-week treatment (22.7%±9.0% vs. 14.1%±8.8%, P<0.05). The increasement of non-progressive grade sperms at both groups was observed at 8- and 12-week treatment with statistical difference (all P<0.05), however, the treatment group showed remarkable improvement compared with the control group at 12-week treatment (38.7%±14.1% vs. 26.2%±15.4%, P<0.05). (3) Secondary outcomes: no significant statistical differences were found in semen volume and density (4, 8, and 12-week treatment) and pregnancy probability of patients' wives (12-week treatment) between two groups (all P>0.05), however, the CM syndrome score of the treatment group significantly declined compared with baseline level at each time points (all P<0.05). (4) Safety: no obvious side reactions were found during the treatment in both groups.Conclusions:QZD could improve the progressive and non-progressive grade sperm in the treatment of idiopathic asthenozoospermia. It is safe with no obvious side effects.  
      Keywords:idiopathic asthenozoospermia;Qixiong Zhongzi Decoction;Chinese medicine;random controlled trial   
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      Review

    • Yun-yun LI,Yi-kong LIN,Xin-hua LIU,Li WANG,Min YU,Da-jin LI,Yi-zhun ZHU,Mei-rong DU
      2020, 26(2): 152-160. DOI: 10.1007/s11655-019-3453-0
      Abstract:Leonurus japonicus Houtt, a Chinese traditional herbal medicine, has been widely used to cure gynecological diseases, such as incomplete abortion and menoxenia. Leonurine, a major active alkaloid compound only be found in Leonurus japonicus Houtt, has been successfully extracted and purified. Recent evidence has shown that leonurine can regulate a variety of pathologic processes including oxidative stress, inflammation, fibrosis, apoptosis, and multiple metabolic disorders. Here, we have reviewed the pharmacological actions and biological functions of leonurine, with a focus on the role of leonurine in the amelioration of various pathological processes. Insights into the related signaling pathways and molecular mechanisms have strengthened our understanding on the function of leonurine in the alleviation of multiple pathological states. Our summary of the existing researches should help direct future research into the basic science and clinical applications in related diseases.  
      Keywords:leonurine;Leonurus japonicus Houtt;Chinese medicine;oxidative stress;inflammation;fibrosis;clinical application   
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