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Three advantages of using traditional Chinese medicine to prevent and treat tumor
Chang-quan Ling​, Xiao-qiang Yue, Chen Ling​
Journal of Integrative Medicine    2014, 12 (4): 331-335.   DOI: 10.1016/S2095-4964(14)60038-8
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Traditional Chinese medicine (TCM), an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM has been increasingly used in the last decades and become well known for its significant role in preventing and treating cancer. We believe that TCM possesses advantages over Western medicine in specific aspects at a certain stage of cancer treatment. Here we summarize the advantages of TCM from three aspects: preventing tumorigenesis; attenuating toxicity and enhancing the treatment effect; and reducing tumor recurrence and metastasis.

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Cited: Baidu(242)
Efficacy of polyphenolic ingredients of Chinese herbs in treating dyslipidemia of metabolic syndromes
Zemin Yao​, Li Zhang​, Guang Ji​
Journal of Integrative Medicine    2014, 12 (3): 135-146.   DOI: 10.1016/S2095-4964(14)60023-6
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There is an increasing interest and popularity of Chinese herbal medicine worldwide, which is accompanied by increasing concerns about its effectiveness and potential toxicity. Several ingredients, such as polyphenolic compounds berberine, flavonoids, and curcumin, have been studied extensively by using various animal models. Effectiveness of treatment and amelioration of metabolic syndromes, including insulin resistance and dyslipidemia, has been demonstrated. This review summarizes the major checkpoints and contributing factors in regulation of exogenous and endogenous lipid metabolism, with particular emphasis centered on triglyceride-rich and cholesterol-rich lipoproteins. Available experimental evidence demonstrating the lipid-lowering effect of berberine, flavonoids and curcumin in cell culture and animal models is compiled, and the strengths and shortcomings of experimental designs in these studies are discussed.

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Cited: Baidu(209)
Extract of buckwheat sprouts scavenges oxidation and inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages (RAW264.7)
Rajendra Karki, Cheol-Ho Park, Dong-Wook Kim
Journal of Chinese Integrative Medicine    2013, 11 (4): 246-252.   DOI: 10.3736/jintegrmed2013036
Abstract974)   HTML    PDF      

Objective

Buckwheat has been considered as a potential source of nutraceutical components on the world market of probiotic foodstuffs. The purpose of this study was to evaluate the effects of tartary buckwheat (Fagopyrum tataricum) sprouts on oxidation and pro-inflammatory mediators.


Methods

The anti-oxidant effects of buckwheat extract (BWE) and rutin were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH)- and nitric oxide (NO)-scavenging activities, serum peroxidation and chelating assays. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used to evaluate anti-inflammatory activities of buckwheat and rutin. NO production in LPS-stimulated RAW264.7 cells was determined by using Griess reagent. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB) p65 subunit in cytosolic and nuclear portions were determined by Western blot analysis. Also, the production of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was determined by enzyme-linked immunosorbent assay.


Results

Inhibitory concentration 50 values for DPPH- and NO-scavenging activities of BWE were 24.97 and 72.54 μg/mL respectively. BWE inhibited serum oxidation and possessed chelating activity. Furthermore, BWE inhibited IL-6 and TNF-α production in LPS-stimulated RAW264.7 cells. Also, BWE inhibited iNOS and COX-2 expression and NF-κB p65 translocation.


Conclusion

Buckwheat sprouts possessed strong antioxidant activity and inhibited production of pro-inflammatory mediators in the applied model systems. Thus, buckwheat can be suggested to be beneficial in inflammatory diseases by inhibiting the free radicals and inflammatory mediators.

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Cited: Baidu(202)
Natural modulators of liver X receptors
Cheng Huang​
Journal of Integrative Medicine    2014, 12 (2): 76-85.   DOI: 10.1016/S2095-4964(14)60013-3
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Nuclear receptor transcription factors are ligand-activated proteins that control various biological events from cell growth and development to lipid metabolism, and energy and glucose homeostasis. Nuclear receptors are important drug targets for metabolic diseases. Liver X receptors (LXRs) are nuclear receptor transcription factors that play essential roles in regulation of cholesterol, triglyceride, fatty acid, and glucose homeostasis. LXR-deficient mice have shown the association of LXR-signaling pathway dysfunction with several human pathologies including atherosclerosis, hyperlipidemia, Alzheimer’s disease and cancer. Thus, LXRs are promising pharmacological targets for these diseases. Synthetic LXR agonists may lower cholesterol, but increase triglyceride and induce fatty liver. The naturally occurring LXR ligands, with moderate activity, may serve as nutraceuticals for prevention or treatment of the disorders, while minimizing potential side effects. In this review, recent advances in natural LXR modulators are summarized including agonist, antagonist and the modulator of LXR pathway.

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Cited: Baidu(201)
Advances in mesenchymal stem cells combined with traditional Chinese medicine therapy for liver fibrosis
Shu Dong, Shi-bing Su​
Journal of Integrative Medicine    2014, 12 (3): 147-155.   DOI: 10.1016/S2095-4964(14)60022-4
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Liver fibrosis is a primary cause of liver cirrhosis, and even hepatocarcinoma. Recently, the usage of mesenchymal stem cells (MSCs) has been investigated to improve liver fibrosis. It has been reported that the differentiation, proliferation and migration of MSCs can be regulated by traditional Chinese medicine treatment; however, the mechanisms are still unclear. In this article, the authors review the characteristics of MSCs such as multidirectional differentiation and homing, and its application in animal experiments and clinical trials. The authors also list areas that need further investigation, and look at the future prospects of clinical application of MSCs.

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Cited: Baidu(191)
Research advances on the usage of traditional Chinese medicine for neuroprotection in glaucoma
Xue-song Mi, Jing-xiang Zhong, Raymond Chuen-Chung Chang, Kwok-Fai So
Journal of Chinese Integrative Medicine    2013, 11 (4): 233-240.   DOI: 10.3736/jintegrmed2013037
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Progressive loss of retinal ganglion cells (RGCs) and their axons is the main pathogenesis of glaucoma. The cause of glaucoma is not fully understood, but the neurodegeneration of glaucoma involves many mechanisms such as oxidative stress, glutamate toxicity and ischemia/reperfusion insult. In order to target these mechanisms, multiple neuroprotective interventions have been investigated to prevent the death of RGCs. Of note are some tonic herbs from the traditional Chinese medicine (TCM) pharmacopeia that have shown neuroprotective effects in glaucoma. TCM differs from Western medicine in that TCM exhibits complicated bioactive components, triggering many signaling pathways and extensive actions on vital organs. Modern scientific approaches have demonstrated some of their underlying mechanisms. In this review, we used Lycium barbarum and Ginkgo biloba as examples to elaborate the characteristics of TCM and their potential applications in neuroprotection in glaucoma.

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Cited: Baidu(161)
Chemical components of Centella asiatica and their bioactivities
Cheng-jian Zheng, Lu-ping Qin
Journal of Chinese Integrative Medicine    2007, 5 (3): 348-351.   DOI: 10.3736/jcim20070324
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Cited: Baidu(143)
A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory
Zhi-mei Wang, Bin Zhang
Journal of Chinese Integrative Medicine    2010, 8 (11): 1097-1100.   DOI: 10.3736. jcim20101116
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Cited: Baidu(135)
Differential effects of adulterated versus unadulterated forms of linoleic acid on cardiovascular health
Stephen D. Anton, Kacey Heekin, Carrah Simkins, Andres Acosta
Journal of Chinese Integrative Medicine    2013, 11 (1): 2-10.   DOI: 10.3736/jintegrmed2013002
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According to the classic “diet-heart” hypothesis, high dietary intake of saturated fats and cholesterol combined with low intake of polyunsaturated fats can increase levels of serum cholesterol and lead to the development of atherogenic plaques and ultimately cardiovascular diseases. Recently, the beneficial health effects of omega-6 polyunsaturated fatty acids, particularly linoleic acid (LA), on cardiovascular health have been called into question with some scientists suggesting that consumption of LA should be reduced in Western countries. The focus of this critical review is on the controversy surrounding the effects of dietary intake of LA on cardiovascular health. Specifically, we critically examined the effects of both unadulterated and adulterated forms of LA on cardiovascular health outcomes based on findings from epidemiological studies and randomized controlled trials. Additionally, we address common concerns surrounding dietary intake of LA regarding its relationship with arachidonic acid, the ratio of omega-6 to omega-3 fatty acids, and its relationship with inflammation. Our critical review indicates that unadulterated forms of LA are cardioprotective and should be consumed as part of a healthy diet. In contrast, abundant evidence now indicates that adulterated forms of LA, predominantly hydrogenated vegetable oils, are atherogenic and should not be considered part of a healthy diet. The ability to adulterate the natural omega-6 fatty acid, LA, has contributed to mixed findings regarding the effects of this fatty acid on cardiovascular health. Thus, it is critical that the source of LA be taken into account when drawing conclusions about the physiological effects of this fatty acid. The findings of the present review are in line with current dietary recommendations of the American Heart Association.

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Cited: Baidu(123)
Traditional Chinese medicine for treatment of liver diseases: Progress, challenges and opportunities
Chang-qing Zhao, Yang Zhou, Jian Ping, Lie-ming Xu
Journal of Integrative Medicine    2014, 12 (5): 401-408.   DOI: 10.1016/S2095-4964(14)60039-X
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Traditional Chinese medicine (TCM) is commonly used in treating liver diseases worldwide, especially in China. The advantages of using TCM for treatment of liver diseases include: protecting hepatocytes, inhibiting hepatic inflammation and antifibrosis in the liver. In this article, we introduce TCM herbal preparations from the Chinese materia medica (such as Fuzheng Huayu) that are typically used for the treatment of liver diseases. Literature surrounding the mechanisms of TCM therapy for treatment of liver diseases is presented and discussed. We propose that side effects of herbal compounds are often under-appreciated, and that more care should be taken in the prescription of potentially hepatotoxic medicines. Further, to deepen the understanding of TCM mechanisms, new techniques and methodologies must be developed. Future studies will lead to the enhancement of clinical outcomes of TCM. As complementary and alternative therapies, TCMs will play an expanding role in the future of liver disease treatment.

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Cited: Baidu(121)
Role of adult resident renal progenitor cells in tubular repair after acute kidney injury
Hui-ling Wang, Nan-mei Liu, Rui Li
Journal of Integrative Medicine    2014, 12 (6): 469-475.   DOI: 10.1016/S2095-4964(14)60053-4
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Acute kidney injury is a serious global health problem and determinant of morbidity and mortality. Recent advancements in the field of stem cell research raise hopes for stem cell-based regenerative approaches to treat acute kidney diseases. In this review, the authors summarized the latest research advances of the adult resident renal progenitor cells (ARPCs) on kidney repair, the role of ARPCs on tubular regeneration after acute kidney injury, the current understanding of the mechanisms related to ARPC activation and modulation, as well as the challenges that remain to be faced.

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Cited: Baidu(116)
The role of central nervous system on hypoglycemia and the feasibility of the brain theory in traditional Chinese medicine on treatment of diabetes mellitus
Hai-li Jiang, Jing-jing Ni, Wei-fei Zhang, Wen-jin Huang​, Ming-yue Zhou​, Wen-jun Sha​, Jun-yan Li​, Fu-feng Li​, Zhu Ting​​, Xin Xia, Jun Zhang​, Yuan-dong Shen​, Li-gang Zhou​
Journal of Integrative Medicine    2014, 12 (1): 1-6.   DOI: 10.1016/S2095-4964(14)60008-X
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The central nervous system (CNS) plays a key regulatory role in glucose homeostasis. In particular, the brain is important in initiating and coordinating protective counterregulatory responses when blood glucose levels fall. This may due to the metabolic dependency of the CNS on glucose, and protection of food supply to the brain. In healthy subjects, blood glucose is normally maintained within a relatively narrow range. Hypoglycemia in diabetic patients can increase the risk of complications, such as heart disease and diabetic peripheral neuropathy. The clinical research finds that the use of traditional Chinese medicine (TCM) has a positive effect on the treatment of hypoglycemia. Here the authors reviewed the current understanding of sensing and counterregulatory responses to hypoglycemia, and discuss combining traditional Chinese and Western medicine and the theory of iatrogenic hypoglycemia in diabetes treatment. Furthermore, the authors clarify the feasibility of treating hypoglycemia on the basis of TCM theory and CNS and have an insight on its clinical practice.

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Cited: Baidu(108)
Effects of Yanggan Lidan Granule on insulin resistance in guinea pigs with induced cholesterol gallstones
Bang-jiang Fang, Shuang Zhou, Xin-jun Pei, Jin-yang Huang, Bao-jin Chen, Yun Geng , Li-kun Yang
Journal of Chinese Integrative Medicine    2009, 7 (12): 1159-1163.   DOI: 10.3736/jcim20091213
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Objective

To observe the effects of Yanggan Lidan Granule (YGLDG), a compound traditional Chinese herbal medicine, on insulin resistance in guinea pigs with induced cholesterol gallstones.
Methods

Eighty guinea pigs were randomly divided into normal control group, untreated group, YGLDG group and ursodeoxycholic acid (UDCA) group, with 20 guinea pigs in each group. Except the normal control group, gallstones were induced by high-cholesterol diet in the guinea pigs. The guinea pigs in the normal control group and the untreated group were administered with normal saline. UDCA and YGLDG were given to the guinea pigs in the corresponding groups for seven weeks. Eight guinea pigs of each group were used to measure the glucose infusion rate (GIR) by using hyperinsulinemic-euglycemic clamp technique. At the end the guinea pigs were killed and their gallstone formation was observed.
Results

The gallstones in guinea pigs were identified as cholesterol stones by qualitative analysis through infrared spectrum. The incidence rate of cholelithiasis of the untreated group was 82.35%. The GIR of guinea pigs in the untreated group was obviously lowered down as compared with the normal control group. Compared with the untreated group, the GIRs of the YGLDG group and the UDCA group were obviously increased, especially in the YGLDG group. Conclusion: YGLDG may improve insulin resistance in guinea pigs with cholesterol gallstones by elevating GIR obviously.

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Cited: Baidu(105)
Curcumin alters motor coordination but not total number of Purkinje cells in the cerebellum of adolescent male Wistar rats
Ginus Partadiredja, Taufik Nur Yahya, Christiana Tri Nuryana, Rina Susilowati
Journal of Chinese Integrative Medicine    2013, 11 (1): 32-38.   DOI: 10.3736/jintegrmed2013006
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Objective

The present study aimed at investigating the effects of curcumin on the motor coordination and the estimate of the total number of cerebellar Purkinje cells of adolescent Wistar rats exposed to ethanol.


Methods

The total of 21 male Wistar rats aged 37 d old were divided into three groups, namely ethanol, ethanol-curcumin, and control groups. The ethanol group received 1.5 g/kg ethanol injected intraperitoneally and water given per oral; the ethanol-curcumin group received 1.5 g/kg ethanol injected intraperitoneally and curcumin extract given per oral; the control group received saline injection and oral water. The treatment was carried out daily for one month, after which the motor coordination performance of the rats was examined using revolving drum apparatus at test days 1, 8, and 15. The rats were finally sacrificed and the cerebellum of the rats was further processed for stereological analysis. The estimate of the total number of Purkinje cells was calculated using physical fractionator method.


Results

The ethanol-curcumin group performed better than both ethanol and control groups in the motor coordination ability at day 8 of testing (P<0.01). No Purkinje cell loss was observed as a result of one month intraperitoneal injection of ethanol.


Conclusion

Curcumin may exert beneficial effects on the motor coordination of adolescent rats exposed to ethanol via undetermined hormetic mechanisms.

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Cited: Baidu(102)
Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: A multicenter randomized controlled trial
Xiao-feng Zhai, Zhe Chen, Bai Li, Feng Shen, Jia Fan, Wei-ping Zhou, Yun-ke Yang, Jing Xu, Xiao Qin, Le-qun Li, Chang-quan Ling
Journal of Chinese Integrative Medicine    2013, 11 (2): 90-100.   DOI: 10.3736/jintegrmed2013021
Abstract1060)   HTML    PDF      

Background

Disease recurrence is a main challenge in treatment of hepatocellular carcinoma (HCC). There is no generally accepted method for preventing recurrence of HCC after resection.


Objective

To compare the efficacy of a traditional herbal medicine (THM) regimen and transarterial chemoembolization (TACE) in preventing recurrence in post-resection patients with small HCC.



Design, setting, participants and interventions

This is a multicenter, open-label, randomized, controlled study, which was undertaken in five centers of China. A total of 379 patients who met the eligibility criteria and underwent randomization were enrolled in this trial. One hundred and eighty-eight patients were assigned to the THM group and received Cinobufacini injection and Jiedu Granule, and the other 191 patients were assigned to the TACE group and received one single course of TACE.


Main outcome measures

Primary outcome measures were the annual recurrence rate and the time to recurrence. Incidence of adverse events was regarded as the secondary outcome measure.


Results

Among the 364 patients who were included in the intention-to-treat analysis, 67 patients of the THM group and 87 of the TACE group had recurrence, with a hazard ratio of 0.695 (P = 0.048). Median recurrence-free survival of the patients in the THM and TACE groups was 46.89 and 34.49 months, respectively. Recurrence rates at 1, 2 and 3 years were 17.7%, 33.0% and 43.5% for the THM group, and 28.8%, 42.5% and 54.0% for the TACE group, respectively (P = 0.026). Multivariate analysis indicated that the THM regimen had a big advantage for prolonging the recurrence-free survival. Adverse events were mild and abnormality of laboratory indices of the two groups were similar.


Conclusion

In comparison with TACE therapy, the THM regimen was associated with diminished risk of recurrence of small-sized HCC after resection, with comparable adverse events.


Trial registration identifier

This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-07000033.

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Cited: Baidu(100)
Effects of berberine on differentiation and bone resorption of osteoclasts derived from rat bone marrow cells
WEI Peng, JIAO Lei, QIN Lu-ping, YAN Fei, HAN Ting, ZHANG Qiao-yan
Journal of Chinese Integrative Medicine    2009, 7 (4): 342-348.   DOI: 10.3736/jcim20090408
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Objective: To observe the effects of berberine on osteoclastic differentiation and bone resorption action in vitro, and to investigate the cellular mechanism of its inhibitory effects on bone resorption.
Methods: The multinucleated osteoclasts (MNCs) were derived by 1,25-dihydroxyvitamin D3 and dexamethasone from bone marrow cells in the coculture system with primary osteoblastic cells. The tartrate-resistant acid phosphatase (TRAP) staining and image analysis of bone resorption pit on dental slices were used to identify osteoclast. The activity of TRAP was measured by p-nitrophenyl sodium phosphate assay. The bone resorption pit area on the bone slices formed by osteoclasts was measured by computer image processing.
Results: At the concentrations of 0.1, 1 and 10 μmol/L, berberine dose-dependently suppressed the formation of TRAP-positive multinucleated cells, the TRAP activity and the osteoclastic bone resorption. The strongest inhibitory effect was exhibited at the concentration of 10 μmol/L, with the inhibiting rate of 60.45%, 42.12% and 72.69% respectively.
Conclusion: Berberine can decrease bone loss through inhibition of osteoclast formation, differentiation and bone resorption.

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Cited: Baidu(100)
Metabonomic study of syndrome of liver qi stagnation and spleen deficiency in rats
He-gu Luo, Jie Ding, Guang-xin Yue, Jia-xu Chen
Journal of Chinese Integrative Medicine    2007, 5 (3): 307-313.   DOI: 10.3736/jcim20070315
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Objective: To determine the changes of the plasma metabolic phenotype in rats with chronic restraint stress (rats with syndrome of liver qi stagnation and spleen deficiency), so as to reveal the biological features of the syndrome of liver qi stagnation and spleen deficiency, and to examine potential application of metabonomic analysis in studies of syndromes in traditional Chinese medicine.Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups: group A, 7 d normal control group; group B, 21 d normal control group; group C, 7 d stress group; and group D, 21 d stress group, with 6 rats in each group. Chronic restraint was used to induce stress in rats. Blood was collected from the cardio-ventricle under anesthesia on the 8th (groups A and C) or 22nd day (groups B and D) and detected by using the Fourier variable superconducting nuclear magnetic resonance (NMR) spectrometer (Varian UnityInova 600 M). Free induction decay signals were transferred into one-dimensional NMR spectrogram via 32 k Fourier transformation. Segmental integral calculus (0.04 ppm per segment) was performed from 4.5-0.5 ppm (Carr-Purcell-Meiboom-Gill, CPMG) or 6.0-0 ppm (longitudinal eddy-delay, LED) as defaulted 1H spectra values by using the VNMR software. Data were saved as text or excel files after normalization and then used for pattern recognition analyses. All the data were analyzed by principal component analysis (PCA) using the SIMCA-P 10.0 software (Umetrics AB, Umea, Sweden).Result: The PCA analysis of rat plasma 1H NMR spectra revealed different metabolic spectra between stress and control groups, which were consistent with alterations of in vivo metabolisms in rats under stress stimuli. Compared with the normal control group, rats with repeated stress displayed significant changes in spectral peak shapes of acetate, lactate, tyrosine, low-density lipoprotein, and unknown compounds (3.44 ppm). These altered metabolites can be used as biomarkers of syndrome of liver qi stagnation and spleen deficiency for further studies. Conclusion: The 1H NMR spectra of metabolites in the rat blood are differentially changed after chronic stress. Specific, characteristic metabolic products can be identified by analyses of metabonomics, which lead to interpretation of biological feature of Chinese medicine syndromes. Therefore, metabonomic analysis is an approach with good development prospects to studies of TCM syndromes.

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Cited: Baidu(96)
Effects of astragalosides and Panax notoginseng saponins combination on oxidative stress of cerebral ischemic reperfusion injury in mice
Hua Tan, Xiao-ping Huang, Chang-qing Deng
Journal of Chinese Integrative Medicine    2010, 8 (5): 448-452.   DOI: 10.3736/jcim20100508
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Objective

To investigate the influence of astragalosides (AST) and Panax notoginseng saponins (PNS) combination on oxidative stress of brain tissues in C57BL/6 mice with cerebral ischemia-reperfusion injury.
Methods

Eighty C57BL/6 mice were randomly divided into sham-operated group, untreated group, high-dose combination group (AST at a dose of 220 mg/kg plus PNS at a dose of 230 mg/kg), medium-dose combination group (AST at a dose of 110 mg/kg plus PNS at a dose of 115 mg/kg), low-dose combination group (AST at a dose of 55 mg/kg plus PNS at a dose of 57.5 mg/kg), AST (110 mg/kg) group, PNS (115 mg/kg) group and edaravone (4 mg/kg) group. AST and PNS were administered by gavage once daily for 4 days and edaravone was administered by intraperitoneal injection twice daily for 4 days. On the fourth day, bilateral common carotid arteries were ligated for 20 minutes to induce cerebral ischemia, followed by 60 minutes of reperfusion. Ischemic brain tissue was used to prepare tissue homogenate, then contents of malonaldehyde (MDA), glutathione (GSH) and nitric oxide (NO), and activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in the homogenate were detected. Two×two analysis of variance of factorial design was used to analyze whether there was an interaction between AST at 110 mg/kg and PNS at 115 mg/kg.
Results

Compared with sham-operated group, contents of MDA and NO, and activity of NOS in the untreated group were remarkably increased (P<0.01), activity of SOD and content of GSH were decreased (P<0.01). Compared with the untreated group, content of MDA in the AST group was decreased (P<0.01) and activity of SOD was increased (P<0.01), however, contents of GSH and NO and activity of NOS had no obvious changes (P>0.05). Contents of MDA and NO in the PNS group was decreased as compared with the untreated group (P<0.01), but activities of SOD and NOS and content of GSH had no changes (P>0.05). Contents of MDA and NO and activity of NOS in brain tissues in the edaravone group were decreased (P<0.01, P<0.05), and activity of SOD was increased (P<0.05), while content of GSH had no changes (P>0.05). Contents of MDA and NO and activity of NOS in brain tissue in the AST and PNS combination groups were decreased (P<0.01, P<0.05), the activity of SOD increased (P<0.01, P<0.05), the content of GSH increased (P<0.01, P<0.05), and activity of SOD and content of GSH were increased (P<0.01, P<0.05). The results of analysis of variance of factorial design showed that there were interactions between AST (110 mg/kg) and PNS (115 mg/kg) (P<0.01).
Conclusion

Combination of AST (110 mg/kg) and PNS (115 mg/kg) has a restraint effect on the early oxidative stress injury in the brain after ischemia-reperfusion, and the combination has a synergistic or additive effect.

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Cited: Baidu(93)
Investigation of the nutraceutical potential of monofloral Indian mustard bee pollen
Sameer S. Ketkar, Atul S. Rathore, Sathiyanarayanan Lohidasan, Lakshmi Rao​, Anant R. Paradkar, Kakasaheb R. Mahadik
Journal of Integrative Medicine    2014, 12 (4): 379-389.   DOI: 10.1016/S2095-4964(14)60033-9
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Objective

This study was designed to investigate the nutraceutical potential of monofloral Indian mustard bee pollen (MIMBP). 

Methods

The nutritional value of MIMBP was examined in terms of proteins, fats, carbohydrates, and energy value. Its chemical composition in terms of total polyphenol and flavonoid content was determined. MIMBP was screened for free flavonoid aglycones by developing and validating a high-performance liquid chromatography-photo diode array (HPLC-PDA) method. MIMBP was analyzed for in vitro antioxidant effect in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity. 

Results

MIMBP was found to be comprised of proteins ((182.2±5.9) g/kg), fats ((137.7±6.8) g/kg) and carbohydrates ((560.6±17.4) g/kg), which result in its high energy value ((17 616.7±78.6) kJ/kg). MIMBP was found to contain polyphenols ((18 286.1±374.0) mg gallic acid equivalent/kg) and flavonoids ((1 223.5±53.1) mg quercetin equivalent/kg). The HPLC-PDA analysis revealed the presence of kaempferol ((65.4±0.5) mg/kg) and quercetin ((51.4±0.4) mg/kg) in MIMBP, which can be used as markers for determining the quality of bee pollen. The MIMBP extract showed DPPH free radical-scavenging activity with a half maximal inhibitory concentration of 54.79 μg/mL. 

Conclusion

The MIMBP was found to be a rich source of nutrients providing high caloric value, which makes it a candidate for a potential nutraceutical agent. The study also illustrated the high antioxidant content of MIMBP, especially in the principle polyphenols and flavonoids, which suggests its potential role in the prevention of free radical-implicated diseases. The DPPH-scavenging effect of MIMBP further confirmed its antioxidant potential. Additionally, we developed a simple, specific and accurate HPLC-PDA method for the identification and quantification of free flavonoid aglycones. This can be applied in future screenings of the quality of pollen collected by honeybees.

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Cited: Baidu(84)
Mechanism of resveratrol on the promotion of induced pluripotent stem cells
Dao-fang Ding, Xiao-feng Li, Hao Xu, Zhen Wang, Qian-qian Liang, Chen-guang Li, Yong-jun Wang
Journal of Chinese Integrative Medicine    2013, 11 (6): 389-396.   DOI: 10.3736/jintegrmed2013039
Abstract927)   HTML    PDF      

Objective

To investigate the effects of resveratrol (RV) in reprogramming mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) and the related mechanism.


Methods

Primary MEFs were isolated from E13.5 embryos and used within three passages. Retroviruses expressing Sox2 and Oct4 were produced by transfecting GP2-293t cells with recombinant plasmids murine stem cell virus (MSCV)-Sox2 and MSCV-Oct4. Supernatants containing retroviruses were obtained after 48-hour transfection and MEFs were then infected. Different concentrations (0, 5, 10 and 20 μmol/L) of RV were added to embryonic stem cell (ESC) medium to culture MEFs 48 h post-infection. iPSC clones emerged and were further cultured. Expression of pluripotent markers of iPSCs was identified by cell immunofluorescence and reverse transcription-polymerase chain reaction. Both cytotoxicity and cell proliferation were assayed by Western blot analysis after RV was added into ESC medium. The ultrastructure change of mitochondria was observed by electron microscopy.


Results

More than 2.9-fold and 1.3-fold increases in colony number were observed by treatment with RV at 5 and 10 μmol/L, respectively. The reprogramming efficiency was significantly decreased by treatment with 20 μmol/L RV. The proliferation effect on MEFs or MEFs infected by two factors Sox2/Oct4 (2 factors-MEFs, 2F-MEFs) was investigated after RV treatment. At 20 μmol/L RV, induced cell apoptosis and proliferation inhibition were more obvious than those of 5 and 10 μmol/L treatments. Clones were selected from the 10 μmol/L RV-treated group and cultured. Green fluorescent protein expression from one typical clone was silenced one month later which expressed ESC-associated marker genes Gdf3, Nanog, Ecat1, Fgf4 and Foxd3. Electron transmission microscope showed obvious cavitations in mitochondria. The expression of hypoxia-inducible factor-1α was up-regulated when 2F-MEFs were treated with RV compared to the control group.


Conclusion

RV improved the efficiency of reprogramming 2F-MEFs into iPSCs at low and moderate concentrations (5 and 10 μmol/L). The effect of 10 μmol/L RV on reprogramming was much greater than that of 5 μmol/L RV. However, high concentration of RV (20 μmol/L) led to more severe cavitations in mitochondria and caused cytotoxic effects. Taken together, these findings suggest that RV mimics hypoxia in cells and promotes reprogramming at a low concentration.

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The roles of traditional Chinese medicine in gene therapy
Chang-quan Ling​, Li-na Wang, Yuan Wang​, Yuan-hui Zhang​, Zi-fei Yin, Meng Wang​, Chen Ling​
Journal of Integrative Medicine    2014, 12 (2): 67-75.   DOI: 10.1016/S2095-4964(14)60019-4
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The field of gene therapy has been increasingly studied in the last four decades, and its clinical application has become a reality in the last 15 years. Traditional Chinese medicine (TCM), an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM is well-known for its various roles in preventing and treating infectious and chronic diseases, and its usage in other modern clinical practice. However, whether TCM can be applied alongside gene therapy is a topic that has not been systematically examined. Here we provide an overview of TCM theories in relation to gene therapy. We believe that TCM theories are congruent with some principles of gene therapy. TCM-derived drugs may also act as gene therapy vehicles, therapeutic genes, synergistic therapeutic treatments, and as co-administrated drugs to reduce side effects. We also discuss in this review some possible approaches to combine TCM and gene therapy.

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Protective effect of diosmin against diabetic neuropathy in experimental rats
Dilpesh Jain​, Manish Kumar Bansal, Rahul Dalvi​, Aman Upganlawar​, Rahul Somani​
Journal of Integrative Medicine    2014, 12 (1): 35-41.   DOI: 10.1016/S2095-4964(14)60001-7
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Objective

The present study was undertaken to evaluate the effect of diosmin in diabetic neuropathy in type 2 diabetic rats. 

Methods

Type 2 diabetes was induced in male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin (35 mg/kg) and high-fat diet. Four weeks after the confirmation of diabetes, diabetic rats were treated with diosmin (50 and 100 mg/kg, p.o.) for next 4 weeks. Rats were evaluated for biochemical, behavioral and oxidative stress parameters. Eddy’s hot plate and tail immersion test were performed on 6th, 7th, 8th, 9th and 10th weeks of experiment to assess thermal hyperalgesia and cold allodynia respectively. Further, the walking function test was performed for assessing the motor responses at the end of the treatment schedule. 

Results

Rats were fed with high-fat diet throughout the experiment schedule and administration of low-dose streptozotocin induced significant elevation in blood glucose level and insulin resistance which was confirmed by oral glucose tolerance test. Treatment with diosmin at doses of 50 and 100 mg/kg significantly restored the reduced body weight, elevated blood sugar and lipid profiles. Further the dose-dependent improvement was observed in thermal hyperalgesia, cold allodynia and walking function in diabetic rats treated with diosmin. Elevated levels of malondialdehyde, and nitric oxide and decreased glutathione levels and superoxide dismutase activity in diabetic rats were restored significantly after the 4 weeks of diosmin treatment. 

Conclusion

Diosmin has shown beneficial effect in preventing the progression of early diabetic neuropathy in rats.

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A review of research on the development of instruments for therapeutic efficacy evaluation of traditional Chinese medicine
Wei-hua Xu, Ze-huai Wen, Wei-xiong Liang, Qi Wang
Journal of Chinese Integrative Medicine    2012, 10 (7): 726-737.   DOI: 10.3736/jcim20120702
Online available: 15 July 2018

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Objective: Due to the differences between Chinese and Western cultures, Chinese version of foreign research instruments may not be totally applicable for use in evaluating the therapeutic effect of traditional Chinese medicine (TCM). Great efforts have been made by Chinese researchers to develop scales for evaluation of the therapeutic effects of TCM. This study aims to understand the current situation of research in the development of evaluation instrument in TCM.
Methods: Database searches of Chinese Biomedical Literature Database, China Academic Journal Network Publishing Database and Chinese Scientific Journals Database were undertaken to identify published studies with the purpose of developing instruments in assessing the effectiveness of TCM, including papers regarding the construction of conceptual framework of instrument, item generation and selection and the evaluation of measurement properties.
Results: A total of 60 pieces of literature involving 36 instruments were included. The first article on the development of each of the instruments was published between 2005 and 2011 and the instruments were used in many kinds of medical conditions, including cardiocerebrovascular, respiratory, digestive and infectious diseases. The number of items ranged from 10 to 52. Of the 36 instruments, 13 (36.1%) defined the hypothesized concepts measured by the instrument, 30 (83.3%) reported the domains of the questionnaires before measurement property testing and all of them were multidomain. Of 32 studies regarding item selection and the instrument’s property evaluation, 14 (43.8%) articles reported the administration mode, 24 (75%) reported response option types, and 10 (31.5%) provided scoring algorithm for the scale, but none of these 32 studies specified the recall period. In 29 studies aiming at testing instrument’s measurement property, 28 articles tested the Cronbach’s α coefficient of the full scale and/or subscales, and retest reliability was also detected in 15 studies. Twenty-seven studies evaluated the construct validity by exploratory factor analysis and among them there were two studies applying confirmatory factor analysis. Content validity, responsiveness and feasibility of instruments were assessed in 11, 16 and 16 studies, respectively.
Conclusion: This study shows that in recent years many instruments have been developed in an attempt to evaluate the therapeutic effects of TCM, but some problems still exist in their practical implementation, including negligence in outlining the hypothesized concepts of the TCM instruments and in the reporting of instrument’s content validity such as administration mode, scoring and recall period. Some instrument attributes and testing methods were misunderstood and/or misused. Revision of instruments is rarely carried out, though the development of an instrument is an iterative process. Researchers should have a thorough understanding of the general procedure and steps before starting to develop an instrument.

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Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria: a randomized placebo-controlled trial
Tian-zhan Wang, Yu Chen, Yan-ming He, Xiao-dong Fu, Wang Yi, Yan-qiu Xu, Hong-jie Yang, Hong-li Xue, Yi Liu, Xiao-tao Feng, Teng Zhang, Wen-jian Wang
Journal of Chinese Integrative Medicine    2013, 11 (3): 175-183.   DOI: 10.3736/jintegrmed2013032
Abstract902)   HTML    PDF      

Background

Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients.


Objective

To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment.


Design, setting, participants and interventions

Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks.


Main outcome measures

Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed.


Results

Compared with the control group, CHF treatment significantly decreased BMI (P<0.05), WC (P<0.01) and WHR (P<0.01). Both groups had significant decreases in FPG, 2-hPPG, HbA1c, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P<0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P<0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P>0.05), whereas it significantly increased with CHF treatment (P<0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P<0.01). However, there was no significant difference between the two groups (P>0.05).


Conclusion

Combined treatment of Yiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism.


Trial registration identifier

This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

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Effect of Saikokeishito, a Kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts
Takanobu Takata, Yoshiharu Motoo, Naohisa Tomosugi
Journal of Integrative Medicine    2014, 12 (6): 495-503.   DOI: 10.1016/S2095-4964(14)60052-2
Abstract910)   HTML    PDF(pc) (1328KB)(74)      

Objective

Saikokeishito (TJ-10) is a Kampo (traditional Japanese herbal) medicine, clinically used for hundreds of years in East Asia. Among its various mechanisms elucidated so far, TJ-10 inhibits the production of transforming growth factor-β1 (TGF-β1) and development of pancreatic fibrosis in vivo. Oxidative damage of normal human dermal fibroblasts (NHDFs) in the corium is a cause of human dermal senescence. Our aim was to determine whether TJ-10 protects NHDFs from premature senescence by hydrogen peroxide (H2O2).

Methods

Premature senescence was induced in NHDFs by 200 μmol/L H2O2 for 4 h. Cell viability and the expressions of p53, AMP-activated protein kinase α1 (AMPKα1), AMPKα2, and 14-3-3 protein sigma (14-3-3 σ) were measured in NHDFs treated with TJ-10 for 48 h before exposure to H2O2 for 4 h. 

Results

Cell viability after treatment with 200 μmol/L H2O2 for 4 h was similar (about 80%) to after pre-treatment with TJ-10. Ascorbic acid as a control did not protect NHDFs from damage by 200 μmol/L H2O2. Treatment with 200 μmol/L H2O2 tended to up-regulate p53 and to down-regulate SIRT1 and AMPKα1, but had no effect on AMPKα2 and 14-3-3 σ expression. Pretreatment with TJ-10 inhibited H2O2-induced up-regulation of p53 and enhanced AMPKα1 expression. 

Conclusion

It is suggested that Saikokeishito has a protective effect on oxidative stress-induced senescence of NHDFs.

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Literature review and analysis of the development of health outcomes assessment instruments in Chinese medicine
Feng-bin Liu, Zheng-kun Hou, Yun-ying Yang, Zheng-zheng Zhang, Di Xie, Nelson Xie, Hong Thach Nguyen
Journal of Chinese Integrative Medicine    2013, 11 (2): 80-89.   DOI: 10.3736/jintegrmed2013018
Abstract889)   HTML    PDF      

Objective

To evaluate the development of health outcomes assessment instruments in Chinese medicine.


Methods

A comprehensive literature search for all published articles in China National Knowledge Infrastructure Database, Chongqing VIP Database and WANFANG Data was conducted. The studies that met the inclusion and exclusion criteria were used to extract information according to a predesigned assessment instrument.


Results

A total of 97 instruments for health outcome assessment in Chinese medicine were identified. Of these questionnaires, 7 were generic, 12 were condition-specific and 78 were disease-specific. All instruments were suitable for adults, children, and both men and women. These instruments aimed to evaluate the health-related quality of life, signs and symptoms as well as patient satisfaction and doctor-reported outcome. However, the descriptions were poorly constructed for some of the most basic parameters, such as the domains and items, administrative mode, response options, memory recall periods, burden evaluation, format, copyright, content validity, and other properties.


Conclusion

The instrument development for health outcomes assessment in Chinese medicine is increasing rapidly; however, there are many limitations in current methodologies and standards, and further studies are needed.

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Cited: Baidu(80)
Protective effects of Chailing Guiqi Decoction combined with lumbrukinase on renal function in rats with adriamycin nephropathy
Fen-fang Zhang, Xi-dong Wang, Huan-fang Fan, Zhi-qiang Chen, Zhi-wei Yin, Wei Zhang
Journal of Chinese Integrative Medicine    2005, 3 (4): 294-298.   DOI: 10.3736/jcim20050414
Abstract886)   HTML2)    PDF(pc) (98KB)(56)      

Objective

To study the protective efffects of Chailing Guiqi Decoction (CLGQD) combined with lumbrukinase on renal function in rats with adriamycin nephropathy.

Methods

Thirty-six SD rats were randomly divided into four groups: normal control group, untreated group, simvastatin-treated group and CLGQD -treated group. Adriamycin nephropathy was induced by intravenous injection with 5 mg/kg adriamycin. After seven-day treatment, quantitative measurement of 24-h urine protein was determined with trichloroacetic acid, and serum total protein (TP), albumin (Alb), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine (Cr) and blood urea nitrogen (BUN) were assessed using automatic biochemistry analyzer. The pathomorphological changes of renal tissues were observed with light and electron microscopes.

Results

In the untreated group, the 24-h urine protein excretion, serum TC, TG, LDL, Cr and BUN were significantly higher than those in the normal control group (P<0.05 or P<0.01), while the serum TP, Alb, HDL were significantly lower than those in the normal control group (P<0.01). In the CLGQD-treated group, the 24-h urine protein excretion, serum TC, TG, LDL, Cr and BUN were significantly lower as compared with those in the untreated group (P<0.05 or P<0.01), while the serum TP, Alb and HDL were significantly higher as compared with those in the untreated group (P<0.05 or P<0.01). The pathomorphological findings of the renal tissues under the light microscope in the untreated group showed focal segmental glomerulosclerosis in a few of glomerulus, degenerated and swelled proximal tubular epithelial cells, proteins in cast formation in some renal tubules and scattered fibrosis in interstitial tissues of the kidney, while the electron microscope images showed the fusion of foot processes in glomerular epithelial cells. The pathomorphological changes in the CLGQD-treated group were slighter than those in the untreated group.

Conclusion

CLGQD combined with lumbrukinase can reduce proteinuria, regulate lipid metabolism, protect renal function, and delay progressive renal damage in rats.

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Cited: Baidu(79)
Promoting integrative medicine by computerization of traditional Chinese medicine for scientific research and clinical practice: The SuiteTCM Project
Arthur de Sá Ferreira
Journal of Chinese Integrative Medicine    2013, 11 (2): 135-139.   DOI: 10.3736/jintegrmed2013013
Abstract920)   HTML    PDF      

Background

Chinese and contemporary Western medical practices evolved on different cultures and historical contexts and, therefore, their medical knowledge represents this cultural divergence. Computerization of traditional Chinese medicine (TCM) is being used to promote the integrative medicine to manage, process and integrate the knowledge related to TCM anatomy, physiology, semiology, pathophysiology, and therapy.


Methods

We proposed the development of the SuiteTCM software, a collection of integrated computational models mainly derived from epidemiology and statistical sciences for computerization of Chinese medicine scientific research and clinical practice in all levels of prevention. The software includes components for data management (DataTCM), simulation of cases (SimTCM), analyses and validation of datasets (SciTCM), clinical examination and pattern differentiation (DiagTCM, TongueTCM, and PulseTCM), intervention selection (AcuTCM, HerbsTCM, and DietTCM), management of medical records (ProntTCM), epidemiologic investigation of sampled data (ResearchTCM), and medical education, training, and assessment (StudentTCM).


Discussion

The SuiteTCM project is expected to contribute to the ongoing development of integrative medicine and the applicability of TCM in worldwide scientific research and health care. The SuiteTCM 1.0 runs on Windows XP or later and is freely available for download as an executable application.

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Clinical observation of cinobufacini injection used to treat moderate and advanced primary liver cancer
Zhe Chen, Xiao-feng Zhai, Yong-hua Su, Xu-ying Wan, Jin Li, Jue-min Xie, Bo Gao
Journal of Chinese Integrative Medicine    2003, 1 (3): 184-186.   DOI: 10.3736/jcim20030311
Abstract863)   HTML0)    PDF(pc) (55KB)(54)      

Objective

To observe the clinical effect of cinobufacini injection in treating moderate and advanced primary liver cancer (PLC).


Methods

One hundred patients with moderate and advanced PLC were randomly divided into cino-treated group (50 patients) and control group (50 patients). The quality of life, tumor size, some changes of laboratory tests, and survival time were observed.


Results

The progressive rate of cino-treated group (18%) was lower than that of the control group (32%). The quality of life of the cino-treated group (80%) was better than that of the control group (72%), but witbout statistical significance. The survival rate of >12 months of the cino-treated group (30%) was higher than that of the control group (18%). The patients' liver function such as serum total bilirubin and ALT decreased obviously in the cino-treated group while increased a lot in the control group. The level of AFP increased after treatment with statistical significance in the control group while there was no statistical significance in the cino-treated group.


Conclusion

Cinobufacini injection can not only inhibit the proliferation of cancer, but also protect liver function, improve quality of life and prolong survival time.

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Cited: Baidu(75)
Establishment of a rat model of alcoholic liver fibrosis induced by complex factors
Lei Wang, Guang Ji, Pei-yong Zheng, Ai-hua Long
Journal of Chinese Integrative Medicine    2006, 4 (3): 281-284.   DOI: 10.3736/jcim20060312
Abstract868)   HTML0)    PDF(pc) (198KB)(49)      

Objective

To establish a model of alcoholic liver fibrosis (ALF) in rats induced by complex factors.

Methods

Forty-seven healthy male rats were divided into three groups: normal control group (n=12), minor CCl4 group (n=12) and complex factors group (n=27). The rats in the complex factors group were fed a complex diet including alcohol, corn oil and pyrazole, and administered with intraperitoneal injection of minor CCl4 to induce ALF. During induction process, the histopathological changes of liver tissue and the values of liver-to-body weight ratio were both observed regularly. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (γ-GT) in these three groups were all examined at the 12th week of the induction process.

Results

At the 12th week of the induction process, the model of ALF induced by complex factors was successfully established in rats, and the histopathological presentations showed alcoholic fatty liver, hepatitis and liver fibrosis in a sequence along with the induction process. The value of liver-to-body weight ratio and the serum levels of ALT, AST and γ-GT of rats in the complex factors group were all significantly different from those in the other two groups.

Conclusion

It is a steady and effective way to induce ALF in rats with complex diet and minor CCI4 injection.

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Chinese medicines for prevention and treatment of human hepatocellular carcinoma: Current progress on pharmacological actions and mechanisms
Xuanbin Wang, Ning Wang, Fan Cheung, Lixing Lao, Charlie Li, Yibin Feng
Journal of Integrative Medicine    2015, 13 (3): 142-164.   DOI: 10.1016/S2095-4964(15)60171-6
Abstract988)   HTML    PDF      

Hepatocellular carcinoma (HCC) is one of leading causes of death in the world. Although various treatments have been developed, the therapeutic side effects are far from desirable. Chinese medicines (CMs, including plants, animal parts and minerals) have drawn a great deal of attention in recent years for their potential in the treatment of HCC. Most studies have shown that CMs may be able to retard HCC progression with multiple actions, either alone or in combination with other conventional therapies to improve quality of life in HCC patients. Additionally, CMs are used for preventing HCC occurrence. The aim of this study is to review the potential prophylactic and curative effects of CMs on human HCC and the possible mechanisms that underlie these pharmacological actions. Publications were collected and reviewed from PubMed and China National Knowledge Infrastructure from 2000 to 2014. Keywords for literature searches include “Chinese medicine”, “Chinese herb”, “traditional Chinese Medicine”, “hepatocellular carcinoma” and “liver cancer”. CMs in forms of pure compounds, isolated fractions, and composite formulas are included. Combination therapies are also considered. Both in vitro and in vivo efficacies of CMs are being discussed and the translational potential to bedside is to be discussed with clinical cases, which show the actions of CMs on HCC may include tumor growth inhibition, antimetastatic activities, anti-inflammation, anti-liver cancer stem cells, reversal on multi-drug resistance and induction/reduction of oxidative stress. Multiple types of molecules are found to contribute in the above actions. The review paper indicated that CMs might have potential to both prevent HCC occurrence and retard HCC progression with several molecular targets involved.

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Framework and practice of network-based studies for Chinese herbal formula
Shao Li
Journal of Chinese Integrative Medicine    2007, 5 (5): 489-493.   DOI: 10.3736/jcim20070501
Abstract938)   HTML2)    PDF(pc) (1197KB)(89)      

The ZHENG (syndrome of traditional Chinese medicine) oriented effects and the multiple-targets' mechanism are the main challenges encountered by recent researches for Chinese herbal formula. Using methods of bioinformatics and systems biology, we proposed a biological network-based framework for understanding the mechanism of Chinese herbal formula, and reviewed our studies under this framework which aimed to explore the relationship between Chinese herbal formula and corresponding ZHENGs, as well as the synergism of herbal combinations. These studies include the network construction for cold or heat ZHENG and its relationship with herbal formula of hot or cold nature, the biological network construction of angiogenesis, and the network regulation-based emergent property of an herbal combination with anti-angiogenesis synergism extracting from the cold formula. It is shown that the ZHENG-oriented effects and the herbal synergism can be nicely explicated by such network-based approaches. Thus, the network-based drug combination discovery, as well as the "traditional Chinese medicine bioinformatics (TCMB)" and "TCM computational systems biology" combining with computational and experimental approaches, is conceivable and can open a new avenue for understanding Chinese herbal formula.

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In vivo effect of casticin on acute inflammation
Shan Lin, Hong Zhang, Ting Han, Jin-Zhong Wu, RAHMAN Khalid, Lu-Ping Qin
Journal of Chinese Integrative Medicine    2007, 5 (5): 573-576.   DOI: 10.3736/jcim20070520
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Objective: To investigate the anti-inflammatory effect of casticin of Fructus Viticis.Methods: Observations were made on the anti-inflammatory effect of casticin in the models of acute inflammation in vivo.Results: Casticin inhibited significantly xylene-induced mouse ear edema, egg albumen-induced rat paw edema and acetic acid-induced mouse vascular permeability.Conclusion: Casticin has significant anti-inflammatory effect on acute inflammation, which is probably related to the inhibition of the inflammation factors. Casticin is the effective constituent contributing to the anti-inflammatory effect of Fructus Viticis.

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Relationships between constitutional types of traditional Chinese medicine and hypertension
Yan-bo Zhu, Qi Wang, Qi-wei Deng, Jing Cai, Xiao-hong Song, Xue Yan
Journal of Chinese Integrative Medicine    2010, 8 (1): 40-45.   DOI: 10.3736/jcim20100108
Abstract1255)   HTML7)    PDF(pc) (1122KB)(145)      

Objective

To investigate the relationships between constitutional types of traditional Chinese medicine (TCM) and hypertension so as to provide epidemiological evidence for the theory of correlation between constitution and disease.
Methods

A cross-sectional survey of TCM constitution data from a population of 7 782 from Beijng and 8 provinces of China (Jiangsu, Anhui, Gansu, Qinghai, Fujian, Jilin, Jiangxi, and Henan) was made in the study. The survey of TCM constitutions was performed by standardized TCM Constitution Questionnaire. Discriminatory analysis was used to judge the individual constitutional types including normal constitution, and qi deficiency, yang deficiency, yin deficiency, phlegm-dampness, damp-heat, blood stasis, qi stagnation and special constitutions. A multiple stepwise logistic regression analysis was applied to explore the significantly influential constitutional factors of hypertension.
Results

After controlling several factors like gender, age, marital status, occupation, and educational background, three TCM constitutional factors according to different degrees of relative risks were entered into the multiple stepwise logistic regression model. The three factors were phlegm-dampness, yin deficiency and qi deficiency constitutions, and the odds ratio (OR) and 95% confidence interval (CI) were 2.00 [1.58, 2.55], 1.66 [1.33, 2.08] and 1.37 [1.13, 1.66] respectively. The main constitutional influential factors of hypertension in male patients were phlegm-dampness and yin deficiency constitutions, with OR and 95% CI of 1.61 [1.22, 2.14] and 1.60 [1.17, 2.19]. Phlegm-dampness, yin deficiency and qi deficiency constitutions were the main constitutional influential factors of hypertension in female patients. The OR and 95% CI were 2.80 [1.79, 4.39], 1.55 [1.13, 2.14] and 1.39[1.05, 1.84] respectively. Phlegm-dampness constitution had more influence on hypertension in female patients than other constitution types.
Conclusion

Phlegm-dampness, yin deficiency, and qi deficiency constitutions are the main influential factors of hypertension. Hypertensive patients with different gender have different constitutional influential factors.

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Cited: Baidu(68)
Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo
Yuan-hui Zhang, Yuan Wang, Yusufali Ali Hussein, Frederick Ashby, Daniel Zhang, Zi-fei Yin, George V. Aslanidi, Arun Srivastava, Chang-quan Ling, Chen Ling
Journal of Integrative Medicine    2014, 12 (6): 483-494.   DOI: 10.1016/S2095-4964(14)60057-1
Abstract930)   HTML    PDF(pc) (4567KB)(68)      

Objective

Little effort has been made to study the protein-encoding genes isolated from traditional Chinese medicine (TCM) drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated virus (rAAV) vectors has not been attempted.

Methods

We synthesized the cDNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged cDNAs were subcloned into a rAAV plasmid vector. The protein expression was confirmed by Western blot assay. Various cancer cell lines were transfected with the above plasmids and cell growth was monitored both in vitro and in vivo. The best cytotoxic gene was further packaged into rAAV vectors, under the control of a liver cancer-specific promoter. The liver tumor growth was then monitored following intratumor administration of the rAAV vectors. 

Results

The expression plasmids, encoding individual potential cytotoxic genes tagged with FLAG epitope, were successfully generated and sequenced. Among these genes, trichosanthin (TCS) gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome-inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Furthermore, intratumor injection of rAAV vectors containing the TCS gene significantly inhibited the growth of human hepatocellular carcinoma tumors in a murine xenograft model. 

Conclusion

Our studies suggest that the use of TCM cytotoxic genes is a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular.

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Cited: Baidu(67)
Pristimerin enhances recombinant adeno-associated virus vector-mediated transgene expression in human cell lines in vitro and murine hepatocytes in vivo
Wang Li-na, Wang Yuan, Lu Yuan, Yin Zi-fei, Zhang Yuan-hui, V. Aslanidi George, Srivastava Arun, Ling Chang-quan, Ling Chen
Journal of Integrative Medicine    2014, 12 (1): 20-34.   DOI: 10.1016/S2095-4964(14)60003-0
Abstract930)   HTML    PDF(pc) (3483KB)(53)      

Objective

In the present study, we systemically evaluated the ability of two bioactive compounds from traditional Chinese medicine, celastrol and pristimerin, to enhance recombinant adeno-associated virus (rAAV) serotype vector-mediated transgene expression both in human cell lines in vitro, and in murine hepatocytes in vivo.
Methods

Human cell lines were infected with rAAV vectors with either mock treatment or treatment with celastrol or pristimerin. The transgene expression, percentage of nuclear translocated viral genomes and the ubiquitination of intracellular proteins were investigated post-treatment. In addition, nonobese diabetic/severe combined immunodeficient gamma (NSG) mice were tail vain-injected with rAAV vectors and co-administered with either dimethyl sulfoxide, celastrol, pristimerin or a positive control, bortezomib. The transgene expression in liver was detected and compared over time. 

Results

We observed that treatment with pristimerin, at as low as 1 μmol/L concentration, significantly enhanced rAAV2 vector-mediated transgene expression in vitro, and intraperitoneal co-administration with pristimerin at 4 mg/(kg·d) for 3 d dramatically facilitated viral transduction in murine hepatocytes in vivo. The transduction efficiency of the tyrosine-mutant rAAV2 vectors as well as that of rAAV8 vectors carrying oversized transgene cassette was also augmented significantly by pristimerin. The underlying molecular mechanisms by which pristimerin mediated the observed increase in the transduction efficiency of rAAV vectors include both inhibition of proteasomal degradation of the intracellular proteins and enhanced nuclear translocation of the vector genomes. Conclusion

These studies suggest the potential beneficial use of pristimerin and pristimerin-containing herb extract in future liver-targeted gene therapy with rAAV vectors.

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Antidiarrheal properties of different extracts of Chinese herbal medicine formula Bao-Xie-Ning
Jing Li, Xin-lin Wu, Yuling Chen, Zhi Tang, Yue-hong Xu, Jian-min Jiang, Yue-yu Gu, Jian-ping Chen, De-po Yang, Dong-mei Wang
Journal of Chinese Integrative Medicine    2013, 11 (2): 125-134.  
Abstract895)   HTML    PDF      

Objective

Bao-Xie-Ning (BXN), a traditional Chinese herbal medicine (CHM) formula composed of Fructus Evodiae, Flos Caryophylli and Cortex Cinnamomi, and used for the treatment of infant diarrheal illness, was subject to systematic assessment for its putative multiple pharmacodynamic effects and pharmacological antidiarrheal mechanisms.


Methods

High-performance liquid chromatography-diode array detector-electrospray ionization-mass spectrometric/mass spectrometry was developed and validated for identification and quantification of the main constituents in different extracts of BXN. Male Kunming mice weighing 20 to 25 g were used for detecting the antidiarrheal activity of the extracts. Ethanolic extract (EE), volatile oil extract (VOE), and aqueous extract (AE) of BXN were respectively subjected to pharmacodynamic and pharmacological comparison in assessing antidiarrheal effects with senna-induced diarrhea, castor oil-induced diarrhea, acetic acid-induced writhing assay, and isolated duodenum test.


Results

The highest yields of three detected components of BXN, rutaecarpine, eugenol and cinnamaldehyde were observed in EE. EE showed the most remarkable antidiarrheal activity in dose-dependent and time-dependent manners in both senna- and castor oil-induced diarrhea models, and presented dose-dependent analgesic activity in acetic acid-induced algesthesia model. In addition, EE extract of BXN also exhibited strong antimobility action on the intestine and strongest depression on spontaneous contraction of isolated duodenum.


Conclusion

Ethanol extraction is an efficient method to extract the active constituents of BXN. BXN extract demonstrated multiple pharmacological activities affecting the main mechanisms of diarrhea, which validated BXN’s usage in the comprehensive clinical treatment of diarrhea.

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Constructing protein-protein interaction network of hypertension with blood stasis syndrome via digital gene expression sequencing and database mining
Yong-hong Lian, Mei-xia Fang, Li-guo Chen
Journal of Integrative Medicine    2014, 12 (6): 476-482.   DOI: 10.1016/S2095-4964(14)60058-3
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Objective

To construct a protein-protein interaction (PPI) network in hypertension patients with blood-stasis syndrome (BSS) by using digital gene expression (DGE) sequencing and database mining techniques. 

Methods

DGE analysis based on the Solexa Genome Analyzer platform was performed on vascular endothelial cells incubated with serum of hypertension patients with BSS. The differentially expressed genes were filtered by comparing the expression levels between the different experimental groups. Then functional categories and enriched pathways of the unique genes for BSS were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) to select those in the enrichment pathways. Interologous Interaction Database (I2D) was used to construct PPI networks with the selected genes for hypertension patients with BSS. The potential candidate genes related to BSS were identified by comparing the number of relationships among genes. Confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), gene ontology (GO) analysis was used to infer the functional annotations of the potential candidate genes for BSS. 

Results

With gene enrichment analysis using DAVID, a list of 58 genes was chosen from the unique genes. The selected 58 genes were analyzed using I2D, and a PPI network was constructed. Based on the network analysis results, candidate genes for BSS were identified: DDIT3, JUN, HSPA8, NFIL3, HSPA5, HIST2H2BE, H3F3B, CEBPB, SAT1 and GADD45A. Verified through qRT-PCR and analyzed by GO, the functional annotations of the potential candidate genes were explored. 

Conclusion

Compared with previous methodologies reported in the literature, the present DGE analysis and data mining method have shown a great improvement in analyzing BSS.

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Psychosocial and spiritual needs of patients with chronic diseases: Validation of the Chinese version of the Spiritual Needs Questionnaire
Arndt Büssing, Xiao-feng Zhai, Wen-bo Peng, Chang-quan Ling
Journal of Chinese Integrative Medicine    2013, 11 (2): 106-115.   DOI: 10.3736/jintegrmed2013020
Abstract955)   HTML    PDF      

Objective

Even in secular societies, a small portion of patients find their spirituality to help cope with illness. But for the majority of patients, psychosocial and spiritual needs are neither addressed nor even considered a relevant factor by health care professionals. To measure such specific needs, the Spiritual Needs Questionnaire (SpNQ) was developed. The aim of this study was to validate the Chinese version of the SpNQ (SpNQ-Ch) and thus to measure psychosocial and spiritual needs of Chinese patients.


Methods

This was a cross-sectional study among 168 patients with chronic diseases who were recruited in the Changhai Hospital of Traditional Chinese Medicine, Shanghai, China using standardized questionnaires. We performed reliability and factor analyses, as well as analyses of variance, first order correlations and regression analyses.


Results

The 17-item SpNQ-Ch had a similar factorial structure as the original version with two main and three minor factors which accounted for 64% of variance, and internal consistency estimates (Cronbach’s α) ranging from 0.51 to 0.81. Included were the 4-item scale Inner Peace Needs, the 5-item scale Giving/Generativity Needs, the 5-item scale Religious Needs (with 2 sub-constructs, Praying and Sources), and a 3-item scale Reflection/Release Needs. In Chinese patients with cancer (63%), pain affections (10%), or other chronic conditions (23%), the needs for Giving/Generativity (which refer to categories of Connectedness and Meaning) and Inner Peace Needs scored highest, while Religious Needs and the Reflection/Release Needs scored lower.


Conclusion

The SpNQ-Ch is congruent with its primary version, and can be used in future studies with the mostly nonreligious patients from China. First findings indicate specific psychosocial and spiritual needs which should be addressed by health care professionals to support patients in their struggle with chronic illness in terms of psycho-emotional stabilization, finding hope and meaning, and thus achieving peaceful states of mind despite chronic illness.

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Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis: Study protocol of a multicenter randomized controlled trial
Jian Liu, Chuan-bing Huang, Yuan Wang, Gui-qin Xu, Yuan-yuan Cheng, Yun-xia Feng, Lei Liu, Ya-jun Qi
Journal of Chinese Integrative Medicine    2013, 11 (6): 428-434.   DOI: 10.3736/jintegrmed2013059
Abstract901)   HTML    PDF      

Background

Rheumatoid arthritis (RA), as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA.


Methods and design

This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1:1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo (imitation leflunomide). The control group will receive leflunomide and an herbal placebo (imitation Xinfeng Capsule). The American College of Rheumatology (ACR) Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate (ACR20), which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment.


Discussion

The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA.


Trial registration

This trial has been registered in ClinicalTrials.gov. The identifier is NCT01774877.

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Extending the CONSORT Statement to moxibustion
Chung-wah Cheng, Shu-fei Fu, Qing-hui Zhou, Tai-xiang Wu, Hong-cai Shang, Xu-dong Tang, Zhi-shun Liu, Jia Liu, Zhi-xiu Lin, Lixing Lao, Ai-ping Lü, Bo-li Zhang, Bao-yan Liu, Zhao-xiang Bian
Journal of Chinese Integrative Medicine    2013, 11 (1): 54-63.   DOI: 10.3736/jintegrmed2013009
Abstract930)   HTML    PDF      

The STandards for Reporting Interventions in Clinical Trials Of Moxibustion (STRICTOM), in the form of a checklist and descriptions of checklist items, were designed to improve reporting of moxibustion trials, and thereby facilitating their interpretation and replication. The STRICTOM checklist included 7 items and 16 sub-items. These set out reporting guidelines for the moxibustion rationale, details of moxibustion, treatment regimen, other components of treatment, treatment provider background, control and comparator interventions, and precaution measures. In addition, there were descriptions of each item and examples of good reporting. It is intended that the STRICTOM can be used in conjunction with the main CONSORT Statement, extensions for nonpharmacologic treatment and pragmatic trials, and thereby raise the quality of reporting of clinical trials of moxibustion. Further comments will be solicited from the experts of the CONSORT Group, the STRICTA Group, acupuncture and moxibustion societies, and clinical trial authors for optimizing the STRICTOM.

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Value of four scoring systems for predicting prognosis of severe acute pancreatitis
Jing-yun Fan, Zong-wen Huang, Jia Guo
Journal of Chinese Integrative Medicine    2009, 7 (1): 34-40.   DOI: 10.3736/jcim20090105
Abstract900)   HTML2)    PDF(pc) (1898KB)(59)      

Objective

To evaluate the value of Ranson, acute physiology and chronic health evaluationⅡ (APACHEⅡ), Balthazar CT and pancreatitis outcome prediction (POP) scoring systems in predicting the prognosis of severe acute pancreatitis (SAP).
Methods

A total of 253 consecutive patients with SAP, admitted into West China Hospital of Sichuan University from January 2004 to August 2007 were studied retrospectively. Data associated to Ranson, APACHEⅡ, Balthazar CT and POP scoring systems after admissions were recorded. Four outcome signals including death, local complications, operation transformation, and development of multiple organ dysfunction syndrome (MODS) were analyzed. The receiver operating characteristic (ROC) curves were also drawn and the areas under the ROC curve (AUC) were obtained to compare the sensitivity, specificity, Youden index, and likelihood ratio positive test (LRPT) of the clinical scoring systems in assessing the prognosis of SAP.
Results

Through comparison of AUC, Ranson score could be used to predict the outcomes except for local complications (P=0.00), and all its diagnosis threshold was 5. APACHEⅡscore showed that it could assess the outcomes of SAP except for local complications (P=0.00). Its thresholds in mortality, operation transformation, and incidence of MODS were 14, 10, and 12 respectively. Balthazar CT could predict all the outcomes, and the threshold was 6. POP score could predict all the outcomes except for local complications, and its predictive value in mortality was particularly prominent. The sensitivity and specificity of POP in predicting death were 0.90 and 0.92 as the cutoff was no less than 14. The thresholds of POP in mortality, operation transformation, and incidence of MODS were 14, 8, and 10 respectively.
Conclusion

The prognostic ability of the four scoring systems is not the same. Ranson, APACHEⅡ and POP scoring systems can predict the severity of SAP and entire complication, but they can't predict the local complications. POP score may predict the mortality well, and Balthazar CT scanning can predict all the outcomes, but the sensitivity and specificity are low.

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Simultaneous determination of five anthraquinones in a Chinese traditional preparation by RP-HPLC using an improved extraction procedure
Yan-bin Shi, Hui-li Li, Hai-qin Wang, Yan-biao Yang, Xiao-yun Zhang, Hui Wang, Zong-jie Zhu, Zhi-ye Zhang, Cheng-an Zhang
Journal of Integrative Medicine    2014, 12 (5): 455-462.   DOI: 10.1016/S2095-4964(14)60037-6
Abstract902)   HTML    PDF(pc) (971KB)(113)      

Objective

The stable quality of Chinese herbal medicines is a critical factor for their reliable clinical efficiency. An improved liquid-liquid extraction procedure and a liquid chromatographic method were developed to simultaneously analyze five anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) in a Chinese traditional hospital preparation, Fuyankang mixture, in order to quantitatively control its quality in a more effective way. 

Methods

A more economical and repeatable extraction procedure based on conventional liquid-liquid extraction technique was developed and used to extract five marker components in Fuyankang mixture. These anthraquinones were separated in less than 20 min on a C18 column with methanol and 0.1% phosphoric acid (88:12, v/v) as mobile phase. The method was validated for specificity, precision, spiked recovery and stability. 

Results

Compared to conventional liquid-liquid extraction, the improved liquid-liquid extraction was found to be more effective for simultaneous extraction of anthraquinones from an aqueous Chinese herbal preparation, especially for hydrophobic compounds. The improved extraction method was successfully applied to determine the content of five marker components in Fuyankang mixture by the means of reverse phase high-performance liquid chromatography. 

Conclusion

The improved extraction procedure may be suitable for routine quality control of Fuyankang mixture and other traditional preparations at city-level hospitals in China.

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Complementary and alternative medicine use in Iranian patients with diabetes mellitus
Mohammad Hashem Hashempur, Mojtaba Heydari, Seyed Hamdollah Mosavat, Seyyed Taghi Heydari, Mesbah Shams
Journal of Integrative Medicine    2015, 13 (5): 319-325.   DOI: 10.1016/S2095-4964(15)60196-0
Abstract1032)   HTML    PDF      
Objective
There is increasing interest in complementary and alternative medicine generally, and especially by those affected by chronic diseases, such as diabetes mellitus. We aimed to determine the prevalence and pattern of complementary and alternative medicine use among patients suffering from diabetes mellitus in Shiraz, southern Iran. Another objective was to explore associated factors for use of complementary and alternative medicine among patients with diabetes mellitus.
Methods
A 19-item semi-structured questionnaire (open- and close-ended) was administered to 239 patients with diabetes mellitus in this cross-sectional study. It was carried out in two outpatient diabetes clinics affiliated with the Shiraz University of Medical Sciences, Shiraz, Iran.
Results
One hundred and eighty patients (75.3%) used at least one type of complementary and alternative medicine in the last year prior to the interview. Patients with diabetes mellitus who were living in a large family (≥ 5 members), not taking insulin, and believed that complementary and alternative medicine have synergistic effects with conventional medicine, were independently and significantly (Pvalues: 0.02, 0.04, and 0.01, respectively) more likely to use complementary and alternative medicine. Most of the users (97.7%) reported use of herbal preparations, and 89.4% of users did not change their medication, neither in medication schedule nor its dosage.
Conclusion
The use of complementary and alternative medicine, especially herbal remedies, is popular among diabetes patients in Shiraz, Iran. This use is associated with patients’ family size, type of conventional medications and their view about concomitant use of complementary and conventional medicine.
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Systematic review on methodology of randomized controlled trials of post-marketing Chinese patent drugs for treatment of type 2 diabetes
Li-xin Ma, Yu-yi Wang, Xin-xue Li, Jian-ping Liu
Journal of Chinese Integrative Medicine    2012, 10 (3): 279-292.   DOI: 10.3736/jcim20120306
Online available: 15 April 2018

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Background: Randomized controlled trial (RCT) is considered as the gold standard for the efficacy assessment of medicines. With the increasing number of Chinese patent drugs for treatment of type 2 diabetes, the methodology of post-marketing RCTs evaluating the efficacy and specific effect has become more important.
Objective: To investigate post-marketing Chinese patent drugs for treatment of type 2 diabetes, as well as the methodological quality of post-marketing RCTs.
Search strategy: Literature was searched from the books of Newly Compiled Traditional Chinese Patent Medicine and Chinese Pharmacopeia, the websites of the State Food and Drug Administration and the Ministry of Human Resources and Social Security of the People’s Republic of China, China National Knowledge Infrastructure Database, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biomedical Database (SinoMed) and Wanfang Data. The time period for searching ran from the commencement of each database to August 2011.
Inclusion criteria: RCTs of post-marketing Chinese patent drugs for treatment of type 2 diabetes with intervention course no less than 3 months.
Data extraction and analysis: Two authors independently evaluated the research quality of the RCTs by the checklist of risk bias assessment and the data collection forms based on the CONSORT Statement. Independent double data-extraction was performed.
Results: The authors identified a total of 149 Chinese patent drugs for treatment of type 2 diabetes. According to different indicative syndromes, the Chinese patent drugs can be divided into the following types, namely, yin deficiency and interior heat (n=48, 32%), dual deficiency of qi and yin (n=58, 39%) and dual deficiency of qi and yin combined with blood stasis (n=22, 15%). A total of 41 RCTs meeting the inclusion criteria were included. Neither multicenter RCTs nor endpoint outcome reports were found. Risk bias analysis showed that 81% of the included studies reported randomization for grouping without sequence generation, 98% of these studies did not report concealment of random numbers, 5% used placebo, 10% reported outcome attrition bias and no study employed the analysis of intention-to-treat and 98% reported the diagnostic criteria for type 2 diabetes. The participants mainly consisted of outpatients without complications (76%). The minimum and maximum sample size was 40 and 300 (106±60), respectively.
Conclusion: The inclusion and exclusion criteria and outcome measures did not match the purposes and contents of post-marketing research in the included studies. They also failed to reflect the basic principles of traditional Chinese medicine in the process of diagnosis and treatment. The demographic characteristics of the patients, the indications for medicine and the syndrome differentiation process were not reported sufficiently and transparently. In order to improve the post-marketing research and promote the rational use of Chinese patent drugs, it is recommended that phase Ⅳ clinical trials should establish clear research purpose as well as hypothesis first, and choose scientific and evidence-based study design and outcome measures. In addition, guidelines for implementation of post-marketing research should be developed.

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Absorption and transport of 6 coumarins isolated from the roots of Angelica pubescens f. biserrata in human Caco-2 cell monolayer model
Xiu-wei Yang, Qing-mei Guo, Ying Wang
Journal of Chinese Integrative Medicine    2008, 6 (4): 392-398.   DOI: 10.3736/jcim20080413
Abstract893)   HTML4)    PDF(pc) (1335KB)(47)      

Objective: To study the absorption and transepithelial transport of six coumarins (umbelliferone, osthole, columbianadin, columbianetin acetate, angelol-A and angelol-B, isolated from the roots of Angelica pubescens f. biserrata) in the human Caco-2 cell monolayer model.
Methods: The in vitro cultured human colon carcinoma cell line, Caco-2 cell monolayer model, was applied to study the absorption and transport of the six coumarins from apical (AP) to basolateral (BL) side and from BL to AP side. The six coumarins were measured by reversed-phase high-performance liquid chromatography (HPLC) coupled with ultraviolet absorption detector. Transport parameters and apparent permeability coefficients (Papp) were calculated and compared with those of propranolol as a control substance of high permeability and atenolol as a control substance of poor permeability. The transport mechanism of angelol-B was assayed by using iodoacetamide as a reference standard to inhibit ATP-dependent transport and MK571 as a well-known inhibitor of MRP2.
Results: The absorption and transport of six coumarins were passive diffusion as the dominating process. The Papp values of umbelliferone, osthole, columbianadin, columbianetin acetate, angelol-A and angelol-B from AP to BL side were (2.679±0.263)×10 -5, (1.306±0.324)×10 -5, (0.595±0.086)×10 -6, (2.930±0.410)×10 -6, (1.532±0.444)×10 -5 and (1.413±0.243)×10 -5 cm/s, and from BL to AP side were (3.381±0.410)×10 -5, (0.898±0.134)×10 -5, (0.510±0.183)×10 -6, (0.222±0.025)×10 -6, (1.203±0.280)×10 -5 and (0.754±0.092)×10 -5 cm/s, respectively. In this assay, the Papp value of propranolol was 2.18×10 -5 cm/s and the Papp value of atenolol was 2.77×10 -7 cm/s. Among the 6 coumarins, the Papp values of umbelliferone, osthole, angelol-A and angelol-B from AP to BL side were identical with that of propranolol, and columbianadin and columbianetin acetate lied between propranolol and atenolol. When replaced the HBSS with EBSS, and iodoacetamide or MK-591 were used in the experiment, the Papp of angelol-B had no statistical difference as compared with the control group. In the mean total recoveries, umbelliferone was (83.31±3.52) %, angelol-A was (77.39±7.38) %, osthole, columbianadin and angelol-B were between 50% to 65%, and columbianetin acetate was lower than 10%. The accumulation rates of osthole and columbianadin in the Caco-2 cells were (36.15±5.87) % and (53.90±4.39) %, respectively.
Conclusion: The absorption and transport of umbelliferone, osthole, columbianadin, columbianetin acetate, angelol-A and angelol-B are passive diffusion as the dominating process in Caco-2 cell monolayer model. Umbelliferone, osthole, angelol-A and angelol-B are estimated to be highly absorbed compounds, and columbianadin and columbianetin acetate are estimated to be moderately absorbed compounds. In the Caco-2 cells, osthol and columbianadin appear to accumulate, and columbianetin acetate may be metabolited. The absorption and transport of angelol-B are not influenced by the change of pH and the presence of iodoacetamide or MK571.

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Electroacupuncture protects the brain against acute ischemic injury via up-regulation of delta-opioid receptor in rats
Xue-song Tian, Fei Zhou, Ru Yang, Ying Xia, Gen-chen Wu, Jing-chun Guo
Journal of Chinese Integrative Medicine    2008, 6 (6): 632-637.   DOI: 10.3736/jcim20080617
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Objective: To explore the effect of δ-opioid receptor (DOR) in electroacupuncture (EA) protecting the brain against acute ischemic injury.
Methods: Fifty-one rats were randomly divided into sham ischemia group, ischemia group, sham EA group, EA group, and EA+DOR antagonist (naltrindole) group. Transient focal cerebral ischemia (1 hour) was induced in rat brain by middle cerebral artery occlusion (MCAO) method. EA was applied on Shuigou (GV 26) and Neiguan (PC 6) for 30 min, starting immediately after the onset of reperfusion. Neurological deficit scores and volume of cerebral infarction were detected after 24-hour reperfusion. Other 12 rats were randomly divided into sham ischemia group, ischemia group, EA group and EA+naltrindole group. DOR protein expressions were assessed by Western blotting after 24-hour reperfusion.
Results: In comparison with the ischemia group and sham EA group, EA significantly reduced ischemic infarction and neurological deficits (P<0.05); EA significantly increased the expression of 60 kD DOR protein (P<0.05) and tended to increase that of 36 kD DOR protein (P>0.05). When naltrindole was combined with EA, the naltrindole completely abolished the EA-induced protection in ischemic infarction and neurological deficits, and also arrested the expression of DOR.
Conclusion: EA can up-regulate DOR expression and protect the brain from ischemia-reperfusion injury.

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Effects of salvianolic acid B on expressions of TGF-β1 and its receptors in liver of rats with dimethylnitrosamine-induced hepatic fibrosis
Xiao-ning Wang, Yi-yang Hu, Cheng-hai Liu, Ping Liu, Da-yuan Zhu
Journal of Chinese Integrative Medicine    2005, 3 (4): 286-288.   DOI: 10.3736/jcim20050411
Abstract887)   HTML1)    PDF(pc) (93KB)(50)      

Objective

To study the therapeutic mechanism of salvianolic acid B (SA-B) in treating hepatic fibrosis.

Methods

Twenty-four Wistar rats were randomly divided into 3 groups: normal control group, untreated group and SA-B-treated group. Rats in the untreated and SA-B-treated groups were injected intraperitoneally with 0.5% dimethylnitrosamine (DMN) for 4 weeks, daily for 3 days each week at a dose of 10 μg/kg, to induce hepatic fibrosis. Then, rats in the SA-B-treated group were given SA-B orally for another 4 weeks. Hydroxyproline (Hyp) contents in liver tissue of the rats in 3 groups were determined with HCl hydrolysis, and collagen typeⅠ, transforming growth factor-beta 1 (TGF-β1), transforming growth factor-beta receptor typeⅠ(TβRⅠ) and transforming growth factor-beta receptor typeⅡ(TβRⅡ) were detected by Western blotting.

Results

The Hyp content and the expressions of collagen typeⅠ, TGF-β1, TβRⅠ and TβRⅡ in the liver tissue of rats in the untreated group increased significantly as compared with those in the normal control group, while those in SA-B-treated group decreased significantly as compared with those in the untreated group.

Conclusion

The therapeutic mechanism of SA-B in treating hepatic fibrosis may be related to inhibiting the expressions of TGF-β1 and its receptors.

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Univariate analysis of syndrome differentiation in traditional Chinese medicine and clinical correlative factors in gastric cancer
Li Tao, Jin-kun Yang
Journal of Chinese Integrative Medicine    2007, 5 (4): 398-402.   DOI: 10.3736/jcim20070407
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Objective: The research is aimed at investigating the developing rule and the relationship between syndrome differentiation in traditional Chinese medicine (TCM) and clinical factors of gastric cancer, so that it can be helpful to the clinical work and indicating the prognosis.Methods: We collected the medical records and the information of four diagnostic methods of 325 cases of gastric cancer sufferers in the way of clinical epidemiological survey, and divided them into 6 syndromes including dysfunction of spleen, disharmony of liver and stomach, blood stagnation in stomach, yin deficiency of stomach, phlegm dampness stagnation and deficiency of both qi and blood. Then we used univariate analysis of variance, rank sum test and chi square test to analyse the relationship between syndrome differentiation and clinical-related factors such as age, gender, Karnofsky score and clinical stage, etc.Result: The syndrome of dysfunction of spleen plays the primary role in the disease. Disharmony of liver and stomach always happens in early stage of stomach cancer, usually more often in radical operation cases and less in metastasis ones. It also has a high proportion in female. Phlegm dampness stagnation and blood stagnation in stomach usually can be seen in middle or advanced stage of the disease, which have lower Karnofsky score. Deficiency of both qi and blood is the syndrome of stomach cancer in advanced stage, which results in lower living quality, and with high rate of relapse and metastasis. Syndrome of yin deficiency of stomach has lower proportion in stomach cancer cases, and the clinical-related factors have low influence on it.Conclusion: Syndrome in TCM of gastric cancer is relevant to some clinical factors and varies in progress.

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Saffron (Crocus sativus L.) and major depressive disorder: A meta-analysis of randomized clinical trials
Heather Ann Hausenblas, Debbie Saha, Pamela Jean Dubyak, Stephen Douglas Anton
Journal of Chinese Integrative Medicine    2013, 11 (6): 377-383.   DOI: 10.3736/jintegrmed2013056
Abstract928)   HTML    PDF      

Background

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder (MDD). Of these, accumulating trials reveal positive effects of the spice saffron (Crocus sativus L.) for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted.


Objective

The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD.


Search strategy

We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies.


Inclusion criteria

The criteria for study selection included the following: (1) adults (aged 18 and older) with symptoms of depression, (2) randomized controlled trial, (3) effects of saffron supplementation on depressive symptoms examined, and (4) study had either a placebo control or antidepressant comparison group.


Data extraction and analysis

Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta-analysis 2 was used to analyze the data.


Results

Based on our pre-specified criteria, five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms (M ES = 1.62, P < 0.001), revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups (M ES = -0.15) indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials.


Conclusion

Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron’s efficacy and safety for treating depressive symptoms.

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ISSN 2095-4964
CN 31-2083/R

Editors-in-Chief:
Lixing Lao, Virginia, USA
Frequency: 6 issues per year
Publisher: Science Press, China

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