Production of ginsenoside compound K by microbial cell factory using synthetic biology-based strategy: a review.

Ginsenoside compound K (CK) is a major intestinal bacterial metabolite of the protopanaxadiol-type ginsenoside family that can be absorbed in the systemic circulation. CK possesses diverse and important pharmacological properties. The low production and high cost of traditional manufacturing methods based on the extraction and biotransformation of total ginsenosides from ginseng have limited their medical application. However, considerable progress has been made in the area of de novo CK production via microbial cell factories using synthetic biology-based strategies. By introducing key enzymes responsible for CK biosynthesis into microbial cells, CK was produced via a series of in vivo enzymatic reactions that utilize the inherent precursors in microbial cells. After systematic optimization using various metabolic engineering strategies, the yield of CK increased significantly and exceeded the traditional plant extraction-biotransformation method, implying the commercial feasibility of this approach. This review summarizes recent novel advancements in the production of CK using microbial cell factories.

Feasibility analysis and mechanism exploration of Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) against COVID-19.

Introduction. As a novel global epidemic, corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 brought great suffering and disaster to mankind. Recently, although significant progress has been made in vaccines against SARS-CoV-2, there are still no drugs for treating COVID-19. It is well known that traditional Chinese medicine (TCM) has achieved excellent efficacy in the treatment of COVID-19 in China. As a treasure-house of natural drugs, Chinese herbs offer a promising prospect for discovering anti-COVID-19 drugs.Hypothesis/Gap Statement. We proposed that Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) may have potential value in the treatment of COVID-19 patients by regulating immune response, protecting the cardiovascular system, inhibiting the production of inflammatory factors, and blocking virus invasion and replication processes.Aim. We aimed to explore the feasibility and molecular mechanisms of RS against COVID-19, to provide a reference for basic research and clinical applications.Methodology. Through literature mining, it is found that a Chinese herbal pair, RS, has potential anti-COVID-19 activity. In this study, we analysed the feasibility of RS against COVID-19 by high-throughput molecular docking and molecular dynamics simulations. Furthermore, we predicted the molecular mechanisms of RS against COVID-19 based on network pharmacology.Results. We proved the feasibility of RS anti-COVID-19 by literature mining, virtual docking and molecular dynamics simulations, and found that angiotensin converting enzyme 2 (ACE2) and 3C-like protease (3 CL pro) were also two critical targets for RS against COVID-19. In addition, we predicted the molecular mechanisms of RS in the treatment of COVID-19, and identified 29 main ingredients, 21 potential targets and 16 signalling pathways. Rhein, eupatin, (-)-catechin, aloe-emodin may be important active ingredients in RS. ALB, ESR1, EGFR, HMOX1, CTSL, and RHOA may be important targets against COVID-19. Platelet activation, renin secretion, ras signalling pathway, chemokine signalling pathway, and human cytomegalovirus infection may be important signalling pathways against COVID-19.Conclusion. RS plays a key role in the treatment of COVID-19, which may be closely related to immune regulation, cardiovascular protection, anti-inflammation, virus invasion and replication processes.

The Separation of Antler Polypeptide and Its Effects on the Proliferation and Osteogenetic Differentiation of Bone Marrow Mesenchymal Stem Cells.

BACKGROUND: Colla Cornus Cervi (CCC) has been used as a traditional Chinese medicine in the treatment of osteoporosis and osteonecrosis of the femoral head. However, the bioavailability of CCC is seriously limited owing to its large molecular weight and complex ingredients. In the present study, antler polypeptide was separated from CCC, and the effects of antler polypeptide on rat bone marrow mesenchymal stem cells (BMSCs) were investigated. METHODS: Antler polypeptide was separated from Colla Cornus Cervi by ultrafiltration into different samples according to the molecular weight. The total peptide content of these samples was determined by the biuret method. The content of antler polypeptide in different samples was quantified by high-performance liquid chromatography (HPLC). The effects of antler polypeptide at different concentrations on the proliferation, cell cycle, alkaline phosphatase activity, and BMP7 expression of BMSCs were investigated. RESULTS: Antler polypeptide was separated by ultrafiltration into different samples: A (molecular weight <800 Da), B (molecular weight 800-1500 Da), and C (molecular weight >1500 Da). The total peptide contents of A, B, and C were 0.602 mg/mL, 8.976 mg/mL, and 38.88 mg/mL. Antler polypeptide B eluted at 14.279∼15.351 min showed that the content of antler polypeptide was significantly higher than that of A and C with a peak area of 933.80927. The BMSCs proliferation rate (84.66%) of polypeptide B was the highest at the concentration of 1.578 × 10-2 g/mL. Antler polypeptide B significantly promoted the proliferation of BMSCs with a proliferation index of 38.68%, which was significantly higher than that of the other groups. Antler polypeptide B significantly enhanced the activity of alkaline phosphatase in BMSCs compared to that of the blank group (P < 0.001). Antler polypeptide B increased the BMP7 protein expression in BMSCs. CONCLUSIONS: Results suggested that antler polypeptide may promote the proliferation and osteogenic differentiation of BMSCs. Our study lays an experimental foundation for the further development and application of antler polypeptide in medicine.

Anemia in patients with Takayasu arteritis: prevalence, clinical features, and treatment.

BACKGROUND: Anemia is a common comorbidity of patients with Takayasu arteritis (TA). This study evaluated the prevalence, clinical characteristics, and treatment in Chinese TA patients with anemia. METHODS: This retrospective study included 533 consecutive patients hospitalized for TA from January 2009 to April 2018. Anemia was diagnosed on the basis of hemoglobin level, according to World Health Organization criteria. RESULTS: A total of 194 patients (36.4%) were diagnosed with anemia. Most had mild anemia (177, 91.2%). Female patients were predominant (92.8% of anemic patients). Normocytic anemia (62.9%) was the most common pattern. Anemic patients were more likely than non-anemic patients to have dizziness (29.4% vs. 21.2%), low body mass index (22.0 ± 3.6 vs. 22.9 ± 3.4 kg/m2), and active disease stage (64.9% vs. 50.1%); pulmonary involvement (12.4% vs. 26.8%), pulmonary hypertension (12.9% vs. 20.1%) and pulmonary hypertensive-target drugs (2.8% vs. 11.6%) were less common among anemic than non-anemic patients (all P < 0.05). Larger left ventricular end-diastolic diameter and lower left ventricular ejection fraction were observed in anemic patients. Over a median follow-up of four months, the increase of hemoglobin in anemic patients was associated with the use of iron supplementation. CONCLUSIONS: Anemia is a very common concurrent condition in TA, especially in young, female patients. Patients with anemia are more likely to be in the active disease stage. Iron supplementation helps increase hemoglobin.

The effects of Chinese herbal medicines for treating diabetic foot ulcers: A systematic review of 49 randomized controlled trials.

OBJECTIVE: To assess the effects and associated risks of Chinese herbal medicine (CHM) for diabetic foot ulcer (DFU). METHODS: We systematically searched seven electronic databases for randomized controlled trials (RCTs) about Chinese herbal medicines for treating diabetic foot ulcers. The methodological quality of RCTs was assessed by the Cochrane risk of bias tool. Data was synthesized using review manager (RevMan) 5.3. Meta-analysis was conducted if the data were available. A summary of finding table was generated by The GRADEpro Guideline Development Tool (GDT) online. RESULTS: Forty-nine RCTs, all conducted in China, involving 3646 participants were included. Most of the included trials had unclear or high risk of bias. Twenty-six trials could be pooled in five Meta-analyses, the remaining trials could not be pooled due to the obvious clinical heterogeneity. Only low evidence showed CHM therapy may have 42%-60.4% participants healed completely after treatment, approximately twice (RR 1.42-1.76) as much as the healed rates in conventional therapy (or plus hot water foot bath) group. Majority of the included trials reported benefit of CHM group on shortening healing time (4-23 days) and reducing ulcer wound size (at least 2 cm2). No serious adverse events were reported related to the medication in all trials. CONCLUSION: Weak evidence showed benefit of CHM as add-on treatment of conventional therapy on increasing number of ulcer heals in patients with DFU. That's about twice the healing rate of the conventional treatment (or plus hot water foot bath) group. With insufficient information, we could not draw confirmative conclusion on safety of CHM administration. These findings need to be tested in further large, rigorous trials.

[Anti-inflammatory mechanism of heat-clearing and detoxifying Chinese herbs].

Heat-clearing and detoxifying Chinese herbs (HDCHs) are mainly used to treat carbuncle, sore throat, erysipelas, gills, dysentery and other diseases induced by heat-toxicity. Inflammation is a defensive response to damaging factors in living organism with vascular system. In recent years, a large amount of experimental and clinical studies showed that HDCHs had good therapeutic effect on inflammation. This review analyzed the anti-inflammatory mechanism of 11 HDCHs by retrieving literature in past 5 years, including Lonicerae Japonicae Flos (Jinyinhua), Lonicerae Flos (Jinyinhua), Lonicerae Japonicae Caulis (Rendongteng), Forsythiae Fructus (Lianqiao), Rhizoma Coptidis（Huanglian）, Gardeniae Fructus (Zhizi), Andrographis Herba (Chuanxinlian), Taraxaci Herba (Pugongying), Scrophulariae Radix (Xuanshen), Pulsatillae Radix (Baitouweng), and Agrimoniae Herba (Xianhecao). The data showed that the regulatory effect of HDCHs on inflammation may be involved mainly in the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) or janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, with similarity of action links among these three. Based upon the analysis of literature, we proposed some promising directions in this research field, providing a reliable theoretical basis for both experimental researches and clinical practices of HDCHs.

Anti-parasitic effects of water-soluble alkaloid fractions from ethanolic extracts of Sophora moorcroftiana seeds in Caenorhabditis elegans.

Parasite infections of humans and animals remain a major global health problem, with limited choice of drugs being available to the treatment of parasitosis in the clinic. Sophora moorcroftiana (S. moorcroftiana) is a shrub that grows in Tibet Plateau of China. Decoction of the seeds has been used as a traditional Tibetan medicine to treat parasitosis for years. But the anti-parasitic effects of water-soluble fractions in the seeds need further investigation. In the present study, the water-soluble alkaloid fractions (E2) were obtained from S. moorcroftiana seeds by refluxing extraction with 60% ethanol and low polarity fraction (E2-a) and high polarity fraction (E2-b) were subsequently isolated from E2 using column chromatography. As a parasite model, Caenorhabditis elegans (C. elegans) were treated with different fractions and their survivals were recorded. The results showed that that E2-a induced a lower survival rate in C. elegans than E2-b and E2. The protoscoleces of Echinococcus granulosus (E. granulosus) were cultured in the presence of E2-a. Compared with E2-b and E2, protoscoleces exhibited decreased survival rate following E2-a treatment. Furtherly, the effects of E2-a on the behavior, brood size, and lifespan of the worms were investigated. Body bend frequencies of the worms treated with the high concentration of E2-a were reduced by two-thirds compared with the control group (P < 0.01). Compared with non-E2-a-treated group, exposure of nematodes to E2-a led to a decrease in head thrashes and pharyngeal pumps frequency (P < 0.01). E2-a treatment resulted in a significantly lower brood size (P < 0.01). Additional E2-a treatment induced a significantly shortened lifespan, compared with the control (P < 0.05). These findings indicated that water-soluble fraction E2-a from S. moorcroftiana seeds was a potential helminthic agent.

Oxymatrine Sensitizes the HaCaT Cells to the IFN-γ Pathway and Downregulates MDC, ICAM-1, and SOCS1 by Activating p38, JNK, and Akt.

Decreased interferon (IFN)-γ levels and increased levels of macrophage-derived chemokine (MDC) and intercellular adhesion molecule (ICAM)-1 are known to be involved in allergic skin diseases, such as eczema and atopic dermatitis. Activation of the IFN-γ and its downstream interleukin-12 (IL-12) pathway can correct these diseases. Suppressor of cytokine signaling 1 (SOCS1) is a cytokine signaling inhibitor that blocks downstream pathways of IFN-γ by blocking the mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling pathways. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the herbal medicine Radix Sophorae flavescentis, is used to treat allergic skin diseases in China. The non-cytotoxic concentrations of OMT in HaCaT cells were determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Tumor necrosis factor (TNF)-α and IFN-γ were used to stimulate HaCaT cells, and OMT was added to this system with tacrolimus (FK506) as a positive control. The mRNAs of cytokines, MDC, ICAM-1, IL-12p35, IL-12p40, and IFN-γ receptor (IFN-γR)α were detected by RT-PCR. Western blot analyses were performed to assess activation of the MAPK (p38, Jun N-terminal kinase, and extracellular signal-regulated kinase) and Akt signaling pathways. OMT increased the mRNA levels of the IL-12 and IFN-γRα, reduced the mRNA levels of ICAM-1, MDC, and SOCS1. But FK506 increased the mRNA levels of IL12 and inhibited the expression of ICAM-1 mRNAs and had no effects on the IFN-γRα, MDC, and SOCS1 mRNA in HaCaT cells stimulated with TNF-α and IFN-γ. Thus, the mechanisms through which OMT and FK506 ameliorate allergic skin diseases differ.

Efficacy of topical administration of Radix Euphorbiae Ebracteolatae on multiple plantar warts: A parallel randomized trial.

OBJECTIVE: To investigate the clinical efficacy of Radix Euphorbiae Ebracteolatae in treating multiple plantar warts. METHODS: Twenty-eight patients with multiple plantar warts on both left and right feet were recruited. Warts on the left feet (treatment group) of all patients were externally treated with moderate ethanol extract of Radix Euphorbiae Ebracteolatae which was made of 30 g Radix Euphorbiae Ebracteolatae putting into 100 mL of medical ethanol (75%). For the control group, moderate dose of 0.1% vitamin A acid ointment was externally applied onto the right-foot warts. The topical application of each treatment was conducted 3 times a day for both groups. After 4 and 8 weeks, the efficacy and side effects including skin erythema and blister were evaluated and observed. RESULTS: Compared with the pre-treatment, warts size of the control group was reduced after 8-week treatment (P<0.05). After 4 and 8 weeks, the average wart size in the treatment group was both significantly reduced respectively (P<0.01). There were significant differences in warts size and total effective rate between the two groups after 4-week treatment respectively (P<0.05 or P<0.01). More significant differences in wart size and total effective rate were observed after 8-week treatment (P<0.05 or P<0.01). The percentage reduction in wart size was significantly different between the two groups after 4 and 8-week treatment (P<0.01). CONCLUSION: Radix Euphorbiae Ebracteolatae was significantly superior to vitamin A acid ointment in treating multiple plantar warts.

[Effect of Acupuncture Therapy on Body Compositions in Patients with Obesity].

OBJECTIVE: To observe the clinical effectiveness of acupuncture intervention in weight reduction by modulating body compositions in obesity patients. METHODS: A total of 71 obesity patients during weight-loss procedure were allocated to acupuncture+nutrition-consultation group (n=40) and simple nutrition-consultation group (n=31). The patients of the acupuncture +nutrition-consultation group were treated by acupuncture stimulation of Zhongwan (CV 12), Xiawan (CV 10), Tianshu (ST 25), Wailing (ST 26), Qihai (CV 6), Guanyuan (CV 4), etc. for 30 min, once every other day, 3 times per week, 12 times altogether, and also given with weekly nutrition consultation (including subjective query, objective measurement, analysis, program for nutrition support) at the same time. The patients of the simple nutrition-consultation group were treated by only weekly nutrition consultation for 4 weeks. Before and after the treatment, the patients' body weight, body mass index (BMI), fat mass, percentage of body fat, muscle mass, protein quality, water quality and bone mass were measured by using a composition analyzer. RESULTS: After 4 weeks' treatment, the body mass, BMI, fat mass and fat percentage in both acupuncture+nutrition-consultation and simple nutrition-consultation groups were significantly decreased (P<0.01), while the weight levels of muscle, protein, bone and water content had no apparent changes (P>0.05). The therapeutic effect of acupuncture+nutrition-consultation group was markedly superior to that of the simple nutrition-consultation group in increasing the improved degrees of body weight, BMI, fat mass and fat percentage (P<0.01). CONCLUSIONS: Acupuncture plus nutrition consultation is effective in reducing body mass, fat mass and percentage of body fat in obesity patients.

[Effect of Acupuncture Therapy in Combination with Nutrition Control on Body-weight Reduction in Postpartum Obesity Subjects].

OBJECTIVE: To observe the clinical effect of acupuncture therapy in the treatment of postpartum obesity subjects. METHODS: A total of 71 postpartum obesity subjects were allocated to treatment group (n=35) and control group (n=36). Participants of the control group were asked to receive weekly nutrition consultation (body-weight management) for calorie intake control during 4 weeks' treatment, and those of the acupuncture group were treated by manual acupuncture stimulation of Zhongwan (CV 12), Zhongji(CV 3), Qihai(CV 6), Shuifen (CV 9), and Guanyuan (CV 4), bilateral Tianshu (ST 25), Guilai (ST 29), Shousanli (LI 10), Zusanli (ST 36), Fenglong (ST 40), and Yinlingquan (SP 9) in combination with nutrition consultation. The treatment was conducted once every other day, continuously for 4 weeks. The body weight(BW), body mass index (BMI), percent of body fat (PBF) and waist-to-hip ratio (WHR) were determined before and after the treatment. RESULTS: After the treatment, the BW, BMI, PBF and WHR in the acupuncture group, and the BW and WHR in the control group were significantly decreased (P<0.01, P<0.05), and the therapeutic effect of the acupuncture group was notably superior to that of the control group in reducing BW and WHR (P<0.05, P<0.01). CONCLUSIONS: Acupuncture therapy combined with nutritional calorie control has a positive role in relieving obesity in postpartum obesity participants.

Retrieval of Au, Ag, Cu precious metals coupled with electric energy production via an unconventional coupled redox fuel cell reactor.

The recovery of heavy metals from aqueous solutions or e-wastes is of upmost importance. Retrieval of Au, Ag, and Cu with electricity generation through building an ethanol-metal coupled redox fuel cells (CRFCs) is demonstrated. The cell was uniquely assembled on PdNi/C anode the electro-oxidation of ethanol takes place to give electrons and then go through the external circuit reducing metal ions to metallic on the cathode, metals are recovered. Taking an example of removal of 100mgL-1 gold in 0.5M HAc-NaAc buffer solution as the catholyte, 2.0M ethanol in 1.0M alkaline solution as the anolyte, an open circuit voltage of 1.4V, more than 96% of gold removal efficiency in 20h, and equivalent energy production of 2.0kWhkg-1 of gold can be readily achieved in this system. When gold and copper ions coexist, it was confirmed that metallic Cu is formed on the cathodic electrode later than metallic Au formation by XPS analysis. Thus, this system can achieve step by step electrodeposition of gold and copper while the two metal ions coexisting. This work develops a new approach to retrieve valuable metals from aqueous solution or e-wastes.

Development, reliability and validity of Traditional Chinese Medicine Health Self-Evaluation Scale (TCM-50).

OBJECTIVE: To develop a health-evaluating scale from a Chinese medicine (CM) perspective and reflecting CM conception of health. METHODS: The Traditional Chinese Medicine Health Self-Evaluation Scale (TCM-50) was developed by verification of dimensions, formation of item pool, verification of scoring methodology, and pilot test of scale and item analysis. RESULTS: TCM-50 composed of 50 items that could be classified into 4 dimensions including physiology and health, psychology and health, nature and health, and society and health. An examination of reliability and validity of TCM-50 yielded Cronbach's α coefficient of 0.927, and half coefficient of was 0.876. The intraclass correlation coefficient of total score was 0.912. After using SF-36 questionnaire to evaluate the criterion validity, the Pearson of the score of the two scales from the same participant was 0.740. CONCLUSIONS: TCM-50 has good reliability and validity, and can yield similar levels of efficacy as SF-36 in terms of evaluating people's overall health level. As a scale based on CM theory, TCM-50 is suitable for self-measuring the general health of Chinese patients.

Recent highlights of Chinese herbs in treatment of allergic disease: Acting via mitogen-activated protein kinase signal pathway.

The histamine receptor antagonists in the treatment of allergic disease have limitations. The treatments of Chinese herbs have some curative effects on allergic skin lesions. Present research indicates that the mitogen-activated protein kinase (MAPK) signaling pathway might be equally important in allergic reactions. It was found that the inhibition of MAPK signaling pathways might relieve allergy symptoms, and some herbs can inhibit the MAPK pathway, which yields anti-allergy effects. Chinese medicines (CMs) have immense potential in the development of treatments for allergic disease.

Safflower polysaccharide induces NSCLC cell apoptosis by inhibition of the Akt pathway.

Lung cancer is the leading cause of cancer death in the world. Safflower polysaccharide (SPS) has been used for the improvement of immunomodulatory activities and treatment of cancers. However, studies on the effect of SPS on the progression of lung cancer have rarely been reported. To study the antitumor effect of SPS on human lung cancer and its potential mechanism, non-small cell lung cancer cell lines (NSCLC), A549 and YTMLC-90 were treated with SPS at various concentrations ranging from 0.04 to 2.56 mg/ml and BALB/c nude tumor-bearing mice were injected intraperitoneally with SPS at concentrations ranging from 15 to 135 mg/kg. Results showed that SPS suppressed the proliferation of A549 and YTMLC-90 cells and induced apoptosis by increasing mRNA levels of bax and caspase-3, and inhibited tumor growth in vivo. SPS induced cell cycle arrest in the G2/M phase by decreasing the expression of cdc25B and cyclin B1. Moreover, SPS decreased the expression of Akt, p-Akt and PI3K. In mice, SPS injection enhanced immunomodulatory activities by increasing levels of TNF-α and IL-6 in tumor-bearing mice. Our findings suggest that SPS suppresses tumor growth by enhancing immunomodulatory activities and blocking the PI3K/Akt pathway. This study provides new insight into the anticancer mechanism of SPS.

[Metabonomics on toxicity reduction of Glycyrrhizae Radix et Rhizoma for Aconiti Lateralis Radix Preparata in Sini Tang].

To analyze the endogenous metabolite changes in rat plasma after intervention by Sini Tang and Sini Tang without Glycyrrhizae Radix et Rhizoma based on GC-MS metabonomics technology, and study the toxicity reduction effect of Glycyrrhizae Radix et Rhizoma in Sini Tang on Aconiti Lateralis Radix Preparata. Eighteen SD rats were randomly divided into normal group, Sini Tang group and Sini Tang without Glycyrrhizae Radix et Rhizoma group on average. The rats in Sini Tang group and Sini Tang without Glycyrrhizae Radix et Rhizoma group were treated respectively with physic liquor by intragastric administration at the dose of 0.02 mL•g ⁻¹ (equivalent to 0.8 g•mL ⁻¹ crude drugs) once a day for 7 days. The rats in normal group were given with equal volume of saline solution. The plasma samples were collected from each rat 0.5 h after the last administration for GC-MS detection. The data was used for multivariate statistical analysis to obtain 14 potential metabolic markers(13 of them were identified). Then their relative content and metabolic pathways were analyzed. Compared with Sini Tang without Glycyrrhizae Radix et Rhizoma group, seven metabolic markers of were reduced in Sini Tang group. Analysis on physiological functions of these potential metabolic markers showed that the Glycyrrhizae Radix et Rhizoma in Sini Tang could reduce the toxicity of Aconiti Lateralis Radix Preparata by adjusting the glycolysis, lipid metabolism, citrate cycle and some amino acids metabolism.

[Treatment of chemotherapy-induced leucopenia in patients with malignant tumor by Chinese herbal medicine: a systematic review and meta-analysis of randomized clinical trials].

OBJECTIVE: To assess the effectiveness and safety of traditional Chinese herbal medicine (TCHM) for chemotherapy-induced leucopenia in patients with malignant tumor. METHODS: Chinese database (CNKI, VIP, CBM, Wanfang Database) and English database (Medline, Cochrane Library) were retrieved with the deadline of September 2013. Participants were cancer patients confirmed by pathology waiting for chemotherapy. We included randomized clinical trials (RCTs) testing chemotherapy plus TCHM vs. chemotherapy plus placebo, chemotherapy alone, conventional treatment, or TCHM plus chemotherapy combined with conventional treatment vs chemotherapy combined with conventional treat ment. The primary outcomes were WBC count, leucopenia incidence, and adverse reactions. Assessments of methodological quality, including randomization, allocation, concealment, blindness, dropping-out, loss of follow-ups were also conducted according to the Cochrane Handbook for Systematic Review of Interventions. Meta-analysis was performed using RevMan5. 2 Software provided by Cochrane Collaboration. RESULTS: Eighty-seven RCTs (involving 8 468 patients) were included. All these studies were published in Chinese. Of these only two papers were of high quality. Methods of randomization, scheme concealment, blindness, dropping-out, loss of follow-up, samples estimation were not accurately reported in the rest RCTs. The pooled results of WBC count showed that chemotherapy combined with TCHM was generally better than chemotherapy alone [MD =0. 64 x 109/L (0.41, 0.88), P < 0.01]. Auxiliary treatment of Compound Ejiao Syrup, Diyu Shengbai Tablet, Chinese compounds for invigorating Pi and supplementing Shen during the chemotherapeutic course could elevate peripheral blood WBC counts, and decrease the incidence of leucopenia. CONCLUSION: Chinese herbal medicine might have potential effects in preventing the occurrence of leucopenia, which need to be confirmed by launching higher quality clinical trials.

Sex dependent pharmacokinetics, tissue distribution and excretion of peimine and peiminine in rats assessed by liquid chromatography-tandem mass spectrometry.

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillaria thunbergii Miq. has been traditionally used in China as antitussive and expectorant herbs, and newly used in the clinical treatment of leukemia in recent years. AIM: To investigate whether gender exerted a significant influence on the pharmacokinetics, tissue distribution and excretion of peimine and peiminine in Sprague-Dawley rats who were given a single oral administration of 4.25 g/kg Fritillaria thunbergii Miq. extract. MATERIALS AND METHODS: Sprague-Dawley rats were assigned into two groups based on the gender and orally administered 4.25 g/kg Fritillaria thunbergii Miq. extract for each individual pharmacokinetics, tissue distribution and excretion study. RESULTS: Compared with female rats, peimine and peiminine were eliminated slowly from male rat plasma, and significant gender-related differences were observed in the pharmacokinetic parameters. Drug blood and tissue levels in male rats were significantly higher than the female counterparts except for several tissues, such as fat, muscle and skin. Gender also exerted a significant influence on the urine excretion but such effect was not observed in the feces excretion study. CONCLUSIONS: Gender exerted a significant influence on the pharmacokinetics, tissue distribution and urine excretion of peimine and peiminine. It is assumed that the sex-associated differences of peimine and peiminine in rats might be mainly result from sex-dependent expression and activity of drug metabolism enzymes and P-glycoprotein.

[Treatment of diabetic nephropathy by integrative medicine: a multi-center prospective cohort study].

OBJECTIVE: To assess the efficacy and safety of integrative medicine (IM) treatment for diabetic nephropathy (DN), and to explore the medication laws by Chinese medicine (CM) syndrome typing. METHODS: One hundred and seventy outpatients or inpatients with DN at Dongfang Hospital of Beijing University of Chinese Medicine, Xiyuan Hospital of China Academy of Chinese Medical Sciences, and China-Japan Friendship Hospital of the Ministry of Health were recruited from March 2008 to July 2009. They were allocated into the IM group (116 cases) or the Western medicine group (54 cases) according to whether or not they were willing to receive CM syndrome typing. The incidence of endpoint events and secondary outcome measures [such as body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), urinary albumin excretion rate (UAER), 24 h urinary protein (24 hU), serum creatinine (SCr), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c)] of two groups were observed at 3, 6, 12, 18, and 24 months respectively during the follow-ups. Patients in the IM group were syndrome typed. The CM recipes were collected to calculate the frequency of Chinese materia medica used. The liver function, blood routines, and ECG were observed and compared during the follow-ups. RESULTS: The follow-up period was 3 to 24 months with the mean of 14 months. Data suitable for analysis mainly covered the 3rd, 6th, 12th and 18th month of the follow-up. Both PPS and FAS analysis showed that there were no significant difference in the incidence of endpoint between two groups (11.2% vs 7.4%, P>0.05). The level of body mass index (BMI) [(25.0 +/- 3.1) kg/m2] and fasting blood glucose (FBG) [(7.9 +/- 1.5) mmol/L] in the IM group were lower than those of the Western medicine group [(28.6 +/- 4.4) kg/m2 and (8.8 +/- 2.9) mmol/L respectively] at the 6-month follow-up (P<0.05). The levels of FBG [(7.9 +/- 1.4) mmol/L] and HbA1c [(7.8 +/- 1.4)%] in the IM group were lower than those of the Western medicine group [(9.6 +/- 2.8) mmol/L and (8.5 +/- 1.6)% respectively] at the 12-month follow-up (P<0.05). There was no significant difference in other indices between the two groups at the 3- or 12-month follow-ups. The level of SCr in the IM group and the Western medicine group before follow-up were (96.8 +/- 35.2) micromol/L and (80.5 +/- 24.6) micromol/L respectively, showing statistical difference (P<0.01). There were no significance difference in SCr between the two groups at 3, 6, 12, 18-month follow-ups for center 2 (Xiyuan Hospital of China Academy of Chinese Medical Sciences) and center 3 (China-Japan Friendship Hospital of the Ministry of Health), while the level of SCr in the IM group [(82.4 +/- 25.7) micromol/L, (78.1 +/- 25.9) micromol/L, (80.3 +/- 24.0) micromol/L, respectively] were lower than that of the Western medicine group [(101.4 +/- 37.2) micromol/L, (96.5 +/- 34.1) micromol/L, (93.9 +/- 25.9) micromol/L, respectively] for center 1 (Dongfang Hospital of Beijing University of Chinese Medicine) at 3, 6, 12-month follow-ups (P<0.05). The top ten drugs used most frequently in the 237 prescriptions collected was astragali (68.4%), ophiopogonis tube (67.5%), rehmannia dried rhizome (67.1%), danshen root (49.4%), Codonopsis pilosula (41.8%), figwort root (35.4%), Chinese magnolia-vine fruit (29.5%), safflower (27.9%), peach seed (26.2%), and angelica root (25.3%). There was no abnormal liver function, blood abnormalities, and serious adverse events in two groups during the follow-ups. CONCLUSIONS: CM treatment based on syndrome typing in combination with routine Western medicine for DN could reduce the levels of BMI, FBG, HbA1c, and SCr at partial time points, showing favorable safety. Chinese medicinals applied in treatment based on syndrome typing for DN covered mainly supplementing qi, nourishing yin, and activating blood circulation to remove blood stasis.