[Correlation between ecological factors and effective component content, flower, and leaf traits of Epimedium pubescens].

No systematic research has been reported on the correlation between different ecological factors and the effective component content, flower, and leaf traits of Epimedium pubescens. In this study, 21 kinds of E. pubescens in different regions were investigated, and the content of two effective components of icariin(I) and Epimedin C(C), as well as six leaf traits and 12 flower traits were determined. The correlation between 11 ecological factors and the above traits in different regions for five consecutive years was explored. The results showed that no significant correlation was observed between the ecological factors and the total content of two effective components(I+C) of E. pubescens. Latitude and temperature(including annual average temperature, annual average minimum temperature, and soil temperature of each soil layer) were significantly positively and negatively correlated with the ratio of the content of the two effective components(C/I)(P<0.01), respectively. There was a significant correlation between ecological factors and flower traits, and the annual average soil temperature of each soil layer, annual average temperature, and annual average minimum temperature were significantly correlated with most flower traits in multiple years(P<0.01). However, a weak correlation between ecological factors and leaf traits was detected. A significant positive correlation of the annual average soil temperature of each soil layer and annual average humidity(P<0.01) with the width of nutrient leaf in only a few years was detected. Therefore, it was concluded that the total content of effective components of E. pubescens was determined by genetics, with a slight influence of ecological factors. The annual average temperature, annual average minimum temperature, and soil temperature of each soil layer were the ecological factors that had the most significant impact on flower traits, which showed significant differences in different regions, and similar results were not found in leaf traits. Overall, this study systematically conducted a correlation analysis between ecological factors and the effective components, as well as flower and leaf traits, providing guidance for the quality improvement, introduction, and domestication of E. pubescens.

[Effect of combined application of organic and chemical fertilizers on yield and quality of Epimedium pubescens].

To investigate the effects of different ratios of organic and chemical fertilizers on the yield and quality of Epimedium pubescens,so as to provide a scientific basis for the fertilization of high-yield and high-quality E. pubescens cultivation. In this experiment,a field plot test was conducted,and CK(without fertilizer) was set as the control group,with five treatment groups with different ratios of organic fertilizers and chemical fertilizers set up,namely OF0(100% chemical fertilizers),OF25(25% organic fertilizers),OF50(50% organic fertilizers),OF75(75% organic fertilizers),and OF100(100% organic fertilizers). The effects of different fertilization patterns on the agronomic traits,yield,effective component content,nutrient accumulation,and soil physicochemical properties of E. pubescens were determined,and the yield and quality of the medicinal herb were comprehensively evaluated by using the CRITIC weights method. It was found that the herb yield of each treatment group was significantly increased compared with the CK group,although the yield of the groups with both organic fertilizer and chemical fertilizer was slightly lower than that of OF0. However,there was no significant difference,which indicated that the organic fertilizer combined with chemical fertilizer could ensure the herb yield. With the increase in organic fertilizer ratios,the medicinal components epimedin A,epimedin B,and epimedin C showed a tendency of first increasing and then decreasing,with the highest content in the OF25,while icariin showed a rising trend,with the best in the OF100. However,overall,the total flavonol glycosides ABCI accumulated the most in the OF25. The results of the CRITIC method showed that the top three fertilization treatments in terms of the comprehensive scores of the medicinal herb were OF25,OF50,and OF75. Organic fertilizer combined with chemical fertilizer is conducive to improving the soil's fertilizer holding and supply capacity,and the soil indexes are optimal in OF100. The soil enzyme activity is the highest in OF75. Meanwhile,organic fertilizer combined with chemical fertilizer can help the plant's uptake and accumulation of nutrients,and OF25 shows the most obvious effect.By comprehensively considering the influence of different ratios of organic and chemical fertilizers on the yield,effective component content,nutrient accumulation,and other indexes of E. pubescens,it is recommended that a 25% ratio(7 500 kg·hm~(-2)) of organic fertilizers and chemical fertilizers should be used in E. pubescens production in the first year,so as to promote the E. pubescens industry to increase yield and improve quality.

Peripheral nerve blocks for analgesia following cesarean delivery A narrative review.

Spinal and epidural blocks are commonly employed for pain relief during and following cesarean section. Intrathecal morphine (ITM) has been the gold standard for the same for many years. In recent times, many peripheral nerve blocks (PNBs) have been tried for postoperative analgesia following cesarean delivery (PACD). This article has reviewed the common PNBs used for PACD. The role of PNBs along with ITM has been studied and the current best strategy for PACD has also been explored. Currently, Ilio-inguinal nerve and anterior transversus abdominis plane block in conjunction with intrathecal morphine have been found to be the most effective strategy, providing lower rest pain at 6 hours as compared to ITM alone. In patients not receiving intrathecal morphine, recommended PNBs are lateral transversus abdominis plane block, single shot local anesthetic wound infiltration, or continuous wound infiltration with catheter below rectus fascia. PNBs are recommended for PACD. They have an opioid-sparing effect and are devoid of adverse effects associated with central neuraxial blocks such as hypotension, bradycardia, and urine retention. However, caution must be observed with PNBs for possible local anesthetic toxicity due to the large volumes of drug required.

Multi-component immune knockout: A strategy for studying the effective components of traditional Chinese medicine.

Periploca forrestii Schltr., a traditional Chinese medicine (TCM), is commonly used to treat autoimmune diseases such as rheumatoid arthritis (RA). However, its mechanism, involving a variety of cardiac glycosides, remains largely unknown. The immune knockout strategy can highly selectively deplete target components by immunoaffinity chromatography (IAC). We aimed to identify the common structural features of cardiac glycosides in P. forrestii and design IAC to specifically recognize these features to achieve the multi-component knockout of potential active substances from the extracts of P. forrestii. A content detection experiment confirmed that the content of a compound with periplogenin structure (CPS) in the extract of P. forrestii was reduced by 45% by IAC of periplogenin. The immunosuppressive ability of the extract on H9 human T lymphocytic cells was weakened after CPS knockout from P. forrestii extract. Molecular biology experiments showed that mRNA expression of interferon-γ (IFN-γ), interleukin-2 (IL-2), and interleukin-6 (IL-6) in H9 cells was up-regulated after CPS knockout, while no significant changes in the expression of interleukin-4 (IL-4) were found. CPS knockout from P. forrestii extract did not cause significant changes in the proliferation of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells incubated with this extract. These results indicate that CPS exhibited immunosuppressive effects via inhibiting the T helper 1 (Th1) cell immune response and not via the anti-inflammatory components in P. forrestii. This is the first use of IAC to achieve multi-component knockout in TCM extracts for identifying effective compounds. This method is effective and reliable and warrants further exploration.

Extraction of effective components of Psoralea corylifolia and efficacy evaluation in the treatment of vitiligo / 中国药房

OBJECTIVE To extract the effective components of Psoralea corylifolia and evaluate its efficacy in the treatment of vitiligo. METHODS The concentrations of psoralen， isopsoralen， neobavaisoflavone， corylin， psoralidin， corylifolinin， and bakuchiol in P. corylifolia extract were determined by ultra-performance liquid chromatography. Based on the analytic hierarchy process （AHP） and Plackett-Burman design， with the concentrations of the 7 components as evaluation indexes and the crushing degree， ethanol concentration， and soaking time as factors， the extraction process of P. corylifolia was optimized by Box-Behnken response surface methodology and the validation test was conducted. Zebrafish were divided into blank control group， positive control group （8-methoxypsoralen， 10.8 μg/mL）， and low-， medium-， and high-concentration groups of P. corylifolia extract （500， 1 000， 2 000 μg/mL）， with 6 fish in each group. The effects of P. corylifolia extract on the melanin production of zebrafish were studied by density analysis. RESULTS The best extraction process was P. corylifolia powder over 60 meshes and soaked in 80% ethanol for 72 hours. The average comprehensive score of three validation experiments was 98.27， with an RSD of 1.36%， and the relative error was 1.02% compared with the predicted value of the fitting equation （97.28）. Compared with the blank control group， the melanin pigmentation of zebrafish in the low-， medium-， and high-concentration groups of P. corylifolia extract was significantly increased （P＜0.01）. CONCLUSIONS The optimized extraction process of P. corylifolia is reasonable and feasible， and the obtained P. corylifolia extract can significantly promote the production of melanin in zebrafish.

Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway.

BACKGROUND: Effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) demonstrates positive effects on stable chronic obstructive pulmonary disease (COPD). PURPOSE: To investigate the mechanisms of ECC-BYF III on COPD rats from the aspect of airway epithelial cell senescence. METHODS: COPD model rats (Sprague-Dawley rat) were treated with ECC-BYF III for 8 weeks, and the efficacy was evaluated. Cigarette smoke extract (CSE)-induced senescence model of airway epithelial cells was treated with ECC-BYF III, and related enzymes and proteins involved in oxidative stress and mitophagy were detected. RESULTS: ECC-BYF III markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including the reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 levels, increase of the level in total superoxide dismutase (T-SOD), and decease in the p21 level in the airways. Furthermore, ECC-BYF III suppressed p16 and p21 expressions and senescence-associated ß-galactosidase (SA-ß-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF III upregulated mitophagy-related proteins, including the co-localizations of TOM20 and LC3B, PINK1 and PARK2, and improved mitochondrial function by upregulating mitochondrial mitofusin (MFN)2 and reducing dynamin-related protein 1 (DRP1) expression. ECC-BYF III enhanced the activities of T-SOD and GSH-PX by up-regulating NRF2, thus inhibiting oxidative stress. After intervention with NRF2 inhibitor, the regulation effects of ECC-BYF III on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed. CONCLUSIONS: ECC-BYF III exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through the activation of NRF2 signaling.

The transported active mulberry leaf phenolics inhibited adipogenesis through PPAR-γ and Leptin signaling pathway.

The effective components of mulberry leaf polyphenols (MLPs) should be absorbed and transported by the intestinal cells before regulating lipid metabolism. The Caco-2 intestinal epithelial cell and 3 T3-L1 adipocytes were coupled to screen the effective components of MLPs that are being absorbed and transported by intestinal cells. The regulation and molecular mechanism by which the effective components affect adipogenesis were analyzed in this study. Among the 12 main components identified, five main compounds were well absorbed with Papp in the order of benzoic acid > chlorogenic acid > astragaloside > hyperoside > rutin. Chlorogenic acid and benzoic acid were mainly absorbed through passive diffusion, while rutin, astragaloside, and hyperoside were mainly by active transport, of which chlorogenic and rutin absorption were mediated by the efflux protein, P-glycoprotein (P-pg). Based on the transport volume of 2 mg/ml MLPs within 2 h, 25% of the maximum transported MLPs (TMLPs) was a safe concentration for 3 T3-L1 preadipocytes. Except for astragaloside, the other four components showed a significant inhibitory effect on lipid droplets, TG and TC, and chlorogenic acid and benzoic acid had the strongest effect. Additionally, we observed a synergistic effect as TMLPs were the most effective. We hypothesized that TMLPs, chlorogenic acid and benzoic acid suppressed adipogenesis and regulated lipid metabolism by inhibiting PPAR-γ, C/EBP-α, and FAS mRNA while promoting ADIPO and Leptin mRNA expression. PRACTICAL APPLICATIONS: The absorption and adipogenesis inhibition effect of mulberry leaf phenolics were evaluated in this study. The results provided guideline for the development of functional foods in regulating lipid metabolism.

[Effect of combined application of inorganic and organic fertilizers on growth and quality of Salvia miltiorrhiza].

The study is aimed through field experiments to study the effect of combined application of organic and chemical fertilizers on the growth and quality of Salvia miltiorrhiza, provide ideas for reducing fertilization while increasing the efficiency as well as improving the quality of produces. The experiment included 6 treatments viz., no fertilization(CK), full application of chemical fertilizer(F), 25% orga-nic fertilizer with 75% chemical fertilizer(M25), 50% organic fertilizer with 50% chemical fertilizer(M50), 75% organic fertilizer with 25% chemical fertilizer(M75), and fully apply organic fertilizer(M100). The results showed that:(1)from the perspective of yield and economic benefits, M75 was the best and M100 second;(2)for effective components, the combined application of organic and chemical fertilizers increased the content of main water-soluble components and the total content of effective components, among which M25 and M50 were better.

Pharmacokinetics-based comprehensive strategy to identify multiple effective components in Huangqi decoction against liver fibrosis.

BACKGROUND: Huangqi decoction (HQD) has been used to treat chronic liver diseases since the 11th century, but the effective components in HQD against liver fibrosis have not been definitively clarified. PURPOSE: To investigate and identify multiple effective components in HQD against liver fibrosis using a pharmacokinetics-based comprehensive strategy. METHODS: The absorbed representative components in HQD and their metabolites were detected in human plasma and urine using high-resolution mass spectrometry combined with a database-directed method, and then pharmacokinetics in multiple HQD components in human plasma was analyzed by ultra-performance liquid chromatography coupled with triple-quadruple mass spectrometry. Furthermore, the anti-fibrotic effect of potential effective HQD components was studied in LX-2 cells and that of a multi-component combination of HQD (MCHD) was verified in a mouse CCl4-induced hepatic fibrosis model. RESULTS: Twenty-four prototype components in HQD and 17 metabolites were identified in humans, and the pharmacokinetic characteristics of 14 components were elucidated. Among these components, astragaloside IV, cycloastragenol, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, and isoliquiritigenin downregulated the mRNA expression of α-SMA; cycloastragenol, calycosin-7-O-ß-D-glucoside, formononetin, glycyrrhetinic acid, liquiritin, and isoliquiritin downregulated the mRNA expression of Col I; and calycosin, liquiritigenin, isoliquiritigenin, cycloastragenol, and glycyrrhetinic accelerated the apoptosis of LX-2 cells. MCHD reduced serum aminotransferase activity and hepatic collagen fibril deposition in mice with CCl4-induced hepatic fibrosis. CONCLUSION: Using the pharmacokinetics-based comprehensive strategy, we revealed that multiple effective HQD components act together against liver fibrosis.

Effect of combined application of inorganic and organic fertilizers on growth and quality of Salvia miltiorrhiza / 中国中药杂志

The study is aimed through field experiments to study the effect of combined application of organic and chemical fertilizers on the growth and quality of Salvia miltiorrhiza, provide ideas for reducing fertilization while increasing the efficiency as well as improving the quality of produces. The experiment included 6 treatments viz., no fertilization(CK), full application of chemical fertilizer(F), 25% orga-nic fertilizer with 75% chemical fertilizer(M25), 50% organic fertilizer with 50% chemical fertilizer(M50), 75% organic fertilizer with 25% chemical fertilizer(M75), and fully apply organic fertilizer(M100). The results showed that:(1)from the perspective of yield and economic benefits, M75 was the best and M100 second;(2)for effective components, the combined application of organic and chemical fertilizers increased the content of main water-soluble components and the total content of effective components, among which M25 and M50 were better.

Compatibility characteristics of Bufei Yishen formula Ⅲ in regulating chronic obstructive pulmonary disease mucus hypersecretion / 中华危重病急救医学

Objective:To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYFⅢ) in regulating mucus hypersecretion of chronic obstructive pulmonary disease (COPD).Methods:According to the efficacy of the original Chinese medicine, the components of ECC-BYFⅢ were divided into four categories: Buqi (Ginsenoside Rh1+Astragaloside), Bushen (Icariin), Huatan (Nobiletin), and Huoxue (Paeonol). The four categories were divided into 14 groups based on the method of mathematical permutation. ① The rats were divided into control group, model group, ECC-BYFⅢ, and different components compatibility groups according to the random number table, totaling 17 groups. COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The corresponding drugs were given by gavage at the 9th week of modeling, and the samples were collected at the end of the 16th week. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase 1 (TIMP-1) in serum and bronchoalveolar lavage fluid (BALF), and the levels of mucin (MUC) 5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay (ELISA). ② Human lung epithelial cells BEAS-2B were divided into blank group, model group, and different components compatibility groups. Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment. The mRNA expressions of MUC5AC, MUC5B, and MUC1 were detected by quantitative polymerase chain reaction (PCR). The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region (R) value comprehensive evaluation method.Results:① Compared with the control group, MMP-9 in serum and BALF from the model group were significantly increased, the level of TIMP-1 was significantly decreased, and MUC5AC in lung tissue and BALF were significantly increased. The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups, ECC-BYFⅢ and other components compatibility groups significantly corrected mucus hypersecretion in COPD rats, ECC-BYFⅢ, Bushen Quxie, Fuzheng Huatan, and Quxie groups were much better (R values were 2.15±0.42, 2.11±0.23, 2.16±0.23 and 2.16±0.55, respectively), compared with the model group (R value: 3.00±0.00), the differences were statistically significant (all P < 0.05). ② Compared with the blank group, the mRNA expressions of MUC5AC, MUC5B, and MUC1 increased in the model group. But different components compatibility groups had no significant effects on the mucus secretion of BEAS-2B cells. ③ The comprehensive evaluation results of R value about each in vivo and in vitro index showed that ECC-BYFⅢ, Huoxue, Quxie, Bushen Huoxue, Fuzheng Huatan, Buqi Quxie groups significantly corrected the mucus hypersecretion (R values were 2.30±0.43, 2.33±0.44, 2.12±0.68, 2.27±0.64, 2.24±0.27 and 2.29±0.47, respectively), compared with the model group (R value: 3.00±0.00), the difference was statistically significant (all P < 0.01). The order was: Quxie > Fuzheng Huatan > Bushen Huoxue > Buqi Quxie > ECC-BYFⅢ > Huoxue. Conclusions:Different components compatibility of ECC-BYFⅢ had different effects on COPD mucus secretion. The components containing Huatan (Nobiletin) or Huoxue (Paeonol) showed a better inhibitory effect on mucus secretion.

Research progress of effective components of traditional Chinese medicine in anti-aging and anti-tumor mechanism / 药学学报

Increasing research have found a high correlation between senescence and tumor. Cellular senescence can inhibit tumorigenesis while the cellular microenvironment altered by senescent cells can promote the proliferation and metastasis of tumor cells. Some cellular signaling pathways are commonly involved in aging process and carcinogenesis. The deregulation and imbalance of these pathways results into senescence and tumor development. Thus, agents that balance these pathways may effective for anti-aging and anti-tumor. Traditional Chinese medicine (TCM) has been used for the activation of multiple signaling pathways and molecular targets both associated with aging and tumor, with few side effects. Therefore, the article reviewed the cellular signalings that cross between the aging and tumors, and on this basis, summarized the current effective components of TCM with anti-aging and anti-cancer properties, as well as the potential mechanisms of these components in the cross signalings, to provide new research strategies and perspectives for effective components of TCM to treat aging and tumors.

Development of an overall evaluation system for traditional Chinese medicine / 药学学报

This paper reviews modern science and technology with regard to traditional Chinese medicine (TCM) research methods, quality control, and discusses the establishment and improvement of the evaluation system for TCM, focusing on the following issues: 1) How to incorporate the efficacy of TCM in the overall evaluation of TCM quality; 2) how to quantify the efficacy and properties of TCM; 3) how to understand the correlation between the efficacy and properties of TCM and its application; 4) how to reflect the specificity of the effective components in the overall evaluation of TCM quality; and 5) how to reflect the quality value transfer of effective components in the whole process of production and metabolism in vivo to the overall evaluation of TCM quality. The overall quality evaluation of TCM needs to better reflect its clinically safety and effectiveness. It is suggested to establish a clinical quality assessment method based on the content of the chemical components of TCM to explore and establish an overall evaluation method of TCM quality that reflects the efficacy of TCM and conforms with clinical practice.

Effective-component compatibility of Bufei Yishen formula II inhibits mucus hypersecretion of chronic obstructive pulmonary disease rats by regulating EGFR/PI3K/mTOR signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: The effective-component compatibility of Bufei Yishen formula I (ECC-BYF I), a combination of 10 compounds, including total ginsenosides, astragaloside IV, icariin, and paeonol, etc., is derived from Bufei Yishen formula (BYF). The efficacy and safety of ECC-BYF I is equal to BYF. However, the composition of ECC-BYF I needs to be further optimized. Based on the beneficial effects of BYF and ECC-BYF I on chronic obstructive pulmonary disease (COPD), this study aimed to optimize the composition of ECC-BYF I and to explore the effects and mechanisms of optimized ECC-BYF I (ECC-BYF II) on mucus hypersecretion in COPD rats. MATERIALS AND METHODS: ECC-BYF I was initially optimized to six groups: optimized ECC-BYF I (OECC-BYF I)-A~F. Based on a COPD rat model, the effects of OECC-BYF I-A~F on COPD rats were evaluated. R-value comprehensive evaluation was used to evaluate the optimal formula, which was named ECC-BYF II. The changes in goblet cells and expression of mucins and the mRNA and proteins involved in the epidermal growth factor receptor/phosphoinositide-3-kinase/mammalian target of rapamycin (EGFR/PI3K/mTOR) pathway were evaluated to explore the effects and mechanisms of ECC-BYF II on mucus hypersecretion. RESULTS: ECC-BYF I and its six optimized groups, OECC-BYF I-A~F, had beneficial effects on COPD rats in improving pulmonary function and lung tissue pathology, reducing inflammation and oxidative stress, and improving the protease/anti-protease imbalance and collagen deposition. R-value comprehensive evaluation found that OECC-BYF I-E (paeonol, icariin, nobiletin, total ginsenoside, astragaloside IV) was the optimal formula for improving the comprehensive effects (lung function: VT, MV, PEF, EF50, FVC, FEV 0.1, FEV 0.1/FVC; histological changes: MLI, MAN; IL-1ß, IL-6, TNF-α, MMP-9, TIMP-1, T-AOC, LPO, MUC5AC, Collagen I and Collagen III). OECC-BYF I-E was named ECC-BYF II. Importantly, the effect of ECC-BYF II showed no significant difference from BYF and ECC-BYF I. ECC-BYF II inhibited mucus hypersecretion in COPD rats, which manifested as reducing the expression of MUC5AC and MUC5B and the hyperplasia rate of goblet cells. The mRNA and protein expression levels of EGFR, PI3K, Akt, and mTOR were increased in COPD rats and were obviously downregulated after ECC-BYF II administration. CONCLUSION: ECC-BYF II, which consists of paeonol, icariin, nobiletin, total ginsenoside and astragaloside IV, has beneficial effects equivalent to BYF and ECC-BYF I on COPD rats. ECC-BYF II significantly inhibited mucus hypersecretion, which may be related to the regulation of the EGFR/PI3K/mTOR pathway.

Safety assessment of spine MRI in deep brain stimulation patients.

OBJECTIVE: Many centers are hesitant to perform clinically indicated MRI in patients who have undergone deep brain stimulation (DBS). Highly restrictive guidelines prohibit the use of most routine clinical MRI protocols in these patients. The authors' goals were to assess the safety of spine MRI in patients with implanted DBS devices, first through phantom model testing and subsequently through validation in a DBS patient cohort. METHODS: A phantom was used to assess DBS device heating during 1.5-T spine MRI. To establish a safe spine protocol, routinely used clinical sequences deemed unsafe (a rise in temperature > 2°C) were modified to decrease the rise in temperature. This safe phantom-based protocol was then used to prospectively run 67 spine MRI sequences in 9 DBS participants requiring clinical imaging. The primary outcome was acute adverse effects; secondary outcomes included long-term adverse clinical effects, acute findings on brain MRI, and device impedance stability. RESULTS: The increases in temperature were highest when scanning the cervical spine and lowest when scanning the lumbar spine. A temperature rise < 2°C was achieved when 3D sequences were modified to 2D and when the number of slices was decreased by the minimum amount compared to routine spine MRI protocols (but there were still more slices than allowed by vendor guidelines). Following spine MRI, no acute or long-term adverse effects or acute findings on brain MR images were detected. Device impedances remained stable. CONCLUSIONS: Patients with DBS devices may safely undergo spine MRI with a fewer number of slices compared to those used in routine clinical protocols. Safety data acquisition may allow protocols outside vendor guidelines with a maximized number of slices, reducing the need for radiologist supervision.Clinical trial registration no.: NCT03753945 (ClinicalTrials.gov).

Effects of Guizhi Fuling Capsules and Its Main Components on Intestinal Flora of Primary Dysmenorrhea Model Rats / 中国药房

OBJECTIVE：To investigate the effects of Guizhi ful ing capsules and its principal components （paeoniflorin， paeonol and amygdalin ）on the intestinal flora of primary dysmenorrhea model rats. METHODS ：Female SD rats were randomly divided into normal group ，model group ，capsule group（Guizhi fuling capsule ，1 000 mg/kg），paeoniflorin group （15.0 mg/kg）， paeonol group （10.3 mg/kg）and amygdalin group （12.1 mg/kg），with 6 rats in each group. Except for normal group ，other groups were given estradiol benzoate subcutaneously on the back of rats and oxytocin intraperitoneally to induce primary dysmenorrhea model. From the 4th day after subcutaneous injection of estradiol benzoate ，normal group was given constant volume of normal saline intragastrically ；model group was given constant volume of 0.5％CMC-Na solution intragastrically ；administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. The writhing times and the contents of and MDA in uterus tissue of rats were determined ，and then com the contents of short-chain fatty acids （SCFAs）such as acetic acid，propionic acid ，butyric acid in colonic contents were detected by GC method. Using diver sity index as index ， Rep-PCR and Eric-PCR were used to evaluate the d iversity of intestinal flora in feces of rats. RESULTS ：Compared with normal group，the writhing times of rats were increased significantly in model group ；the contents of NO and MDA in uterus were increased significantly ，while the contents of acetic acid ，propionic acid and butyric acid in colonic contents and total content of SCFAs were decreased significantly （P＜0.05 or P＜0.01）；the number of DNA electrophoresis bands of intestinal flora was significantly reduced ，the brightness of most bands was significantly reduced ，and the diversity indexes （by Rep-PCR and Eric-PCR method ，hereinafter）1 h after administration were significantly reduced （P＜0.05 or P＜0.01）. Compared with model group，writhing times of rats were decreased significantly in capsule group ，paeoniflorin group and paeonol group ；the contents of NO in uterus of rats in capsule group and paeoniflorin group as well as the contents of MDA in capsule group ，paeoniflorin group and paeonol group were decreased significantly （P＜0.05 or P＜0.01）；the propionic acid content and total content of SCFAs in colon of rats in capsule group ，the contents of acetic acid ，propionic acid and butyric acid ，total content of SCFAs in paeoniflorin group as well as the contents of propionic acid and butyric acid ，total content of SCFAs in paeonol group were increased significantly；the content of isovaleric acid was decreased significantly in paeoniflorin group （P＜0.05 or P＜0.01）；DNA electrophoresis bands and its brightness of intestinal flora changed to different extents in administration groups ，and the diversity indexes of intestinal flora 1 h after administration were increased significantly in capsule group and paeoniflorin group ，while those indexes were decreased significantly in paeonol group and amygdalin group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Guizhi fuling capsules can significantly reduce writhing times and the contents of NO and MDA in uterus of primary dysmenorrhea model rats. At the same time ，the capsules also can regulate SCFAs content in colonic contents and intestinal flora diversity of rats. The above effects may be related to paeoniflorin and paeonol in the capsules.

3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences.

OBJECTIVE: Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients' accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research. METHODS: A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from "the worst" to "the most common."In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed. RESULTS: In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event. CONCLUSIONS: Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.

The hepatoprotective effects of Sedum sarmentosum extract and its isolated major constituent through Nrf2 activation and NF-κB inhibition.

BACKGROUND: Sedum sarmentosum, which is recorded in Chinese Pharmacopoeia, has been applied clinically to treat liver and gallbladder diseases. PURPOSE: This study aimed to explore the hepatoprotective effect of S. sarmentosum less polar extract (SSE) against ANIT-induced liver injury in rats, and the protective activity and mechanism of one major constituent isolated from this extract on D-GalN-induced human hepatic QSG7701 cell damage. METHODS: Rats were divided into groups and then administrated intragastrically with SSE at doses of 100, 200 and 400 mg/kg for 7 days. They were modeled in the experiments with ANIT (70 mg/kg) to induce liver injury after the sixth day administration. The levels of serum biochemical markers ALT, AST, ALP, GGT/γ-GT, DBiL, TBiL, ALB, TP, and bile flow rate, as well as the histopathology of the liver tissue were used as indices of liver damage and measured. The inflammatory response and oxidative stress were thought to be key contributors to ANIT-induced liver injury in rats. Therefore, the inflammatory mediators (TNF-α, IFN-γ, IL-4) and oxidative stress (ROS, SOD, GSH-PX) were measured in the serum and liver homogenates, respectively. Next, phytochemical research was performed to produce the main component, and the isolated compound was evaluated for its hepatoprotective activity against QSG7701 cell injured by D-GalN through the measurement of cell viabilities, ALT, AST, IL-1ß, TNF-α, IL-6, ROS, GSH-PX and SOD productions. Furthermore, the protein expression of the Nrf2 and NF-κB pathways were analyzed by western blotting. RESULTS: SSE had an obvious effect on the decreases of ALT, AST, ALP, GGT/γ-GT, DBiL and TBiL levels, the increases of ALB and TP levels in serum, and the ANIT-induced deceleration in bile flow for liver injury. Meanwhile, SSE pretreatment alleviated ANIT-induced liver pathological injuries exhibited by HE stain of the liver. Moreover, SSE significantly suppressed levels of pro-inflammatory cytokines TNF-α and IFN-γ, and elevated level of anti-inflammatory cytokine IL-4 in serum. SSE also attenuated oxidative stress by reducing ROS level and by enhancing antioxidative enzymes (SOD and GSH-PX) activities after ANIT administration in liver tissue. Further, the major compound shown in HPLC was isolated from SSE. Its structure was identified by the spectroscopic data analysis and comparison with literature values. The principal constituent had potent protective effect on D-GalN-induced QSG7701 cells damage in a dose dependent manner with survival rates of 58.2% and 69.5% at 10 µM and 20 µM, respectively. Its cytoprotective effect was associated with the reduction of ALT, AST, IL-1ß, TNF-α, IL-6 and ROS levels, and the elevation of GSH-PX and SOD productions in QSG7701 cells induced by D-GalN. Western blotting showed that this compound enhanced the expression of Nrf2, HO1, NQO1 and GCLC, and inhibited D-GalN-induced IκBα and NF-κB p65 phosphorylation. CONCLUSIONS: Current study showed that SSE treatment exerted a protective effect on ANIT-induced liver injury. The main compound δ-amyrone isolated from the extract was characterized as the effective component with hepatoprotective activity by promoting Nrf2 antioxidant defense and suppressing NF-κB inflammatory response.

Screening and validation of antithrombotic effective components group from Trichosanthes extract / 药学学报

To screen the antithrombotic effective components group of Trichosanthes extract, and to verify its pharmacodynamics and analyze its mechanism, the HPLC fingerprint of Trichosanthes extract (0.09, 0.45, 0.9 g·kg-1) was established, and the pharmacodynamic indexes of antithrombosis in rats with aspirin (0.01 g·kg-1) as positive control group were determined (the animals used in this experiment were approved by the Medical Ethics Committee of Wannan Medical College). The antithrombotic spectrum-activity relationship of Trichosanthes extract was studied and the effective antithrombotic ingredients group was screened by grey relational analysis. The monomer compound mixed solution (0.006, 0.03, 0.06 g·kg-1) was prepared according to the content of each component in the active component group, and the pharmacodynamics and action mechanism were studied to verify the correctness of the spectrum-effect relationship. The correlation between the 22 components of Trichosanthes extract and antithrombotic efficacy was different and showed dose-effect relationship. Cytosine, uracil, guanine, hypoxanthine, xanthine, adenine, guanosine, and adenosine are the main antithrombotic components of Trichosanthes extract. The ratio of cytosine, uracil, guanine, hypoxanthine, xanthine, adenine, guanosine and adenosine was 3∶12∶10∶5∶2∶8∶13∶14. Compared with the model group, the thrombus dry weight of each effective components group could be effectively reduced (P<0.01 or P<0.05), but there was no significant difference between each effective components group and the Trichosanthes extract group. Compared with the model group, the TXB2 content in group (0.06 g·kg-1, 0.03 g·kg-1) could be effectively reduced (P<0.01 or P<0.05), and the content of 6-keto-PGF1α could be increased in each group (P<0.01), and the TXB2/6-keto-PGF1α tended to be normal and showed a dose-effect relationship. The effect was better than that in the Trichosanthes extract group (0.45 g·kg-1) (P<0.01). The effective ingredients group has a good antithrombotic effect, its mechanism is to inhibit platelet aggregation and improve vascular endothelial function.

Multiple Effective Components Determination in Essential Oil from Curcuma phaeocaulis by GC-MS and Its Integrated Pharmacokinetic Study in Rats / 中国药房

OBJECTIVE:To develop the determination method for plasma concentration of effective components in essential oil from Curcuma phaeocaulis,and to study its integrated pharmacokinetics. METHODS:Sixteen rats were given the extract of essential oil from C. phaeocaulis 1.0 g/kg(by crude drug)intragastrically;blood samples 300-400 μL from orbit were collected 0, 0.17,0.5,1,2,2.5,3,4,6,8,10,12,24 h after medication. The plasma concentration of α-pinene,1,8-cineole,borneol, β-elemene,curcumol,germacrone and curdione in rats were determined by GC-MS. The determination was performed on DB-5 capillary column,using helium as carrier gas,at the flow rate of 1.2 mL/min. The injector temperature was 270 ℃,by temperature programming,and split ratio was 20∶1. The sample size was 1 μ L. The ion source was electrospray ion source. The selective reaction monitoring mode was used for the positive ion scanning in the range of m/z 20-500. Pharmacokinetic parameters of above effective components were calculated by using DAS 2.0 software. The weight coefficients were customized according to the proportion of AUC0-∞in the sum of AUC0-∞. The integrated pharmacokinetic parameters of multiple effective components in essential oil from C. phaeocaulis were calculated. RESULTS:The linear range of α-pinene,1,8-cineole,borneol,β-elemene, curcumol, germacrone, and curdione were 2.71-173.54, 7.76-496.88, 3.37-215.72, 21.68-1 387.50, 40.21-2 573.44, 24.84-3 179.69,47.78-3 057.81 ng/mL,respectively (r＞0.99). The lower limits of quantitation were 2.71,7.76, 3.37,21.68,40.21,24.84,47.78 ng/mL,respectively. The precision,accuracy and matrix effects were in line with related requirements of quantitative analysis of biological samples. The pharmacokinetic parameters of α-pinene,1,8-cineole,borneol, β-elemene,curcumol,germacrone,and curdione were as follows that cmaxwere (34.72 ± 9.97),(99.86 ± 5.54),(16.10 ± 3.37), (248.98±86.19),(673.75±104.15),(2 353.64±637.83),(2 420.04±708.51)ng/mL;tmaxwere(2.33±0.29),(0.67±0.29), (1.33±0.58),(1.83±0.76),(0.83±0.29),(0.89±0.18),(1.17±0.76)h;t1/2were(8.64±1.46),(8.98±1.63),(12.43± 2.88),(19.86 ± 4.05),(15.63 ± 5.50),(14.17 ± 4.13),(7.14 ± 0.67)h;AUC0-twere (189.78 ± 89.10),(454.74 ± 82.43), (100.55±8.27),(1 067.37±216.55),(3 154.16±405.94),(16 501.24±663.88),(12 524.92±3 222.10)ng·h/mL;AUC0-∞were(229.57±93.50),(524.32±81.67),(146.28±10.74),(2 092.70±416.18),(5 388.65±661.86),(28 198.87±4 102.62), (14 139.35 ± 3 109.19)ng·h/mL,respectively. After integration,the pharmacokinetic parameters were as follows that cmaxwas 1 880.94 ng/mL; tmaxwas 0.50 h; t1/2was 11.22 h;AUC0-twas 13 050.89 ng·h/mL;AUC0- ∞was 19 015.21 ng·h/mL. CONCLUSIONS: The method can be used for the detection of plasma concentration of effective components in rats;pharmacokinetic parameters of essential oil from C. phaeocaulis after integration are greatly different from single effective component,which can provide reference for characterization of its overall pharmacokinetics.