最新刊期
卷 34 ， 期 17 ， 2023
- 摘要：In order to promote the rational clinical use of gadolinium-based contrast agents （GBCA） and to provide a reference for physicians to prescribe such contrast agents and for pharmacists to review prescriptions， the consensus working group launched the preparation project of “Consensus on whole-process pharmaceutical care for GBCA” according to domestic and foreign guidelines and consensus. The Zhujiang Hospital of Southern Medical University took the lead and cooperated with clinical experts and pharmaceutical experts from several domestic medical institutions to discuss and summarize the basic pharmacological effect of GBCA， types， pharmacokinetics， pharmacodynamics， indications， contraindications， precautions， usage and dosage， adverse drug reactions， and finally forms the consensus. The main contents of this consensus include an overview of various types of GBCA， rational clinical use of drugs， security management and whole-process pharmaceutical care process， etc.， for reference by physicians and pharmacists in medical institutions at all levels.关键词：rational drug use;adverse drug reactions;pharmaceutical care;whole-process;consensus
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发布时间：2023-09-14 - 摘要：ince the Guangdong alliance launched the centralized procurement of Chinese patent medicine， manufacturers have engaged in fierce price competition to obtain the qualification for selection. In order to ensure that manufacturers have lowered the price without decreasing quality， the evaluation criteria for the quality of Chinese patent medicine is constructed on the basis of the characteristics of traditional Chinese medicine. The evaluation criteria consist of the production process and therapeutic effect evaluation. The evaluation indicators involve raw materials， processing and clinical use covering the whole life cycle of Chinese patent medicine. The evaluation of production process includes 3 secondary indicators （the quality of traditional Chinese medicine， the quality of traditional Chinese medicine decoction pieces and the quality of Chinese patent medicines） and 13 tertiary indicators （standardized production， quality inspection， processing specifications， technical processes， safety risk control， etc.）， which fully reflect the quality control of key links in the production of Chinese patent medicine. The therapeutic effect evaluation includes 5 secondary indicators （theoretical origin of formulation， proactive research by production enterprises， evidence-based medical evidence， clinical use， and technological embodiment） and 18 tertiary indicators （theoretical sources， post-market effectiveness re-evaluation， clinical guidelines， expert consensus， etc.） to assess the quality and efficacy of Chinese patent medicine from multiple perspectives and levels. This study is a useful supplement to the scheme of centralized procurement of Guangdong alliance， which can not only provide data support for selecting “low-cost and high-quality” Chinese patent medicine， but also provide information reference for hospitals to make procurement decisions.关键词：centralized procurement;quality evaluation;quality control;therapeutic effect
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发布时间：2023-09-14 - 摘要：OBJECTIVETo study the improvement effects of Shaoyao gancao decoction （SGD） on acute lung injury （ALI） in rats and its effects on the intestinal flora.METHODSSixty SD rats were randomly divided into normal group （CON group， normal saline）， model group （MOD group， normal saline）， positive control group （DEX group， 5 mg/kg dexamethasone）， SGD low-dose， medium-dose and high-dose groups （SGD-L， SGD-M， SGD-H groups， 5.8， 11.6， 23.2 g/kg， calculated by crude drug）， with 10 rats in each group. Each group was given relevant medicine 10 mL/kg intragastrically， for 7 consecutive days. Thirty minutes after the last administration， CON group was given constant volume of normal saline via airway infusion， and other groups were given lipopolysaccharide （5 mg/kg） via airway infusion to induce ALI model. After 12 hours of modeling， the lung tissue wet/dry weight ratio was calculated， and the contents of interleukin 1β （IL-1β）， IL-6 and tumor necrosis factor α（TNF-α） in rat bronchial alveolar lavage fluid （BALF） were all detected； the pathological changes of lung tissue were observed after hematoxylin-eosin staining. The intestinal flora of rat feces was analyzed by 16S rRNA sequencing technology， and the correlation of differential bacteria genera with inflammatory factors was also analyzed.RESULTSCompared with MOD group， the infiltration of inflammatory cells in the lung tissue of rats in each SGD dose group was decreased， and the thickening of alveolar septum and pulmonary edema improved； lung tissue wet/dry weight ratio， the levels of IL-1β， IL-6 and TNF-α in BALF significantly decreased （P＜0.05 or P＜0.01）. SGD （low dose） could improve the intestinal flora disorder in ALI rats， restore the diversity and richness of intestinal flora， regulate the structure of flora， reduce the abundance of Lactobacillus， Streptococcus and Escherichia-Shigella， and increase the abundance of Firmicutes， Lachnospira， Ruminococcus， Clostridia， Dubosiella and Akkermansia. Through correlation analysis， it was found that the relative abundance of Lactobacillus， Streptococcus and Escherichia-Shigella was positively related to the levels of inflammatory factor IL-1β， IL-6 and TNF-α （P＜0.05 or P＜0.01）. The relative abundance of Lachnospira， Dubosiella， Firmicutes was significantly negatively correlated with the levels of inflammatory factors mentioned above （P＜0.05 or P＜0.01）.CONCLUSIONSSGD may improve ALI by reducing lung tissue injury and inflammatory response and regulating flora structure in rats.关键词：acute lung injury;intestinal flora;16S rRNA sequencing;inflammatory response
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发布时间：2023-09-14 - 摘要：OBJECTIVETo establish a quantitative analysis of multi-components by single marker （QAMS） method based on a variety of internal reference substances for the content determination of 6 components in Jinlian qingre granules， such as mangiferin， 2″-O-β-L-galactopyranosylorientin， orientin， veratric acid， vitexin， harpagoside.METHODSThe determination was performed on Agilent Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution （gradient elution） at the flow rate of 1 mL/min. The column temperature was 30 ℃， and the detection wavelength was set at 270 nm. Taking orientin， vitexin and 2″-O-β-L-galactopyranosylorientin as internal references， the relative correction factors （RCF） of the other 5 components to be determined and internal substances were determined by QAMS. The contents of 6 components in 21 batches of Jinlian qingre granules were calculated and then compared with the results of the external standard method.RESULTSThe contents of mangiferin， 2″-O-β-L-galactopyranosylorientin， orientin， veratric acid， vitexin and harpagoside in 21 batches of samples were determined by QAMS in the range of 0.234-0.516， 1.804-2.270， 2.143-2.606， 0.190-0.223， 0.594-0.782， 0.080-0.152 mg/g； the contents of them determined by external standard method were 0.235-0.523， 1.798-2.265， 2.137-2.599， 0.190-0.224， 0.597-0.786， 0.077-0.151 mg/g， respectively. The percentage difference between the results measured by the two methods should not exceed 4.00%.CONCLUSIONSQAMS has been constructed for the simultaneous determination of 6 components in Jinlian qingre granules based on a variety of internal reference substances. The results obtained by this method are not significantly different from those obtained by the external standard method， and can be used for the quality control of Jinlian qingre granules.关键词：quantitative analysis of multi-components by single marker;mangiferin;2″-O-β-L-galactopyranosylorientin;orientin;veratric acid;vitexin;harpagoside;content determination
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发布时间：2023-09-14 - 摘要：OBJECTIVETo establish a method for simultaneous determination of 15 bile acids in Tongren niuhuang qingxin pills， and to determine the contents of 15 batches of samples.METHODSUsing dehydrocholic acid as internal standard， the determination was performed by ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method. The determination was performed on Hypersil GOLD C18 column with methanol-0.1% formic acid solution as the mobile phase by gradient elution at the flow rate of 0.2 mL/min. The column temperature was 40 ℃， and the sample size was 2 µL. Using heated electrospray ion source， parallel reaction monitoring mode scanning was performed in negative ion mode. SPSS 24.0 software was used for chemical pattern recognition analysis of content determination results.RESULTSThe 15 bile acid components had a good linear relationship with peak area （all R2≥0.998 9）； their precision， repeatability and stability were all good （all RSD≤5.49%）； the average recoveries were 93.8%-105.7% （RSD was 0.5%-5.8%）. The average contents of taurocholic acid， 7-oxodeoxycholic acid， 12-dehydrocholic acid， glycocholic acid， 3-oxo-7α， 12α-hydroxy-5β-cholanoic acid， taurochenodeoxycholic acid， 3α-hydroxy-7-oxo-5β-cholanic acid， hyocholic acid， taurodeoxycholic acid sodium salt hydrate， hyodeoxycholic acid， cholic acid， glycochenodeoxycholic acid， glycodeoxycholic acid， chenodeoxycholic acid and deoxycholic acid were 670.56， 25.97， 10.54， 280.12， 4.04， 29.81， 182.98， 813.55， 120.95， 220.31， 797.37， 18.37， 68.59， 30.13， 59.82 μg/g， respectively. Both cluster analysis and principal component analysis divided 15 batches of Tongren niuhuang qingxin pills into 2 categories， S1-S12 as one category and S13-S15 as the other category.CONCLUSIONSThe established method is accurate， sensitive and specific， and can determine many types of bile acids. It also can quickly achieve the quantitative analysis of 15 bile acids in Tongren niuhuang qingxin pills， which is suitable for the quality control of this drug.关键词：ultra-high performance liquid chromatography-tandem mass spectrometry;bile acids;content determination;chemical pattern recognition analysis
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发布时间：2023-09-14 - 摘要：OBJECTIVETo study the intervention effect of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis （AD） mice，and to explore the mechanism of action.METHODSFifty mice were randomly divided into 5 groups，i.e. normal control group （group A），model group （group B），dexamethasone intervention group （positive control，group C），H. rhamnoides oil intervention group （group D），dexamethasone+H. rhamnoides oil intervention group （group E），with 10 mice in each group. Except for group A，other groups were given 2，4-dinitrochlorobenzene+staphylococcal enterotoxin B to induce the AD mice model. Starting from the 7th day of the experiment，groups C，D and E were given dexamethasone （1.5 mg/kg） and/or H. rhamnoides oil （10 mL/kg） intragastrically，once a day，for 28 consecutive days. After the last medication，the pathomorphological changes of ear tissue were observed by HE staining； the serum levels of immunoglobulin E （IgE） and interleukin 4（IL-4） were detected by enzyme-linked immunosorbent assay. Positive cell count of glucocorticoid receptor α （GRα） and GRβ in the ear tissue of mice was detected by tyramide signal amplification. The expressions of GRα protein，GRβ protein，and protein kinase B （AKT）/ribosomal protein S6 kinase 1，S6K1 （S6K1） signaling pathway-related proteins were determined by Western blot assay.RESULTSCompared with group B，the skin inflammation in the left ear of the mice was significantly reduced in groups C，D and E，the serum levels of IgE and IL-4 were decreased significantly in groups D and E （P＜0.05），while the number of GRα positive cells and GRα protein expression were increased significantly （P＜0.05）； the protein levels of G protein inhibitory subunit 1 （Gαi1），Gαi3，phosphorylated S6K1 （p-S6K1） and phosphorylated AKT （p-AKT） were decreased significantly （P＜0.05）； the number of GRβ positive cells and protein expression of GRβ was decreased significantly in group E（P＜0.05）. Compared with group C，the skin inflammation in the left ear of the mice was almost clear away in group E，the serum levels of IgE and IL-4 were decreased significantly （P＜0.05）； the number of GRα positive cells and GRα protein expression were increased significantly in groups D and E （P＜0.05）； the protein levels of GRβ，Gαi1，p-S6K1 and p-AKT were all decreased significantly in groups D and E（P＜0.05）； and protein level of Gαi3 was decreased significantly in group E （P＜0.05）.CONCLUSIONSH. rhamnoides oil has an intervention effect on superantigen-induced glucocorticoid resistance of AD mice，which may be exerted by inhibition of the Gαi1/3-induced AKT/S6K1 signaling pathway.关键词：superantigen;atopic dermatitis;glucocorticoid resistance;AKT/S6K1 signaling pathway
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发布时间：2023-09-14 - 摘要：OBJECTIVETo study the pharmacokinetics of small molecule inhibitor SYHA1809 in Beagle dogs.METHODSLC-MS/MS method was adopted. Beagle dogs were randomly divided into single intravenous administration group （3.75 mg/kg）， single low-dose intragastric administration group （3.75 mg/kg）， single medium-dose intragastric administration group （7.5 mg/kg）， single high-dose intragastric administration group （15 mg/kg） and multiple intragastric administration group （7.5 mg/kg， once a day， for 7 consecutive days）， with 6 dogs in each group， half male and half female. The plasma samples of Beagle dogs were collected in each group according to the set time point， and underwent LC-MS/MS quantitative analysis after preprocessing. The pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.0 software using obtained data.RESULTSAfter intravenous injection， CL of SYHA1809 in Beagle dogs was （2.70±0.48） mL/（min·kg）， steady-state distribution volume was 0.757 L/kg， and t1/2 was （3.35±1.36） h； after single intragastric administration of low-dose， medium-dose and high-dose of SYHA1809， average tmax was （0.53±0.02） h， and the blood drug concentration increased with the increase of dose； after single intragastric administration of 3.75 mg/kg SYHA1809， the absolute bioavailability was 83.5%； within the dose range of 3.75-15 mg/kg， the increase in cmax and AUC of SYHA1809 was positively correlated with the dose； after intragastric administration of 7.5 mg/kg SYHA1809 for 7 consecutive days， the pharmacokinetic parameters of SYHA1809 were comparable to those of a single intragastric administration of the same dose， with no statistically significant difference （P＞0.05）.CONCLUSIONSSYHA1809 is absorbed rapidly in Beagle dogs， shows the dose-dependent blood concentration， high bioavailability， no obvious accumulation after multiple intragastric administration， and good pharmacokinetic behavior.关键词：SYHA1809;LC-MS/MS;pharmacokinetics
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发布时间：2023-09-14 - 摘要：OBJECTIVETo explore the effects of Yupingfeng granules on the improvement of epithelial barrier function and the inhibition of tumor metastasis by regulating epithelial-mesenchymal transition （EMT）.METHODSThirty C57BL/6 mice were randomly divided into the normal group （distilled water），model group （distilled water） and Yupingfeng granule group （40 g/kg），with 10 mice in each group. The model group and Yupingfeng granule group were inoculated with Lewis lung cancer cells subcutaneously in the right armpit to induce the spontaneous lung metastasis model. After modeling，each group was given water/relevant medicine intragastrically，once a day，for 15 consecutive days. The effects of Yupingfeng granules on tumor metastasis were investigated by observing or determining the pathomorphology of lung tissue，metastatic lesion count on the surface of the lung，tumor metastatic lesion and the expression of carcinoembryonic antigens. qRT-PCR and Western blot assay were used to detect the mRNA and protein expressions of β-catenin，E-cadherin and vimentin in the lung tissue of mice.RESULTSCompared with the model group，the total number of pulmonary metastases on the surface was decreased significantly in Yupingfeng granule group （P＜0.05），the general morphology of lung tissue was recovered，and the expression of carcinoembryonic antigen in lung tissue was significantly decreased （P＜0.05）. mRNA and protein expressions of E-cadherin in lung tissue were significantly increased （P＜0.05），while mRNA and protein expressions of vimentin and β-catenin were significantly decreased （P＜0.05）.CONCLUSIONSYupingfeng granules can inhibit EMT by regulating the expression of β-catenin，thus improving epithelial barrier function，and inhibiting the ability of tumor cells to invade and metastasize.关键词：epithelial-mesenchymal transition;epithelial barrier;tumor metastasis;β-catenin
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发布时间：2023-09-14 - 摘要：OBJECTIVETo optimize the water extraction process of Maxing kechuan granules.METHODSWith the contents of ephedrine hydrochloride， bergenin， prim-O-glucosylcimifugin， 5-O-methylvisamin， naringin and hesperidin and the rate of extraction as the evaluation indexes， the weight was determined by the analytic hierarchy process（APH）-entropy weight method， and the comprehensive score was calculated as the response value. Based on the single-factor test， the Box-Behnken response surface method was used to investigate the factors， and the best water extraction process of Maxing kechuan granules was optimized； process validation was also carried out.RESULTSThe best water extraction process of Maxing kechuan granules optimized was as follows： soaking for 40 minutes， adding 8 times water， and extracting for 180 minutes. After three validation tests， the comprehensive score was 94.82 （RSD＝0.96%， n＝3）， which had a small difference from the predicted value of 94.64.CONCLUSIONSThe water extraction process of Maxing kechuan granules is stable and reliable， which can provide a reference for the development of the preparation.关键词：water extraction process;Box-Behnken response surface method;analytic hierarchy process;entropy weight method;weight;comprehensive score
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发布时间：2023-09-14 - 摘要：OBJECTIVETo study the protective effects of Dachengqi decoction （DCQD） on intestinal septic mice， and to explore the possible mechanisms from the Toll-like receptor 4（TLR4）/myeloid differentiation factor 88（MyD88） signaling pathway.METHODSThe SPF male C57BL/6J mice were randomly divided into Sham group， Sham+DCQD-H group， model （CLP） group， DCQD-L group， DCQD-H group and Positive group. The model of intestinal sepsis was established by cecal ligation and puncture in CLP group， DCQD-L group， DCQD-H group and Positive group. Three days before the operation and seven days after the operation， DCQD-L group and DCQD-H group were given DCQD intragastrically at 4， 8 g/kg （calculated by crude drug）， respectively. Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation （at 50 000 U/kg）. In Sham group and Sham+DCQD-H group， only cecum of mice was exposed without ligation and puncture. Sham+DCQD-H group was given DCQD intragastrically （8 g/kg，calculated by crude drug） 3 days before the operation and 7 days after the operation. Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day， for 10 consecutive days. After the operation， the severity of sepsis was assessed， and the 7 d survival rate of mice was assessed. One hour after the last medication， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum and ileum of mice were determined； the pathological and morphological changes of mice’s liver， lung， kidney and ileum were observed； mRNA expressions of the TLR4 and MyD88 in ileum were tested.RESULTSCompared with CLP group， sepsis score， the levels of TNF-α and IL-6 in serum and ileum （except for IL-6 in ileum of DCQD-L group）， damage score of the liver， lung， kidney and ileum， mRNA expressions of TLR4 and MyD88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group （P＜0.05 or P＜0.01）， while 7 d survival rate （except for DCQD-L group） was increased significantly （P＜0.05）. The damage to liver tissue in mice was significantly improved， and inflammation infiltration and apoptosis were reduced； lung tissue damage had been alleviated， with varying degrees of improvement in alveolar atrophy， bleeding and edema； the renal tissue damage was improved and weakened dilation of renal tubular lumen was weakened； the damage and edema of ileal tissue were significantly improved.CONCLUSIONSDCQD may exert a protective role on intestinal septic model mice. The mechanism may be related to the inhibition of systemic inflammation， the reduction of multiple organ damage， and down-regulation of TLR4/MyD88 signaling pathway.关键词：sepsis;inflammatory factor;organ damage;TLR4/MyD88 signaling pathway
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发布时间：2023-09-14 - 摘要：OBJECTIVETo investigate the improvement effects and mechanism of scutellarin （Scu） on neuroinflammation in rats with traumatic brain injury （TBI）.METHODSThe modified Feeney method was applied to construct TBI rat model. The rats were randomly grouped into TBI group，Scu low-dose group （40 mg/kg），Scu high-dose group （80 mg/kg），cyclic guanylate-adenylate synthase （cGAS） inhibitor group （cGAS inhibitor RU.521，450 μg/kg），with 24 rats in each group. Other 24 rats were included in the sham operation group. The modified neurological deficit score （mNSS） method was applied to assess the neurological function of rats； the brain water content of rats was measured by dry/wet specific gravity method； hematoxylin-eosin and TdT-mediated dUTP nick-end labeling staining were applied to observe the pathological changes and apoptosis of brain tissue in rats； the levels of interferon-β （IFN-β），CXC chemokine ligand-10 （CXCL10），tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rat brain tissue were detected by enzyme-linked immunosorbent assay； Western blot method was applied to detect the expression of cGAS/interferon gene stimulating protein （STING） signal pathway-related proteins in brain tissue of rats.RESULTSCompared with the sham operation group，the mNSS，brain water content，apoptosis rate，the contents of IFN-β，CXCL10，TNF-α and IL-6，and the relative expressions of cGAS and STING proteins in TBI group increased significantly （P＜0.05）； there were edema，bleeding and pathological damage to neurons in the brain tissue. Compared with TBI group，the above indicators and pathological changes of rats in administration groups were improved significantly （P＜0.05），and the effect of Scu was in a dose-dependent manner （P＜0.05）； however，there was no statistically obvious difference in the above indicators between the Scu high-dose group and the cGAS inhibitor group （P＞0.05）.CONCLUSIONSScu may alleviate neuroinflammation，reduce brain tissue damage and apoptosis，and promote the recovery of neural function in TBI rats by inhibiting the activation of cGAS/STING signaling pathway.关键词：traumatic brain injury;neuroinflammation;cyclic guanylate-adenylate synthase;interferon gene stimulating protein
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发布时间：2023-09-14 - 摘要：OBJECTIVETo explore the material basis and mechanism of expectorant and cough relief effects of the fruits of Phellodendron chinense var. glabriusulum Schneid.METHODSThe expectorant and cough relief effects of volatile oil and water decoction of the fruits of P. chinense var. glabriusulum Schneid. were studied by ammonia water cough induction and drug expectorant model mice experiments； GC-MS and UPLC-MS technologies were used to identify its volatile oils and non-volatile components of the fruits of P. chinense var. glabriusulum Schneid. The active ingredients， core targets and pathways of expectoration and cough relief were analyzed by network pharmacology.RESULTSThe volatile oil （0.8， 0.2 g/kg， calculated by volatile oil） and water decoction （12， 3 g/kg， calculated by crude drug） of the fruits of P. chinense var. glabriusulum Schneid. both had obvious expectorant and cough relief effects， and showed obvious dose-dependent relationship. A total of 38 volatile oil components were identified from the medicinal herbs， and the relative percentage contents of 8 components were greater than 1%， such as α-pinene， myrcene， β-caryophyllene， germanene D， isospathulenol； a total of 69 non-volatile oil components were identified， mainly including phenolic compounds， alkaloids， and flavonoids. The active ingredients screened from the identified components included 13 compounds such as α-pinene， myrcene， chlorogenic acid， luteolin， berberine. There were a total of 55 intersection targets with diseases， and the core targets were tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， vascular endothelial growth factor A （VEGFA）， serine/threonine kinase proteins （AKT1） and Toll-like receptor 4 （TLR4）. The molecular docking results showed that the active ingredients and the core targets had good binding ability. GO functional analysis found that the targets were significantly enriched in biological processes such as the reaction affecting lipopolysaccharides， the positive regulation of peptidyl serine phosphorylation， and the positive regulation of the biosynthesis process of nitric oxide. KEGG pathway enrichment analysis found that the targets were significantly enriched in the signaling pathways such as cancer， non-small cell lung cancer， proteoglycans in cancer.CONCLUSIONSFruits of P. chinense var. glabriusulum Schneid. have obvious expectorant and cough relief effects， and its material basis may be α-pinene， myrcene， chlorogenic acid， luteolin， berberine， etc.， and mainly act on TNF， EGFR， VEGFA， AKT1， TLR4 and its significantly enriched signaling pathway.关键词：volatile oil;water decoction;expectoration;cough relief;network pharmacology;material basis;mechanism of action
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发布时间：2023-09-14 - 摘要：OBJECTIVETo explore the mechanism of Kuaisong yin in the prevention and treatment of constipation.METHODSSlow transit constipation （STC） model was established with Compound difenoxylate tablet in mice and rats. Two batches of mice were divided into blank group， model group， positive control group （Maren soft capsule， 0.64 g/kg）， Kuaisong yin low-dose， medium-dose and high-dose groups （3.2， 6.4， 12.8 g/kg）， with 10 mice in each group. The effect of Kuaisong yin on constipation in mice was evaluated by intestinal propulsion experiment and defecation experiment. Rats were divided into blank group， model group， positive control group （Maren soft capsule，0.36 g/kg）， Kuaisong yin low-dose and high-dose groups （2.4， 4.8 g/kg）， with 7 or 8 rats in each group. They were given relevant medicine once a day for 1 week. The metabonomics of serum and urine of rats were analyzed by UPLC-Q-TOF-MS/MS technology.RESULTSCompared with model group， the ink propulsion rate and 5 h defecation volume of mice in Kuaisong yin high-dose group were significantly increased （P＜0.05）； the first defecation time of mice in Kuaisong yin medium-dose and high-dose groups was significantly shortened， and the quality of defecation was significantly reduced within 5 h （P＜0.05 or P＜0.01）. Serum metabonomics screened 16 compounds （such as proline， propionylcarnitine， hemolytic phosphatidylcholine， etc.） and 6 metabolic pathways （such as sphingomyelin metabolism， arginine and proline metabolism， sphingolipid biosynthesis-lactose and neolactone series）. Urine metabonomics screened 20 different metabolites （such as prostaglandin A2， L-valine， phosphatidylcholine， sphingomyelin， etc.） and 8 metabolic pathways （such as valine， leucine and isoleucine biosynthesis， sphingomyelin metabolism， pyruvate metabolism， etc.）.CONCLUSIONSKuaisong yin can play a role in improving constipation by regulating different metabolites such as hemolytic phosphatidylcholine， phosphatidylcholine， prostaglandin A2， L-valine， proline， and regulating metabolic pathways such as multiple amino acid metabolism， sphingomyelin metabolism， etc.关键词：constipation;pharmacodynamics;metabolomics;slow transit constipation
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发布时间：2023-09-14 - 摘要：OBJECTIVETo investigate the effects of andrographolide （Andro） on angiogenesis in rats with diabetic foot and to explore its mechanism of action based on the Hippo-Yes-associated protein （YAP） signaling pathway.METHODSThe rat model of type 2 diabetes was established by using low-dose streptozotocin combined with high-fat and high-glucose diet. On the basis of successful modeling， the rat model of diabetes foot was established by scalding. Model rats were randomly divided into 5 groups with 12 rats in each group： model group， Andro low-dose， medium-dose， and high-dose groups （1， 10， and 20 mg/kg）， as well as inhibitor group （20 mg/kg Andro+100 mg/kg of verteporfin， an specific inhibitor of Hippo-YAP signaling pathway）； other 12 healthy rats were included in the Control group. Rats in each group were intragastrically and intraperitoneally injected with solvents or corresponding drugs， once a day， for 2 consecutive weeks. The wound healing， fasting blood glucose （FBG） and fasting insulin （FINS） were detected in rats after medication. HE staining was performed to observe the tissue damage and capillary number of rat trauma； the number of endothelial progenitor cells （EPCs） in peripheral blood of rats was counted by using flow cytometry； the contents of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） in rats were determined by fully automatic biochemical analyzer； the expressions of hypoxia-inducible factor 1α （HIF-1α）， vascular endothelial growth factor （VEGF） and Hippo-YAP signaling pathway-related proteins in the traumatic tissues of rats in each group were detected by Western blot.RESULTSCompared with Control group， the wound healing rate， capillary number， the proportion of EPCs， HDL-C content， as well as the protein expression levels of HIF-1α and VEGF and the phosphorylation levels of mammalian Ste20-like kinase 1， large tumor suppressor gene 1 and YAP proteins were significantly reduced in the model group， while the FBG， FINS levels and TC， TG and LDL-C contents were significantly increased （P＜0.05）. Compared with model group， the above indexes were significantly reversed in Andro low-dose， medium-dose and high-dose group， in a dose-dependent manner （P＜0.05）； verteporfin attenuated the above reversal effect of Andro （P＜0.05）.CONCLUSIONSAndro has the effects of lowering blood glucose and blood lipids， promoting blood vessel formation and wound healing in rats with diabetic foot， and its mechanism of action may be related to the activation of Hippo-YAP signaling pathway.关键词：diabetic foot;angiogenesis;Hippo-YAP signaling pathway
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发布时间：2023-09-14 - 摘要：OBJECTIVEMETHODSBy sorting out the situation and pricing methods of multi-indication drugs in China’s health insurance negotiation in recent years， the experience of typical countries （Sweden， Germany， Britain， Italy， etc.） in the value measurement， access and management of multi-indication drugs were explored with 3 methods， namely， branded pricing， weighted average bidding pricing， and single bidding pricing under the risk sharing agreement. The advantages and disadvantages of the 2 types of multi-indication drug pricing methods， such as single bidding pricing and indication-based pricing， and conditions of use were explored， so as to put forward a pricing method suitable for multi-indication drugs in China.RESULTSCONCLUSIONSThe pricing of multi-indication drugs by single bidding pricing mode has certain disadvantages at this stage， and should be supplemented and improved by agreement pricing. Based on international experience， China can explore a reasonable management mode of drug indications， adopt a pricing mode with agreement pricing as the main mode and multiple pricing modes as the coexisting mode， and promote the development of pharmacoeconomic evaluation and the improvement of drug use information collection mechanism.＆To explore the pricing methods of multi-indication drugs suitable for China from the economic perspective.关键词：negotiated pricing;value pricing;medicare insurance access;payment standards for medicare insurance drug
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发布时间：2023-09-14 - 摘要：OBJECTIVETo accurately identify the rare adverse drug reactions （ADR） of vancomycin-pancytopenia in order to promote its safe use. METHODS Through a case report of a child with suppurative hip arthritis who developed pancytopenia combined with delayed drug fever caused by intravenous infusion of vancomycin，Naranjo score method and related literature were used to summarize the association between the ADR and vancomycin and its possible mechanism， and suggestions for rational use of vancomycin in pediatric patients were put forward. RESULTS &CONCLUSIONS The association of pancytopenia combined with delayed drug fever and vancomycin in this child is “very likely”. In clinical practice， it is difficult to distinguish between pancytopenia combined with delayed drug fever from fever and hematopenia caused by aggravation of infection. Medical staff should increase their awareness of vancomycin rare ADR such as pancytopenia， and pharmacists should assist medical staff in timely screening for ADR. The initial dose of vancomycin infusion for children should start from 60 mg/（kg·d），and the blood concentration should be monitored 48 h after the first infusion and the dose should be adjusted in time to maintain the valley concentration of vancomycin at 5-15 mg/L to prevent the occurrence of ADR caused by excessive blood concentration. For children who have been using vancomycin for more than one week，the blood routine should be rechecked regularly. Once pancytopenia occurs，the drug should be stopped immediately，and symptomatic treatment should be given according to the situation.关键词：children;pancytopenia;delayed drug fever;case analysis
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发布时间：2023-09-14 - 摘要：OBJECTIVETo conduct data mining on drugs causing liver failure in underage populations based on the FDA Adverse Event Reporting System （FAERS） database， so as to provide reference for clinical use of related drugs.METHODSThe data on reported adverse drug event （ADE） of liver failure in this population （under 18 years old） from the first quarter of 2013 to the third quarter of 2022 were retrieved from the FAERS database for mining and analysis； they were divided into infants（≤1 year old）， young children（＞1-＜6 years old）， children（6-＜12 years old） and adolescents（12-＜18 years old） according to the age. The reporting odds ratio （ROR）， proportional reporting ratio and Bayesian confidence propagation neural network of the proportional imbalance method were used to screen ADE signals.RESULTSA total of 1 051 ADE reports of liver failure were collected from the underage population involving 60 drugs. The highest incidence was found in adolescents （410 cases， 39.01%）， followed by young children （297 cases， 28.26%）. The instructions of 14 drugs did not mention hepatobiliary system injury and liver failure risk， including 31 cases of levetiracetam （2.95%），18 cases of metronidazole （1.71%）， 16 cases of each of topiramate and methylprednisolone （1.52% each）， 12 cases of dexamethasone （1.14%）， 11 cases of tisagenlecleucel （1.05%）， 10 cases of each of ferrous sulfate， metformin and busulfan （0.95% each）， 9 cases of propofol （0.86%）， 8 cases of onasemnogene abeparvovec （0.76%）， 5 cases of each of diphenhydramine and omeprazole （0.48% each）， 4 cases of sebeliesterase α （0.38%）， totaling 165 cases， accounting for 15.70% of the total reported cases. Metformin was contrary to the known liver safety， and metronidazole and levetiracetam were new risk signals， which caused more serious clinical outcomes.CONCLUSIONSFourteen new pharmacovigilance signals which cause liver failure in the underage population are found in this study； the liver function of patients should be closely monitored when using these drugs. Among those drugs， metformin neither undergoes liver metabolism nor has been reported in the relevant literature， and the liver-related ADE caused by metformin deserves further attention. The clinical outcomes caused by metronidazole and levetiracetam are relatively serious and need to be given sufficient attention.关键词：liver failure;FDA adverse event reporting system;data mining;medication safety;adverse drug event
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发布时间：2023-09-14 - 摘要：OBJECTIVETo investigate the risk factors for hypokalemia caused by amphotericin B liposome， and to provide reference for clinical use of drugs.METHODSA retrospective analysis was used to collect the information of patients who used amphotericin B liposome during the hospitalization in First Affiliated Hospital of Hainan Medical College from January 2012 to December 2021. The details of use information about amphotericin B liposome and the potassium supplementation were collected. The patients were divided into hypokalemia group and normal group according to the occurrence of hypokalemia. Univariate and multi-variate Logistic regression analyses were used to analyze the risk factors for hypokalemia induced by amphotericin B liposome.RESULTSOf the 121 patients included in this analysis， 60 patients were in hypokalemia group， 61 patients were in normal group. The following parameters of the hypokalemic group were significantly higher or longer than those of the normal group， such as the maintenance dose， cumulative dose and maximum daily dose （in patients with severe hypokalemia） of amphotericin B liposome， treatment days， the maintained days of hypokalemia， daily dose of potassium supplement （in patients with moderate or severe hypokalemia）， the duration of potassium supplement （in patients with moderate hypokalemia）. Results of single factor analysis showed that the cumulative dose of amphotericin B liposome ≥200 mg and the duration of treatment ≥5 days were independent risk factors of hypokalemia caused by this drug （P＜0.05）. Multi-variate analysis results showed that the presence of basic hypokalemia， body weight ＜50 kg， cumulative dose of amphotericin B liposome ≥200 mg and the duration of treatment ≥5 days were the independent risk factors for hypokalemia caused by amphotericin B liposome （P＜0.05）.CONCLUSIONSThe incidence of hypokalemia caused by amphotericin B liposome is high， the independent risk factors for hypokalemia include cumulative dose ≥200 mg， treatment days ≥5 days， the presence of basic hypokalemia and body weight ＜50 kg. It is suggested that serum potassium should be elevated to normal level before amphotericin B liposome treatment， and the level of serum potassium should be monitored during medication to reduce the occurrence of hypokalemia.关键词：hypokalemia;risk factors
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发布时间：2023-09-14 - 摘要：OBJECTIVETo investigate the efficacy and safety of different doses of zinc in the treatment of diarrhea in children， and to provide a reference for clinical safe and rational drug use.METHODSRetrieved from PubMed， Cochrane Library， Embase database， randomized controlled trials about zinc （zinc group） versus placebo or conventional treatment （control group） in the treatment of diarrhea in children were collected from the inception to October 2022. Then， the quality of the included literature was evaluated by the Cochrane Handbook 6.0， and meta-analysis and sensitivity analysis were performed by RevMan 5.3 software.RESULTSFinally， 25 RCTs were included， with a total of 8 618 children. The results of meta-analysis showed that in terms of duration of diarrhea， in zinc ＜20 mg group， the zinc group was significantly shorter than the control group [SMD＝ －0.39， 95%CI（－0.71， －0.08）， P＝0.01]， but in subgroups of ＜6 months old， there was no significant difference between the two groups [SMD＝0.01， 95%CI（－0.10， 0.11）， P＝0.88]. In zinc 20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.52， 95%CI（－0.80， －0.23）， P＝0.000 3]. In zinc ＞20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.83， 95%CI（－1.39， －0.27）， P＝0.004]. In zinc ＞10 mg （age ≤12 months） or zinc ＞20 mg （age ＞12 months） group （short for “constant dose group”）， the zinc group was significantly shorter than the control group [SMD＝－0.16， 95%CI（－0.27， －0.06）， P＝0.003]. In the aspect of diarrhea rate after 7 days of treatment， there was no significant difference in the diarrhea rate after 7 days of treatment between the zinc group and the control group： in zinc ＜20 mg group[OR＝1.28，95%CI （0.96，1.70），P＝0.09]， in zinc 20 mg group [OR＝0.40， 95%CI （0.15，1.01），P＝0.05]， in constant dose group [OR＝0.64， 95%CI （0.28， 1.44）， P＝0.28]. In terms of vomiting rate， in zinc ＜20 mg group， the vomiting rate of zinc group was significantly higher than that of the control group [OR＝2.13， 95%CI （1.68， 2.70）， P＜0.001]； in constant dose group， vomiting rate of zinc group was significantly higher than that of the control group [OR＝1.84， 95%CI （1.44， 2.34）， P＜0.001].CONCLUSIONSZinc can significantly shorten the duration of diarrhea in children（6 months and above）， but low doses can increase the risk of vomiting， which should be taken attention in clinical.关键词：dose;diarrhea;duration of diarrhea;vomiting;meta-analysis
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发布时间：2023-09-14 - 摘要：OBJECTIVETo explore the pharmaceutical care model for elderly patients with drug-related problems （DRPs） based on the comprehensive medication management review （CMMR）， and to observe the effect of pharmaceutical care under the model.METHODSThe pharmaceutical care new model for elderly patients was established by concerning CMMR guidelines in Australia. In other words， clinical pharmacists receive medical care through referral by health practitioners and active consultation by patients or their caregivers. Visits were made by a combination of face-to-face and telephone interviews. Follow-up was carried out in the form of outpatient follow-up， telephone follow-up， appointment， and home guidance to know about the treatment of DRPs by healthcare practitioners or patients.Under this model， the occurrence status and classification of DRPs in elderly patients were studied through cross-sectional investigation. The effect of pharmaceutical care was evaluated from the aspects of hospitalization rate， adverse drug reaction （ADR） incidence， medication compliance， the number of medications， blood lipid level， etc.， through self-before-after comparison.RESULTSIn this study， a patient-centered， evaluation-intervention-reevaluation closed-loop pharmaceutical care model was formed. Among 317 study subjects， the average number of DRPs was 1.03 （0-7） cases. Compared before and after the intervention， the number of drug types increased from 2.00（0.00，3.00） to 2.00（1.00，3.00）， but the level of low-density lipoprotein cholesterin in patients decreased from 3.48 （2.58， 4.29） mmol/L to 3.11 （2.29，3.81） mmol/L （P＜0.05）. There was no statistical significance in hospitalization rate， ADR incidence within or medication compliance.CONCLUSIONSCMMR-based pharmaceutical care model can effectively identify and manage the patients’ DRPs and reduce the level of blood lipid.关键词：elderly patient;comprehensive medication management review;pharmaceutical care
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发布时间：2023-09-14 - 摘要：Ulcerative colitis （UC） is a chronic non-specific inflammatory disease characterized by the damage of the epithelial barrier of the colon and the destruction of immune homeostasis. It has a long course， no recovery and high recurrence rate， and is recognized as a difficult digestive disease. MicroRNA （miRNA） has been confirmed to be specifically or differentially expressed in both UC patients and UC animal models， so miRNA can be used as markers for UC diagnosis or reference for treatment evaluation. TCM therapy has a definite therapeutic effect， a wide range of effects， and minimal side effects in the treatment of UC， so this article takes miRNA as the starting point and systematically elaborates on the mechanism of TCM regulating UC related signaling pathways by regulating the expression of miRNA. The results show that chlorogenic acid， Anchang decoction， and Fuyang huoxue jiedu formula can regulate the expressions of miR-155， miR-146a and miR-31-5p， etc.， thereby inhibiting signal transducer and activator of transcription （STAT） signal pathway transduction to improve UC. Limonin， ginsenoside Rh2， artesunate， etc. can inhibit nuclear factor-κB （NF-κB） signaling pathway conduction to improve UC by regulating the expressions of miR-214， miR-155 and miR-19a， etc. Nitidine chloride， berberine， resveratrol， etc. can regulate the expressions of miR-31， miR-146a， miR-146b， etc.， thereby inhibiting the Toll-like receptor 4 （TLR4） signaling pathway to improve UC. Mango polyphenolics， Compound qinbai granules， and Astragalus membranaceus polysaccharides can regulate the expressions of miR-126 and miR-193a-3p， thereby inhibiting the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/AKT/mTOR） signaling pathway to improve UC.关键词：microRNA;signaling pathway;traditional Chinese medicine;mechanism of action
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发布时间：2023-09-14 - 摘要：Traditional Chinese medicine has the characteristics of multiple components， pathways， and targets in the treatment of fracture healing， and has good therapeutic advantages and potential for fractures with complex pathological mechanisms. Based on this， the author summarized the mechanism of promoting fracture healing by the monomer components and compound formulas of traditional Chinese medicine and found that visfatin A， puerarin， and others can activate the mitogen-activated protein kinase （MAPK） signaling pathway； Xugudan， Guben zenggu formula and others can activate bone morphogenetic protein （BMP） signaling pathway； baicalin， Achyranthes bidentata polysaccharides and others can activate Wnt/β-catenin signaling pathway； apigenin， notoginsenoside and others can activate receptor activator of nuclear factor-κB （NF-κB）/receptor activator of NF-κB ligand/osteoprotegerin （RANK/RANKL/OPG） signaling pathway； Compound huoxue jiegu capsule， Jiangu granule and others can inhibit phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway； icariin can activate Notch signaling pathway； Taohong siwu decoction， crocin and others can activate Hippo signaling pathway； jujuboside A and osthole can inhibit NF-κB signaling pathway， and thus promote fracture healing.关键词：monomer components;compound formulas;fracture healing;signaling pathway;osteogenic differentiation
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发布时间：2023-09-14
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