Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond / 中国中药杂志

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Retrospective Analysis of ADR in Elderly Patients in Sichuan Province during 2013-2019 / 中国药房

OBJECTIVE：To investigate the situ ation and characteristics of ADR reports in the elderly patients （≥65 years old ） of Sichuan province ，and to provide reference for guaranteeing the safety of drug use. METHODS ：ADR reporting data of elderly patients collected by spontaneous reporting system of Sichuan ADR monitoring center from 2013 to 2019 were collected ，and then analyzed in respects of report types ，reproting institution ，relationship，patienst’age，gender，nationality，drug type ，organ/system invovled. RESULTS & CONCLUSIONS ：In the past seven years ，175 431 cases spontaneous ADR were collected by Sichuan ADR monitoring center ，and the annual proportion of “general”ADR reports decreased from 78.93％ in 2013 to 60.50％ year by year ； the annual proportion of “new general ”and“serious”ADRs increased year by year ，among which that of “new general ”ADR increased more obviously. The main reporting institutions were medical institutions ，accounting for 92.79％-98.87％ of the total annual reports. The enthusiasm of enterprises and individuals to report ADR needed to be improved ；8 031 cases（4.58％）were “positive”relationship，21 283 cases（12.13％）were“likely”，146 117 cases（83.29％）were“possible”. Except that the gender of 272 cases were not reported ，there were 88 176 male cases and 86 983 female cases ；most of them were 65-74 years old （104 962 cases，59.83％）. The reports covered 19 nationalities，among which the re were 166 752 cases（98.72％）of Han nationality. The distribution of ADR related drug categories in elderly patients of Yi ， Tibetan and Qiang nationalities was significantly different from that of Han nationality （P＜0.01）. The top three drug categories in the total frequency were anti-infective drugs （31.10％），traditional Chinese medicine com （18.27％），and central nervous system drugs （9.99％）. The injection route was the most likely to cause ADR （72.12％）. ADR mainly involved s kin and its appendants （21.47％）， gastrointestinal system （19.61％）and central and peripheral nervous system （18.55％）. Aminophylline injection was the only dr ug in the top 10 drugs leading to “new general ”ADR for consecutive 7 years. Cefotaxime sodium for injection ，Ceftriaxone sodium for injection ，Cefoperazone sodium and sulbactam sodium for injection were the top 10 drugs causing “severe”ADR in consecutive 7 years，which should be paid more attention in clinic.

Quality evaluation of Magnoliae Officinalis Cortex based on combinative method of fingerprint,quantitative analysis of multicomponents and chemometrics / 中国中药杂志

This study aims to establish a combinative method based on fingerprint,assay of multi-component and chemometrics for quality evaluation of Magnoliae Officinalis Cortex. Twenty batches of samples were determined by UPLC and a common mode of fingerprint was established. The similarities between fingerprints of 20 batches of samples were over 0. 90 and the common mode were evaluated. Eight components were identified as syringing, magnocurarine, magnoflorine, magnoloside B, magnoloside A, honokiol,magnolol,and piperitylmagnolol by comparison with reference substances and their content in samples were simultaneously determined.Based on the results,the fingerprint had good consistency between the same origin and minor diversity between the different sources.Piperitylmagnolol and peak 13 could be used as a distinction with the different sources. According to content of 8 components,Fisher discriminant analysis model was established and different source sample was classified pursuant to the discriminant fraction. It is indicated that simultaneous quantification of multi components coupled with chemometrics analysis could be a well-acceptable strategy to identify and evaluate the quality of Magnoliae Officinalis Cortex.

Identification of Illicium difengpi and Its Fake I. jiadifengpi Using DNA Barcoding / 中国实验方剂学杂志

Objective:To evaluate and compare the identification of several DNA barcoding candidate sequences on Illicium difengpi and its fake I. jiadifengpi. Method:Samples from different origins of I. difengpi and I. jiadifengpi, were collect extraction of total DNA,nuclear gene ITS2 sequence,chloroplast rbcL,matK gene sequence were selected for PCR amplification,product purification and sequencing,and CondonCode Aligner V3.7.1 was used to proofread stitching. Result:PCR amplification and sequencing of rbcL sequences of I. difengpi and I. jiadifengpi were not satisfactory. It is assumed that their rbcL sequences were too long with slow evolution,which was unsuitable for interbreeding. The success rate of matK sequencing of I. difengpi and I. jiadifengpi was 0 and 76.8%,which may be because primer standards were different for matK sequences of different groups. The results of PCR amplification and sequencing of ITS2 on I. difengpi and I. jiadifengpi were successful,with the success rate of sequencing was 89.3% and 91.2%. Analysis sequencing results, the total length of ITS2 sequences was 268 bases,and there were 2 variation sites of I. difengpi. The total length of ITS2 sequences was 430 bases,and there were 4 or 3 variation sites of I. jiadifengpi. It shows that ITS2 sequences of I. difengpi and I. jiadifengpi were short and has obvious variability and can be amplify,that ITS2 sequence was better than rbcL and matK sequence in molecular identification of I. difengpi and I. jiadifengpi. Conclusion:DNA barcoding based on ITS2 sequence was a powerful and efficient tool for identification of I. difengpi and its fake I. jiadifengpi.

Nitrogenous Chemical Constituents from Brassica campestris Seeds / 中国实验方剂学杂志

Objective:To study nitrogenous chemical constituents from the seeds of Brassica campestris. Method:The aerial parts of nonfat seeds were extracted with 75% ethanol heat refluxing method,then suspended in H2O and separated with ligarine and ethyl acetate to obtain respective fractions.Chemical constituents were isolated and purified by various chromatographic methods and identified by physicochemical characters and spectroscopic analysis or comparison with standard compounds. Result:Thirteen nitrogenous chemical compounds were isolated and identified as coixspirolactam C (1),indole-3-acetonitrile (2),2-β-D-glucopyranosylsulfanyl-1H-indole-3-acetonitrile (3),nicotinic acid (4),adenosine (5), 1H-indole-3-carbaldehyde (6),4-hydroxy-1H-indole-3-carbaldehyde (7),6-hydroxy-1H-indole-3-carboxylic acid (8),ethyl 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylate (9),5-hydroxy-4(1H)-quinazolinone (10),4-hydroxy-2-quinazolinone (11),5-hydroxy-quinazoline-2(1H),4(3H)-dione (12),5-allyloxazolidin-2-one (13). Conclusion:All of the compounds were isolated from this plant for the first time, and compounds 1,3 and 13 were isolated from Brassica for the first time.

Grade Evaluation of Magnoliae Officinalis Cortex Processed with Ginger Juice Based on Relative Quality Constant / 中国实验方剂学杂志

Objective: To establish the grade evaluation standard for Magnoliae Officinalis Cortex processed with ginger juice by combining traditional morphology evaluation with modern intrinsic quality evaluation. Method: The morphological parameters and contents of intrinsic pharmacodynamic index components of 28 batches of Magnoliae Officinalis Cortex processed with ginger juice were determined, and the relative quality constants were calculated. Assuming that the average relative quality constant was 100%, more than 120%of the samples were classified as the first grade, 60%to 120%as the second grade, the remaining as the third grade. Result: The relative quality constant of Magnoliae Officinalis Cortex processed with ginger juice ranged from 0.09 to 1.78. The relative quality constant of the first grade was ≥ 0.64, the second grade was 0.32-0.64, while the third grade was ≤ 0.32. Conclusion: Relative quality constant combines external indexes of traditional morphology and internal indexes of pharmacodynamic components, which can objectively, reasonably and scientifically classify the grade of Magnoliae Officinalis Cortex processed with ginger juice, and provide reference for establishing and improving the grade evaluation standard of this decoction pieces.

Retrospective Analysis of Gestational Adverse Drug Reactions from Sichuan Center for Adverse Drug Reaction Monitoring from Nov. 2016 to Nov. 2017 / 中国药房

OBJECTIVE： To investigate the characteristics and regularity of gestational （including perinatal period） adverse drug reactions （ADR） in Sichuan province， and to provide evidence for ensuring the safety and effectiveness of drug use in clinic. METHODS： Gestational ADR reported to Sichuan provincial ADR monitoring center from Nov. 2016 to Nov. 2017 were statistically analyzed in respects of report source， personnel distribution， general information of patients， route of administration， drug types and main drugs， involved system/organ， grading and outcome， etc. RESULTS： A total of 1 309 gestational ADR cases   （1 340 case time） were collected， in which 1 305 were from medical institutions， 3 from enterprises and 1 from manufacturer. There were 986 physicians， 188 nurses， 133 pharmacists and 2 commissioners for drug safety. 859 cases （65.62％） were 21-30 years old， accounting for the largest proportion. 867 case time were caused by intravenous administration （64.70％）. ADR-inducing drug types mainly included reproductive system drugs （491 case time， 36.64％）， antimicrobial drugs （479 case time， 35.75％） and blood system drugs （110 case time， 8.21％）. Main of them were Carboprost tromethamine injection （187 case time， 13.96％）， Cefazolin sodium for injection （122 case time， 9.10％） and Oxytocin injection （105 case time， 7.84％）. ADR mainly involved skin and its appendants （517 case time， 33.95％）， gastrointestinal system （387 case time， 25.41％）， whole body （175 case time， 11.49％）.  In 1 309 gestational ADR， 1 251 cases （95.57％） were general ADR； 58 cases （4.43％） were severe ADR， including 14 life-threatening cases， 7 extended hospital stay and 37 others； 592 （45.22％） patients improved， 716 （54.70％） recovered and 1 （0.08％） did not improve. CONCLUSIONS： In clinical practice， it is necessary to strengthen the monitoring of drug use in patients during gestational， especially monitor ADR of uterine contraction drugs and antimicrobial drugs during gestational， use drug cautiously and promote clinical medication safety in gestational patients.

A systematic review of stem cells in treatment of spinal cord injury and a network Meta-analysis of the therapeutic effects via different transplantation ways / 中国组织工程研究

BACKGROUND:Stem cell transplantation has been used in the clinical treatment of spinal cord injury.However,the efficacy and safety are still controversial.Although there are many approaches for stem cell transplantation,which one is better is unclear as yet.OBJECTIVE:To systematically evaluate the efficacy and safety of stem cell transplantation for spinal cord injury,and to compare the therapeutic difference in stem cell transplantation via different approaches.METHODS:A computer-based online search was conducted in PubMed,The Cochrane Library (Issue 4,2016),Embase,CNKI,VIP,CBM,and Wan-Fang databases up to May 13,2016 to screen the relevant randomized clinical controlled trials of stem cells in the treatment of spinal cord injury.Two reviewers independently selected the studies,extracted information,and assessed the quality of included trials.Data extracted from eligible studies was pooled and meta-analyzed using Stata13.1 and Gemtc0.14.3 software.RESULTS AND CONCLUSION:A total of 10 randomized controlled trials involving 546 patients (294 in stem cells group and 252 in rehabilitation treatment group) were included.The results of meta-analysis showed that stem cell transplantation had an advantage over rehabilitation treatment in increasing American Spinal Cord Injury Association (ASIA) motor score,ASIA sensory score,Barthel Index,and decreasing the bladder residual urine volume.The incidence of low fever,abdominal distension,headache,lower limb numbness,and meningeal irritation was 14％,7％,7％,8％,and 7％,respectively.Taking the rehabilitation treatment as a common reference,the results of the network meta-analysis showed that there were no significant differences in ASIA motor score,ASIA sensory score,Barthel Index,and incidence of complications among subarachnoid injection,intravenous injection,and intralesional injection.Compared with the rehabilitation treatment,only stem cell transplantation via subarachnoid injection had significant differences in ASIA motor score [MD=9.77,95％CI (0.26,21.46)],and ASIA sensory score [MD=25.79,95％CI (10.07,45.27)].To conclude,the stem cells transplantation via subarachnoid injection is considered the most effective transplantation method.Due to the limitations of the included studies,more high-quality randomized controlled trials are required to verify the above conclusion.In addition,future studies should focus on the long-term efficacy and safety of stem cell transplantation in the treatment of spinal cord injury,and should investigate the clinical effects on spinal cord injury with different ASIA grades,types of stem cells,and transplantation time.

Safety evaluation and risk control measures of Psoralea corylifolia / 中国中药杂志

Through a systematic and comprehensive study of domestic and foreign literatures and information, this study aims to trace the herbal origin and the toxicity recorded in ancient and current documents, analyze the safety case reports of Psoralea corylifolia and experimental studies on toxicity in recent years, and make a preliminary summary about the clinical characteristics and potential risk factors of cases related to the safety of P. corylifolia and its preparations. The study involved 84 patients in the safety case reports of P. corylifolia. The adverse events were mainly liver damage (55.95%) and light toxic contact dermatitis (38.10%), sugguesting that P. corylifolia may lead to liver damage and photo toxicity. However, reproductive toxicity and renal damage were only reported in animal studies, but not in clinical reports. Because of its complicated ingredients, the toxic components and mechanisms of P. corylifolia have not been clear at present. Therefore, the authors proposed to strictly apply P. corylifolia in clinic, use it rationally and combine it with other medications. Besides, efforts shall be made to strength the guidance for doctors, the safety monitoring of P. corylifolia and relevant preparations, and actively carry out safety-related basic and clinical studies, so as to give a better guidance to safe medication, full exert the efficacy and avoid the medication risk.

Preparetion of tectorigenin self micro-emulsifying drug delivery system and evaluation on its in vitro dissolution / 中草药

Objective: To prepare self micro-emulsifying drug delivery system (SMEDDS) of tectorigenin (TG), and investigate its dissolution. Methods: The formulation was optimized using Design Expert based on D-optimal design. The microemulsion's physicochemical and in vitro dissolution were evaluated after self-microemulsification. Results: The particle size and Zeta potential of the final formulation were (14.95 ± 0.31) nm and (-12.53 ± 0.80) mV after it was diluted by 10 times with pure water. The microemulsion appeared to be spheres with homogeneous size, which can be observed through a transmission electron microscope. The drug loading capacity was 20 mg/g, and the average content was (99.03 ± 0.70)%. The results of in vitro dissolution study showed that the accumulative dissolution could be close to 100% after 10 min in both hydrochloric acid solution (pH 1.2) and PBS (pH 6.8). Conclusion: D-optimal design could be used to optimize the formulations of TG-SMEDDS successfully. The TG-SMEDDS exhibits a larger accumulation dissolution than TG. This formulation would be easier absorbed through gastrointestinal tract compared to TG. The results of this study are expected to offer data support and reference for the TG's formulation design and clinical application.

Effects of 1,25-dihydroxyvitamin D3 on high glucose-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells / 中华内分泌代谢杂志

[Summary] The HK-2 cells with different culture media were divided into normal glucose group (NG group,5.5 mmol/L D-glucose) ; high glucose group (HG group,30 mmol/L D-glucose) ; mannitol group (MG group,5.5mmol/L D-glucose+24.5 mmol/L mannitol) ; 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] groups (V1-V3 group)which were exposed to medium containing 30 mmol/L D-glucose and different concentrations of 1,25-(OH)2D3 ;Nethyl-cysteim control group (NAC group,30 mmoL/L D-glucose + 1.0 mmol/L N-Nethyl-cysteim) ; and ethanol control group(SG group,30 mmol/L D-glucose+6.86 × 10-2 mol/L ethanol).The level of intracellular reactive oxygen species,mitochondrial membrane potential,activity of total-superoxide dismutase (T-SOD),level of malondialdehyde,expression of UCP2 mRNA and protein in HK-2 cells were detected.Compared with NG group,the mitochondrial membrane potential significantly decreased in HG group (P＜0.01),and the mitochondrial membrane potential in V group was lower than that in HG group(P＜0.01).The activity ofT-SOD in HG group was significantly lower than that in NG group(P＜0.01),while its level of malondialdehyde was significantly higher than that in NG group(P＜0.01).Compared with HG group,the activity of T-SOD in V groups was significantly increased (P＜0.05)and the level of malondialdehyde in these groups significantly decreased (P＜0.01).The mRNA expression of UCP2 in HG group was increased significantly in comparison with NG group (P ＜ 0.05) and the expression in V groups was significantly decreased in comparison with HG group (P＜0.01).The results suggest that 1,25-(OH)2D3 could reduce the mitochondrial membrane potential,the production of reactive oxygen species,and regulate the expression of UCP2 in order to suppress the oxidative stress induced by high glucose.