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Objective To develop a pharmacogenomics study of ticagrelor in patients with acute coronary syndrome (ACS), identify the genetic factors that can predict individual differences in antiplatelet aggregation effects of ticagrelor, and provide a reference for the development of individualized regimens for ticagrelor. Methods 75 ACS patients of Chinese Han in a hospital in Fujian province in 2018 who met the entry criteria were recruited. The patient was given the tests for platelet function test, platelet aggregation rate and DNA detection. The whole exon sequencing method (WES) was used to detect the single nucleotide polymorphisms of SLO1B1, UGT2B7, P2Y12, PEAR1, ITGA2B and ITGB3. At the same time, the general clinical data of the patients were collected and recorded. The correlation between antiplatelet aggregation effects of ticagrelor and pharmacogenetic polymorphism was analyzed by one-way analysis of variance, multiple linear regression analysis and binary logistic regression analysis. Results One-way analysis of variance showed that SLCO1B1 rs2306283 mutant allele G could affect the antiplatelet aggregation effect of ticagrelor, the average platelet aggregation rate of patients carrying at least one allele G (AG+GG type) was significantly lower than that of wild homozygotes AA patients (8.07%±6.17% vs 13.88%±6.39%, P≤0.05). However, multivariate regression analysis after adjusting for confounding factors showed that SLCO1B1 rs2306283 mutant allele G was not an independent variable affecting the antiplatelet effects of ticagrelor (P>0.05). Conclusion Single nucleotide polymorphisms of genes related to ticagrelor transport receptors, targets, and platelet membrane receptors (including SLO1B1, UGT2B7, P2Y12, PEAR1, ITGA2B, ITGB3) in ACS patients of Han Chinese in Fujian province will not significantly affect the antiplatelet aggregation effect of ticagrelor, which provides a new treatment option for patients with genetic defects who are not suitable for clopidogrel.
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Objective To evaluate cardiovascular benefits in patients with type 2 diabetes mellitus treated with the marketed 11 sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like polypeptide-1 (GLP-1) receptor agonism by Bayesian network meta-analysis system. Methods MEDLINE, Embase and Cochrane Library were searched from the establishment of the database to 18 July 2020. The endpoint of the study was adverse cardiovascular events. The effect measures were hazard ratios (HR) and 95% credible intervals (CI). Results Compared with placebo, empagliflozin, canagliflozin, dapagliflozin, albiglutide, dulaglutide, exenatide, liraglutide, semaglutide reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes with HR and 95% CI ranging between 0.75(0.60-0.95)~0.90(0.82-0.99); The risk of heart failure was reduced by empagliflozin, canagliflozin, dapagliflozin and ertugliflozin, with HR and 95%CI ranging between 0.64(0.49-0.82)~0.74(0.65-0.85); Empagliflozin, canagliflozin, dapagliflozin, exenatide, liraglutide and oral semaglutide reduced the incidence of all-cause mortality with HR and 95%CI ranging between 0.52(0.33-0.84)~0.89(0.80-0.99); Empagliflozin, canagliflozin, liraglutide and oral semaglutide can reduce the risk of cardiovascular death events, with HR and 95% CI ranging between 0.54(0.30-0.95)~0.83(0.71-0.96) . Conclusion The order of the cardiovascular benefits of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes mellitus complicated with atherosclerotic cardiovascular disease are canagliflozin (the best), empagliflozin, dulaglutide, liraglutide; for patients with type 2 diabetes and heart failure. The order of the cardiovascular benefits for patients with type 2 diabetes and heart failure are empagliflozin, canagliflozin, ertugliflozin, and dapagliflozin.
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Objective To explore the formulation and adjustment of nutritional therapy by nutrition support pharmacists in patient with acute prerenal failure complicated with urinary tract infection, and to provide a reference for nutritional therapy in such patient. Methods With nutrition support pharmacists participated in nutrition treatment management and case analysis of a patient with acute prerenal failure complicated with urinary tract infection, we explored the nutritional support treatment plan for this type of patient. Results Nutrition support pharmacists provided pharmaceutical care throughout the course for patient with acute prerenal failure and designed an individualized low-calorie and high-protein nutritional support treatment according to the change of patient's condition, to increase the patient's serum albumin level and maintain at 35 g/L, at the same time the infection was effectively controlled and the creatinine value decreased to normal. Conclusion Small-volume, low-calorie, high-protein nutritional support solution ≤1 000 ml, calorie intake is about 1, 000 kcal, and protein is maintained at 1.2 g/(kg·d) throughout the course of acute prerenal renal failure with urinary tract infected patients can obtain better clinical outcomes and prognosis, and can better maintain clinical operability, and fully improve the safety, effectiveness and economics of nutritional support treatment.
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Objective To review and analysis the clinical manifestations, occurrence rules, treatment and outcomes of adverse drug reactions caused by anlotinib in order to provide reference for safety and reasonable use of anlotinib in clinical practice. Methods The cases reports of anlotinib were searched in Web of Science, Pubmed, Wiley Online Library, CNKI, Wanfang and VIP. The basic patient information, adverse reaction time, characters, treatment, outcomes and involved systems or organs were collected and analyzed. Results A total of 20 cases were collected, 10 females and 10 males, with a median age of 63.5(36～76 years old). Adverse drug reactions mostly occurred within 2 months after the medication. 52 cases occurred in total, involving 9 systems/organs, of which blood and lymphatic system disorders (all were hypertension) were the most common (21.2%). Conclusion After the administration of anlotinib, the incidence rate of adverse reactions in the cardiovascular system is relatively high. The medication process should be closely monitored, and attention should be paid to monitoring the potential adverse reactions mentioned in the instructions.
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Objective To investigate the overall incidence and risk of hypertension in the treatment of cancer patients who receive anlotinib and compare the differences between anlotinib and other VEGFR inhibitors. Methods Pubmed, Embase, Cochrane Library, ASCO, CNKI, Wangfang, VIP and CBM databases were searched. Eligible studies were phase II and III prospective clinical trials on cancer patients who received anlotinib and had the hypertension data available. Meta-analysis for the incidence and risk of anlotinib was performed by using R software (version 3.6.0). SPSS software (version 26.0) was used to compare the difference between anlotinib and other VEGFR inhibitors. Results A total of 1387 cancer patients from 13 clinical trials were included in the Meta-analysis. The overall incidences of all grade and high grade hypertension in cancer patients who received anlotinib were about 47.1% (95%CI: 37.7%−56.6%) and 10.6% (95%CI: 7.4%−14.2%). The use of anlotinib was associated with significantly increased risk of all grade (RR=5.58, 95%CI: 2.29−13.60, P<0.01) and high grade hypertension (RR=27.78, 95%CI: 3.56−216.86, P<0.01). In addition, the incidence of high grade hypertension associated with anlotinib was similar to axitinib (RR=0.79, 95%CI: 0.61−1.02, P=0.066) and cabozantinib (RR=0.87, 95%CI: 0.67−1.13, P=0.290). The incidences of rest of other VEGFR inhibitors were lower than that of anlotinib. Conclusions There is a high incidence and significant risk of developing hypertension in cancer patients receiving anlotinib. Adequate monitoring and timely treatment of hypertension is recommended.
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Type 2 diabetes is a high risk factor for atherosclerotic cardiovascular disease. Studies have found that SGLT-2 inhibitor and GLP-1 receptor agonists have cardiovascular protective effects in patients with type 2 diabetes and cardiovascular disease. Therefore, from the aspects of cardiovascular safety test and its Meta-analysis and net-like Meta-analysis, the research progress of cardiovascular safety of SGLT-2 inhibitors and GLP-1 receptor agonists is summarized.
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Objective To prepare, investigate and optimize the drug stability of compound adapalene ointment.Methods The ointment containing adapalene and mupirocin were prepared with PEG400and PEG3350as matrix.Stress test was usedto evaluate and optimize the stability of drugs in the ointment.The drug stability was further tested by the acceleration test and long-term test.Results The raw adapalene was stable under high temperature, high humidity and strong light irradiation.The raw mupirocin was stable under high humidity and strong light irradiation, but was highly unstable under high temperature condition.Degradation of adapalene and mupirocin was found with pH≤7.At pH 7.5, the best stability was achieved, with over95％of the drugs remaining at day 10.Favorable ointment was prepared with PEG400∶PEG3350=2∶1.The drug stability was promoted by addition of 0.2％triethanolamine significantly.In the acceleration test and long-term test, the percentages of adapalene and mupirocin were above 95％.Conclusion The compound adapalene ointment was successfully prepared and the drug stability was excellent.
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Objective:To optimize and improve the content determination method for nitroglycerin ointment. Methods:An HPLC method was used,the column was Hypersil ODS(150 mm × 4. 6 mm,5 μm),the mobile phase was acetonitrile ∶water(50 ∶50),the detection wavelength was set at 220 nm,the flow rate was 1 ml·min-1 ,the column temperature was 30℃,and the injection volume was 20 μl. Results: The results showed a good linear relationship within the concentration range of 0. 020 3-0. 203 3 mg · ml-1 ( r =0. 999 9),and the average recovery was 99. 51%(RSD=1. 06%,n=9). Conclusion: The method is rapid,accurate and reproduci-ble,and can be used to determine the content of nitroglycerin in nitroglycerin ointment.
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Objective To prepare compound ketoconazole ointment and perform the stability study .Methods Ketocon-azole ,mupirocin and mometasone furoate were used as active pharmaceutical ingredients (API) .PEG mixture was used as ma-trix to prepare the ointment .Stability of the API in the ointment was evaluated by the stress tests .Results The optimal ratio of PEG400 to PEG3350 for the ointment matrix was 2:1 .Mometasone furoate and mupirocin in the ointment were stable to the high temperature(40 ℃)while ketoconazole had some degradation .The stability of the API was improved by addition of 0 .5％ of L-A .During the accelerate test ,the ointment had no color change and the API percentages were above 98％ .Conclu-sion The novel compound ketoconazole ointment was successfully prepared and the formulation stability was excellent .
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Objective:To establish and improve the quality standard for Lanqiao Jiedu oral liquid. Methods:A TLC was used for the qualitative identification of Forsythiae Fructus, Sophorae Tonkinensis Radix Et Rhizoma and Anemarrhenae Rhizoma. An HPLC was used for the qualitative identification of Isatidis Radix. Forsythin in Forsythiae Fructus was quantitatively identified by HPLC. Results:Forsythiae Fructus, Sophorae Tonkinensis Radix Et Rhizoma and Anemarrhenae Rhizoma showed clear spots and there was no interfer-ence from the negative control. The HPLC further confirmed Isatidis Radix was ( R, S)- epigoitrin. Quantitative study of forsythin re-vealed good specificity without interference from the negative control. Conclusion: The study provides an improved quality standard with high specificity and reproducibility, which can be applied in the quality control of Lanqiao Jiedu oral liquid.
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OBJECTIVE:To optimize and improve the quality standard for Compound pediatric anticough oral solution. METH-ODS:TLC was adopted for the qualitative identification of Glycyrrhiza uralensis;chemical reaction was adopted for the qualitative identification of ipecac tincture,ammonium chloride;and HPLC was adopted for the content determination of ammonium glycyrrhi-zinate:the column was Agilent Zorbax XDB C18 with mobile phase of acetonitrile-0.2 mol/L ammonium acetate(20∶80,V/V)at a flow rate of 1.0 ml/min,the detection wavelength was 250 nm,column temperature was 30℃,and the injection volume was 10 μl. RESULTS:TLC spots of G. uralensis were clear and well-separated,negative control without interference. Differential response of ipecac tincture and ammonium chloride showed significant positive characteristics. The linear range of ammonium glycyrrhizinate was 6.08-72.96 μg/ml (r=0.999 9);RSDs of precision,stability and reproducibility tests were lower than 1.0%;recovery was 99.69%-100.28%(RSD=0.20%,n=6). CONCLUSIONS:Optimizing and improving the standard are helpful for the quality con-trol of Compound pediatric anticough oral solution.
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Objective To establish an HPLC method for determination of ephedrine hydrochloride and pseudoephedrine hydrochloride in Maxing oral solution .Methods Phenomenex Hydro-RP (250 mm × 4 .6 mm ,4 μm) was adopted .Acetonit-nile (A) and 0 .1% phosphonic acid solution (0 .1% triethanolamine solution)(B) was used as gradient mobile phase(0-20 min , 3% →10% A)at flow rate was 1 .0 ml/min and the program of UV gradient absorbance detection was 210 nm .The sample vol-ume was 20 μl .Results A good linearity was obtained over the concentration range of 0 .99-39 .6 μg/ml for ephedrine hydro-chloride (r=0 .999 9) and 1 .09-43 .6 μg/ml for pseudoephedrine hydrochloride (r=0 .999 9) .The average recovery of ephed-rine hydrochloride was 101 .5% with RSD of 1 .77% (n=6) ,and the average recovery of pseudoephedrine hydrochloride was 100 .8% with RSD of 1 .96% (n=6) .Conclusion This method was simple ,accurate and quick ,which could be used for deter-mination and quality control of Maxing oral solution with good selectivity and repeatability .
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Objective To consummate a method of quality control of peppermint water .Methods Thin layer chromatog-raphy was used for the identification of peppermint oil .Gas chromatography was used for the determination of mentholum . Results The identification of peppermint oil was highly specific by TLC .The linear range of mentholum was from 5 .0-80 .0 μg/ml ,r=0 .999 9 .The average recovery of mentholum was 103 .16% and RSD was 1 .81% .Conclusion These methods were easy to operate with accurate results ,which washigh sensitivity andgoodrepeatability .This quality standard could effective-ly control the quality of peppermint water .
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Objective The biological half-life in vivo of local anesthesia is short, high concentration in local tissue is in-clined to cause central nerve and cardiovascular toxicity due to the drug absorption into blood by blood vessels.The research was to pre-pare the poly ( lactide-co-glycolide) nanoparticle loaded with ropivacaine ( RVC-PLGA-NPS) , optimize its process, and determine its characteristics in vitro. Methods An oil-in-water emulsion solvent evaporation technique was adopted to prepare the RVC-PLGA-NPS.The formulation was optimized by central composite design/response surface method(CCD-RSM), with the encapsulation effi-ciency( EE) , drug loading( DL) and particle size as the indexes.Research was also made on itsin vitro release by fitting different model equations. Results The acquired nanoparticals were smooth, with the mean particle size (331.21±2.11) nm, DL (13.81±1.35)%and EE (74.82±2.53)%.The accumulative release rate of the nanoparticals was about 73%in 96 h, which showed that Higuchi func-tion fitted the release curve. Conclusion The RVC-PLGA-NPS made by emulsion solvent evaporation technique have obvious drug-release behaviour in vitro.
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Objective To prepare insulin thiolated hyaluronic acid nanoparticles (Ins-HA-Cys-NPs)and study its physicochemical properties. Methods The Ins-HA-Cys-NPs was prepared by ultrasonic emulsifying method,and the properties of nanoparticles including morphology,mean diameter,Zeta potential,entrapment efficiency and drug loading efficiency were studied,as well as the cryoprotectant selection.Results The prepared nanoparticles was round in appearance and the mean diameter was(178.5 ±0.8)nm,the polydispersity index was (0.214 ±0.013)and the Zeta potential was -(38.47 ±0.46 )mV,while the entrapment efficiency was (48.85 ±0.66 )%,drug loading efficiency was (4.79 ±0.13 )%;10%mannitol as cryoprotectant provided uniform and well dispersed suspension of nanoparticles with blue opalescence after redispersion.Conclusion The thiolated hyaluronic acid nanoparticles may be used as the carrier for oral drug delivery system of insulin,and it provides a basis for studies on rats in vivo.
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Objective To explore the best ratio of platelet-rich plasma (PRP) to activator and the synergistic action of thrombin and the growth factors in PRP gel on proliferation of human marrow-derived mesenchymal stem cells (hBMSCs). Methods The activator was made up of 1000 U bovine thrombin and 1 mL 10% calcium chloride solution. PRP was mixed with the activator at the ratios of 1:1, 5:1, 10:1, 20:1, 40:1 respectively in groups A, B, C, D and E. A quantitative sandwich enzyme-linked immunosorbent assay (ELISA) was used for examining the amounts of transforming growth factor-β1 (TGF-β1) and platelet derived growth factnr-AB (PDGF-AB) in PRP gel in each group after incubation for 0,1,8,24, and 120 hours. MTT assay was used to evaluate the effect of PRP gel in each group on hBMSCs proliferation. Results When PRP was mixed with thrombin, concentrations of PDGF-AB and TGF-β1 in PRP gel increased immediately and reached the peak value in 1 hour. The PRP gel in groups B, C, and D contained the highest amounts of PDGF-AB and TGF-β1, and accelerated hBMSCs growth re-markably. The cells proliferation in group A was inhibited. Conclusions The effect of PRP on the hBMSCs proliferation depends on the concentrations of PDGF-AB and TGF-β1 in PRP. Thrombin may influ-ence the hBMSCs proliferation by regulating concentrations of growth factors in PRP to certain extent, but too high a level of thrombin may inhibit hBMSCs growth.
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BACKGROUND:The poly-lactic acid and its ramifications have many advantages, such as eligible biocompatibility,nontoxicity of degradation product, easy procession and suitable intensity. Thus, they have been widely used in bone tissue engineering.OBJECTIVE: To study the cellular biocompatibility and in vitro adhesion of poly(lactic-co-glycolic acid) (PLGA) scaffold and bone marrow stromal stem cells (BMSCs) so as to provide a basis for preparation a PLGA scaffold that can load many cytokines.DESIGN: Contrast observation.SETTING: Department of Orthopaedics and Traumatology in Nanfang Hospital of Southern Medical University.MATERIALS: The experiment was carried out in Key Laboratory of Tissue Construction and Detection of Guangdong Province from September 2004 to June 2005. One New Zealand healthy male rabbit (2 months old, 1.5-2.0 kg weight)was adopted in this study. Experimental materials: PLGA scaffold was obtained from Institute of Polymer Science in Sun Yat-sen University); beta-tricalcium phosphate (β-TCP) was supplied by AO Company (Switzerland).METHODS: Bone marrow was aspirated from the New Zealand rabbit. Mononuclear cells were harvested using whole bone marrow culturing, then were induced and amplified in the conditional culture medium. BMSCs were inoculated onto the PLGA and β-TCP at a concentration of 1 ×109 L-1, while those in the medium without materials were taken as blank control group. The development of implanted cells and the adhesion between cells and materials were observed with phase contrast microscope and scanning electron microscope. The proliferation and cycle of cells were tested with MTT method and flow cytometry.MATN OUTCOME MEASURES: ①Phase contrast microscope was used to observe the development of cells and the adherence between cells and materials at a fixed time every day. ②Cellular development on days 1, 3, 6 was observed by scanning electron microscope. ③Cellular proliferation was detected by MTT method. ④Alkaline phosphatase (ALP) activity was determined by chemical colorimetry.⑤Flow cytometer test: The effects of PLGA and β-TCP on the cellular cycle, content of DNA and polyploid levels of BMSCs were investigated. The DNA index of the candidate cells was also calculated.RESULTS: ①Phase contrast microscope observation: In the blank control group, cells culture for 7-10 days presented a larger number of shuttle-shaped, and no contact inhibition effect was observed. The time of cells beginning adherence in PLGA group was obviously later than that in β-TCP group. Cells began to develop on the circumambience and surface of the materials, with the prolonging of culture time. Most of the cells were multangular. The cells in both PLGA and β-TCP groups were similar to those in control group in items of cellular development and shape. ②Scanning electron microscope observation: On the seventh day of culture, the cells of control group remained a monolayer and amalgamated to be a patch with multangular-shaped ones increasing. There were substances in granule shape on the surface of the cells and micro-silk links between cells. In PLGA group, the cells After 7 days' cultivation proliferated sharply, and the compressed-shaped ones were inosculated to be a patch through integrations among cells, resulting in a large number of matrixes. While in β-TCP group, the number of cells increased from the 7th day. The cells were combined together to be a monolayer and moved to pores with matrixes creating out of cells.③Cellular proliferation: The number of the cells in each group all increased to some extents. However, there was no significant difference between the PLGA group and the control group, as well as the PLGA group and the β-TCP group (P ＞ 0.05).④ALP activity: The content of ALP in all the groups enhanced without exception, while the activities between the PLGA group and the Both control group, as well as the PLGA group and the β-TCP group had no significant difference (P ＞ 0.05).⑤Cellular cycle:Both PLGA and β-TCP had slight effects on cellular cycle of BMSCs. The cells in each group were all normal diploid,and no heteroploid cells were discovered.CONCLUSION: This type of PLGA scaffold possesses good cellular biocompatibility, and can be used as a carrier of many factors in bone tissue engineering.
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BACKGROUND: Many experiments indicate that the angiogenesis of tissue engineered bone graft plays a key role in the osteogenesis.OBJECTIVE: An experimental pattern was set up designed to prepare a kind of vascularized engineered-bone graft for repairing rhesus tibia defects and analyze the relation of angiogenesis and osteogenesis in vivo by rontgenographic and morphological approaches.DESIGN: Random controlled animal experiment.SETTING: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University.MATERIALS: The composite graft was constructed by seeding the induced bone marrow stem cells (BMSCs) on to a beta-tricalcium phosphate(3-TCP) scaffold in vitro, a circular cylinder (20 mm × 8 mm diameter) with a slit (width 2 mm and length 3 mm ) open to both ends and slot. Porosity 60% and pore diameter 100-150 μm. Twenty-nine healthy rhesuses aged 4-5 years and weighted 3.5-5 kg were adopted without gender limitation.METHODS: The experiment was conducted in the Department of Orthopaedics and Traumatology, Nanfan Hospital, Southern Medical University from October 2003 to July 2005. ①Bone-periosteum defect of 20 mm was made in the middle part of right tibia of the 27 rhesuses, and randomly divided into 3 groups equally. ②The defect gaps in fascia-blood vessel group (A) were plugged with in vitro engineered composites constructed by bone marrow stem cells and 3-TCP scaffold, which were totally hugged by a sheet of pedicled deep fascia and additionally a corresponding portion of saphenous artery and veins. The gaps in fascia group (B) and control group(C), however, were inserted with fascia-coated tissue engineered bone and tissue engineered bone only, respectively. Furthermore, two rhesuses without filling materials on the defect were picked up as blanks fixed by steel pins. ③The angiogenesis and osteogenesis for each treatment was assessed by radioactive imaging, roentgenographic analyses, blocking density and vaso-area image analysis at time intervals of 4, 8 and 12 weeks postoperative.MAIN OUTCOME MEASURE: The score of radioactive imaging,roentgenographic, morphological and vaso-area image analyses RESULTS: Totally 29 rhesuses were involved in the result analysis.① General observation of samples: In group A, all the surfaces of the implanted material and the central part were wholly wrapped up or replaced by bonelike tissues which were hard and could not be broken. And 2/3 materials had been absorbed; In group B and C, partial materials of the medial surface and the front were not coated or replaced by bonelike tissues, which could be broken with force, and 1/3 material had been absorbed.②Histological observation of scaffolds: With time passing, the scaffold materials were absorbed to different degrees in group A, B and C, among which, group A was most significant; Under the microscope, the implanted materials at 12 weeks were completely coated with the bonelike tissues, while the blood vessels structures in the materials were mostly alveoli alike and multi-braches. In group B, most of the materials at 12 weeks were wrapped up by the new bone, and few blood vessels could be seen in the center of the materials. In group C, the implanted materials at 12 weeks were slightly absorbed. The new bone and the vascular structures were both increased a little, but still very few.③Analyses of vaso-area: The vaso-areas of both central and peripheral parts in group A were significantly bigger than those of group B and C (P ＜ 0.05). Furthermore, it tended to increase with the time.④X-rays observation: At 12 weeks, group A's images presented obviously decreased density which was lower than that of the normal bone in individual areas and the continual bony callus manifested. Whereas group B and C's images showed slightly decreased density and the continual bony callus appeared on the sections. ⑤The roentgenographic scores of bone defects: The results indicates that the scores of group A was better than those of group B and C at 4, 8 and 12 weeks, respectively (P ＜ 0.05).CONCLUSION: ①This study shows that a feasible and effective angiogenesis approach of tissue engineered bone can accelerate osteogenesis in vivo. ②The absorption level is positively related to local angiogenesis.