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OBJECTIVE To study the effect and potential mechanism of eriodictyol on non-alcoholic fatty liver disease （NAFLD）. METHODS Sixteen C57BL/6J mice were randomly divided into control group， NAFLD model group， and eriodictyol low-dose and high-dose groups （50， 100 mg/kg）， with 4 mice in each group. Except for control group， the other groups were fed with high fat diet to induce NAFLD model. After four weeks of preprocessing， they were given relevant medicine intraperitoneally （0.01 mL/g）， once a day， for 6 consecutive weeks. The body weight and liver weight of mice were measured， and the pathological damage of liver tissue in mice was observed. The levels of aspartate aminotransferase （AST）， alanine aminotransferase（ALT）， and triglycerides （TG） in serum， as well as the protein expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were determined. In vitro NAFLD model was established by using 0.5 mmol/L oleic acid （OA） in HepG2 cells. Normal control group， NAFLD model group and eriodictyol low-， medium- and high-concentration groups （50， 100， 150 μmol/L） were set up. HepG2 cells in drug groups were treated with eriodictyol for 24 h at the time of modeling. The lipid deposition was observed in cells， and the levels of TG， malondialdehyde （MDA） and reactive oxygen species （ROS） as well as the phosphorylation levels of the mitogen-activated protein kinase （MAPK） signal pathway related proteins [extracellular signal-regulated kinase （ERK）， c- Jun N-terminal kinase （JNK）] and the protein expressions of Nrf2 and HO-1 were all determined. RESULTS In the in vivo experiment， compared with the NAFLD model group， the body weight， liver weight， the serum levels of AST， ALT and TG were all decreased significantly in eriodictyol low- and high-dose groups （except for serum level of AST in eriodictyol low-dose group） （P＜0.01）； liver lipid deposition was reduced significantly and the protein expressions of Nrf2 and HO-1 in liver tissues were further up-regulated （P＜0.01）. In the in vitro experiment， compared with the NAFLD model group， the lipid deposition in hepatocytes was reduced in eriodictyol low-， medium- and high-concentration groups （P＜0.01）， and the levels of ROS， MDA and TG were down-regulated （P＜0.05 or P＜0.01）； the phosphorylation levels of ERK and JNK were significantly down-regulated （P＜0.01）， while the protein expressions of Nrf2 and HO-1 were up-regulated significantly （P＜0.01）. CONCLUSIONS Eriodictyol can inhibit MAPK signaling pathway and activate Nrf2/HO-1 signaling pathway to alleviate NAFLD.
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OBJECTIVE To provide a reference for safe drug use in clinic. METHODS ADE reports related to nilotinib from the first quarter of 2007 to the fourth quarter of 2022 were collected from the US FDA adverse event reporting system database. The reporting odds ratio （ROR） and proportional reporting ratio （PRR） of disproportionality measures were used to mine potential ADE signals，which were compared with drug instruction and related case report， and were screened and analyzed according to the designated medical events （DME） list formulated by the European Medicines Agency. RESULTS Totally 23 332 cases of ADE with nilotinib as the primary suspected drug were reported. A total of 359 positive signals were obtained，involving 24 system organ classes （SOC），mainly concentrated in various examinations，heart organ diseases，vascular and lymphatic diseases，all kinds of nervous system diseases，etc. Among them，ADEs such as vertebral artery stenosis，coronary artery stenosis，arterial disease，liver infection and the second primary malignant tumor were not mentioned in the instructions. Seven DMEs were detected，of which bone marrow failure，pulmonary hypertension and deafness were not mentioned in the drug instruction. CONCLUSIONS The common ADE signals of nilotinib excavated in this study are consistent with the instructions. In clinical use，special attention should be paid to DME not mentioned in the instructions such as bone marrow failure，pulmonary hypertension and deafness； cardiac function， blood glucose and blood lipid indexes should be monitored closely.
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OBJECTIVE To explore the construction of a new scientific management model for temporary drug purchase，and to provide a reference for hospitals to improve the level of rational drug use. METHODS Guided by clinical diagnosis and treatment needs and patient medication safety， our hospital carried out the whole process management practice of temporarily purchased drugs by optimizing the review process， creating a review team， formulating pre-audit and post follow-up evaluation standards based on comprehensive drug evaluation， and evaluated the practice effect through the number of temporary purchase applications， implementation rate， drug structure optimization and other indicators. RESULTS Since January 2021， our hospital had implemented a new mode of temporary drug purchase management. By December 2022， clinical pharmacists had reviewed 111 temporary drug procurement applications， effectively intercepted 13 irrational drug use applications （11.71%）， reduced the overall implementation rate of temporary drug procurement by 8.36%，and proposed five batches of drug structure optimization suggestions； 24 drugs were successively introduced such as camrelizumab，sorafenib，busulfan. After optimizing the management mode，the number of temporary drug procurement applications decreased by more than half from 133 in 2019 and 138 in 2020 to 66 in 2021 and 45 in 2022. CONCLUSIONS The model is helpful to optimize the hospital drug catalog， strengthen rational drug use，ensure the safety of patients’ drug use， and fully reflects the professional value of clinical pharmacists in hospital pharmacy management and rational drug use.
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Objective To study the influence of different moment-to-force ratios (M/F) and forces on canine displacement and periodontal ligament (PDL) stress. Methods A three-dimensional (3D) mandibular model was established based on CT images. The orthodontic force systems without a moment and with various M/F were applied to the canine for numerical calculation of its translation. An optimum force system to realize canine translation was validated by analyzing translation displacement of the canine in each case. Results The PDL stress increased with an increase in force magnitude in all cases. The PDL stress first decreased with an increase in the M/F before the M/F reached the optimum value (M/F=10.1 mm), and then increased with an increase in the M/F. The initial displacement of the canine was inclined movement, which was most close to translation when the precise optimum M/F was applied. Conclusions The canine movement requires an appropriate force to prevent root absorption, whereas the translation movement requires an optimal M/F value which is within the physiological range. Understanding the influence of force and moment on tooth translation can help to apply more reasonable orthodontic force system and design more reasonable orthodontic device.
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Objective@#To explore the effectiveness of exercise combined with nutrition intervention on body mass index (BMI), blood glucose and blood lipid in obese adolescents.@*Methods@#Eighty obese adolescents who participated in a weight-loss training camp were selected as the intervention group, and 50 healthy adolescents were selected as the control group. Adolescents in the intervention group received 8-week weight-loss training and nutritional intervention, while those in the control group maintained their original lifestyle. The changes in body weight, body fat percentage, blood glucose, lipid and inflammatory indicators were compared before and after intervention in both groups.@*Results@#After intervention, weight, BMI, body fat percentage and waisthip ratio of the intervention group were significantly lower than those before intervention (P<0.05). The levels of insulin, HOMA-IR, TG and LDL in the intervention group before intervention were significantly higher than those in the control group (P<0.05). There was no significant difference in blood glucose after intervention (P>0.05). The levels of insulin, HOMA-IR, TG and LDL after intervention were significantly lower than those before intervention (P<0.05). There was no significant difference in HOMA-IR, TG and LDL levels between the intervention and the control group (P>0.05). The levels of TNF-α and hs-CRP in the intervention group before intervention were significantly higher than those in the control group (P<0.05); the levels of TNF-α and hs-CRP in the study group after intervention were significantly lower than those before intervention(P<0.05); the levels of TNF-α and hs-CRP in the control group before and after intervention had no significant changes (P>0.05).@*Conclusion@#Exercise combined with nutrition intervention can effectively reduce body fat and body weight, improve insulin resistance, regulate glycolipid metabolism and reduce inflammation in adolescent obese patients.
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Objective To study the effects of different parameters (thickness,orthodontic displacement,elastic modulus) from Invisalign on canine displacement and periodontal ligament (PDL) stress during mandibular canine intrusion treatment.Methods Forty-eight different Invisalign models were used to simulate canine intrusion treatment by using the finite element method.Results The initial displacement of the canine and stress on canine PDL were proportional to the thickness,intrusion displacement,and elastic modulus of the Invisalign,and the intrusion displacement had the greatest influence on canine displacement.During canine intrusion treatment,the compressive stress on PDL was the most sensitive and changed easily with the change of parameters.Conclusions The canine displacement may increase with the thickness,intrusion displacement and elastic modulus of Invisalign increasing,however,the stress on PDL will also increase,showing the largest increasing magnitude in compressive stress on PDL meanwhile.Therefore,to accelerate tooth movement in Invisalign treatment,it is suggested to use the assisted devices or some other measures such as attachment,supplement of bracket-wires treatment,or implant anchorage.
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Objective To establish a method to detect the content of propylene glycol in the recombinant human glucagon-like peptide-1(rhGLP-1)(7-36) injection by gas chromatography(GC). Methods GC was performed using a quartz capillary column (30 m ×320 μm,0.5 μm) with the mobile phase of N2 and inlet temperature of 230℃ at the flow rate of 1ml/min and column temperature of 250 ℃, the injection volume was 1μl. Results The calibration curve was linear within the range of 0.5-1.5 mg/ml, r=0.9991. The average recovery rate was 100.2%; under different chromatographic conditions, the method had good stability, RSD was less than 2.0%. Conclusion This method is simple, accurate and reproducible, and can be applied in the determination of propylene glycol content in rhGLP-1(7-36) injection.
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Objective To study the protective effect of hyperin( Hyp) on the acute liver injury in rats induced by CCl4 . Methods The acute liver injury model was induced by CCl4 . The effect of Hyp on acute liver injury of rat liver histopathology was observed;and the impact of changes of homogenates total superoxide dismutase ( T-SOD) ,glutathione ( GSH) activity and malondialdehyde ( MDA) in liver were de-tected. Results The acute liver injury of tissue induced by CCl4,apparent pathological inflammation and fibrous tissue degeneration and necrosis were observed by HE staining;At the high doses of 60 mg/kg and medium doses of 30 mg/kg treated by Hyp,liver pathology changes was significantly obvious. The T-SOD,GSH activity of liver tissue was significantly increased in the groups of Hyp treatment,MDA content was significantly decreased,which related to the dosages. Conclusion In the rat model of acute liver injury induced by CCl4 . A better therapeu-tic effect of Hyp was shown,the mechanism may be related to its antioxidant activity.