The Doha Declaration has entrusted to the members of WHO the right to use the compulsory licensing for drug patents in the face of global public health crises.Although the basic compulsory licensing system for drug patents has been established in China, the efficiency of its implementation is low, the responsibility of its executive departments is unclear, the related rules are not fully understood by pharmaceutical enterprises, it is thus necessary to improve and perfect the relevant legal provisions and systems in order to effectively improve the accessibility of drugs.

Objective To observe the therapeutic effect of folic acid on transient ischemic attack(TIA)patients with homocysteinaemia (Hcy ). Methods 129 patients of primary TIA with Hcy were divided into two groups randomly. The observation group ( n = 65 )was administered with conventional therapy and folic acid, and the control group ( n=64 ) was only given conventional therapy. The variances of the plasma HCA level three months later were compared, and remission rate of TIA and complete stroke incidence one year later were analyzed between two groups. Results The Hcy incidence rate of TIA patients was up to 41.4%. Three months later, the plasma HCA level of observation group was lower than control group( ( 14.27 ± 6. 13 ) μmol/L vs (24.99 ± 6.87 )μmol/L, t=2.799, P＜0. 01 ) ,and much lower than that of the control group post-treatment ( ( 14. 27 ±6. 13)μmol/L vs (24.68 ± 6.89) μmol/L, t = 2.735, P ＜ 0.01 ). One year later, the complete stroke incidence of TIA in observation group was lower than that of the control group(9.8% vs 25.0%, P＜0.05 ) ,and complete remission rate was higher than the latter(73.8% vs 50.0%, P ＜ 0. 01 ). Conclusion Folic acid can decrease the plasma HCA level of TIA patients with Hcy efficiently,and improve the prognosis of such patients.

OBJECTIVETo investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress, TNF-α and TGF-β1 in rats with diet-induced non-alcoholic fatty liver disease (NAFLD).

METHODSThirty male rats were randomly divided into 3 equal groups and fed for 16 weeks with normal diet (ND), high-fat diet (HFD), or high-fat diet with intraperitoneal injection of liraglutide (GLP-1, administered in the later 4 weeks). The rats were then sacrificed to obtain blood samples and liver tissues for analyzing the levels of blood aminotransferase (ALT), triglyceride (TG), and total-cholesterol (TC) using an automatic biochemical analyzer and the levels of superoxide dismutase (SOD), malondial-dehyde (MAD), free fatty acid (FFAs), TNF-α in the liver homogenates and TGF-β1 in serum by radioimmunoassay or ELISA.

RESULTSCompared with ND group, HFD group showed significantly increased body weight, liver index, serum levels of ALT, TG, TC, and TGF-β1, and TG, TC, MAD, FFAs, and TNF-α in the liver homogenates, with also significantly increased degree of hepatic steatosis and inflammation activity (P<0.05) and lowered level of SOD. All these changes were markedly ameliorated in GLP-1 group (P<0.05).

CONCLUSIONLiraglutide can reduce high-fat diet-induced hepatic steatosis, improve oxidative stress and lipid peroxidation, and decrease TGF-β1 and TNF-α levels in serum and liver homogenates, suggesting its potential as a therapeutic agent for NAFLD.

Alanine Transaminase ; blood ; Animals ; Cholesterol ; blood ; metabolism ; Fatty Acids, Nonesterified ; metabolism ; Hypoglycemic Agents ; pharmacology ; Liraglutide ; pharmacology ; Liver ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Non-alcoholic Fatty Liver Disease ; blood ; metabolism ; pathology ; Oxidative Stress ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta1 ; blood ; Triglycerides ; blood ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective: To investigate the role of piperine on the transformation of endothelial cells into fibroblasts. Methods: Cultured human umbilical vein endothelial cells (HUVECs, 4-6 passage) were used for the main experiments. The transformation models of endothelial cells into fibroblasts were induced by transforming growth factor β (TGF-β) stimulation. HUVECs were divided into 6 groups: control group, TGF-β group and 4 groups treated with various concentrations of piperine (1, 5, 10, 20 μmol/L). CKK-8 was used to detect cell proliferation. The CD31/α-smooth muscle actin (α-SMA) expression level was detected by fluorescent staining. The vascular endothelial cadherin (VE-cadherin)/vimentin expression was detected by immunofluorescence staining. RT-PCR was used detect the mRNA expressions of transformation markers. Western blot was used to detect the protein expression of snail and twist. Results: TGF-β increased HUVECs proliferation (P<0.05), which could be significantly inhibited by 10 and 20 μmol/L of piperine, but not by 1 and 5 μmol/L of piperine. Immunofluorescence results demonstrated that TGF-β increased HUVECs transformation to fibroblasts as shown by downregulated expression of endothelial markers CD31, VE-cadherin, and upregulated expression of α-SMA and vimentin, again, these effects could be attenuated by 10 and 20 μmol/L piperine. The expression levels of collagen type Ⅰ and type Ⅲ were significantly higher in TGF-β group than in control group (P<0.05), significantly lower in TGF-β+10 μmol/L piperine group and TGF-β+20 μmol/L piperine group than in TGF-β group (P<0.05).In addition, RT-PCR results showed that TGF-β increased mRNA expression of transformation markers (snail1, snail2, twist1, twist2), while 10 and 20 μmol/L of piperine could significantly downregulated the mRNA expressions of these markers. The protein expression levels of snail and twist were significantly higher in TGF-β group than in control group (both P<0.05), which was significantly lower in TGF-β+20 μmol/L piperine group than in TGF-β group (both P<0.05). Conclusions Piperine can inhibit the transformation of endothelial cells into fibroblasts. This effect might be viewed as one of the potential mechanisms of reduced myocardial fibrosis post piperine treatment.

Purpose: This study aimed to investigate reproductive concerns among breast cancer patients of reproductive age, analyze the influencing factors, explore the relationship between coping styles, fear of progression (FOP), and reproductive concerns, and identify the multiple effects of coping styles on the relationship between FOP and reproductive concerns among Chinese breast cancer patients. Methods: A cross-sectional, descriptive study was conducted among breast cancer patients in four tertiary grade A hospitals in Fujian, China, from January 2022 to September 2022. A total of 210 patients were recruited to complete paper-based questionnaires, which included the general data questionnaires, the Reproductive Concerns After Cancer Scale (RCACS), the Fear of Progression Questionnaire-Short Form (FOP-Q-SF), and the Medical Coping Modes Questionnaire (MCMQ). Structural equation models were utilized to evaluate the multiple effects of coping styles on FOP and reproductive concerns. Results: Reproductive concerns in breast cancer patients had a mean score of 53.02 (SD, 10.69), out of a total score of 90, and coping styles for cancer (confrontation, avoidance) were closely associated with FOP and reproductive concerns. FOP showed a significant positive correlation with reproductive concerns (r = .52, p < .01). At the same time, confrontation was significantly negatively correlated with both FOP (r = −.28, p < .01) and reproductive concerns (r = −.39, p < .01). Avoidance was positively correlated to both FOP (r = .25, p < .01) and reproductive concerns (r = .34, p < .01). The impact of FOP on reproductive concerns is partially mediated by confrontation and avoidance, with effect sizes of .07 and .04, respectively. These mediating factors account for 22.0% of the total effect. Conclusions The FOP directly impacted reproductive concerns, while coping styles could partially mediate the association between FOP and reproductive concerns. This study illustrates the role of confrontation and avoidance in alleviating reproductive concerns, suggesting that it is necessary to focus on the changes in reproductive concerns among reproductive-age breast cancer patients. Healthcare professionals can improve disease awareness and reduce patients' FOP, thereby promoting positive psychological and coping behaviors and ultimately alleviating reproductive concerns.

Objective:To investigate the application value of small private online course (SPOC) based on the concept of outcomes-based education (OBE) in rehabilitation nursing training for elderly patients after lumbar surgery.Methods:A total of 46 clinical nurses in Department of Spinal Surgery in our hospital were selected as subjects, and they were divided into control group and observation group using a simple random number table, with 23 nurses in each group. The nurses in the control group were trained by the traditional teaching method, while those in the observation group were trained by SPOC teaching based on the educational concept of OBE. The two groups were assessed in terms of the effect of training, professional core competencies, and degree of satisfaction with the training mode. SPSS 22.0 was used to perform the chi-square test and the t-test. Results:Compared with the control group, the observation group had significantly better overall evaluation [（89.52±5.07）vs.（86.48±4.13）], mastery of practical operation skills (91.30% vs. 65.22%), and proficiency in the operation of commonly used clinical instruments (95.65% vs. 80.95%)( P<0.05). The observation group had a significantly better score of the professional core competence scale than the control group ( P<0.05). Compared with the control group, the observation group had a significantly higher degree of satisfaction with the training ( P<0.05). Conclusion:In rehabilitation nursing training for elderly patients after lumbar surgery, SPOC teaching based on the educational concept of OBE can improve the training effect of clinical nurses, enhance their professional core abilities, and increase the degree of satisfaction with training.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

OBJECTIVE： To observe neuroprotective effects of low-molecular-weight chondroitin sulfate （CS） on dopaminergic neurons in Parkinson’s disease （PD） mice model induced by 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）. METHODS： C57BL/6 mice were randomly divided into control group， MPTP injury group， low-molecular-weight CS low-dose and high-dose groups （100， 400 mg/kg）. Control group and MPTP injury group were given constant volume of normal saline intragstrically， administration groups were given relevant medicine intragastrically， once a day， for consecutive 17 d. Since 11th day after medication， except for control group， other groups were given MPTP solution （20 mg/kg） intraperitoneally to induce PD model， once a day， consecutive 5 d. After last medication， behavioral changes of mice （10 mice in each group） were evaluated by rotary rod fatigue tester. The damage of dopamine neurons （the percentage of TH positive cell and the percentage of fluorescence intensity） in substantia nigra of mice （3 mice in each group） was detected by immunohistochemistry and immunofluorescence. The content of dopamine in striatum was determined by HPLC （6 mice in each group）. The changes of oxidant stress indexes （SOD， GSH-Px， MDA） in substantia nigra of mice were determined by chemical colorimetry （6 mice in each group）. RESULTS： Compared with control group， retention time of mice on rotating rods was shortened significantly in MPTP injury group； TH positive cells of substantia nigra were decreased significantly， fluorescence intensity was obviously weakened； the percentage of positive cells and fluorescence intensity， the content of dopamine in striatum， the activities of SOD and GSH-Px in substantia nigra were decreased significantly， while the content of MDA was increased significantly （P＜0.01）. Compared with MPTP injury group， retention time of mice on the rotating rods was prolonged significantly in low-molecular-weight CS groups， the number of TH positive cells was increased significantly in substantia nigra and fluorescence intensity was increased significantly； the percentage of positive cells， the percentage of fluorescence intensity and the content of dopamine in striatum were increased significantly， while above indexes of high-dose group were significantly longer or higher than those of low-dose group （P＜0.05 or P＜0.01）. The activities of SOD and GSH-Px in substantia nigra were increased significantly in low-molecular-weight CS groups， while the content of MDA in substantia nigra was decreased significantly in low-molecular-weight CS high-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Prophylactic administration of low-molecular-weight CS can relieve the damage of dopaminergic neurons in substantia nigra of PD model mice induced by MPTP in a dose-dependent manner， and increase the secretion of dopamine in striatum. The effect may be related to the inhibition of lipid peroxidation and the enhancement of antioxidant capacity of tissues.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*