ABSTRACT
Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.
ABSTRACT
Objective:To explore national standard of occupational skills for assistive technology consultants in China based on the study of relevant international standards. Methods:After analyzing the international and some other national job content, work requirements, professional education and vocational training, and vocational standards of assistive technology consultants, the national occupational skills standard for assistive technology consultants in China was established referring to the compiling rules of national occupational skills standard. Results:According to the compiling rules of national occupational skills standard, the national occupational skills standard for assistive technology consultants in China included career situation, basic requirements, job requirements, and weight table, etc. Conclusion:The vocational development, structural framework and content of professional capacity for assistive technology consultants are studied. The draft of national occupational skills standard for rehabilitation assistive technology consultants has been compiled.
ABSTRACT
Gegen Qinliantang， a classic traditional Chinese medicine（TCM） compound， has been verified in modern research to possess various pharmacological effects such as anti-inflammation，anti-oxidative stress，protecting intestinal mucosal barrier， and regulating intestinal flora and immune response. Ulcerative colitis （UC） is a chronic idiopathic inflammatory disease involving the colorectal mucosa， which mainly results from genetic susceptibility， intestinal mucosal barrier damage， abnormal immune response， intestinal flora disturbance， and bile acid metabolism disorders. By reviewing the literature published in recent years， this paper sorted out the relevant pathways and mechanisms involved in the treatment of UC by Gegen Qinliantang to provide ideas for further clinical and basic research. This literature review uncovered that Gegen Qinliantang exerted the therapeutic effects against UC mainly via interleukin-6（IL-6）/Janus tyrosine kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3） signaling pathway， Toll like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB） signaling pathway，Notch signaling pathway， and matrix metalloproteinase-9（MMP-9）/p38 mitogen-activated protein kinase（p38 MAPK） signaling pathway. Gegen Qinliantang regulates the intercellular molecular transmission in multiple pathways to protect the intestinal mucosal barrier， adjust the immune response and anti-oxidative stress， and relieve UC， demonstrating the multi-target， multi-mechanism， and multi-pathway advantages of TCM compounds.
ABSTRACT
BACKGROUND@#Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring.@*METHODS@#Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting.@*RESULTS@#There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment.@*CONCLUSIONS@#The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.
Subject(s)
Animals , Female , Male , Pregnancy , Rats , Cytoskeletal Proteins/metabolism , Gene Expression Regulation , Hippocampus/metabolism , Insulin-Like Growth Factor II/metabolism , Learning , Learning Disabilities/psychology , Memory Disorders/psychology , Nerve Tissue Proteins/metabolism , Prenatal Exposure Delayed Effects/psychology , Random Allocation , Rats, Wistar , Social Environment , Stress, Psychological/geneticsABSTRACT
OBJECTIVE: To analyze the prevalence and influencing factors of work-related musculoskeletal disorders(WMSDs) in civil aviation flight attendants. METHODS: A total of 810 flight attendants from three civil aviation airlines in China were selected as research subjects using the convenient sampling method. The revised Musculoskeletal Disorders Investigating Questionnaire was used to investigate the prevalence of WMSDs in various parts of the body in the past year. RESULTS: The total prevalence of WMSDs in flight attendants in this survey was 64.4%(522/810). The prevalence of WMSDs in various parts of the body from high to low was: neck(48.0%), shoulder(38.6%), lower back/waist(26.0%), upper back(19.8%), feet(15.1%), knee(14.0%), hip and leg(11.0%), hand and wrist(9.0%) and elbow(5.1%). The results of multivariate logistic regression analysis showed that working with an uncomfortable posture and the shortage of staff in the work sector were risk factors for neck WMSDs(all P<0.05). The protective factors were sufficient rest time and voluntary decision when to take a break during work(all P<0.05). Carrying heavy objects >20 kg, working in uncomfortable posture and shortage of staff were risk factors for shoulder WMSDs(all P<0.05). Working in uncomfortable posture and repeated an operation every minute were risk factors for lower back/waist WMSDs(all P<0.05), and sufficient rest time was its protective factor(P<0.05). CONCLUSION: The prevalence of WMSDs in civil aviation flight attendants is high, and the neck, shoulder and ower back/waist are the most commonly affected part of the body. The main influencing factors are poor ergonomics and work organization.
ABSTRACT
BACKGROUND@#Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective.@*METHODS@#A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively.@*RESULTS@#In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results.@*CONCLUSION@#Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.
ABSTRACT
Background@#Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective.@*Methods@#A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively.@*Results@#In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results.@*Conclusion@#Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.
ABSTRACT
Objective The purpose of this study was to identify a pathogenic variant in a Chinese family with Alport syndrome and analyze the pathogenicity of the variant. Methods Using targeted region capture and high-throughput sequencing technology, we identified the genetic variant of the proband with Alport syndrome, verified the variant in the family members by Sanger sequencing, and analyzed its influence on the pre-mRNA splicing process by in vitro minigene assay. Results A heterozygous variant c.2767G>T (p.Gly923Cys) was identified as a novel variant in exon 32 of the COL4A5 gene in the proband, which was confirmed by Sanger sequencing to be cosegregated with disease in the family. The minigene assay demonstrated that the c.2767G>T variant induced deletion of exon 32 of the COL4A5 gene. Conclusion A novel COL4A5 mutation was identified by targeted region capture and high-throughput sequencing, which has enriched the gene mutation spectrum of Alport syndrome. The exonic mutation c.2767G>T confirmed to be a splicing mutation by in vitro minigene assay, which may lead to a deeper insight into the molecular pathogenesis of Alport syndrome.
ABSTRACT
Objective: To investigate the clinical features in patients with respiratory disease and/or hypoxia related severe pulmonary hypertension. Methods: Our research included in 2 groups: Hypoxia related pulmonary hypertension group, the patients with respiratory disease and/or hypoxia combining severe pulmonary hypertension, n=31 and Severe idiopathic pulmonary hypertension group, n=41. The diagnosis was confirmed by right heart catheterization; the patients treated in our hospital from 2016-01 to 2017-01 were consecutively enrolled and studied. Clinical features and treatment were compared between 2 groups. Results: Compared with Severe idiopathic pulmonary hypertension group, the patients' mean age, BMI and blood pressure were higher in Hypoxia related pulmonary hypertension group, while the majority clinical features were similar between 2 groups. In Hypoxia related pulmonary hypertension group, more patients had obstructive sleep apnea-hypopnea syndrome (OSAHS) with the higher AHI and the lower mean blood oxygen pressure at night, increased diameters of left atria and ventricle, elevated NT-proBNP level and reduced 6 minutes walking distance; some patients tried target drug therapy, calcium channel blocker therapy or continuous positive airway pressure therapy. Conclusion: Respiratory disease especially OSAHS should be screened from the patients with severe pulmonary hypertension. In addition to basic respiratory and hypoxia medication, further investigation is needed to confirm whether the prognosis could be improved by calcium channel blocker therapy and target drug therapy.
ABSTRACT
Aim To investigate the effect of baicalein on insulin secretion from rat islets and the underlying mechanism. Methods Pancreatic islets were obtained from the pancreas of male Wistar rats by collagenase P digestion and histopaque-1077 density gradient separa-tion. Single islet cells were dispersed from pancreatic islets by Dispase II digestion. Insulin secretion experi-ment was applied to observe insulin release after baica-lein stimulation. To study the potential mechanism, calcium imaging technique and patch-clamp experiment were applied to measure intracellular Ca2+ concentra-tion and voltage-dependent potassium channel currents (Kv). Results In 16. 7mmol·L-1 glucose, baica-lein accelerated insulin secretion in a dose-dependent manner. Baicalein promoted the intracellular Ca2+ con-centration. The patch-clamp experiment showed that baicalein inhibited Kv current in a dose-dependent manner. Conclusion Baicalein can increase the in-tracellular Ca2+ concentration by inhibiting Kv chan-nels and eventually promoting insulin secretion.