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OBJECTIVE To explore the pricing methods of multi-indication drugs suitable for China from the economic perspective. METHODS By sorting out the situation and pricing methods of multi-indication drugs in China’s health insurance negotiation in recent years， the experience of typical countries （Sweden， Germany， Britain， Italy， etc.） in the value measurement， access and management of multi-indication drugs were explored with 3 methods， namely， branded pricing， weighted average bidding pricing， and single bidding pricing under the risk sharing agreement. The advantages and disadvantages of the 2 types of multi-indication drug pricing methods， such as single bidding pricing and indication-based pricing， and conditions of use were explored， so as to put forward a pricing method suitable for multi-indication drugs in China. RESULTS＆＆CONCLUSIONS The pricing of multi-indication drugs by single bidding pricing mode has certain disadvantages at this stage， and should be supplemented and improved by agreement pricing. Based on international experience， China can explore a reasonable management mode of drug indications， adopt a pricing mode with agreement pricing as the main mode and multiple pricing modes as the coexisting mode， and promote the development of pharmacoeconomic evaluation and the improvement of drug use information collection mechanism.
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Objective:To observe any effect of intermittent theta burst stimulation (iTBS) on the spatially-delayed responses of working memory using cynomolgus macaques.Methods:The working memory of six male cynomolgus macaques (8-9 years old) was trained using a spatially-delayed response task. They were then randomly divided into an iTBS group and a control group, each of 3. The iTBS group was given iTBS at an intensity of 35% of the maximum output, with 2 seconds of stimulation followed by 8 seconds of rest with trains of 50Hz bursts repeated at a frequency of 5Hz over a period of 192 seconds once daily for 5 days, while the control group was given sham iTBS. Before and after the 5 days, the body weight and working memory of each animal were evaluated. The total number of effective feeding episodes, and of effective feeding episodes with short and long delay periods were recorded.Results:There was no significant change in the average body weight of either group before and after the modeling and iTBS intervention. After the intervention the number of total effective feeding cases and those with a short delay period were both significantly higher in the iTBS group than in the control group. However, no significant inter-group differences in the effective feeding cases with a long delay period were observed.Conclusions:iTBS is effective in improving the spatially-delayed responses of working memory, at least in cynomolgus macaques.
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Objective:To investigate the epidermal growth factor receptor (EGFR) mutation rate, mutation characteristics and distribution characteristics of different mutation types in patients with non-small cell lung cancer (NSCLC) in Fuyang of Yunnan province, to provide the clinical individualized targeted therapy of NSCLC in this region.Methods:A total of 328 NSCLC patients whose native place were Fuyuan and who underwent EGFR test in Fuyuan County People's Hospital in Yunnan Province from January 2018 to August 2020 were selected, and their clinical data such as gender, age, ethnicity, pathological type and the results of EGFR test were collected for statistical analysis.Results:The EGFR mutation rate of NSCLC patients was 40.55% (133/328). The EGFR mutation rate of female patients was higher than that of males ( P < 0.01). The EGFR mutation rate showed a downward trend with age, the EGFR mutation rate of patients ≤ 60 years old was higher than that of patients > 60 years old ( P = 0.014). The EGFR mutation rate in ethnic minority was not statistically different from Han nationality ( P = 0.789). The EGFR mutation rate of patients without smoking history was higher than that of patients with smoking history ( P<0.01). Patients with adenocarcinoma had a higher EGFR mutation rate than squamous cell carcinoma ( P = 0.002). The EGFR mutation rate in patients with stage Ⅰ-Ⅱwere higher than that in patents with stage Ⅲ-Ⅳ ( P = 0.013). The EGFR mutation rate in tissue samples were higher than that in peripheral blood samples ( P = 0.009). In 328 patients the EGFR single-point mutation rate was 24.70% (81/328), and the compound mutation rate was 15.85% (52/328); the common mutation rate was 17.07% (56/328), and the rare mutation rate was 23.48% (77/328). The top 5 mutation types were L858R (10.06%), G719X+S768I (7.32%), 19-Del (7.01%), G719X+L861Q (6.40%), and G719X (4.21%). In 133 patients with EGFR mutation, the proportion of patients with rare mutation [57.89% (77/133)] was higher than the proportion of patients with common mutation [42.11% (56/133)]. Conclusion:The EGFR mutation rates of female, adenocarcinoma, non-smoking and young NSCLC patients in Fuyuan area are high, and the rare mutation rate is high.
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Inflammatory cytokines can mediate many biological processes and are tightly regulated by the body. Loss of control can trigger a range of diseases such as autoimmune inflammation and cancer. Therefore, a number of biological agents that can effectively regulate the biological effects of inflammatory cytokines such as recombinant anti-inflammatory cytokines, cytokine receptors and neutralizing antibodies have been extensively used in the treatment of related diseases caused by the imbalance of inflammatory cytokines. In recent years, in particular, a number of new innovative biological agents for blocking and regulating cytokine activities are emerging. In this article, we review the recent development and clinical use of the biologics targeting TNF-α, IL-1, IL-6 and IL-17, and point out their inherent limitations and clinical risks. Finally, based on the research findings of our own and other scholars, we suggest some approaches and methods for reducing their side-effects and clinical risk. We consider that using modern biotechnology to improve the tissue specificity to inflammatory site and tumor will be an important development direction of such biologics.
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Humans , Biological Products , Metabolism , Cytokines , InflammationABSTRACT
BACKGROUND:Mechanical stimulation triggers a muscle tissue remodeling, during which, myoblast process is a multi-stage development process. Many signals in extracellular matrix are involved in myoblast process, and mechanical signals are considered as important external factors for muscle formation and regeneration. Numerous studies concerning cyclic tensile stress effects on myoblast proliferation and apoptosis have been reported, but the specific mechanism underlying the mechanical stimulation in muscle formation is stil unclear. OBJECTIVE:To study the effects of cyclic stretch on proliferation of C2C12 myoblasts and its mechanism. METHODS:C2C12 myoblasts were cultured in vitro under 10%cyclic stretch for 6, 12 and 24 hours. RESULTS AND CONCLUSION:The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that with the time of cyclic stretch, the proliferation of C2C12 myoblasts and the rate of S-phase fraction were gradual y increased and peaked at 12 hours (P<0.05), and then decreased. Western blot assay showed that the expression of nuclear transcription factorκB protein was decreased with time, which was inversely correlated to the proliferation of C2C12 myoblasts, but increased at 24 hours under the cyclic stretch. These findings indicate that the cyclic stretch can induce C2C12 myoblasts proliferation and alter the cellcycle. Nuclear transcription factorκB may be involved in this process.
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ObjectiveTo explore the anatomy and clinical significance of fixation combined with limited outside cut restoration gram needle internal fixation for distal radial fractures. MethodsBased on the anatomical observation and measurement of the forearm and hand. Found out the distal radial fractures fixed bracket screws and gram needle safety area and the needle into the body, and made reasonable angle respectively, to formulate standardized orientation, and applied to clinical procedures, and the clinical cases were followed up. The clinical curative effect was observed. ResultsThe place for the fixed bracket screws of the second metacarpal was the nail parts of radial dorsal partial ends. The proximal fracture for external fixation stents bolt into the nail near abductor muscle and manipulation long in the thumb short extensormuscles. Its feet side for stabbing abductor muscle and refers to a long stretch of radial side for tendon, radial side wrist short stretch muscles. The farthest distance between the lister nodule was (63.69 ±3.00) mm,nearest distance between the lister nodule was(123.64 ±5.00)mm. Gram needle do limited internal fixation security clearance for thumb long stretch tendon and refers to stretch tendons,radial side wrist length stretch tendons, thumb short extensor tendons, stretch retinaculum and this gap proximal distance lister nodule for ( 33. 52 ± 4.20) mm, remote distance lister nodule for( 8.81 ± 0. 88) mm. In clinical applications, wrist imaging recovery, function of ratings had no significant difference ( P ＞ 0.05). But the postoperative complications of the two sets of patients had statistically significant difference ( P ＜ 0. 05 ). ConclusionAccording to the anatomy of distal radial fractures,from the results of our research applied in fixation distal radial fractures in the operation,it had the advantages of simple operation,reset good,fixed firmly,and small trauma. It was worth of used widely in clinical.
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Objective: To investigate hard tissue changes produced by maxillary protraction in patients with skeletal Class III malocclusion at different bone age,and to determine the relationship between the effect of maxillary protraction and bone age.Methods:75 subjects of skeletal Class III malocclusion with retruded maxilla were treated by maxillary protraction and rapid maxillary expansion for 6 months.Cephalometric radiographs were taken before and after treatment.The bone age of individual patients was assessed using cephalometric radiographs at the initiation of treatment on the basis of cervical vertebrace maturation indicators(CVMI).Patients were divided into three groups:Prepubertal growth peak group (CVMI Ⅰ-Ⅱ,8.2-11.3 years old), pubertal growth peak group (CVMI Ⅲ,10.2-12.3 yeasr old), and postpubertal growth peak group (CVMI Ⅳ-Ⅵ,11.5-14.5 years old).Results:(1)There was no difference in the maxillary advancement after maxillary protraction between the prepubertal growth peak and the pubertal growth peak groups;(2) in the postpubertal growth peak group, there was a decrease in maxillary skeletal advancement, whereas the dentoalveolar advancement was increased; (3) the posteroinferior rotation of mandible, the increase of lower facial height, and the eruption of maxillary molars showed no correlation with bone age.Conclusion:The importance of performing a biologic evaluation of bone age in the diagnosis and treatment planning of skeletal Class III malocclusions in individual patients must be emphasized.