Quantitative evaluation of the medicine innovation policy in China: based on the PMC-Index model

IntroductionMedicine innovation is crucial in promoting the sustainable development of medicine undertakings, which has significant economic and social benefits. China is the main force in global medicine consumption, with a huge demand for innovative medicines. Thus, the Chinese government releases a series of policies aimed at providing scientific and reasonable guidance for medicine innovation. However, there is inadequate quantitative evaluation and comparison of various medicine innovation policies in the existing studies.MethodsThis paper adopts the approach of text mining and the Policy Modeling Consistency Index (PMC-Index) model to construct an evaluation system and then quantitatively evaluates and compares the traditional Chinese medicine innovation policies (TCMIPs), the biological medicine innovation policies (BMIPs), and the multiple medicine innovation policies (MMIPs) in China.ResultsThe results indicate that: (1) The three types of drug innovation policies have similarities in content and goal through comparative analysis of high-frequency words, while they also have their own characteristics. (2) The average PMC-Index of 29 TCMIPs is 5.77, which has the highest policy bad rate (21%); the average PMC-Index of 12 BMIPs is 6.21, which has the highest policy good rate (92%); moreover, the average PMC-Index of 35 MMIPs is 6.06, which has the highest policy excellence rate (26%). (3) The BMIPs, MMIPs, and TCMIPs have similar scores on policy object, policy orientation, policy timeliness, policy evaluation, and policy accessibility, while they differ significantly mainly on policy nature, incentive method, policy function, policy issuing agency, and policy instrument.DiscussionThis study contributes to a comprehensive understanding of medicine innovation policies in China, in order to provide theoretical support for future policy formulation and optimization in the medicine industry. Moreover, we expand the application scenarios of policy diffusion theory

Protective Efficacy of Vitamins C and E on p,p′-DDT-Induced Cytotoxicity via the ROS-Mediated Mitochondrial Pathway and NF-κB/FasL Pathway

Dichlorodiphenoxytrichloroethane (DDT) is a known persistent organic pollutant and liver damage toxicant. However, there has been little emphasis on the mechanism underlying liver damage toxicity of DDT and the relevant effective inhibitors. Hence, the present study was conducted to explore the protective effects of vitamin C (VC) and vitamin E (VE) on the cytotoxicity of DDT in HL-7702 cells and elaborate the specific molecular mechanisms. The results demonstrated that p,p′-DDT exposure at over 10 µM depleted cell viability of HL-7702 cells and led to cell apoptotic. p,p′-DDT treatment elevated the level of reactive oxygen species (ROS) generation, induced mitochondrial membrane potential, and released cytochrome c into the cytosol, with subsequent elevations of Bax and p53, along with suppression of Bcl-2. In addition, the activations of caspase-3 and -8 were triggered. Furthermore, p,p′-DDT promoted the expressions of NF-κB and FasL. When the cells were exposed to the NF-κB inhibitor (PDTC), the up-regulated expression of FasL was attenuated. Strikingly, these alterations caused by DDT treatment were prevented or reversed by the addition of VC or VE, and the protective effects of co-treatment with VC and VE were higher than the single supplement with p,p′-DDT. Taken together, these findings provide novel experimental evidences supporting that VC or/and VE could reduce p,p′-DDT-induced cytotoxicity of HL-7702 cells via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway

Carbon nanotube multilayered nanocomposites as multifunctional substrates for actuating neuronal differentiation and functions of neural stem cells

Carbon nanotubes (CNTs) have shown potential applications in neuroscience as growth substrates owing to their numerous unique properties. However, a key concern in the fabrication of homogeneous composites is the serious aggregation of CNTs during incorporation into the biomaterial matrix. Moreover, the regulation mechanism of CNT-based substrates on neural differentiation remains unclear. Here, a novel strategy was introduced for the construction of CNT nanocomposites via layer-by-layer assembly of negatively charged multi-walled CNTs and positively charged poly(dimethyldiallylammonium chloride). Results demonstrated that the CNT-multilayered nanocomposites provided a potent regulatory signal over neural stem cells (NSCs), including cell adhesion, viability, differentiation, neurite outgrowth, and electrophysiological maturation of NSC-derived neurons. Importantly, the dynamic molecular mechanisms in the NSC differentiation involved the integrin-mediated interactions between NSCs and CNT multilayers, thereby activating focal adhesion kinase, subsequently triggering downstream signaling events to regulate neuronal differentiation and synapse formation. This study provided insights for future applications of CNT-multilayered nanomaterials in neural fields as potent modulators of stem cell behavior

Protective Effect of Freeze-Dried Fruit Powder of Phyllanthus emblica L. on Acute and Chronic Hyperuricemia and Liver and Kidney Injuries in Mice

Objective: To explore the protective effect of the freeze-dried fruit powder of Phyllanthus emblica L. (PEFP) against acute and chronic hyperuricemia (HUA) and liver and kidney injuries in mice. Methods: Mouse models of acute and chronic HUA were established by intraperitoneal injection of hypoxanthine and potassium oxazinate, respectively. Meanwhile, PEFP at 75, 150 and 300 mg/kg mb were orally given to the mice in the intervention group for seven days. The levels of uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum, and the activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum and liver were detected. Liver and kidney indexes were calculated, and the pathological characteristics of liver and kidney tissues were observed by hematoxylin and eosin (HE) staining. Results: Compared with the model group, PEFP at 150 and 300 mg/kg mb significantly reduced the liver and kidney indexes (P < 0.01) and lowered serum UA, BUN, CRE, and AST levels in mice with acute hyperuricemia (P < 0.05 or P < 0.01). PEFP at 75, 150 and 300 mg/kg mb significantly inhibited serum and liver XOD and ADA activities (P < 0.01), and PEFP at 300 mg/kg mb lowered serum ALT levels in mice with acute hyperuricemia (P < 0.01). Meanwhile, all three doses of PEFP significantly reduced the liver and kidney indexes (P < 0.01), lowered serum UA, BUN and ALT levels (P < 0.01), and inhibited serum and liver XOD activities and serum ADA activity in mice with chronic hyperuricemia (P < 0.01). PEFP at 150 and 300 mg/kg mb lowered serum CRE and AST levels and liver ADA activity (P < 0.01). PEFP ameliorated the pathological changes of the liver and kidney in mice with acute and chronic hyperuricemia. Conclusion: PEPP can effectively decrease serum UA levels in mice with acute and chronic hyperuricemia, which may be related to the inhibition of XOD and ADA activities in the serum and liver, and the promotion of renal uric acid excretion, and can also exert renal and hepatoprotective effects

Greenhouse gas emissions in a subtropical jasmine plantation managed with straw combined with industrial and agricultural wastes

The effects of straw alone or combined with industrial and agricultural wastes as fertilizers on greenhouse gas (GHG) emissions are still poorly known in cropland areas. Here, we studied the effects of 3.5 Mg ha−1 straw and 3.5 Mg ha−1 straw combined with 8 Mg ha−1 of diverse wastes on GHG emission in a subtropical Jasminum sambac plantation in southeastern China. There were five treatments in a completely randomized block design: control, straw only, straw + biochar, straw + steel slag, and straw + gypsum slag. Emissions of carbon dioxide were generally higher in the treatments with waste than in the control or straw-only treatments, whereas the contrary pattern was observed in CH4 and N2O emission rates. Moreover, the total global warming potentials (GWPs) were no significantly higher in most of the amended treatments as compared to the control and straw-only treatments. In relation to the treatment with only straw, GWPs were 9.4% lower when steel slag was used. This finding could be a consequence of Fe amount added by steel slag, which would limit and inhibit the emissions of GHGs and their transport from soil to atmosphere. Our results showed that the application of slags did not increase the emission of GHGs and that the combination of straw with steel slag or biochar could be more effective than straw alone for controlling GHGs emission and improve soil C and nutrient provision

An Evil Backstage Manipulator: Psychological Factors Correlated with Health-Related Quality of Life in Chinese Patients with Crohn's Disease

Health-related quality of life (HRQoL) is recommended as one of essential parameters to evaluate treatment effect and clinical outcome in patients with Crohn's disease (CD). Recent studies reported that psychological factors might play a role in HRQoL in Western and American CD patients. Sufficient evidences in Chinese CD patients are still unavailable. This study is dedicated to investigate the correlation of various psychological factors with HRQoL in Chinese CD patients. We prospectively collected 40 active and 40 quiescent CD patients in China and found that psychological factors, especially neuroticism and anxiety, significantly correlate with and affect HRQoL in both active and quiescent CD groups. This is the first report revealing correlation between psychological factors and HRQoL in Chinese CD patients. Therefore, we assume that our results can contribute to a better understanding of etiology and tailoring of management in Chinese patients with Crohn's disease and are beneficial to our colleagues to compare the heterogeneous characteristics of Crohn's disease in different ethnic groups

Ischemia/reperfusion-activated ferroptosis in the early stage triggers excessive inflammation to aggregate lung injury in rats

ObjectiveLung ischemia/reperfusion injury (LIRI) is a clinical syndrome of acute lung injury that occurs after lung transplantation or remote organ ischemia. Ferroptosis and inflammation are involved in the pathogenesis of LIRI according to the results of several studies on animal models. However, the interactive mechanisms between ferroptosis and inflammation contributing to LIRI remain unclear.MethodsHE staining and indicators of oxidative stress were used to evaluated the lung injury. The reactive oxygen species (ROS) level was examined by DHE staining. The quantitative Real-time PCR (qRT-PCR) and western blot analysis were employed to detect the level of inflammation and ferroptosis, and deferoxamine (DFO) was used to assess the importance of ferroptosis in LIRI and its effect on inflammation.ResultsIn the present study, the link of ferroptosis with inflammation was evaluated at reperfusion 30-, 60- and 180-minute time points, respectively. As the results at reperfusion 30-minute point shown, the pro-ferroptotic indicators, especially cyclooxygenase (COX)-2 and acyl-CoA synthetase long-chain family member 4 (ACSL4), were upregulated while the anti-ferroptotic factors glutathione peroxidase 4 (GPX4), cystine-glumate antiporter (XCT) and ferritin heavy chain (FTH1) were downregulated. Meanwhile, the increased level of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α) and IL-1β were observed beginning at reperfusion 60-minute point but mostly activated at reperfusion 180-minute point. Furthermore, deferoxamine (DFO) was employed to block ferroptosis, which can alleviate lung injury. Expectedly, the survival rate of rats was increased and the lung injury was mitigated containing the improvement of type II alveolar cells ultrastructure and ROS production. In addition, at the reperfusion 180-minute point, the inflammation was observed to be dramatically inhibited after DFO administration as verified by IL-6, TNF-α and IL-1β detection.ConclusionThese findings suggest that ischemia/reperfusion-activated ferroptosis plays an important role as the trigger for inflammation to further deteriorate lung damages. Inhibiting ferroptosis may have therapeutic potential for LIRI in clinical practice

Longitudinal associations of concurrent falls and fear of falling with functional limitations differ by living alone or not

BackgroundFalls and fear of falling (FOF) are independent risk factors for functional limitations in older adults. However, the combined effect of falls and FOF on functional limitations and the moderating role of living alone or not is unclear. We aimed to examine (1) the independent and combined effect of falls and FOF on functional limitations in older adults and (2) whether living alone moderates these associations.MethodsWe used data from the National Health and Aging Trends Study (NHATS) and included 5,950 U.S. community-dwelling older adults aged 65 and older from Round 1 (Year 2011) and Round 2 (Year 2012). Falls and FOF were ascertained by asking participants whether they had any falls in the last year and whether they had worried about falling in the previous month at R1. Assessed functional limitations included any difficulties with mobility, self-care, or household activities at R2. Poisson regression models were used to examine the longitudinal associations of falls and FOF with functional limitations and the moderation effects of baseline living alone.ResultsOf the 5,950 participants, 16.3% had falls only; 14.3% had FOF only; 14.3% had both, and 55.1% had neither at baseline. In the adjusted model, those who experienced concurrent falls and FOF in R1 had a higher risk of functional limitations at R2 than those with neither (Mobility: Incidence risk ratio [IRR] = 1.34, 95% CI: 1.24–1.45; Self-care: IRR = 1.18, 95% CI: 1.11–1.26; Household: IRR = 1.20, 95% CI: 1.11–1.30). Moreover, living alone significantly moderated the longitudinal associations of concurrent falls and FOF with mobility activity limitations.ConclusionThe findings suggest that strategies to improve falls and FOF together could potentially help prevent functional limitations. Older adults who live with others and have falls or FOF should receive interventions to promote their mobility activities

Nonlinear Free Vibration Analysis of Axisymmetric Polar Orthotropic Circular Membranes under the Fixed Boundary Condition

This paper presents the nonlinear free vibration analysis of axisymmetric polar orthotropic circular membrane, based on the large deflection theory of membrane and the principle of virtual displacement. We have derived the governing equations of nonlinear free vibration of circular membrane and solved them by the Galerkin method and the Bessel function to obtain the generally exact formula of nonlinear vibration frequency of circular membrane with outer edges fixed. The formula could be degraded into the solution from small deflection vibration; thus, its correctness has been verified. Finally, the paper gives the computational examples and comparative analysis with the other solution. The frequency is enlarged with the increase of the initial displacement, and the larger the initial displacement is, the larger the effect on the frequency is, and vice versa. When the initial displacement approaches zero, the result is consistent with that obtained on the basis of the small deflection theory. Results obtained from this paper provide the accurate theory for the measurement of the pretension of polar orthotropic composite materials by frequency method and some theoretical basis for the research of the dynamic response of membrane structure

Blow to the northeast? Intraspecific differentiation of populus davidiana suggests a northeastward skew of a phylogeographic break boundary in East Asia

Aim There is increasing interest in the role that biological traits, and historical and biogeographic processes, play in the formation of phylogeographic patterns. An arid belt that once existed in northern China might have affected many plants, but this has yet to be tested in an arid-tolerant, wind-dispersed species. Here, we tested how intrinsic and extrinsic factors have affected the phylogeography of Populus davidiana. Location East Asia. Methods Genetic variation was surveyed across 40 populations (555 individuals) covering the Chinese range of P. davidiana, using 16 nuclear microsatellite loci (nSSRs) and four chloroplast fragments (cpDNA). Demographic and migration hypotheses were tested using coalescent-based approaches, and the present and past potential distributions were predicted using species distribution modelling. Results Molecular data divide P. davidiana into two lineages, north-eastern China (NECR) and central and northern China (CNCR); however, the dividing line is around 118ºE for nSSRs, but 122ºE for cpDNA. The range and habitat of the two lineages barely overlap at present, and their ecological separation may have initiated around the Pliocene-Quaternary boundary, when major intraspecific cpDNA clades diverged. NECR and CNCR experienced post-glacial north-eastward and northward range shifts respectively. Bi-directional historical gene flow was detected between NECR and CNCR for both bi-parentally inherited nSSRs and maternally inherited cpDNA. Demographic inferences suggest a severe bottleneck for CNCR and especially NECR, around the latest Pleistocene. Main conclusions The phylogeographic break within P. davidiana reflects the impacts of biogeographic history, climate and biological traits. Its plumed, wind-dispersed seeds might be especially significant because prevailing south-western spring winds may have moved the NECR-CNCR boundary further east than similar phylogenetic breaks in other species, and also moved the cpDNA boundary relative to that for nuclear markers. Biological traits, therefore, should also be considered when examining the genetic and ecological differentiation between closely related taxa