Association of lipid lowering drugs and the risk of systemic lupus erythematosus: a drug target Mendelian randomization

Background and objective: An interaction between low-density lipoprotein level, lipid-lowering drugs, and systemic lupus erythematosus (SLE) was reported by previous studies. However, whether lipid-lowering drugs provided protective effect for reducing the risk of SLE was unclear. We aimed to clarify this causal relationship through a drug-target Mendelian randomization (MR) study.Methods: Genetic instruments—single nucleotide polymorphism (SNPs)—were utilized to proxy inhibition of the three genes—3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-Like 1(NPC1L1), which was corresponded to three lipid-lowering drugs—statins, evolocumab, and ezetimibe. Low-density lipoprotein (LDL) cholesterol was selected as the biomarker for the measurement of the inhibitors of HMGCR, PCSK9, and NPC1L1, and the genetic data were acquired from the Global Lipids Genetics Consortium, which consisted of 1.3 million participants of European ancestry and 146.5 thousand participants of East Asian ancestry. The genetic dataset of SLE was acquired from two large-scale GWAS studies; one recruited 23,210 participants (7,219 SLE cases and 15,991 controls) of European ancestry and the other one recruited 12,653 participants (4,222 SLE cases and 8,431 controls) of Chinese ancestry. The primary analysis used the inverse variance weighted (IVW) method. Four additional sensitivity analyses, colocalization analysis, and stratification analysis were performed.Results: The primary analysis showed that inhibition of PCSK9 (evolocumab) was associated with a significantly lower risk of SLE [odds ratio (OR) 0.51, 95%CI 0.34 to 0.76, p = 0.001] in the European population. The secondary analyses had similar findings. Stratification analysis demonstrated that the preventive effect of PCSK9 inhibition for SLE was similar in both males and females. However, the results were not replicated in the East Asian population. The inhibition of HMGCR (statins) and NPC1L1 (ezetimibe) did not cause a lower risk of SLE.Conclusion: Evolocumab might provide a protective effect on the risk of SLE in the European population, but statins and ezetimibe might not have the protective effect. Further research is necessary to elucidate the specific mechanisms and potential therapeutic applications of PCSK9 inhibitors (evolocumab) in the context of SLE protection

DOK7V1 influences the malignant phenotype of lung cancer cells through PI3K/AKT/mTOR and FAK/paxillin signaling pathways

Downstream of tyrosine kinase 7 transcript variant 1 (DOK7V1) is a docking protein mediating signal transduction between receptors and intracellular downstream molecules. Our previous study indicated that DOK7V1 was decreased in lung cancer and its lower expression was associated with a decreased survival rate. The 5‑year overall survival rate for patients with lung cancer was 20.2 and 18.6% for high and low DOK7 expression, respectively; the 5‑year disease‑free survival rate for patients with lung cancer was 14.3 and 16.9% for high and low DOK7 expression, respectively. DOK7V1 inhibited proliferation and migration, but enhanced adhesion, of lung cancer cells. In the present study, the effect of DOK7V1 and its domains [pleckstrin homology (PH) and phosphotyrosine‑binding (PTB) domain] on the malignant phenotype and associated signaling pathway in lung cancer cells was investigated. The results indicated that truncation of DOK7V1 domains (DOK7V1Δ‑PH and DOK7V1Δ‑PTB) inhibited the proliferation and migration of lung cancer cells which exhibited the same trend as DOK7V1, whereas DOK7V1Δ‑PH and DOK7V1Δ‑PTB exhibited different functions from those of DOK7V1 in cell matrix adhesion. Consistently, DOK7V1 overexpression in lung cancer cells suppressed the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathways, but activated the focal adhesion kinase (FAK)/paxillin signaling pathway. Taken together, these results indicate that DOK7V1 may inhibit proliferation and migration via negatively regulating the PI3K/AKT/mTOR signaling pathway, and increase adhesion by upregulating the FAK/paxillin signaling pathway in lung cancer cells

Availability and use of essential medicines in China: manufacturing, supply, and prescribing in Shandong and Gansu provinces

<p>Abstract</p> <p>Background</p> <p>The current health care reform in China launched in 2009 tackles the problem of access to appropriate medicines for its 1.3 billion people by focusing on providing essential medicines to all. To provide evidence for the reform process, we investigated the manufacturing, purchasing, and prescribing of essential medicines in two provinces.</p> <p>Methods</p> <p>We conducted surveys in 2007 of all manufacturers (n = 253) and of 59 purposively selected retail and 63 hospital pharmacies in Shandong and Gansu provinces to assess production and supply of products on the 2004 National Essential Medicines List (NEML), as well as factors underlying decision making about production and supply. We also reviewed prescriptions (n = 5456) in health facilities to calculate standard indicators of appropriate medicines use.</p> <p>Results</p> <p>Overall, manufacturers in Shandong and Gansu produced only 62% and 50%, respectively, of the essential medicines they were licensed to produce. Of a randomly selected 10% of NEML products, retail pharmacies stocked up to 60% of Western products. Median availability in hospital pharmacies ranged from 19% to 69%. Manufacturer and retail pharmacy managers based decisions on medicines production and stocking on economic considerations, while hospital pharmacy managers cited clinical need. Between 64% and 86% of prescriptions contained an essential medicine. However, overprescribing of antibiotics (34%-77% of prescriptions) and injectables (22%-61%) for adult non-infectious outpatient consultations was common.</p> <p>Conclusions</p> <p>We found that manufacturers, retail pharmacies, and hospital pharmacies paid limited attention to China's 2004 NEML in their decisions to manufacture, purchase, and stock essential medicines. We also found that prescribing of essential medicines was frequently inappropriate. These results should inform strategies to improve affordable access to essential medicines under the current health care reform.</p

Importance of Comprehensive Ecological Restoration of Mountains, Rivers, Forests, Farmland, Lakes and Grass: A Case Study of the Shichuan River

With China's economic development and population growth, China's ecological environment continues to deteriorate. The comprehensive ecosystem restoration of the Shichuan River aims to build an ecosystem containing "mountains, rivers, forests, farmland, lakes and grass" by determining scientific and reasonable thickness of foreign soil, pollution restoration, ecological reconstruction, safeguard measures, etc. It brings new vitality to local ecological environment remodeling and economic development

Effects of Iron and Zinc Fertilizers on Antioxidant Activity of Pear-Jujube in Loess Hilly Region

With eight-year-old pear-jujube trees with uniform and good growth as the research object, different concentrations of iron and zinc fertilizers were sprayed to the leaves, and the changes in the contents of vitamin C, total flavonoids, enzyme, as well as the removal rates of hydroxyl radicals, 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and hydrogen peroxide by polyphenols in pear-jujube were studied, so as to explore the effects of iron and zinc fertilizers on antioxidant activity of pear-jujube in loess hilly region. The results showed that different treatments affected the content of vitamin C and significantly increased the content of total flavonoids in pear-jujube. In the treatment of 0.6% FeSO4+0.3% ZnSO4 (L3), the contents of vitamin C and total flavonoids were both highest, 2.86 mg/g and 3.02 mg/g, 21.8% and 105.4% higher than CK (P<0.05). Different fertilization treatments effectively reduced the activities of ascorbate oxidase and polyphenol oxidase in pear-jujube. The activity of ascorbate oxidase was lowest in the treatment of 0.6% FeSO4+0.3% ZnSO4 (oxidized ascorbic acid 0.069 mg/(g·min) FW), 75.1% lower than CK); and the activity of polyphenol oxidase was lowest in the L3 treatment (oxidized ascorbic acid 0.146 mg/(g·min) FW, 42.0% lower than CK). Polyphenols of pear-jujube could effectively remove hydroxyl radicals, DPPH· and hydrogen peroxide. This was more significant in L3 treatment, of which the antioxidant activity was the best

Rules of Changes in Soil Nutrients and Enzyme Activities of Larix principis-rupprechtii in Different Forest Ages

In this study, three different ages of Larix principis-rupprechtii forests in 5, 10 and 20 years were selected as the research objects, and the changes in soil nutrient and soil enzyme activities in different growth stages were analyzed. The results showed that the contents of organic matter and available phosphorus in the soil of different growth stages showed a significant downward trend with the increase of soil depth. For different forest ages in the same soil layer, the soil available phosphorus content declined with the increase of the forest age. The organic matter content of 40-60 cm in 20 years of forest age was the lowest in July, which was 4.17 g/kg, significantly lower than that in other soil layers. Besides, the soil available phosphorus content of 5 years of forest age reached the maximum in July, with an average of 4.44 mg/kg, which was higher than the available phosphorus content in soil in May and September, but the difference between the three months was not significant. The changes of ammonium nitrogen and nitrate nitrogen content in soil with different forest ages were consistent with the changes in the soil depth, showing a downward trend. In the new leaf stage, the ammonium nitrogen content of the L. principis-rupprechtii forest land in 5 years of age at 20-40 cm and 40-60 cm of the soil depth was 13.47 mg/kg and 9.09 mg/kg, respectively, which was 46.9% and 64.2% lower than that at 0-20 cm (25.36 mg/kg) of the soil depth. The soil nitrate nitrogen content of 20 years of forest age was 19.24 mg/kg, which was 25.8% lower than that of 10 years of forest age, showing significant difference (P < 0.05). In addition, with the increase of the age of L. principis-rupprechtii, soil catalase (CAT), alkaline phosphatase (ALP) and urease (Ure) decreased, and the decline of ALP was slow, while CAT and Ure decreased significantly. In summary, it is concluded that the soil fertility of forest land declined with the increase of forest age on the basis of change trend of soil nutrient and soil enzyme activity in the surveyed forest age

Effects of organic fertilizer on water use, photosynthetic characteristics, and fruit quality of pear jujube in northern Shaanxi

This experiment is based on the 7-year-old dwarf and densely planted pear jujube in northern Shaanxi. The effects of applying organic fertilizer on water use, photosynthetic characteristics, and fruit quality of pear jujube are studied. The test has been carried out for two consecutive years. The results showed that fertilization treatments could promote soil moisture retention and utilization. Compared with the control (CK) in 2011, the average soil water content (SWC) of soybean cake fertilizer (SC) and sheep manure (SM) increased by 3.69 and 3.18 percentage points, respectively. The effect of SC on chlorophyll content was most significant. Fertilization can effectively improve the canopy structure of pear jujube. The transmittance of SC and SM decreased by 20.20% and 17.38%, respectively, in 2012. The gap scores were opposite to the leaf area index (LAI). Continuous application of organic fertilizer can significantly increase the net photosynthetic rate and stomatal conductance of pear jujube. The instantaneous water use efficiency of chemical fertilizer (CF), SC, SM, and biogas fertilizer (BM) increased by 0.44, 1.33, 0.96, and 0.61 percentage points, respectively. Organic fertilizer effectively increased the fruit setting rate, yield, and quality of fruits. After fertilization for two consecutive years, the quality of pear jujube fruit improved significantly. It indicated that long-term fertilization could effectively promote the growth and development, increase yield, and significantly improve the fruit quality of pear jujube in the loess hilly region of northern Shaanxi. The effect of soybean cake fertilizer was the most significant

Effects of different mulch materials on the photosynthetic characteristics, yield, and soil water use efficiency of wheat in Loess tableland

Abstract Due to the lack of precipitation and poor temporal and spatial stability in the Loess Plateau for a long time, it is necessary to adopt mulching technology to support the stable and high yield of wheat cultivation system. This study aims at exploring different mulching materials on the soil water content, photosynthetic characteristics, wheat yield, and yield components of winter wheat in the gully region of the Loess Plateau. The results showed that the traditional flat soil water content is the lowest in the seedling stage. In the jointing stage and heading stage of many crop water requirements, ridge film mulching treatment can effectively promote the growth of wheat and increase the water use efficiency. The leaf area index (LAI) of different treatments wheat showed a trend of increasing first and then decreasing. In the jointing stage, ordinary mulching film (T1) and liquid mulching film (T3) had the highest LAI content, which were 3.78 and 3.71 respectively. The Pn and Gs in wheat flag leaves of T3 treatment is higher than that of CK throughout the entire growth period, and T3 significantly increased Ci and WUEi in different growth stage. And the grain number per panicle and grain weight of T3 treatment were 24.44 and 41.00 g, which were 19.3% and 5.4% higher than CK, respectively. Through the actual production calculation of the final harvest, the ridge film mulching has a significant increase in production compared with the CK. The yield of T3 treatment was 4980.25 kg hm−2, which was 29.37% higher than CK. It was significantly different from CK (P < 0.05). Based on the comprehensive analysis, the ridge film mulching treatment significantly affected the soil water content and wheat yield. And the liquid mulching film had the best effect. Exploring the impact of different covering techniques on the wheat cultivation system in the Loess Plateau region, to promote the scientific promotion of this technology