Chlorfenapyr is a liposoluble insecticide belonging to the pyrrole family.Chlorfenapyr is activated when the N-ethoxymethyl side chain breaks,forming a toxic metabolite,which uncouples oxidative phosphorylation in the...Chlorfenapyr is a liposoluble insecticide belonging to the pyrrole family.Chlorfenapyr is activated when the N-ethoxymethyl side chain breaks,forming a toxic metabolite,which uncouples oxidative phosphorylation in the mitochondria,inhibits the production of adenosine triphosphate (ATP),and leads to the death of cells and targe organisms.[1] Symptoms of chlorfenapyr poisoning in patients are mild and atypical in the early stage,especially in patients receiving low dose exposure;however,such cases are rare and may be ignored by physicians,often leading to delayed treatment.[2,3].展开更多
In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-...In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.展开更多
The utility of the polygenic risk score(PRS)to identify individuals at higher risk of stroke beyond clinical risk remains unclear,and we clarified this using Chinese population-based prospective cohorts.Cox proportion...The utility of the polygenic risk score(PRS)to identify individuals at higher risk of stroke beyond clinical risk remains unclear,and we clarified this using Chinese population-based prospective cohorts.Cox proportional hazards models were used to estimate the 10-year risk,and Fine and Gray’s models were used for hazard ratios(HRs),their 95%confidence intervals(CIs),and the lifetime risk according to PRS and clinical risk categories.A total of 41,006 individuals aged 30–75 years with a mean follow-up of 9.0 years were included.Comparing the top versus bottom 5%of the PRS,the HR was 3.01(95%CI 2.03–4.45)in the total population,and similar findings were observed within clinical risk strata.Marked gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk categories.Notably,among individuals with intermediate clinical risk,the 10-year risk for those in the top 5%of the PRS(7.3%,95%CI 7.1%–7.5%)reached the threshold of high clinical risk(≥7.0%)for initiating preventive treatment,and this effect of the PRS on refining risk stratification was evident for ischemic stroke.Even among those in the top 10%and 20%of the PRS,the 10-year risk would also exceed this level when aged≥50 and≥60 years,respectively.Overall,the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk.展开更多
Gout is a disease of purine metabolic disorders which results from long-term hyperuricemia and the sodium urate deposition in and around the joints. Selaginella tamariscina （ST） is an important traditional Chinese h...Gout is a disease of purine metabolic disorders which results from long-term hyperuricemia and the sodium urate deposition in and around the joints. Selaginella tamariscina （ST） is an important traditional Chinese herbal medicine and is used for the treatment of gout and hyperuricemia. In this study, the rat model of acute gout with hyperuricemia was established by intraperitoneal injection of xanthine and oxonic acid potassium salt and articular injection monosodium urate （MSU）. The effect of ST in the treatment of gout was investigated by measuring joint swelling, the expression of IL-1 !3 in serum and histological changes of joint by haematoxylin eosin （H＆E） staining. Subsequently, urine metabolomics analysis for biomarkers discovery in acute gout with hyperuricemia rats was performed by the ultra-performance liquid chromatography-electrospray ionization quadruple time-of-flight mass spectrometry （UPLC-ESI-QTOF/MS） combined with chemometric approach. Principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to detect potential biomarkers. A total of 18 potential biomarkers were identified mainly including tryptophan metabolism; tyrosine metabolism; ly- sine methylation; pyrimidine metabolism; purine metabolism; TCA cycle and fatty acid metabolisms. This study in- dicates that ST could efficiently ameliorate the disease of acute gout with hyperuricemia in rats. The related meta- bolic biomarkers could provide useful information and the metabolic mechanism could be used for further study about the model of acute gout with hyperuricemia in rats.展开更多
基金supported by a grant from the National Key R&D Program of China (2019YFC16063000)。
文摘Chlorfenapyr is a liposoluble insecticide belonging to the pyrrole family.Chlorfenapyr is activated when the N-ethoxymethyl side chain breaks,forming a toxic metabolite,which uncouples oxidative phosphorylation in the mitochondria,inhibits the production of adenosine triphosphate (ATP),and leads to the death of cells and targe organisms.[1] Symptoms of chlorfenapyr poisoning in patients are mild and atypical in the early stage,especially in patients receiving low dose exposure;however,such cases are rare and may be ignored by physicians,often leading to delayed treatment.[2,3].
基金supported by a grant from the National Key Basic Research Program of China,No.2014CB542202 and 2014CB542205the National Natural Science Foundation of China,No.30973095&81371354+2 种基金a grant from Science and Technology Project of Guangzhou,in China,No.12C32121609the Natural Science Foundation of Guangdong Province of China,No.S2013010014697 to Guo JSHong Kong SCI Fund to Wu WT
文摘In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.
基金supported by the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2021-I2M-1-010,2019-I2M-2-003,and 2017-I2M-1-004)the National High Level Hospital Clinical Research Funding(2022-GSP-GG-1,2022-GSPGG-2)+5 种基金Research Unit of Prospective Cohort of Cardiovascular Diseases and Cancers,CAMS(2019RU038)the National Key Research and Development Program of China(2018YFE0115300 and 2017YFC0211700)the National Natural Science Foundation of China(82030102,1212660291857118)Taikang Yicai Public Health and Epidemic Control Fund(TKYC-GW-2020)the National Clinical Research Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences(NCRC2020006)。
文摘The utility of the polygenic risk score(PRS)to identify individuals at higher risk of stroke beyond clinical risk remains unclear,and we clarified this using Chinese population-based prospective cohorts.Cox proportional hazards models were used to estimate the 10-year risk,and Fine and Gray’s models were used for hazard ratios(HRs),their 95%confidence intervals(CIs),and the lifetime risk according to PRS and clinical risk categories.A total of 41,006 individuals aged 30–75 years with a mean follow-up of 9.0 years were included.Comparing the top versus bottom 5%of the PRS,the HR was 3.01(95%CI 2.03–4.45)in the total population,and similar findings were observed within clinical risk strata.Marked gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk categories.Notably,among individuals with intermediate clinical risk,the 10-year risk for those in the top 5%of the PRS(7.3%,95%CI 7.1%–7.5%)reached the threshold of high clinical risk(≥7.0%)for initiating preventive treatment,and this effect of the PRS on refining risk stratification was evident for ischemic stroke.Even among those in the top 10%and 20%of the PRS,the 10-year risk would also exceed this level when aged≥50 and≥60 years,respectively.Overall,the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk.
基金The authors thank the participants who participated. They are also grateful to the staff of the National Center of Mass Spectrometry in Changchun ＆ Chemical Biol- ogy Laboratory. This work was supported by the Na- tional Natural Science Foundation of China （Nos. 81303280, 81573574, 81530094, 81473537, 31670356） and the Natural Science Foundation of Jilin Province （No. 20150101077JC）.
文摘Gout is a disease of purine metabolic disorders which results from long-term hyperuricemia and the sodium urate deposition in and around the joints. Selaginella tamariscina （ST） is an important traditional Chinese herbal medicine and is used for the treatment of gout and hyperuricemia. In this study, the rat model of acute gout with hyperuricemia was established by intraperitoneal injection of xanthine and oxonic acid potassium salt and articular injection monosodium urate （MSU）. The effect of ST in the treatment of gout was investigated by measuring joint swelling, the expression of IL-1 !3 in serum and histological changes of joint by haematoxylin eosin （H＆E） staining. Subsequently, urine metabolomics analysis for biomarkers discovery in acute gout with hyperuricemia rats was performed by the ultra-performance liquid chromatography-electrospray ionization quadruple time-of-flight mass spectrometry （UPLC-ESI-QTOF/MS） combined with chemometric approach. Principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to detect potential biomarkers. A total of 18 potential biomarkers were identified mainly including tryptophan metabolism; tyrosine metabolism; ly- sine methylation; pyrimidine metabolism; purine metabolism; TCA cycle and fatty acid metabolisms. This study in- dicates that ST could efficiently ameliorate the disease of acute gout with hyperuricemia in rats. The related meta- bolic biomarkers could provide useful information and the metabolic mechanism could be used for further study about the model of acute gout with hyperuricemia in rats.
