Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematic...Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematically examined the potential impacts of M/NPs on ocular health,focusing on exposure pathways,toxicological mechanisms,and resultant damage to the eye.Ocular exposure to M/NPs can occur via direct contact and oral ingestion,with the latter potentially leading to the penetration of particles through ocular biological barriers into ocular tissues.The review highlighted that M/NPs can induce adverse effects on the ocular surface,elevate intraocular pressure,and cause abnormalities in the vitreous and retina.Mechanistically,oxidative stress and inflammation are central to M/NP-induced ocular damage,with smaller particles often exhibiting greater toxicity.Overall,this review underscored the potential risks of M/NPs to ocular health and emphasized the need for further research to elucidate exposure mechanisms,toxicological pathways,and mitigation strategies.展开更多
In the implementation of the rural revitalization strategy,the banking and financial institutions in Jingzhou City,Hubei Province,under the guidance of the Jingzhou Branch of the People's Bank of China,strive to i...In the implementation of the rural revitalization strategy,the banking and financial institutions in Jingzhou City,Hubei Province,under the guidance of the Jingzhou Branch of the People's Bank of China,strive to improve and develop the financial service system adapted to the characteristics of the countryside in the new period.It has innovated financial service products,improved the quality and efficiency of financial services,increased financial support,and achieved remarkable results.On the basis of the investigation,combined with the relevant written materials and statistical data collected,this paper makes an empirical study on the reality of the city's banking and financial institutions serving the revitalization of rural areas.展开更多
BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary...BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive.Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.METHODS The retrospective cohort study of 1546 men aged 69.74±11.30 years conducted in Beijing,China from 2015 to 2022.And the incidence of primary osteoporosis was annually recorded.LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C.The association of baseline LDL-C for osteoporosis was estimated using hazard ratio(HR)with 95%CI in Cox proportional hazard model,while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio(OR)with 95%CI in logistic regression model.RESULTS During the median 6.2-year follow-up period,70 men developed primary osteoporosis.The higher level of baseline LDLC(HR=1.539,95%CI:1.012–2.342)and mean LDL-C(OR=2.190,95%CI:1.443–3.324)were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates.Compared with those in the LDL-C trajectory of low-stable decrease,participants with medium-fluctuant trajectory,whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease,were negatively associated with osteoporosis risk(OR=2.451,95%CI:1.152–5.216).And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk(OR=0.718,95%CI:0.212–2.437).CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men.Early controlling a stable level of LDL-C is also essential for bone health.展开更多
Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian cloc...Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.展开更多
The incidence and prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)have continued to increase in recent years,making it one of the most common chronic liver diseases worldwide.MASLD is high...The incidence and prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)have continued to increase in recent years,making it one of the most common chronic liver diseases worldwide.MASLD is highly comorbid with obesity,type 2 diabetes,cardiovascular disease,and chronic kidney disease,posing a serious threat to public health and creating a significant medical and socioeconomic burden.Despite advances in research,current clinical practice still faces considerable challenges in early screening,risk stratification,prognostic prediction,and long-term therapeutic monitoring.Recent advances in artificial intelligence(AI)have provided transformative opportunities to address these challenges.AI has demonstrated unique advantages in imaging interpretation,multiomics integration,electronic health record analysis,and remote health management,significantly improving the accuracy and efficiency of the noninvasive diagnosis,individualized risk stratification,precision therapy,and dynamic disease monitoring of MASLD.In this mini-review,the latest advances in AI applications for MASLD diagnosis and management are systematically summarized,and a forward-looking perspective on the role of AI in enabling the next generation of smart health care systems for MASLD is offered,with the aim of providing theoretical and practical guidance for the clinical management of this disease.展开更多
BACKGROUND Acute variceal bleeding(AVB)in patients with cirrhosis remains life-threatening;moreover,the current risk stratification methods have certain limitations.Rebleeding and mortality after AVB remain major chal...BACKGROUND Acute variceal bleeding(AVB)in patients with cirrhosis remains life-threatening;moreover,the current risk stratification methods have certain limitations.Rebleeding and mortality after AVB remain major challenges.Although preemptive transjugular intrahepatic portosystemic shunt(p-TIPS)can improve outcomes,not all patients benefit equally.Accurate risk stratification is needed to guide treatment decisions and identify those most likely to benefit from p-TIPS.AIM To develop an artificial intelligence(AI)-driven model to guide AVB treatment decisions,and identify candidates eligible for p-TIPS.METHODS Patients with cirrhosis and AVB,from two multicenter retrospective cohorts in China,who received endoscopic variceal ligation plus pharmacotherapy(n=1227)or p-TIPS(n=1863)were included.Baseline data within 24 hours of hospital admission were obtained.The AI-AVB model,based on the six-week failure and one-year mortality rates,was developed to predict treatment efficacy and compared with standard risk scores.Outcomes and adverse events of the treatments were compared across the high-and low-risk subgroups stratified using the AI-AVB model.RESULTS The AI-AVB model demonstrated superior predictive performance compared to traditional risk stratification methods.In the internal validation cohort,the model achieved an area under the curve(AUC)of 0.842 for predicting six-week treatment failure and 0.954 for one-year mortality.In the external validation cohort,the AUCs were 0.814 and 0.889,respectively.The model effectively identified patients at high risk of first-line treatment failure who may benefit from aggressive interventions such as p-TIPS.In contrast,advancing the treatment strategy for low-risk patients did not notably improve the short-term prognosis.CONCLUSION The AI-AVB model can predict treatment outcomes,stratify the failure risk in cirrhotic patients with AVB,aid in clinical decisions,identify p-TIPS beneficiaries,and optimize personalized treatment strategies.展开更多
Plant roots interact with diverse fungi that are essential for maintaining the productivity and sustainability of pasture ecosystems,but how these root-associated fungi(RAF)differ between forage species and how they r...Plant roots interact with diverse fungi that are essential for maintaining the productivity and sustainability of pasture ecosystems,but how these root-associated fungi(RAF)differ between forage species and how they respond to nutrient enrichment and fungicide application are not well understood.Here,we constructed an 11-year experiment involving fungicide application(with or without)nested within four levels of experimental nitrogen(N)addition treatments in an alpine pasture,and the RAF communities,root traits,tissue nutrients,and shoot biomass of two dominant forage species(Carex capillifolia and Elymus nutans)were analyzed.The RAF community composition showed striking differences between the plant species and was strongly affected by both N addition level and fungicide applications.Fungicide,but not N application,dramatically reduced the RAF richness of all functional guilds in both plant species,and fungicide also simplified the co-occurrence network of the RAF for C.capillifolia.The RAF community correlated strongly with root traits,whereas their relationships became weakened or even vanished at the level of the individual plant species.The importance of RAF to plant nutrients and productivity varied between plant species,with significant contributions in C.capillifolia but not in E.nutans.This is the first report elucidating the long-term effect of fungicides on RAF in alpine pastures,and our findings emphasize the host-specific responses of RAF community structure and function to anthropogenic disturbances.展开更多
Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,hav...Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,have been found to participate in the progression of MASLD.Sodium butyrate(NaB),one of the most important SCFAs,shows therapeutic potentials in MASLD and its mechanisms have not been fully understood.The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis(MASH)associated fibrosis as well as the underlying mechanisms.Methods:Male Sprague-Dawley rats were randomly assigned to three groups:(i)control group,stan-dard chow for 24 weeks;(ii)HFD group,high-fat and high-cholesterol diet(HFD)for 24 weeks;and(iii)HFD+NaB group,HFD for 24 weeks and NaB gavage for the last 16 weeks.Body weight,liver index(liver weight/body weight×100%),serum parameters,and liver histology were analyzed to evaluate MASH and fibrosis severity.AML12,RAW264.7 and LX2 cell lines were used for in vitro study.Results:Compared to MASH rats with fibrosis induced by 24-week HFD,NaB intervention alleviated the degree of hepatic steatosis,inflammation,hepatocyte ballooning,and fibrosis.Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats,and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1(SOCS1)in both hepatocytes and hepatic stellate cells(HSCs)were blunted when they were treated with NaB.Fur-thermore,NaB also significantly decreased the production of platelet-derived growth factor-BB(PDGF-BB),a pro-fibrotic mediator,in hepatocytes.NaB treatment on AML12 cells markedly impaired the prolifera-tion ability of co-cultured LX2 cells.Moreover,NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.Conclusions:NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats.NaB might be a potential agent for the treatment of fibrosis in patients with MASH.展开更多
Esculetin,a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini,has demonstrated significant pharmacological activities,including anticancer properties.Ferroptosis,an iron-dependent form...Esculetin,a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini,has demonstrated significant pharmacological activities,including anticancer properties.Ferroptosis,an iron-dependent form of regulated cell death,has garnered considerable attention due to its lethal effect on tumor cells.However,the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma(HCC)effects remains poorly understood.This study investigated the impact of esculetin on HCC cells both in vitro and in vivo.The findings indicate that esculetin effectively inhibited the growth of HCC cells.Importantly,esculetin promoted the accumulation of intracellular Fe^(2+),leading to an increase in ROS production through the Fenton reaction.This event subsequently induced lipid peroxidation(LPO)and triggered ferroptosis within the HCC cells.The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde(MDA)levels,the depletion of glutathione peroxidase(GSH-Px)activity,and the disruption of mitochondrial morphology.Notably,the inhibitor of ferroptosis,ferrostatin-1(Fer-1),attenuated the anti-tumor effect of esculetin in HCC cells.Furthermore,the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells.Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4,consequently alleviating esculetin-induced ferroptosis.In conclusion,this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis,thereby triggering ferroptosis in HCC cells.These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.展开更多
Track irregularity from rail alternate side wear is manifested as uneven rail wear waveforms alternating in the left and right rails with equal intervals,which will cause carbody sway behaviour of railway vehicles and...Track irregularity from rail alternate side wear is manifested as uneven rail wear waveforms alternating in the left and right rails with equal intervals,which will cause carbody sway behaviour of railway vehicles and greatly influences the passenger comfort.In this work,the carbody sway behaviour and mechanism due to track irregularity from rail alternate side wear and possible solutions to this issue were studied by the field testing and numerical calculation approaches.First,the carbody sway of an urban rail transit train is introduced with full-scale field tests,through which the rail alternate side wear is characterized and the formatted track irregularity are presented.Then,multibody vehicle dynamic models are developed to reproduce the carbody sway behaviour induced by the track irregularity from the rail alternate side wear.The creep forces acting on the wheel and rail are preliminarily discussed to study the influence of the carbody sway on the wear of the wheel flange and the rail corner.Finally,some potential solutions,e.g.improving the damping ratio of carbody rigid mode and rail grinding,are proposed to relieve this issue.It is concluded that an increased damping ratio of the carbody mode can alleviate the carbody sway and wheel–rail interactions,while properly maintaining track conditions can improve the vehicle performance.展开更多
This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a compr...This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a comprehensive literature review and case analysis,the research investigates the current state,challenges,and practical barriers to embedding NM into PHC systems,while proposing targeted strategies for improvement.The findings suggest that NM fosters stronger doctor-patient trust,enhances healthcare quality,and promotes humanistic care.However,primary hospitals face numerous challenges in advancing medical humanities,including a lack of trust between doctors and patients,tensions arising from the commercialization of healthcare,institutional limitations,unequal distribution of resources,and issues related to physicians'professional competencies and stress management.These interrelated obstacles detract from the quality of PHC services and the overall patient experience.Drawing on successful case studies from primary hospitals,the paper outlines effective strategies for overcoming these challenges.The study provides both theoretical and practical insights for advancing medical humanities in PHC,contributing to improvements in healthcare service quality and supporting the development of high standards in the healthcare sector.Ultimately,the findings aim to promote the broader adoption and ongoing refinement of NM within PHC institutions.展开更多
<strong>Background:</strong> As a common surgical disease, pressure injury has become a long-standing problem in clinical treatment and nursing process. This research was conducted to explore the feasibili...<strong>Background:</strong> As a common surgical disease, pressure injury has become a long-standing problem in clinical treatment and nursing process. This research was conducted to explore the feasibility of Ji Desheng Snake Pills combined with hypertonic glucose external application in the treatment of stage III and IV pressure injuries. <strong>Methods:</strong> Patients with stage III and IV pressure injuries, who received treatment in our hospital between December 2018 and December 2019 were selected and divided into experimental group, conventional treatment group, and control group, 30 cases for each. The three groups received Ji Desheng Snake Pills combined with hypertonic glucose external application, moist dressing external application and surgical dressing change, respectively. The safety, therapeutic effect and cost benefit of the three treatment methods were compared. <strong>Results:</strong> There were no adverse reactions in the three groups of patients. The PUSH scores of the experimental group and the conventional treatment group were significantly lower than that of the control group on the 14<sup>th</sup>, 21<sup>th</sup>, and 28<sup>th</sup> days, and the result was statistically significant (p < 0.05), while there was no significant difference between the experimental group and the conventional treatment group (p > 0.05). The wound healing rates of the experimental group (70.14 ± 8.27%) and the conventional treatment group (73.99 ± 7.15%) were significantly higher than that of the control group (43.25 ± 8.53%) on the 28<sup>th</sup> day, with statistical significance (p < 0.05);there was no significant difference between the experimental group and the conventional treatment group (p > 0.05). The total treatment costs of the three groups were 569.73 ± 78.12 yuan, 1043.40 ± 135.31 yuan, and 186.47 ± 30.29 yuan. The cost of the conventional treatment group was the highest, followed by the experimental group, and the control group was the lowest. The result was statistically significant (p < 0.05). <strong>Conclusion:</strong> In the treatment of stage III and IV pressure injuries, there was no significant difference in the safety and therapeutic effect between the experimental group (Ji Desheng Snake Pills combined with hypertonic glucose external application) and the conventional treatment group (moist dressing external application), but the experimental group had better cost benefit.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic diseases in the world.Nowadays,the percentage of non-obese or lean patients with NAFLD is increasing.NAFLD in non-obese populations,e...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic diseases in the world.Nowadays,the percentage of non-obese or lean patients with NAFLD is increasing.NAFLD in non-obese populations,especially the lean subgroup with a normal waist circumference(WC),might lead to more problems than obese individuals,as these individuals may not visit clinics for NAFLD diagnosis or ignore the diagnosis of NAFLD.If the precise characteristics of these populations,especially the lean subgroup,are identified,the clinicians would be able to provide more appropriate advice and treatment to these populations.AIM To investigate the prevalence,clinical characteristics,risk factors,and possible indicators for NAFLD in lean Chinese adults with a normal WC.METHODS People without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included.Their fatty liver index(FLI),abdominal ultrasonography results,and controlled attenuation parameter were all assessed.Genotyping for single-nucleotide polymorphisms associated with NAFLD was performed in another small group consisting of biopsy-proven NAFLD subjects and healthy controls.RESULTS A total of 2715 subjects who underwent routine health examinations were included in the study.Among 810 lean participants with a normal WC,142(17.5%)fulfilled the diagnostic criteria for NAFLD.Waist-height ratio,hemoglobin,platelets,and triglycerides were significant factors associated with the presence of NAFLD in these participants.The appropriate cut-off value of the FLI score in screening for NAFLD in the lean subjects with a normal WC was 25.15,which had a 77.8%sensitivity and 75.9%specificity.There was no significant difference in the single-nucleotide polymorphisms in the SIRT1,APOC3,PNPLA3,AGTR1,and PPARGC1A genes between lean subjects with and without NAFLD(P<0.05).CONCLUSION NAFLD is not uncommon in lean Chinese adults even with a normal WC.Metabolic factors,rather than genetic factors,may play important roles in the development of NAFLD in this population.A lower cut-off value of the FLI score in screening for NAFLD should be used for lean Chinese adults with a normal WC.展开更多
Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similaritie...Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.展开更多
To solve the problem of difficult machining, the near-net shaped Al/SiCP composites with high volume fraction of SiC particles were fabricated by vacuum-pressure infiltration. The SiCP preform with a complex shape was...To solve the problem of difficult machining, the near-net shaped Al/SiCP composites with high volume fraction of SiC particles were fabricated by vacuum-pressure infiltration. The SiCP preform with a complex shape was prepared by gelcasting. Pure Al, Al4Mg, and Al4Mg2Si were used as the matrices, respectively. The results indicate that the optimal parameters of SiCP suspension in gelcasting process are pH value of 10, TMAH content of 0.5 wt.%, and solid loading of 52 vol.%. The Al matrix alloyed with Mg contributes to improving the interfacial wettability of the matrix and SiC particles, which increases the relative density of the composite. The Al matrix alloyed with Si is beneficial to inhibiting the formation of the detrimental Al4C3 phases. The Al4Mg2Si/SiCP composite exhibits high relative density of 99.2%, good thermal conductivity of 150 W·m^-1·K^-1, low coefficient of thermal expansion of 10.1×10^-6 K^-1, and excellent bending strength of 489 MPa.展开更多
A sensitive, rapid, simple and economical ultra-performance liquid chromatography-tandem mass spectrometric method （UPLC-MS/MS） was developed and validated for simultaneous determination of imatinib, dasatinib and n...A sensitive, rapid, simple and economical ultra-performance liquid chromatography-tandem mass spectrometric method （UPLC-MS/MS） was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard （IS）. Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A （aqueous phase： 0.15% formic acid and 0.05% ammonium acetate） and B （organic phase： aeetonitrile） （A：B=40：60, v/v）. The flow rate was 0.25 mL/min and the total run time was 6 min. The multiple reaction monitoring （MRM） transitions, m/z 494.5-394.5 for imatinib, 488.7-401.5 for dasatinib, 530.7-289.5 for nilotinib and 528.5-403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6-5250.0 ng/mL for imatinib, 2.0-490.0 ng/mL for dasatinib, and 2.4-4700.0 ng/mL for nilotinib. The method showed acceptable results on sensitivity, specificity, recovery, precision, accuracy and stability tests. This UPLC-MS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentrations among the SLC22A5 -1889T 〉 C or SLCOIB3 699G 〉 A genotypes （P 〉 0.05）. This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors （TKIs）.展开更多
基金Supported by the Guangdong Provincial Natural Science Foundation(No.2114050001527).
文摘Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematically examined the potential impacts of M/NPs on ocular health,focusing on exposure pathways,toxicological mechanisms,and resultant damage to the eye.Ocular exposure to M/NPs can occur via direct contact and oral ingestion,with the latter potentially leading to the penetration of particles through ocular biological barriers into ocular tissues.The review highlighted that M/NPs can induce adverse effects on the ocular surface,elevate intraocular pressure,and cause abnormalities in the vitreous and retina.Mechanistically,oxidative stress and inflammation are central to M/NP-induced ocular damage,with smaller particles often exhibiting greater toxicity.Overall,this review underscored the potential risks of M/NPs to ocular health and emphasized the need for further research to elucidate exposure mechanisms,toxicological pathways,and mitigation strategies.
文摘In the implementation of the rural revitalization strategy,the banking and financial institutions in Jingzhou City,Hubei Province,under the guidance of the Jingzhou Branch of the People's Bank of China,strive to improve and develop the financial service system adapted to the characteristics of the countryside in the new period.It has innovated financial service products,improved the quality and efficiency of financial services,increased financial support,and achieved remarkable results.On the basis of the investigation,combined with the relevant written materials and statistical data collected,this paper makes an empirical study on the reality of the city's banking and financial institutions serving the revitalization of rural areas.
基金supported by the Multi-center RCT Clinical Project of the National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital(NCRCGPLAGH-2023001)the Beijing Nova Program(No.20220484020)+1 种基金the Beijing Natural Science Foundation(No.7252181)the Capital’s Funds for Health Improvement and Research(No.2024-2G-5033).
文摘BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive.Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.METHODS The retrospective cohort study of 1546 men aged 69.74±11.30 years conducted in Beijing,China from 2015 to 2022.And the incidence of primary osteoporosis was annually recorded.LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C.The association of baseline LDL-C for osteoporosis was estimated using hazard ratio(HR)with 95%CI in Cox proportional hazard model,while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio(OR)with 95%CI in logistic regression model.RESULTS During the median 6.2-year follow-up period,70 men developed primary osteoporosis.The higher level of baseline LDLC(HR=1.539,95%CI:1.012–2.342)and mean LDL-C(OR=2.190,95%CI:1.443–3.324)were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates.Compared with those in the LDL-C trajectory of low-stable decrease,participants with medium-fluctuant trajectory,whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease,were negatively associated with osteoporosis risk(OR=2.451,95%CI:1.152–5.216).And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk(OR=0.718,95%CI:0.212–2.437).CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men.Early controlling a stable level of LDL-C is also essential for bone health.
基金supported in part by grants from the National Key R&D Program of China(2021YFC2400400/04 to L.L.C.)the National Natural Science Foundation of China for Key Program Projects(82030070 to L.L.C.)+2 种基金the National Natural Science Foundation of China for Distinguished Young Scholars(22025102 to Q.W.)the National Natural Science Foundation of China(82271036 to Y.F.W.,22277033 to J.Z.,22177034 to L.K.M.)the Young Elite Scientist Sponsorship Program by CAST(2022QNRC001 to Y.F.W.)。
文摘Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.
基金Supported by Shanghai Pujiang Program,No.24PJD071National Natural Science Foundation of China,No.82100605Star Program of Shanghai Jiao Tong University,No.YG2021QN54.
文摘The incidence and prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)have continued to increase in recent years,making it one of the most common chronic liver diseases worldwide.MASLD is highly comorbid with obesity,type 2 diabetes,cardiovascular disease,and chronic kidney disease,posing a serious threat to public health and creating a significant medical and socioeconomic burden.Despite advances in research,current clinical practice still faces considerable challenges in early screening,risk stratification,prognostic prediction,and long-term therapeutic monitoring.Recent advances in artificial intelligence(AI)have provided transformative opportunities to address these challenges.AI has demonstrated unique advantages in imaging interpretation,multiomics integration,electronic health record analysis,and remote health management,significantly improving the accuracy and efficiency of the noninvasive diagnosis,individualized risk stratification,precision therapy,and dynamic disease monitoring of MASLD.In this mini-review,the latest advances in AI applications for MASLD diagnosis and management are systematically summarized,and a forward-looking perspective on the role of AI in enabling the next generation of smart health care systems for MASLD is offered,with the aim of providing theoretical and practical guidance for the clinical management of this disease.
基金Supported by Key Research and Development Program of Jiangsu Province,No.BE2023767Xuzhou Key Research and Development Program under Grant,No.KC23273+1 种基金Affiliated Hospital of Xuzhou Medical University,No.2022ZL26Construction Project of High-Level Hospital of Jiangsu Province,No.GSPSJ20240802.
文摘BACKGROUND Acute variceal bleeding(AVB)in patients with cirrhosis remains life-threatening;moreover,the current risk stratification methods have certain limitations.Rebleeding and mortality after AVB remain major challenges.Although preemptive transjugular intrahepatic portosystemic shunt(p-TIPS)can improve outcomes,not all patients benefit equally.Accurate risk stratification is needed to guide treatment decisions and identify those most likely to benefit from p-TIPS.AIM To develop an artificial intelligence(AI)-driven model to guide AVB treatment decisions,and identify candidates eligible for p-TIPS.METHODS Patients with cirrhosis and AVB,from two multicenter retrospective cohorts in China,who received endoscopic variceal ligation plus pharmacotherapy(n=1227)or p-TIPS(n=1863)were included.Baseline data within 24 hours of hospital admission were obtained.The AI-AVB model,based on the six-week failure and one-year mortality rates,was developed to predict treatment efficacy and compared with standard risk scores.Outcomes and adverse events of the treatments were compared across the high-and low-risk subgroups stratified using the AI-AVB model.RESULTS The AI-AVB model demonstrated superior predictive performance compared to traditional risk stratification methods.In the internal validation cohort,the model achieved an area under the curve(AUC)of 0.842 for predicting six-week treatment failure and 0.954 for one-year mortality.In the external validation cohort,the AUCs were 0.814 and 0.889,respectively.The model effectively identified patients at high risk of first-line treatment failure who may benefit from aggressive interventions such as p-TIPS.In contrast,advancing the treatment strategy for low-risk patients did not notably improve the short-term prognosis.CONCLUSION The AI-AVB model can predict treatment outcomes,stratify the failure risk in cirrhotic patients with AVB,aid in clinical decisions,identify p-TIPS beneficiaries,and optimize personalized treatment strategies.
基金supported by the National Key Research and Development Program of China(2023YFF0805602)the National Natural Science Foundation of China(U21A20186,32171579,32371592 and 32471674)the Natural Science Foundation of Gansu Province,China(23JRRA1029 and 23JRRA1034)。
文摘Plant roots interact with diverse fungi that are essential for maintaining the productivity and sustainability of pasture ecosystems,but how these root-associated fungi(RAF)differ between forage species and how they respond to nutrient enrichment and fungicide application are not well understood.Here,we constructed an 11-year experiment involving fungicide application(with or without)nested within four levels of experimental nitrogen(N)addition treatments in an alpine pasture,and the RAF communities,root traits,tissue nutrients,and shoot biomass of two dominant forage species(Carex capillifolia and Elymus nutans)were analyzed.The RAF community composition showed striking differences between the plant species and was strongly affected by both N addition level and fungicide applications.Fungicide,but not N application,dramatically reduced the RAF richness of all functional guilds in both plant species,and fungicide also simplified the co-occurrence network of the RAF for C.capillifolia.The RAF community correlated strongly with root traits,whereas their relationships became weakened or even vanished at the level of the individual plant species.The importance of RAF to plant nutrients and productivity varied between plant species,with significant contributions in C.capillifolia but not in E.nutans.This is the first report elucidating the long-term effect of fungicides on RAF in alpine pastures,and our findings emphasize the host-specific responses of RAF community structure and function to anthropogenic disturbances.
基金supported by grants from the National Natural Science Foundation of China(81873565 and 81900507).
文摘Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,have been found to participate in the progression of MASLD.Sodium butyrate(NaB),one of the most important SCFAs,shows therapeutic potentials in MASLD and its mechanisms have not been fully understood.The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis(MASH)associated fibrosis as well as the underlying mechanisms.Methods:Male Sprague-Dawley rats were randomly assigned to three groups:(i)control group,stan-dard chow for 24 weeks;(ii)HFD group,high-fat and high-cholesterol diet(HFD)for 24 weeks;and(iii)HFD+NaB group,HFD for 24 weeks and NaB gavage for the last 16 weeks.Body weight,liver index(liver weight/body weight×100%),serum parameters,and liver histology were analyzed to evaluate MASH and fibrosis severity.AML12,RAW264.7 and LX2 cell lines were used for in vitro study.Results:Compared to MASH rats with fibrosis induced by 24-week HFD,NaB intervention alleviated the degree of hepatic steatosis,inflammation,hepatocyte ballooning,and fibrosis.Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats,and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1(SOCS1)in both hepatocytes and hepatic stellate cells(HSCs)were blunted when they were treated with NaB.Fur-thermore,NaB also significantly decreased the production of platelet-derived growth factor-BB(PDGF-BB),a pro-fibrotic mediator,in hepatocytes.NaB treatment on AML12 cells markedly impaired the prolifera-tion ability of co-cultured LX2 cells.Moreover,NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.Conclusions:NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats.NaB might be a potential agent for the treatment of fibrosis in patients with MASH.
基金supported by the Natural Science Foundations of Fujian Province(Nos.2021J05063 and 2023J01541)a startup grant for High-level Talents of Fujian Medical University(No.XRCZX2021014)。
文摘Esculetin,a natural dihydroxy coumarin derived from the Chinese herbal medicine Cortex Fraxini,has demonstrated significant pharmacological activities,including anticancer properties.Ferroptosis,an iron-dependent form of regulated cell death,has garnered considerable attention due to its lethal effect on tumor cells.However,the exact role of ferroptosis in esculetin-mediated anti-hepatocellular carcinoma(HCC)effects remains poorly understood.This study investigated the impact of esculetin on HCC cells both in vitro and in vivo.The findings indicate that esculetin effectively inhibited the growth of HCC cells.Importantly,esculetin promoted the accumulation of intracellular Fe^(2+),leading to an increase in ROS production through the Fenton reaction.This event subsequently induced lipid peroxidation(LPO)and triggered ferroptosis within the HCC cells.The occurrence of ferroptosis was confirmed by the elevation of malondialdehyde(MDA)levels,the depletion of glutathione peroxidase(GSH-Px)activity,and the disruption of mitochondrial morphology.Notably,the inhibitor of ferroptosis,ferrostatin-1(Fer-1),attenuated the anti-tumor effect of esculetin in HCC cells.Furthermore,the findings revealed that esculetin inhibited the Nrf2-xCT/GPx4 axis signaling in HCC cells.Overexpression of Nrf2 upregulated the expression of downstream SLC7A11 and GPX4,consequently alleviating esculetin-induced ferroptosis.In conclusion,this study suggests that esculetin exerts an anti-HCC effect by inhibiting the activity of the Nrf2-xCT/GPx4 axis,thereby triggering ferroptosis in HCC cells.These findings may contribute to the potential clinical use of esculetin as a candidate for HCC treatment.
基金supported by the National Natural Science Foundation of China(Grant Nos.52002344,U2034210,and 61960206010)the Development Project of State Key Laboratory of Rail Transit Vehicle System(Grant No.2022TPL_T09)。
文摘Track irregularity from rail alternate side wear is manifested as uneven rail wear waveforms alternating in the left and right rails with equal intervals,which will cause carbody sway behaviour of railway vehicles and greatly influences the passenger comfort.In this work,the carbody sway behaviour and mechanism due to track irregularity from rail alternate side wear and possible solutions to this issue were studied by the field testing and numerical calculation approaches.First,the carbody sway of an urban rail transit train is introduced with full-scale field tests,through which the rail alternate side wear is characterized and the formatted track irregularity are presented.Then,multibody vehicle dynamic models are developed to reproduce the carbody sway behaviour induced by the track irregularity from the rail alternate side wear.The creep forces acting on the wheel and rail are preliminarily discussed to study the influence of the carbody sway on the wear of the wheel flange and the rail corner.Finally,some potential solutions,e.g.improving the damping ratio of carbody rigid mode and rail grinding,are proposed to relieve this issue.It is concluded that an increased damping ratio of the carbody mode can alleviate the carbody sway and wheel–rail interactions,while properly maintaining track conditions can improve the vehicle performance.
基金Supported by National Natural Science Foundation of China,No.82272204 and No.824721882022 Key Clinical Specialty of Zhejiang Province(Critical Care Medicine)+4 种基金“Pioneer”and“Leading Goose”R&D Program of Zhejiang,No.2023C03084Wenzhou Major Science and Technology Innovation Project,No.ZY2023005Central Guiding Local Technology Development,No.2024ZY01012Zhejiang Provincial College Students'Science and Technology Innovation Activity Program,No.2024R413A037National Innovation and Entrepreneurship Training Program for College Students,No.202410343030.
文摘This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a comprehensive literature review and case analysis,the research investigates the current state,challenges,and practical barriers to embedding NM into PHC systems,while proposing targeted strategies for improvement.The findings suggest that NM fosters stronger doctor-patient trust,enhances healthcare quality,and promotes humanistic care.However,primary hospitals face numerous challenges in advancing medical humanities,including a lack of trust between doctors and patients,tensions arising from the commercialization of healthcare,institutional limitations,unequal distribution of resources,and issues related to physicians'professional competencies and stress management.These interrelated obstacles detract from the quality of PHC services and the overall patient experience.Drawing on successful case studies from primary hospitals,the paper outlines effective strategies for overcoming these challenges.The study provides both theoretical and practical insights for advancing medical humanities in PHC,contributing to improvements in healthcare service quality and supporting the development of high standards in the healthcare sector.Ultimately,the findings aim to promote the broader adoption and ongoing refinement of NM within PHC institutions.
文摘<strong>Background:</strong> As a common surgical disease, pressure injury has become a long-standing problem in clinical treatment and nursing process. This research was conducted to explore the feasibility of Ji Desheng Snake Pills combined with hypertonic glucose external application in the treatment of stage III and IV pressure injuries. <strong>Methods:</strong> Patients with stage III and IV pressure injuries, who received treatment in our hospital between December 2018 and December 2019 were selected and divided into experimental group, conventional treatment group, and control group, 30 cases for each. The three groups received Ji Desheng Snake Pills combined with hypertonic glucose external application, moist dressing external application and surgical dressing change, respectively. The safety, therapeutic effect and cost benefit of the three treatment methods were compared. <strong>Results:</strong> There were no adverse reactions in the three groups of patients. The PUSH scores of the experimental group and the conventional treatment group were significantly lower than that of the control group on the 14<sup>th</sup>, 21<sup>th</sup>, and 28<sup>th</sup> days, and the result was statistically significant (p < 0.05), while there was no significant difference between the experimental group and the conventional treatment group (p > 0.05). The wound healing rates of the experimental group (70.14 ± 8.27%) and the conventional treatment group (73.99 ± 7.15%) were significantly higher than that of the control group (43.25 ± 8.53%) on the 28<sup>th</sup> day, with statistical significance (p < 0.05);there was no significant difference between the experimental group and the conventional treatment group (p > 0.05). The total treatment costs of the three groups were 569.73 ± 78.12 yuan, 1043.40 ± 135.31 yuan, and 186.47 ± 30.29 yuan. The cost of the conventional treatment group was the highest, followed by the experimental group, and the control group was the lowest. The result was statistically significant (p < 0.05). <strong>Conclusion:</strong> In the treatment of stage III and IV pressure injuries, there was no significant difference in the safety and therapeutic effect between the experimental group (Ji Desheng Snake Pills combined with hypertonic glucose external application) and the conventional treatment group (moist dressing external application), but the experimental group had better cost benefit.
基金National Key R&D Program of China,No.2017YFC0908900National Natural Science Foundation of China,No.81873565 and No.81900507Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.17CSK04 and No.15LC06.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic diseases in the world.Nowadays,the percentage of non-obese or lean patients with NAFLD is increasing.NAFLD in non-obese populations,especially the lean subgroup with a normal waist circumference(WC),might lead to more problems than obese individuals,as these individuals may not visit clinics for NAFLD diagnosis or ignore the diagnosis of NAFLD.If the precise characteristics of these populations,especially the lean subgroup,are identified,the clinicians would be able to provide more appropriate advice and treatment to these populations.AIM To investigate the prevalence,clinical characteristics,risk factors,and possible indicators for NAFLD in lean Chinese adults with a normal WC.METHODS People without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included.Their fatty liver index(FLI),abdominal ultrasonography results,and controlled attenuation parameter were all assessed.Genotyping for single-nucleotide polymorphisms associated with NAFLD was performed in another small group consisting of biopsy-proven NAFLD subjects and healthy controls.RESULTS A total of 2715 subjects who underwent routine health examinations were included in the study.Among 810 lean participants with a normal WC,142(17.5%)fulfilled the diagnostic criteria for NAFLD.Waist-height ratio,hemoglobin,platelets,and triglycerides were significant factors associated with the presence of NAFLD in these participants.The appropriate cut-off value of the FLI score in screening for NAFLD in the lean subjects with a normal WC was 25.15,which had a 77.8%sensitivity and 75.9%specificity.There was no significant difference in the single-nucleotide polymorphisms in the SIRT1,APOC3,PNPLA3,AGTR1,and PPARGC1A genes between lean subjects with and without NAFLD(P<0.05).CONCLUSION NAFLD is not uncommon in lean Chinese adults even with a normal WC.Metabolic factors,rather than genetic factors,may play important roles in the development of NAFLD in this population.A lower cut-off value of the FLI score in screening for NAFLD should be used for lean Chinese adults with a normal WC.
基金supported by grants from the Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01)the National Natural Science Foundation of China (81873565 and 82100605)+2 种基金Shanghai Jiao Tong University Transmed Awards Research (20190104)Star Program of Shanghai Jiao Tong University (YG2021QN54)Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (17CSK04 and 15LC06)。
文摘Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.
基金Project (CXZZ20140506150310438) supported by the Science and Technology Program of Shenzhen City, ChinaProject (2017GK2261) supported by the Science and Technology Program of Hunan Province, ChinaProject (2017zzts111) supported by the Fundamental Research Funds for the Central Universities, China。
文摘To solve the problem of difficult machining, the near-net shaped Al/SiCP composites with high volume fraction of SiC particles were fabricated by vacuum-pressure infiltration. The SiCP preform with a complex shape was prepared by gelcasting. Pure Al, Al4Mg, and Al4Mg2Si were used as the matrices, respectively. The results indicate that the optimal parameters of SiCP suspension in gelcasting process are pH value of 10, TMAH content of 0.5 wt.%, and solid loading of 52 vol.%. The Al matrix alloyed with Mg contributes to improving the interfacial wettability of the matrix and SiC particles, which increases the relative density of the composite. The Al matrix alloyed with Si is beneficial to inhibiting the formation of the detrimental Al4C3 phases. The Al4Mg2Si/SiCP composite exhibits high relative density of 99.2%, good thermal conductivity of 150 W·m^-1·K^-1, low coefficient of thermal expansion of 10.1×10^-6 K^-1, and excellent bending strength of 489 MPa.
文摘A sensitive, rapid, simple and economical ultra-performance liquid chromatography-tandem mass spectrometric method （UPLC-MS/MS） was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard （IS）. Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A （aqueous phase： 0.15% formic acid and 0.05% ammonium acetate） and B （organic phase： aeetonitrile） （A：B=40：60, v/v）. The flow rate was 0.25 mL/min and the total run time was 6 min. The multiple reaction monitoring （MRM） transitions, m/z 494.5-394.5 for imatinib, 488.7-401.5 for dasatinib, 530.7-289.5 for nilotinib and 528.5-403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6-5250.0 ng/mL for imatinib, 2.0-490.0 ng/mL for dasatinib, and 2.4-4700.0 ng/mL for nilotinib. The method showed acceptable results on sensitivity, specificity, recovery, precision, accuracy and stability tests. This UPLC-MS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentrations among the SLC22A5 -1889T 〉 C or SLCOIB3 699G 〉 A genotypes （P 〉 0.05）. This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors （TKIs）.
