Atherosclerosis is a chronic inflammatory disease and the root cause of most cardiovascular diseases.Soluble guanylate cyclase(sGC)agonists play an important role in the regulation of atherosclerotic diseases by nitric oxide(NO)/sGC/cyclic guanosine phosphate(cGMP)signaling pathway.sGC plays an anti-atherosclerotic role in reducing blood lipid levels,improving endothelial dysfunction,reducing inflammatory responses,inhibiting platelet activation,in-hibiting smooth muscle cell proliferation and apoptosis via activating downstream cGMP.This article reviews the effect of sGC agonists on atherosclerosis and its mechanism,in order to provide a theoretical basis for the clinical application of sGC agonists.

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.

Objective To study the pharmacokinetic profile of zidovudine and lamivudine tablets(ZL)in Chinese healthy subjects and to evaluate its bioequivalence and safety.Methods A randomized,open,single-dose,two-sequence,four-cycle and fully replicated crossover bioequivalence trial was conducted in 32 healthy subjects both fasting and postprandial,and two preparations of ZL tablets were administered orally in each cycle,with a washout period of 5 days.The concentrations of zidovudine and lamivudine in plasma were determined using high performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic evaluation index parameters were statistically analyzed using Phoenix WinNonlin version 8.1 data statistical software to evaluate bioequivalence.Results The Cmax of zidovudine under fasting and postprandial conditions between ZL and the reference drugs after a single dose were(3 782.499±1 921.649)vs.(3 543.164±1 946.076)ng·mL-1 and(1 585.827±914.246)vs.(1 667.595±862.945)ng·mL-1,respectively.And the AUC0-t for fasting and postprandial conditions of zidovudine was(3 177.091±819.538)vs.(3 071.375±972.145)h·ng·mL-1 and(2 437.999±478.147)vs.(2 402.725±477.792)h·ng·mL-1,respectively;while the AUC0-∞ were(3 225.674±825.131)vs.(3 093.448±972.340)h·ng·mL-1and(2 464.310±480.790)vs.(2 427.693±477.933)h·ng·mL-1,respectively.The Cmax of a single dose of lamivudine under fasting and postprandial conditions between ZL and the reference drugs were(1 923.329±490.572)vs.(1 830.570±476.947)ng·mL-1 and(1 922.711±589.130)vs.(1 881.857±527.577)ng·mL-1,respectively.The AUC0-t for preprandial and postprandial lamivudine was(7 598.265±1 376.774)vs.(7 283.422±1 356.146)h·ng·mL-1 and(7 554.169±958.379)vs.(7 329.376±924.075)h·ng·mL-1,respectively,whereas the AUC0-∞ were(7 734.038±1 326.907)vs.(7 405.088±1 340.036)h·ng·mL-1 and(7 660.916±958.694)vs.(7 435.102±930.448)h·ng·mL-1,in fasting and fed tests,the 90％confidence intervals(CI)of the geometric mean ratios of the main pharmacokinetic parameters between test and reference preparations were all within the range of 80％-125％,respectively.A total of 37 adverse events occurred during the trial period,including 21 in the fasting group and 16 in the postprandial group,and no serious adverse events occurred.Conclusion The test formulations of zidovudine and lamivudine tablets were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions compared to the reference tablets.

Atherosclerosis is a chronic inflammatory disease and the root cause of most cardiovascular diseases.Soluble guanylate cyclase(sGC)agonists play an important role in the regulation of atherosclerotic diseases by nitric oxide(NO)/sGC/cyclic guanosine phosphate(cGMP)signaling pathway.sGC plays an anti-atherosclerotic role in reducing blood lipid levels,improving endothelial dysfunction,reducing inflammatory responses,inhibiting platelet activation,in-hibiting smooth muscle cell proliferation and apoptosis via activating downstream cGMP.This article reviews the effect of sGC agonists on atherosclerosis and its mechanism,in order to provide a theoretical basis for the clinical application of sGC agonists.

Objective To study the pharmacokinetic profile of zidovudine and lamivudine tablets(ZL)in Chinese healthy subjects and to evaluate its bioequivalence and safety.Methods A randomized,open,single-dose,two-sequence,four-cycle and fully replicated crossover bioequivalence trial was conducted in 32 healthy subjects both fasting and postprandial,and two preparations of ZL tablets were administered orally in each cycle,with a washout period of 5 days.The concentrations of zidovudine and lamivudine in plasma were determined using high performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic evaluation index parameters were statistically analyzed using Phoenix WinNonlin version 8.1 data statistical software to evaluate bioequivalence.Results The Cmax of zidovudine under fasting and postprandial conditions between ZL and the reference drugs after a single dose were(3 782.499±1 921.649)vs.(3 543.164±1 946.076)ng·mL-1 and(1 585.827±914.246)vs.(1 667.595±862.945)ng·mL-1,respectively.And the AUC0-t for fasting and postprandial conditions of zidovudine was(3 177.091±819.538)vs.(3 071.375±972.145)h·ng·mL-1 and(2 437.999±478.147)vs.(2 402.725±477.792)h·ng·mL-1,respectively;while the AUC0-∞ were(3 225.674±825.131)vs.(3 093.448±972.340)h·ng·mL-1and(2 464.310±480.790)vs.(2 427.693±477.933)h·ng·mL-1,respectively.The Cmax of a single dose of lamivudine under fasting and postprandial conditions between ZL and the reference drugs were(1 923.329±490.572)vs.(1 830.570±476.947)ng·mL-1 and(1 922.711±589.130)vs.(1 881.857±527.577)ng·mL-1,respectively.The AUC0-t for preprandial and postprandial lamivudine was(7 598.265±1 376.774)vs.(7 283.422±1 356.146)h·ng·mL-1 and(7 554.169±958.379)vs.(7 329.376±924.075)h·ng·mL-1,respectively,whereas the AUC0-∞ were(7 734.038±1 326.907)vs.(7 405.088±1 340.036)h·ng·mL-1 and(7 660.916±958.694)vs.(7 435.102±930.448)h·ng·mL-1,in fasting and fed tests,the 90％confidence intervals(CI)of the geometric mean ratios of the main pharmacokinetic parameters between test and reference preparations were all within the range of 80％-125％,respectively.A total of 37 adverse events occurred during the trial period,including 21 in the fasting group and 16 in the postprandial group,and no serious adverse events occurred.Conclusion The test formulations of zidovudine and lamivudine tablets were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions compared to the reference tablets.

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

[摘 要] 目的：探讨多结节非小细胞肺癌（NSCLC）组织中的驱动基因突变情况与临床病理特征的关系，为多结节NSCLC患者治疗提供分子诊断依据。方法：本研究共纳入2018年1月至2023年10月间云南省肿瘤医院分子诊断中心检测的121例多结节NSCLC患者的253个肺结节肿瘤组织标本，以第二代测序（NGS）技术或扩增阻滞突变系统PCR（ARMS-PCR）技术检测多结节NSCLC 组织中驱动基因突变情况，分析其与患者临床病理特征的关系，比较不同结节间肺癌驱动基因的突变异质性。结果：与非“宣威”NSCLC相比，“宣威”多结节NSCLC患者驱动基因突变具有显著的地域特点，表现在“宣威”患者具有较低（20%）的EGFR敏感突变（L858R、19-del）及较高（27.26%）的EGFR少见突变（主要为G719/S768I、G719）；“宣威”多结节NSCLC患者的KRAS突变率（27.27%）亦显著高于非“宣威”患者突变率（12.59%）（P<0.05）。此外，“宣威”多结节NSCLC患者驱动基因突变不一致率高达69.23%，远高于非“宣威”患者驱动基因突变不一致率（55.07%）（P<0.05）。结论：“宣威”多结节NSCLC患者具有较高的EGFR少见突变及KRAS突变率，同一患者不同病灶之间存在更高的驱动基因突变异质性，本研究将为“宣威”多结节NSCLC的诊疗策略提供更多的选择。