OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease （ASCVD） following percutaneous coronary intervention （PCI）. METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1， 2023 and December 31， 2024. According to the lipid-lowering regimen， the patients were categorized into evolocumab group （ n ＝86） and probucol group （ n ＝70）. Changes in lipid parameters [total cholesterol （TC）， low-density lipoprot ein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， triglycerides， lipoprotein （a）， and lipid goal achievement rate ] ， inflammatory markers [interleukin-6 （IL-6） and C-reactive protein （CRP） ] ， and cardiac function indices （left ventricular ejection fraction， left ventricular end-systolic diameter， left ventricular end-diastolic diameter， and N-terminal pro-B-type natriuretic peptide） were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment， including acute myocardial infarction， in-stent restenosis， acute heart failure， cerebral hemorrhage， and stroke， was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline （ P ＞0.05）. After 6 months of treatment， both groups demonstrated significant improvements in lipid profiles （except HDL-C） and inflammatory markers compared to those at baseline （ P ＜0.05）. The evolocumab group exhibited greater reductions in TC， LDL-C， IL-6， and CRP， along with a higher lipid target achievement rate， compared with the probucol group （ P ＜0.05）. There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups， nor in the incidence of adverse events during the treatment （ P ＞0.05）. CONCLUSIONS For ultra-high-risk ASCVD patients after PCI， both of the above treatment options are associated with improvements in blood lipid and inflammatory response， with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC， LDL-C and inflammatory markers reduction and lipid target achievement， compared to probucol.

Objective To comprehensively analyze the current epidemic characteristics and disease burden of brucellosis in Tongliao City, and to provide a basis for the prevention and control strategy of brucellosis in Tongliao City. Methods The report data of brucellosis in Tongliao City from 2018 to 2023 were collected. Descriptive methods were used for data analysis, and the disability-adjusted life years and indirect economic losses were calculated. Results From 2018 to 2023, a total of 22 034 cases were reported in Tongliao City, with an average annual incidence of 136.17/100 000. The incidence was statistically different between men and women ( χ²=12.23, P=0.032). The majority of cases were farmers (94.25%), followed by herdsmen (1.67%). The age group was concentrated between 30-60 years old (79.30%), among which the majority of cases were in the 40-50 years group (6 883/22 034). The onset time had seasonal characteristics, and the peak period was from March to August (the seasonal index was between 115.40%-151.29%). In terms of regional distribution, cases were reported in all counties (banners). The average annual incidence was highest in Kulun Banner (233.85/100 000) and Zalut Banner (210.13/100 000), and lowest in Keerqin District (42.28/100 000) and Holingol City (31.87/100 000). The analysis of disease burden showed that a total of 677.55 person-years (YLD) were lost from 2018 to 2023, with an average annual loss of 112.92 person-years. The total indirect economic loss was 59.3576 million yuan, with an average annual loss of 9.892 9 million yuan, and the people over 60 years old had the lowest annual loss. Conclusion The overall brucellosis epidemic in Tongliao City has shown a fluctuating downward trend. The epidemic prevention and control should be strengthened in farmers, people aged 40-50 years old, and areas such as Zalut Banner and Kulun Banner to further control the epidemic of brucellosis.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

[Purpose]To analyze cancer incidence and mortality in Liaoning cancer registration areas from 2016 to 2020 and the trends from 2006 to 2020.[Methods]Cancer data in cancer registra-tion areas in Liaoning Province from 2016 to 2020 were collected.The incidence and mortality,age-standardized rate,cumulative rate(0～74 years old),and age-specific rate were calculated.Age-standardized incidence and mortality rate were calculated by the Chinese standard popula-tion(ASIRC,ASMRC)and Segi world standard population(ASIRW,ASMRW).Joinpoint software was applied to analyze the trends of incidence and mortality.[Results]From 2016 to 2020,the crude incidence rate of cancer in Liaoning cancer registration areas was 422.30/105,the ASIRC and ASIRW were 215.67/105 and 209.52/105.The ASIRC was higher in urban areas(225.00/105)than that in rural areas(190.15/105),and higher in male(221.47/105)than that in female(213.03/105).The crude mortality rate was 254.22/105,the ASMRC and ASMRW were 113.26/105 and 112.91/105.The ASMRC in urban areas(113.12/105)was the same as that in rural areas(113.01/105),and higher in male(146.86/105)than that in female(83.46/105).The ASIRW of lung cancer was 46.13/105,and the ASMRW was 32.04/105,both ranking the first of all cancers.From 2006 to 2020,the crude incidence,ASIRC and ASIRW in urban areas showed an increasing trend(AAPC=3.921％,t=16.222,P＜0.05;AAPC=0.823％,t=2.409,P＜0.05;AAPC=0.875％,t=2.933,P＜0.05).The crude incidence,ASIRC and ASIRW in urban female were all rising(AAPC=4.151％,t=15.888,P＜0.05;AAPC=1.597％,t=4.819,P＜0.05;AAPC=1.514％,t=4.752,P＜0.05).During the same period,the cancer mortality in urban areas showed an increasing trend(AAPC=3.175％,t=14.745,P＜0.05),and the ASMRW showed a decreasing trend(AAPC=-0.908％,t=-2.273,P＜0.05).The crude mor-tality of both men and women showed an increasing trend(AAPC=3.010％,t=6.032,P＜0.05;AAPC=2.820％,t=5.921,P＜0.05),while the crude mortality and ASMRW for female showed a significant downward trend(AAPC=-1.487％,t=-2.437,P＜0.05;AAPC=-2.680％,t=-2.246,P＜0.05).From 2016 to 2020,the crude incidence,ASIRC and ASIRW in rural areas showed no significant change;however,the crude incidence in male was increasing(AAPC=2.025％,t=3.853,P＜0.05).In the same period,the crude mortality rate in rural areas increased(AAPC=3.577％,t=9.377,P＜0.05),while there was no significant change in the ASMRC and ASMRW.The crude mortality of both men and women showed an increasing trend(AAPC=3.377％,t=10.615,P＜0.05;AAPC=3.978％,t=7.245,P＜0.05),while there was no significant change in ASMRC and ASMRW.[Conclusion]The cancer burden in Liaoning from 2016 to 2020 was higher than the average level in China,can-cer prevention and control should be further strengthened in the provice.

This study aims to investigate the changes in blood biochemical indicators of tongue roll-ing(TR)behavior in cattle and their correlation with changes in oral microbiota,laying a founda-tion for further exploring the relationship between animal oral microbiota,biochemical indicators,and behavioral changes.It also provides theoretical basis for preventing and treating TR behavior through regulating oral microbiota.This study intends to analyze and compare the blood biochemi-cal indicators and changes in oral microbiota of cattle with TR behavior and healthy cattle without TR behavior(healthy control,H),in order to explore the blood biochemical indicators of TR cattle and their correlation with changes in oral microbiota.Blood samples from the caudal vein of cattle in each group were collected for the detection of blood biochemical indicators and stress-related hormone indicators.Oral swabs from cattle in each group were collected for 16S rRNA gene se-quencing to analyze the composition,structure,and functional changes of their oral microbiota.The results of blood biochemical indicators in H and TR groups showed that the concentrations of al-bumin(ALB),aspartate aminotransferase(AST),calcium ion(Ca2+),and cortisol in TR group were significantly higher than those in H group(P＜0.05).There were significant differences in beta diversity of oral microbiota between TR and H groups(P＜0.05).At the genus level,the rela-tive abundances of Pseudomonas,Enterobacter,Xanthomonas,and other genera in the oral micro-biota of TR group were significantly higher than those in H group(P＜0.05).However,the rela-tive abundances of Tessaracoccus,Turicibacter,Monoglobus,Dietzia,Bifidobacterium,and other genera in the oral microbiota of TR group were significantly lower than those in H group(P＜0.05).In the KEGG metabolic pathway at the third level,the relative abundances of thiamine me-tabolism,lipoate metabolism,cysteine and methionine metabolism in the oral microbiota of TR group were significantly lower than those in H group(P＜0.05).Spearman correlation analysis showed that ALB and AST were significantly positively correlated with the relative abundances of Pseudomonas and Stenotrophomonas.Therelative abundances of Pseudomonas,Stenotrophomonas,and Sphingomonas were significantly positively correlated with fatty acid metabolism,phosphate and phosphonate metabolism,and lipoate metabolism.ALB was significantly positively correlated with inositol phosphate metabolism and phosphate and phosphonate metabolism.The study found that there were significant differences in blood biochemical indicators and oral microbiota between TR and H groups.In addition,there is a certain correlation between the composition,structure,and function of oral microbiota and the biochemical function of the host.This indicates that TR behav-ior may be associated with changes in the biochemical indicators of the host and the composition,structure,and function of oral microbiota.

Objective:To investigate the feasibility of varicocele ligation with mobile phone microscope.Methods:The high-performance mobile phone and mobile phone stand were combined to act as a mobile phone microscope.And the varicocele ligation was performed under the mobile phone microscope.Results:All five patients successfully underwent varicocelectomy under the guidance of a mobile phone microscope.The average operation time was(112.8±52.2)with ranged from 74.0 to 195.0 minutes.Three pa-tients completed the follow-up after the operation with the proportion of improved sperm quality reaching 100.0％(3/3).Conclusion:High-performance mobile phone microscope can be used for varicocele ligation.

Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

Objective:To observe the tumor control and the degree of radiation-induced lung injury (RILI) between FLASH irradiation and conventional dose rate (CONV) irradiation, and compare the changes in plasma proteomic profiles of mice following whole-lung FLASH and CONV irradiation using proteomics method.Methods:A mouse model with metastatic lung cancer was established. After whole-lung irradiation, changes in normal lung capacity were monitored using CT scans. Then, a RILI model was constructed to examine pathological alterations in lung tissues following whole-lung CONV and FLASH irradiation. Plasma samples were collected from mice receiving whole-lung CONV irradiation ( n = 5) and whole-lung FLASH irradiation ( n = 5), followed by comparison with samples from the control group of healthy mice (also referred to as the healthy control group). These plasma samples were analyzed using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics, followed by the screening and identification of differentially expressed proteins using high-throughput bioinformatics. Moreover, protein-protein interaction (PPI) network analysis was conducted to identify hub genes using the STRING database and Cytoscape software. Results:Whole-lung FLASH and CONV irradiation produced consistent tumor control, with the former significantly reducing RILI compared to the latter. A total of 609 proteins were identified through proteomic analysis. Among them, 89 differentially expressed proteins were detected in the whole-lung FLASH group. Gene Ontology (GO) enrichment analysis indicated that up-regulated genes were primarily associated with stress and inflammatory responses, whereas down-regulated genes were related to ATP metabolism and angiogenesis regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that up-regulated genes were predominantly enriched in unfolded protein response pathways, while down-regulated genes were mainly involved in metabolic pathways and oxidative phosphorylation. Integrated PPI analysis and subsequent validation via reverse transcription-polymerase chain reaction (RT-PCR) revealed four key genes.Conclusions:Compared to the whole-lung CONV irradiation, whole-lung FLASH irradiation reduces the RILI of normal lung tissues while maintaining equivalent tumor control in metastatic lung cancer. Proteomic analysis of differentially expressed proteins in plasma after whole-lung FLASH and CONV irradiation provides valuable insights into the molecular mechanisms underlying the FLASH effect.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

Objective To systematically evaluate the safety and efficacy of replacing tyrosine kinase inhibitors(TKIs)with similar drugs after they cause liver injury,based on case reports and case series studies.Methods PubMed,Embase,Cochrane,Web of Science,CNKI,Wanfang,and VIP databases were searched up to October 2023.Two reviewers independently screened the literature,extracted data,and assessed the quality of the studies.Descriptive and statistical analyses were performed.Results Twenty-six studies(22 case reports and 4 case series)were included,involving 75 patients who switched to similar drugs for TKI-induced liver injury,primarily targeting the epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),and multiple targets.The results indicate that majority of patients have favorable safety profiles after switching drugs,with normal liver function or no severe liver injury.Only one patient reported a serious liver adverse reaction,characterized by(grade 3 total bilirubin elevation).In terms of clinical efficacy,most patients responded well to the new TKIs,maintaining stable disease,or showing no progression during follow-up.Disease progression occurred in only two patients who switched from gefitinib to erlotinib after dose reduction due to non-hepatic adverse effects.Additionally,one patient who switched from erlotinib to afatinib experienced worsening tumor symptoms.Conclusion Evidence from published case reports and case series suggests that continuing treatment with similar drugs after TKI-induced liver injury,targeting EGFR,ALK,and multiple targets,demonstrates a certain degree of safety,efficacy,and clinical practicability.This can be a strategy after TKI discontinuation due to liver injury.However,there are no clear guidelines on drug selection,timing,and dosage,and further research is urgently needed.