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 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.

Morinda officinalis is one of the “Four Great Southern Medicines” and is commonly used in clinical practice to treat erectile dysfunction and nocturnal emissions caused by kidney yang deficiency， uterine cold infertility， menstrual disorders， low abdominal pain， rheumatism， and muscle and bone weakness. Based on the principle of “treating raw and cooked differently”， this article summarizes the effects of different processing methods on the chemical constituents and pharmacological effects of M. officinalis . Research has found that processing can affect the content and structure of sugars， iridoids， and anthraquinones in M. officinalis ， thereby regulating its pharmacological effects such as anti-osteoporosis， immune regulation， anti-fatigue， and anti-depression. Among them， salt M. officinalis shows outstanding performance in anti-osteoporosis and enhancing immunity. Although previous studies have preliminarily elucidated the major chemical constituents of M. officinalis and their pharmacological characteristics， the dynamic transformation paths of constituents during the processing remain to be further clarified， especially the es tablishment of a quality marker system associated with the processing technology， to achieve the precision and intelligent development of the processing.

Morinda officinalis is one of the “Four Great Southern Medicines” and is commonly used in clinical practice to treat erectile dysfunction and nocturnal emissions caused by kidney yang deficiency， uterine cold infertility， menstrual disorders， low abdominal pain， rheumatism， and muscle and bone weakness. Based on the principle of “treating raw and cooked differently”， this article summarizes the effects of different processing methods on the chemical constituents and pharmacological effects of M. officinalis . Research has found that processing can affect the content and structure of sugars， iridoids， and anthraquinones in M. officinalis ， thereby regulating its pharmacological effects such as anti-osteoporosis， immune regulation， anti-fatigue， and anti-depression. Among them， salt M. officinalis shows outstanding performance in anti-osteoporosis and enhancing immunity. Although previous studies have preliminarily elucidated the major chemical constituents of M. officinalis and their pharmacological characteristics， the dynamic transformation paths of constituents during the processing remain to be further clarified， especially the es tablishment of a quality marker system associated with the processing technology， to achieve the precision and intelligent development of the processing.

ObjectiveTo systematically characterize the in vitro chemical constituents of Entada phaseoloides and its absorbed prototype compounds and metabolites in a neuropathic pain （NP） model， thereby elucidating the potential pharmacological material basis underlying its analgesic activity. MethodsUltra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to analyze the constituents of the 80% methanol extract of E. phaseoloides. Thirty-six mice were divided into a blank group， low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， an aspirin group （400 mg·kg^-1）， and a morphine group （10 mg·kg^-1）， with six mice in each group. The tail-flick threshold was measured. Twenty-four mice were randomly divided into a blank group and low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， with six mice in each group， and motor coordination was evaluated. A spinal nerve ligation （SNL） model was established in mice. Twenty-four mice were randomly divided into a sham-operated （Sham） group， an SNL group， an SNL + E. phaseoloides extract group （750 mg·kg^-1）， and an SNL + pregabalin group （20 mg·kg^-1）， with 6 mice in each group. Mechanical allodynia and thermal hyperalgesia were evaluated. Behavioral assessments were combined to determine the optimal onset time of the analgesic effect， and plasma samples were collected at this time point. Absorbed components and metabolites were systematically identified based on accurate mass， MS/MS fragmentation patterns， retention time， and comparisons with literature data and reference standards. Meanwhile， network pharmacology， target similarity analysis， and molecular docking validation were integrated to evaluate the potential effects of absorbed components on disease intervention. ResultsCompared with the blank group， the high-dose E. phaseoloides extract group and morphine group showed significantly increased pain response thresholds （P<0.01）， without affecting motor coordination in normal mice. Compared with the Sham group， the SNL group exhibited significantly decreased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. Compared with the SNL group， the SNL + E. phaseoloides extract group and SNL + pregabalin group showed significantly increased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. The analgesic effect of E. phaseoloides was most significant at 2 h after administration. A total of 70 constituents were identified in vitro， and 22 prototype compounds and 29 metabolites were detected in plasma. The targets of the absorbed components were mainly enriched in biological processes associated with pain signal perception and transmission and showed a high degree of overlap with disease genes related to neuropathic pain. In addition， multiple components exhibited strong binding energies with core pain-related targets. Based on integrated analysis of in vitro content， plasma exposure levels， and target associations， ketanthamide A-β-D-pyranoside and ketengzide were identified as the most representative pharmacologically active substances responsible for the analgesic effect. ConclusionThis study systematically elucidates the material basis of E. phaseoloides intervention in neuropathic pain from three aspects， including chemical constituent characteristics， in vivo behavioral characteristics， and potential targets， providing important theoretical foundations and experimental support for further studies on its pharmacological mechanism and analgesic drug development.

Background:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCM v2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-κB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.

Objective To investigate the value of prone-position MRI of lumbar spine for diagnosing pediatric occult tethered cord syndrome(OTCS).Methods A total of 67 children with suspected tethered cord syndrome(TCS)and confirmed OTCS by surgery were prospectively enrolled as OTCS group,while 73 healthy subjects were recruited as control group.Supine-and prone-position lumbar MR examinations were performed in both groups.The position of filum terminale on prone axial T2WI and the presence or absence of"sunset sign"(i.e.filum terminale located within the dorsal 1/2 of spinal canal on prone axial T2WI)were observed,spinal cord conus mobility was calculated.The efficacy of"sunset sign"for diagnosing OTCS in children was calculated through comparison between groups.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of spinal cord conus mobility.Results On prone-position axial T2WI,"sunset sign"was found in 58 cases(58/67,86.57％)but not in 9 cases(9/67,13.43％)in OTCS group,which was not even observed in control group.The sensitivity of"sunset sign"for diagnosing pediatric OTCS was 86.57％(58/67),with specificity of 100％(73/73),positive predictive value of 100％(58/58)and negative predictive value of 89.02％(73/82).The spinal cord conus mobility was(19.30±5.89)％in OTCS group and(31.71±6.58)％in control group,being statistically different between groups(t=-11.722,P＜0.001).The sensitivity,specificity and AUC of spinal cord conus mobility for diagnosing pediatric OTCS was 80.60％,90.41％and 0.920,respectively.Conclusion Prone-position MRI of lumbar spine could be used in diagnosing pediatric OTCS.

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 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.