ObjectiveTo investigate the mechanism by which Notoginsenoside R1 （NGR1） ameliorates hypoxia/reoxygenation （H/R）-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations （0， 6.25， 12.5， 25， 50， 100， 200， 300， 400， 500 μmol/L）. AC16 cells were divided into the following groups： control group （Control）， model group （H/R）， and treatment groups （H/R + NGR1 at 100， 200 and 300 μmol/L）. Mitochondrial membrane potential （ΔΨm） was measured using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Transcriptional levels of mitophagy-related genes （Parkin， Pink1， P62） were quantified by reverse transcription-quantitative PCR （RT-qPCR）. Protein expression of mitophagy-related markers （Parkin， Pink1， P62， and LC3BⅡ） was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy （TEM）. ResultsCompared to the control group， cell viability in the H/R group significantly decreased （P<0.01）. Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group （P<0.01）. H/R induced a significant decrease in mitochondrial membrane potential （P<0.01）， which was restored by NGR1 treatment （P<0.01）. The mRNA levels of Parkin， Pink1， and P62 in the H/R group were upregulated compared to the control group （P<0.05）， while NGR1 intervention downregulated their expression （P<0.05）. Protein expression levels of Parkin， Pink1， and LC3BⅡ in the H/R group significantly increased， while P62 expression decreased compared to the control group （P<0.01）. In contrast， different doses of NGR1 treatment significantly reduced the expression of Parkin， Pink1， and LC3BⅡ while increasing P62 expression （P<0.05）. TEM revealed that the mitochondrial structure in the H/R group was severely disrupted， with fragmented and disorganized cristae， which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury， and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.

Exportin 1 (XPO1) is aberrantly overexpressed in various malignant tumors and can lead to the loss of anti-tumor effects of important tumor suppressor proteins such as p53, RB1, and FOXO by mediating their nuclear export. Although XPO1 inhibitor Selinexor has entered clinical application, its single-agent anti-tumor activity remains suboptimal, which is closely related to the compensatory activation of multiple signaling pathways in response to XPO1 inhibition. Focusing on the core regulatory role of XPO1 in tumor cells, this article systematically summarizes the current landscape of combination therapies involving XPO1 inhibitors and various targeted agents, including inhibitors of CDK4/6, FLT3, BET, ATR, and BCL2/MDM2, aiming to provide some reference for the development of XPO1-centered combination therapy strategies.

ObjectiveTo establish preliminary diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients and provide a basis for standardized diagnosis and treatment of ischemic stroke. MethodsRelevant literature on the diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients was retrieved， and data were mined and extracted to form an item pool. Based on the formation of the item pool， this study used the Delphi method to initiate two rounds of questionnaire surveys with selected experts to complete the initial screening of items and the discrimination of symptom importance. A prospective clinical investigation method was adopted to collect clinical information from patients， and statistical analysis methods and data mining techniques were comprehensively used to determine their primary and secondary symptoms. Based on the clear main and secondary symptoms identified， combined with expert group discussions， the study established preliminary diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients. ResultsA total of 25 relevant syndrome differentiation standards were included. After splitting， standardizing， and screening the items， the study established a pool of 48 items. The first round of questionnaire survey consulted 30 experts， with both the positive coefficient of experts and the effectiveness rate of the questionnaire reaching 100%. The Kendall's coefficient of concordance was 0.359. According to the item screening criteria， 26 items were retained in this round of questionnaire survey. A total of 176 cases were collected through clinical information investigation， including 94 cases with spleen and kidney deficiency syndrome and 82 cases without spleen and kidney deficiency syndrome. The statistical results were as follows： ① Descriptive statistics： The main symptoms with a frequency of ≥ 30% included mental fatigue and lack of strength， weakness of the lower back and knees， etc. The secondary symptoms with a frequency of ≥ 10% and ≤ 30% were lassitude and disinclination to talk， shortness of breath， etc. ② Binary logistic regression analysis： The main symptoms with an odds ratio （OR） value of ≥ 3 were mental fatigue and lack of strength， weakness of the lower back and knees， etc. The secondary symptoms with an OR value of ≥ 1 and ≤ 3 were lassitude and disinclination to talk， shortness of breath， etc. Artificial neural network： The main symptoms with a weight value（W_ij）of ≥ 0.5 and < 1 were mental fatigue and lack of strength， lassitude and disinclination to talk， etc. The secondary symptoms with W_ij of ≥ 0.3 and < 0.5 were shortness of breath， flaccid limbs， etc. In the second round of questionnaire survey， a total of 37 experts were consulted， with both the positive coefficient of experts and the effectiveness rate of the questionnaire reaching 100%. The Kendall's coefficient of concordance was 0.237. According to the criteria to determine primary and secondary symptoms based on the Delphi method， the main symptoms included in this round of the questionnaire were mental fatigue and lack of strength， lassitude and disinclination to talk， etc.， and the secondary symptoms were shortness of breath， dizziness， etc. ConclusionThe main symptoms of spleen and kidney deficiency syndrome in ischemic stroke patients are mental fatigue and lack of strength， weakness of the lower back and knees， loose stool， pale and edematous tongue texture possibly with tooth marks， and deep and thready pulse or weak pulse. The secondary symptoms include shortness of breath， dizziness， tinnitus and deafness， decreased appetite or postprandial abdominal distension， pale complexion， frequent micturition at night， dull tongue texture， and white and slippery tongue coating. The preliminarily established diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients can provide a standardized and objective basis， thereby better guiding clinical diagnosis and treatment of ischemic stroke.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective This study aims to investigate the work fatigue risks of clinical nursing staff in a tertiary hospital in Xingguo County and analyze the influencing factors,providing a reference for formulating scientific work processes and systems and improving nursing quality.Methods A convenience sampling was conducted to select 179 clinical nurses from a tertiary hos-pital in Xingguo County from March to April 2025.A self-designed general information questionnaire,a clinical nursing staff work fatigue risk assessment questionnaire,and the nurse work stressor scale were used for the investigation.Univariate and multiple linear regression analyses were conducted to identify the influencing factors of work fatigue risks.Results A total of 186 ques-tionnaires were distributed,with 7 excluded as invalid and 179 valid responses(96.24％).The work fatigue risk assessment score of the 179 clinical nurses was(84.39±10.26),indicating a relatively high level of fatigue.There were significant differ-ences in work fatigue risk scores across genders,weekly working hours,years of work experience,contract types,and work stress levels(P＜0.05).Multiple linear regression analysis showed that gender(B=0.624,95％CI=0.194～1.054),weekly work-ing hours(B=0.037,95％CI=0.067～0.007),years of work experience(B=0.028,95％CI=0.010～0.046),contract type(B=-0.517,95％CI=-0.997～-0.037),and work stress(B=0.127,95％CI=0.050～0.204)were the influen-cing factors of work fatigue risks(P＜0.05).Conclusion The work fatigue risks of clinical nursing staff in a tertiary hospital in Xingguo County are at a relatively high level.Gender,weekly working hours,years of work experience,contract type,and work stress are the main influencing factors.Nursing managers should pay attention to these factors and take targeted measures to inter-vene and reduce the work fatigue risks of nursing staff.

Objective To explore the molecular mechanisms of moxibustion in improving osteoporosis in rats using high-throughput micro-RNA(miRNA)sequencing analysis.Methods A total of 18 female Sprague-Dawley(SD)rats were randomly divided into an operation group(12 rats),which was subjected to ovariectomy to induce osteoporosis,and a sham operation control(SO)group(6 rats).The 12 osteoporosis model rats were randomly divided into a model(OVX)group and a moxibustion(MOX)group(6 rats per group),which were treated with once-daily moxibustion at the"Shenshu"(BL23)and"Guanyuan"(CV4)acupoints for 20 minutes each time,for 12 weeks.Micro-computed tomography(CT)scans of the rat femur were taken to analyze the trabecular bone thickness(Tb.Th),trabecular separation(Tb.Sp),and bone volume total volume(BV/TV)ratio of the trabecular bone.Hematoxylin and eosin staining was used for morphological observation of tibial tissues.Serum alkaline phosphatase(ALP)and osteocalcin(OCN)levels were measured using ELISA.Three randomly selected rats from each group were used for miRNA high-throughput sequencing to screen for differentially expressed miRNAs,which were subjected to functional enrichment analysis and target gene prediction.Results Micro-CT images showed that,compared with the OVX group,the MOX group had superior bone density,significant increases in the Tb.Th and BV/TV score,and a significant decrease in Tb.Sp(P＜0.05).ELISA indicated that,compared with the OVX group,the MOX group showed a significant decrease in serum ALP activity and a significant increase in serum OCN content(P＜0.05).The miRNA sequencing result showed that 34 miRNAs were commonly expressed between the OVX group and the intervention group,and 15 miRNAs were commonly expressed between the OVX group and the intervention group.KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly enriched in signaling pathways involving MAPK,Ras,FoxO,TNF,and cancer-related microRNAs.For the top five most differentially expressed microRNAs,namely miR-153-5p,miR-201-5p,miR-449c-5p,miR-451-3p,and miR-153-3p,target gene predictions yielded 10 major targets:Ebf2,Rtn4,Fbxl3,Naa15,Vamp2,Daam1,Akap6,Camta1,Ptprz1,and Lamp1.Conclusions Acupuncture slowed the progression of osteoporosis,improved bone microstructure,and balanced bone metabolism in rats.This therapeutic effect may be achieved through regulation of the expression of microRNAs and their target genes;however,the underlying mechanism requires further exploration.

Objective:To clarify the morphological relationship between the upper airway and TMJ in patients with normal-angle skeletal Ⅱ and skeletal Ⅰ malocclusion.Methods:30 skeletal class Ⅰ and 22 skeletal class Ⅱ patients with normal-angle were included.CBCT examination was performed,and Mimics 21.0 software was used to conduct 3D reconstruction and measurements of the samples.Data was analyzed by using independent t-test and the Pearson correlation test.Results:12 measurements,including the sagittal diameter of nasopharyngeal segment,the sagittal,coronal diameter,minimum cross-sectional area,the volume of palato-pharyngeal segment and glossopharyngeum segment,the total volume of upper airway,posterior oblique slope of the articular eminence and the length of the condylar showed significant differences between skeletal Ⅱ and skeletal Ⅰ subjects with normal-angle(P＜0.05).The posterior oblique slope of the articular eminence showed a positive correlation with the sagittal diameter of the palatopharyngeal segment,volume and minimum cross-sectional area of glossopharyngeum lingual segment(P＜0.05).The liner ratio showed a negative correction with the coronal diameter of palatopharyngeal and glossapharyngeal segment as well as minimum cross-section area of glos-sapharyngeal segment(P＜0.05).Conclusion:The structure of upper airway is correlated with that of TMJ.Differences in the upper airway are statistically significant between skeletal Ⅱ and skeletal Ⅰ malocclusion with normal-angle(P＜0.05).

Objective:To explore the value of paediatric age-adjusted shock index（SIPA）in early identification of septic shock in children，and to evaluate the relationship between SIPA and disease severity and prognosis.Methods:The infected children admitted to the department of critical care medicine of the Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2023 to July 2024 were collected. Dynamic assessment was performed 0 to 6 hours after admission. Patients diagnosed with sepsis without septic shock were classified as the sepsis group and those diagnosed with sepsis with septic shock were classified as the septic shock group. According to whether the blood pressure of the children decreased，they were divided into two groups：compensated septic shock group and decompensated septic shock group. The difference of SIPA among the three groups was analyzed，and the predictive value of SIPA on case fatality rate，lactate level，pediatric critical illness score，ventilator utilization rate and length of hospital stay were analyzed.Results:Among 203 children with sepsis，112 were males and 91 were females. There were 146 cases in the sepsis group，37 cases in the compensated septic shock group and 20 cases in the decompensated septic shock group. There was no significant difference between the three groups in gender（ P>0.05），but there was a statistically significant difference in age（ χ 2=32.905， P<0.001）. There was no significant difference in age between the sepsis group and the compensated septic shock group（ P>0.05）. The age of sepsis group and decompensated septic shock group，compensated septic shock group and decompensated septic shock group were statistically significant（ χ 2=29.431， P<0.001； χ 2=19.764， P=0.001）. The proportion of increased SIPA was statistically different among the three groups，with both the compensated septic shock group and the decompensated septic shock group being higher than the sepsis group（ χ2=20.383， P<0.001； χ2=33.600， P<0.001）. The decompensated septic shock group was higher than the compensated septic shock group（ χ2=6.555， P=0.01）. SIPA was correlated with case fatality rate，lactate level，pediatric critical illness score，ventilator use rate and length of stay of the children，with statistically significant differences（ P<0.05）. Conclusion:The increase of SIPA can be used for the early identification of septic shock in children，and it has a certain early warning value for the prognosis assessment of sepsis and septic shock.

Objective To investigate the effect of fraxetin(FXT)on the malignant biological behavior of ovarian cancer cells by regulating Toll-like receptor 4(TLR4)/signal transducer and activator of transcription 3(STAT3)pathway.Methods Ovarian cancer cell lines SKOV3 and SW626 and ovarian epithelial cell line IOSE80 were treated with different concentrations of FXT(0,10,20,40,60,80 and 100 μmol/L),and the cytotoxicity of FXT was detected by methylthiazolyl diphenyl-tetrazolium bromide(MTT)assay.SKOV3 and SW626 cells were randomly divided into control group,FXT low,medium,high dose(40,60,80 μmol/L)group and FXT(80 μmol/L)+colivelin(STAT3 agonist,0.5 μmol/L)group.Colony formation assay and Transwell assay were used to detect cell proliferation,invasion and migration.The expressions of epithelial-mesenchymal transition and TLR4/STAT3 pathway related proteins were measured by Western blot.Results Compared with IOSE80 cells,SKOV3 and SW626 cell survival gradually decreased with increasing FXT concentration,and the differences were statistically significant(F=134.283,146.831,P<0.001).Compared with the control group,the relative colony lineage rates of SKOV3 and SW626 cells in the FXT low-,medium-and high-dose groups,invasion rate and mobility were reduced(t=4.433～45.909),E-cadherin were increased(t=5.879～17.345),and the expression of N-cadherin,zinc finger transcription factors(snail),vimentin,TLR4,phosphorylated(p)-STAT3/STAT3,cell cycle protein D1(Cyclin D1)and MYC oncogenes(Cancer-myc,C-myc)expression were sequentially reduced(t=7.348～50.117),and the differences were statistically significant(all P<0.01),respectively.Compared with the high-dose FXT group,the relative colony formation rate,cell invasion rate and migration rate of SKOV3 and SW626 cells in the FXT+colivelin group increased(t=9.224～20.703),while the expression of E-cadherin protein decreased(t=3.104,5.041),the expression of N-cadherin,snail,vimentin,TLR4,p-STAT3/STAT3,Cyclin D1,and C-myc increased(t=8.403～42.175),and the differences were statistically significant(all P<0.05),respectively.Conclusion FXT may exert antitumor effects by antagonizing the activation of TLR4/STAT3 signaling pathway and inhibiting ovarian cancer cell proliferation,migration,invasion and epithelial mesenchymal transition.

Objectives:To investigate the risk factors of acute myocardial infarction(AMI)patients with a family history of premature coronary heart disease(FHpCHD)in China and analyze the relationship between these risk factors and premature myocardial infarction.Methods:Using data form the Chinese Acute Myocardial Infarction(CAMI)Registry which enrolled a total of 28 070 patients with AMI from 108 hospitals between January 1,2013 to September 30,2014.We compared the demographic data,cardiovascular risk factors,clinical characteristics,and prognosis in AMI patients with and without FHpCHD.FHpCHD is defined as the history of myocardial infarction,angina,sudden cardiac death and/or revascularization(including coronary artery bypass grafting and percutaneous coronary intervention)among first-degree relatives(father,mother,brother and sister)aged≤55 years old for men or≤65 years old for women.The risk factors included obesity,hypertension,diabetes,hyperlipidemia,unhealthy diet,lack of physical activity,smoking,and frequent alcohol consumption.The correlation between family history and premature AMI was calculated by the multivariate Logistic regression analysis.The risk contribution values of the affected first-degree relatives were determined by applying the Shapley algorithm.Results:A total of 893 cases(4.12%)of AMI patients had FHpCHD.Among patients with premature AMI,467 cases(6.20%)had FHpCHD.AMI patients with FHpCHD were younger,and had a higher proportion of male,obesity/overweight,hypertension,hyperlipidemia,and stroke history,unhealthy lifestyle(such as frequent alcohol consumption and current smoking),and a higher proportion of multi-vessel lesions in coronary angiography compared to those without FHpCHD(all P<0.05).AMI patients with FHpCHD had a significantly higher proportion of risk factors(P<0.01).After adjusting for sociodemographic factors,lifestyle,and cardiovascular risk factors,multivariate Logistic analysis revealed that FHpCHD was significantly associated with premature AMI(OR=1.793,95%CI:1.553-2.070,P<0.0001).The calculation using the Shapley algorithm showed that the father had the highest risk contribution value(40.27%).Conclusions:AMI patients with FHpCHD exhibit a clustering of family unhealthy lifestyle and cardiovascular risk factors,with an earlier onset age and more severe coronary artery disease.FHpCHD is associated with AMI,independent of lifestyle and cardiovascular risk factors.