BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

OBJECTIVES: To evaluate the one-year outcomes of valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) using SAPIEN 3 valve for treating mitral bioprosthetic valve failure. METHODS: A retrospective analysis was conducted on 26 patients with mitral bioprosthetic valve failure who underwent ViV-TMVR at West China Hospital, Sichuan University, between November 2022 and July 2024. The age of patients was 71.5 (64.5, 74.5) years, and 69.2% were female. Bioprosthetic valve failure occurred at (9.7±3.7) years after initial surgical implantation, with the most common failure mode being mixed stenosis and regurgitation (53.8%). The SAPIEN 3 valve was implanted via either a transseptal or transapical approach. Echocardiography was performed preoperatively, immediately post-procedure, and at 1 month, 6 months, and 1 year post-procedure. Outcomes included all-cause mortality, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score, and postoperative complications. RESULTS: The procedure was performed via the transseptal approach in 21 patients (80.8%) and the transapical approach in 5 patients (19.2%). All procedures were technically successful. No paravalvular leakage was observed immediately post-procedure, and mitral valve hemodynamics improved significantly. At the 1-year follow-up, 2 patients had died. Two patients (8.3% of survivors) were of NYHA functional class Ⅲ, and KCCQ-12 score improved to (88.4±14.6) points (both P<0.01). Echocardio-graphy at 1 year postoperatively showed significant reductions in peak mitral valve velocity [to (2.29±0.32) m/s] and mean transvalvular pressure gradient [to (9.5±3.5) mmHg, 1 mmHg=0.133 kPa] compared to baseline (both P<0.05). No moderate or severe mitral regurgitation or paravalvular leakage was observed. The proportion of patients with moderate-to-severe pulmonary hypertension decreased from 65.4% preoperatively to 13.0% at 1 year (P<0.05). CONCLUSIONS ViV-TMVR with the SAPIEN 3 valve for mitral biopro-sthetic valve failure is associated with high procedural success, significantly improved valve hemodynamics of the mitral value, alleviation of pulmonary hypertension, enhanced quality of life, and a low rate of complications at 1 year after the operation.
Humans ; Female ; Male ; Retrospective Studies ; Aged ; Bioprosthesis ; Heart Valve Prosthesis ; Mitral Valve/surgery* ; Heart Valve Prosthesis Implantation/methods* ; Middle Aged ; Prosthesis Failure ; Treatment Outcome ; Mitral Valve Insufficiency/surgery*

Objective:To investigate human factors underlying radiotherapy planning safety incidents and quantitatively explore their interrelationships.Methods:A total of 1 619 safety incidents recorded in the automated plan checking system developed by West China Hospital of Sichuan University were utilized. Human factors were identified and statistically analyzed using the Human Factors Analysis and Classification System (HFACS). A Bayesian network model was developed and combined with sensitivity analysis for quantitative assessment.Results:Key contributing factors included organizational processes (12.89%), inadequate supervision (11.85%), and personnel factors (13.50%). Utilizing the established HFACS Bayesian network hybrid model in conjunction with sensitivity analysis, it has been found that the most significant influences on skill‐based errors and decision errors were condition of operators and environmental factors, with corresponding indices of 0.96 and 0.76. Additionally, personnel factors had the greatest impact on routine, with an index of 3.51.Conclusions:Key contributing factors span all HFACS levels, with organizational processes, supervision, personnel, and condition of operators each playing a significant role. Upstream factors — such as organizational climate, environment factors, and personnel factors — strongly influence downstream risks. These offer actionable insights for developing targeted safety protocols.

Acupuncture and moxibustion have their unique advantages in treating tumors,but the theoretical framework of acupuncture and moxibustion intervention in tumors needs to be improved,and the academic system still needs to be sorted out.In this paper,we try to describe the commonalities between Chinese medical theories and modern medical technologies in order to consolidate the theoretical foundation of acupuncture intervention in tumor.Specifically:① Acupuncture regulates immune function and energy metabolism,which is a specific form of tonifying the spleen and stomach to support positive qi.② Tumors belong to the broad definition of"sores and ulcers"in traditional Chinese medicine,which is a special kind of chronic inflammation,and acupuncture intervenes in tumors by intervening in inflammatory reactions from ulcers.③ Tumor is a"dynamic pseudo-organ"with yin and yang attributes and"life attributes".Acupuncture and moxibustion can regulate various cells and factors in the tumor environment in a multi-targeted way,so as to make it tend to the state of yin and yang equilibrium.④ Acupuncture and moxibustion have unique advantages in the reduction of toxicity,enhancement of efficacy,tonicity,rejuvenation,treatment of complications,etc.,which complement the allopathic therapies of modern medicine,and can help to realize survival with tumors.

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

Objective:To investigate the influence of different ratios of contrast agent(CA)to saline on image quality of coronary computed tomography angiography(CCTA)in dual-flow injection technique.Methods:A prospective study included 102 patients who were clinically diagnosed as suspected coronary heart disease(CHD)to undergo CCTA scan at Beijing Friendship Hospital,Capital Medical University,between March 2024 and October 2024.Ultimately,90 patients were enrolled,who adopted CA injection protocol of dual-flow injection technique.Patients were randomly divided into three groups using a random number table,with 30 patients in each group.The different ratios of CA to saline were adopted,which were respectively Group A(1:9),Group B(2:8),and Group C(3:7).For the reconstructed images,the computed tomography(CT)values of heart-related anatomical structures,which included superior vena cava,right atrium,right ventricle,left atrium,left ventricle,interventricular septum and each segment of the coronary artery,were measured respectively.At the same time,two radiologists,who possessed over 10 years of diagnostic experience of CCTA examination,conducted subjective evaluations for image quality.For the cases of disagreement,the consensus between them was reached through discussion.Results:In three groups,the total CA doses were respectively(42.75±5.22)ml,(47.08±5.83)ml and(50.64±6.29)ml,and the differences of that among the three groups was statistically significant(F=13.964,P<0.05).The differences of CT values of superior vena cava,right atrium,right ventricle,left atrium,left ventricle and aorta among three groups were significant(F=29.141,24.194,39.308,9.643,8.178,6.881,P<0.05).There were significant differences in the CT values of the proximal,mid,and distal segments of the left anterior descending(LAD),and the proximal and mid segments of the left circumflex(LCx)and right coronary artery(RCA)among three groups(F=7.114,9.106,3.851,6.075,4.025,7.349,5.756,P<0.05).However,there was not statistically significant difference was found among the three groups in the CT value of the distal segments of the LCx and RCA(P>0.05).There were significant differences in the subjective scores for the superior vena cava,right atrium and right ventricle among the three groups(H=8.939,29.105,32.180,P<0.05).The number of cases with 3-4 points at the superior vena cava,right atrium and right ventricle were respectively 25(83.3%),29(96.7%)and 30(100%)in group B,there was no case with 1 point.In addition,the imaging quality of right heart in group B was better than that in group A and C.There were no significant differences at left atrium,left ventricle,and each segment of coronary artery among three groups(P>0.05).Conclusion:For patients with clinically non-extreme body weight,the selection of the ratio(2:8)of CA to saline can effectively show relevantly anatomic structures of heart,and coronary artery vessels,including the right heart system,which belongs to the optimal solution.

Objective To explore the risk factors for premature delivery after transvaginal cervical cerclage,construct and validate a predictive model.Methods A total of 209 single-tonsus cervicitis patients who underwent McDonald cervical ring ligation at the Third Affiliated Hospital of Zhengzhou University from January 2022 to December 2024 were selected as subjects,and they were divided into preterm group(n=86)and full-term group(n=123)according to the postoperative pregnancy outcomes.LASSO regression analysis was used to screen variables,and the prediction model was constructed by multivariate Logistic regression.The performance of the model was evaluated by receiver operating characteristic curve,calibration curve and decision curve.Results Body mass index,amniotic sac protrusion,preoperative white blood cell,and cervical length before cerclage＜25mm were identified as independent risk factors for preterm birth(P＜0.05).The prediction model demonstrated an area under the curve of 0.823(95％CI:0.765-0.881),with sensitivity of 77.91％and specificity of 77.24％.Both the calibration curve and decision analysis confirmed the model's strong consistency and clinical net benefit.Conclusion The predictive model constructed in this study has a good predictive effect and can be used as a reference for the stratification of preterm risk after cervical cerclage.

Objective To investigate the establishment and evaluation method of a rat model for cold asthma syndrome during the acute exacerbation phase of asthma.Methods Thirty-two rats were randomly allocated into four distinct groups:normal control group,asthma group,cold asthma group,and Shegan Mahuang Decoction group(SMD).While the normal control group was not subjected to any modeling procedures,the remaining groups were induced to develop asthma by a combination of intraperitoneal injections and atomized inhalation of ovalbumin sensitization solution.Furthermore,to emulate the traditional Chinese medicine syndrome of cold asthma,the cold asthma group and the SMD underwent an additional protocol involving"swimming,cold water consumption,and external cold stimulation."Commencing from the 14th day of the experiment,the SMD received daily gavage administration of Shegan Mahuang Decoction for a consecutive period of 14 days.The cold asthma rat model was comprehensively evaluated from both macroscopic and microscopic perspectives.Results ①Following model induction,both the asthma and cold asthma groups exhibited significant increases in asthmatic behavioral scores,sluggish weight gain,and airway hyperreactivity.Additionally,there was a notable rise in eosinophils(EOS)in the bronchoalveolar lavage fluid(BALF),decreased expression of aquaporin-5(AQP5)in lung tissue,and altered immune balances with reduced Th1/Th2 ratios and elevated Th17/Treg ratios in the spleen.Hemorheological changes included increased whole blood viscosity,relative high-shear,and low-shear indices,alongside a marked decline in erythrocyte aggregation index.The cold asthma group further displayed pronounced cold asthma symptoms,slower weight gain,and more significant increases in whole blood viscosity and low-shear relative index compared to the asthma group.②Administration of SMD alleviated asthmatic behaviors and traditional Chinese medicine syndrome manifestations in cold asthma rats,resulting in enhanced weight gain.SMD also mitigated airway hyperreactivity,reduced EOS percentage in BALF,and ameliorated lung tissue damage and inflammatory cell infiltration.The treatment increased AQP5 expression levels and rectified the immune imbalances of Th1/Th2 and Th17/Treg in cold asthma rats.Furthermore,SMD significantly lowered whole blood viscosity,relative high-shear,and low-shear indices in these rats.Conclusion The research effectively established a model for cold asthma syndrome in TCM through a method that integrates intraperitoneal injection,nebulized ovalbumin sensitization,and a triad of swimming,cold water intake,and external cold exposure.This model consistently displays the symptoms of cold asthma and corresponds with the microscopic pathological alterations seen in asthma,thereby validating the robustness of the model's creation process.

Objective:To investigate the association of the interaction and combined effect of renal function and body mass index (BMI) with the risk for all-cause death in patients with type 2 diabetes mellitus (T2DM) in communities of Jiangsu Province.Methods:The study subjects were from the Comprehensive Research Project of Diabetes Prevention and Control conducted in Jiangsu from December 2013 to January 2014, and follow up was conducted for them until September 30, 2023. A total of 20 025 subjects were included in the study. Cox proportional hazards regression model was used to analyze the association of renal function with risk for death in T2DM patients, and the association of interaction between renal function and BMI and their combined effect with all-cause death risk in T2DM patients.Results:In the follow up for 198 370 person-years, a total of 4 459 deaths were recorded. Cox proportional hazards regression model analysis showed that renal dysfunction was associated with 71% risk of all-cause mortality in all T2DM patients [hazard ratio ( HR) =1.71, 95% CI: 1.59-1.84], as well as in all BMI subgroups. Likelihood ratio test indicated an interaction between renal function and BMI (interaction for P=0.030). Compared with patients with normal renal function and normal BMI, those with normal renal function and over weight or obesity had a lower risk of all-cause mortality, and those with renal dysfunction and low weight had the highest risk for death ( HR=2.78, 95% CI: 1.87-4.14). Conclusions:There is association of interaction between renal function and BMI with all-cause mortality in T2DM patients. T2DM patients with renal dysfunction and low body weight had significant higher risk for death.