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.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

ObjectiveTo identify key factors influencing cognitive function in the elderly, including traditional Chinese medicine (TCM) constitutional classification, and to rank their relative importance.MethodsWe used cross-sectional data from seven geographical regions across mainland China. The Changsha version of the Montreal Cognitive Assessment was used to assess cognitive function. A “least absolute shrinkage and selection operator” (LASSO) model, multivariate linear regression analysis, and random forest (RF) model were used. Subgroup analyses were performed to examine the correlation between key TCM constitution types and cognitive function in different population subgroups.ResultsA total of 24 803 individuals aged 60 and above were included in the study. We selected 18 influential factors using the LASSO model. Higher education, being married, and having insurance were positively correlated with cognitive function in the elderly (all P .05). In contrast, poor sleep, vision impairment, hearing impairment, basic activities of daily living disability, instrumental activities of daily living disability, depression, hypertension, coronary heart disease, diabetes, stroke, yang-deficiency constitution (YADC), yin-deficiency constitution (YIDC), qi deficiency constitution (QDC), and blood stasis constitution (BSC) were negatively correlated with cognitive function (all P .05). YIDC and BSC affected all dimensions of cognitive function (all P .05). YADC mainly affected attention, language, abstraction (verbal analogies), memory, and orientation to time and place dimensions (P .001). QDC mainly affected language and abstraction (verbal analogies) dimensions (P .05). The negative correlations between BSC, YADC, YIDC, and QDC scores and cognitive function revealed statistically significant differences across most subgroups. The RF model identified education, BSC, and poor sleep quality as the three most influential factors in our study.ConclusionBSC, YADC, YIDC, and QDC were associated with cognitive decline in the elderly. Our findings provide new perspectives and significant references for interventions for early-stage cognitive disorders.

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.

This article reports a case of multiple cranial nerve injury after gamma knife radiosurgery treated with acupuncture and moxibustion combined with rehabilitation therapy. The patient presented with weakness of facial and tongue muscles, hoarseness, choking on water, and swallowing difficulties. The syndrome was attributed to qi and blood deficiency, and blood stasis obstructing the collaterals. The treatment principle focused on replenishing qi and blood, promoting blood circulation and unblocking collaterals. Yintang (GV24⁺), Lianquan (CV23), Qihai (CV6), Guanyuan (CV4), and Cuanzhu (BL2), Yangbai (GB14), Jingming (BL1), Sizhukong (TE23), Yingxiang (LI20), Sibai (ST2), Juliao (ST3), Quanliao (SI18), Dicang (ST4), Jiache (ST6), Xiaguan (ST7), Taiyang (EX-HN5) on the affected side, bilateral Jinjin (EX-HN12), Yuye (EX-HN13), Hegu (LI4), Zusanli (ST36), Sanyinjiao (SP6), Tianshu (ST25) were selected. Among these, bilateral Jinjin (EX-HN12) and Yuye (EX-HN13) were treated with pricking, Dicang (ST4) and Jiache (ST6) on the affected side were connected to an electroacupuncture device, and warming acupuncture was applied at Guanyuan (CV4). Rehabilitation therapy and electromyographic biofeedback were also incorporated. The treatments were given 2-3 times a week. After 18 months of intermittent treatment, the patient reported significant improvement, House Brackmann (H-B) facial nerve function grade was Ⅳ, and Sunnybrook facial nerve rating scale score was 53 points. After 2-month of follow-up, the patient reported normal swallowing ability and restored social engagement.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Cranial Nerve Diseases/therapy*

This article reports a case of adult scoliosis with limb tremor treated with electroacupuncture. The patient presented with neck stiffness accompanied with limb tremor as the primary symptoms. The pattern was attributed to yang qi deficiency, and the treatment principle focused on unblocking the governor vessel, warming yang, and regulating qi. Acupuncture was applied to Dazhui (GV14), below the spinous processes of C₄-C₆ and bilateral C₄-C₆ Jiaji (EX-B2) points, Feishu (BL13), Xinshu (BL15), Pishu (BL20), Ganshu (BL18), Shenshu (BL23), Dachangshu (BL25). After achieving deqi sensation, bilateral C₄ Jiaji (EX-B2) and C₆ Jiaji (EX-B2) points were separately connected to an SDZ-Ⅴ electroacupuncture device, with continuous wave, 2 Hz of frequency, intensity should be within the tolerance of the patient, the needles were retained for 20 min. For the first 5 months, the treatment was 1-2 times a week, then reduced to 1-2 times a month thereafter. After 30 times of treatment, the patient's bilateral lower limb tremor resolved, the clinical rating scale for tremor (CRST) score was 13 points, the scoliosis showed improvement with about 10° reduction in Cobb angle. At 1-month follow-up, the condition remained stable without progression of scoliosis.
Adult ; Humans ; Acupuncture Points ; Electroacupuncture ; Scoliosis/physiopathology* ; Tremor/complications*

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*