Background: Malignant vasovagal syncope (VVS) is characterized by cardiac arrest lasting more than 3 seconds during a syncope episode or head-up tilt test (HUTT). We aim to conduct a risk assessment for potential malignant VVS before the HUTT by using economic, simple and convenient demographic data, in order to prevent adverse outcomes for pediatric VVS.Purpose: To explore the correlation between demographic factors and pediatric malignant VVS, and verify the value of these factors in early risk assessment for malignant VVS before HUTT, so as to optimize test safety and reduce adverse events. Methods: We conducted a retrospective analysis of the clinical data of 3,734 children who were initially diagnosed with VVS due to unexplained syncope and presyncope. Finally, 122 children who met the diagnostic criteria for malignant VVS were included in the malignant VVS group, and 661 children who did not meet the criteria during the same period were matched as the control group. By analyzing demographic data and other factors, we attempted to clarify the association between these factors and malignant VVS. Results: Linear relationship: age and body mass index (BMI) have independent protective effects on malignant VVS. For every 1-year increase in age and every 1 kg/m2 increase in BMI, the risk of malignant VVS decreases by 12% and 9%, respectively. Nonlinear relationship: When the age is <12.9 years old, for every additional year of age, the risk of malignant VVS decreases by 20%. For ages 12.9 years and above, the efficacy is not significant. There is no significant nonlinear relationship between BMI and malignant VVS. Conclusion Age and BMI are independent protective factors for pediatric malignant VVS. Before the age of 12.9 years, the incidence of malignant VVS gradually decreases with the increase in age, and thereafter there is no significant impact.

Background: Although the relationship between gut bacteria and pain is increasingly well understood, research on the role of oral bacteria in pain remains limited. Porphyromonas gingivalis (P. gingivalis), a major pathogen in periodontal disease, is known to drive the progression of infection in the oral cavity, leading to inflammation and tissue destruction. However, unlike other conditions, patients with periodontal disease exhibit variable pain responses. This unique presentation suggests that P. gingivalis exerts multifaceted effects on pain modulation. Methods: The bibliographic databases of PubMed, Embase, Google Scholar, and the Cochrane Library were searched for original and reviewed in vitro, animal, and human studies. Key data on pain, inflammation, and neuroimmune pathways were extracted. Studies that did not address pain mechanisms or were limited to non-oral/systemic conditions without a clear link to orofacial pain were excluded. Results: This review summarizes the current evidence on how P. gingivalis influences inflammation and pain, highlighting the interactions between its cell wall components (e.g., lipopolysaccharide and fimbriae), metabolic byproducts (e.g., nitric oxide and butyric acid), and the host immune response. Conclusion The diverse pain manifestations in P. gingivalis-induced periodontitis may reflect the different stages of disease. Early pain suppression may result from bacterial immune evasion, wherein therapies adjunctive to scaling and root planing, such as host modulation therapy or gingipain inhibitors, may help restore host immunity and improve clinical outcomes.

ObjectiveCerebral ischemic injury triggers a complex pathological cascade characterized by excessive reactive oxygen species (ROS) accumulation, persistent oxidative stress, and sustained neuroinflammation in the injured brain microenvironment. These events collectively drive mitochondrial dysfunction, microglial overactivation, pro-inflammatory cytokine release, and progressive neuronal apoptosis, ultimately leading to severe and irreversible neurological deficits. However, conventional therapeutic strategies face critical limitations, including poor blood-brain barrier penetration, insufficient local drug concentration, uncontrolled drug release, and off-target systemic side effects. To address this pathological process, we rationally designed and fabricated an injectable ROS-responsive hydrogel loaded with polydopamine nanoparticles (PDA NPs) for spatiotemporally controlled antioxidation, anti-inflammation, and neuroprotection in the ischemic injury microenvironment. The present study aimed to systematically characterize the physicochemical properties, ROS-responsive drug release behavior, biocompatibility, and neuroprotective efficacy of this composite hydrogel system in vitro. MethodsPDA NPs were fabricated via oxidative self-polymerization. The ROS-responsive hydrogel was cross-linked using N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1, 3-diaminium (TSPBA) and polyvinyl alcohol (PVA). Morphology, particle size, Zeta potential, and structure of PDA NPs were characterized by dynamic light scattering (DLS), Zeta potential analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Microstructure, rheological properties, shear-thinning behavior, and ROS-triggered release profiles of the hydrogel were examined by SEM and rheometry. Biocompatibility was evaluated using HT22 mouse hippocampal neurons with CCK-8 and live/dead staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established to simulate ischemic injury in vitro. ROS levels and neuronal apoptosis were detected by DHE staining and TUNEL assay. Microglial polarization and pro-inflammatory cytokine expression were analyzed using immunofluorescence and RT-qPCR in BV-2 microglia. Transwell co-culture was used to verify the indirect neuroprotection mediated by modulated microglia. ResultsCharacterization results confirmed that the as-prepared PDA NPs were monodispersed spherical nanoparticles with uniform diameter and negative surface potential, demonstrating favorable dispersibility and robust ROS-scavenging activity. The TSPBA-PVA hydrogel exhibited a highly porous interconnected network, suitable mechanical strength, and obvious shear-thinning behavior, supporting its application as an injectable implant. More importantly, the hydrogel displayed typical ROS-responsive degradation and on-demand PDA NP release in a ROS-concentration-dependent manner. In vitro cellular experiments demonstrated that the PDA NP-loaded hydrogel possessed excellent biocompatibility with HT22 cells. In the OGD/R model, the hydrogel significantly reduced intracellular ROS accumulation and markedly suppressed neuronal apoptosis. Furthermore, the composite hydrogel effectively redirected BV-2 microglia from the pro-inflammatory M1 toward the anti-inflammatory M2 phenotypes, downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, and reduced inflammatory damage. Transwell co-culture assays further validated that M2-polarized microglia mediated by the hydrogel significantly enhanced the survival of OGD/R-injured HT22 neurons and attenuated apoptosis. ConclusionIn this study, we successfully developed a novel injectable ROS-responsive hydrogel loaded with PDA NPs for synergistic antioxidative and anti-inflammatory neuroprotection. This intelligent hydrogel system enables ROS-triggered on-demand release of PDA NPs, efficiently scavenges excessive ROS, inhibits oxidative stress injury, modulates microglial polarization, and suppresses neuroinflammation, thereby exerting robust neuroprotective effects in vitro. This biomaterial platform provides a promising strategy for the targeted and controlled delivery of bioactive nanomaterials in the central nervous system diseases and establishes a solid experimental foundation for the development of in situ injectable therapies for ischemic brain injury.

Objective:This study aimed to evaluate the long-term efficacy and safety of rituximab(RTX)combined with calcineurin inhibitors(CNI)in the treatment of refractory nephrotic syndrome(RNS).Methods:A total of 80 patients with steroid-dependent/resistant RNS were prospectively enrolled and randomly assigned to an observation group(RTX+CNI,n=40)and a control group(CNI monotherapy,n=40).Patients were followed up for 24 months.Dynamic comparisons were made between the two groups regarding complete remission rate,relapse rate,24-hour urinary protein,kidney injury molecule-1(KIM-1),and adverse reactions.Results:The complete remission rate(CR)in the observation group was significantly higher than that in the control group at all time points(24-month CR:100％vs 90％,P＜0.05).The 24-month relapse rate was significantly lower in the observation group compared to the control group(0％vs 10％,P＜0.05).Combination therapy significantly reduced 24-hour urinary protein levels(6 months:2.13±0.63 vs 3.86±1.01 g/24 h,P＜0.001)and the renal injury marker KIM-1(6 months:1.53±0.41 vs 2.23±0.65 ng/mL,P＜0.001),and increased the CD4+/CD8+ ratio(24 months:2.03±0.52 vs 1.72±0.41,P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(15％vs 20％,P=0.556).Conclusion:RTX combined with CNI significantly improves the long-term remission rate and reduces the risk of relapse in RNS.Its dual immunomodulatory and multi-target renal protective effects provide evidence-based support for optimizing the treatment of refractory nephrotic syndrome.

Objective:To investigate the expression and clinical significance of urinary C-X-C motif chemokine ligand 10(CXCL10)and C-X-C motif chemokine ligand 16(CXCL16)in patients with idiopathic membranous nephropathy(IMN).Methods:A total of 131 patients with IMN(IMN group)who were treated in Zhejiang Provincial Corps Hospital of the Chinese People's Armed Police Force from December 2020 to June 2022 were prospectively selected,131 healthy volunteers(control group)who underwent physical examination during the same period were selected.Patients with IMN were divided into stage Ⅰ group(25 cases),stage Ⅱ group(68 cases),stage Ⅲ group(22 cases)and stage Ⅳ group(16 cases)according to pathological staging,patients were divided into non-remission group(33 cases)and remission group(98 cases)based on the therapeutic efficacy after a 2-year follow-up.Urinary CXCL10 and CXCL16 levels were measured by enzyme-linked immunosorbent assay.Clinical data of patients with IMN were collected,The relationship between urinary CXCL10,CXCL16 levels and pathological staging in patients with IMN was analysied by Spearman/pearson correlation.Multivariate logistic regression analysis influencing factors on non-remission treatment in patients with IMN,and receiver operating characteristic(ROC)curves were used to assess the predictive value Of urinary CXCL10,CXCL16 levels for non-remission treatment in patients with IMN.Results:Urinary CXCL10 and CXCL16 levels in the IMN group were significantly higher than those in the control group(P＜0.05).Urinary CXCL10 and CXCL16 levels were the highest in stage Ⅳ group,urinary CXCL10 and CXCL16 levels in stage Ⅲ group were higher than those in stage Ⅱ group and stage Ⅰ group,and urinary CXCL10 and CXCL16 levels in stage Ⅱ group were higher than those in stage Ⅰ group(P＜0.05).Urinary CXCL10 and CXCL16 levels in patients with IMN were positively correlated with pathological staging,urinary CXCL10 were positively correlated with CXCL16(P＜0.05).Urinary CXCL10 and CXCL16 in non-remission group were higher than those in the remission group(P＜0.05).pathological staging Ⅲ～Ⅳ,elevated 24 h urine protein level,and elevated urinary CXCL10 and CXCL16 levels were independent risk factors for non-remission treatment in patients with IMN(P＜0.05).The areas under the curve(AUC)of urinary CXCL10 and CXCL16 levels for predicting non-remission treatment in patients with IMN alone and in combination were 0.783,0.785,and 0.875,respectively,the combined detection had the highest predictive efficacy(P＜0.05).Conclusion:Urinary CXCL10 and CXCL16 levels are elevated in patients with IMN,it is closely related to the pathological staging of patients and the therapeutic efficacy,the combined detection of urinary CXCL10 and CXCL16 has a high value in predicting the therapeutic efficacy in patients with IMN.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective Using event-related potentials(ERPs)technology to study the effect of long term emotional distress on selective attention distraction inhibition function in college students and its neuroelectrophysiological mechanism.Methods The Eysenck personality questionnaire(EPQ)adult version was used to screen the high and low neuroticism groups among college students,and 35 subjects in each group were included in the long term emotional distress group and the emotional smoothness control group,respectively,and the response time,correct rate,N2 and P3 amplitude and latency results of the participants to complete the negative priming paradigm task were collected and analyzed.Results Compared with the control group,① the long term emotional distress group showed a prolonged response trend(P=0.072).② the long term emotional distress group had a prolonged N2 and P3 latency(P<0.05).Conclusion Selective attention distraction inhibition in college students with long term emotional distress decreased,and the decline mechanism may be related to the decline of inhibition processing and attention resource allocation ability.

Objective:This study aimed to evaluate the long-term efficacy and safety of rituximab(RTX)combined with calcineurin inhibitors(CNI)in the treatment of refractory nephrotic syndrome(RNS).Methods:A total of 80 patients with steroid-dependent/resistant RNS were prospectively enrolled and randomly assigned to an observation group(RTX+CNI,n=40)and a control group(CNI monotherapy,n=40).Patients were followed up for 24 months.Dynamic comparisons were made between the two groups regarding complete remission rate,relapse rate,24-hour urinary protein,kidney injury molecule-1(KIM-1),and adverse reactions.Results:The complete remission rate(CR)in the observation group was significantly higher than that in the control group at all time points(24-month CR:100％vs 90％,P＜0.05).The 24-month relapse rate was significantly lower in the observation group compared to the control group(0％vs 10％,P＜0.05).Combination therapy significantly reduced 24-hour urinary protein levels(6 months:2.13±0.63 vs 3.86±1.01 g/24 h,P＜0.001)and the renal injury marker KIM-1(6 months:1.53±0.41 vs 2.23±0.65 ng/mL,P＜0.001),and increased the CD4+/CD8+ ratio(24 months:2.03±0.52 vs 1.72±0.41,P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(15％vs 20％,P=0.556).Conclusion:RTX combined with CNI significantly improves the long-term remission rate and reduces the risk of relapse in RNS.Its dual immunomodulatory and multi-target renal protective effects provide evidence-based support for optimizing the treatment of refractory nephrotic syndrome.

Objective Using event-related potentials(ERPs)technology to study the effect of long term emotional distress on selective attention distraction inhibition function in college students and its neuroelectrophysiological mechanism.Methods The Eysenck personality questionnaire(EPQ)adult version was used to screen the high and low neuroticism groups among college students,and 35 subjects in each group were included in the long term emotional distress group and the emotional smoothness control group,respectively,and the response time,correct rate,N2 and P3 amplitude and latency results of the participants to complete the negative priming paradigm task were collected and analyzed.Results Compared with the control group,① the long term emotional distress group showed a prolonged response trend(P=0.072).② the long term emotional distress group had a prolonged N2 and P3 latency(P<0.05).Conclusion Selective attention distraction inhibition in college students with long term emotional distress decreased,and the decline mechanism may be related to the decline of inhibition processing and attention resource allocation ability.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.