ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

ObjectiveTo investigate the current status of assistive device use and unmet needs among persons with disabilities in Sichuan-Chongqing region, and to identify the key factors associated with satisfaction with these devices. MethodsFrom October, 2024 to February, 2025, quota sampling was adopted to recruit 1 040 persons with disabilities in Sichuan and 260 persons with disabilities in Chongqing. Telephone and online questionnaires were used to collect data on demographic characteristics, status of assistive device utilization and unmet assistive device needs, as well as satisfaction with assistive device use. Correlation analysis, multiple linear regression analysis and structural equation modeling were performed to identify key factors associated with satisfaction. ResultsA total of 1 186 valid responses were collected, of which 942 were from Sichuan Province and 244 from Chongqing Municipality. The utilization rate of assistive devices among persons with disabilities in Sichuan-Chongqing region was 61.9%, and the rate of unmet assistive device needs was 30.6%. The assistive device utilization rate of participants with agricultural household registration (57.98%) was lower than that of participants with non-agricultural household registration (66.86%). The utilization rate showed a J-shaped upward trend with the increase of educational attainment. Educational attainment (P = 0.002), perceived usefulness of assistive devices (P < 0.001), home living environment (P < 0.001), public environment (P < 0.001) and disability type (significant differences were found in visual and hearing disabilities compared with physical disability, P < 0.05) were key predictors of satisfaction with assistive device use. The impact of public environment on satisfaction was exerted through two indirect mediating paths: mediating effect via perceived usefulness of assistive devices (ind₁ = 0.357, 95%CI 0.279 to 0.437, P < 0.001), contributing approximately 70% of the total indirect effect; mediating effect via home living environment (ind₂ = 0.129, 95%CI 0.006 to 0.242, P = 0.038), contributing approximately 25% of the total indirect effect. ConclusionThere is a structural imbalance between assistive device use and demand in Sichuan-Chongqing region. People with psycho-intellectual disabilities are most likely to be excluded from the service chain because they neither perceive need nor access information. Education exerts a robust positive effect on both adoption and satisfaction, so training content must be tailored to different educational levels. Satisfaction is shaped by disability type, device usefulness and environmental factors. Future product development should therefore integrate functional and psychosocial dimensions. Priority should be given to micro-scale home-and-community accessibility retrofits before extending upward to public transportation and employment settings, to maximize the cost-effectiveness of limited funds.

Objective To explore the effect and predictive value of ultrasound-guided needling assisted motor evoked potentials(MEP)and electromyography(EMG)monitoring on neurological recovery in spinal surgery.Methods A retrospective analysis was conducted on the clinical data of 80 patients who underwent spinal surgery at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2024.A total of 41 patients in the observation group received ultrasound-guided needling assisted MEP and EMG monitoring,and 39 patients in the control group received conventional method for MEP and EMG monitoring.The operative time,intraoperative blood loss,and the proportions of intraoperative MEP and EMG warnings were compared between the two groups,and the sensitivity and specificity of intraoperative MEP monitoring were compared between the two groups.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to analyze the efficiency of MEP warning in predicting the dysfunction of postoperative spinal cord.Results There were no significant differences in the operative time,intraoperative blood loss,or the proportions of intraoperative MEP and EMG warnings(P>0.05).The sensitivity,specificity and AUC of intraoperative MEP monitoring in the observation group were significantly higher than those in the control group,with statistically significant differences(P<0.05).The sensitivity,specificity,and AUC of postoperative MEP warning in predicting the dysfunction of spinal cord in the observation group were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion Ultrasound-guided needling assisted MEP and EMG monitoring can effectively enhance the intraoperative neural monitoring accuracy,and postoperative MEP warning demonstrates superior predictive value for postoperative neurological dysfunction.

Momordica antiviral protein 30 kD(MAP30)is a type Ⅰ ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To in-crease its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mecha-nism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significant-ly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indica-ting its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential ther-apeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

Purpose To investigate the correlation between molecular typing of urothelial carcinoma(UC)and its clinicopathologic features and prognosis,in order to explore the prognostic markers and therapeutic targets for UC.Methods 115 patients with UC were retrospectively analyzed.Immunohistochemical markers GATA-3,CK20,CK5/6 and CD44 were used for molecular typing of UC(luminal-like type,basal-like type and null).Correlations between molecular typing and clinicopathological features were analyzed using the Chi-square test and Fisher precise test.Sur-vival analysis was performed using the Kaplan-Meier test and Log-rank test.Results The expression of GATA-3 and CK20 was negatively correlated with the clinical stage of UC,while the expression of CD44 was positively correlated with the clinical stage of UC(both P＜0.05).CK20 was a marker of good prognosis(P=0.03).The proportion of clinically advanced UC with basal-like type was significantly higher than that of luminal-like type(78.4％vs 53.4％,P=0.033).Among the histologic variants,UC with neuroendocrine differentiation(100％),sarcomatoid carcinoma(80.0％)and squamous differentiation(77.8％)were basal-like type.All plasmacytoid and lymphoepithelioma-like types,as well as 81.8％of micropapillary UC.Among the null phenotypes,the differential variant predominated(66.7％).Compared with the luminal-like type,although the prognosis of basal-like UC was worse,there was no sta-tistically significant difference(P＞0.05).Conclusion Patients with CK20-expressing UC had a significantly better prognosis.The main histologic variants types of basal-like type and coelomofacial type are different.Molecular typing of UC using immunohistochemical markers is suggestive of clinical staging and prognosis of patients.

Objective:To analyze the effects of citric acid anticoagulation on coagulation function and inflammatory factors in patients with sepsis and high-risk bleeding treated with continuous renal replacement therapy (CRRT).Methods:A total of 80 patients with sepsis with high-risk bleeding who received CRRT treatment in the Affiliated Hospital of Jining Medical University from February 2018 to August 2023 were retrospectively selected as the study objects, 40 cases were treated with low molecular weight heparin (control group) and 40 cases were treated with citric acid (observation group).Both groups were treated continuously, and the anticoagulant effect, coagulation function, electrolyte and inflammatory factor levels of the two groups were compared 7 d after medication.Results:The total effective rate of anticoagulation in the observation group after treatment was higher than that in the control group: 97.50% (39/40) vs. 75.00% (30/40), there was statistical difference ( χ2 = 8.54, P<0.05). After treatment, the levels of activated partial thrombin time (APTT), thrombin time (TT) and prothrombin time (PT) in the observation group were lower than those in the control group: (31.08 ± 8.31) s vs. (41.76 ± 8.36) s, (23.41 ± 5.02) s vs. (29.05 ± 5.13) s, (15.47 ± 3.50) s vs. (19.96 ± 4.75) s, there were statistical differences ( P<0.05). There were no statistical differences in the levels of potassium, chloride, sodium and calcium between the two groups after treatment ( P>0.05). After treatment, the levels of C-reactive protein (CRP) and procalcitonin (PCT) in the observation group were lower than those in the control group :(2.60 ± 0.86) mg/L vs. (4.35 ± 1.12) mg/L, (0.11 ± 0.03) μg/L vs. (0.19 ± 0.05) μg/L, there were statistical differences ( P<0.05). Conclusions:The application of citric acid anticoagulant in patients with sepsis and high-risk bleeding treated with CRRT can achieve significant curative effect, which can not only improve the anticoagulant effect, stabilize coagulation function and electrolyte level, but also down-regulate the level of inflammatory factors.

Purpose To investigate the relationship between the expression of POSTN and NECTIN-3 in urothelial carcinoma(UC)and its clinicopathologic features and prognosis.Methods Clinical data of 115 UC patients were col-lected.EnVision two-step method was used for immunohistochemical analysis to determine the expression of POSTN and NECTIN-3 in UC and their correlation with clinicopathological features and prognosis.Transcriptomic data from TCGA database were used to analyze the correlation between the expression of POSTN and NECTIN-3 in bladder cancer and the pathological stage and prognosis of bladder cancer.qPCR and Western blot were used to detect the expression levels of POSTN and NECTIN-3 in tumor tissues and adjacent tissues of patients.Results TCGA database analysis showed that the expression level of NECTIN-3 in urinary bladder urothelial carcinoma(UBUC)was significantly lower than that in paracancer tissues,and POSTN expression was positively correlated with pathological stage.Prognostic a-nalysis showed that POSTN expression was negatively correlated with the overall survival of UBUC(P＞0.05),and NECTIN-3 expression was negatively correlated with disease-free survival of UBUC(P＞0.05).The experimental re-suits showed that patients with positive POSTN expression were more prone to perineural invasion[25 cases(86.2％)vs 4 cases(13.8％),P=0.019],vascular invasion[36 cases(83.7％)vs 7 cases(16.3％),P=0.007],and lymph node metastasis[24 cases(88.9％)vs 3 cases(11.1％),P=0.033].Additionally,the positive expression rate of POSTN in UBUC was significantly higher than that in upper tract urothelial carcinoma(UTUC)(75.0％vs 54.3％,P=0.028).Higher expression levels of POSTN and NECTIN-3 were associated with shorter overall survival,but the difference was not statistically significant(P＞0.05).Conclusion There is no significant correlation between NECTIN-3 and the clinicopathological features and prognosis of urothelial carcinoma,while the expression of POSTN is correlated with the invasive clinicopathological features of UC,which has certain suggestive significance for clinical stage and prognosis.

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.

Objective To construct the K64 capsule depolymerase recombinant protein,Dep44,and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Methods The de-polymerase-encoding phage vB_Kpn_HF1013(GenBank:PP803128)was isolated and genomically analyzed to screen for candidate depolymerases.The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity.Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by bio-film disruption and serum sterilization assays.Results The tail spike protein of phage vB_Kpn_HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule.Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial bio-films relative to the control.Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum,dependent on the complement system,as Dep44 alone lacked bactericidal properties.Conclusion Dep44 effec-tively targets and degrades K64 CRKP capsule,disrupts biofilms,and enhances serum bactericidal activity,high-lighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.