Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

The visual crowding effect refers to the phenomenon that the observers' ability to identify the target object significantly decreases when it is flanked by surrounding objects.A variety of ophthalmic diseases,including amblyopia,strabismus,glaucoma,macular degeneration and nystagmus,involve structural or functional abnormalities in different parts of the visual system.These abnormalities will exacerbate the visual crowding effect,thereby impairing the ability in multi-line visual identification,reading and other daily visual activities of patients.Since intervention on visual crowding can im-prove patients' ability to process complex visual information,optimize the use of residual vision and improve prognosis,it is of great clinical value to develop targeted intervention methods.This article systematically reviews the characteristics of visual crowding in patients with oculopathy and its impact on functional vision,and summarizes the current intervention strategies,in order to provide theoretical basis and practical guidance for future clinical practice.

Objective To comparatively analyze the disparities in informatization construction between primary healthcare institu-tions in remote and non-remote areas,clarify the causes and manifestations of regional digital divides,and provide empirical evidence for optimizing resource allocation in remote areas and promoting health equity.The study also offers policy insights for advancing the"Internet+Healthcare"strategy based on local conditions.Methods A stratified sampling survey was conducted among 1 255 primary healthcare institutions in Sichuan Province to systematically compare informatization construction differences between remote and non-remote areas.Results Compared with non-remote areas,remote areas exhibited significant gaps in the coverage of informa-tization infrastructure and the construction of core system integration platforms.Remote areas also had higher absence rates of clinical service systems and notable disparities in institutional informatization investment and the allocation of dedicated IT person-nel.However,remote areas demonstrated strengths in the deployment of health terminals(e.g.,integrated health devices,smart follow-up kits,and wearable devices)and the construction of systems for infection control/communicable disease management and patient follow-up management.Conclusion Regional digital divides are primarily constrained by three factors:fiscal invest-ment,talent reserves,and technical adaptability.A differentiated policy support system is needed to address these challenges.

Objective To investigate the correlation between the expression of human leukocyte antigen class I(HLA-I)and programmed cell death ligand 1(PD-L1)with clinicopathological features and cellular immune infiltration.Methods A total of 150 patients with bladder cancer diagnosed and treated in Anhui Provincial Hospital from May 2020 to April 2023 were retrospectively selected as the study objects.The positive expression rates and positive scores of HLA-I and PD-L1 were compared between cancerous tissues and adjacent tissues.The positive scores of HLA-I and PD-L1 in cancer tissues of patients with different clinical characteristics were compared,and the correlation between HLA-I,PD-L1 and clinical characteristics of patients with bladder cancer was analyzed by Kendall's tau-b method.Logistic regression model was used to establish the combined model parameters of HLA-I and PD-L1 positive scores,and receiver operating characteristic(ROC)curve was drawn to analyze the HLA-I and PD-L1 positive scores and the area under the curve(AUC),sensitivity and specificity of the combined diagnosis of bladder cancer.Results The positive expression rate of HLA-I in cancer tissues was lower than that in paracancer tissues[38.67%(58/150)vs 81.33%(122/150)],while the positive expression rate of PD-L1 was higher than that in paracancer tissues[57.33%(86/150)vs 14.00%(21/150)],and the differences were statistically siginficant(χ2=56.889,61.377,all P<0.05).The HLA-I positive score of cancer tissues was lower than that of paracancer tissues[2.00(1.00,3.00)vs 3.00(3.00,5.00)],while the PD-L1 positive score was higher than that of paracancer tissues[3.00(2.00,5.00)vs 2.00(1.00,2.00)],and the fifferences were statistically significant(Z=-8.409,-6.346,all P<0.05).There was no significant difference in HLA-I and PD-L1 positive scores among different sex,age and tumor diameter(ZHLA-1=-1.834,-0.622,-0.543;ZPD-L1=0.811,0.812,0.919,all P＞0.05).The difference of HLA-I and PD-L1 positive scores among different pathological stages,lymph node metastasis,differentiation degree,CD4+,CD8+and CD68+were statistically significant(ZHLA-1=-7.034～3.814;ZPD-L1=-4.479～3.257,all P＜0.05).Kendall's tau-b correlation analysis showed that HLA-I was negatively correlated with pathological stage,lymph node metastasis,degree of differentiation,and positively correlated with negative infiltration of CD4+,CD8+and CD68+(r=-0.528～-0.286,all P<0.05).PD-L1 was positively correlated with pathological stage,lymph node metastasis,degree of differentiation and negatively correlated with negative infiltration of CD4+,CD8+and CD68+(r=-0.243～0.334,all P<0.05).ROC curve analysis showed that the positive scores of HLA-I and PD-L1 and the AUC values of the combined diagnosis of bladder cancer were 0.773,0.702 and 0.856,respectively.Sensitivity was 61.30%,57.30%and 82.00%.The specificity was 81.30%,86.00%and 73.30%.Conclusion The expression of HLA-I and PD-L1 is abnormal in patients with bladder cancer,and their expression is affected by the positive infiltration of immune cells.Observing the positive expression of HLA-I and PD-L1 is beneficial to provide guidance for clinical diagnosis and treatment.

Aim To explore the effects of apolipoprotein A Ⅰ(ApoA Ⅰ)and apolipoprotein A Ⅰ binding protein(AIBP)on THP-1-derived macrophage pyroptosis.Methods The lactate dehydrogenase(LDH)detection kit was used to evaluate cell membrane integrity,Hoechst33342/PI staining was used to observe cell membrane permeability,ELISA was used to detect the levels of inflammatory factors such as interleukin-1 β(IL-1β)and interleukin-18(IL-18),Western blot was used to detect the expression of pyroptosis-related protein nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3),gasdermin D(GSDMD),cleaved Caspase-1,IL-1β and IL-18.Results Oxidized low density lipoprotein(ox-LDL)upregulated the expression of NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β and IL-18 in THP-1-derived macrophages in a concentration-dependent manner,and promoted the release of IL-1β,IL-18 and LDH(P＜0.05 or P＜0.01),indicating that ox-LDL induced pyroptosis in THP-1-derived macrophages in a concentration-dependent manner.Co-treatment of macrophages with ApoA Ⅰ and AIBP significantly downregulated the ex-pression of NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β and IL-18,reduced the release of IL-1 β,IL-18 and LDH,and inhibited ox-LDL induced pyroptosis(P＜0.05 or P＜0.01).After ATP-binding cassette transporter A1(ABCA1)siRNA transfection,co-treatment with ApoA Ⅰ and AIBP had no significant effect on the expression of pyroptosis-related proteins and secretion of inflammatory factors(P＞0.05).Co-treatment of macrophages with ApoA Ⅰ and AIBP significantly re-duced the expression of purinergic 2X7R receptor(P2X7R)on the cell membrane,inhibited P2X7R mediated protein ki-nase R(PKR)phosphorylation and NLRP3 inflammasome assembly(P＜0.05 or P＜0.01).After P2X7R siRNA trans-fection,co-treatment with ApoA Ⅰ and AIBP had no significant effect on the expression of pyroptosis-related proteins and secretion of inflammatory factors(P＞0.05).Conclusion ApoA Ⅰ and AIBP reduce the expression of P2X7R on the cell membrane through ABCA1,inhibiting P2X7R/PKR/NLRP3 mediated macrophage pyroptosis.

Objective To investigate the dosimetric effects of tumor treating fields(TTFields)patches on different radiotherapy modes for glioblastoma(GBM)patients who wear TTFields patches during radiotherapy,thereby providing dosimetric guidance for determining the appropriate radiotherapy mode.Methods With the TTFields data from GBM patients,artifact-free radiotherapy CT images were obtained utilizing 3D-printed TPU TTFields patches(3D-Print-TTFields)and anthropomorphic phantoms,and then a TTFields-synchronized radiotherapy image model was constructed.Furthermore,the treatment planning system was used to construct a dosimetric calculation model for TTFields-synchronized radiotherapy by simulating and fitting the ray attenuation rate of TTFields patches measured by accelerators.Using these models,3 kinds of radiotherapy plans were simulated and developed.Specifically,P1 simulated the conventional radiotherapy mode;P2 simulated the TTFields-combined radiotherapy mode(TTF-Com-RT),in which patients underwent radiotherapy using the P1 plan while wearing TTFields patches;and P3 simulated the TTFields-synchronized radiotherapy(TTF-Syn-RT)mode where the TTFields patches were worn throughout the entire radiotherapy process.The paired t-test was used to analyze dosimetric parameters such as target dose(D95),average scalp dose(D-skin),conformity index(CI)and homogeneity index(HI)in 3 plans(P1,P2,and P3),as well as the D95 and D-skin parameters for intensity-modulated radiotherapy(IMRT)and volumetric modulated arc therapy(VMAT)techniques in the P3 plan.Results The D95 simulated by P2 decreased by 1.35%as compared with P1(P<0.05),and the D95 simulated by P3 was 1.31%higher than that in P2(P<0.05).Compared with P1,P2 and P3 increased the D-skin by 12.56%and 14.30%,respectively(P<0.05),and the D-skin simulated by P3 increased by 1.55%as compared with P2(P<0.05).However,there were trivial differences in D95 between P3 and P1,CI and HI among all plans,D95 and D-skin between IMRT and VMAT techniques in P3 plan(P>0.05).Conclusion Based on GBM patient data,CT simulation images obtained from 3D-Print-TTFields combined with anthropomorphic phantom are artifact-free and meet radiotherapy requirements.The target and scalp dose differences between TTF-Com-RT and TTF-Syn-RT are less than 2%,and the dosimetric difference of TTF-Syn-RT using IMRT/VMAT techniques is insignificant.Therefore,clinicians can choose radiotherapy modes and techniques according to actual needs.

Objective To comparatively analyze the disparities in informatization construction between primary healthcare institu-tions in remote and non-remote areas,clarify the causes and manifestations of regional digital divides,and provide empirical evidence for optimizing resource allocation in remote areas and promoting health equity.The study also offers policy insights for advancing the"Internet+Healthcare"strategy based on local conditions.Methods A stratified sampling survey was conducted among 1 255 primary healthcare institutions in Sichuan Province to systematically compare informatization construction differences between remote and non-remote areas.Results Compared with non-remote areas,remote areas exhibited significant gaps in the coverage of informa-tization infrastructure and the construction of core system integration platforms.Remote areas also had higher absence rates of clinical service systems and notable disparities in institutional informatization investment and the allocation of dedicated IT person-nel.However,remote areas demonstrated strengths in the deployment of health terminals(e.g.,integrated health devices,smart follow-up kits,and wearable devices)and the construction of systems for infection control/communicable disease management and patient follow-up management.Conclusion Regional digital divides are primarily constrained by three factors:fiscal invest-ment,talent reserves,and technical adaptability.A differentiated policy support system is needed to address these challenges.

Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4％(21/52),pCR 42.9％(9/21).The other 31 cases have complete response 5.8％(3/52),PR 25.0％(13/52),PD 11.5％(6/52),SD 17.3％(9/52).The overall objective response rate(ORR)was71.2％(37/52),and the disease control rate(DCR)was 88.5％(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.

Objective To investigate the correlation between the expression of human leukocyte antigen class I(HLA-I)and programmed cell death ligand 1(PD-L1)with clinicopathological features and cellular immune infiltration.Methods A total of 150 patients with bladder cancer diagnosed and treated in Anhui Provincial Hospital from May 2020 to April 2023 were retrospectively selected as the study objects.The positive expression rates and positive scores of HLA-I and PD-L1 were compared between cancerous tissues and adjacent tissues.The positive scores of HLA-I and PD-L1 in cancer tissues of patients with different clinical characteristics were compared,and the correlation between HLA-I,PD-L1 and clinical characteristics of patients with bladder cancer was analyzed by Kendall's tau-b method.Logistic regression model was used to establish the combined model parameters of HLA-I and PD-L1 positive scores,and receiver operating characteristic(ROC)curve was drawn to analyze the HLA-I and PD-L1 positive scores and the area under the curve(AUC),sensitivity and specificity of the combined diagnosis of bladder cancer.Results The positive expression rate of HLA-I in cancer tissues was lower than that in paracancer tissues[38.67%(58/150)vs 81.33%(122/150)],while the positive expression rate of PD-L1 was higher than that in paracancer tissues[57.33%(86/150)vs 14.00%(21/150)],and the differences were statistically siginficant(χ2=56.889,61.377,all P<0.05).The HLA-I positive score of cancer tissues was lower than that of paracancer tissues[2.00(1.00,3.00)vs 3.00(3.00,5.00)],while the PD-L1 positive score was higher than that of paracancer tissues[3.00(2.00,5.00)vs 2.00(1.00,2.00)],and the fifferences were statistically significant(Z=-8.409,-6.346,all P<0.05).There was no significant difference in HLA-I and PD-L1 positive scores among different sex,age and tumor diameter(ZHLA-1=-1.834,-0.622,-0.543;ZPD-L1=0.811,0.812,0.919,all P＞0.05).The difference of HLA-I and PD-L1 positive scores among different pathological stages,lymph node metastasis,differentiation degree,CD4+,CD8+and CD68+were statistically significant(ZHLA-1=-7.034～3.814;ZPD-L1=-4.479～3.257,all P＜0.05).Kendall's tau-b correlation analysis showed that HLA-I was negatively correlated with pathological stage,lymph node metastasis,degree of differentiation,and positively correlated with negative infiltration of CD4+,CD8+and CD68+(r=-0.528～-0.286,all P<0.05).PD-L1 was positively correlated with pathological stage,lymph node metastasis,degree of differentiation and negatively correlated with negative infiltration of CD4+,CD8+and CD68+(r=-0.243～0.334,all P<0.05).ROC curve analysis showed that the positive scores of HLA-I and PD-L1 and the AUC values of the combined diagnosis of bladder cancer were 0.773,0.702 and 0.856,respectively.Sensitivity was 61.30%,57.30%and 82.00%.The specificity was 81.30%,86.00%and 73.30%.Conclusion The expression of HLA-I and PD-L1 is abnormal in patients with bladder cancer,and their expression is affected by the positive infiltration of immune cells.Observing the positive expression of HLA-I and PD-L1 is beneficial to provide guidance for clinical diagnosis and treatment.

Aim To explore the effects of apolipoprotein A Ⅰ(ApoA Ⅰ)and apolipoprotein A Ⅰ binding protein(AIBP)on THP-1-derived macrophage pyroptosis.Methods The lactate dehydrogenase(LDH)detection kit was used to evaluate cell membrane integrity,Hoechst33342/PI staining was used to observe cell membrane permeability,ELISA was used to detect the levels of inflammatory factors such as interleukin-1 β(IL-1β)and interleukin-18(IL-18),Western blot was used to detect the expression of pyroptosis-related protein nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3),gasdermin D(GSDMD),cleaved Caspase-1,IL-1β and IL-18.Results Oxidized low density lipoprotein(ox-LDL)upregulated the expression of NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β and IL-18 in THP-1-derived macrophages in a concentration-dependent manner,and promoted the release of IL-1β,IL-18 and LDH(P＜0.05 or P＜0.01),indicating that ox-LDL induced pyroptosis in THP-1-derived macrophages in a concentration-dependent manner.Co-treatment of macrophages with ApoA Ⅰ and AIBP significantly downregulated the ex-pression of NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β and IL-18,reduced the release of IL-1 β,IL-18 and LDH,and inhibited ox-LDL induced pyroptosis(P＜0.05 or P＜0.01).After ATP-binding cassette transporter A1(ABCA1)siRNA transfection,co-treatment with ApoA Ⅰ and AIBP had no significant effect on the expression of pyroptosis-related proteins and secretion of inflammatory factors(P＞0.05).Co-treatment of macrophages with ApoA Ⅰ and AIBP significantly re-duced the expression of purinergic 2X7R receptor(P2X7R)on the cell membrane,inhibited P2X7R mediated protein ki-nase R(PKR)phosphorylation and NLRP3 inflammasome assembly(P＜0.05 or P＜0.01).After P2X7R siRNA trans-fection,co-treatment with ApoA Ⅰ and AIBP had no significant effect on the expression of pyroptosis-related proteins and secretion of inflammatory factors(P＞0.05).Conclusion ApoA Ⅰ and AIBP reduce the expression of P2X7R on the cell membrane through ABCA1,inhibiting P2X7R/PKR/NLRP3 mediated macrophage pyroptosis.