With the continuous advancement of neuroimaging technologies, clinical research has discovered the phenomenon of cognitive-motor dissociation in patients with disorders of consciousness (DoC). This groundbreaking finding has provided new impetus for the development and application of brain-computer interface (BCI) in clinic. Currently, BCI has been widely applied in DoC patients as an important tool for assessing and assisting behaviorally unresponsive individuals. This paper reviews the current applications of BCI in DoC patients, focusing four main aspects including consciousness detection, auxiliary diagnosis, prognosis assessment, and rehabilitation treatment. It also provides an in-depth analysis of representative key techniques and experimental outcomes in each aspect, which include BCI paradigm designs, brain signal decoding method, and feedback mechanisms. Furthermore, the paper offers recommendations for BCI design tailored to DoC patients and discusses future directions for research and clinical practice in this field.
Humans ; Brain-Computer Interfaces ; Consciousness Disorders/physiopathology* ; Electroencephalography ; Brain/physiopathology* ; Consciousness

The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Objective To analyze the causes and compensation characteristics of medical damage disputes in Anhui Province in recent years,and provide reference suggestions for effectively controlling and reducing the incidence of medical errors and doctor-patient conflicts.Methods The 1 876 cases of medical damage disputes in Anhui Province from 2017 to 2022 were included in the judgment documents network,and their occurrence years and causes of disputes were analyzed.Results The number of medical malpractice cases did not decrease significantly,and the average amount of compensation continued to increase;the top three causes of disputes were improper treatment or surgery(54.6%),and the average first place of actual compensation was improper medication or adverse drug reactions,and in terms of hospital level,1 009 cases(53.8%)were concentrated in tertiary public hospitals,the average actual compensation amount of private hospitals ranked first;the top three departments were surgery(44.62%);the highest incidence of damage was death(40.2%),and the average compensation amount for first-class disability was the highest.Hospitals were mainly responsible for secondary responsibilities(38.7%).Conclusion The contradiction between doctors and patients is still serious,so it is necessary to promote the construction of tight medical association and medical community,guide the allocation of medical resources,pay attention to risk sharing and management optimization,and reduce the incidence of medical damage disputes.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Objective To explore the pharmaceutical care clinical pharmacists provide for anti-infective therapy in patients undergoing continuous renal replacement therapy(CRRT)after lung transplantation.Methods The clinical pharmacist utilized a limited sampling strategy and participated in the entire anti-infective treatment process for an adult lung transplant recipient based on pharmacokinetic monitoring results.The CRRT duration was flexibly adjusted,the dosing regimen was optimized,and adverse drug reactions were monitored.Result The clinical pharmacist assisted the physician in optimizing the polymyxin B anti-infective therapy post-transplantation,leading to successful infection control and patient discharge.Conclusion Clinical pharmacists can conduct real-time drug concentration monitoring in lung transplant patients based on pharmacokinetic characteristics,develop individualized dosing regimens,and improve medication safety and efficacy during anti-infective therapy.

Objective To explore the role of sevoflurane(SEV)in sepsis-induced acute lung injury(ALI)and observe its impact on the Wnt/β-catenin signaling pathway.Methods Forty C57 mice were randomly divided into 4 groups(n=10 each):Sham,CLP,SEV,and SEV+XAV(β-catenin inhibitor).A sepsis model was established via cecal ligation and puncture.Lung injury was evaluated using HE staining,lung wet/dry weight ratio,and TUNEL staining.Levels of inflammatory factors(TNF-α,IL-1β,IL-6)were detected by ELISA.Oxidative stress indices(SOD,MDA,ROS)were measured by colorimetry and flow cytometry.Hindlimb blood perfusion and oxygenation were assessed with laser speckle flowmetry.Expressions of key Wnt pathway molecules and down-stream target genes(c-Myc,Cyclin D1)were detected by RT-qPCR and Western blot.Co-localization of β-catenin and SP-C(a marker of type Ⅱ alveolar epithelial cells)in lung tissues was determined by immunofluorescence staining.Results Compared with the Sham group,the CLP group exhibited significant increases in sepsis severity,lung pathological damage including alveolar structure destruction,inflammatory infiltration,and apoptosis,elevation in pro-inflammatory cytokine levels,and significant decrease in SOD and increase in MDA and ROS.Additionally,lower limb blood flow and oxygenation levels were significantly reduced,while the expression of β-catenin and its downstream target genes,as well as the co-localization signal and fluorescence intensity of β-catenin with SP-C,were significantly downregulated(all P<0.05).Compared with the CLP group,the SEV group showed significant improvements in all these indicators.However,compared with the SEV group,the SEV+XAV group demon-strated a reversed protective effect,with all indicators approaching the levels observed in the CLP group(all P<0.05).Conclusion Sevoflurane alleviates sepsis-induced ALI by activating Wnt/β-catenin signaling pathway,exerting anti-inflammatory and antioxidant effects,and enhancing the expression and localization of β-catenin in type Ⅱ alveolar epithelial cells.

Objective A targeted nanopeptides(VEGF/TIE-2 targeted nanopeptides,VTN)that simultaneously inhibits vascu-lar endothelial growth factor(VEGF)/tyrosine kinase with immunoglobulin-like and EGF-like domains-2(TIE-2)signaling pathways were designed and synthesized,and explore its inhibitory effect on angiogenesis in renal clear cell carcinoma(ccRCC).Methods VTN and non-self-assembling control VTN-C were prepared by solid-phase peptide synthesis technology,and the molecular structures of VTN and VTN-C were analyzed by electrospray ionization mass spectrometry(ESI-MS).The CCK-8 method was used to evaluate the effect of VTN on the cell viability of human umbilical vein endothelial cells(HUVEC).The cell scratch assay,Transwell invasion assay and angiogenesis assay were used to detect the inhibitory effects of VTN on migration,invasion and angiogenesis of HUVEC.Western blot was used to detect the effect of VTN on the phosphorylation of downstream proteins of VEGF and TIE-2 signaling pathways.A 786-O cell mouse model was established,and the effects of VTN on tumor angiogenesis and tumor progression were observed through animal ex-periments.Results ESI-MS showed that the main charge state peaks of both synthesized VTN and VVTN-C pointed to the same molec-ular weight,which was highly consistent with the corresponding theoretical molecular mass.Immunofluorescence showed that VTN co-lo-calized with VEGF and TIE-2.VTN combined with MMP-2 could significantly inhibit the activity of HUVEC(P<0.001).The cell inva-sion rate and scratch closure rate in the VTN group were reduced by(78.30±1.35)%and(37.09±3.49)%compared those in the PBS group,respectively(P<0.001).Angiogenesis experiments showed that VTN could significantly inhibit the angiogenesis of HUVEC(P<0.001).Western blot showed that VTN significantly inhibited the phosphorylation of Akt and ERK(P<0.001).The results from animal experimentsshowed that tumor volume in the VTN group was decreased by(87.16±1.30)%compared with the control group,and the CD31-positive area was reduced(P<0.001).Conclusion VTN significantly blocks ccRCC angiogenesis and delays tumor progression by inhibiting VEGF and TIE-2 signaling pathways and downregulating Akt and ERK phosphorylation.

Objective A targeted nanopeptides(VEGF/TIE-2 targeted nanopeptides,VTN)that simultaneously inhibits vascu-lar endothelial growth factor(VEGF)/tyrosine kinase with immunoglobulin-like and EGF-like domains-2(TIE-2)signaling pathways were designed and synthesized,and explore its inhibitory effect on angiogenesis in renal clear cell carcinoma(ccRCC).Methods VTN and non-self-assembling control VTN-C were prepared by solid-phase peptide synthesis technology,and the molecular structures of VTN and VTN-C were analyzed by electrospray ionization mass spectrometry(ESI-MS).The CCK-8 method was used to evaluate the effect of VTN on the cell viability of human umbilical vein endothelial cells(HUVEC).The cell scratch assay,Transwell invasion assay and angiogenesis assay were used to detect the inhibitory effects of VTN on migration,invasion and angiogenesis of HUVEC.Western blot was used to detect the effect of VTN on the phosphorylation of downstream proteins of VEGF and TIE-2 signaling pathways.A 786-O cell mouse model was established,and the effects of VTN on tumor angiogenesis and tumor progression were observed through animal ex-periments.Results ESI-MS showed that the main charge state peaks of both synthesized VTN and VVTN-C pointed to the same molec-ular weight,which was highly consistent with the corresponding theoretical molecular mass.Immunofluorescence showed that VTN co-lo-calized with VEGF and TIE-2.VTN combined with MMP-2 could significantly inhibit the activity of HUVEC(P<0.001).The cell inva-sion rate and scratch closure rate in the VTN group were reduced by(78.30±1.35)%and(37.09±3.49)%compared those in the PBS group,respectively(P<0.001).Angiogenesis experiments showed that VTN could significantly inhibit the angiogenesis of HUVEC(P<0.001).Western blot showed that VTN significantly inhibited the phosphorylation of Akt and ERK(P<0.001).The results from animal experimentsshowed that tumor volume in the VTN group was decreased by(87.16±1.30)%compared with the control group,and the CD31-positive area was reduced(P<0.001).Conclusion VTN significantly blocks ccRCC angiogenesis and delays tumor progression by inhibiting VEGF and TIE-2 signaling pathways and downregulating Akt and ERK phosphorylation.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Objective To explore the pharmaceutical care clinical pharmacists provide for anti-infective therapy in patients undergoing continuous renal replacement therapy(CRRT)after lung transplantation.Methods The clinical pharmacist utilized a limited sampling strategy and participated in the entire anti-infective treatment process for an adult lung transplant recipient based on pharmacokinetic monitoring results.The CRRT duration was flexibly adjusted,the dosing regimen was optimized,and adverse drug reactions were monitored.Result The clinical pharmacist assisted the physician in optimizing the polymyxin B anti-infective therapy post-transplantation,leading to successful infection control and patient discharge.Conclusion Clinical pharmacists can conduct real-time drug concentration monitoring in lung transplant patients based on pharmacokinetic characteristics,develop individualized dosing regimens,and improve medication safety and efficacy during anti-infective therapy.