N6-methyladenosine(m6A)methylation modification is the most common post-transcriptional modification in eukaryotic RNA and plays an important role in RNA metabolism,immune cell stability,and immunomodulation.Systemic lupus erythematosus(SLE)is a diffuse,systemic autoimmune disease caused by the binding of autoantibodies to corresponding autoimmune antigens to form immune complex deposits.The pathogenesis of SLE is complex.With the continuous deepening of research,it has been discovered in recent years that m6A methylation modification can participate in the occurrence of SLE by regulating immune cells and promote the development of SLE from aspects such as oxidative stress and inflammatory response.This article reviews the research progress on the three proteins modified by m6A methylation and their relationship with the pathogenesis of SLE.

Connective tissue disease(CTD)is based on chronic inflammation of blood vessels and connective tissue,often involving multiple systems.The basic pathological changes are necrotizing vasculitis,myxedema,fibrin like deformation,etc.It belongs to systemic autoimmune disease.Due to the complex pathogenesis and heterogeneity of CTD,developing personalized manage-ment strategies remains extremely challenging.Therefore,exploring the new mechanisms and treatment targets of CTD is the focus of CTD research work.In recent years,with the continuous deepening of research on CTD,it has been discovered that there is a new form of cell death in the pathological process of CTD,namely copper death.Similar to ferroptosis,copper induces cytotoxicity mediated cell death through increased mitochondrial dependent energy metabolism and accumulation of reactive oxygen species.This article mainly attempts to explore the relationship between copper death and the pathological mechanism of confirmed CTD,as well as its impact on various immune cells,as well as the opportunities and challenges faced by therapeutic targets and clinical drugs.

Objective To evaluate the efficacy of cefoperazone-sulbactam(CS)combined with ulinastatin in the treatment for stroke-associated pneumonia(SAP)after endovascular treatment of acute large vessel occlusive stroke(AIS-LVO).Methods This study retrospectively included patients who developed SAP after endovascular treatment of AIS-LVO admitted to the intensive care unit of the Department of Neurology at the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to December 2023.Patients were randomly divided into the ulinastatin group(combined application of ulinastatin and CS)and the control group(sole application of CS)using a random number table.Baseline and clinical data,including sex,age,infarct laterality,culprit vessel,trial of Org 10172 in acute stroke treatment(TOAST)classification,baseline National Institutes of Health stroke scale(NIHSS)score,baseline Glasgow coma scale(GCS)score,medical history(hypertension,diabetes,coronary heart disease,atrial fibrillation,past history of stroke),history of smoking and alcohol consumption,admission baseline blood pressure,laboratory test results at admission(including red blood cell count,white blood cell count,neutrophil count,platelet count,random blood glucose levels,albumin,creatinine,low-density lipoprotein cholesterol,uric acid,and D-dimer),and endovascular therapies(including mechanical retrieval of thrombus,stenting,balloon dilatation,arterial thrombolysis and combination therapy)were collected from both groups.After the diagnosis of SAP,patients in both groups underwent conventional treatment such as sputum expectoration and clearance,antipyretic and antitussive treatment,oxygen therapy,respiratory support,fluid and nutrition support,along with CS anti-infective therapy.In contrast to the control group,the ulinastatin group additionally received continuous ulinastatin treatment for at least 7 days.The adverse reactions of the two groups after initiating SAP treatment including allergic reactions(such as sudden dyspnea,skin redness,and shock),decrease in peripheral white blood cell count(below 4.0 × 109/L),nausea and vomiting,diarrhea,rash and/or itching,and liver enzymes(aspartate aminotransferase or alanine aminotransferase)elevation(more than twice the upper limit of normal)were compared between the two groups.The efficacy indicators encompassing arterial blood gas analysis(oxygenation index)and inflammatory factor indicators(interleukin-6[IL-6],procalcitonin)after 7 days of SAP treatment,pneumonia-related symptoms and signs before and after SAP treatment(including body temperature,heart rate,respiratory rate,sputum volume and characteristics,changes in lung rales,etc.),imaging examinations(such as head CT and chest CT).The evaluation of therapeutic efficacy is classified as(1)markedly effective:following treatment,significant relief was observed on pneumonia-related symptoms and signs,with body temperature returned to normal,and arterial blood gas analysis and inflammatory factor indicators returned to normal levels;post-treatment imaging studies reveal that over 2/3 of lung inflammation has been absorbed;(2)effective:after treatment,some improvement was observed in pneumonia-related symptoms and signs,with mild improvement in arterial blood gas analysis and inflammatory factor indicators;post-treatment imaging studies reveal some absorption of lung inflammation;(3)ineffective:no improvement or further deterioration of pneumonia-related symptoms,arterial blood gas analysis,and inflammatory factor indicators after treatment.The arterial blood gas analysis,inflammatory factor indicators and efficacy indicators were evaluated and compared between the control and the ulinastatin group.Compare the prognosis(improvement of the lesion in the chest CT after 7 days of treatment,length of stay in the intensive care unit,total length of hospital stay,and modified Rankin scale[mRS]score assessed via telephone follow-up or outpatient revisit 90 days after endovascular treatment[with an mRS score ≤2 indicating a good prognosis],as well as mortality).Results A total of 99 patients with AIS-LVO who developed SAP after endovascular treatment were included in this study,with 69 males(69.7％)and 30 females(30.3％),and an average age of(68±10)years.Among them,there were 46 cases in the ulinastatin group and 53 cases in the control group.(1)No statistically significant differences were observed in baseline or clinical characteristics between the two groups(all P＞0.05).(2)The overall effective(markedly effective and effective)rate of SAP treatment was greater in the ulinastatin group than that in the control group(89.1％[41/46]vs.69.8％[37/53],P=0.019).(3)No statistically significant differences were observed in serum IL-6 levels,procalcitonin levels,or arterial oxygenation index between the ulinastatin group and the control group before treatment(all P＞0.05).seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[64.39±52.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.31±0.20]μg/L)in the ulinastatin group were significantly lower compared to those before treatment(all P＜0.01),and the arterial oxygenation index was significantly higher than that before treatment([359.35±92.56]mmHg vs.[273.34±95.65]mmHg,P＜0.01).Seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[31.90±21.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.26±0.24]μg/L)in the ulinastatin group were significantly lower than those in the control group(all P＜0.01),and the arterial oxygenation index was significantly higher than that of the control group([359.35±92.56]mmHg vs.[314.81±81.97]mmHg,P=0.020).(4)In the ulinastatin group,there was 1 case of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 6.5％(3/46).In the control group,there were 2 cases of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 7.5％(4/53).No statistically significant differences were observed in the adverse reaction rate between the two groups(P＞0.05).(5)After 7 days of treatment,the ulinastatin group exhibited a greater improvement rate in chest CT lesions compared to the control group(93.5％[43/46]vs.77.4％[41/53],P=0.026).No statistically significant differences were observed between the two groups in terms of the length of stay in the intensive care unit or the total length of hospital stay(both P＞0.05).Additionally,the 90-day mortality rate after intravascular treatment was lower in the ulinastatin group compared to the control group(6.5％[3/46]vs.20.8％[11/53],P=0.040).No statistically significant differences were observed in the good prognosis rate between the two groups(P=0.119).Conclusions Combined treatment with CS and ulinastatin can improve the clinical symptoms,inhibit inflammatory factors and reduce mortality rate in SAP patients after receiving endovascular treatment for AIS-LVO.The results of this study still need to be further confirmed by large-scale prospective studies.

This report described a fetus with prenatal ultrasound findings of microcephaly, lateral ventriculomegaly, and shallow lateral Sylvian fissures, ultimately diagnosed with complex cortical dysplasia with other brain malformations 4 through family-based whole-exome sequencing. At 25 weeks of gestation, prenatal ultrasound revealed fetal microcephaly, mild ventriculomegaly, and shallow Sylvian fissures. Neither chromosomal karyotyping nor chromosomal microarray analysis detected abnormalities. Family-based whole-exome sequencing identified a de novo heterozygous missense variant in TUBG1 gene [c.511G>C (p.Val171Leu)], leading to a diagnosis of complex cortical dysplasia with other brain malformations 4. Following genetic counseling, the pregnancy was terminated.

Objective To investigate the risk factors for stroke-associated pneumonia(SAP)in patients with acute anterior circulation large-vessel occlusion stroke after endovascular treatment(EVT).Methods A total of 115 patients with acute anterior circulation large-vessel occlusion stroke who received EVT in the Department of Neurology,The First Affiliated Hospital of Xi'an Jiaotong University,from March 2022 to May 2023 were continuously included.Their clinical data were retrospectively collected.The patients were divided into SAP group(55 cases)and non-SAP group(60 cases)according to the occurrence of SAP after the operation.Differences in baseline data,surgical and perioperative indicators were compared between the two groups,and the risk factors for SAP after EVT were analyzed using the multivariate Logistic regression analysis.Results Univariate analysis showed there were significant differences in the Glasgow Coma Scale(GCS)score and the National Institute of Health Stroke Scale(NIHSS)score at admission,incidence of dysphagia,duration of the surgery,proportion of general anesthesia,rate of unsuccessful vascular recanalization and the rate of immediate CT high-density sign between SAP group and non-SAP group(all P＜0.05).Multivariate Logistic regression analysis of the above indicators showed that duration of the surgery(OR=1.014,95％CI:1.001-1.028,P＜0.05),dysphagia(OR=6.137,95％CI:1.694-22.232,P＜0.01)and unsuccessful vascular recanalization(OR=6.043,95％CI:1.062-34.382,P＜0.05)were independent risk factors for SAP after EVT.Conclusion Long duration of EVT,dysphagia and unsuccessful vascular recanalization are directly related to the occurrence of SAP after EVT in patients with acute anterior circulation large-vessel occlusive infarction.Therefore,targeted measures should be taken as soon as possible to reduce the incidence of SAP after EVT and thus improve the clinical prognosis of these patients.

Purpose To measure the spatial resolution in MRI quality control testing automatically based on the American College of Radiology(ACR)phantom using the support vector machine(SVM)method,and the feasibility,accuracy and measurement speed of this method are explored.Materials and Methods Quality control tests were performed using eight MRI devices at Beijing Friendship Hospital of Capital Medical University.A retrospective study was conducted on 71 MRI quality control test images collected based on ACR phantoms between 2017 and 2019.The images were preprocessed by binarization,extraction region of interest and so on.An SVM-based classification model was constructed for analyzing the spatial resolution of dot arrays in row and column directions.The dataset was randomly split into a training set and a test set.The generalization performance of the classification model in this study was evaluated through accuracy,precision,recall and F1 score on the test set.Comparing the results of spatial resolution measurements obtained by both manual and automatic method,we demonstrated the feasibility and accuracy of the method.Additionally,the time taken for the automatic spatial resolution measurement was recorded.Results In this study,the proposed method of automatically measuring the spatial resolution of ACR phantom test images using SVM was feasible,high accuracy and short time.In classification performance test,the accuracy of the spatial resolution of the row directional latices was 95%,the precision was 100%.The accuracy of the spatial resolution of the column directional latices was 97%,the precision was 100%.Among the test cases,the results of automatic measurements matched those of manual measurements in 13 out of 14 cases.On average,automatic spatial resolution measurement took 0.158 seconds per case.Conclusion This study achieves automatic measurement of spatial resolution in MRI quality control based on the ACR phantom using SVM method.The method demonstrates high accuracy and fast measurement speeds,holding significant implications for future rapid MRI quality control stability testing.

BACKGROUND: Post-stroke disability diminishes the physical activity (PA) level of survivors, potentially affecting their long-term prognosis. This study endeavors to explore the correlation between daily PA level and the all-cause mortality in patients with a history of stoke in the United States. METHODS: Data of stroke survivors were sourced from the National Health and Nutritional Examination Survey (NHANES) 2007-2018. The population was stratified into three groups based on their PA level. Kaplan-Meier method with log-rank tests for significance was used for survival analysis. Weighted Cox proportional hazards regression models were employed to estimate the hazard ratios (HRs) for all-cause mortality. Subgroup analysis was conducted to strengthen the results. RESULTS: A total of 1395 participants were recruited, comprising 679 males and 716 females, with a median age of 68 years. Based on their PA levels, 779 individuals were classified as inactive, 156 as insufficiently active, and 460 as sufficiently active. Following a median observation period of 59 months, there were 476 recorded deaths, with 349, 47, and 80 cases in the three respective groups. Compared to the inactive group, the HRs and 95% confidence intervals (CIs) for all-cause mortality in participants who were insufficiently active and sufficiently active were 0.58 (0.40, 0.84) and 0.47 (0.33, 0.67), respectively. The Kaplan-Meier curve revealed a significant difference in overall survival between the three groups, as confirmed by the log-rank test (P < 0.0001). Subgroup analysis further validated our results and demonstrated that the protective impact of PA on stroke prognosis varies according to distinct characteristics. CONCLUSIONS The results indicate that increased levels of PA are associated with a protective effect on long-term mortality among stroke survivors. Further prospective longitudinal studies are necessary to elucidate the optional PA level and special exercise guideline targeting this population.
Humans ; Male ; Female ; Aged ; Exercise ; Middle Aged ; Nutrition Surveys ; Stroke/mortality* ; United States/epidemiology* ; Survivors/statistics & numerical data* ; Aged, 80 and over ; Mortality

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective To evaluate the efficacy of cefoperazone-sulbactam(CS)combined with ulinastatin in the treatment for stroke-associated pneumonia(SAP)after endovascular treatment of acute large vessel occlusive stroke(AIS-LVO).Methods This study retrospectively included patients who developed SAP after endovascular treatment of AIS-LVO admitted to the intensive care unit of the Department of Neurology at the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to December 2023.Patients were randomly divided into the ulinastatin group(combined application of ulinastatin and CS)and the control group(sole application of CS)using a random number table.Baseline and clinical data,including sex,age,infarct laterality,culprit vessel,trial of Org 10172 in acute stroke treatment(TOAST)classification,baseline National Institutes of Health stroke scale(NIHSS)score,baseline Glasgow coma scale(GCS)score,medical history(hypertension,diabetes,coronary heart disease,atrial fibrillation,past history of stroke),history of smoking and alcohol consumption,admission baseline blood pressure,laboratory test results at admission(including red blood cell count,white blood cell count,neutrophil count,platelet count,random blood glucose levels,albumin,creatinine,low-density lipoprotein cholesterol,uric acid,and D-dimer),and endovascular therapies(including mechanical retrieval of thrombus,stenting,balloon dilatation,arterial thrombolysis and combination therapy)were collected from both groups.After the diagnosis of SAP,patients in both groups underwent conventional treatment such as sputum expectoration and clearance,antipyretic and antitussive treatment,oxygen therapy,respiratory support,fluid and nutrition support,along with CS anti-infective therapy.In contrast to the control group,the ulinastatin group additionally received continuous ulinastatin treatment for at least 7 days.The adverse reactions of the two groups after initiating SAP treatment including allergic reactions(such as sudden dyspnea,skin redness,and shock),decrease in peripheral white blood cell count(below 4.0 × 109/L),nausea and vomiting,diarrhea,rash and/or itching,and liver enzymes(aspartate aminotransferase or alanine aminotransferase)elevation(more than twice the upper limit of normal)were compared between the two groups.The efficacy indicators encompassing arterial blood gas analysis(oxygenation index)and inflammatory factor indicators(interleukin-6[IL-6],procalcitonin)after 7 days of SAP treatment,pneumonia-related symptoms and signs before and after SAP treatment(including body temperature,heart rate,respiratory rate,sputum volume and characteristics,changes in lung rales,etc.),imaging examinations(such as head CT and chest CT).The evaluation of therapeutic efficacy is classified as(1)markedly effective:following treatment,significant relief was observed on pneumonia-related symptoms and signs,with body temperature returned to normal,and arterial blood gas analysis and inflammatory factor indicators returned to normal levels;post-treatment imaging studies reveal that over 2/3 of lung inflammation has been absorbed;(2)effective:after treatment,some improvement was observed in pneumonia-related symptoms and signs,with mild improvement in arterial blood gas analysis and inflammatory factor indicators;post-treatment imaging studies reveal some absorption of lung inflammation;(3)ineffective:no improvement or further deterioration of pneumonia-related symptoms,arterial blood gas analysis,and inflammatory factor indicators after treatment.The arterial blood gas analysis,inflammatory factor indicators and efficacy indicators were evaluated and compared between the control and the ulinastatin group.Compare the prognosis(improvement of the lesion in the chest CT after 7 days of treatment,length of stay in the intensive care unit,total length of hospital stay,and modified Rankin scale[mRS]score assessed via telephone follow-up or outpatient revisit 90 days after endovascular treatment[with an mRS score ≤2 indicating a good prognosis],as well as mortality).Results A total of 99 patients with AIS-LVO who developed SAP after endovascular treatment were included in this study,with 69 males(69.7％)and 30 females(30.3％),and an average age of(68±10)years.Among them,there were 46 cases in the ulinastatin group and 53 cases in the control group.(1)No statistically significant differences were observed in baseline or clinical characteristics between the two groups(all P＞0.05).(2)The overall effective(markedly effective and effective)rate of SAP treatment was greater in the ulinastatin group than that in the control group(89.1％[41/46]vs.69.8％[37/53],P=0.019).(3)No statistically significant differences were observed in serum IL-6 levels,procalcitonin levels,or arterial oxygenation index between the ulinastatin group and the control group before treatment(all P＞0.05).seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[64.39±52.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.31±0.20]μg/L)in the ulinastatin group were significantly lower compared to those before treatment(all P＜0.01),and the arterial oxygenation index was significantly higher than that before treatment([359.35±92.56]mmHg vs.[273.34±95.65]mmHg,P＜0.01).Seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[31.90±21.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.26±0.24]μg/L)in the ulinastatin group were significantly lower than those in the control group(all P＜0.01),and the arterial oxygenation index was significantly higher than that of the control group([359.35±92.56]mmHg vs.[314.81±81.97]mmHg,P=0.020).(4)In the ulinastatin group,there was 1 case of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 6.5％(3/46).In the control group,there were 2 cases of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 7.5％(4/53).No statistically significant differences were observed in the adverse reaction rate between the two groups(P＞0.05).(5)After 7 days of treatment,the ulinastatin group exhibited a greater improvement rate in chest CT lesions compared to the control group(93.5％[43/46]vs.77.4％[41/53],P=0.026).No statistically significant differences were observed between the two groups in terms of the length of stay in the intensive care unit or the total length of hospital stay(both P＞0.05).Additionally,the 90-day mortality rate after intravascular treatment was lower in the ulinastatin group compared to the control group(6.5％[3/46]vs.20.8％[11/53],P=0.040).No statistically significant differences were observed in the good prognosis rate between the two groups(P=0.119).Conclusions Combined treatment with CS and ulinastatin can improve the clinical symptoms,inhibit inflammatory factors and reduce mortality rate in SAP patients after receiving endovascular treatment for AIS-LVO.The results of this study still need to be further confirmed by large-scale prospective studies.

Connective tissue disease(CTD)is based on chronic inflammation of blood vessels and connective tissue,often involving multiple systems.The basic pathological changes are necrotizing vasculitis,myxedema,fibrin like deformation,etc.It belongs to systemic autoimmune disease.Due to the complex pathogenesis and heterogeneity of CTD,developing personalized manage-ment strategies remains extremely challenging.Therefore,exploring the new mechanisms and treatment targets of CTD is the focus of CTD research work.In recent years,with the continuous deepening of research on CTD,it has been discovered that there is a new form of cell death in the pathological process of CTD,namely copper death.Similar to ferroptosis,copper induces cytotoxicity mediated cell death through increased mitochondrial dependent energy metabolism and accumulation of reactive oxygen species.This article mainly attempts to explore the relationship between copper death and the pathological mechanism of confirmed CTD,as well as its impact on various immune cells,as well as the opportunities and challenges faced by therapeutic targets and clinical drugs.