Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

Ring finger protein 213(RNF213)was first identified as a susceptible gene for Moyamoya disease,and also found to be associated with various vascular related diseases such as intracranial artery occlusion/stenosis,ischaemic stroke,intracranial aneurysm,cerebral arteriovenous malformation,etc.This article systematically reviewed the literature of RNF213,providing an overview of the association and possible mechanisms between RNF213 variation and related diseases,in order to provide reference for the prevention,diagnosis,and treatment of related diseases.

Objective:To examine the prevalence of frailty among elderly patients in the emergency department and to investigate the potential relationship between vitamin D nutritional status and frailty.Methods:This study collected clinical data from elderly patients aged over 65 years in the emergency intensive care unit and emergency observation ward of Beijing Bo'Ai Hospital from January to September 2021.The data included blood routine, biochemical indicators, circulating interleukin-6, cortisol, thyrotropin, and 25-hydroxyvitamin D[25(OH)D], which were detected within 24 hours after enrollment.Additionally, the Frailty Screening Questionnaire(FSQ), FRAIL scale, and Clinical Frailty Scale(CFS)were used to score the patients.Based on the scores, the patients were divided into frail or non-frail groups, and the prevalence of frailty was reported accordingly using the criteria of the aforementioned scales.The consistency of the three scales was evaluated using the Spearman rank test and Kappa coefficient.We compared the differences in clinical data and laboratory indicators of patients between the frail and non-frail groups.Additionally, we used a multivariable Logistic regression model to analyze the association between vitamin D nutritional status and frailty.We also analyzed the prevalence of frailty in different vitamin D nutritional statuses and evaluated the predictive ability of serum 25(OH)D for frailty using the receiver operating characteristic(ROC)curve.Results:A total of 317 patients were included in the study.The prevalence of frailty in elderly patients in the emergency department was found to be 47.0%, 55.2%, and 69.4% according to the FSQ, FRAIL, and CFS scales, respectively.The study evaluated the consistency of these three scales, revealing a Spearman rank correlation coefficient of 0.761(95% CI: 0.715-0.806, P<0.001)and a Kappa coefficient of 0.536(95% CI: 0.451-0.621, P<0.001)between FSQ and FRAIL, which were the highest correlations observed.Logistic regression analysis, after adjusting for age, gender, BMI, and other factors, indicated that vitamin D deficiency( OR=5.994, 95% CI: 1.232-29.169, P=0.027)was independently associated with an increased prevalence of frailty as defined by FSQ criteria.The prevalence of frailty increased with the severity of vitamin D malnutrition.In the vitamin D deficiency group, the prevalence was higher compared to the vitamin D insufficiency and sufficiency groups( P<0.05 for all).The area under the ROC curves(AUCs)of serum 25(OH)D levels to predict frailty, as defined by FSQ, FRAIL, and CFS, were 0.806(95% CI: 0.744-0.868), 0.748(95% CI: 0.679-0.817), and 0.768(95% CI: 0.701-0.826)( P<0.001 for all).The optimal cut-off values were 12.0, 9.76, and 11.65 μg/L, respectively, yielding a Youden index of 0.553, 0.419, and 0.462. Conclusions:FSQ, FRAIL, and CFS demonstrated a strong level of consistency in assessing frailty.Additionally, serum 25(OH)D can serve as an independent predictor of frailty, aiding in the identification of frail individuals and enhancing the risk stratification of elderly patients in the emergency department.

Objective:To compare the image quality and the diagnostic efficiency for breast malignant lesions using simultaneous multi-slice single shot echo planar imaging (SMS+SS-EPI) and readout segment of long variable echo trains (RESOLVE) for breast diffusion-weighted imaging (DWI).Methods:This study was a cross-sectional study. Clinical and imaging data of 102 patients with breast lesion from March 2021 to February 2023 in the First Hospital Affiliated to Ningbo University were prospectively analyzed. All patients underwent routine breast MRI scans and cross-sectional RESOLVE and SMS+SS EPI sequence DWI, and the image quality of 2 types sequences of DWI was evaluated. The subjective evaluation was based on a 5-point scale, including geometric distortion, artifact blurring, fat suppression, overall image quality, and lesion conspicuity of the breast. The objective evaluation included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) value of the lesion. Wilcoxon signed rank sum test was used to compare the subjective and objective parameters between the two sequences. Finally, the receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the effectiveness of ADC values for diagnosing breast malignant lesions based on two sequence images.Results:All 102 female patients had single lesions, aged from 25 to 68 years and 60 lesions were malignant and 42 were benign. The acquisition time for SMS+SS-EPI sequence imaging was 1 min 50 s, and the acquisition time for RESOLVE sequence imaging was 3 min 43 s.The subjective scores from both SMS+SS-EPI and RESOLVE sequence were over than 3 points. The geometric distortion, artifact blurring, and overall image quality scores of RESOLVE sequence images were higher than those of SMS+SS-EPI (all P<0.001). The overall lesion conspicuity score, malignant lesion conspicuity score, and benign lesion conspicuity score of DWI and ADC images combined with SMS+SS-EPI sequence were higher than those of the RESOLVE sequence (all P<0.05). There were no statistically difference in SNR, CNR, overall ADC value, malignant ADC value, and benign ADC value between SMS+SS-EPI and RESOLVE sequence DWI images of breast lesions (all P>0.05). The AUC of RESOLVE sequence ADC value in diagnosis of breast cancer was 0.973, the sensitivity was 0.929, and the specificity was 0.915; The AUC of SMS+SSC-EPI sequence ADC value in diagnosis of breast cancer was 0.956, the sensitivity was 0.977, and the specificity was 0.850. Conclusions:In breast DWI, the subjective score of SMS+SS EPI image quality can basically meet the diagnostic requirements and the conspicuity of lesions is better than that of the RESOLVE sequence. Both have good diagnostic efficacy for malignant breast lesions.

Objective:To explore the association of frailty and serum C-terminal agrin fragment(CAF)with the prognosis of elderly patients with acute coronary syndrome(ACS).Methods:In this prospective cohort study, clinical data of 207 older patients with ACS between January 2020 and May 2022 were collected.Serum samples were obtained within 24 hours after enrollment to detect CAF levels.Meanwhile, the thrombolysis in myocardial infarction(TIMI)and frailty screening questionnaire(FSQ)scores were assessed on admission.Patients were followed up for major adverse cardiovascular and cerebrovascular events(MACCE)for 90 days.Multivariate logistic regression was used to analyze the influencing factors of MACCE.The receiver operating characteristic(ROC)curve was performed to evaluate the predictive ability of the FSQ score, serum CAF and their combination for MACCE.According to 90-day mortality, patients were divided into a survival group(n=176)and a death group(n=31). The Cox proportional hazards regression model was used for survival analysis.Results:The FSQ score( Z=4.412, P<0.001)and serum CAF( Z=6.702, P<0.001)in the MACCE group were higher than those in the non-MACCE group.Logistic regression analysis showed that after adjusting for age, sex, TIMI score and complete revascularization, frailty defined by FSQ( OR=1.714; 95% CI: 1.059-2.775; P=0.028)and high serum CAF( OR=1.230; 95% CI: 1.122-1.350; P<0.05)were independent risk factors for MACCE.The area under the ROC curve(AUC)of the FSQ score for predicting MACCE was 0.797(95% CI: 0.735-0.850; P<0.001), the predictive cut-off point was an FSQ score >2, and the Youden index(YI)was 0.419, yielding a sensitivity of 0.708 and a specificity of 0.711.In addition, the AUC of serum CAF for predicting MACCE was 0.766(95% CI: 0.701-0.822; P<0.001), the predictive cut-off point was >6.01 μg/L, and YI was 0.460, yielding a sensitivity of 0.750 and a specificity of 0.710.The predictive ability of FSQ combined with CAF for MACCE was higher than FSQ( Z=2.294, P=0.022)or CAF( Z=2.545, P=0.011)alone.Cox regression analysis showed that frailty defined by FSQ( HR=3.487; 95% CI: 1.329-9.153; P=0.011)was independently associated with all-cause mortality within 90 days after ACS. Conclusions:Frailty assessment and serum CAF detection can improve the risk stratification of elderly patients with ACS.

Objective:To establish a 14-day prognosis model for emergency patients with acute ischemic cerebral stroke and evaluate its predictive efficacy.Methods:A prospective cohort study was conducted. Patients with acute ischemic stroke admitted to the emergency department of Beijing Bo’ai Hospital within 72 hours of onset from October 2018 to December 2020 were enrolled. Univariate and multivariate logistic regression analysis were used to screen the risk factors of poor prognosis. The ROC curve was drawn to determine the cut-off value of continuous variables and discretise data with reference to clinical practice. The corresponding scores were set up according to the β regression coefficient of each variable, and the clinical scale prediction model of short-term prognosis of acute cerebral infarction was established. Patients with ischemic stroke in the hospital from January to December 2021 were selected as the internal validation, to verify the constructed predictive model.Results:A total of 321 patients were included in the study, including 223 in the training set and 98 in the internal validation set. Multivariate logistic regression analysis showed that age, hypersensitive C-reactive protein, prealbumin (PA), infarct volume, Frailty Screening Questionnaire (FSQ) and National Institute of Health Stroke Scale (NIHSS) were independent risk factors for poor short-term prognosis of acute cerebral infarction. The total score of the clinical prediction scoring system for short-term prognosis of acute cerebral infarction in the emergency department was 15 points, including age ≥74 years (1 point), PA ≤373 mg/L (2 points), large artery atherosclerosis (1 point), cardiogenic embolism (2 points), infarct volume ≥ 2.18 cm 3 (2 points), FSQ ≥3 points (1 point), NIHSS ≥4 points (6 points); The area under the ROC curve (AUC) of the scoring system for predicting short-term poor prognosis of acute cerebral infarction was 0.927 (95% CI: 0.894-0.960). The optimal cut-off value was ≥5 points, and the sensitivity and specificity were 0.770 and 0.976, respectively. In the internal validation set, the scoring system had similar predictive value for poor outcomes (AUC=0.892, 95% CI:0.827-0.957). Conclusion:The scoring system for short-term prognosis prediction of acute ischemic cerebral infarction has good diagnostic efficacy, and could guide clinicians to judge the prognosis of emergency patients in the early stage.

Objective:To analyze the activation of primary somatosensory cortex(S1)neurons in post-traumatic stress disorder(PTSD)mice after tactile stimulation of whiskers and the changes of S1 cortical neurons in PTSD mice.Methods:Using the neuron cytoskeleton-associated protein(Arc)labeling strategy and immunofluorescence staining technique,the Arc of S1 cortical neurons in PTSD mice and control mice after whisker stimulation was marked and ob-served.By analyzing the difference in the spatial expression position of Arc labeled neurons and the number of positive cells,the activation level of S1 cortical neurons in the two groups was compared and analyzed.The pyramidal neurons of S1 cortex were labeled by sparse virus labeling method,and the number of dendrites and the morphology and number distribution of dendritic spines were compared between the two groups.Results:After whisker stimulation,it was found that Arc positive neurons were distributed from shallow layer to deep layer of S1,and more densely distributed in layersⅡ/Ⅲ and V.Compared with the control group,the number of positive neurons in different layers of the PTSD group was significantly increased.The results of cell morphology and structure analysis showed that,compared with the control group,the density of dendritic spines in layer Ⅱ/Ⅲ of mice with PTSD increased,and the number of mushroom dendrit-ic spines increased,while the number of filamentous pseudopod dendritic spines decreased.The number of dendritic spines of Si V layer mushroom type and slender type was higher,but the total number of dendritic spines was not sig-nificantly different.Conclusion:After whisker stimulation in PTSD mice,S1 neurons were over-activated,and the structure and morphology of neurons changed significantly.

Objective:To investigate the association between serum interleukin (IL) -6 and silent information regulator (SIRT) -1 and frailty in elderly patients in the emergency department.Methods:This was a cross-sectional study. Patients aged 60 years and above treated in the emergency department of Beijing Bo'Ai Hospital from January to December 2022 were collected. Blood routine, biochemical indicators, and serum IL-6 were detected within 24 h after enrollment. At the same time, fasting venous blood 2 mL was collected and the serum was stored at minus 80℃ after centrifugation. The level of SIRT-1 was detected by enzyme-linked immunosorbent assay. Nutritional risk screening 2002 was performed within 72 h, Barthel index was used to assess the ability of daily living and grip strength was measured. The patients were divided into frailty and non-frailty groups according to Fried frailty phenotype (FP). The differences of clinical data and laboratory indicators were compared between the two groups. Multivariable logistic regression model was used to analyze the association between serum IL-6, SIRT-1 and frailty. The predictive ability of serum IL-6 and SIRT-1 for frailty was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 316 elderly patients in the emergency department were included in this study and divided into frailty group ( n=156) and non-frailty group ( n=160) according to Fried FP criteria. Univariate analysis showed that serum IL-6 [33.3 (13.0, 69.2) ng/L vs. 20.0 (9.2, 41.3) ng/L, P=0.001] and SIRT-1 [(9.98±1.23) μg/L vs. (8.98±1.65) μg/L, P<0.001] of patients in the frailty group were higher than those in the non-frailty group. Multivariable logistic regression analysis showed that serum IL-6 ( OR=1.006, 95% CI: 1.001-1.011, P=0.036) and SIRT-1 ( OR=1.838, 95% CI: 1.475-2.290, P<0.001) were independently associated with frailty after adjusting for age, sex, body mass index, Barthel index and grip strength. The area under the curve (AUC) of serum IL-6 for predicting frailty was 0.671 (95% CI: 0.604-0.738, P<0.001), the predictive cut-off point was 33.8 ng/L. The AUC of SIRT-1 for predicting frailty was 0.736 (95% CI: 0.674-0.799, P<0.001), the predictive cut-off point was 9.13 μg/L. The AUC of the model of IL-6 combined with SIRT-1 was 0.765 (95% CI: 0.707-0.823, P<0.001), the sensitivity and specificity were 0.776 and 0.726, respectively, and its predictive efficacy was superior to that of IL-6 alone ( Z=2.119, P=0.034). Conclusion:Serum IL-6 and SIRT-1 are independent predictors of frailty in elderly patients in the emergency department.

Objective:To explore the predictive value and prognosis effect of calprotectin on acute kidney injury (AKI) in patients with sepsis.Methods:A prospective observational study was conducted. From December 2018 to November 2020, patients with sepsis admitted to the Emergency Department of China Rehabilitation Research Center were enrolled. General clinical data of patients were collected continuously, and the acute physiology and chronic health evaluationⅡ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score and calprotectin were evaluated in 24 h after admission. The patients were divided into the AKI group and non-AKI group according to the occurrence of AKI within 7 days after admission. Calprotectin level and other clinical data were compared between the two groups. Logistic regression was used to analyze the risk factors for AKI in patients with sepsis, and receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of calprotectin for AKI in patients with sepsis. The patients with AKI were further divided into the survival group and death group according to the 28-day outcome, and the calprotectin levels between the two groups were compared.Results:A total of 207 patients with sepsis were enrolled, and the incidence of AKI was 68.12% (141/207). The level of calprotectin in patients with AKI was higher than that in patients without AKI [4.65 (3.25, 5.61) μg/mL vs. 3.42 (2.29, 4.09) μg/mL, P < 0.001]. Multivariable Logistic regression analysis showed that APACHEⅡ score ( OR=1.090, 95% CI: 1.043-1.139), C-reactive protein ( OR=1.004, 95% CI: 1.001-1.008) and calprotectin ( OR=1.590, 95% CI: 1.269-1.991) were independent risk factors for AKI in patients with sepsis. The area under ROC curve (AUC) of calprotectin for predicting AKI was 0.716 (95% CI: 0.643-0.788). The cutoff value of prediction was 4.63 μg/mL with the Yoden index of 0.405, which yielded a sensitivity of 0.511 and a specificity of 0.894. When calprotectin was combined with APACHE II score and SOFA score respectively, the predictive ability was significantly improved with the AUC of 0.768 (95% CI: 0.701-0.834) and 0.769 (95% CI: 0.701-0.837), respectively. We further divided patients with AKI into the survival group and non-survival group according to the 28-day outcome and there was no significant difference in calprotectin between the two groups [4.80 (3.40, 5.76) μg/mL vs. 4.19 (2.89, 5.29) μg/mL, P < 0.05]. Conclusions:The level of calprotectin in the AKI group is higher than that in the non-AKI group. Calprotectin can be regarded as an effective predictor of AKI in patients with sepsis, and the combination with APACHEⅡ score or SOFA score will improve its predictive efficacy. However, there is no significant difference in the concentration of calprotectin for patients with sepsis associated AKI with different prognosis.

Objective:To establish a prediction model for major adverse cardiovascular and cerebrovascular events (MACCE) in elderly patients with emergency acute coronary syndrome (ACS) within 1 year, and to evaluate its prediction efficiency.Methods:This was a prospective cohort study. Elderly ACS patients who were admitted to the Cardiovascular Care Unit (CCU) or the Emergency Intensive Care Unit (EICU) in Beijing Bo'Ai Hospital through emergency department from January 2019 to December 2021 were successively enrolled. General data of the patients were collected within 24 h after admission, the incidence of malignant arrhythmia, complete revascularization and acute kidney injury (AKI) during hospitalization were recorded. Within 24 h, laboratory indexes such as serum creatinine (Scr), albumin (Alb), hypersensitive C-reactive protein (hs-CRP), creatine kinase isoenzyme MB (CK-MB), D-dimer, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were measured. In addition, transthoracic echocardiography and the Frailty Screening Questionnaire (FSQ) were performed. Patients were followed up for the occurrence of MACCE within 1 year. The influencing factors of MACCE were screened by univariable and multivariable logistic regression analysis. The cut-off values of continuous variables were determined by receiver operating characteristic (ROC) curve and discretization was carried out with reference to clinical practice. Corresponding scores were set up according to the β regression coefficient of each variable to establish a clinical prediction score scale of MACCE. Finally, ROC curve was used to evaluate its prediction efficiency.Results:The study enrolled 322 elderly ACS patients, and the incidence of MACCE within 1 year was 24.5%. After preliminary screening of independent variables by univariable logistic regression analysis, the influencing factors of MACCE ( P<0.2) were as follows: ① Continuous indicators: age, body mass index (BMI), Alb, hs-CRP, D-dimer, NT-pro-BNP, ejection fraction (EF), Killip grade and FSQ score; ② Discrete indicators: ≥3 comorbidities, incomplete revascularization, and AKI. Multivariable logistic regression analysis after discretization of continuous indicators showed that age ≥84 years old [odds ratio ( OR)=4.351, 95% confidence interval (95% CI): 1.635-11.576, P=0.003], incomplete revascularization ( OR=6.580, 95% CI: 2.397-18.060, P < 0.001), combined with AKI ( OR=2.647, 95% CI: 1.085-6.457, P=0.032), EF ≤50% ( OR=2.742, 95% CI: 1.062-7.084, P=0.037), and FSQ≥3 points ( OR=9.345, 95% CI: 3.156-27.671, P < 0.001) were independent risk factors for MACCE. The total score of the clinical prediction system for MACCE was 8 points, including age ≥84 years old (2 points), incomplete revascularization (2 points), FSQ ≥3 points (2 points), EF ≤50% (1 point), and combined with AKI (1 point). The area under ROC curve (AUC) of the scoring system for predicting MACCE was 0.891, (95% CI: 0.844-0.938, P < 0.001). The optimal cut-off value was >3 points, and the sensitivity and specificity were 0.825 and 0.792, respectively. Conclusions:The prediction score scale of MACCE has a good diagnostic efficacy and has certain guiding value for clinicians to judge the prognosis of elderly ACS patients.