This review delves into the pivotal role of necrotic apoptosis in Alzheimer's disease(AD),with a focus on treatment strategies,drug development,prospects,and challenges,highlighting its significance in the progression of the disease.Firstly,necrotic apoptosis plays a crucial role in the pathogenesis of AD,particularly in association with the abnormal metabolism of β-amyloid(Aβ)and Tau proteins.The primary focus of drug design is to regulate the metabolism pathways of these two proteins to slow down or inhibit the progression of necrotic apoptosis.Secondly,the progress in drug development further emphasizes the importance of necrotic apoptosis in treating AD.Current research mainly focuses on drugs that affect the metabolism of Aβ and Tau proteins,such as lecanemab.Still,inconsistent result underscore the necessity for a more comprehensive understanding of the molecular mechanisms of necrotic apoptosis.Finally,the prospects and challenges of necrotic apoptosis research in AD are thoroughly discussed.A deeper understanding of necrotic apoptosis contributes to a better comprehension of the pathological mechanisms of AD but also may reveal new therapeutic targets.However,challenges such as multifactorial influences and the selection of treatment timing necessitate further in-depth research in the future.In conclusion,this review advocates for future research to deepen the understanding of the molecular mechanisms of necrotic apoptosis,enhance research on treatment strategies,gain a deeper understanding of its cross-regulation with other cell death pathways,and promote collaboration between basic research and clinical practice to advance the comprehensive understanding and treatment of Alzheimer's disease and necrotic apoptosis.

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

Objective:To investigate the association between frailty and prognosis of elderly patients in the emergency department, and to validate frailty screening tools suitable for the emergency department.Methods:This was a prospective cohort study. Clinical data of elderly patients over 60 years old treated in the emergency department of Beijing Bo'Ai Hospital from January to December 2021 were collected. The Frailty Screening Questionnaire (FSQ), FRAIL Scale (FRAIL) and Clinical Frailty Scale (CFS) were used to score patients, and patients were divided into frail or non-frail group according to the criteria of the above three scales. Twelve-month all-cause mortality was the primary endpoint, dependence and re-admission to the emergency department within 12 months were secondary outcomes. Receiver operating characteristic curves were used to evaluate the ability of the FSQ, FRAIL and CFS scores to predict the primary and secondary endpoints, and the areas under the curve (AUC) were calculated and compared. Survival analysis was performed using Cox hazard proportional regression model, and relative risk was expressed as hazard ratio ( HR) and 95% CI. Results:A total of 406 patients were included in the study. The AUCs (95% CI) of FSQ, FRAIL and CFS scores for predicting 12-month all-cause mortality were 0.879 (0.844-0.909), 0.838 (0.798-0.872), 0.906 (0.873-0.933), respectively (all P<0.001). The AUCs of 3 scores for predicting secondary endpoints ranged from 0.820 to 0.889 (all P<0.001). Pairwise comparisons of the AUCs showed that the CFS was superior to one or both of the other frailty screening scales in predicting 12-month all-cause mortality and dependence except for re-admission to emergency room within 12 months after discharge (all P<0.05). Cox regression analysis revealed that, after adjusting for sex, age, body mass index and comorbidities, frailty as defined by the FSQ, FRAIL, and CFS scales was independently associated with 12-month all-cause mortality, with the HRadj of 3.267 (95% CI: 2.406-4.435), 2.465 (95% CI: 1.819-3.341), 3.523 (95% CI: 2.648-4.687), respectively (all P<0.001). Conclusions:FSQ, FRAIL and CFS scores can predict adverse outcomes, the CFS is a practical frailty screening tool in the emergency department, and frailty screening can improve the risk stratification of older patients.

Objective:To explore the association between acute muscle wasting during hospitalization and poor prognosis in older patients with severe community-acquired pneumonia (SCAP) in emergency department.Methods:This study was a prospective cohort study. From January 1, 2022 to October 31, 2022, consecutive patients aged ≥65 years who met the diagnostic criteria of SCAP and had an interval of 14 days between two CT scans in the emergency department of Beijing Chao-Yang Hospital were enrolled. The general clinical data and cross-sectional area of the erector spinae muscle (ESMcsa) of the thoracic 12 level derived from chest CT on day 1 and day 14 were recorded and the differences between the two measurements were calculated. Patients were divided into survival group and non-survival group based on whether they died within 28 days. Two independent samples t-test and Mann Whitney U test were used to compare the dynamic changes of ESMcsa between two groups, and paired t-test and Wilcoxon signed rank test were used to compare the changes of ESMcsa within two groups. Multivariable Cox regression analysis was used to identify the risk factors for 28-day mortality, and receiver operating characteristic (ROC) curves were used to determine the predictive value of ESMcsa loss for 28-day mortality. The optimal cutoff value was determined on the basis of the Youden index (YI), patients were divided into a high muscle loss group and a low muscle loss group, and Kaplan Meier survival curve was drawn. Results:A total of 106 older patients with SCAP were included, with a median age of 82.0 years and 59 were men (55.7%). The ESMcsa levels of patients in non-survival group were lower than those in survival group both at admission and on the 14th day (both P<0.01). The ESMcsa levels on admission were lower than those on the 14th day in non-survival group ( P<0.001). The loss of ESMcsa in non-survival group [3.01 (-1.51, 7.73) cm 2vs. 0.80 (-2.58, 4.57) cm 2, P=0.020] was higher than that in the survival group. Multivariable Cox regression showed that ESMcsa loss was an independent risk factor for 28-day mortality ( HR=1.116, 95%CI: .029-1.210, P=0.010), the AUC for predicting 28-day mortality was 0.646 (95% CI: 0.528-0.763, P=0.020), and the optimal cut-off value was 6.22 cm 2. Kaplan Meier survival curve showed that the 28-day mortality risk in the high muscle loss group was higher than that in the low muscle loss group ( χ2=11.412, P=0.001). Conclusion:Acute muscle wasting during hospitalization was associated with 28-day mortality among older patients with SCAP, which provides a basis for improving patient prognosis from a muscle perspective.

Objective:To develop and validate a prediction model by combining clinical data and biomarkers to evaluate the probability of frailty among older emergency patients.Methods:A cross-sectional study was conducted. From January 2021 to December 2021, patients aged 60 years and older admitted to the emergency department of China Rehabilitation Research Center were enrolled. Data of patient's clinical information were collected. The patients were divided into frail group and non-frail group according to the Fried's frailty phenotype and clinical data were compared between the two groups. LASSO regression was used to deal with dimension reduction and multivariate logistic regression was employed to construct a prediction model based on variables selected by the LASSO regression. Nomogram was used to visualize the prediction model. The area under the receiver operating characteristic curve, calibration curve, decision curve analysis and bootstrap were used to evaluate the discrimination, calibration, clinical applicability, and internal validity of the model respectively.Results:A total of 348 patients were enrolled, and the incidence of frailty was 53.74% (187/348). Education, coronary heart disease, chronic obstructive pulmonary disease, albumin, fibrinogen, N-terminal pro-brain natriuretic peptide, decreased creatinine, and underweight were independent predictors for frailty in older emergency patients ( P < 0.05). A nomogram model was built based on the above predictors and the model showed good discrimination, calibration and clinical applicability. Conclusions:The study utilized objective clinical data and biomarkers to establish a predictive model for the occurrence of frailty in elderly emergency department patients. This model aids in risk stratification and targeted intervention for elderly emergency patients, thereby improving patient outcomes.

Objective:To evaluate the effect of ultrasound and CT three-dimensional reconstruction in open reduction and internal fixation of fractured ribs.Methods:A retrospective case-control study was conducted to analyze the clinical data of 112 patients with chest trauma and rib fractures admitted to Yan′an People′s Hospital from January 2021 to September 2023. According to the different preoperative positioning methods used, the reconstruction group was divided into a reconstruction group ( n=61) and a combined group ( n=51). The reconstruction group positioned the surgical incision position based on conventional CT three-dimensional reconstruction, while the combined group positioned the rib fracture end based on CT three-dimensional reconstruction combined with ultrasound. Record clinical data of two groups of patients and compare their preoperative positioning accuracy, average incision length, exposure time of fracture ends, fracture healing time, incision infection rate, surgical related indicators, visual analogue pain score (VAS) at one month after surgery, and surgical incision healing levels. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter group comparison; Comparison of count data between groups using chi-square test; The comparison of grade data were conducted using Mann-Whitney U test. Results:The preoperative localization accuracy, postoperative VAS at one month, and surgical incision healing grade A of the combined group patients were 94.4%, (2.26±0.48) points, 96.1%, respectively, the reconstruction group were 84.1%, (4.52±1.34) points, 72.1%, the combined group was better than the reconstructed group, the difference between the two groups was statistically significant ( P<0.05); The average incision length, fracture exposure time, fracture healing time, surgical time, and thoracic tube retention time of the combined group were (7.32±2.44) cm, (18.06±4.78) min, (48.16±4.58) d, (55.46±7.48) min, and (3.57±1.28) min, respectively. The reconstruction group were (10.16±2.86) cm, (29.45±5.65) min, (55.36±4.45) d, (64.36±7.52) min, and (7.49±1.52) min, respectively, the difference between the two groups was statistically significant ( P<0.05). Conclusion:Application of ultrasound combined with CT three-dimensional reconstruction in open reduction and internal fixation of fractured ribs can increase the preoperative positioning accuracy, which can guide the surgical incision, thus alleviating postoperative pain, facilitating postoperative healing, minimizing surgical trauma, and improving the patient′s prognosis.

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.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

With the improvement of China's socioeconomic status,the issue of aging has become increasingly prominent,making cerebral infarction a common disease among the elderly.In recent years,research on cerebral infarction has gradually deepened,shifting focus from merely protecting and repairing neurons to emphasizing the complex interplay between inflammatory response and autophagy in the brain vascular unit,covering various aspects such as the blood-brain barrier,astrocytes,microglia,and autophagy.This shift in research direction has provided us with a profound understanding of the mechanisms underlying cerebral infarction,offering strong support for innovative future treatment strategies.In this review,we delved into the importance of the interplay between inflammatory response and autophagy in the pathogenesis of cerebral infarction,emphasized the intricate interactions among these biological components,which might lay the groundwork for more effective managements and treatments of cerebral infarction.By comprehensively reviewing existing literatures,we proposed future research directions,aiming to provide more scientific and systematic guidance for the clinical management and treatment of cerebral infarction.

Objective:To develop and validate a predictive nomogram for 28-day mortality among very older patients with sepsis, to identify high-risk patients early and improve prognosis.Methods:This study was conducted from January 1, 2022, to November 30, 2022. Very older patients aged≥80 years with sepsis admitted to the emergency department of Beijing Chao-Yang Hospital, Capital Medical University were consecutively recruited. Their clinical data within 24 h of admission and 28-day mortality was recorded. The participants were divided into training (70%) and validation cohort (30%) (random number). In the training cohort, the risk factors of 28-day mortality were selected via least absolute shrinkage and selection operator (LASSO) regression analysis and multivariable Cox proportional hazard model, and a nomogram was developed. The prediction model was verified in validation cohort.Results:In total, 507 very older patients with sepsis were included, among which the mortality rate was 31.2%. In training cohort, the independent risk factors for 28-day mortality were identified: increased age [hazard ratio ( HR)=1.059, 95% confidence interval (95% CI)=1.017-1.103, P=0.005], cognitive impairment ( HR=2.100, 95% CI=1.322-3.336, P=0.002), frailty ( HR=2.561, 95% CI=1.183-5.545, P=0.017), decreased mean arterial pressure ( HR=0.987, 95% CI=0.976-0.998, P=0.017), decreased prealbumin ( HR=0.997, 95% CI=0.994-1.000, P=0.040), increased blood urea nitrogen ( HR=1.028, 95% CI=1.010-1.045, P=0.001), increased procalcitonin ( HR=1.008, 95% CI=1.001-1.016, P=0.019) via LASSO regression analysis and multivariable Cox regression analysis. The nomogram was developed using these seven predictors. In the training and validation cohorts, the calibration curves, time-dependent AUC curves, and decision curve analysis showed that the nomogram had good calibration degree, discrimination and clinical net benefits. Conclusions:Increased age, cognitive impairment, frailty, decreased mean arterial pressure, decreased prealbumin, increased blood urea nitrogen, and increased procalcitonin are independent risk factors for 28-day mortality in very older patients with sepsis. The nomogram, which included the seven predictors, have good predictive performance, and might be helpful for prognosis assessment.