[Objective]To investigate the effects of amyloid precursor protein intracellular domain(AICD)on neurogenesis,learning and memory in Alzheimer's disease(AD)model mice.[Methods]Immunofluorescence staining was used to detect the proliferation and differentiation of neural progenitor cells(NPCs)cultured in vitro,numbers of neural stem cells and neurons in embryonic cerebral cortex and adult hippocampal dentate gyrus(DG)derived from AICD transgenic mice.The morris water maze was applied to evaluate learning and memory ability of old AICD transgenic mice,and bioinformatics to predict and analyze the underlying molecular mechanisms.[Results]Immunofluorescence staining showed that NPCs,numbers of neural stem cells and neurons in embryonic cerebral cortex and hippocampal DG region were decreased(P<0.05),indicating that AICD inhibited neurogenesis in AD model mice at different periods.Morris water maze revealed that AICD increased escape latency of AD model mice,reduced numbers of platform crossing and neuron numbers in DG region(P<0.05).Bioinformatics results found 1 723 targets of AICD involved in the regulation of neurogenesis,learning and memory in the pathogenesis of AD,in which the key targets were TP53,CTNNB1,Akt1,EGFR,SRC,EP300,HDAC1,STAT3,HSP90AA1 and MAPK1.KEGG pathway annotation analysis showed that signaling pathways like PI3K-Akt and HIF-1 play a crucial role in the regulation of neurogenesis,learning and memory by AICD.[Conclusions]AICD could inhibit hippocampal neurogenesis in AD model mice,thus impair their learning and memory ability,which may be related to PI3K-Akt and HIF-1 signaling pathways.This study provides an experimental basis for further understanding the role of AICD in the pathogenesis of AD.

Objective To explore the characteristics of blood vitamins A, B2, B6, B12, D, E, K1, K2 and folic acid and their correlation with severity in patients with metabolic-related fatty liver disease (MAFLD). Methods　From September to December 2022, a total of 473 cases of residents were recruited through community MAFLD screening activities and their health information was obtained through questionnaire survey and physical examination. The severity of hepatic steatosis was determined with FibroScan, and vitamin concentrations were determined with liquid chromatography-tandem mass spectrometry. Two independent samples' t-tests were used to assess the differences between the two groups, and univariate chi-square tests and multivariate logistic regression analysis were used to explore the related factors of MAFLD. Results　Of the 473 inhabitants, 195 (41.23%, 195/473) met the diagnostic criteria for MAFLD, including mild 43 (22.05%, 43/195) cases of fatty liver, 88 (45.13%, 88/195) cases of moderate fatty liver, and 64 (32.82%, 64/195) cases of severe fatty liver. Using healthy residents collected during the same period as controls, the overall mean of vitamins A, E, K1, and K2 in the MAFLD group was higher than that of the healthy group, with a statistical difference (P<0.05). Furthermore, the concentrations of vitamins A, E, K1 and K2 increased with the severity of fatty liver [R=0.149, P=0.004; R=0.245, P<0.001; R=0.110, P=0.032; R=0.129，P=0.012]. There were statistically significant differences (P<0.05) in the blood levels of vitamin A and E between patients with moderate or severe fatty liver and the healthy population. The blood vitamins K1 and K2 in severe fatty liver patients were also different from those of healthy people (P<0.05). However, there was no significance between folic acid, vitamin D, B2, B6, B12, and MAFLD (P>0.05). Through univariate chi-square analysis and multivariate logistic regression analysis, it was found that male [Wald=5.789, P=0.034，OR=1.598(1.037-2.463)] and vitamin E≥8.13 μg/mL[Wald=14.632，P<0.001，OR=2.378(1.522-3.674)] were risk factors for moderate and severe MAFLD. Conclusions The concentrations of vitamin A, E, and K in the blood are increased in patients with MAFLD compared to the healthy population, and they are positively correlated with the severity of MAFLD. ale gender and high levels of vitamin E may be related to moderate to severe MAFLD.

The online and offline hybrid teaching model of evidence-based medicine (EBM) is currently in the stage of development. Previous teaching focused on the teaching process in the classroom, and did not organically combine all the course contents before, during, and after class. The BOPPPS model can be used to establish coherence and integrity in the EBM teaching process. Considering the discipline characteristics and teaching objectives of EBM, this study initially explored and designed a BOPPPS-based online and offline hybrid teaching model. Taking the "diagnostic evidence" module as an example, the teaching implementation details were introduced. A pre-designed questionnaire was used to conduct baseline survey and follow-up survey on students before and after class to evaluate the teaching model and effect. The surveys showed that half of the students (77/154) preferred the new online and offline hybrid teaching model of EBM. The students found that all aspects of BOPPPS teaching were generally acceptable and satisfactory. Compared with before teaching, the students' proficiency in EBM was significantly improved after the teaching ( P<0.001), particularly in their ability to retrieve literature and evaluate the quality of evidence, which is of great significance for expanding their knowledge and clinical thinking.

Objective:To summarize the clinical features associated with respiratory syncytial virus (RSV) infection in patients following the hematopoietic stem cell transplant (HSCT) and exploring the risk factors for death.Methods:Patients who had RSV infection after undergoing HSCT from October 2023 to January 2024 in the hematology department of Peking University People’s Hospital were enrolled in the study. The clinical characteristics of the participating patients were summarized. The clinical characteristics of the surviving and the dying patients were compared, and the risk factors of death were analyzed by binary logistic regression.Results:Among the 43 RSV-positive HSCT patients, 20 (46.5%) were hypoxemic, six (14.0%) were admitted to the ICU for further treatment, four (9.3%) required tracheal intubation assisted ventilation, and seven patients (16.3%) died. A comparison of the clinical features of the surviving patients and the deceased patients demonstrated that the deceased patients had a lower PLT when infected with RSV [74.5 (8.0-348.0) ×10 9/L vs 15.0 (10.0-62.0) ×10 9/L, P=0.003], a higher incidence of simultaneous bacterial infections (85.7% vs 41.7%, P=0.046), and a higher rate of hematological recurrence (71.4% vs 13.9%, P=0.004). Hematological recurrence ( OR=15.500, 95% CI 2.336-102.848, P=0.005), influenza A viral infection ( OR=14.000, 95% CI 1.064-184.182, P=0.045), and low PLT at the time of RSV infection ( OR=0.945, 95% CI 0.894-0.999, P=0.048) were the factors associated with death following HSCT. Conclusion:Patients infected with RSV after undergoing HSCT have a poor prognosis, and active prevention and treatment of RSV in the autumn and winter requires urgent attention.

Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the impact of two target body temperatures on inflammatory response, oxidative stress, cerebral metabolism, outcomes and complications in patients undergoing extracorporeal cardiopulmonary resuscitation. Methods A retrospective analysis was conducted on the clinical data of 107 patients undergoing extracorporeal cardiopulmonary resuscitation. Fifty-three patients with a target body temperature controlled at 32.0 to 34.0 ℃ were included in the moderate hypothermia group, and 54 patients with a target body temperature controlled at 34.1 to 36.0 ℃ were included in the mild hypothermia group. Inflammatory response indicators [C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1β (IL-1β), nuclear factor kappa-B subunit p65 (NF-κB p65)], oxidative stress indicators [superoxide dismutase (SOD), total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA)], and cerebral metabolism indicators [arterial-jugular venous oxygen content difference (Da-jvO₂), cerebral oxygen extraction ratio (CERO₂)] were compared between the two groups before temperature management and when the target temperature was achieved. Additionally, occurrence of complications and outcomes [prognosis outcomes and Glasgow-Pittsburgh Cerebral Performance Categories (CPC) score] were compared. Results When the target temperature was achieved, the levels of CRP, IL-6, IL-1β, and NF-κB p65 in both groups were lower than those before temperature management, and their levels in the moderate hypothermia group were lower than those in the mild hypothermia group(P < 0.05). At the target temperature, the levels of SOD and TAC in both groups were higher than those before temperature management, and the levels in the moderate hypothermia group were higher than those in the mild hypothermia group (P < 0.05). Meanwhile, the levels of TOS and MDA in both groups were lower than those before temperature management, and the levels in the moderate hypothermia group were lower than those in the mild hypothermia group (P < 0.05). When the target temperature was achieved, the Da-jvO₂ and CERO₂ in both groups were lower than those before temperature management, and their levels in the moderate hypothermia group were lower than those in the mild hypothermia groups (P < 0.05). There was no statistically significant difference in the incidence of complications between the two groups (P>0.05). The CPC score and prognosis in the moderate hypothermia group were slightly better than those in the mild hypothermia group, but the difference was not statistically significant (P>0.05). Conclusion Target body temperature management after cardiopulmonary resuscitation can effectively promote the recovery of cerebral function. A target body temperature of 32.0 to 34.0 ℃ is more conductive to reducing inflammatory response as well as oxidative stress, and improving cerebral metabolism and outcomes.

Objective To analyze the risk factors of coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2M) in Suining area, and build a risk prediction model to provide theoretical basis for the prevention and treatment of CHD in PATIENTS with T2M. Methods A total of 476 T2M patients treated in our hospital from January 2021 to December 2021 were selected and divided into experimental group (n=79) and control group (n=397) according to whether they had coronary heart disease. The angiographic characteristics of coronary artery lesions in patients with T2M combined with coronary heart disease were observed. Age, sex, body mass index (BMI), smoking, alcohol consumption , T2M course, FBG, FINS, HOMA, TC, LDL-C, SBP, DBP and UA levels of all patients were analyzed. Univariate analysis and Logistic regression were used to analyze the influencing factors of coronary heart disease and establish a risk prediction model. ROC curve was used to predict the efficiency of the model. Results A total of 79 cases (16.60%) of patients with T2M complicated with coronary heart disease, including 64 cases (81.01%) of patients with T2M complicated with coronary artery disease. Mild stenosis in 5 cases (6.33%), moderate stenosis in 20 cases (25.32%) and severe stenosis in 54 cases (68.35%); The mean age, smoking proportion, BMI, T2M course and the levels of FBG, FINS, HOMA-IR, TC, LDL-C, SBP, DBP and UA in experimental group were significantly higher than those in control group (P<0.05). Multivariate logistic regression analysis showed that advanced age, increased SBP, increased LDL-C, and increased FBG were independent risk factors for CORONARY heart disease in T2M patients in Suining area (OR=1.476 , 2.674 , 2.984 , 3.572 , P<0.05). According to the above four independent factors and their corresponding regression coefficients, the expression of risk prediction model was P=1/[1+e^{-(-0.513+0.919×(old age)+1.129×(increased SBP)+ 1.724×(increased FBG)+ 1.529×(increased LDL-C)}]. ROC curve was used to analyze the predictive performance of the regression model. The results showed that the AUC of the risk prediction model for coronary heart disease in T2M patients was 0.728, 95% CI (0.651-0.829). Conclusions T2M patients in Suining have a high risk of coronary heart disease. For elderly patients with elevated SBP, LDL-C and FBG, the risk of coronary heart disease can be assessed by predictive model and targeted intervention measures can reduce the risk of coronary heart disease in T2M patients.

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.