Alzheimer's disease(AD)is a neurodegenerative disease with highly heterogeneous pathological and clinical manifesta-tions,and it is the most common cause of dementia.This heterogeneity poses challenges for diagnosis,treatment,and evaluating novel pharmacological efficacy.This review summarizes the latest progress in the major clinical subtypes of AD based on clinical manifesta-tions,genetic,and pathological features.Early-onset and late-onset AD clinical subtypes may share the same symptoms but differ in etiology,age of onset,mode of presentation,disease progression,and associated comorbidities.Typical and atypical AD differ signifi-cantly in clinical manifestations,pathological features,and diagnostic criteria.Research on AD subtypes based on imaging and omics data has also made considerable progress.This review also outlines the molecular pathological heterogeneity of AD.A deep understand-ing of these heterogeneities is crucial for diagnosis,the formulation of pharmacological treatment strategies,and clinical management.

Objective:Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection.Due to lack of effective treatments,it has always been the difficulty and focus of clinical treatment of sepsis.Studies have shown that pro-brain-derived neurotrophic factor(proBDNF)binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor(p75NTR),which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis.This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. Methods:From the healthy donors(control group,n=40)and sepsis patients(sepsis group,n=40)admitted to the hospital for the first time,peripheral blood samples and blood routine clinical detection indicators were obtained.By using flow cytometry,the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined.The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide(LPS).Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets.On this basis,we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. Results:White blood cell count,neutrophil count,and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group;on the contrary,lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group(all P＜0.001).The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group(both P＜0.05).In the peripheral blood of sepsis patients,proBDNF expression was upregulated on CD19+ B cells,whereas p75NTR expression was elevated on B cells,CD4+ T cells,and CD8+ T cells(all P＜0.05).ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group(P＜0.05),and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group.Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages,cytokine expression of IL-4 and IL-10,and reduced IL-1β and IL-6 production(all P＜0.05). Conclusion:The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils.ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients,and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.

Objective:To evaluate the effect of white noise on reducing procedural pain of premature infants.Methods:Randomized controlled trials (RCTs) on the effect of white noise on reducing procedural pain in premature infants were searched for in PubMed, Embase, Web of Science, Cochrane Library, CINAHL, CNKI, VIP, Wanfang database and China Biology Medicine disc. The retrieval time was from the establishment of the databases to January 12, 2023. After independent literature screening, data extraction and bias risk assessment by two researchers, Meta-analysis was conducted using RevMan 5.3 software.Results:A total of 8 RCTs with 689 premature infants were finally included. The Meta-analysis results showed that compared with conventional procedures, the use of white noise alone could reduce the pain score ( SMD=-2.29, 95% CI: -2.78--1.79, P<0.000 01) in preterm infants during and after procedures ( SMD=-2.55, 95% CI: -4.52--0.58, P=0.01) , reduce the heart rate ( MD=-7.38, 95% CI: -7.97--6.80, P<0.000 01) during and after procedures ( MD=-10.36, 95% CI: -13.58--7.14, P<0.000 01) , and increase blood oxygen saturation during operation ( MD=3.78, 95% CI: 3.54-4.02, P<0.000 01) and after operation ( MD=2.19, 95% CI: 1.84-2.54, P<0.000 01) . Conclusions:White noise can effectively relieve the procedural pain of premature infants and maintain the stability of physiological indicators. In the future, more high-quality and large sample randomized controlled trials should be conducted to verify the application effect of white noise in relieving pain of premature infants.