Sleep deprivation (SD) has emerged as a significant modifiable risk factor for Alzheimer’s disease (AD), with mounting evidence demonstrating its multifaceted role in accelerating AD pathogenesis through diverse molecular, cellular, and systemic mechanisms. SD is refined within the broader spectrum of sleep-wake and circadian disruption, emphasizing that both acute total sleep loss and chronic sleep restriction destabilize the homeostatic and circadian processes governing glymphatic clearance of neurotoxic proteins. During normal sleep, concentrations of interstitial Aβ and tau fall as cerebrospinal fluid oscillations flush extracellular waste; SD abolishes this rhythm, causing overnight rises in soluble Aβ and tau species in rodent hippocampus and human CSF. Orexinergic neurons sustain arousal, and become hyperactive under SD, further delaying sleep onset and amplifying Aβ production. At the molecular level, SD disrupts Aβ homeostasis through multiple converging pathways, including enhanced production via beta-site APP cleaving enzyme 1 (BACE1) upregulation, coupled with impaired clearance mechanisms involving the glymphatic system dysfunction and reduced Aβ-degrading enzymes (neprilysin and insulin-degrading enzyme). Cellular and histological analyses revealed that these proteinopathies are significantly exacerbated by SD-induced neuroinflammatory cascades characterized by microglial overactivation, astrocyte reactivity, and sustained elevation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) through NF‑κB signaling and NLRP3 inflammasome activation, creating a self-perpetuating cycle of neurotoxicity. The synaptic and neuronal consequences of chronic SD are particularly profound and potentially irreversible, featuring reduced expression of critical synaptic markers (PSD95, synaptophysin), impaired long-term potentiation (LTP), dendritic spine loss, and diminished neurotrophic support, especially brain-derived neurotrophic factor (BDNF) depletion, which collectively contribute to progressive cognitive decline and memory deficits. Mechanistic investigations identify three core pathways through which SD exerts its neurodegenerative effects: circadian rhythm disruption via BMAL1 suppression, orexin system hyperactivity leading to sustained wakefulness and metabolic stress, and oxidative stress accumulation through mitochondrial dysfunction and reactive oxygen species overproduction. The review critically evaluates promising therapeutic interventions including pharmacological approaches (melatonin, dual orexin receptor antagonists), metabolic strategies (ketogenic diets, and Mediterranean diets rich in omega-3 fatty acids), lifestyle modifications (targeted exercise regimens, cognitive behavioral therapy for insomnia), and emerging technologies (non-invasive photobiomodulation, transcranial magnetic stimulation). Current research limitations include insufficient understanding of dose-response relationships between SD duration/intensity and AD pathology progression, lack of long-term longitudinal clinical data in genetically vulnerable populations (particularly APOE ε4 carriers and those with familial AD mutations), the absence of standardized SD protocols across experimental models that accurately mimic human chronic sleep restriction patterns, and limited investigation of sex differences in SD-induced AD risk. The accumulated evidence underscores the importance of addressing sleep disturbances as part of multimodal AD prevention strategies and highlights the urgent need for clinical trials evaluating sleep-focused interventions in at-risk populations. The review proposes future directions focused on translating mechanistic insights into precision medicine approaches, emphasizing the need for biomarkers to identify SD-vulnerable individuals, chronotherapeutic strategies aligned with circadian biology, and multi-omics integration across sleep, proteostasis and immune profiles may delineate precision-medicine strategies for at-risk populations. By systematically examining these critical connections, this analysis positions sleep quality optimization as a viable strategy for AD prevention and early intervention while providing a comprehensive roadmap for future mechanistic and interventional research in this rapidly evolving field.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To investigate the clinical effect of extraperitoneal robot-assisted laparoscopic modified Y-V plasty(LMYVP)in the treatment of refractory bladder neck contracture(BNC).Methods:We retrospectively analyzed the clinical data on 10 cases of refractory BNC after transurethral resection of the prostate between September 2020 and January 2023,all with a history of recurrent urethral dilatation and at least two failures in transurethral surgical treatment of scarring.After definite diagnosis and re-moval of some of the scar tissues to flatten the elevated bladder neck under the cystoscope,we performed robot-assisted LMYVP using the da Vinci Si robotic system and a four-port extraperitoneal approach.The surgical procedure involved an inverted T-shaped incision in the bladder neck and urethral stricture ring,an inverted V-shaped excision of the scar area at the 3-9 o'clock position on the ventral side of the prostatic urethra,continuous full-layer suturing of the bladder neck and inverted V-shaped urethra with 3-0 barbed thread,and indwelling of an F20 silicone catheter for 2 weeks.At 3 months after surgery,we performed cystoscopic examination,measured the maximum urinary flow rate(Qmax),and obtained the IPSS and quality of life(QOL)scores of the patients.Results:Operations were successfully completed in all the cases.At 3 months after surgery,the patients showed significantly increased Qmax([3.65±1.27]vs[20.3±1.77]ml/s,P＜0.05),IPSS(5.9±2.02 vs 30±1.15,P＜0.05)and QOL score(1.3±0.95 vs 5.2±0.79,P＜0.05)compared with the baseline.Cystoscopy revealed a wide and flat bladder neck with good survival and hemody-namics of the bladder flap.All the patients met the criteria for clinical cure at a median follow-up of 13.2 months.Conclusion:Extraper-itoneal robot-assisted LMYVP provides a new strategy for urinary tract reconstruction in the management of refractory BNC,with the ad-vantages of minimal invasiveness,high efficiency and high success rate.

Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

Aim To investigate the effects of HXL130 on the proliferation, invasion and migration of prostate cancer PC3 cells and its molecular mechanism. Methods MTT assay was used to detect the effect of HXL130 on the proliferation of prostate cancer PC3 cells. Hoechst 33258 staining and flow cytometry were used to detect the effects on apoptosis and cell cycle of cancer cells. Transwell was used to detect the effects of compounds on the invasion and migration of cancer cells. Proteomic sequencing was employed to detect differentially expressed proteins (DEPs) induced by compound treatment of cancer cells. Bioinformatics was used to analyze the functions of DEPs and the related signaling pathways regulated by DEPs, and Western blot was used to verify the result. Results The survival rate of PC3 cells decreased with the increase of HXL130 concentration and treatment time. HXL130 could significantly induce cell apoptosis and block G

AIM To explore the clinical effects of San'ao Decoction combined with salbutamol on patients with cough variant asthma.METHODS Eighty patients were randomly assigned into control group(40 cases)for 3-month administration of salbutamol,and observation group(40 cases)for 3-month administration of both San'ao Decoction and mifepristone.The changes in clinical efficacy,TCM syndrome scores,serum MMP-9,VEGF and sex hormones(E2,FSH,PRL)and incidence of adverse reactions were detected.The changes in clinical efficacy,EOS,SIgG4,TIgE,Eotaxin,NKA,LTD4,IL-27,SP,R5-R20,Fres,R5,Zrs,PEF diurnal variation rate,FEF25,PEF,ACT score,PAQLQ score,recurrence rate and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05),along with lower recurrence rate(P<0.05).After the treatment,the two groups displayed decreased EOS,TIgE,Eotaxin,NKA,LTD4,SP,R5-R20,Fres,R5,Zrs and PEF diurnal variation rate(P<0.05),and increased SIgG4,IL-27,FEF25,PEF,ACT score,PAQLQ score(P<0.05),especially for the observation group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with cough variant asthma,San'ao Decoction combined with salbutamol can improve EOS,TIgE,Eotaxin,SIgG4 levels and airway resistance indices,lung function indices,regulate neurogenic mediators,alleviate airway inflammation injury,enhance life quality,and reduce recurrence rate.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid ; Epimedium ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Multivariate Analysis