Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

Psychological factors have become significant contributors to the onset and progression of insomnia. This article explored the treatment of insomnia from the perspective of “liver governs wei qi （defensive qi）”. The concept of “liver governs wei qi （defensive qi）” is summarized in three aspects， firstly， the liver assists the spleen and stomach in transformation and transportation， governing the generation of wei qi； secondly， the liver aids lung qi diffusion and dispersion， governing the distribution of wei qi； thirdly， the liver regulates circadian rhythms， governing the circulation of wei qi. It is proposed that the clinical treatment of insomnia should focus on the following methods： for regulating the liver to harmonize the five viscera， and facilitate the circulation of wei qi， medicinals entering the liver channel include Chaihu （Bupleuri radix）， Baishao （Paeoniae Radix Alba）， Zhizi （Gardeniae Fructus）， and Suanzaoren （Ziziphi Spinosae Semen） could be commonly used； for nourishing the liver， the treatment should align with the day-night rhythm， and herbs such as Baihe （Lilium）， Hehuan （Albizia julibrissin）， and Yejiaoteng （Polygoni multiflori caulis） are commonly used； for soothing the liver and address both mental and physical health to calm wei qi， treatment should advocate verbal counseling， psychological regulation， and health education. Ultimately， this treatment approach can free liver qi to flow， soothe qi movement， restore the motion of wei qi， regulate during day and night， balance yin and yang， and resolve insomnia effectively.

Objective:To compare the dosimetric characteristics of three fractionated stereotactic radiotherapy techniques,i.e.,tomo-therapy(TOMO),volumetric-modulated arc therapy(VMAT),and CyberKnife(CK),in the treatment of intracranial oligometastases,and to assess their dose distribution,treatment efficiency,and difference in dose delivered to organs at risk(OARs).Methods:A retro-spective analysis was performed for the clinical data of 54 patients with intracranial oligometastases who underwent fractionated stereo-tactic radiotherapy in The First Affiliated Hospital of Army Medical University in 2021-2023.Varian Eclipse 16.1 Physician Worksta-tion was used to perform tumor target volume delineation,and MANTEIA AccContour 3.2 software was used to perform the delineation of OARs,such as brainstem,spinal cord,and optical nerves.The delineated structures and images were transmitted to TOMO,CK,and Eclipse treatment planning systems to design three different radiotherapy treatment plans.Related key parameters were analyzed using the dose-volume histogram to evaluate the dosimetric characteristics of these three radiotherapy techniques,including conformity index(CI)of the target,dose homogeneity index(HI),beam-on time,the number of monitor units(MU),and the exposure dose of OARs.Results:All three treatment plans(TOMO,VMAT,and CK)met the requirements for prescribed dose.TOMO had a slightly better CI than VMAT and CK(1.05 vs.1.09 and 1.17,P<0.001).VMAT had a better HI than CK and TOMO(1.15 vs.1.28 and 1.46,P<0.001).In terms of execution efficiency,VMAT had a significantly shorter beam-on time than TOMO and CK(5 minutes,1 633 MU vs.10 minutes,8 932 MU and 39 minutes,5 191 MU,P<0.001).In terms of the exposure dose of OARs,CK provided the best protection for the lens,with a maximum dose of 15 cGy for the right lens and 17 cGy for the left lens,and TOMO had an advantage in dose control for the right cochlea,with a mean dose of 88 cGy,while VMAT had the best performance in limiting the dose for the spinal cord,with a maximum dose of 31 cGy(P<0.05).Conclusion:This study shows that TOMO,VMAT,and CK all meet the requirements for the prescribed dose and can effectively protect OARs in the treatment of in-tracranial oligometastases.In clinical practice,the most appropriate technique should be selected based on the features of lesions and treatment goals to achieve individualized treatment.

Objective To summarize and evaluate the treatment strategies and clinical outcomes of bladder inflammatory myofibroblastic tumor(IMT),so as to provide reference for the diagnosis and treatment of this rare entity.Methods A retrospective analysis was conducted on the clinical data of two patients with bladder IMT treated at Shandong Provincial Hospital Affiliated to Shandong First Medical University.In combination with literature analysis,the clinical characteristics,treatment methods and prognosis of this disease were analyzed.Results Both patients presented with painless terminal macroscopic hematuria.Patient 1 was a 42-year-old male with a 6 cm bladder mass detected by cystoscopy,with no muscular involvement.Transurethral en bloc resection with a 1470 nm diode laser was performed,followed by a second transurethral resection.Patient 2 was a 21-year-old male with a 5 cm bladder mass visualized on cystoscopy,with no muscular invasion.Transurethral en bloc resection using a 1470 nm diode laser was conducted,followed by transurethral laser marking the margin of the wound and laparoscopic partial cystectomy.Preoperative cystoscopic biopsy and postoperative pathology diagnosed it as IMT,which invaded the superficial muscular layer and the margin was negative.Patient 1 was followed for 40 months and patient 2 for 15 months.Follow-up cystoscopy performed every 3 months showed no evidence of recurrence.This article also summarized the relevant literature on bladder IMT over the past five years.Conclusion Bladder IMT is an extremely rare neoplasm with nonspecific clinical manifestations,posing challenges in both diagnosis and treatment.However,early recognition and definitive pathological diagnosis,combined with bladder-sparing surgical strategies such as en bloc resection,often result in favorable outcomes,with reduced risk of recurrence and improved quality of life.

N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl₄) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.

Objective·To explore the causal relationship between air pollution and the risk of Alzheimer's disease(AD)by using two-sample Mendelian randomization(MR).Methods·Based on the data from the genome-wide association study(GWAS),a two-sample MR analysis was conducted to evaluate the causal relationship between air pollution and the risk of AD.Air pollution indicators,including particulate matter 2.5(PM2.5),particulate matter 2.5-10(PM2.5-10),particulate matter 10(PM10),nitrogen dioxide and nitrogen oxides,were used as exposure factors,and summarized data were aggregated from the UK Biobank database.The PM2.5 dataset included 423 796 cases,with correlation analysis conducted on 9 851 867 single nucleotide polymorphisms(SNPs);the PM2.5-10 dataset included 423 796 cases,with correlation analysis conducted on 9 851 867 SNPs;the PM10 dataset included 455 314 cases,with correlation analysis conducted on 9 851 867 SNPs;the nitrogen dioxide dataset included 456 380 cases,with correlation analysis conducted on 9 851 867 SNPs;the nitrogen oxides dataset included 456 380 cases,with correlation analysis conducted on 9 851 867 SNPs.AD was used as the outcome factor,and data were obtained from the International Genomics of Alzheimer's Project(IGAP).The AD dataset included 25 580 cases and 48 466 controls,with correlation analysis of 7 067 513 SNPs.SNPs significantly associated with AD were used as instrumental variables.The main analysis was conducted by using the inverse variance weighted(IVW)method,and four methods including weighted median,MR-Egger regression,mode-based simple estimation and mode-based weighted estimation were used for quality control.Heterogeneity testing,gene pleiotropy testing and sensitivity analysis were conducted to assess the reliability of the study results.Results·Heterogeneity testing indicated no evidence of heterogeneity among SNPs associated with air pollution indicators and AD(both IVW and MR-Egger results,P＞0.05).Gene pleiotropy testing did not detect any pleiotropic effects(MR-Egger results,P＞0.05).Sensitivity analysis confirmed the stability of the PM2.5 results.IVW analysis revealed a statistically significant association between PM2.5 and AD in European populations(P＜0.001),while no statistically significant associations were observed between PM2.5-10(P=0.664),PM10(P=0.664),nitrogen dioxide(P=0.284),nitrogen oxides(P=0.567)and AD.Conclusion·There is a significant causal relationship between PM2.5 exposure and the risk of AD,with PM2.5 exposure increasing the incidence of AD.However,no evidence has been found to suggest that PM2.5-10,PM10,nitrogen dioxide or nitrogen oxides cause an increased risk of AD.

Objective:To analyze the correlation between caregiver characteristics and clinical manifestations of patients with Alzheimer′s disease (AD) dementia.Methods:It was a cross-sectional study. A total of 167 patients with AD dementia and 167 matched caregivers from Chinese Imaging, Biomarkers, and Lifestyle study of Alzheimer′s Disease (CIBL) study between January 1 and December 31, 2023 were consecutively selected as the study subjects. The data such as gender, age, body max index (BMI), waist to hip ratio, educational years, combined chronic diseases, disease course and the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL), Mini-Nutritional Assessment (MNA), and Dietary Diversity Score (DDS) of the patients were collected. The data such as gender, educational years, the relationship with patients, and the Caregiver Burden Inventory (CBI) score in the caregivers were also evaluated. According to the gender of caregivers, the patients were divided into female caregiver group (108 cases) and male caregiver group (59 cases). The Spearman correlation and multiple linear regression analyses were used to assess the impact of the caregiver characteristics on the cognitive function, NPS, activities of daily living, and nutritional status of the patients with AD dementia.Results:Among the 167 patients with AD dementia, 80 cases were men, and 87 cases were women, with a mean age of (68.43±7.51) years. Among the 167 matched caregivers, 59 were spouse, 98 were offspring, and 10 were others (nanny or other relatives). The AD patients in the male caregiver group had lower BMI and MNA scores than those in female caregivers′ group [(23.35±3.70) vs (24.80±3.33) kg/m 2, 22.00 (20.00, 24.50) vs 24.00 (21.00, 26.00) points] (both P<0.05). The educational years of the caregivers was negatively related to the ADL score ( r=-0.196), and was positively related to the MNA score of the patients ( r=0.180) (both P<0.05); while the CBI score of the caregiver was positively related to the age ( r=0.180), NPI score ( r=0.568) and ADL scores ( r=0.702) in the patients, and it was negatively related to the BMI ( r=-0.163), MMSE score ( r=-0.499), MoCA score ( r=-0.491) and MNA scores ( r=-0.387) in the patients (all P<0.05). The shorter educational years and elevated CBI score were independent risk factors for the decline in the MMSE score ( β=0.310, 95% CI: 0.021-0.598; β=-0.225, 95% CI:-0.297--0.154) and MNA score ( β=0.204, 95% CI: 0.067-0.340; β=-0.082, 95% CI:-0.116--0.049), as well as the increase in the NPI score ( β=-0.628, 95% CI:-1.208--0.047; β=0.575, 95% CI: 0.431-0.718) and ADL score ( β=-0.519, 95% CI:-0.860--0.179; β=0.361, 95% CI: 0.277-0.445) in the patients with AD dementia (all P<0.001). Conclusions:A low educational level of caregivers and a heavy caregiver burden are associated with decreased cognitive function, worsening NPS, reduced ADL, and declining nutritional status in patients with AD dementia.

Objective:To analyze the association of physical activity (PA) levels with the cognitive function and mental health among health check-up population.Methods:It is a cross-sectional study. The data from 869 health check-up population were consecutively collected from Beijing Tiantan Hospital, Capital Medical University between January 1, 2023 and December 31, 2023, including sex, age, body mass index (BMI), waist to hip ratio (WHR), educational years, medical history and personal history. The Global Physical Activity Questionnaire (GPAQ) was used to evaluate the PA levels, the Montreal Cognitive Assessment (MoCA) was performed to assess the global cognitive function, and the Patient Health Questionnaire 9 (PHQ-9) and the 7-item Generalized Anxiety Disorder (GAD-7) was used to screen for depression and generalized anxiety, respectively. Laboratory examination of lipid metabolism-related biomarkers included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein(a) [Lp(a)], apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB), small dense low-density lipoprotein (sdLDL) and remnant cholesterol (RC). The differences in general data, scale evaluation, and lipid metabolism-related biomarkers were compared among three groups [sufficiently active group:≥600 (metabolic equivalent,MET)-min/week, insufficiently active group: 1-599 MET-min/week, and inactive group: 0 MET-min/week]. The multiple linear regression was used to analyze the correlation between the PA or sitting time and MoCA, PHQ-9 or GAD-7 scores, respectively.Results:A total of 869 health check-up population was finally included, with the age of (51.22±10.09) years old; among these, 545 patients were men (62.72%), 324 cases were women (37.28%), 153 cases with cognitive impairment (17.61%). Participants in sufficiently active group had lower WHR [(0.88±0.07) vs (0.89±0.07)], sitting time [7.00 (4.00, 10.00) vs 10.00 (6.00, 12.00) h], PHQ-9 [2.00 (0, 5.00) vs 3.00 (0, 7.00) scores], GAD-7 [2.00 (0, 4.00) vs 3.00 (0, 6.00) scores], and sdLDL levels [0.93 (0.60, 1.32) vs 1.09 (0.70, 1.45) mmol/L] than those in inactive group (all corrected P<0.05). Population in sufficiently active group was older than those in insufficiently active group[(52.10±9.90) vs (49.88±9.88) years], and had lower BMI [(25.73±3.82) vs (26.13±3.54) kg/m 2], WHR [(0.88±0.07) vs (0.90±0.07)], proportion in medical history of alcohol consumption (14.46% vs 23.61%), sitting time [7.00 (4.00, 10.00) vs 9.15 (6.00, 12.00) h], PHQ-9 [2.00 (0, 5.00) vs 3.00 (0, 5.00) scores], and GAD-7 [2.00 (0, 4.00) vs 2.00 (0, 5.00) scores] than those in insufficiently active group (all corrected P<0.05). The sitting time ( β=-0.081, 95% CI:-0.134, -0.028), age ( β=-0.089, 95% CI:-0.111, -0.067), and WHR ( β=-7.069, 95% CI:-11.667, -2.472) were negatively correlated with the MoCA scores; the PA levels ( β=-1.06×10 -4, 95% CI:-1.06×10 -4, -3.05×10 -5), age ( β=-0.077, 95% CI:-0.106, -0.049), BMI ( β=-0.098,95% CI:-0.192, -0.005), educational years ( β=-0.090, 95% CI:-0.151, -0.029), and HDL-C levels ( β=-4.236, 95% CI:-6.171, -2.301) were negatively correlated with the elevation of PHQ-9 scores, while the PA ( β=-9.14×10 -6, 95% CI:-6.76×10 -6, 8.58×10 -5), age ( β=-0.089, 95% CI:-0.118, -0.060), and HDL-C levels ( β=-3.442, 95% CI:-5.403, -1.480) were negatively correlated with the of GAD-7 scores (all P<0.05). Conclusion:Decreased physical activity level significantly increases the risk of depression, anxiety, and cognitive impairment among health check-up population, suggesting that early screen for physical activity and active intervention for exercise and sedentary behavior are of great significance for preventing cognitive decline, anxiety and depression.

Objective:To analyze the mediating effect of the inflammation on the sex differences in cognitive function among middle-aged and elderly individuals receiving health checkups.Methods:This cross-sectional study consecutively collected data from 757 middle-aged and elderly individuals receiving health checkups at Beijing Tiantan Hospital, Capital Medical University between January 1, 2023 and December 31, 2023. The gender, age, body mass index (BMI), waist to hip ratio (WHR), educational years, medical history and personal history were collected. The Montreal Cognitive Assessment (MoCA) were performed to assess the cognitive function. Inflammation indicators included the single blood inflammatory markers [white blood cell (WBC), high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and erythrocyte sedimentation rate (ESR)], inflammatory markers derived from blood cell counts, including neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-monocyte to lymphocyte ratio (NMLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI); and inflammatory markers derived from blood cell counts and high-density lipoprotein cholesterol (HDL-C), including neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were all recorded. The simple mediation effect model in the SPSS 29.0 PROCESS macro was used to analyze the mediation effects of the inflammation indicators on the gender differences in cognitive function among middle-aged and elderly individuals receiving health checkups.Results:Among the 757 health checkup population in the final analysis, 466 were male (61.56%), and 291 were female (38.44%), with a mean age of (54.24±8.42) years. The male had higher BMI, WHR, educational years, frequency of hypertension and diabetes mellitus, MoCA scores, and inflammation indicators, including hs-CRP, WBC, NLR, MLR, NMLR, SIRI, AISI, NHR, MHR, LHR and PHR than those in the female [(26.41±3.20) vs (24.32±3.06) kg/m 2, (0.93±0.05) vs (0.83±0.06), 12 (9, 16) vs 11 (8, 15) years, 37.77% vs 21.31%, 16.52% vs 8.93%, 26 (24, 28) vs 26 (22, 28) points, 0.81 (0.38, 1.61) vs 0.63 (0.27, 1.63) mg/L, 5.75 (4.96, 6.78) vs 5.08 (4.27, 6.05)×10 9/L, 2.06 (1.67, 2.64) vs 1.87 (1.50, 2.37), 0.21 (0.17, 0.25) vs 0.17 (0.13, 0.21), 2.26 (1.84, 2.88) vs 2.02 (1.68, 2.55), 0.71 (0.51, 1.01) vs 0.49 (0.35, 0.67), 153.43 (108.91, 220.63) vs 113.34 (78.06, 164.27), 0.16 (0.12, 0.20) vs 0.11 (0.08, 0.14), 0.02 (0.01, 0.02) vs 0.01 (0.01, 0.01), 0.08 (0.06, 0.01) vs 0.06 (0.04, 0.07), 9.33 (7.82, 11.33) vs 8.36 (6.37, 10.21)] (all P<0.05). ESR and dNLR levels in the male were both lower than those in the female [6 (2, 11) vs 11 (6, 18) mm/h, 0.87 (0.85, 0.89) vs 0.89 (0.87, 0.91)] (both P<0.05). The MoCA score was negatively correlated with age, WHR, hs-CRP, IL-6, NLR, dNLR, NMLR, SIRI, NHR ( r=-0.355, -0.103, -0.115, -0.085, -0.094, -0.078, -0.093, -0.074, -0.108), and positively correlated with educational years ( r=0.512) (all P<0.05). After adjustment for confounding factors, including age, BMI, WHR, educational years, hypertension, and diabetes mellitus, dNLR and NHR mediated 13.11% and 12.80% association between gender and MoCA scores, respectively; after adjustment for above-mentioned confounders adding hs-CRP and IL-6, dNLR mediated 13.07% association between gender and MoCA score (all P<0.05), whereas no significant mediating effect was found of NHR on this association. Conclusions:Inflammation performed potential mediating effect on the association between sex difference and cognitive function among middle-to-old aged health checkup population, and the sex difference in cognitive function was partly mediated by the dNLR and NHR.

Objective To evaluate the effect of exercise on freezing of gait in Parkinson's disease.Methods After constructing a PICO framework,randomized controlled trials(RCTs)about exercise for freezing of gait in Parkinson's disease were systematically retrieved from Web of Science,PubMed,Cochrane Library,Embase,CNKI,VIP and Wanfang Data,from the establishment of the databases to March,2025.The PEDro scale was used to evaluate the quality of literature,Stata 17.0 was used for meta-analysis,and GRADE was used to assess the evidence quality.Results A total of twelve RCTs involving 463 patients were included,with PEDro scale scores of five to eight.Exercise improved the scores of Freezing of Gait Questionnaire(FOGQ)(SMD=-0.61,95%CI-0.85～-0.36,P<0.001)and Unified Parkinson's Disease Rating Scale Ⅲ(UPDRSⅢ)(SMD=-0.84,95%CI-1.27～-0.41,P<0.001).Subgroup analysis revealed that the patients aged 59 to 68 years,the course of disease