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.

Andrological diseases have become an important public health problem threatening men's health worldwide， which significantly affects the quality of life of patients and brings a heavy disease burden. Western medicine often faces the dilemma of obvious side effects and limited efficacy. Traditional Chinese medicine has unique advantages in the prevention and treatment of andrological diseases and has accumulated rich clinical experience. Epimedii Folium， as a traditional Chinese medicine for strengthening kidney and Yang， exerts a key therapeutic effect on andrology diseases through multi-component synergy， multi-target regulation， and multi-pathway intervention. Recent studies have found that the main active components of Epimedii Folium， such as icariin， icariside， and icaritin， are the key material basis for the treatment of andrological diseases. The active components of Epimedii Folium can play a role in common andrological diseases such as erectile dysfunction， male infertility， and prostate cancer by regulating the activity of the nitric oxide/cyclic guanosine monophosphate （NO/cGMP） pathway， participating in oxidative stress response， regulating the secretion of hypothalamic-pituitary-gonadal axis hormones， improving spermatogenic dysfunction， and inhibiting the proliferation of cancer cells. However， the systematic action network and molecular mechanisms of the active components of Epimedii Folium have not been fully elucidated， thereby limiting its potential for clinical translation and application. In the future， it is necessary to combine cutting-edge technologies such as metabolomics， single-cell sequencing， and targeted nanoscale drug delivery systems， strengthening the research on the compatibility rules of active components and organ-specific delivery， providing a scientific basis for the development of innovative andrology traditional Chinese medicine formulas with international competitiveness， and promoting the innovation and breakthrough of andrology disease treatment modes.

Gastric cancer remains a highly prevalent malignancy worldwide, with surgical resection currently constituting the cornerstone of treatment aimed at improving long-term patient survival. Owing to their notable advantages, including reduced surgical trauma and accelerated postoperative recovery, minimally invasive procedures are progressively supplanting conventional open surgery and have become the mainstream approach in gastric cancer management. Concurrently, the rapid advancement of artificial intelligence (AI) technologies has enabled real-time intraoperative monitoring of surgical scenes, thereby furnishing novel technical support for adjunctive decision-making, surgical navigation, and skill assessment during gastrectomy. This article provides a systematic review of the current status of AI applications in minimally invasive gastric cancer surgery, with a particular focus on research progress pertaining to instrument recognition, surgical phase identification, delineation of normal anatomical structures, detection of metastatic foci, and early warning of intraoperative adverse events. Furthermore, we discuss the potential value of AI in enhancing surgical efficiency, ensuring patient safety, and optimizing surgical education. On this basis, we further analyze the principal challenges and inherent risks confronting current AI systems, with the aim of informing future technological innovation and facilitating clinical translation.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.

Objective To evaluate the safety and efficacy of total arterial off-pump coronary artery bypass grafting (OPCABG) using a left internal thoracic artery (LITA) combined with bilateral radial arteries (RAs). Methods We retrospectively analyzed the clinical data of patients with severe multi-vessel coronary artery disease who underwent total arterial OPCABG with a LITA and bilateral RAs at Sichuan Provincial People’s Hospital from November 2020 to April 2023. Results A total of 24 patients were included, comprising 23 males and 1 female, with a mean age of (53.63±4.33) years. The New York Heart Association (NYHA) functional class was Ⅱ to Ⅲ. The mean number of distal anastomoses was 3.17±0.38. A Y-graft was constructed in 12 patients and sequential grafting was performed in 4 patients. Concomitant procedures included coronary endarterectomy in 1 patient, intra-aortic balloon pump (IABP) implantation in 10 patients, and thymoma resection in 1 patient. The mean operative time was (308.13±30.39) min, mechanical ventilation time was (15.42±7.42) h, ICU stay was (46.08±27.32) h, and postoperative hospital stay was (11.71±1.90) d. There were no in-hospital deaths. Postoperative complications included one patient of acute renal failure and one patient of cerebral infarction. Pre-discharge color Doppler echocardiography revealed that the left ventricular end-diastolic diameter was significantly smaller than before surgery (P<0.05), while the left ventricular ejection fraction and fractional shortening were significantly higher (P<0.05). Coronary computed tomography angiography (CTA) showed that all arterial grafts were patent. During a mean follow-up of (14.58±8.75) months, no patients experienced angina recurrence or mortality. Repeat coronary CTA or angiography in 16 patients one year postoperatively confirmed that all arterial grafts remained patent. Conclusion Total arterial OPCABG using a LITA and bilateral RAs is a safe and effective treatment for patients with severe multi-vessel coronary artery disease. For high-risk patients, intraoperative IABP support is recommended.

Objective To retrospectively analyze the results of serum beta-amyloid 42(Aβ42)tests conducted in the laboratory and explore potential issues associated with this testing.Methods All the Aβ42 test data collected up to the initiation of this study were compiled,and the positive rates for various diagnoses,including Alzheimer's disease(AD),cognitive decline,and dementia were ana-lyzed.Accuracy of the test kit was preliminarily validated using the kit's own reference,mouse brain tissue,and in vitro cultured cell-based reference samples.Results Data from 546 patients were col-lected,with 166 positive cases(positive rate of 30.4％).Among them,3 out of 6 AD patients tested positive;among 149 patients diagnosed with cognitive decline and 59 dementia patients,there were 29 and 24 positive cases respectively,with positive rates of 19.5％and 40.7％.The kit's detection of its own reference was affected by the serum matrix and failed to effectively detect positive mouse brain tissue and cellular reference samples.The kit's detection was generally unaffected by the amyloid precursor protein(APP)of Aβ,but it did not demonstrate good recovery rates for its own reference samples added to various clinical serum specimens.Conclusion The positive rate of serum Aβ42 test results in laboratory is lower than expected,and the accuracy of the test kit may require further improvement.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Objective: To improve the efficiency and standardization of preoperative anemia diagnosis and treatment by establishing a systematic intelligent management platform for preoperative anemia. Methods: A multidisciplinary collaborative model was adopted to develop a preoperative anemia management system that integrates intelligent early warning, standardized treatment pathways, and quality control. The system utilizes natural language processing technology to automatically capture laboratory data and establish evidence-based medical decision support functions. A pre-post study design was employed to compare changes in preoperative anemia screening rates, preoperative anemia intervention rates, reasonable use of iron supplements, and perioperative red blood cell transfusion rates before and after system implementation. Results: After system implementation, the standardization of anemia diagnosis and treatment significantly improved: 1) Screening effectiveness: The anemia screening rate increased to 50.00% (an increase of 27.24%); 2) Intervention effectiveness: The anemia treatment rate rose to 56.30% (an increase of 14.02%); 3) Treatment standardization: The reasonable use rate of iron supplements increased to 55.33% (an increase of 21.02%); the red blood cell transfusion rate decreased to 18.29% (a decrease of 4.07%), and the amount of red blood cell transfusions was reduced by 291 units. Conclusion: This system achieves full-process management of preoperative anemia through information technology, significantly enhancing the standardization of diagnosis and treatment as well as intervention effectiveness, providing an effective solution for perioperative anemia management.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*