Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.

Lung cancer is one of the most lethal cancers, and the overall survival rate of lung cancer patients is very low. With the increasing research on lung cancer, the critical role of intestinal flora in lung cancer treatment has been gradually discovered. Among the various therapeutic approaches targeting the intestinal flora, fecal microbiota transplantation (FMT) is considered as a potential strategy to treat lung cancer by interfering with the homeostasis of the intestinal flora. FMT can improve the efficacy of lung cancer treatment and attenuate the side effects associated with immunotherapy, chemotherapy, and radiotherapy by remodeling the microbial composition, modulating the metabolites, and activating immune responses. The aim of this paper is to discuss the current status and potential mechanisms of FMT in lung cancer treatment, and to provide a new strategy for regulating the intestinal flora to enhance the prevention and treatment of lung cancer.

ObjectiveTo evaluate the comparative clinical outcomes of zero-profile interbody fusion （Zero-P） and traditional anterior cervical discectomy and fusion with titanium plate （ACDF-plate） for three-level cervical spondylosis， providing a reference to optimize surgical strategies for three-level cervical spondylosis. MethodsIn this retrospective comparative study， 113 patients were included and assigned to either the Zero-P group （n=51） or the ACDF-plate group （n=62） according to their surgical approaches. Clinical outcomes were evaluated and compared between the two groups using operative time， intraoperative blood loss， length of hospital stay， visual analog scale （VAS） scores， cervical range of motion （ROM）， neck disability index （NDI）， Cervical Disability Index （CDI）， Japanese orthopaedic association （JOA） scores， and postoperative complication rates. ResultsCompared with the ACDF-plate group， the Zero-P group had a shorter operative time and less intraoperative blood loss （P<0.05）； the neck pain VAS score was lower on the 1st day and 1st week after surgery （P<0.05）； the cervical flexion range of motion was higher at 1 month after surgery （P<0.05）； the JOA score was higher at 3 months after surgery， while the NDI and CDI scores were lower （P<0.05）； the total incidence of complications （11.76%） was significantly lower than that in the plate fixation group （35.48%）， and the incidence of neck foreign body sensation/stiffness was lower （P<0.05）. ConclusionZero-P not only demonstrates safety and efficacy comparable to the ACDF-plate， but also highlights the significant value of the minimally invasive concept in facilitating early recovery. Both procedures have their respective emphasis on biomechanical maintenance and minimally invasive benefits， providing a clear evidence-based reference for individualized and precise surgical decision-making in three-level cervical spondylosis.

ObjectiveTo observe the clinical efficacy and safety of Tianmeng Lingjiao Formula（天礞羚角方， TLF） as an adjunctive therapy for paroxysmal atrial fibrillation （PAF） with phlegm-heat harassing the interior syndrome. MethodsNinety patients with PAF and phlegm-heat harassing the interior syndrome were enrolled and randomly assigned in a 2∶1 ratio to test group （60 cases） and control group （30 cases）. The control group received conventional western medicine， while the test group received TLF in addition to the conventional treatment， with one dose administered daily. The treatment course for both groups was 4 weeks. The efficacy of traditional Chinese medicine （TCM） syndrome and the rate of atrial fibrillation （AF） conversion were compared between groups. Assessments included AF burden， frequency and duration of AF episodes， TCM syndrome scores， and European Heart Rhythm Association （EHRA） AF symptom classification before and after treatment. Safety indicators such as blood routine， urine routine， stool routine， liver function， kidney function， and electrolytes were also monitored. Adverse events were recorded. ResultsA total of 82 patients completed the study （54 in the test group and 28 in the control group）. After treatment， AF burden， the frequency and duration of AF episodes， and TCM syndrome scores were significantly reduced in both groups， and the test group showed lower indicators than the control group （P＜0.01 or P＜0.05）. The AF conversion rate was 25.93% （14/54） in the test group， significantly higher than 3.57% （1/28） in the control group （P＜0.05）. The total effective rate for TCM syndrome efficacy was 83.33% （45/54） in the test group， which was significantly higher than 67.86% （19/28） in the control group （P＜0.05）. After treatment， the EHRA atrial fibrillation symptom severity in the test group showed significant improvement， and the improvement in atrial fibrillation symptoms was superior to that in the control group （P＜0.01or P＜0.05）. No significant abnormalities were observed in safety indicators， and no adverse events occurred during the trial. ConclusionTLF as an adjunctive therapy can reduce AF burden， enhance the conversion rate of AF， decrease the frequency and duration of episodes， and improve clinical symptoms in patients with paroxysmal atrial fibrillation presenting with phlegm-heat harassing the interior syndrome， with a favorable safety profile.

ObjectiveBased on the zebrafish model， the hepatotoxicity and anti-osteoporotic activity of evodiamine （EVO） were studied. The mechanism of EVO in treating osteoporosis was explored by using network pharmacology and real-time polymerase chain reaction（Real-time PCR）. MethodsThree days after fertilization （3 dpf）， zebrafish were randomly selected and exposed to different concentrations of EVO solution for 96 hours. The mortality rate of zebrafish at different concentrations was calculated at the exposure endpoint， and a "dose-toxicity" curve was drawn. The 10% lethal concentration （LC₁₀） was calculated. Liver phenotype， acridine orange staining， and pathological tissue sections of liver-transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP））］ were used to confirm hepatotoxicity of EVO. On this basis， prednisolone was used to create a model of osteoporosis in zebrafish. The skull development， area of the skull stained by alizarin red， and cumulative optical density were used as indicators to evaluate the anti-osteoporotic activity of EVO in a safe dose. Based on network pharmacology， the mechanism of action of EVO in the treatment of osteoporosis was predicted and verified through Real-time PCR. ResultsThe LC₁₀ of EVO on zebrafish （7 dpf） was determined to be 0.4 mg·L^-1. Compared with the control group， sublethal concentrations （10=0.36 mg·L^-1 and 1/2LC₁₀=0.18 mg·L^-1） significantly decreased the fluorescence area of zebrafish liver （P<0.05，P<0.01） and increased the number of liver cell apoptosis. The arrangement of liver tissue was disordered and loose， and the vacuole was obvious， especially in the 0.36 mg·L^-1 group. Compared with the control group， under safe dose conditions， 0.08 and 0.02 mg·L^-1 of EVO had no significant effect on the liver. Prednisolone administration significantly reduced the mineralization area and cumulative optical density of zebrafish skulls （P<0.01） compared with the control group. The mineralization area and cumulative optical density of zebrafish skulls in the 0.08 and 0.02 mg·L^-1 groups of EVO were significantly increased compared with the model group （P<0.01）. Network pharmacology prediction suggested that EVO may regulate key targets such as avian sarcoma viral oncogene homolog （SRC）， signal transducer and activator of transcription 3 （STAT3）， interleukin-8 （CXCL8） and tyrosine kinase receptor 2 （ERBB2） to regulate signaling pathways related to lipid and atherosclerosis in diabetic complications， as well as the regulation of inflammatory mediators of tryptophan （TRP） channels. Real-time PCR experiment results indicated that EVO could regulate the above-mentioned targets， as well as genes related to osteoblasts and osteoclasts. ConclusionExcessive doses of EVO can lead to hepatotoxicity in zebrafish. Under safe dosage conditions， EVO can regulate relevant targets to exert anti-osteoporotic activity， providing a reference for the clinical safe use of EVO and ideas for the development of new drugs for osteoporosis.

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.

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.

Objective:To investigate the effects of CO2 intracavitary laser combined with pelvic floor magnetic stimulation on surface electromyography(sEMG)values and pelvic floor three-dimensional ultrasound parameters in female patients with stress urinary incontinence(SUI).Methods:A prospective study was conducted on 92 female SUI patients treated at the outpatient department of Meizhou People's Hospital from October 2021 to July 2023.The patients were randomly divided into an observation group and a control group(n=46 each)using a random number table.Both groups received home-based pelvic floor muscle training.The control group additionally received pelvic floor magnetic stimulation,while the observation group was treated with CO2 intracavitary laser combined with pelvic floor magnetic stimulation.The urinary leakage status,treatment efficacy,pelvic floor muscle sEMG,pelvic floor three-dimensional ultrasound parameters,quality of life,and sexual quality of life were compared between the two groups.Assessments included the International Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF),the Incontinence Impact Questionnaire-Short Form(IIQ-7),and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire(PISQ-12).Results:1-hour leakage volume:0 g(observation group)vs.3 g(control group),24-hour leakage episodes:0 times(observation group)vs.0 times(control group),the observed differences were statistically significant(Z=-2.866,-2.355,P<0.05).Total effective rate:95.65%(observation)vs.58.70%(control),the observed differences were statistically significant(x2=4.083,P<0.05).Pelvic floor muscle sEMG(after treatment):Maximal fast contraction:(40.78±3.28)μV(observation)vs.(35.17±5.10)μV(control),Mean tonic contraction:(31.56±4.20)μV(observation)vs.(25.87±3.82)μV(control),Mean endurance contraction:(29.34±2.58)μV(observation)vs.(25.37±2.67)μV(control),all differences between the two groups were statistically significant(t=2.736,19.919,3.025,15.426,P<0.05).After treatment,both groups showed reductions in bladder neck descent(BND)during Valsalva maneuver,bladder-symphysis distance(BSD),urethral rotation angle(URA),and posterior vesicourethral angle(RVA).However,the observation group demonstrated significantly greater reductions compared to the control group(post-treatment data:observation group(24.30±3.21)mm,(2.34±0.23)mm,(56.40±5.87)°,(89.54±9.21)°;control group(26.21±3.48)mm,(3.57±0.35)mm,(60.29±6.45)°,(126.71±13.50)°.These differences were statistically significant(t=2.736,19.919,3.025,15.426,P<0.05).Similarly,both groups exhibited decreased scores on the ICIQ-SF and IIQ-7 scales,along with increased scores on the PISQ-12.Again,the observation group showed superior improvement,with statistically significant differences(t=11.478,13.168,6.631,P<0.05).Conclusion:On the basis of pelvic floor muscle training,CO2 intracavitary laser therapy combined with pelvic floor magnetic stimulation can effectively alleviate urinary incontinence symptoms in patients with female stress urinary incontinence(FSUI),enhance therapeutic efficacy,improve pelvic floor muscle strength and the stability of pelvic support structures,and promote quality of life and sexual function.

A child aged 5 years with pulmonary arterial hypertension was admitted to the First Affiliated Hospital of Xiamen University in December 2017. A truncated mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene [Chr2(GRCh37):g.203395656delA] was detected, which might be responsible for the disease and the diagnosis of hereditary pulmonary arterial hypertension (HPAH) was confirmed. Genetic testing revealed that the child′s father also carried the same mutation in BMPR2 gene, but no gene mutation was detected in child′s mother and young brother; however, no HPAH was developed in child′s father and other family members. The child was treated with targeted drugs for pulmonary arteries with poor response, and died in April 2019. Later, the child′s mother accidentally became pregnant. Gene sequencing test of the amniotic fluid showed that the fetus also carried the BMPR2 gene mutation; the pregnancy was terminated after genetic counseling. HPAH has the clinical characteristics of early onset, rapid progression, and poor prognosis, and the BMPR2 gene mutation is an important pathogenic factor. For HPAH patients with unknown etiology, particularly for pediatric patients, genetic testing is recommended to identify the cause and to make an appropriate clinical management plan.