Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.

With the extensive application of low-dose ionizing radiation (LDIR) in medicine, aerospace, and other fields, the potential for exposure among the general population and occupationally exposed workers has increased, raising growing public health concerns regarding its possible effects on cognitive function. Current occupational and environmental radiation protection frameworks are primarily established based on cancer risk estimates derived from epidemiological evidence under high-dose exposure and extrapolation across dose ranges, whereas evidence regarding non-cancer outcomes, including potential cognitive effects of LDIR, remains limited and inconsistent, and the underlying neurobiological mechanisms have not been fully elucidated. This review summarized recent advances in research on the effects of LDIR on cognitive function and the associated neural mechanisms. Existing evidence indicates that LDIR may adversely affect cognitive domains including spatial memory and object recognition memory under certain exposure conditions, with potential mechanisms involving alterations in synaptic plasticity, microglia activation, neurodevelopmental processes, epigenetic regulation, and DNA damage and repair pathways. In contrast, studies using pathological models, including stroke and neurodegenerative diseases, have reported potential protective effects of LDIR, which may be mediated by attenuation of oxidative stress, neuroinflammation and activation of endogenous repair pathways. This indicates that LDIR has both damaging and protective effects on brain function; a deeper understanding of its patterns and mechanisms can provide a scientific basis for establishing occupational and environmental radiation protection standards. Furthermore, re-examining the LDIR risk assessment system may also offer new insights into exploring the therapeutic potential of LDIR for brain diseases.

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 evaluate the clinical efficacy of a sphincter-preserving technique combining cutting seton and loose seton drainage for the treatment of ischiorectal abscess.Methods A prospective ran-domized controlled trial was conducted involving 184 patients with ischiorectal abscess,who were randomly di-vided into an experimental group(n=92)and a control group(n=92).The experimental group underwent sphincter-preserving surgery combining cutting seton and loose seton drainage,while the control group re-ceived single-stage incision and seton drainage.Clinical outcomes,anal function,operative time,postoperative pain intensity,wound healing time,and pruritus ani were compared between the two groups.Results The sur-gical time of the experimental group was longer than that of the control group[31.50(25.00,40.00)min vs.20.00(20.00,30.00)min],and the difference was statistically significant(P<0.05).On postoperative days 1,3,and 7,the NRS scores for pain were lower than those in the control group,and the wound healing time was shorter than that in the control group[24.00(20.00,25.75)days vs.29.00(26.00,32.00)days],with statistically significant differences(P<0.05).The recent cure rate of the experimental group was lower than that of the control group(88.04%vs.94.57%),and the difference was not statistically significant(P>0.05).After follow-up,the long-term cure rate of the experimental group was lower than that of the control group(84.78%vs.93.48%),and the Wexner score for anal incontinence was lower than that of the control group[1.00(0.00,1.00)vs.1.00(0.00,2.00)],with statistically significant differences(P<0.05).Conclu-sion The sphincter-preserving technique combining cutting seton and loose seton drainage for ischiorectal ab-scess reduces postoperative pain,shortens wound healing time,and effectively protects anal function with reli-able short-term efficacy.However,further improvements are needed to enhance long-term clinical outcomes.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

The plants of the genus Caragana Fabr. are desert plants of the Leguminosae family, which are widely used in traditional ethnomedicine, with the effects of nourishing Yin and nourishing blood, dispelling wind and removing dampness, clearing heat and detoxifying toxins. The anti-inflammatory effect of Caragana Fabr. has attracted much attention, the research on the related mechanism has made some progress, but it lacks systematic collation. By summarising the anti-inflammatory effects of the active ingredients of Caragana Fabr., the authors found that they have good anti-inflammatory activities on different inflammatory cell models in vitro, and have good improvement effects on rheumatoid arthritis, colitis, complex nephritis, and acute lung injury and other disease models. The anti-inflammatory effects of the active components of this genus mainly include the reduction of the levels of a variety of pro-inflammatory factors, and the signalling pathways involved mainly include TLR4/NF-κB, TLR4/MAPK, TLR4/NF-κB/IRF3, JAK/STAT-1, ERK/STAT-1 and so on. Therefore, the paper mainly reviews the research progress on the anti-inflammatory effects and mechanisms of the Caragana Fabr. plants and their active components according to disease types, with a view to providing reference for the in-depth study of their anti-inflammatory activities and the development of new products with related functions.