The Golgi body, a core organelle in eukaryotic cells, plays a critical role in protein modification, sorting, vesicular transport, and serves as a key site for lipid synthesis and glycosylation. Glucose and lipid metabolism are central processes for cellular energy maintenance and biosynthesis, and are closely linked to Golgi function. Recent studies have revealed the extensive involvement of the Golgi body in regulating glucose and lipid metabolism, where maintaining its structural and functional homeostasis is crucial for normal physiological activity. Under various stress conditions such as acidosis, hypoxia, and nutrient deficiency, the Golgi body undergoes structural and functional disruption, leading to Golgi stress. This in turn activates specific signaling pathways, such as those mediated by the cAMP-responsive element binding protein 3 (CREB3) and proteoglycans, to alleviate Golgi stress and enhance Golgi function. Golgi stress contributes to glucose and lipid metabolic disorders by affecting the activity of insulin receptors, glucose transporters, and lipid metabolism-related enzymes. For example, Golgi stress triggers the cleavage and release of the active fragment of CREB3, which enters the nucleus and upregulates the transcription of ADP-ribosylation factor 4 (ARF4) and key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). ARF4 promotes vesicle retrograde transport between the Golgi and endoplasmic reticulum, maintains secretory capacity, and enhances hepatic glucose output. This pathway is particularly active under high-fat or lipotoxic stress, leading to fasting hyperglycemia. When damaged Golgi components accumulate beyond a tolerable threshold, the cell initiates an autophagic response, selectively encapsulating the damaged Golgi into autophagosomes, which then fuse with lysosomes to form autolysosomes, leading to Golgiphagy. This process results in the degradation and clearance of damaged Golgi, thereby regulating Golgi quantity, quality, and function. Golgiphagy also plays a significant role in regulating glucose and lipid metabolism. For instance, under high-glucose conditions, autophagic flux may be suppressed, impairing the timely clearance and renewal of damaged Golgi, compromising its normal function, and further exacerbating glucose metabolism disorders. Additionally, Golgiphagy may participate in lipid degradation and influence lipid synthesis and transport. Research indicates that Golgi stress and Golgiphagy play important roles in glucose and lipid metabolism-related diseases. For example, the leucine zipper protein (LZIP) under Golgi stress conditions can promote hepatic steatosis. In mouse primary cells and human tissues, LZIP induces the expression of apolipoprotein A-IV (APOA4), which increases peripheral free fatty acid uptake, resulting in lipid accumulation in the liver and contributing to the development of fatty liver disease. This review systematically outlines the structure and function of the Golgi apparatus, the molecular regulatory mechanisms of Golgi stress and Golgiphagy, and their synergistic roles. It further elaborates on how Golgi stress and Golgiphagy participate in the regulation of glucose and lipid metabolism, discusses their clinical significance in related diseases such as diabetes, fatty liver disease, and obesity, and highlights potential novel therapeutic strategies from the perspective of Golgi-targeted medicine. Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.

The Golgi body, a core organelle in eukaryotic cells, plays a critical role in protein modification, sorting, vesicular transport, and serves as a key site for lipid synthesis and glycosylation. Glucose and lipid metabolism are central processes for cellular energy maintenance and biosynthesis, and are closely linked to Golgi function. Recent studies have revealed the extensive involvement of the Golgi body in regulating glucose and lipid metabolism, where maintaining its structural and functional homeostasis is crucial for normal physiological activity. Under various stress conditions such as acidosis, hypoxia, and nutrient deficiency, the Golgi body undergoes structural and functional disruption, leading to Golgi stress. This in turn activates specific signaling pathways, such as those mediated by the cAMP-responsive element binding protein 3 (CREB3) and proteoglycans, to alleviate Golgi stress and enhance Golgi function. Golgi stress contributes to glucose and lipid metabolic disorders by affecting the activity of insulin receptors, glucose transporters, and lipid metabolism-related enzymes. For example, Golgi stress triggers the cleavage and release of the active fragment of CREB3, which enters the nucleus and upregulates the transcription of ADP-ribosylation factor 4 (ARF4) and key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). ARF4 promotes vesicle retrograde transport between the Golgi and endoplasmic reticulum, maintains secretory capacity, and enhances hepatic glucose output. This pathway is particularly active under high-fat or lipotoxic stress, leading to fasting hyperglycemia. When damaged Golgi components accumulate beyond a tolerable threshold, the cell initiates an autophagic response, selectively encapsulating the damaged Golgi into autophagosomes, which then fuse with lysosomes to form autolysosomes, leading to Golgiphagy. This process results in the degradation and clearance of damaged Golgi, thereby regulating Golgi quantity, quality, and function. Golgiphagy also plays a significant role in regulating glucose and lipid metabolism. For instance, under high-glucose conditions, autophagic flux may be suppressed, impairing the timely clearance and renewal of damaged Golgi, compromising its normal function, and further exacerbating glucose metabolism disorders. Additionally, Golgiphagy may participate in lipid degradation and influence lipid synthesis and transport. Research indicates that Golgi stress and Golgiphagy play important roles in glucose and lipid metabolism-related diseases. For example, the leucine zipper protein (LZIP) under Golgi stress conditions can promote hepatic steatosis. In mouse primary cells and human tissues, LZIP induces the expression of apolipoprotein A-IV (APOA4), which increases peripheral free fatty acid uptake, resulting in lipid accumulation in the liver and contributing to the development of fatty liver disease. This review systematically outlines the structure and function of the Golgi apparatus, the molecular regulatory mechanisms of Golgi stress and Golgiphagy, and their synergistic roles. It further elaborates on how Golgi stress and Golgiphagy participate in the regulation of glucose and lipid metabolism, discusses their clinical significance in related diseases such as diabetes, fatty liver disease, and obesity, and highlights potential novel therapeutic strategies from the perspective of Golgi-targeted medicine. Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective To systematically evaluate the efficacy and safety of single-port thoracoscopic surgery (SPTS) in the treatment of spontaneous pneumothorax. Methods Computer searches were conducted in PubMed, The Cochrane Library, Web of Science, Embase, CNKI, WanFang, and the Chinese Medical Association databases to collect randomized controlled trials (RCTs) and cohort studies on the comparison of efficacy and safety of SPTS and three-port thoracoscopic surgery (TPTS) for the treatment of spontaneous pneumothorax from their inception to March 2024. The Cochrane RCT bias risk assessment tool and the Newcastle-Ottawa Scale (NOS) were used to assess the quality of RCTs and cohort studies, respectively. Meta-analysis was performed using RevMan 5.4.1. Results A total of 68 studies were included, comprising 23 RCTs and 45 cohort studies with a total of 5403 patients. The NOS scores of the cohort studies were 7-8 points. Meta-analysis results showed that compared with TPTS, SPTS had less intraoperative blood loss [SMD=−1.58, 95%CI (−1.93, −1.22), P<0.001], shorter postoperative hospital stay [SMD=−1.05, 95%CI (−1.29, −0.82), P<0.001], shorter postoperative drainage tube placement time [SMD=−0.75, 95%CI (−1.00, −0.50), P<0.001], fewer postoperative complications [OR=0.34, 95%CI (0.26, 0.45), P<0.001], fewer postoperative recurrences [OR=0.48, 95%CI (0.32, 0.72), P<0.001], and less pain at 24, 48, and 72 h postoperatively [SMD=−1.71, 95%CI (−2.13, −1.30), P<0.001; SMD=−1.70, 95%CI (−2.35, −1.06), P<0.001; SMD=−1.72, 95%CI (−2.16, −1.29), P<0.001]. Conclusion SPTS is safe and effective in the treatment of spontaneous pneumothorax with high clinical value and can be further promoted in clinical practice. Considering the limitations in the number and quality of included studies, researches with larger sample sizes and higher quality are needed to validate the above conclusions.

ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.

ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective:To explore the association between sleep and myopia among students aged 6-15 years in Tianjin.Methods:A cross-sectional study was conducted.A total of 218 864 primary and secondary school students aged 6-15 years in Tianjin were recruited from January 2023 to May 2023.Basic information and responses to the Children's Sleep Habits Questionnaire (CSHQ) were collected.Logistic regression models were used to assess the association between myopia and sleep.The study followed the Declaration of Helsinki, and the research protocol was approved by the Medical Ethics Committee of Tianjin Medical University Eye Hospital (No.ChiCTR2200065710). All questionnaires and demographic information were collected with parental consent.Results:It was found that 68 121(31.12%) students were myopic and 178 514(81.56%) had sleep disorders.The prevalence of myopia among students with average daily sleep durations of ≤8 hours, >8-9 hours, >9-10 hours, and >10 hours was 52.17%(9 288/17 803), 35.35%(31 037/87 787), 25.18%(24 481/97 216), and 20.64% (3 315/16 058), respectively, and the difference was statistically significant ( χ2=6 835.649, P<0.001). After adjusting for sex, age, body mass index, and potential confounding factors, compared with students with average daily sleep duration of >10 hours, students with average daily sleep durations of ≤8 hours ( OR=1.496, 95% CI: 1.415-1.581, P<0.001), >8-9 hours ( OR=1.364, 95% CI: 1.383-1.447, P<0.001), and >9-10 hours ( OR=1.257, 95% CI: 1.202-1.316, P<0.001) had a higher risk of myopia.Students with sleep disorders, bedtime resistance, sleep-onset delay, irregular sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness were more likely to be myopic. Conclusions:Sleep is a key factor influencing myopia among schoolchildren aged 6-15 years in Tianjin.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.