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.

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.

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.

AIM: To evaluate the clinical efficacy of intense pulsed light(IPL)therapy in patients with primary Sjogren's syndrome-related dry eye(SS-DE).METHODS:In this prospective randomized trial, 82 cases(82 eyes)diagnosed with moderate-to-severe SS-DE at our hospital from January 2023 to December 2023 were selected. If both eyes meet the criteria, one eye will be randomly selected for inclusion, and if one eye meets the inclusion criteria, the eye will be selected for enrollment. They were randomly assigned to either an experiment group receiving dextran hydroxypropyl methylcellulose eye drops and 0.05% cyclosporine A eye drops plus IPL therapy, or a control group receiving dextran hydroxypropyl methylcellulose eye drops and 0.05% cyclosporine A eye drops. Ocular surface disease index(OSDI)score, tear meniscus height(TMH), noninvasive tear breakup time(NITBUT), meibomian gland loss score, Schirmer I test(SⅠt), corneal fluorescein staining(CFS)score, conjunctival lissamine green staining(CLGS)score, lipid layer thickness(LLT), blink frequency, corneal Langerhans cell density(CLCD)and complications of both groups were assessed at baseline and at 4, 8, and 12 wk after treatment.RESULTS:There were 6 cases lost to follow-up in the experiment group, with a missing rate of 14.6%, and 1 case was lost to follow-up in the control group, with a missing rate of 2.4%, and valid data were eventually obtained from 35 cases(35 eyes)in the experiment group and 40 cases(40 eyes)in the control group. Baseline parameters did not differ significantly between the two groups of patients(all P>0.05). At 4, 8 and 12 wk after treatment, both groups showed significant reductions in OSDI scores, CFS scores, CLGS score, blink frequency, and CLCD, while the reductions were significantly greater in the experiment group compared to the control group(all P<0.05). The experiment group also demonstrated significant increases in TMH, SⅠt, and NITBUT at 4, 8 and 12 wk after treatment, which were significantly greater than those observed in the control group(all P<0.05). No significant intergroup differences were observed in LLT, meibomian gland loss score in the experiment group at any time point(all P>0.05). Furthermore, no severe ocular or cutaneous complications were associated with IPL treatment.CONCLUSION:IPL significantly improves ocular signs and symptoms, enhances aqueous tear secretion, and reduces ocular surface inflammation in patients with SS-DE, with no significant adverse reactions observed.

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

OBJECTIVES: To explore the risk factors of feeding intolerance (FI) in critically ill children receiving enteral nutrition (EN) and to construct a prediction nomogram model for FI. METHODS: A retrospective study was conducted to collect data from critically ill children admitted to the Pediatric Intensive Care Unit of Xiangya Hospital, Central South University, between January 2015 and October 2020. The children were randomly divided into a training set (346 cases) and a validation set (147 cases). The training set was further divided into a tolerance group (216 cases) and an intolerance group (130 cases). Multivariate logistic regression analysis was used to screen for risk factors for FI in critically ill children receiving EN. A nomogram was constructed using R language, which was then validated on the validation set. The model's discrimination, calibration, and clinical net benefit were evaluated using receiver operating characteristic curves, calibration curves, and decision curves. RESULTS: Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition were identified as independent risk factors for FI in critically ill children receiving EN (P<0.05). Based on these factors, a nomogram prediction model for FI in critically ill children receiving EN was developed. The area under the receiver operating characteristic curve for the training set and validation set was 0.934 (95%CI: 0.906-0.963) and 0.852 (95%CI: 0.787-0.917), respectively, indicating good discrimination of the model. The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit (χ 2=12.559, P=0.128). Calibration curve and decision curve analyses suggested that the model has high predictive efficacy and clinical application value. CONCLUSIONS Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition are independent risk factors for FI in critically ill children receiving EN. The nomogram model developed based on these factors exhibits high predictive efficacy and clinical application value.
Humans ; Critical Illness ; Enteral Nutrition/adverse effects* ; Male ; Risk Factors ; Female ; Child, Preschool ; Infant ; Nomograms ; Retrospective Studies ; Child ; Logistic Models

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

BACKGROUND: Mild cognitive impairment (MCI) is common in atrial fibrillation (AF) patients and may develop earlier in those with multiple cardiovascular comorbidities, potentially impairing self-management and treatment adherence. This study aimed to characterize the prevalence and profile of MCI in AF patients, examine its associations with cardiovascular comorbidities, and assess how these comorbidities influence specific cognitive domains. METHODS: This cross-sectional study analyzed data from AF patients who underwent cognitive assessment between 2017 and 2021. Cognitive status was categorized as MCI or non-MCI based on the Montreal Cognitive Assessment. Associations between comorbidities and MCI were assessed by logistic regression, and cognitive domains were compared using the Mann-Whitney U test. RESULTS: Of 4136 AF patients (mean age: 64.7 ± 9.4 years, 64.7% male), 33.5% of patients had MCI. Among the AF patients, 31.2% of patients had coronary artery disease, 20.1% of patients had heart failure, and 18.1% of patients had hypertension. 88.7% of patients had left atrial enlargement, and 11.0% of patients had reduced left ventricular ejection fraction. Independent factors associated with higher MCI prevalence included older age (OR = 1.04, 95% CI: 1.03-1.05, P < 0.001), lower education level (OR = 1.51, 95% CI: 1.31-1.73, P < 0.001), hypertension (OR = 1.28, 95% CI: 1.07-1.52, P = 0.001), heart failure (OR = 1.24, 95% CI: 1.04-1.48, P = 0.020), and lower left ventricular ejection fraction (OR = 1.43, 95% CI: 1.04-1.98, P = 0.028). A higher CHA₂DS₂-VASc score (OR = 1.27, 95% CI: 1.22-1.33, P < 0.001; ≥ 2 points vs. < 2 points), and greater atherosclerotic cardiovascular disease burden (OR = 1.45, 95% CI: 1.02-2.08, P = 0.040; 2 types vs. 0 type) were linked to increased MCI risk. These above factors influenced various cognitive domains. CONCLUSIONS MCI is common in AF and closely associated with cardiovascular multimorbidity. Patients with multiple comorbidities are at higher risk, highlighting the importance of routine cognitive assessment to support self-management and integrated care.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding