Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

Objective To evaluate the position of the talus on the axial images of magnetic resonance imaging(MRI)of the ankle joint in patients with chronic ankle instability(CAI)and to identify the indirect signs for diagnosing CAI.Methods Fifty patients hospitalized in our hospital between January 1,2021 and July 1,2023 for chronic ankle instability(CAI)were selected into the experimental group,while 50 counterparts treated in our hospital for other diseases were chosen into the control group.The basic information of both groups was recorded.The internal measurement tools of the Picture Ar-chiving and Communication System(PACS)were used to measure the malleolar talus index(MTI)and two new measurement methods:talus movement index(TMI)and talus comprehensive index(TCI)on the axial images of ankle MRI to evaluate the position of the talus in the ankle mortise.Sta-tistical analysis was then performed.Results There was no significant difference between the two groups in terms of age,sex ratio,affected side ratio,height,weight and body mass index(BMI)(P>0.05).Compared with the control group,the MTI(86.56°±3.54° vs.85.28°±2.77°,P<0.05),TMI(2.00°±2.36° vs.-2.00°±2.54°,P<0.001)and TCI(4.70°±2.98° vs.1.90°±2.01°,P<0.001)of the experi-mental group increased.The area under the ROC curve of TMI and TCI was 0.841 and 0.794,respec-tively.The optimal cut-off points for diagnosing CAI based on TMI and TCI were 0.5° and 4.5°,re-spectively.Conclusion Patients with CAI show changes in the bony structure of the ankle joint.Specifi-cally,on the axial MRI images of the ankle joint,there are simultaneous posterior displacement and internal rotation of the talus,which may be an indirect sign for the diagnosis of CAI.

This study investigated the drug resistance and genetic relationships among strains co-existing in animals,the environ-ment,and the living quarters of employees at large-scale pig farms in certain regions of Shandong Province,to provide a scientific ba-sis for elucidating the transmission mechanisms of drug-resistant bacteria through bacterial traceability analysis.Samples were col-lected from two pig farms,and bacteria were isolated and purified.The species of the isolated strains were identified via 16S rRNA gene sequencing.Antimicrobial susceptibility testing was conducted with a VITEK-2 Compact system and the disk diffusion method for strains present in pigs,the environment,and living areas.Furthermore,whole-genome sequencing was performed on the Illumina Miniseq platform to annotate drug resistance genes,and multilocus sequence typing(MLST)and core genome single nucleotide poly-morphism(cgSNP)analyses were used to trace the resistant strains.Three species—Staphylococcus aureus,Pseudomonas aeruginosa,and Bacillus cereus—were isolated and cultured from animals,the environment,and employee living areas,and their distributions were analyzed.These strains exhibited diverse drug resistance spectra and genetic diversity.Additionally,the strains displayed highly consistent resistance profiles,resistance genes,ST types,and SNP loci in pig urine,soil both inside and outside the facility,human drinking water,and the cafeteria and dormitories.Our findings indicated a potential risk of transmission of opportunistic pathogens be-tween the pig farming area and the living quarters.Particular attention should be paid to the environmental transmission of methicillin-resistant Staphylococcus aureus.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

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.

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To compare the blood flow perfusion area in different retinal vascular plexuses between adults and children using swept-source optical coherence tomography angiography(SS-OCTA)and explore the correlation of the retinal blood flow perfusion area with spherical equivalent(SE)and axial length(AL).Methods A total of 112 partici-pants,including 58 children(116 eyes,aged 8-13 years)and 54 adults(108 eyes,aged 18-30 years),were recruited from Eye Hospital,Wenzhou Medical University from December 2020 to December 2024.Based on SE,these children and adults were further divided into the emmetropia(-0.50＜SE ≤+0.50 D),low myopia(-3.00＜SE≤-0.50 D),and moderate myopia(-6.00＜SE≤-3.00 D)groups.SS-OCTA was used to acquire the perfusion area data across retinal vascular layers.The inner vascular network of the retina was subdivided into the peripapillary radial vascular network,su-perficial vascular plexus(SVP),middle vascular plexus(MVP),and deep vascular plexus(DVP).The blood flow perfu-sion areas across retinal vascular layers were compared between adults and children.Pearson correlation analysis was per-formed to assess the correlation of the blood flow perfusion areas across retinal vascular layers with AL and SE in adults and children,respectively.Results SE was negatively correlated with AL in both adults and children(r=-0.781 and-0.667,respectively;both P＜0.001).The total inner retinal perfusion area was negatively correlated with AL in both adults and children(r=-0.239 and-0.299,respectively;both P＜0.05).In children,the perfusion area in the peripapil-lary radial vascular network,SVP,and DVP was negatively correlated with AL(r=-0.443,-0.315,and-0.220,respec-tively;all P＜0.05).In adults,the perfusion area in SVP,MVP,and DVP was negatively correlated with AL(r=-0.243,-0.230,and-0.364,respectively;all P＜0.05).Adults with low/moderate myopia exhibited a significantly larger perfu-sion area in the peripapillary radial vascular network compared with children with corresponding myopia levels,and the differences were statistically significant(both P＜0.001).Conclusion There were significant differences in the perfu-sion area of the peripapillary radial vascular network between adult and pediatric myopic patients.AL showed the strongest correlations with the perfusion area of the peripapillary radial vascular network in adults and the perfusion area of DVP in children,respectively,suggesting distinct effects of retinal vascular layers at different stages of ocular growth.

Objective: To analyze the correlation between the levels of vitamin A, vitamin D, vitamin E with body fat mass percentage(FMP) as well as lifestyle factors among primary school students, so as to provide references for exploring the vitamin nutritional status of primary school students and its potential influencing factors. Methods: From September 1 to October 30, 2021, a cluster sampling method was used to select 750 thirdgrade students from eight primary schools in Luohu District, Shenzhen. Their body composition was measured, and blood samples were collected to detect the serum levels of vitamin A, vitamin D, and vitamin E using a mass spectrometer. Dietary and exercise habits were collected through questionnaires. Mann-Whitney U test and Kruskal-Wallis H rank sum test were used for inter group comparisons, spearman correlation was used for correlation analysis,and Logistic regression model was used to analyze the association between lifestyle and vitamin content. Results: The overall level of vitamin A in school aged children was 0.4 (0.4, 0.5) mg/L, with a deficiency rate of 0 and a marginal deficiency rate of 5.1%; the level of vitamin D was 26.0 (22.0, 30.0) ng/mL, with a deficiency rate of 0.4% and an insufficiency rate of 12.7%; the content of vitamin E was 11.8 (10.1, 13.5) mg/L, with an insufficiency rate of 0.8%. Spearman correlation analysis showed that vitamin A was positively correlated with FMP in the total population, boys, girls, and normal weight population ( r =0.18, 0.18, 0.20, 0.10), and vitamin D was positively correlated with FMP in the total population and obese population ( r =0.08,0.16)(all P <0.05). Logistic regression analysis showed that marginal deficiency of vitamin A was associated with consumption of animal, snack, and dairy/egg/bean foods ( OR =0.45, 0.55, 0.59); whether vitamin D was deficient was influenced by gender ( OR =2.65) and exercise ( OR = 1.96 ) (all P <0.05). Conclusion Vitamin A, vitamin D and vitamin E levels are associated with body fat percentage, with significant variations in vitamin status among individuals of different body types, necessitating targeted supplementation.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome