Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Cancer is a serious global health problem and a major cause of human death. Conventional cancer treatments often run the risk of impairing vital organ functions. Anticancer peptides (ACPs) are considered to be one of the most promising therapeutic agents against common human cancers due to their small sizes, high specificity, and low toxicity. Since ACP recognition is highly limited to the laboratory, expensive, and time-consuming, we proposed pLM4ACP, a model for predicting ACPs based on machine learning and protein language models. In this model, the protein language model ProtT5 was used to extract the features of ACPs, and the extracted features were input into the support vector machine (SVM) classification algorithm for optimization and performance evaluation. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 0.763, F1-score of 0.767, Matthews correlation coefficient of 0.527, and area under the curve of 0.827 on the independent test set. This study constructs an efficient anticancer peptide prediction model based on protein language models, further advancing the application of artificial intelligence in the biomedical field and promoting the development of precision medicine and computational biology.
Machine Learning ; Antineoplastic Agents/chemistry* ; Humans ; Peptides/chemistry* ; Support Vector Machine ; Algorithms ; Computational Biology/methods* ; Neoplasms/drug therapy*

Objective To study the injury risk and fatigue status of firefighters with different training postures under load-bearing conditions to reduce the occurrence of physical injuries and occupational diseases.Methods First,a questionnaire was administered to investigate the training injury conditions of firefighters in a fire-rescue brigade.Considering the exercise fatigue factor,which accounts for the highest proportion of injury causes,lower back analysis,static strength analysis,fatigue analysis,comfort analysis,and other human factor analysis tools in Jack software were used to analyze four common firefighter water-shooting training postures.Training postures while climbing a five-storey building with loads and a hooked ladder were also simulated.Results Injury caused by exercise fatigue accounted for 69.8%of injuries and was the most important injury-causing factor.The risk of knee and ankle joint injuries increased in all four water-shooting postures.The comfort levels of the four water-shooting postures from high to low were shoulder,standing,kneeling,and lying postures.For the entire dynamic training process,while climbing the five-storey building with loads and climbing the hooked ladder,firefighters did not have an increased risk of lower back injury but had an increased risk of ankle and knee joint injuries.Conclusions Some training postures are uncomfortable for firefighters,and they experience body discomfort during firefighting training with loads,thereby increasing injury risk.These results provide scientific references for the prevention and reduction of firefighter training injuries,and the formulation of reasonable training plans and targeted protective measures.

ObjectiveTo provide technical support for the molecular surveillance of pathogenic bacteria strains carrying mobile colistin resistance-1 （mcr⁃1） gene isolate from inlet of wastewater treatment plants （WWTP）. MethodsThe Enterobacteriaceae strains carrying mcr⁃1 resistance gene isolate from inlet of WWTP during April 1 to June 30， 2023 in Shanghai were cultured on blood-rich and SS culture medium and were identified using a mass spectrometry analyzer. The mcr⁃1 gene and copy number were detected by real-time fluorescence quantitative PCR. Drug susceptibility test was performed by microbroth dilution method. The copy numbers of Escherichia coli carrying mcr⁃1 gene isolated from wastewater and human fecel were statistically analyzed by SPSS 25.0. ResultsA total of 14 strains carrying the mcr⁃1 gene were isolated from 49 WWTP samples， and the positive isolation rate was 28.6%， including 12 non-diarrheal E. coli strains and 2 Klebsiella pneumoniae strains. The drug susceptibility results showed that all 14 strains were multi-drug resistant bacteria. They were all sensitive to imipenem and tigecycline， but were ampicillin- and cefazolin-resistant. There was no significant difference in the copy number between human-sourced diarrheal E. coli and wastewater-sourced non-diarrheal E. coli （t=0.647， P>0.05）. ConclusionThe isolation and identification of strains carrying the mcr⁃1 gene from inlet of WWTP samples were firstly established in Shanghai. The multi-drug resistance among the isolated strains is severe. To effectively prevent and control the spread of colistin-resistant bacteria， more attention should be paid to the surveillance of mcr⁃1 gene.

The visual impairment and blindness caused by myopia have become a global burden, and the World Health Organization has included the prevention and control of myopia in the global program for preventing blindness. In China, the development of myopia is showing a trend with higher incidence, younger age, and higher refractive errors. Moving forward the port of prevention and control myopia has become an important strategy to address the current predicament. Premyopia refers to the stage in children where the refractive power is ≤+0.75 D and >-0.50 D, and there are multiple risk factors during this stage that can potentially lead to myopia. Currently, the incidence of premyopia and its transformation into myopia is high, and the key prevention and control measures include building a predictive model for the transformation of premyopia into myopia, emphasizing the reduction of exposure to risk factors, using low-concentration atropine eye drops, red light therapy, and optical defocus intervention. This article provides a comprehensive review of the current situation regarding the incidence of premyopia and its transformation into myopia, as well as the research progress on existing prevention and control measures, with the aim of providing relevant references for the prevention and control of myopia during the premyopia stage.

Objective:To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods:The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results:In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions:Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.

This study aims at developing a dataset for determining the presence of carotid artery plaques in ultrasound images,composed of 1761 ultrasound images from 1165 participants.A deep learning architecture that combines bilinear convolutional neural networks with residual neural networks,known as the single-input BCNN-ResNet model,was utilized to aid clinical doctors in diagnosing plaques using carotid ultrasound images.Following training,internal validation,and external validation,the model yielded an ROC AUC of 0.99(95%confidence interval:0.91 to 0.84)in internal validation and 0.95(95%confidence interval:0.96 to 0.94)in external validation,surpassing the ResNet-34 network model,which achieved an AUC of 0.98(95%confidence interval:0.99 to 0.95)in internal validation and 0.94(95%confidence interval:0.95 to 0.92)in external validation.Consequently,the single-input BCNN-ResNet network model has shown remarkable diagnostic capabilities and offers an innovative solution for the automatic detection of carotid artery plaques.

Objective:To explore the benefits of transradial diagnostic cerebral angiography in elderly patients and its correlation with morphometric parameters of the aortic arch.Methods:Clinical data and aortic arch CTA imaging parameters of patients who underwent cerebral angiography at the Department of Neurosurgery, Beijing Hospital, between May 2022 and April 2023 were retrospectively analyzed.The study aimed to compare the time taken for angiography via radial artery access in elderly patients versus younger patients, as well as via femoral artery access, and to evaluate the associated aortic arch morphology parameters.Results:A total of 101 patients' data were analyzed, with 67 males(66.3%)and an average age of 63.4±12.0 years.Among them, 69 patients(68.3%)were aged 60 and above.The arterial approach for 44 patients(43.6%)was radial, while 57 cases(56.4%)used the femoral artery approach.In the elderly group, 14 cases(20.6%), 31 cases(45.6%), and 23 cases(33.8%)had type Ⅲ aortic arch, respectively.For younger patients, 17 cases(53.1%), 12 cases(37.5%), and 3 cases(9.4%)fell into these categories.The distribution difference was statistically significant( χ2=12.765, P=0.002).Elderly patients had a larger aortic arch width angle compared to younger patients(106°±12°and 100°±12°, t=2.334, P=0.022).The time for whole-brain angiography via radial artery was shorter for elderly patients than via femoral artery(39.8±29.5 minutes and 52.2±28.4 minutes, respectively, t=1.845, P=0.070).In young patients, there was no significant time difference between the two approaches(42.3±30.4 minutes for radial artery and 34.6±11.2 minutes for femoral artery, t=1.026, P=0.313).In the type Ⅱ aortic arch group, the average times for transradial and transfemoral approaches were 38.1±21.7 minutes and 46.7±32.2 minutes, respectively( t=1.020, P=0.314).The average times for the type Ⅲ aortic arch group were 41.9±37.3 minutes and 48.9±20.7 minutes, respectively.Correlation analysis revealed a significant negative correlation between the duration of radial artery access and the distance from the origin of the innominate artery to the left subclavian artery(Pearson correlation coefficien( r=-0.372, P=0.014). Conclusions:In elderly patients, particularly those with type Ⅱ or Ⅲ aortic arch or a wide aortic arch, diagnostic cerebral angiography using transradial access is preferable to femoral access.The distance between the innominate artery and the left subclavian artery origin could impact the duration of the procedure.

Objective:This study introduces a novel approach utilizing a self-made drug delivery cannula implanted into the cerebellomedullary cistern(CMC)of rats to allow repeated administrations in conscious subjects.Methods:A self-made medication cannula is inserted through a drilled hole at the midpoint of the occipital crest of the rat's skull,de-scending along the inner wall of the occipital bone until reaching the CMC,and securing it in place with skull screws and self-curing resin.Lipopolysaccharide(LPS)is injected into the CMC to induce neuroinflammation,and the feasibility of this method is assessed using X-ray imaging,behavioral testing,and immunofluorescence staining.Results:The place-ment of the brain cannula was confirmed using X-ray film and pontamine sky blue staining.Rats in the LPS group exhib-ited a lower facial mechanical pain threshold compared to the Control group(P＜0.001),along with reduced residence time in the open field center(P＜0.01).Immunofluorescence staining revealed LPS-induced activation of caudal spinal trigeminal nucleus(SpVc)microglia.Conclusion:This method proves to be suitable for multiple administrations to the cerebellomedullary cistern of conscious rats,enabling the study of the SpVc's role in pain modulation.