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 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.

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.

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.

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 analyze the results of the practice test and formal test of the annual professional proficiency test for residents in 2022, to investigate related influencing factors and the effectiveness of the practice test, and to propose the measures for improving the results of the annual professional proficiency test.Methods:The scores of the annual professional proficiency test were analyzed for 202 residents who participated in the test in 2022, and the data on sex, education background, type of personnel, whether they passed the medical licensing examination, and practice test scores were analyzed to investigate related influencing factors. SPSS 23.0 and GraphPad Prism 8 were used for the chi-square test, the t-test, the one-way of variance, and the Fisher's exact test. A multiple linear regression analysis was used to identify influencing factors, and a Pearson correlation analysis was also performed. Results:The scores of the annual professional proficiency test for 202 residents were normally distributed with the highest number of the residents with a score of 90-99 points and the lowest number of the residents with a score of <70 points. The residents who passed the medical licensing examination had a significantly higher score of the annual professional proficiency test than those who failed the examination ( t=2.87, P=0.005), and the residents who passed the three practice tests had a significantly higher score of the annual professional proficiency test than those who failed the practice tests ( P<0.05). The score of the second practice test, the score of the third practice test, and the passing of medical licensing examination were independent influencing factors for the score of annual professional proficiency test ( R2=0.236, R2=0.201, F=6.60, P<0.05). The correlation analysis showed that the scores of the three practice tests were positively correlated with the final score ( r=0.189, 0.373, and 0.311, P<0.05). Conclusions:Improving the passing rate of medical licensing examination and strengthening pre-examination practice tests can help to improve the score of annual professional proficiency test. At the same time, it is necessary to improve the quality of training through the measures such as strengthening the homogenization management of different types of students, improving the attention and enthusiasm of all levels, and accelerating the construction of question banks.

Objective:To investigate the application effect of case-based collaborative learning (CBCL) based on data-information-knowledge-wisdom (DKIW) model in the training of the informatization teaching ability of clinical teachers.Methods:From March to August in 2022, 71 clinical teachers from four grade A tertiary hospitals in Tianjin, China, were selected as subjects and were randomly divided into control group with 35 patients and experimental group with 36 patients using a random number table. The teachers in the control group received blended teaching online and offline, and those in the experimental group received CBCL teaching based on DIKW model. The two groups were compared in terms of theoretical assessment score, informatization teaching demonstration score, and informatization teaching ability score before and after intervention. SPSS 27.0 was used for the t-test and the Mann-Whitney U rank sum test. Results:Compared with the control group after intervention, the experimental group had significantly higher scores of theoretical assessment (83.50±3.11) and informatization teaching demonstration (84.19±1.89) ( P<0.05). After intervention, the control group had significant increases in the total score of informatization teaching ability (74.34±4.08) and the scores of each dimension (15.40±1.19, 19.29±1.62, 28.54±1.67, and 11.11±1.79), and the experimental group also had significant increases in the total score of informatization teaching ability (83.64±5.25) and the scores of each dimension (16.53±1.21, 20.94±1.98, 33.03±2.10, and 13.14±1.48); the experimental group had significantly higher scores than the control group ( P<0.05). Conclusions:The CBCL teaching model based on DIKW model can help to improve the comprehensive informatization teaching ability of clinical teachers.

Objective To predict the micro-level energy release rate in the rat femoral cortical bone and investigate the variation in the micro-level energy release rate with age.Methods Based on previous experimental data and numerical simulation of fracture modes for cortical bone,load-displacement curves and fracture modes measured by simulation and experiment were compared,and the micro-level energy release rates of rat femoral cortical bone at different months were predicted by back-calculation.Results It was predicted that the micro-level energy release rate of rat femoral cortical bone at 1-,3-,5-,7-,9-,11-,and 15-month age was 0.08-0.12,0.12-0.14,0.15-0.19,0.25-0.28,0.23-0.25,0.19-0.22,and 0.13-0.16 N/mm,respectively.Conclusions The decrease in the microlevel energy release rate with increasing age led to a decreasing failure load,indicating that the microlevel energy release rate is one of the main factors determining fracture occurrence;however,no significant decrease was observed at the time of fracture,indicating that the microlevel energy release rate was not linearly proportional to the fracture time.These results can help explain the mechanism of cortical bone fractures at the clinical level.