Objective:To explore the value of nomogram model based on multimodal ultrasound features for predicting the malignant risk of micro lesions in breast areola region.Methods:The case data of Beijing Tiantan Hospital affiliated to Capital Medical University from May 2020 to July 2024 were retrospectively analyzed. A total of 50 patients with benign intraductal papilloma（bIDP group）and 54 patients with malignant risk breast tumor（mrBT group）were found to have micro lesions in breast areola region and confirmed by puncture or surgical pathology. Clinical data，conventional ultrasound and contrast-enhanced ultrasound features were compared between the two groups. Multivariate Logistic regression analysis and Lasso regression analysis were performed on statistically significant factors to screen out influencing factors. ROC curves were plotted to evaluate diagnostic efficacy，nomogram model and clinical decision curves were constructed to evaluate clinical benefits.Results:The differences of age，nipple discharge presentation，conventional ultrasound features（including boundary，morphology，aspect ratio，internal echo，internal microcalcification，far-field echo，peripheral irregular hyperechoic ring，dilate of peripheral ducts），and contrast-enhanced ultrasound features（including wash-in time，enhancement intensity，enhancement mode，enhancement scope，blood perfusion defect，crab foot sign，penetrating vessels）were statistically significant between the bIDP group and mrBTgroup（all P<0.05）. Regression analysis showed that age，uniformity of internal echo within the lesion，dilation of surrounding ducts，and enhanced crab foot sign were the affect factors for the diagnosis of mrBT（all P<0.05）. Based on these factors，a nomogram model was constructed with an area under ROC curve（AUC）of 0.907（95% CI=0.851-0.963），a sensitivity of 0.907，and a specificity of 0.780. The decision curve analysis showed that the collective model had good predictive performance. Conclusions:The nomogram model based on multimodal ultrasound features has good value in predicting malignant risk micro breast tumor of areola region.

Objective:To establish a method for the rapid detection of varicella-zoster virus (VZV) by recombinase-aid amplification (RAA) combined with Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system.Methods:Clinical samples of suspected herpes zoster in Shandong province and Shanghai from 2023 to 2024 were collected, nucleic acids of positive samples were extracted, RAA-specific primers and crRNA (CRISPR RNA, crRNA) were designed for the conserved region of VZV, and the fluorescence intensity generated by Cas12a non-specific cleavage of single-stranded fluorescent probes was used to screen highly sensitive crRNAs and optimize the concentrations of crRNA, Cas12a and ssDNA probes. The sensitivity and reproducibility of the RAA-CRISPR/Cas12a detection method were evaluated by using synthesized plasmids and clinical samples, and the specificity of the method was evaluated by using other viral nucleic acids. The method was used to detect clinical samples by using the method and quantitative real-time PCR (qPCR) method, and the detection rate and consistency of the two method were compared.Results:The highly sensitive crRNA-4 was screened from the four crRNAs designed, and a VZV detection method for RAA-CRISPR/CAS12a based on fluorescence intensity measurement was established, which could be detected at 37℃ in 45 min, and the sensitivity of the detection could reach 10 copies/μL, a minimum clinical sample with a Ct value of 38.980 can be detected. It has high specificity and no cross-reactivity with Adenovirus 7, Herpes simplex virus type I, Herpes simplex virus type II, Coxsackieviruses A16, Cytomegalovirus, Epstein-Barr virus, Measles virus, Mumps virus, Enterovirus 71, Japanese encephalitis virus genotype 5. It has good stability, and can be successfully detected in low, medium and high concentrations of viral positive plasmids with good consistency. The detection rate of the clinically positive samples was 100%, which was completely consistent with the qPCR test result.Conclusions:RAA isothermal amplification technology combined with CRISPR-CAS12a technology was used to establish an accurate method for the detection of VZV virus, which was highly sensitive, specific, and had low requirements for experimental conditions, and could be completed within 45 min, which could provide strong technical support for the early detection of VZV.

Objective:To explore the impact of emotion regulation on learning engagement among nursing undergraduates and the mediating role of metacognition, aiming to provide a theoretical basis for developing interventions to enhance learning engagement.Methods:Using a convenience sampling method, a total of 212 nursing undergraduates from Yanbian University were recruited as study participants between October and November 2023. The Metacognitive Ability Scale for College Students, the Gross-John Emotion Regulation Questionnaire, and the Learning Engagement Scale were used for the survey. The Bootstrap method was applied to test the mediating effect of metacognition between emotion regulation and learning engagement.Results:A total of 212 questionnaires were distributed, and 204 valid questionnaires were recovered, with an effective response rate of 96.23% (204/212). The total scores for the Metacognitive Ability Scale for College Students, Gross-John Emotion Regulation Questionnaire, and Learning Engagement Scale were (76.51±7.92), (42.07±8.90), and (64.85±10.49), respectively. Emotion regulation positively predicted metacognition [ β=0.589, 95% CI (0.414, 0.722), P=0.001] and learning engagement [ β=0.310, 95% CI (0.098, 0.494), P=0.006]. Metacognition positively predicted learning engagement [ β=0.492, 95% CI (0.289, 0.690), P=0.001]. The Bootstrap results showed that metacognition partially mediated the relationship between emotion regulation and learning engagement, with a mediating effect value of 0.290, accounting for 48.33% (0.290/0.600) of the total effect. Conclusions:Emotion regulation not only directly influences learning engagement among nursing undergraduates but also indirectly affects their learning engagement through metacognition. Nursing educators and administrators should prioritize the development of emotion regulation and metacognitive abilities among nursing undergraduates to enhance their learning engagement.

Objective:To explore the impact of emotion regulation on learning engagement among nursing undergraduates and the mediating role of metacognition, aiming to provide a theoretical basis for developing interventions to enhance learning engagement.Methods:Using a convenience sampling method, a total of 212 nursing undergraduates from Yanbian University were recruited as study participants between October and November 2023. The Metacognitive Ability Scale for College Students, the Gross-John Emotion Regulation Questionnaire, and the Learning Engagement Scale were used for the survey. The Bootstrap method was applied to test the mediating effect of metacognition between emotion regulation and learning engagement.Results:A total of 212 questionnaires were distributed, and 204 valid questionnaires were recovered, with an effective response rate of 96.23% (204/212). The total scores for the Metacognitive Ability Scale for College Students, Gross-John Emotion Regulation Questionnaire, and Learning Engagement Scale were (76.51±7.92), (42.07±8.90), and (64.85±10.49), respectively. Emotion regulation positively predicted metacognition [ β=0.589, 95% CI (0.414, 0.722), P=0.001] and learning engagement [ β=0.310, 95% CI (0.098, 0.494), P=0.006]. Metacognition positively predicted learning engagement [ β=0.492, 95% CI (0.289, 0.690), P=0.001]. The Bootstrap results showed that metacognition partially mediated the relationship between emotion regulation and learning engagement, with a mediating effect value of 0.290, accounting for 48.33% (0.290/0.600) of the total effect. Conclusions:Emotion regulation not only directly influences learning engagement among nursing undergraduates but also indirectly affects their learning engagement through metacognition. Nursing educators and administrators should prioritize the development of emotion regulation and metacognitive abilities among nursing undergraduates to enhance their learning engagement.

Objective:To establish a method for the rapid detection of varicella-zoster virus (VZV) by recombinase-aid amplification (RAA) combined with Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system.Methods:Clinical samples of suspected herpes zoster in Shandong province and Shanghai from 2023 to 2024 were collected, nucleic acids of positive samples were extracted, RAA-specific primers and crRNA (CRISPR RNA, crRNA) were designed for the conserved region of VZV, and the fluorescence intensity generated by Cas12a non-specific cleavage of single-stranded fluorescent probes was used to screen highly sensitive crRNAs and optimize the concentrations of crRNA, Cas12a and ssDNA probes. The sensitivity and reproducibility of the RAA-CRISPR/Cas12a detection method were evaluated by using synthesized plasmids and clinical samples, and the specificity of the method was evaluated by using other viral nucleic acids. The method was used to detect clinical samples by using the method and quantitative real-time PCR (qPCR) method, and the detection rate and consistency of the two method were compared.Results:The highly sensitive crRNA-4 was screened from the four crRNAs designed, and a VZV detection method for RAA-CRISPR/CAS12a based on fluorescence intensity measurement was established, which could be detected at 37℃ in 45 min, and the sensitivity of the detection could reach 10 copies/μL, a minimum clinical sample with a Ct value of 38.980 can be detected. It has high specificity and no cross-reactivity with Adenovirus 7, Herpes simplex virus type I, Herpes simplex virus type II, Coxsackieviruses A16, Cytomegalovirus, Epstein-Barr virus, Measles virus, Mumps virus, Enterovirus 71, Japanese encephalitis virus genotype 5. It has good stability, and can be successfully detected in low, medium and high concentrations of viral positive plasmids with good consistency. The detection rate of the clinically positive samples was 100%, which was completely consistent with the qPCR test result.Conclusions:RAA isothermal amplification technology combined with CRISPR-CAS12a technology was used to establish an accurate method for the detection of VZV virus, which was highly sensitive, specific, and had low requirements for experimental conditions, and could be completed within 45 min, which could provide strong technical support for the early detection of VZV.

Objective:To explore the value of nomogram model based on multimodal ultrasound features for predicting the malignant risk of micro lesions in breast areola region.Methods:The case data of Beijing Tiantan Hospital affiliated to Capital Medical University from May 2020 to July 2024 were retrospectively analyzed. A total of 50 patients with benign intraductal papilloma（bIDP group）and 54 patients with malignant risk breast tumor（mrBT group）were found to have micro lesions in breast areola region and confirmed by puncture or surgical pathology. Clinical data，conventional ultrasound and contrast-enhanced ultrasound features were compared between the two groups. Multivariate Logistic regression analysis and Lasso regression analysis were performed on statistically significant factors to screen out influencing factors. ROC curves were plotted to evaluate diagnostic efficacy，nomogram model and clinical decision curves were constructed to evaluate clinical benefits.Results:The differences of age，nipple discharge presentation，conventional ultrasound features（including boundary，morphology，aspect ratio，internal echo，internal microcalcification，far-field echo，peripheral irregular hyperechoic ring，dilate of peripheral ducts），and contrast-enhanced ultrasound features（including wash-in time，enhancement intensity，enhancement mode，enhancement scope，blood perfusion defect，crab foot sign，penetrating vessels）were statistically significant between the bIDP group and mrBTgroup（all P<0.05）. Regression analysis showed that age，uniformity of internal echo within the lesion，dilation of surrounding ducts，and enhanced crab foot sign were the affect factors for the diagnosis of mrBT（all P<0.05）. Based on these factors，a nomogram model was constructed with an area under ROC curve（AUC）of 0.907（95% CI=0.851-0.963），a sensitivity of 0.907，and a specificity of 0.780. The decision curve analysis showed that the collective model had good predictive performance. Conclusions:The nomogram model based on multimodal ultrasound features has good value in predicting malignant risk micro breast tumor of areola region.

Objective: To investigate the second-hand smoke behavior at home among smokers, so as to provide the reference for developing home tobacco control strategies. Methods: Permanent residents who were smokers and at the ages of 15 years and above were sampled from 10 streets (townships) in Xuhui District, Shanghai Municipality using the multi-stage random sampling and population-size proportional sampling methods in 2022. Demographic information, smoking status, awareness of second-hand smoke hazards and second-hand smoke behavior at home were collected by questionnaire surveys. Factors affecting second-hand smoke behavior at home were identified using a multivariable logistic regression model. Results: A total of 1 024 smokers were surveyed, including 769 males (75.10%) and 255 females (24.90%). The awareness of hazards of second-hand smoke was 33.59%; the awareness rate of second-hand smoke causing lung cancer in adults was the highest at 76.76%, while the awareness rate of second-hand smoke leading to premature birth and low birth weight in newborns was the lowest at 39.45%. There were 459 smokers with second-hand smoke behavior at home, accounting for 44.82%. Multivariable logistic regression analysis showed that occupation (the retired, OR=2.320, 95%CI: 1.276-4.218), frequency of smoking (often, OR=5.722, 95%CI: 3.977-8.231), smoking duration (a year and above, OR=10.089, 95%CI: 5.508-18.480), electronic cigarette use (occasionally, OR=2.994, 95%CI: 1.283-6.986), living with pregnant women or infants (no, OR=2.171, 95%CI: 1.367-3.448), family indoor smoking restrictions (no restriction, OR=13.926, 95%CI: 7.538-25.727) and awareness of second-hand smoke hazards (unknown, OR=1.562, 95%CI: 1.067-2.287) were the influencing factors for second-hand smoke behavior at home. Conclusion There were 44.82% smokers in Xuhui District with second-hand smoke behavior at home, which was influenced by occupation, living situation, smoking status, family indoor smoking restriction and awareness of second-hand smoke hazards.

Podophyllotoxin is an aryl naphthalene lignan-like secondary metabolite, which is widely existed in plants of the Podophyllum. It exhibits a broad spectrum of antitumor activity and holds significant clinical value as a medicinal natural product of plant origin. This review discusses podophyllotoxin from three aspects: plant distribution, biosynthesis and pharmacological effects. Distribution of podophyllotoxin in nature: Podophyllotoxin and its analogues are mainly found in 12 genera of three families, which are Berberidaceae, Linaceae and Cupressaceae, respectively. They are mostly distributed in East Asia and North America, especially in China, which is not only the diversity center of the Podophyllum, but also the distribution center. Among all these plants, the genera Dysosma and Sinopodophyllum are the focus of the relevant research. Biosynthesis of podophyllotoxin: In order to take the alleviation of the pressure of podophyllotoxin that is in short supply of natural resources, and to protect its existing resources, the biosynthesis of podophyllotoxin, especially synthetic biology, has gradually become a new direction of current research. Compared with chemical synthesis which has the shortcoming of low synthesis efficiency, high production cost and cumbersome steps, biosynthesis has a variety of advantages. It’s not limited by resources, easy to cultivate on a large scale and has fast production speed, low production cost and simple genetic manipulation, so there is a broader prospect for the exact purpose of biosynthetic development. The biosynthesis of podophyllotoxin is divided into four steps in general, including the synthesis of coniferyl alcohol, the synthesis of matairesinol, the synthesis of deoxypodophyllotoxin and the synthesis of podophyllotoxin. It requires various enzymes catalyzed during the synthesis process, such as pinoresinol-lariciresinol reductase(PLR), secoisolariciresinol dehydrogenase(SDH) and others. At present, by means of synthetic biology, heterologous production of natural drugs in microbial cell factories, the synthesis of the intermediate coniferyl alcohol has been achieved in Escherichia coli with an increased yield of (124.9±5.1)mg·L−1, and the concentration of (-)-pluviatolide was elevated to 137 mg·L−1. In addition, p-coumaric acid in Saccharomyces cerevisiae was obtained to 71.71 mg·L−1, and in a tobacco plant production chassis, highly purified (-)-deoxypodophyllotoxin was increased to 0.71 mg·g−1 (dry weight) after chromatographic separation. Overall, the utilization of biosynthesis can significantly increase the yield of podophyllotoxin and improve the research and production efficiency of anti-tumor drugs greatly, which brings a more effective strategy for the treatment of related diseases. The pharmacological activity of podophyllotoxin: Podophyllotoxin and its analogues have strong cytotoxicity and they exert good inhibitory effects on the proliferation of multifarious tumor cells, viruses and bacteria. So they are widely applied to the clinical treatment of various types of tumors, such as colorectal cancer, lung cancer, cervical cancer, hemangioma, breast cancer, esophageal cancer, etc. The molecular mechanism of its cancer treatment is mainly in the G1, G2/M to block the cell cycle to make drugs work. Meanwhile, podophyllotoxin has relatively significant toxic side effects and drawbacks that can’t be ignored as a drug with superior therapeutic effect on specific diseases, which tends to increase the risk of bone marrow suppression, chromosomal aberrations and so forth. In conclusion, this literature sums up the distribution of podophyll plants in China, making review of the biosynthetic steps, applications, and biological research of podophyllotoxin, and outlines the pharmacological activity of podophyllotoxin. It aims to set the foundation for the reasonable application of podophyllotoxin resources, the efficient synthesis of podophyllotoxin, and the development of Podophyllum drugs which are highly effective and low toxic. At the same time, this paper gives full play to the clinical medicinal value of podophyllotoxin, which has important influence and far-reaching significance in the treatment of malignant diseases, and promotes the modernization of traditional Chinese medicine.

Objective To observe the value of cardiac CT angiography(CCTA)for left atrial appendage closure(LAAC).Methods Twelve Labradors were enrolled and underwent LAAC.CCTA examinations were performed before and 7,45 and 90 days after LAAC,and the left atrial appendage(LAA)parameters before and post LAAC occluder compression ratio were recorded.Ninety days after LAAC,the dogs were euthanized for gross anatomical observation,micro CT imaging and pathological examination,and the value of CCTA for LAAC was analyzed.Results Based on CCTA before LAAC,LAA opening depth was(18.8±2.6)mm,the minimum diameter was(16.3±2.0)mm and the maximum diameter was(22.6±3.2)mm,so 28 mm diameter occluders were selected for LAAC.Seven,45 and 90 days after LAAC,no displacement of occluder,thrombi nor device leakage was found on CCTA,while no significant difference of compression ratio was found among different time points(P＞0.05),nor between those measured with CCTA and micro CT 90 days after LAAC(P＞0.05).Ninety days after LAAC,gross dissection revealed complete endothelialization of occlude in 11 dogs and incomplete endothelialization in 1 dog.Pathological examination showed that collagen fibers arranged neatly,with endothelial cells covering the surface,and no inflammatory cell infiltration was observed.Conclusion CCTA could be used to observe LAA and surrounding structures before LAAC,hence guiding to select appropriate occluder,evaluate occlusion effect and monitor complications of LAAC in dogs.

Objective To observe the drainage pathways of interstitial fluid(ISF)and substance clearance pattern in rat brain with fluorescence tracing imaging and treacer-based MRI.Methods Thirty-three male SD rats were randomly divided into fluorescence tracing group(F group,n=18)and treacer-based MRI group(MRI group,n=15),then further divided into thalamic,hippocampal and caudate nucleus subgroups,respectively.Evans blue was injected to rats in F group,and cardiac perfusion was performed after injection,then brain tissue was harvested,and frozen sections were made to observe the drainage pathways of IFS in different subgroups.MRI was performed on rats in MRI group before and after injection of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)to observe signal intensity in ROI of brain regions in different subgroups,the signal unit ratio was calculated,and the changing trend was explored.Results ISF in thalamus,hippocampus and caudate nucleus had different dominant drainage pathways,and the time of tracer reached to adjacent brain regions and whole brain in F group were different.In MRI group,within 4 h after injection of Gd-DTPA,there were differences in direction and clearance rate among tracer in thalamus,hippocampus and caudate nucleus,mainly manifesting as the tracer in thalamus and hippocampus drained to the ipsilateral cortex and lateral ventricle,while the tracer in the caudate nucleus diffused to the cortex and midbrain,and there were differences of the peak time of tracer signal among adjacent drainage brain regions.Conclusion Fluorescence and MR dual-mode imaging showed that there were differences in the dominant drainage pathways of IFS and clearance rates of small molecule substances among hypothalamus,hippocampus and caudate nucleus of rats.