OBJECTIVES: To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites. METHODS: Doxorubicin hydrochloride (DOX)-loaded liposomes (IEL-Lip/DOX) conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method. Two formulations [2-1P: Mol(PC): Mol(DPI)=100:1; 2-3P: 100:3] were prepared and their modification density and in vitro release characteristics were determined. Their targeting efficacy was assessed in a cell model of LPS-induced inflammation, a mouse model of acute lung injury (ALI), a rat femoral artery model of physical injury-induced inflammation, and a zebrafish model of local inflammation. RESULTS: The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm², respectively. Compared with unmodified liposomes, IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5. In the inflammation cell model, IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells, and 2-1P exhibited a higher trans-endothelial ability. In ALI mice, the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71% [Z-(2-1P)] and 93.41% [Z-(2-3P)], and 2-1P had an increased distribution by 24.19% in the inflammatory lung tissue compared to normal mouse lung tissue. In rat femoral artery models, 2-1P had greater injured/normal vessel fluorescence intensity contrast. In the zebrafish models, both 2-1P and 2-3P showed increased aggregation at the site of inflammation. CONCLUSIONS This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site, which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of "one drug for multiple diseases".
Animals ; Liposomes ; Rats ; Nanomedicine ; E-Selectin ; Drug Delivery Systems ; Inflammation/drug therapy* ; Mice ; Doxorubicin/analogs & derivatives* ; Zebrafish ; Acute Lung Injury/drug therapy*

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective: This study aimed to explore the psychiatric symptoms and associated risk and protective factors among religious adolescents after 2-month home confinement against coronavirus disease-2019 (COVID-19) in China. Methods: 11,603 Chinese adolescents in grades 7–9 were recruited in this survey. An online survey was designed to collect the data. Participants were measured using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 Scale. Results: Religious adolescents showed significantly more severe depressive and anxiety symptoms compared to non-religious. 249 (2.2%) reported COVID-19 exposure. Logistic regression analysis revealed that religiosity was a risk factor for the symptoms of depression (p=0.001) and anxiety (p<0.001). Moreover, among those adolescents with religious beliefs, psychological resilience was protective in preventing depressive and anxiety symptoms. At the same time, emotional abuse, emotional neglect, and a poor parent-child relationship were risk factors. Conclusion Our finding indicates that religious adolescents easily develop depressive and anxiety symptoms, compared to non-religious adolescents. Moreover, those with emotional abuse, emotional abuse, and poor parent-child relationships are more likely to suffer from mental distress and should pay more attention to cope with their mental health.

Objective:To investigate the value of MRI in diagnosing the high expression of transcription factor E2F2 in breast cancer, in order to further evaluate the biological aggressiveness of breast cancer.Methods:The study was cross-sectional. The clinical and imaging data of 92 patients with breast cancer who were pathologically diagnosed in the Second Affiliated Hospital of Nantong University from October 2014 to December 2020 were retrospectively analyzed. All patients were female, aged 32 to 82 (56±11) years. All patients underwent MRI, including T 1WI, T 2WI, diffusion-weighted imaging (DWI), and dynamic enhanced MRI. According to the immunohistochemical results, the patients were divided into E2F2 high expression group and E2F2 low expression group. Independent sample t test, Mann-Whitney U test or χ2 test were used to compare the clinical data, MRI features and pathological features of the two groups. Characteristics with P≤0.1 from univariate analyses were included in multivariate logistic regression to screen for independent risk factors predicting high expression of the transcription factor E2F2 in breast cancer. Results:Among 92 patients, 68 were in the high E2F2 expression group and 24 were in the low E2F2 expression group. There were significant differences between the two groups in peritumoral edema, type composition ratio of time-signal intensity curve, estrogen receptor expression, human epidermal growth factor receptor 2 expression, endovascular cancer embolus and molecular type composition ratio (all P<0.05). Multivariate logistic regression analysis showed that peritumoral edema alone ( OR=7.061, 95% CI 1.837—27.144, P=0.004) was an independent risk factor for predicting the high expression of transcription factor E2F2 in breast cancer. Conclusion:MRI show that peritumoral edema is an independent risk factor for predicting high expression of the breast cancer transcription factor E2F2, which is associated with the aggressiveness of breast cancer.

ObjectiveTo evaluate the effect of standardized blood pressure measurement in consulting room （SBPM） model on blood pressure screening of non-hypertensive patients in community. MethodsFour communities were randomly selected from Fengxian District of Shanghai， and non-hypertensive patients in the communities were included for screening. Based on the communities， participants were further classified into the intervention group and control group. A one-year intervention study was conducted from January 1， 2021 to December 31， 2021. The intervention group received the intervention measures of standardized measurement， and the control group remained the routine measurement. The distribution of blood pressure values and last digit of the values between the intervention group and control group were tested using Chi-square test and normality test. Then changes in abnormal blood pressure rate before and after the intervention were determined by double difference method. Statistical analysis was performed using SPSS 20.0. ResultsA total of 15 368 participants were included in the intervention group， and 19 811 participants in the control group. After the intervention， range of the last digit of blood pressure values in the intervention group was 9.55%‒10.41%， of which that of systolic and diastolic blood pressure were equally distributed （P=0.932 and 0.871， respectively）. The range of the last digit in the control group was 1.31%‒42.58%， of which that of systolic and diastolic blood pressure showed unequal distribution （P<0.001）. Through one-year standardized measurement intervention， the abnormal rate of blood pressure in the intervention group was 26.29%， which was 7.61 times as high as that in the control group （OR=7.55， 95%CI： 6.75‒8.57， P<0.001）. ConclusionStandardized blood pressure measurement in consulting room is suitable for the screening of blood pressure measurement in community， which has higher data quality than that of routine measurement.

Objective:To evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for treatment of duodenal lesions.Methods:A retrospective analysis was performed on the data of 45 patients with 46 duodenal lesions who underwent ESD at the Second Xiangya Hospital of Central South University from January 2011 to May 2019. The lesion features, en bloc resection rate, complete resection rate, complications, postoperative pathology and recurrence were assessed.Results:Among the 45 patients, 20 were males and 25 were females, with age of 52.0±11.8 years. Of the 46 lesions, 31 (67.4%) were located in the duodenal bulb, 12 (26.1%) in the descending part, and 3 (6.5%) at the junction of bulb and descending part. The diameter of the lesions was 2.4±1.9 cm. There were 14 (30.4%) lesions originated from mucosal layer, 29 (63.1%) from submucosal layer, and 3 (6.5%) from muscularis propria.Postoperative pathology showed 11 (23.9%) cases of Brunner gland tumors, 9 (19.6%) neuroendocrine tumors, 5 (10.9%) ectopic pancreas, 5 (10.9%) lipomas, and 16 (34.8%) other pathological patterns. All 45 patients with 46 lesions underwent ESD successfully, and the en bloc resection rate was 100.0% (46/46), complete resection rate was 91.3% (42/46). Intraoperative bleeding occurred in 1 case (2.2%), which was successfully treated by endoscopy. One (2.2%) delayed perforation occurred and was treated by surgical intervention. Electrocoagulation syndrome occurred in 1 case (2.2%), which was relieved after conservative medical therapy. Two cases received further surgery after ESD. The mean hospital stay was 6.2 days (ranged 2-21 days) and no death occurred. Forty-one cases were followed up for 1-78 months, with mean time of 30 months. During the follow-up period, local recurrence occurred in 1 patient (2.4%).Conclusion:ESD is an effective and safe treatment for duodenal lesions and has a good clinical practical value.

Simvastatin is one of the important prescription drugs for hypercholesterolemia. Monacolin J is a key intermediate during simvastatin synthesis, and also an intermediate of lovastatin biosynthesis. In this work, we construct a monacolin J producing strain via RNA interference to achieve one-step fermentation to obtain simvastatin. The lovF gene silencing plasmid pMHJ137 was constructed and transformed into Aspergillus terreus by Agrobacterium tumefaciens mediated transformation method. Precursor DMB-S-MMP was supplied during the fermentation to screen positive strains of transformants; which also further confirmed the simvastatin producing capability of MJ1-24 by one-step fermentation. Strain MJ1-24 produced monacolin J rather than lovastatin, and the feeding of DMB-S-MMP resulted in the generation of simvastatin. This study suggested that RNAi can efficiently silence the lovF gene of A. terreus and promote the simvastatin production by one-step fermentation.
3-Mercaptopropionic Acid ; analogs & derivatives ; Aspergillus ; chemistry ; genetics ; Fermentation ; Industrial Microbiology ; Naphthalenes ; chemistry ; RNA Interference ; Simvastatin ; chemistry