Breast cancer is the most common malignant tumor among women, and early diagnosis, coupled with optimized treatment strategies is crucial for improving the prognosis. In recent years, with the advancement of nanotechnology, manganese-based nanomaterials have shown potential in various aspects of early breast cancer diagnosis, drug delivery, and tumor treatment. Compared to other nanomaterials, manganese-based nanomaterials exhibit excellent biocompatibility and have become a significant focus in the research of breast cancer diagnosis and treatment.

Objective:To solve the difficult problem of experimental teaching of MRI equipment by independently designing a virtual simulation teaching system for performance testing of medical magnetic resonance imaging (MRI) equipment.Methods:A total of 202 students of Batch 2016 majoring in 4-year medical imaging technology and 5-year medical imaging of Binzhou Medical University. According to the teaching requirements of MRI equipment in Medical Imaging Equipment Science, a 3D experimental simulation model and experimental scenes were established based on Unity3D engine by using Unity3D, 3D Studio Max, Maya and Visual Studio technology to design experimental learning content and assessment content, develop the teaching system software and perform Web-based online learning. Then, the satisfaction survey on experimental learning was conducted, the statistics of the experimental results of the teaching system on the national virtual simulation experiment teaching platform was collected and the learning effects were evaluated in multiple dimensions. Results:The virtual simulation teaching system was a comprehensive experiment with 12 knowledge points, 12 experimental items and a total of 81 interactive contents and steps. The overall satisfaction rate of 202 students in our school was 96.82%(2 347/2 424). Among the 499 subjects who participated in the learning of the teaching system on the national virtual simulation experiment teaching platform and submitted the experimental report, the average score of the experiment was 78.07 points (the full score of online learning assessment was 90 points), and the overall passing rate was 96.79%(483/499). The average learning time of the 18 students who got 90 points was 54 min.Conclusion:This virtual simulation teaching system possesses comprehensive experimental contents with high fidelity of experimental scenes and strong interactivity of experimental operation, prospecting great learning effects and promotion value.

Objective:To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.Methods:Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy (LVH) who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020, and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members. The cardiac phenotype was evaluated by electrocardiogram, coronary computed tomography angiography (CTA), echocardiography, and cardiac magnetic resonance imaging (MRI) as adjuncts.Results:All whole-exome gene were detected in 52 unrelated patients with LVH, of which 1 patient (1.9%) had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys (proband). Two members of the maternal line of this patient carried p.Glu1389Lys mutation, but there was no obvious clinical phenotype. Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia, but there was no LVH. The male proband, aged 21 years old, presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment, MRI showed that the left ventricular end diastolic diameter was 58 mm. After treatment with angiotensin receptor-enkephalinase inhibitor (ARNI), electrocardiogram showed that the heart rate increased significantly (from 43 bpm to 72 bpm). Echocardiography showed that the left ventricular end diastolic diameter decreased significantly (from 60 mm to 49 mm).Conclusions:The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease. MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia, but there is no LVH phenotype. The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene is more obvious. Asymptomatic LVH and sinus bradycardia can appear in adolescence, but the LVH phenotype can be reversed in a short period of time after ARNI treatment.

ObjectiveTo investigate the clinical significance of highly sensitive nucleic acid detection in precise antiviral therapy for patients with liver cirrhosis and its association with aminotransferase level. MethodsA total of 377 patients with hepatitis B cirrhosis who were hospitalized or attended the outpatient service from May 2013 to April 2019 were enrolled and tested by both domestic HBV DNA detection and highly sensitive Cobas HBV DNA detection. All patients underwent biochemical examination, four blood coagulation tests, routine blood test, and upper abdominal computed tomography or ultrasound. Sensitivity of different HBV DNA detection reagents was compared in liver cirrhosis patients with a low viral load, and the correlation between alanine aminotransferase (ALT) level and viral load was analyzed. The paired t-test was used for comparison of continuous data before and after treatment. The receiver operating characteristic (ROC) curve was used to screen out the optimal predictive values of ALT at different cut-off values of HBV DNA. ResultsAmong the 377 patients with hepatitis B cirrhosis, 215 tested positive and 162 tested negative by domestic HBV DNA, and among these 162 patients, 104 (64.2%) tested positive by Cobas HBV DNA detection, with a mean level of 267.5±42.3 IU/ml. After 24 weeks of antiviral therapy, the 104 patients with hepatitis B cirrhosis had significant improvements in viral replication level, ALT, and Child-Pugh score for liver function; HBV DNA decreased from 267.5±32.2 IU/ml before treatment to 59.6±7.7 IU/ml after treatment (t=3.486, P=0.002), ALT decreased from 871±10.8 U/L before treatment to 36.5±7.6 U/L after treatment (t=3.235, P=0.020), and the Child-Pugh score decreased from 6.5±0.7 before treatment to 5.7±0.5 after treatment (t=2.928, P=0.041). The ROC curve analysis of ALT in predicting HBV DNA decision point showed that an ALT level of 29 IU/L was the most sensitive cut-off value for predicting HBV DNA ＜20 IU/ml, with an area under the ROC curve of 0.904, a sensitivity of 1.0, and a specificity of 0.237. ConclusionPrecise detection helps to guarantee the precise clinical treatment of patients with hepatitis B cirrhosis and improve their treatment outcome and prognosis. An ALT level of 29 IU/L is a sensitive indicator for predicting patients with negative Cobas HBV DNA, so as to achieve individualized precise screening and treatment.

Objective To analyze the epidemic situation of inter-human brucellosis in Zhongwei City of Ningxia from 2005 to 2017,and to provide basis for making scientific and effective prevention and control measures of the disease.Methods Incidence data of brucellosis were collected in Zhongwei City from 2005 to 2017 and prevalence trends and distribution characteristics (place,time,and population distribution) were analyzed by descriptive epidemiological method.Results A total of 1 880 human brucellosis cases were reported in Zhongwei City from 2005 to 2017.The incidence of brucellosis in 2012 and 2015 was 5.03/100 000 and 61.80/100 000,which showed a dramatic and rapid ascent (x2trend =681.40,P ＜ 0.05),while after 2016,it showed a downward trend (xtrend =324.85,P ＜ 0.05),and in 2017 the reported incidence dropped to 25.13/100 000.Zhongning and Haiyuan Counties showed a high incidence from 2005 to 2017,and the incidence was 39.79％(748/1 880) and 36.06％ (678/1 880),respectively;April to September was the peak season;the sex ratio was 2.72:1.00 (1 375/505);1 379 cases (73.35％)occurred between 30 and 64 years old,and 1 616 cases (85.96％) occurred among farmer.Conclusion After 2016,the incidence of human outbreaks in Zhongwei City has declined;Zhongning and Haiyuan Counties are the key areas of morbidity;the key population for prevention and control is farmer.

With the development of liquid biopsy technology, plasma cell-free DNA (cfDNA) becomes one of the research hotspots. Whole-genome bisulfite sequencing of plasma cell-free DNA has shown great potential medical applications such as cancer detection. However, the practical stability evaluation is still lacking. In this study, plasma cell-free DNA samples from two volunteers at different time were collected and prepared for sequencing in multiple laboratories. The library preparation strategies include pre-bisulfite, post-bisulfite and regular whole-genome sequencing. We established a set of quality control references for plasma cell-free DNA sequencing data and evaluated practical stability of blood collection, DNA extraction, and library preparation and sequencing depth. This work provided a technical practice guide for the application of plasma cfDNA methylation sequencing for clinical applications.
Cell-Free Nucleic Acids ; DNA Methylation ; High-Throughput Nucleotide Sequencing ; Humans ; Sequence Analysis, DNA ; Sulfites ; Whole Genome Sequencing

OBJECTIVE： To study the correlation of tacrolimus concentrations among transplant patients’ whole blood， plasma and blood cells， analyze the effects of transplant types and ages on the their correlation， and to provide reference for rational drug use in clinic. METHODS： Totally 20 patients receiving tacrolimus anti-rejection therapy after transplantation and undergoing therapeutic drug monitoring （TDM） were randomly selected. According to the type of transplantation， they were divided into renal transplantation group and lung transplantation group （10 cases for each group）.  According to age， they were divided into three groups： 20-40 years old group， 41-60 years old group and 61-80 years old group （4， 9， 7 cases for each group）. Their residual blood after TDM was collected. Chemiluminescence microparticle immuno assay  （CMIA） was used to detect the concentration of tacrolimus in whole blood. UPLC-MS/MS was used to measure the concentrations of tacrolimus in plasma and blood cells. Pairs plots and Spearman rank correlation analysis were used to analyze the correlation of tacrolimus between whole blood and plasma， between whole blood and blood cells， between plasma and blood cells as well as the effects of transplant types and ages on tacrolimus concentrations among tansplant patient’s whole blood， plasma and blood cells. RESULTS： The correlation of tacrolimus concentrations in whole blood and plasma （r＝0.623，P＜0.01） was slightly stronger than that of whole blood and blood cells （r＝0.591， P＜0.01）； while  the correlation of tacrolimus concentration in plasma and blood cells was relatively weak （r＝0.497，P＜0.05）. Transplant type and age had an effect on the correlation of tacrolimus concentrations among patients’ whole blood， plasma， blood cells. The correlation of tacrolimus concen- tration in whole blood， blood cells and plasma in renal transplantation group was also weak （all r＜0.5）， and was weaker than that in lung transplantation group. The correlation of tacrolimus concentration among whole blood， plasma and blood cells was weak in patients of aged 20-40 years old group （all r＜0.3）， and was weaker than that of patients of aged 41-60 years old group and 61-80 years old group. CONCLUSION： Post-transplantation patients’ tacrolimus concentrations in whole blood， plasma and blood cell have a weak correlation. Rejections and adverse effects should be monitored in these patients， especially those renal transplantation patients or those patients aged 20 to 40.

Objective To explore and discuss the factors for restricting the two-way referral system from the patient's perspective in order to promote the formation of hierarchical medical system in Changsha City.Methods The stratified random sampling method was adopted to divide the Chansha City into the 3 grades of high,middle and low according to the regional economical development situation,2 districts in one grade,including 6 districts.Then each district was redivided into high,middle and low grades according to the economic situation,2 basic medical institutions were selected from each grade.A total of 360 patients were randomly sampled for conducting the questionnaire investigation.The patients and doctors specially participating in the two-way referral conducted the deep interview.Results The patients choosing to primary hospital for first visit accounted for 60.9％.The awareness degree of patients to two-way referral system was 21.1％,and the two-way referral service satisfaction in the patients with two-way referral was 85.7 ％.The patients' will of transfer treatment from primary hospital to superior hospital in case of disease condition need was 82.9 ％.The patients' will for conducting rehabilitation treatment from superior hospital to primary hospital was 77.6 ％.Conclusion Few patients choose primary hospital for first visit.The signing rate of family contract services is low and awareness degree of two-way referral system is not high.

Objective To evaluate the effect of ditching for drain on the control of the breed of Oncomelania hupensis snails in beaches of Dongting Lake. Methods From November,2009 to November,2012,an O. hupensis snail infested beach of the Yueyang jail and an O. hupensis snail infested beach of Junshan District were selected as research fields in the eastern Dongting Lake area,and the former,as the intervention field,was performed with the ditching for drain by excavators and the latter,as the control field,was not. Results Before the project implemented,the average soil moisture contents on the beaches in dry seasons of the two fields were both about 35.56%. After the project implemented,in the intervention field,the average soil mois?ture content was 26.53%which was significantly lower than that(35.56%)in the control field(F=6.53,P<0.05). The under?ground water levels in different heights in the intervention field were lower than those in the control field (χ2 = 33.33,P <0.05). Before the project implemented,the natural death rates of the snails were 0.98%and 0.89%in the two research fields re?spectively(P>0.05),and after the project implemented(in 2012),no adult and young snails were found in the interventional field,but in the control field,the average densities of living snails and young snails were 29.37 snails/0.1 m2 and 213±108.45 snails/0.1 m2 respectively. Conclusion The intervention of ditching for drain can decrease the soil moisture contents quickly and change the ecological condition,therefore,can control the breed of O. hupensis snails in the beaches of Dongting Lake.

The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate (TMPP) in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes: intranasal (i.n.), intragastric (i.g.) and intravenous (i.v.) administration. After i.n., i.g. and i.v. administration of a single-dose at 10 mg/kg, cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals. The concentration of TMPP in the samples was analyzed by HPLC. The area under the concentration-time curve (AUC) and the ratio of the AUCbrain to the AUCplasma (drug targeting efficiency, DTE) was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration. After i.n. administration, TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex (t max=15 min). The ratio of the AUCbrain dialysates value between i.n. route and i.v. injection was 0.68, which was greater than that obtained after i.g. administration (0.43). The systemic bioavailability obtained with i.n. administration was greater than that obtained by the i.g. route (86.33% vs. 50.39%), whereas the DTE of the nasal route was 78.89%, close to that of oral administration (85.69%). These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation, and then crosses the blood-brain barrier (BBB) to reach the cerebral cortex. Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.