Objective To investigate whether microRNA(miR)-199a-5p regulates blood-brain barrier(BBB)integrity through PI3K/Akt pathway after cerebral ischemia.Methods A permanent middle cerebral artery occlusion(MCAO)model was established in SPF adult male SD rats.Totally 48 rats were randomly divided into sham group(n=12),model group(n=12),MCAO+miR-199a-5p group(n=12),and MCAO+miR-199a-5p negative control group(n=12).The Ludmila Bellayev 12 point score was used to evaluate the neurobehavioral performance of rats;The integrity of the BBB after ischemia stroke was detected through Evans blue staining;Immunofluorescent staining was used to determine apoptosis after cerebral ischemia;Western blotting technology was used to detect the protein expression of claudin-5,phosphatidylinositol-3 kinase regulatory subunit 2(PIK3R2),p-Akt,Akt,and vascular endothelial growth factor(VEGF)-A;Real-time PCR was used to investigate the expression levels of miR-199a-5p,claudin-5,and VEGF-A in the ischemic penumbra and infarcted area of the brain.Results The result showed that miR-199a-5p mimic intervention improved proprioception and motor ability in MCAO rats.MiR-199a-5p mimic reduced the expression of PIK3R2 following ischemia stroke,activated the Akt signaling pathway,and increased the expression of claudin-5 and VEGF-A in the ischemic penumbra.In addition,miR-199a-5p alleviated inflammation after cerebral ischemia.MiR-199a-5p mimic reduced BBB permeability and reduced neuronal apoptosis after cerebral ischemia.Conclusion MiR-199a-5p can reduce the expression of PIK3R2 following ischemic stroke,activate the Akt signaling pathway,reduce the expression of inflammatory cytokines,and alleviate the damage to the blood-brain barrier.

Objective:To explore the effects of applying peer-assisted learning (PAL) combined with modular teaching in physiology education, and to explore a more suitable mode for physiology teaching and learning.Methods:We selected a total of 89 undergraduate medical students of grade 2022 from a university offering physiology courses from February 28 to June 30, 2022. They were assigned using a random number table into experimental class (44 students) and control class (45 students). The experimental class adopted PAL with modular teaching, while the control class adopted the online and offline hybrid teaching method. The two classes were compared for teaching effects in terms of the completion rate of task points, final assessment scores, and questionnaire results. SPSS 19.0 was used to perform the independent samples t-test and the chi-square test. Results:The final exam scores for the objective questions of the experimental class and the control class were (43.04±3.25) and (40.24±8.64), respectively; the scores for the subjective items were (44.49±2.80) and (39.21±5.71), respectively; and the total scores were (87.53±4.24) and (79.40±12.08), respectively, all with significant differences between the two classes. There were significant differences in students' learning autonomy, micro-video preview rate, problem discussion participation rate, unit self-test participation rate, and after-class homework completion rate. The questionnaire survey showed that students in the experimental class believed that this teaching model was helpful for improving students' comprehensive qualities.Conclusions:PAL combined with modular teaching can effectively improve physiology teaching effects and students' learning autonomy and comprehensive abilities.

Objective To verify the application effect of the muscle strength training based on Fogg behavior model for elderly frail patients,and provide references and bases for subsequent related research.Methods This paper constructed a muscle strength training program for elderly frail patients based on the Fogg behavior model.The exercise intervention process includes the stages of cultivating exercise awareness,scientific fitness guidance,and developing exercise habits.66 elderly frail people aged 60 and above who were hospitalized in 4 geriatric wards of a tertiary A hospital in Beijing from January to March 2022 were recruited,and they were randomly divided into a control group and an intervention group.The intervention group implemented a muscle strength training based on the Fogg behavior model,while the control group was given routine exercise guidance and education for 6 months.The muscle strength,cardiopulmonary function,and glucose and lipid metabolism of the 2 groups were compared at the end of 3 and 6 months of intervention.Results A total of 65 patients with 33 in the control group and 32 in the intervention group completed the study.The muscle strength of the intervention group showed better changes over time at 6 months compared to the control group(P<0.05).In terms of cardiopulmonary function,the intervention group had better lung capacity than the control group at 3 and 6 months,with statistically significant differences(t=2.166,P=0.034;t=3.385,P=0.001).There was no statistically significant difference in heart rates and left ventricular ejection fraction between the groups(P>0.05).In terms of glucose and lipid metabolism,only high-density lipoprotein in the intervention group was found to be superior to it in the control group at 3 and 6 months,with statistically significant differences(t=2.970,P=0.004;t=4.111,P<0.001).There was no statistically significant difference between blood glucose,low-density lipoprotein,total cholesterol,and triglycerides groups(P>0.05).Conclusion The muscle strength training based on the Fogg behavior model can effectively improve the muscle strength and lung function of frail elderly patients,and can also improve blood lipid metabolism to a certain extent,while there is no obvious effect on heart function and blood glucose control.

Objective:To investigate blood glucose management in elderly diabetic patients and the factors that affected achieving high rates of achieving it.Methods:The quality of blood glucose control by elderly diabetic patients who visited five community health service centers in Beijing in June 2022 was surveyed retrospectively using a questionnaire.Participants were divided into the high-quality group and not high-quality groups by the criteria of glycosylated hemoglobin(HbA 1C)<7% without hypoglycemia and weight gain.Single factor analysis and multiple-stepwise Logistic regression analysis were used to identify the relative risk of factors affecting the achievement of good glucose management. Results:A total of 287 valid questionnaires were collected, including 80 cases(27.9%)in the high-quality group and 207 cases(72.1%)in the not high-quality group.There were significant differences in sex, course of disease, occurrence of hypoglycemia, number of chronic complications, medication, alcohol consumption, dietary changes, missed medication doses, prolonged outpatient visit intervals, and depressive mood between the two groups( P<0.05).Multivariate stepwise logistic regression analysis showed that insulin use, missed medication ≥ 1 time/week, and prolonged outpatient visit intervals were independent risk factors for good control( P<0.05). Conclusions:The percentage of elderly diabetes patients with good blood glucose control was low.Factors affecting the rate included insulin use, medication compliance, and prolonged outpatient visit intervals.

AIM To identify the in vivo metabolites of Cynanchum auriculatum Royle ex Wight extract in functional dyspepsia rats by UHPLC Q-Exactive Plus Orbitrap HRMS.METHODS The rat models for functional dyspepsia were established.The analysis was performed on a 40℃ thermostatic Hypersil GOLD C18 column(2.1 mm×100 mm,1.9 μm),with the mobile phase comprising of water(containing 0.1％formic acid)-acetonitrile(containing 0.1％formic acid)flowing at 0.3 mL/min in a gradient elution manner,and electrospray ionization source was adopted in positive and negative ion scanning.RESULTS Total 4 prototypes(baishouwubenzophenone,deacylmetaplexigenin,qingyangshengenin,syringic)and 110 metabolites were identified,12 of which were common metabolites in feces and urine,56 of which were unique metabolites in urine,42 of which were unique metabolites in feces.The metabolic pathway of prototypes contained phase Ⅰ metabolism(reduction,oxidization,etc.),phase Ⅱ metabolism(sulfonation,glucuronidation,etc.)and phase Ⅰ,Ⅱ composite reactions.CONCLUSION This effective and comprehensive method can lay the theoretical foundation for further discovery of potential active metabolites in C.auriculatum.

Objective To construct a prediction model for postoperative healthcare-associated infection(HAI)in elderly patients with hip fracture,analyze the economic burden,provide a reference and basis for the development of clinical prevention and control programs.Methods 627 elderly patients who underwent hip fracture surgery in a hospital from January 1,2017 to May 31,2023 were selected as the study subjects.Patients were randomly divided into a modeling group and a validation group at a 7:3 ratio.A logistic regression prediction model was constructed based on data from the modeling group,the discriminant and consistency of the model were evaluated by receiver ope-rating characteristic(ROC)curve and Hosmer-Lemeshow test,and the direct economic burden of postoperative HAI in patients was analyzed with 1∶1 propensity score matching(PSM).Results The incidence of postoperative HAI in elderly patients with hip fracture surgery was 12.1％,with pulmonary infection being the most common(52.6％).Logistic regression analysis showed that male,old age,perioperative disturbance of consciousness,gradeⅣ of American Society of Anesthesiologists(ASA)classification,low albumin level,and intensive care unit(ICU)admission were all independent risk factors for postoperative HAI in patients(all P＜0.05).There was good model discrimination and consistency between the training and validation groups in predicting the risk of postoperative HAI.The direct economic burden of postoperative HAI in patients was 7 927.4 Yuan,of which the burden of wes-tern medicine was the largest(3 139.7 Yuan).HAI prolonged patients hospitalization time by 3.6 days.Conclusion Postoperative HAI increases the economic burden of patients,the nomogram model constructed in this study can effectively predict the risk of postoperative HAI in patients,which can provide a basis for the early identification,as well as the implementation of targeted preventive and diagnostic measures for high-risk patients in the clinic.

Objective:To evaluate the value of modified magnetic bead screening for enrichment of cell-free fetal DNA (cffDNA) in non-invasive prenatal testing (NIPT).Methods:This study retrospectively recruited 31 cases with low concentration of cffDNA (<6.00%), Z value in the gray zone (3.00-4.00) at the first detection, or false-positive (confirmed by invasive prenatal diagnosis) or false-negative (confirmed by postnatal chromosome test) results among 11 000 pregnant women who underwent routine NIPT in Beijing Haidian District Maternal and Child Health Care Hospital from October 2017 to December 2019. Plasma samples collected for the first-time routine NIPT were used to enrich cffDNA using modified magnetic beads for NIPT (modified NIPT). Wilcoxon rank sum test was used to compare the modified NIPT with the routine NIPT in detecting the cffDNA concentrations of male fetuses.Results:Among the 31 pregnant women, there were 13 cases with low cffDNA concentration in routine NIPT, 11 having false-positive results in the routine NIPT (three for trisomy 13, four for trisomy 18 and four for trisomy 21, all were confirmed by invasive prenatal diagnosis), six with gray-zone Z values in the first-time NIPT (retesting indicating low risk) and one having false negative result for trisomy 21 (confirmed by postnatal chromosome test). Cell-free DNA (cfDNA) fragments less than 150 bp were effectively enriched using the modified magnetic bead screening and the concentration of cffDNA was increased from 4.43% (2.45%-17.61%) in routine NIPT to 13.46% (7.75%-36.64%) in the modified NIPT ( Z=-14.22, P<0.01). Results of the modified NIPT indicated that 13 cases with low cffDNA concentration of routine NIPT were successfully detected as low risk, as well as the risks in the six cases with gray-zone Z value and six of the 11 false-positive cases in the routine NIPT were low, which were consistent with the retest results of the routine NIPT, while high risk was found in one false-negative case. Conclusions:The modified NIPT could reduce the false positive rate by lowering the failure rate caused by low concentration of cffDNA and is able to identify false-negative cases. Compared with the routine NIPT, it shows a higher success rate and a lower false positive rate.

ABSTARCT Purpose To investigate the clinicopathologic characteristics and genetic mutations of metastatic follicular thy-roid carcinoma(FTC).Methods A total of 22 cases of meta-static FTC were collected,including previous medical history,imaging,treatments and outcomes,and next-generation sequen-cing study and Sanger sequencing were performed in 12 cases.Results There were 16 women and 6 men.Sixteen cases were older than 50 years.Seven cases presented with metastases as the first symptom.Fourteen cases developed metastases 3 to 12 years after thyroid surgery.Sixteen cases developed bone metas-tasis,10 cases had lung metastasis,and 3 cases had brain me-tastasis.Those patients with multiple bone metastases progressed during the follow-up period.The common gene mutations in me-tastases were NRAS p.Q61R(6 cases),HRAS p.Q61R(2 ca-ses)and KRAS p.Q61R(1 case),followed by TERT promoter mutation(8 cases).Other mutated genes included KEL,BRCA1/2,ALK,ROS1,ErbB4,etc.Conclusion FTC has a high misdiagnosis rate.Those diagnosed with FTC should under-go regular systemic examinations to detect potential metastasis,especially in bone,lung,and brain.Further research on the sig-nificance of NRAS and other molecular indicators in FTC metas-tasis will help to better predict its biological behaviors.

Objective:To investigate changes in the self-management ability of chronic diseases in elderly diabetic patients during the novel coronavirus pneumonia pandemic.Methods:A multi-stage cluster sampling method was used to retrospectively collect diabetes management information from elderly diabetic patients treated in five community health service centers in Beijing in June 2022, including 295 elderly diabetic patients, and changes in management of their self-care practices such as diet, exercise, medical treatment and medication, blood glucose monitoring, complication management, and psychological states before and after the outbreak(2019-2022)were analyzed.Results:In 295 elderly diabetic patients, increased glycated hemoglobin( P<0.05)and body mass index(BMI)( P<0.05)were observed during the pandemic.Among 115 patients with underlying diabetic complications, 75.7%(87)of patients had worsening symptoms of chronic complications of diabetes and a shortened weekly exercise time[124(60, 300)min vs.140(60, 300)min, Z=6.00, P<0.05].The number of weekly blood glucose tests was reduced(5.6±4.2 vs.5.8±4.3, t=3.17, P<0.05).The weekly time spent interacting with family members increased( P<0.05).There were no significant differences in body weight, sleep time, and number of times of forgetting to take medication per week before and after the outbreak( P>0.05).21.0% of patients had a decrease in the number of hospital visits, and 72.2% of patients experienced low mood and increased adverse psychological emotions during the pandemic. Conclusions:The pandemic has had a negative impact on the management of chronic diseases in elderly diabetic patients, mainly reflected in the reduction of exercise time and blood glucose monitoring.It also affected regular hospital visits of patients, resulting in negative psychological emotions, poor blood glucose control, increased BMI, and aggravated symptoms of chronic complications, compared with their pre-pandemic conditions.

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.
Animals ; Mice ; Apolipoproteins E ; Atherosclerosis/genetics* ; Beclin-1 ; Cholesterol, LDL ; Intercellular Adhesion Molecule-1 ; Matrix Metalloproteinase 2/genetics* ; Matrix Metalloproteinase 9/genetics* ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism* ; Plaque, Atherosclerotic ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/genetics* ; Vascular Cell Adhesion Molecule-1/genetics*