Objective To investigate the effects of indirubatin derivative E804 on proliferation and migration of non-small cell lung cancer(NSCLC)A549 cells,and to elucidate the possible mechanism of Nrf2-HO-1/GPX4 pathway.Methods Lung cancer A549 cells were used as the cell model.The proliferation and migration of differ-ent specific inhibitors(Nec-1,CQ,Z-VAD,DFO,Fer-1 and Lip-1)in 0,10 μmol/L E804 and 10 μmol/L E804+groups were observed by MTT and cell scratch assay.The contents of reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescence probe method,the contents of Fe2+were detected by colorimetric method,the contents of reduced glutathione(GSH)were detected by spectrophotometry,and the contents of malondialdehyde(MDA)were detected by micromethod.The expression levels of SLC7A11,Transferrin,GPX4,SLC40A1,Nrf2 and HO-1 were detected by Western blot in cells of 0,2.5,5 and 10 μmol/L E804 groups.Results Compared with the control group(0 μmol/L E804),2.5,5 and 10 μmol/L E804 significantly increased intracellular ROS,Fe2+and MDA levels,and decreased intracellular GSH content(P＜0.01).Meanwhile,the expression levels of SLC7A11,GPX4,SLC40A1,Nrf2 and HO-1 significantly decreased(P＜0.01),and the expression level of Transferrin increased(P＜0.05).Compared with the 10 μmol/L E804 group alone,the apoptosis inhibitor(Z-VAD)group and the ferroptosis inhibitor(DFO,Fer-1 and Lip-1)group could significantly reverse the inhibition of proliferation and migration of A549 cells by 10 μmol/L E804(P＜0.01).Conclution E804 can induce ferrop-tosis and inhibit the proliferation and migration of A549 cells,which may be related to the inhibition of Nrf2-HO-1/GPX4 pathway.

Objective:To explore the application effect of breakthrough series (BTS) quality improvement model in the prevention of catheter-related bloodstream infection in hospitalized patients with indwelling non-cuffed catheter (NCC).Methods:Using a non synchronous pre and post control study method, convenience sampling was used to select NCC patients from four hospitals in Tianjin from January to September 2022 who received conventional nursing plans as the control group, and NCC patients from February to October 2023 who received nursing plans based on the BTS quality improvement model as the observation group. Compared the incidence of NCC related bloodstream infections between two groups of patients, the implementation of key preventive measures for NCC related bloodstream infections by nursing staff, and patient satisfaction.Results:Among the 984 patients included in the control group, there were 687 males and 297 females, aged (62.43 ± 13.77) years old; among the 959 patients included in the observation group, there were 651 males and 308 females, aged (61.96 ± 13.89) years old. After applying the improved model, the incidence of NCC related bloodstream infections in the observation group was 0.12‰ (1/8 676), lower than the control group′s 0.71‰ (7/9 827), and the difference was statistically significant ( χ 2=4.37, P<0.05) ;the implementation rate of key measures for preventing NCC related bloodstream infections in the observation group was 90.00% (54/60) for catheter outlet care and 91.67% (55/60) for maximizing sterile barrier, both higher than 70.37% (38/54) and 75.93% (41/54) in the control group, with statistical significance ( χ2=7.03, 5.30, both P<0.05); the total satisfaction rate of patients in the observation group was 92.91% (891/959), which was higher than 58.64% (577/984) in the control group, and the difference was statistically significant ( χ2=15.28, P<0.05). Conclusions:The implementation of BTS quality improvement model is helpful to improve the nursing quality of patients with indwelling NCC dialysis and improve the patient outcomes.

O'Donnell-Luria-Rodan(ODLURO)syndrome is an autosomal dominant genetic disorder caused by mutations in the KMT2E(lysine methyltransferase 2E)gene.The Third Xiangya Hospital of Central South University admitted a 12-year and 9-month-old male patient who presented with growth retardation,intellectual disability,and distinctive facial features.Peripheral blood was collected from the patient,and DNA was extracted for genetic testing.Chromosome karyotyping showed 46XY.Whole-exome sequencing and low-coverage massively parallel copy number variation sequencing(CNV-seq)revealed a 506 kb heterozygous deletion in the 7q22.3 region,which includes 6 genes,including KMT2E.The patient was diagnosed with ODLURO syndrome.Both the patient's parents and younger brother had normal clinical phenotypes and genetic test results,indicating that this deletion was a de novo mutation.The clinical and genetic characteristics of this case can help increase clinicians'awareness of ODLURO syndrome.

Objective:To conduct visualization analysis on the literature on dietary restriction(DR)regulating inflammation based on CiteSpace and VOSviewer visualization software,and to explore research hotspots and trends in this field.Methods:The literature on DR regulation inflammation in Web of Science core databases from January 1 2010 to September 29 2022 were searched.CiteSpace and VOSviewer visualization software was used to conduct quantitative and visual analysis of the annual publication volume,countries,institutions,authors,citation frequency and keywords of the retrieved literature.Results:A total of 1 344 papers related to the topic were included,and the annual number of papers was generally on the rise,with the highest citation frequency of 1 676 times.The United States(481 papers)is the country with the largest number of publications,followed by China(181 papers).The research hotspots in this field focused on calorie restriction(CR),ketogenic diet,aging,metabolic diseases,adipose tissue and gut microbiota.Conclusion:DR regulation of inflammation is increasingly favored by international and domestic researchers,and future research hotspots may be CR mimics(CRMs),intestinal microbiota,neurodegenerative diseases and cardiovascular diseases.The overall research trend is to further clarify the anti-inflammatory mechanism of DR,find new therapeutic targets,and conduct more rigorous clinical trials with more effective regimens that have been proven in vitro and animal models.

Objective To explore the effect and mechanism of miR-208b-3p on energy metabolism in mice with heart failure(HF)induced by transverse aortic constriction(TAC).Methods Twenty-four mice were randomly divided into sham operation group(Sham group,n=6)and surgery group(n=18).TAC was used to establish an HF model in the surgical group,the sham group received the same surgical procedures as TAC,but no ligation of the transverse aortic arc.At the second week after TAC,the surgery group was randomly divided into Antagomir group(n=6),Antagomir-NC group(n=6)and TAC group(n=6).The mice of the Antagomir group and the Antagomir-NC group were injected with miR-208b-3p antagomir reagent(800 μg)and miR-208b-3p antagomir negative control reagent(800 μg),respectively by tail vein,twice a week,for 4 consecutive weeks.Echocardiography was performed at the 6th week after surgery to evaluate the cardiac function.HE staining and Sirius red staining were used to observe myocardial histopathology in mice.ATP assay was employed to detect the ATP level in myocardial tissues.RT-qPCR was applied to detect the expression of miR-208b-3p,mitochondrial genes(ND1,ND2,ND3,ND4,ND4L,ND5,ND6,CO1,CO2,CO3,CYTB,ATP6 and ATP8),POLRMT and 12S rRNA in myocardial tissues.Double luciferase reporter assay was conducted to detect the interaction between miR-208b-3p and the potential target gene POLRMT.Western blotting was utilized to detect the changes in the protein levels of POLRMT and ND1,CO2,CYTB and ATP8 in myocardial tissues.Results The expression of miR-208b-3p was significantly higher in myocardial tissues of the TAC group than the Sham group(P＜0.05).Echocardiography revealed that the ejection fraction,systolic and diastolic functions were significantly improved in the Antagomir group than the TAC group(P＜0.05).Pathological observation showed significantly improved cardiomyocyte hypertrophy,arrangement disorder and myocardial interstititial cell infiltration in the Antagomir group(P＜0.05).Compared with the TAC group,the ATP level was significantly increased(P＜0.05),the expression levels of POLRMT and mitochondrial gene transcripts(12SrRNA and 13 mitochondrial gene-coding polypeptides)were significantly increased(P＜0.05),but there were no changes in SDHA and SDHB levels in the Antagomir group.Double luciferase reporter assay indicated that miR-208b-3p bound to the CDS region of POLRMT.The protein levels of POLRMT,ND1,CO2,CYTB and ATP8 were significantly increased in the myocardial tissues in the Antagomir group than the TAC group(P＜0.05).Conclusion MiR-208b-3p inhibits the expression of mitochondrial genes by targeting POLRMT,aggravates mitochondrial energy metabolism disorder,and deteriorates cardiac insufficiency and ventricular remodeling in HF mice.

Objective:To explore the impact of intradialytic hypotension (IDH) on brain component volume, as well as its relationship with depression and cognitive function changes in maintenance hemodialysis patients.Method:It was a cross-sectional observational study. Clinical data of 119 patients under maintenance hemodialysis in Peking Union Medical College Hospital from July 2013 to July 2014 were collected, retrospectively. Patients were divided into IDH group and non-IDH group. 3.0T Magnetic resonance imaging examination of the head for all patients was completed and the results of volume analysis of each component of the brain were extracted. Cognitive function was assessed by the Chinese version of the simplified mental state examination scale (C-MMSE) and the Chinese version of the Montreal cognitive assessment scale (C-MoCA). Depressive status was assessed by the Hamilton depression scale 17 (HAMD_17) and living ability was assessed by the Alzheimer's disease collaborative study-daily living ability assessment questionnaire. In addition, the Philadelphia word learning test was used to measure memory, the Boston naming test to measure language, the connection test A and B to measure executive ability, and the Stroup test C to measure attention. The differences in brain component volume, cognitive function, emotion, and life ability between two groups of patients were compared, and the correlation between IDH and brain component volume was explored by regression analysis.Result:A total of 119 patients were included in this study, of whom 22 (18.5%) had hypotension during dialysis. The volumes of amygdala, cuneiform lobe, and posterior cingulate gyrus in IDH group were significantly smaller than those in the non-hypotension group [ (1.6±0.2) mm 3vs. (1.7±0.2) mm 3, t=2.674, P=0.009; (6.9±0.8) mm 3vs. (7.4±1.0) mm 3, t=2.187, P=0.031; (6.9±0.8) mm 3vs. (7.4±0.9) mm 3, t=2.252, P=0.024]. The differences of gray matter, white matter volume between the two groups showed a similar trend but did not reach statistical significance. And lacunar infarction and cerebral microbleeds were more common in IDH group. The daily living ability scores of the two groups were similar (65.51±11.52 vs. 65.71±11.53, Z=-0.456, P=0.648). The proportion of patients with cognitive abnormalities was higher in the IDH group, without statistical significance. The proportion of depression was similar. Univariate linear regression analysis showed that IDH was significantly negatively correlated with the volume of amygdala, cuneiform cortex, and posterior cingulate gyrus, which control emotions in the brain ( B=-0.117, 95% CI -0.203--0.030, P=0.009; B=-0.484, 95% CI -0.923--0.046, P=0.031; B=-0.485, 95% CI -0.911--0.058, P=0.026). After multivariate adjustment, decreased amygdala volume was still correlated with IDH ( B=-0.111, 95% CI -0.198--0.025, P=0.026). Conclusion:Recurrent IDH may lead to atrophy of various brain components, which may be one of the reasons for cognitive and emotional changes in maintenance hemodialysis patients.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

The medical massive open online course (MOOC) quality certification standard is the reference for the implementation of medical MOOC quality monitoring. This thesis utilizes data mining, quantitative analysis, qualitative analysis and other methods, taking the comment text of the Chinese medicine courses on the Ai Course (MOOC of China Universities) platform as the data source out of which to extract certain potential indicators for the medical MOOC quality certification standard. Based on the analysis of the existing research results on MOOC quality evaluation domestic and abroad as well as the relevant policies of the Ministry of Education, a medical MOOC quality accreditation standard including 6 first-level indicators are formed, including course content, teaching design and so on. Expert scores and AHP method were used to calculate the weight coefficient of the quality certification standard. Finally, this paper explains the procedure of medical MOOC quality certification in college. This certification system can be used to conduct self-assessment and quality monitoring of medical MOOC in colleges and universities.

This study summarizes related studies on readiness for online teaching in China and globally and constructs an online teaching readiness scale for higher education teachers with reference to related studies on online teaching competency, blended teaching readiness, and influencing factors for online teaching. This scale includes five dimensions, i.e., belief, teaching readiness, technical readiness, online communication readiness, and institutional support. A questionnaire survey and statistical analyses were performed to investigate the rationality of the scale, and then the scale was modified. The results show that the indicators of the scale have a good degree of fitting, and this study provides a necessary standard for examining the online teaching readiness of higher education teachers and new ideas for online teaching in colleges and universities.

Objective:To advance the understanding of X-linked adrenal hypoplasia congenita(XL-AHC)through genetic analysis.Methods:Genomic DNA was extracted from peripheral blood of three patients with XL-AHC and their family members as well. Pathogenic genes were screened with whole exome sequencing followed by Sanger sequencing and pedigree verification.Results:All three probands were diagnosed as primary adrenal insufficiency at early age and developed hypogonadotropic hypogonadism in adolescence. The proband 1 was hemizygous for c. 420delG(p.R141Gfs*123)mutation in exon 1 of NR0B1 gene. His mother was a heterozygous mutation carrier while his brother did not carry the mutation, which was consistent with the X-linked recessive inheritance. A hemizygous mutation c. 212_213delAA(p.K71Rfs*41)of NR0B1 gene was detected in both proband 2 and proband 3. These two novel mutations were not reported in HGMD database.Conclusions:In this study, two novel NR0B1 mutations, c. 420delG and c. 212_213delAA were identified in 3 patients with XL-AHC. For men with early onset of adrenocortical hypofunction, XL-AHC should be considered. Early genetic screening of NR0B1 gene is helpful for early diagnosis.