Resistance to ferroptosis, a form of regulated cell death caused by disruptions in iron ion and intracellular redox homeostasis, is closely related to tumorigenesis and tumor drug resistance; therefore, targeting ferroptosis-related pathways has garnered attention as a potential antitumor therapeutic strategy. However, the molecular mechanisms underlying ferroptosis resistance in tumor cells remain unknown. Zinc-finger estrogen receptor interaction clone 6 (ZER6) consists of two isoforms with distinct N-termini, p52-ZER6 and p71-ZER6. ZER6 is upregulated in tumors and promotes tumorigenic potential; however, whether ZER6 is involved in tumor cell ferroptosis resistance remains unknown. Herein, we identified p52-ZER6 as a novel regulator of tumor cell ferroptosis resistance. p52-ZER6 promotes the transcriptional activity of DAZAP1, an RNA-binding protein. DAZAP1, in turn, enhances the stability of SLC7A11 mRNA by binding to its 3'-UTR region, thereby increasing SLC7A11 expression and cellular glutathione levels. This subsequently reduces lipid peroxide accumulation and enhances tumor cell ferroptosis resistance, eventually promoting tumorigenic potential. These findings reveal a new function of p52-ZER6 in regulating SLC7A11 mRNA stability via DAZAP1, ultimately leading to ferroptosis resistance and tumorigenic potential. Additionally, we also suggest targeting p52-ZER6 as a potential strategy to promote the efficacy of ferroptosis-based antitumor therapies.

Objective:To mine and analyze the signals of the adverse event (AE) of erenumab and provide reference for the safe application of the drug.Methods:The reports of AE from 2004 to the first quarter of 2023 were extracted from the US FDA Adverse Event Reporting System database, and the full data and data after 2018 were analyzed respectively. AEs were classified according to preferred term (PT) and the system organ class (SOC) of Medical Dictionary for Regulatory Activities (MedDRA) 23.0 version for statistical analysis. The reported odds ratio (ROR) method and Bayesian confidence progressive neural network (BCPNN) method were used to mine the AE risk signals.Results:A total of 38 348 AE reports with erenumab as the primary suspect drug were collected, involving 2 629 PTs. The number of risk signals screened by the ROR and BCPNN methods from the full data and data after 2018 was 99 and 115, respectively, involving 19 SOCs. Among them, the most frequently reported AEs were injection site reactions and constipation, which were consistent with the label. Among the top 30 PTs, 13 were not recorded in the label, including pineal cyst, postural tachycardia, positive histone antibody, spastic eye movements, fear of injection, post-concussion syndrome, Raynaud effect, psychogenic seizures, coronary artery dissection, premature menopause, trichorrhexis, collagen disease, and blepharospasm.Conclusion:In clinical application of erenumab, in addition to the adverse reactions recorded in the label, attention should also be paid to the adverse events mined in this study.

Objective:To mine and analyze the signals of the adverse event (AE) of erenumab and provide reference for the safe application of the drug.Methods:The reports of AE from 2004 to the first quarter of 2023 were extracted from the US FDA Adverse Event Reporting System database, and the full data and data after 2018 were analyzed respectively. AEs were classified according to preferred term (PT) and the system organ class (SOC) of Medical Dictionary for Regulatory Activities (MedDRA) 23.0 version for statistical analysis. The reported odds ratio (ROR) method and Bayesian confidence progressive neural network (BCPNN) method were used to mine the AE risk signals.Results:A total of 38 348 AE reports with erenumab as the primary suspect drug were collected, involving 2 629 PTs. The number of risk signals screened by the ROR and BCPNN methods from the full data and data after 2018 was 99 and 115, respectively, involving 19 SOCs. Among them, the most frequently reported AEs were injection site reactions and constipation, which were consistent with the label. Among the top 30 PTs, 13 were not recorded in the label, including pineal cyst, postural tachycardia, positive histone antibody, spastic eye movements, fear of injection, post-concussion syndrome, Raynaud effect, psychogenic seizures, coronary artery dissection, premature menopause, trichorrhexis, collagen disease, and blepharospasm.Conclusion:In clinical application of erenumab, in addition to the adverse reactions recorded in the label, attention should also be paid to the adverse events mined in this study.

Objective:To explore the role of video-assisted feedback in clinical skill teaching in undergraduate classes and its application effect.Methods:The experimental control method was adopted in the study. A total of 185 students from Eight-year program of clinical medicine of Batch 2014 and Five-year program of clinical medicine of Batch 2016 in Tongji Medical College of Huazhong University of Science and Technology were collected as the experimental group, and another 166 students from Eight-year program of clinical medicine of Batch 2013 and Five-year program of clinical medicine of Batch 2015 as the control group. The experimental group adopted the teaching mode of video-assisted feedback and the control group received the traditional teaching mode. By the end of training sessions, the differences between the two groups in both the skill assessments and the theories were compared. A satisfaction survey about the video-assisted feedback was made in the experimental group. GraphPad Prism 5 was used for t test. Results:In the students from Five-year program of clinical medicine, the scores of theoretical assessment in the experimental group were (87.64±0.94) points and the scores of skill assessments were (84.78±0.54) points; the scores of theoretical assessment in the control group were (85.14±0.80) points and the scores of skill assessments were (83.10±0.53) points. In the students from Five-year program of clinical medicine, the difference of both the theoretical and the skill assessment scores between the experimental group and the control group was statistically significant ( P<0.05). In the students from Eight-year program of clinical medicine, the scores of theoretical assessment in the experimental group were (86.46±0.66) points and the scores of skill assessments were (86.38±0.73) points; the scores of theoretical assessment in the control group were (84.90±1.21) points and the scores of skill assessments were (83.79±0.64) points. The difference of the skill assessment scores between the experimental group and the control group was statistically significant ( P<0.05), and no significant difference was found in the theoretical assessment. The questionnaire survey in the experimental group based on video-assisted feedback teaching method showed that 93.3% (168/180) of students said that they would not take the initiative to practice after class if there was no video shooting session; 87.8% (158/180) of the students thought the video-assisted feedback teaching method improved their ability of independent learning; 82.8% (149/180) of students thought this method significantly increased their learning efficiency and confidence in clinic; 71.1% (128/180) of the students felt that after-class video shooting, their self-confidence was improved when they faced the corresponding operation clinically. Conclusion:The application of video-assisted feedback has significantly improved the outcome of clinical skill training for students, as compared to the traditional teaching mode.

Objective:To explore the effect of estrogen-related receptor α (ERRα) on lipopolysaccharide (LPS)-induced vascular endothelial cell apoptosis and tight junction protein degradation.Methods:RPMVECs transfected with shERRα were cultured in vitro and divided into four groups: Normal control group (Ctr group); shERRα knockdown group (shERRα group); normal cells + LPS treated group (LPS group): The cells in the six-well plates were cultured in serum-free medium for 12 h, and then treated with 20 μg/mL LPS for 12 h; and shERRα+LPS group: ERRα knockdown cells were treated as the LPS group. ROS fluorescence kit was used to detect the intracellular ROS levels . Apoptosis ratio was detected by TUNEL staining, AnnexinV-FITC and PI. Cell membrane ZO-1 expression was detected by cellular immunofluorescence, and the levels of apoptosis-related proteins Bcl-2, Bax, Smac, Cytochrome c, and tight junction protein ZO-1, as well as the expression of Occludin, JAM-A and E-Ca at molecular level were detected by Western blot.Results:Compared with the Ctr group and the shERRα group, the ROS level, apoptosis rate (TUNEL test: 16.44 ± 2.55; and flow cytometry test: 23.56 ± 2.22), the expression of pro-apoptotic proteins Bax, Smac and Cytochrome c were increased in the LPS group, while the expression of anti-apoptotic proteins Bcl-2 and tight junction protein were decreased. In the LPS group. Cellular immunofluorescence results showed that the ZO-1 was degraded in the cell membrane and the network structure was broken. Compared with the LPS group, inhibition of ERRα in the shERRα+LPS group increased cell damage.Conclusions:ERRα can negatively regulate the apoptosis and affect the function of pulmonary microvascular endothelial cells, thereby regulating sepsis-induced acute lung injury.

Objective To investigate the effect of estrogen-related receptor alpha(ERRα)on lipopolysaccharide-induced inflammatory response in rat pulmonary microvascular endothelial cells (PMVECs) and its mechanism.Methods PMVECs were cultured in vitro.When the cells were in the logarithmic growth phase,the cell were ransfected with lentivirus,and a stable low-expression ERRα cell line was constructed.The cells were divided into four groups:Ctr group (normal control group),Ctr+LPS group (normal celI+LPS treatment group),shERRα1 (shERRα1 gene knockdown group),and shERRα1+LPS group (shERRα1 gene knockdown +LPS treatment group).After 20 μg/mL LPS stimulated cells in the control group and shERRal group for 6,12 and 24 h,cell counting kit-8 (cck-8) was used to detect the cell proliferation ability of each group,and enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of tumor necrosis factor alpha (TNF-α) and Interleukin-1β (IL-1β) in cell culture fluid.After 12 h LPS stimulation,the expression levels of ERRα and NF-κB related proteins (p-p65,p65,P-IKBα,IKBα) were measured by Western blot.Pairwise comparisons were performed with SNK-q test (two-tailed),and multiple-group comparisons were performed with one-way ANOVA.The non-parametric test of rank transformation was used when homogeneity of variance were not met.P value＜0.05 was considered significantly different.Results Compared with the control group,ERRα expression in the shERRα group was significantly decreased (0.09±0.01 vs 0.15±0.01).At 6,12 and 24 h after LPS stimulation,compared with the control group,the cell proliferation ability (％) of the shERRαl+LPS group was significantly reduced (99.68±4.53 vs 48.62±1.60) and the concentration of TNF-α (ng/mL) (15.76±3.38 vs 5 498.91±367.95) and IL-1β (ng/mL) (14.41±3.86 vs 6 014.92±277.33) in the cell culture supematant were significantly increased.The change was most obvious after 12 h stimulation.Meanwhile the expression of p-p65 (0.30±0.50 vs 1.05±0.07) and p-IKBα (0.27±0.04 vs 0.77±0.06) were increased significantly,while the expression of IKBα (0.96±0.07 vs 0.14±0.04) was decreased significantly in the shERRαl+LPS group (all P＜0.05).Conclusion ERRα gene attenuates LPS-induced inflammatory response in rat pulmonary microvascular endothelial cells by inhibiting NF-κB signaling pathway activation.

Objective: To evaluate the application effect of the medication management training based on Precede-Proceed Model in schizophrenic inpatients. Methods: In this self-control study, 60 schizophrenic inpatients were chosen for this investigation and were undergoing the medication management training on Precede-Proceed Model with conventional nursing care. By using Insight and Treatment Attitudes Questionnaires (ITAQ), The Brief Psychiatric Rating Scale (BPRS) and Nurses′ Observation Scale for Inpatient Evaluation (NOSIE) after the first 3 months and 6 months of the intervention, in order to evaluate their results with their initial readings. Results: The total scores of ITAQ, the total scores of BPRS, lacking in activity factor, reaction factor, hostile-suspiciousness factor, the total scores of NOSIE, total positive and negative factors before the intervention were (183.3±15.0) points, (71.7±10.9) points and (13.6±8.8) points; three months after intervention were (189.0±15.8) points, (75.3±11.1) points and (11.6±7.2) points; six months after intervention were (193.8 months after intervention were15.2) points, (71.8 ±9.6) points and (10.1±7.0) points. There were significant differences between the total score and the total negative factor score before and after treatment (F=43.244, 23.060, P<0.05). Conclusion The Precede-Proceed Model on medication management training in schizophrenic inpatients plays a positive role in promoting recovery and it is worth extending in clinical practice.

Adrenal rest tumor (ART) is a well-known complication in congenital adrenal hyperplasia (CAH), which may occur in all age groups, especially in adolescence and adulthood. Tumors that occur in the testicular known as testicularadrenal rest tumor (TART), in the ovarian and parovarian tissue known as ovarian adrenal rest tumor (OART). ART is one of the major causes of reproductive dysfunction in adult with CAH. Early prevention and treatment is the key to avoid irreversible damage to gonadal function. In the past, we paid more attention to TART in children, while ignored TART and OART in adults. This article will review the origin of tumor cells, pathogenesis, epidemiology, diagnosis, treatment and prognosis of CAH associated with ART, which aims to guide clinical work through the profound understanding of CAH with ART.

Objective To investigate influences of estrogen-related receptor α(ERRα) on pulmonary vascular endothelium of rats undergoing sepsis. Methods Male Sprague-Dawley (SD) rats were divided into four groups according to the random number table method (12 in each group): normal control group (NC group), sham operation group (Sham group), sepsis model caused by cecal ligation and puncture (CLP) group (CLP group), XCT790 intervention group (XCT790 group, given the XCT790 2.5 mg/kg via intraperitoneal injection 30 minutes before CLP). After 24 hours, rats were sacrificed and the organs were harvested. The pathological changes of lung tissue were observed using hematoxylin and eosin (HE) staining, and the ultrastructural changes of lung tissue were observed by double staining of uranium citrate with lead acetate, the degree of apoptosis of pulmonary capillary endothelial cells were observed by TdT-mediated dUTP nike end labeling stain (TUNEL), the permeability of lung vascular endothelial was detected by Evans blue (EB) staining, the levels of serum cytokines were detected by enzyme linked immunosorbent assay (ELISA), and white blood cell count in bronchial alveolar lavage fluid (BALF) was detected. Results Compared with NC group and Sham group, the CLP group and XCT790 group had severe pathological damage and increased lung tissue permeability, the levels of serum cytokines and white blood cell count in BALF were increased. Compared with CLP group, the pathological changes of lung tissue, the degree of ultrastructural damage of lung tissue, the degree of apoptosis of lung capillary endothelial cells in XCT790 group further intensified, the permeability of lung endothelial barrier further increased [the content of EB (μg/g): 116.00±15.46 vs. 60.19±19.79, P < 0.05], and the level of serum cytokines further increased [interleukin-1β(IL-1β, ng/L): 71.38±4.01 vs. 56.58±2.45, interleukin-6 (IL-6, ng/L): 741.62±88.94 vs. 534.22±72.70, tumor necrosis factor-α(TNF-α, ng/L):188.55±7.41 vs. 143.33±11.27, all P < 0.05], the white blood cell count in the BALF increased further (×104/L:193.79±27.46 vs. 99.34±36.41, P < 0.05). Conclusion ERRα can aggravate inflammation in sepsis rats, destroy lung tissue and increase pulmonary permeability.

Bone marrow adipose tissue (MAT) is formed by the accumulation of adipocytes in the bone marrow cavity. Previously, the function of MAT is mainly considered to be filled with bone marrow cavity for the mechanical support. However,with the in-depth study of MAT,it has been gradually understood that MAT is not only a part of the bone marrow microenvironment,may also be a new endocrine "organ". The main component of bone marrow adipocytes(BMA) plays a regulatory role in bone marrow and systemic metabolism through the autocrine and paracrine secretion of adiponectin, leptin, interleukin-6, and a series of cytokines. Though its biological characteristics are somewhat similar with white fat adipose tissue(WAT) and brown adipose tissue(BAT),there are some significant differences,so MAT is thought to be a special adipose tissue. MAT is also involved in the development of hematological diseases,metabolic diseases,degenerative diseases,and may affect their outcomes. MAT may be the auxiliary diagnostic criteria and treatment targets of such diseases. This article will review the MAT's own biological characteristics,the differences and associations among three types of adipose tissue and the link between MAT and the diseases,which aims to explore the new research direction through the profound understanding of MAT.