Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Ischemic heart disease (IHD) is associated with high morbidity and mortality rates. Reperfusion therapy is the best treatment option for this condition. However, reperfusion can aggravate myocardial damage through a phenomenon known as myocardial ischemia/reperfusion (I/R) injury, which has recently gained the attention of researchers. Several studies have shown that Chinese herbal medicines and their natural monomeric components exert therapeutic effects against I/R injury. This review outlines the current knowledge on the pathological mechanisms through which mitochondria participate in I/R injury, focusing on the issues related to energy metabolism, mitochondrial quality control disorders, oxidative stress, and calcium. The mechanisms by which mitochondria mediate cell death have also been discussed. To develop a resource for the prevention and management of clinical myocardial I/R damage, we compiled the most recent research on the effects of Chinese herbal remedies and their monomer components.

Objective:To investigate the quality of life(QOL)of patients undergoing maintenance hemodialysis(MHD)in blood purification centers of three hospitals in Shenyang,and analyze its influencing factors,so as to provide reference for improving QOL of MHD patients.Methods:A total of 343 patients undergoing MHD from Mar to Oct,2021 were included,and their general data,laboratory indicators,hemodialysis indicators,etc.were collected.QOL of patients was evaluated by KDQOL-SFTM1.3 scale(SF-36 score and KDTA score).Multivariable linear regression analysis was used to analyze the factors affecting their QOL.Results:The scores of SF-36 and KDTA in MHD patients were 51.22±19.50 and 60.43±14.50,respectively.Age,marital status,family per capita monthly income,vascular access,monocyte count,blood phosphorus and serum albumin were independent influencing factors of SF-36 score(P＜0.05).And age,education level,family per capita monthly income and serum creatinine were independent influencing factors of KDTA score(P＜0.05).Conclusion:Comprehensive intervention of influencing factors should be paid more attention to improve the QOL of MHD patients.

Objective:To explore the application effect of the modified presentation assimilation discussion combined with heuristic clinical medicine teaching in training of extracorporeal membrane oxygenation specialist nurses.Methods:The convenient sampling method was used to select 62 nurses who participated in training of extracorporeal membrane oxygenation specialist nurses in the Second Affiliated Hospital of Zhengzhou University from January to June 2023 as the research objects. A total of 30 nurses who participated in the 25th training session from January to March 2023 were selected as the control group, and 32 nurses who participated in the 26th training session from April to June 2023 were selected as the observation group. The control group received conventional training method, while the observation group received modified presentation assimilation discussion combined with heuristic clinical medicine teaching. The theoretical knowledge and operational skills of nurses, core competence of extracorporeal membrane oxygenation specialist nurses and training satisfaction were compared between the two groups after training.Results:After training, the scores of theoretical knowledge and operational skills, core competence of extracorporeal membrane oxygenation specialist nurses and training satisfaction in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05) . Conclusions:The modified presentation assimilation discussion combined with heuristic clinical medicine teaching can improve the theoretical knowledge and operational skills of extracorporeal membrane oxygenation specialist nurses, and the nurses' training satisfaction is higher.

Background Research on non-target organ damage of biological pesticides has attracted much attention. Rotenone exposure may be far beyond the occupational environment, and the exposureduring pregnancy may be increased through bioaccumulation, fruit or vegetable residues, and other forms of oral intake. At present, the effects of rotenone on placental development and its mechanism are still unknown. Objective To investigate the developmental damage of rat placenta and evaluate the expression levels of glycogen synthase kinase (GSK-3β) and beta catenin (β-catenin) followed by rotenone exposure through the placental barrier during pregnancy, as well as to propose possible associated mechanisms. Methods Eighteen sexually mature SD female infertile rats without specific pathogens were selected and divided into three groups: blank control group (0.9% saline), corn oil group, and rotenone group (corn oil + 2 mg·kg⁻¹ rotenone) by random number method, six female animals in each group. Another six male rats were selected and mated to the female rats at night with a female to male ratio of 3:1 per cage. Pregnant rats were given 0.9% saline, corn oil, and 2 mg·kg⁻¹ rotenone preparation by isovolumetric gavage once daily for the entire gestation period (19 d), and their conditions were observed after the last dose. The pregnant rats were anesthetized, and the size of the placenta and blood perfusion were detected by ultrasound the next day of the last dose of rotenone. Then, 3 pregnant rats in each group were sacrificed immediately and the placenta and umbilical cord tissues were dissected. The remaining 9 pregnant rats gave birth naturally, and the fetuses were observed for developmental evaluation and weighed. The histopathological changes of umbilical cord and placenta were observed by hematoxylin-eosin staining. The reactive oxygen species levels of placenta tissues were detected by flow cytometry. The Ca²⁺-ATPase activity of placenta tissues was detected by colorimetric method. The localization and levels of GSK-3β and β-catenin expression of placenta were detected by immunohistochemistry. The p-GSK-3β/GSK-3β and p-β-catenin/β-catenin protein expression in placental tissues were measured by Western blotting. Results No injury or death was recorded during the pregnant rats receiving rotennon administration. Adverse pregnancy outcomes such as fetal absorption and postpartum stillbirth were found in the rotenone group, and the weight of the fetal mice decreased (P<0.05). The B-ultrasound showed disc-shaped placenta with a thick middle and thin edge, smooth fetal surface, rough maternal surface, visible placental lobules, granular echotexture of the placenta with comma-like echogenic densities, and chorionic plate showing deep indentations, no calcification, degeneration, or necrosis in each group. Compared with the corn oil group, the fetal surface diameter of the placenta was reduced in the rotenone group (P<0.05). The Doppler color ultrasound showed that interplacental blood flow was reduced in the rotenone group, while interplacental blood flow was abundant in the blank control and the corn oil groups. The hematoxylin-eosin staining results showed that smooth muscle cells in the umbilical cord tissues of rats were loosely arranged, with fuzzy nuclei and inflammatory infiltration in the rotenone group. The placental trophoblast cells were small in size, disorderly arranged with nuclear fragmentation and cytoplasm turbidity. The tissue reactive oxygen species level in the rotenone group was higher than those in the other two groups (P<0.05). The Ca²⁺-ATPase activity of placental tissues was reduced in the rotenone group (P<0.05). The immunofluorescence low-magnification observation showed that GSK-3β and β-catenin were expressed in placental tissue, weak fluorescence expression in the decidua basalis, strong fluorescence expression in the labyrinthine layer structure. The labyrinthine layer under high magnification showed that compared with the blank control group and the corn oil group, the brightness of β-catenin fluorescence expression in the rotenone group decreased (P<0.05), and the brightness of GSK-3β expression increased (P<0.05). The Western blotting results showed that the expression of β-catenin and p-GSK-3β proteins decreased (P<0.01), and the expression of GSK-3β protein increased (P<0.01) in the rotenone group. No significant expression of p-β-catenin protein was detected in the placenta tissue of each group. Conclusion Rotenone exposure during pregnancy induces placental hypoperfusion, growth retardation, and oxidative stress in rats, as well as down-regulation of β-catenin and p-GSK-3β protein expression, and up-regulation of GSK-3β protein expression, which may further lead to abnormal pregnancy and fetal restricted growth.

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

Objective:To clarify the clinical efficacy of first-line oral antiviral drugs tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in the treatment of chronic hepatitis B (CHB) and their safety profiles with lipid, bone, and kidney metabolism.Methods:458 CHB cases diagnosed and treated at the Department of Hepatology of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University from February 2010 to November 2022 were selected. TAF (175 cases), TDF (124 cases), and ETV (159 cases) were used as therapies. At 24 and 48 weeks, the virology, biochemical response, changes in liver stiffness measurement (LSM), and bone, kidney, and blood lipid metabolism safety profiles were compared and analyzed.Results:After 24 and 48 weeks of TAF, TDF, and ETV therapy, HBV DNA load decreased by 3.28, 2.69, and 3.14 log10 IU/ml and 3.28, 2.83, and 3.65 log10 IU/ml, respectively, compared with the baseline, and the differences between the three groups were statistically significant, P < 0.001. The complete virological response rates were 73.95%, 66.09%, 67.19%, and 82.22%, 72.48%, and 70.49%, respectively. The incidence rates of low-level viremia were 16.67%, 21.70%, and 23.08%, while poor response rates were 1.11%, 3.67%, and 4.10%. ALT normalization rates were 64.00%, 63.89%, 67.96%, and 85.33%, 80.56%, 78.64%, respectively, and there was no statistically significant difference among the groups. LSM was significantly improved in patients treated with TAF for 48 weeks, P = 0.022. Serum phosphorus level gradually decreased with the prolongation of TDF treatment. The TAF treatment group had a good safety profile for kidney, bone, and phosphorus metabolism, with no dyslipidemia or related occurrences of risk. Conclusion:There are some differences in the therapeutic effects of first-line anti-HBV drugs. TAF has the lowest incidence of low-level viremia after 48 weeks of treatment and has a good safety profile in kidney, bone, and blood lipid metabolism.

Objective:To investigate the risk factors of venous thromboembolism (VTE) in patients with severe traumatic brain injury (TBI).Methods:A retrospective case-control study was conducted for clinical data of 180 severe TBI patients admitted to West China Hospital, Sichuan University from July 2019 to July 2021, including 137 males and 43 females, aged 18-93 years [(50.8±18.2)years]. Glasgow Coma Scale (GCS) was 3-8 points [4 (3, 6)points].VTE was presented in 95 patients (thrombosis group), but was not seen in 85 patients (non-thrombosis group). Univariate analysis was used to detect the correlation of the following data with the occurence of VTE, inlcuding sex, age, body mass index (BMI), hypertension, diabetes, laboratory indicators measured on admission and at days 3-5 after admission [hemoglobin (Hb), platelet counts (PLT), antithrombin III, prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D)], tracheal intubation or not, operation or not, volume of intraoperative blood transfusion, operation time, anesthesia time, admission to ICU or not, mechanical ventilation or not, pharmacological prophylaxis or not, deep venous catheterization or not, parenteral nutrition or not, tracheal intubation time, tracheotomy or not, pneumonia, stress ulcer, blood transfusion or not and hospital stays. Multivariate Logistic regression analysis was used to identify the independent risk factors for VTE.Results:Univariate analysis showed that the occurence of VTE was correlated with sex, laboratory indicators measured on admission (TT, FIB, D-D), tracheal intubation, operation, intraoperative blood transfusion, operation time, anesthesia time, admission to ICU, mechanical ventilation, laboratory indicators measured at days 3-5 after admission (PLT, TT, FIB, D-D), deep venous catheterization, parenteral nutrition, tracheal intubation, tracheotomy, pneumonia, blood transfusion and hospital stays (all P<0.05 or 0.01), not with age, BMI, hypertension, diabetes, laboratory indicators measured at admission (Hb, PLT, antithrombin III, PT, APTT), laboratory indicators measured at days 3-5 after admission (Hb, antithrombin III, PT, APTT), pharmacological prophylaxis and stress ulcer (all P>0.05). Multivariate Logistic regression analysis showed that higher FIB on admission ( OR=1.27, 95% CI 1.04-1.56, P<0.05), tracheal intubation ≥7 days ( OR=2.98, 95% CI 1.40-6.33, P<0.01), tracheotomy ( OR=2.49, 95% CI 1.11-5.60, P<0.05), blood transfusion ( OR=2.75, 95% CI 1.25-6.06, P<0.05) and hospital stays >14 days ( OR=3.05, 95% CI 1.36-6.85, P<0.01) were significantly related to the occurence of VTE. Conclusion:Higher FIB on admission, tracheal intubation ≥7 days, tracheotomy, blood transfusion and hospital stays >14 days are independent risk factors for the occurence of VTE in severe TBI patients.

Objective:To investigate the immune characteristics of SARS-CoV-2 membrane (M) protein, especially the possibility of inducing antibody-dependent enhancement effect (ADE).Methods:Full-length SARS-CoV-2 M protein was prepared by prokaryotic expression system and purified. BALB/c mice were immunized subcutaneously three times (on day 1, day 14 and day 21) by purified M protein. Serum samples were collected before immunization and after each immunization. The specificity of immune sera against M protein was identified by Western blot, and the antibody titers were detected by ELISA and neutralization test. In the presence of anti-M protein serum, the proliferation of SARS-CoV-2 in dendritic cells, nature killer cells, T and B cells was detected in vitro. Results:The immune sera from BALB/c mice immunized with purified full-length M protein of SARS-CoV-2 specifically recognized viral M protein. The titer of anti-whole virus antibody in immune sera was about 1∶400, but the antibody could not neutralize live virus. Moreover, the antibody could not help the virus to infect and proliferate in the various types of immune cells with Fc receptor (FcR).Conclusions:Non-neutralizing antibody induced by M protein could not cause ADE through FcR pathway.

Objective:To evaluate the standardized residency training of obstetrics and gynaecology in Shengjing Hospital of China Medical University with Milestones evaluation system of obstetrics and gynecology, and to evaluate the feedback effect of the system.Methods:An improved Milestones evaluation form was developed to evaluate the self-evaluation and clinical tutor's scores, collect the results and make a statistical analysis of the 1-3 years standardized training residents of the Shengjing Hospital of China Medical University in September 2019. GraphPad Prism 8 software was used for data collection and statistical analysis, and Box-Plots software was used for drawing analysist. Descriptive statistics method was used for the general situation of the research objects. After the students' self-evaluation and tutor's scores passed the normal distribution and variance homogeneity test, paired t test was performed, and the scores of residents from different sources were analyzed by variance analysis. Results:A total of 164 residents of obstetrics and gynaecology were evaluated, and there were significant differences between self-evaluation and teacher's evaluation in medical knowledge, learning ability and system work ( P<0.05). The competency scores of the first year residents ranged from 3.003 to 4.556, and at the end of the course they increased to 4.921 to 5.974, showing statistically significant differences in each item compared with the first year ( P<0.001). After three years of training, residents from different sources showed significant improvement ( P<0.001). Conclusion:The Milestones evaluation system of the obstetrics and gynecology can be used for the training assessment and feedback of the residents in obstetrics and gynecology specialty. The self-assessment of residents helps to understand the level of self-assessment, and the teacher's evaluation helps to correct the bias generated by self-assessment. The systematic and staged Milestones evaluation system can instruct the clinical tutors to instruct the residents in accordance with their aptitude, and give feedback on the training effect of the residency training base.