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.

Objective:To observe the effects of electroacupuncture(EA)intervention on norepinephrine(NE)andα2A adrenergic receptors(α2A-R)in the dorsal root ganglion(DRG)of mice with spared nerve injury(SNI).Methods:Male C57BL/6 mice were randomly divided into sham surgery group(Sham),model group(SNI),negative control EA group(SNI+NC-EA),and EA group(SNI+EA).Mechanical and thermal stimuli were used to measure the paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL).Immunofluorescence staining was used to detect the sprouting of sympathetic nerve fibers and the co-localization of α2A-R with large-diameter sensory neurons in mouse DRG.Enzyme-linked immunosorbent assay(ELISA)kits were used to measure NE levels in mouse serum and DRG,and Western Blot was used to detect tyrosine hydroxylase(TH)and α2A-R expression levels in DRG.Results:After SNI,the PWMT and PWTL were significantly decreased,and after electroacupuncture treatment,PWMT and PWTL were reversed and increased.Immune fluorescence staining showed that sympathetic ganglion sprouting increased in DRG after SNI,and significantly decreased after electroacupuncture;After SNI,NE,α2A-R,and TH in DRG all significantly increased,and their expression decreased after electroacupuncture intervention,but NE in the serum did not change significantly.Conclusion:In the SNI model,electroacupuncture may regulate the sympathetic-sensory coupling by inhibiting the release of NE and the expression of α2A-R in DRG,thereby producing analgesic effects.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Objective:To compare the efficacy and safety of Castor single-branch stent and in vitro fenestration stent in treating thoracic aortic diseases with insufficient landing zone.Methods:The clinical data of patients with thoracic aortic diseases treated with Castor single-branch stent or in vitro fenestrated stent between December 2017 and June 2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. A total of 184 patients were included, 99 patients were treated with Castor branch stent, and 85 patients with in vitro fenestration stent. All patients′ general clinical data, surgical data, perioperative and follow-up clinical and imaging data, and postoperative complications were collected. The χ2 test was used to compare the incidence of complications between the two groups, and the Kaplan-Meier method was used to plot the survival rate without adverse events between the two groups. Results:Stent placement was successful in all patients, and the success rate of the technique was 100%. Other branches were reconstructed in 2 patients in the Castor group and double fenestrated stent were reconstructed in 12 patients in the fenestrated group. The mean operation time of the Castor group was significantly shorter than that of the fenestrated group, the number of patients who received local anesthesia was significantly lower than that of the fenestrated group, and the endoleak rate during follow-up was significantly lower than that of the fenestrated group ( P<0.05). There was no significant difference in the postoperative hospital stay, the incidence rate of perioperative complications, mortality, the incidence rate of neurological complications, new dissection or aneurysm rate, branch stent stenosis rate, second surgical intervention rate, and false lumen thrombosis between the two groups ( P>0.05). The adverse event-free survival rate of the Castor group was slightly higher than that of the fenestrated group, but its difference was not statistically significant ( P>0.05). Conclusion:Castor branch stent and in vitro fenestration stent have good short-term and mid-term efficacy in the treatment of aortic diseases with insufficient landing zone, which are safe and effective options for reconstruction of LSA and other branch arteries.

Biliary tract cancer is characterized by high invasiveness, occult early clinical manifestations and rapid progression. Surgical resection typically fails to achieve satisfactory outcomes. Biliary tract cancer exhibits low sensitivity to radiotherapy and chemotherapy. The prognosis of patients is extremely poor. Genomics research based on next-generation sequencing technology has made some advances. The gene mutation spectrum of biliary tract cancer has been preliminarily revealed, which lays a foundation for the study of molecular typing. This review summarizes the research progress and clinical application of gene mutation spectrum of biliary tract cancer in recent years, aiming to provide reference for the clinical diagnosis, treatment and basic research.

Biliary tract cancer is characterized by high invasiveness, occult early clinical manifestations and rapid progression. Surgical resection typically fails to achieve satisfactory outcomes. Biliary tract cancer exhibits low sensitivity to radiotherapy and chemotherapy. The prognosis of patients is extremely poor. Genomics research based on next-generation sequencing technology has made some advances. The gene mutation spectrum of biliary tract cancer has been preliminarily revealed, which lays a foundation for the study of molecular typing. This review summarizes the research progress and clinical application of gene mutation spectrum of biliary tract cancer in recent years, aiming to provide reference for the clinical diagnosis, treatment and basic research.

OBJECTIVES: Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO). METHODS: Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting. RESULTS: The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO. CONCLUSIONS Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.
Animals ; Rats ; Blood-Brain Barrier/metabolism* ; Brain Ischemia ; Claudin-5/metabolism* ; Infarction, Middle Cerebral Artery/metabolism* ; Ischemic Stroke/metabolism* ; Occludin/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Reperfusion Injury/metabolism*

Objective:To investigate the reliability of gene detection results using pleural effusion from patients with lung adenocarcinoma, and evaluate the clinical application value of pleural effusion supernatant in gene detection of lung adenocarcinoma.Methods:A total of 145 patients with lung adenocarcinoma pathologically confirmed from February 2015 to December 2019 were included, including 129 patients from Peking University Cancer Hospital & Institute and 16 patients from the First Hospital of Fangshan District. In this study, 55 pleural effusion supernatant samples, 52 plasma samples, and 48 tumor tissue samples were selected to targeted next-generation sequencing (NGS) of 1, 021 cancer-related genes, and the ability of gene detection of pleural effusion supernatant, tumor tissue, and plasma were compared.Results:The mutation rate of pleural effusion supernatant was 100.00%, the median maximum somatic allele frequency (MSAF) was 16.40%, and the chromosomal copy number detection (CNV) was 45.45%, showed no statistically significant difference compared with the tumor tissue samples (95.56%, 26.55% and 45.83%, respectively, P>0.05); However, it showed many advantages compared with plasma samples (90.38%, 2.50% and 9.62%). Among the drug-related driver genes, the percentage of EGFR mutation carrier in pleural effusion supernatant, tumor tissue and plasma were 61.82%, 58.33% and 38.46% respectively, the percentagein pleural effusion was higher than that in plasma ( P<0.05), but had no statistical difference compared with the tissue ( P>0.05). Conclusions:Pleural effusion supernatant has high reliability and effectiveness in detecting gene mutation. When lung adenocarcinoma patients are difficult to obtain tumor tissue clinically, it can be used as a substitute sample for genetic testing.

Objective:To investigate the reliability of gene detection results using pleural effusion from patients with lung adenocarcinoma, and evaluate the clinical application value of pleural effusion supernatant in gene detection of lung adenocarcinoma.Methods:A total of 145 patients with lung adenocarcinoma pathologically confirmed from February 2015 to December 2019 were included, including 129 patients from Peking University Cancer Hospital & Institute and 16 patients from the First Hospital of Fangshan District. In this study, 55 pleural effusion supernatant samples, 52 plasma samples, and 48 tumor tissue samples were selected to targeted next-generation sequencing (NGS) of 1, 021 cancer-related genes, and the ability of gene detection of pleural effusion supernatant, tumor tissue, and plasma were compared.Results:The mutation rate of pleural effusion supernatant was 100.00%, the median maximum somatic allele frequency (MSAF) was 16.40%, and the chromosomal copy number detection (CNV) was 45.45%, showed no statistically significant difference compared with the tumor tissue samples (95.56%, 26.55% and 45.83%, respectively, P>0.05); However, it showed many advantages compared with plasma samples (90.38%, 2.50% and 9.62%). Among the drug-related driver genes, the percentage of EGFR mutation carrier in pleural effusion supernatant, tumor tissue and plasma were 61.82%, 58.33% and 38.46% respectively, the percentagein pleural effusion was higher than that in plasma ( P<0.05), but had no statistical difference compared with the tissue ( P>0.05). Conclusions:Pleural effusion supernatant has high reliability and effectiveness in detecting gene mutation. When lung adenocarcinoma patients are difficult to obtain tumor tissue clinically, it can be used as a substitute sample for genetic testing.

Background::Hepatopancreatoduodenectomy (HPD) has been considered the only curative treatment for metastatic cholangiocarcinoma and some locally advanced gallbladder cancers (GBCs). However, HPD has not yet been included in treatment guidelines as a standard surgical procedure in consideration of its morbidity and mortality rates. The aim of this study was to evaluate the safety and effectiveness of HPD in treating biliary malignancies.Methods::The medical records of 57 patients with advanced biliary cancer undergoing HPD from January 2009 to December 2019 were retrospectively retrieved. A case-control analysis was conducted at our department. Patients with advanced GBC who underwent HPD (HPD-GBC group) were compared with a control group (None-HPD-GBC group). Baseline characteristics, preoperative treatments, tumor pathologic features, operative results, and prognosis were assessed.Results::Thirteen patients with cholangiocarcinoma and 44 patients with GBC underwent HPD at our department. Significant postoperative complications (grade III or greater) and postoperative pancreatic fistula were observed in 24 (42.1%) and 15 (26.3%) patients, respectively. One postoperative death occurred in the present study. Overall survival (OS) was longer in patients with advanced cholangiocarcinoma than in those with GBC (median survival time [MST], 31 months vs. 11 months; P < 0.001). In the subgroup analysis of patients with advanced GBC, multivariate analysis demonstrated that T4 stage tumors ( P = 0.012), N2 tumors ( P = 0.001), and positive margin status ( P = 0.004) were independently associated with poorer OS. Patients with either one or more prognostic factors exhibited a shorter MST than patients without those prognostic factors ( P < 0.001). Conclusion::HPD could be performed with a relatively low mortality rate and an acceptable morbidity rate in an experienced high-volume center. For patients with advanced GBC without an N2 or T4 tumor, HPD can be a preferable treatment option.