Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

The increasing prevalence of metabolic diseases poses a significant threat to public health,high-lighting the urgent need to identify effective therapeutic targets.Humanin(HN),a 24-amino acid linear peptide synthe-sized from mitochondrial DNA,has been previously acknowledged for its neuroprotective properties.Recent research indi-cates that HN can regulate glucose and lipid metabolism and has shown promise in treating metabolic disorders in animal models using either HN or its analogs.This review outlines the fundamental biological functions and signal transduction mechanisms of HN,and comprehensively evaluates its role and therapeutic potential in type 2 diabetes mellitus,nonalco-holic fatty liver disease,atherosclerosis and polycystic ovary syndrome,aiming to examine the potential of HN as a target for the prevention and treatment of metabolic diseases.

Objective:To investigate the effect of ultrasonic debridement mediated by 0.9% sodium chloride solution and 0.5% iodophor volt combined with eddy current washing and high pressure pulse washing on the removal of colonized bacteria on the wound surface of diabetic foot and wound healing.Methods:From March to November 2020, a total of 60 patients using ultrasonic therapy for debridement were divided into control group, experimental group 1, experimental group 2 and experimental group 3 by random digit table in the fourth People′s Hospital of Dalian. The final effective data collected was 15 cases in each group. The control group was given ultrasonic debridement mediated by 0.9% sodium chloride solution and eddy current washing.Experimental group 1 was given ultrasonic debridement mediated by 0.9% sodium chloride solution and high pressure pulse washing. Experimental group 2 received 0.5% iodophor mediated ultrasonic debridement and eddy current washing. Experimental group 3 0.5% iodophor mediated ultrasonic debridement and high pressure pulse washing. The size of the wound was measured, sampled and bacterial cultured before and after the first, fifth and 10th intervention. The wound bacterial clearance rate and wound area reduction rate were calculated and compared.Results:Before and after 3 interventions, the bacterial clearance rate and the total reduction of wound surface in 4 groups were increased ( P<0.01), the total bacterial clearance rate of experimental group 3 was the highest, which was (93.85 ± 9.87)%.The total reduction rate of wound in experimental group 2 was the highest, which was (20.831 4 ± 9.379 8)%. Conclusions:0.5% iodophor mediated ultrasonic debridement combined with high pressure pulse washing is the most effective way in the removal of diabetic foot wounds, and 0.5% iodophor solution mediated ultrasonic debridement combined with eddy current washing is the most effective in reducing diabetic foot wounds.

Ferroptosis is defined as an iron-dependent, non-apoptotic cell death pathway, with specific morphological phenotypes and biochemical changes. There is a growing realization that ferroptosis has significant implications for several neurodegenerative diseases. Even though ferroptosis is different from other forms of programmed death such as apoptosis and autophagic death, they involve a number of common protein molecules. This review focuses on current research on ferroptosis and summarizes the cross-talk among ferroptosis, apoptosis, and autophagy that are implicated in neurodegenerative diseases. We hope that this information provides new ideas for understanding the mechanisms and searching for potential therapeutic approaches and prevention of neurodegenerative diseases.
Apoptosis ; Autophagy ; Cell Death ; Ferroptosis ; Humans ; Neurodegenerative Diseases

Objective:To explore the relationship between genotypes and phenotypes in hypertrophic cardiomyopathy(HCM) patients using whole exome sequencing(WES) and three-dimensional speckle-tracking echocardiography(3D-STE).Methods:Twenty patients with apical HCM(ApHCM) and 25 patients with non-apical HCM(non-ApHCM) from June 2018 to January 2019 in Zhongshan Hospital of Fudan University were enrolled. All subjects underwent venous blood sampling and WES. Regular two-dimensional echocardiography was performed to acquire the following parameters: interventricular septum thickness, left ventricular posterior wall thickness, left ventricular end diastolic diameter, left ventricular end systolic diameter, the maximum thickness of left ventricular walls and left ventricular ejection fraction(LVEF). Full volume images were collected and then off-time analyzed with 3D-STE to acquire global longitudinal strain(GLS), global circumferential strain(GCS), twist and torsion. The relationships between above parameters, genotypes and phenotypes of left ventricle were analyzed.Results:Mutations were found in 73% of HCM patients.The two most common genes MYBPC3 and MYH7 accounted for 18% and 15% of mutations respectively. KCNEc.79C>T(p.Arg27Cys) and PRKAG2c.905G>A (p.Arg302Gln) were detected in both ApHCM group and non-ApHCM group. In ApHCM group, 60% of patients carried genetic mutations, which was significantly lower than non-ApHCM group(84%)( P=0.041). Compared with non-ApHCM group, GLS in ApHCM group was significantly higher ( P=0.008). There was no statistical difference of GLS between patients with mutations and without mutations( P=0.068). GLS demonstrated a moderate correlation with morphologic types of HCM(ApHCM and non-ApHCM)( r=0.364, P=0.012). However, there was no correlation between GLS and the condition of mutations( r=0.269, P=0.062). Conclusions:The relationship between genetics and phenotypic expression of HCM appears to be complex and heterogeneous. There are marked differences in gene mutations and systolic functions between ApHCM and non-ApHCM. The value of GLS correlates with the shape of left ventricle but not with genotypes.

OBJECTIVE: To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments. METHODS: We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing. The relapse following the treatments, defined as hematological, cytogenetic and molecular biological recurrences, were analyzed in these patients. RESULTS: Of the 19 patients with CML-T315I, 14 (73.7%) were in CML-CP stage at the initial diagnosis, and 13 (81.2%) were high-risk patients based on the Sokal scores. All the 19 patients were treated with TKI after the initial diagnosis, and during the treatment, 15 (78.9%) patients were found to have additional chromosomal aberrations, and 10 (52.6%) had multiple mutations; 13 (68.4%) of the patients experienced disease progression (accelerated phase/blast crisis) before the detection of T315I mutation, with a median time of 40 months (5-120 months) from the initial diagnosis to the mutation detection. After detection of the mutation, 12 patients were treated with ponatinib and 7 were managed with the conventional chemotherapy regimen, and their overall survival rates at 3 years were 83.3% and 14.2%, respectively ( < 0.001). CONCLUSIONS CML patients resistant to TKI are more likely to have T315I mutations, whose detection rate is significantly higher in the progressive phase than in the chronic phase. These patients often have additional chromosomal aberrations and multiple gene mutations with poor prognoses and a high recurrence rate even after hematopoietic stem cell transplantation. Long-term maintenance therapy with ponatinib may improve the prognosis and prolong the survival time of the patients.
Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; Humans ; Imidazoles ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mutation ; Pyridazines ; Retrospective Studies

Objective To observe the efficacy of mesalazine combined with probiotics in the treatment of ulcerative colitis. Methods 60 patients with ulcerative colitis who were admitted to our hospital from May 2015 to May 2017 were selected randomly. These patients were divided into two groups according to the treatment method: mesalamine com bined with probiotic group(combination therapy group, n=30) and mesalamine alone treatment group (n=30). The clinical symptom score, endoscopic score, serum CRPlevel, clinical efficacy, incidence of adverse reactions and recurrence in both groups were statistically analyzed. Results Compared with those before treatment, the clinical symptom score, en doscopic score and serum CRPlevel were significantly lower in both groups after treatment(P＜0. 05); After treatment, clinical symptom score, endoscopic score and serum CRPlevel were significantly lower in the combination therapy group than those in the treatment alone group(P＜0. 05). The total effective rate in the combination therapy group was 93. 3％(28/30), significantly higher than 63. 3％(19/30) in the treatment alone group(P＜0. 05). The recurrence rate was 13. 3％ (4/30), significantly lower than that of 33. 3％(10/30) in the treatment alone group(P＜0. 05). However, the incidence rates of adverse reactions in the two groups was 6. 7％(2/30) and 10. 0％(3/30) respectively, which were not significantly different(P＞0. 05). Conclusion The efficacy of mesalazine combined with probiotics in the treatment of ulcerative colitis is more significant than that of mesalazine alone. At the same time, it is also more effective in improving the clinical symptoms, reducing the serum CRPlevel and recurrence rate in the patients, and will not increase the patients' adverse reactions to a great extent, so it is worthy of promotion and application in clinical settings.

Objective To study the influence of high quality nursing mode on the quality of life in endoscopic retrograde cholangiopancreatography (ERCP) patients. Methods A total of 292 patients with ERCP were randomly divided into control group and observation group with 146 cases in each group by the randomized block design method. The control group was given the conventional nursing care. The observation group was given the high quality nursing care based on the conventional nursing care. The score of Quality of Life of the World Health Organization (WHOQOL- 100), Quality of Life Index of Gastrointestinal Tract (GIQLI), Hamilton Anxiety Scale (HAMA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Visual Analogue Scale(VAS) before and after nursing care were observed and compared. The difference impact of two kinds of nursing mode on nursing quality between two groups was evaluated. Results WHOQOL-100 score in the observation group after treatment, including physiology and psychology and environment and social relations state such as grading, was respectively (59.3 ± 6.0), (61.8 ± 7.2), (60.3 ± 6.2), (62.8 ± 7.3) points and GIQLI index included self-conscious symptom and body physiological status and daily and social activities,such as state of emotional and psychological and the overall score, was respectively (79.8±4.9), (19.8±1.8), (14.7±1.9), (19.2±2.8), (105.7±6.6) points, which was (50.9±6.3), (52.5±6.7), (51.4±5.6), (53.4±7.1), (67.2±4.8), (15.6±1.9), (10.2±1.8), (16.3±2.3), (94.4 ± 6.2) points in control group, the difference between two groups was statistically significantly(t=1.876-2.327, P<0.05). HAMA score and SAS scores and SDS score and VAS score in the observation group after nursing was respectively (24.28 ± 4.78), (29.48 ± 6.54), (30.55 ± 7.32), (4.55 ± 1.18) points and respectively (36.68 ± 5.39), (41.72 ± 6.03), (42.65 ± 7.21), (6.07 ± 1.17) points in the control group, the difference between two groups was statistically significantly(t=2.876-4.012, P<0.05). Conclusions High quality nursing mode of ERCP in patients with perioperative patients of psychological and physiological all have different degrees of improvement and is suitable for popularization and application in clinic.

Objective To investigate the effect of chitooligosaccharide (COS) on hepatic triglyceride (TG) metabolism and related mechanisms.Methods The LO2 cells treated by 1 mmol/L fatty acid were used as model group,the cells treated by 1 mmol/L fatty acid and 0.5 mg/ml COS were used as COS group,and the untreated cells were used as control group.The TG content in cells was measured.RT-PCR and Western blot were used to measure the mRNA and protein expression of sterol regulatory element binding protein-1 c (SREBP-1 c),fatty acid synthase (FAS),and camitine palmityl transferase 1A (CPT1A) in each group.Male C57BL/6J mice were randomized into control group,high-fat group,and COS group to receive different treatments.Sixteen weeks later,the liver was harvested for HE and oil red O staining to measure the content of TG in the liver.The t-test or one-way analysis of variance was used for comparison of data between groups,and the SNK method was used for comparison of data between any two groups.Results The LO2 cells in the model group had an increased number of lipid droplets and an increased TG content,and after COS treatment,the TG content was low.The COS group had significantly lower relative mRNA expression of SREBP-1 c and FAS compared with the model group (1.135 ± 0.177 vs 2.322 ± 0.198,F =60.457,P ＜ 0.01;1.226 ± 0.150 vs 1.801 ± 0.159,F =24.753,P ＜ 0.01),while compared with the control group,the COS group had significantly higher mRNA expression of CPT1 A (1.254 ± 0.156 vs 1.908 ± 0.087,F =31.734,P ＜ 0.01).The COS group had significantly lower protein expression of SREBP-1 c and FAS than the model group (0.161 ± 0.081 vs 0.351±0.016,F=188.920,P ＜ 0.01;0.332 ± 0.023 vs 1.238 ± 0.051,F=624.069,P ＜ 0.01),and significantly higher protein expression of CPT1A than the model group (1.014 ± 0.033 vs 0.561 ± 0.046,F =193.793,P ＜ 0.01).COS reduced the TG content in the liver in rats on high-fat diet.Conclusion COS can reduce the accumulation of TG in the hepatocyte model of nonalcoholic fatty liver disease and in the liver in rats on high-fat diet,and the possible mechanism may be related to inhibiting the expression of SREBP-lc and downstream FAS,reducing the synthesis of TG,increasing the expression of CPT1 A,and accelerating the breakdown of TG.

Objective To investigate the relationship between the helper T cell 17 (TH 17)/ Regulatory T cells (Treg cells) balance in peripheral blood with acute graft-versus-host reaction (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT),as well as the impact of anti-thymocyte immunoglobulin (ATG) on helper T cells in peripheral blood.Method Seventyeight hematologic patients underwent allo-HSCT,conditioning with or without ATG.Ten healthy volunteers severed as a control group.The helper T and regulatory T cells in peripheral blood were detected by flow cytometry.Enzyme-linked irnmunosorbent assay (ELISA) was used to detect serum concentrations of interleukin(IL)-17,IL-21,IL22,IL23,γ interferon (IFN-γ),and transforming growth factor β1 (TGF-β1).Result The percentage of Treg cells,TH17 cells and ratio of TH17/Treg cells in patients without aGVHD showed no significant difference from the healthy controls (P＞ 0.05).As compared with control group and non aGVHD group,the ratio of Treg cells was increased,the percentage of TH 17 cells,and TH 17/Treg cells were significantly increased in 1-2-degree aGVHD group (P＜0.01).With increased degree of aGVHD,the difference as above was more significant in 3-4-degree aGVHD recipients (P＜0.01).In aGVHD group,the IL-17,IL-23,IL-21 and IFN-γ concentrations were higher than the healthy group (P＜0.01) and non-aGVHD group (P＜0.05).Serum TGF-β1 level in aGVHD group was significantly decreased as compared with healthy group and non-GVHD group (P＜0.05),while IL-22 concentrations showed no statistically significant difference among three groups (P＞0.05).In anti-thymocyte immunoglobulin (ATG) pretreatment group,the absolute count of peripheral blood lymphocytes was less than in healthy control group (P＜0.01).In ATG group,the absolute counts of TH1 cells,TH17 cells,CD3+ CD4+ cells and non-TH1/17 cells were less than in non-ATG group (P =0.0000),while the absolute counts of lymphocytes,CD3+ CD4-cells,and TH 1/17 cells were less than in non-ATG group,but there was significant difference (P＞0.05).Conclusion The balance of TH 17/Treg cells and related cytokines were closely associated with aGVHD after allo-HSCT,and ATG influences the reconstruction of TH 17 and Th1 cells at early stage.