The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Objective To investigate the expression of miR-143-3p and ATG2B in serum of patients with bladder cancer and their relationship with clinicopathology,prognosis and survival of patients.Methods Eighty-eight patients who underwent radical bladder cancer surgery in our hospital from January 2017 to January 2019 were regarded as the research group,and 80 volunteers who underwent physical examination in our hospital were included as the control group.Quantitative real-time PCR(qRT-PCR)method was performed to detect the levels of miR-143-3p and ATG2B;The predictive value of miR-143-3p and ATG2B for bladder cancer was evaluated by ROC curve.Draw survival curve using Kaplan Meier method;The prognostic factors of bladder cancer patients were analyzed by Cox regression.Results The expression level of miR-143-3p in the serum of bladder cancer patients was lower than that in the control group(0.68±0.12 vs.0.87±0.26),and the expression level of ATG2B was higher(1.02±0.30 vs.0.61±0.18)(P＜0.05);the expression level of miR-143-3p in serum of postoperative patients was higher than that before operation(0.77±0.23 vs.0.68±0.12),and the expression level of ATG2B was lower than that before operation(0.85±0.26 vs.1.02±0.30)(P＜0.05);The study group showed a negative correlation between miR-143-3p and ATG2B expression(r=-0.454,r=-0.407,P＜0.01);The AUC of miR-143-3p in the diagnosis of bladder cancer was 0.846(95％CI:0.783-0.897),the sensitivity and specificity were 79.55％and 78.75％respectively;The AUC of ATG2B in the diagnosis of bladder cancer was 0.883(95％CI:0.824-0.927),the sensitivity and specificity were 78.41％and 81.25％respectively;The AUC for the diagnosis of bladder cancer was 0.939(95％CI:0.891-0.970),the sensitivity and specificity were 87.50％and 88.75％,respectively.The 3-year survival rate of the miR-143-3p low expression group was 34.88％(15/43)lower than that of the high expression group 77.78％(35/45),and the 3-year survival rate of the ATG2B high expression group was 40.91％(18/44)lower than that of the low expression group 72.73％(32/44).The differences were statistically significant(Log rank x2=18.055,8.658,P=0.000,0.003).Lymph node metastasis,distant metastasis,tumor pathological grade,TNM stage,miR-143-3p,ATG2B are all factors influencing the survival of bladder cancer patients.Conclusion The serum expression of miR-143-3p in patients with bladder cancer is low,and the expression of ATG2B is high,and the expressions of the two are closely related to the clinicopathological characteristics and prognosis of patients with bladder cancer.

Objective:To investigate the postnatal changes in urinary metabolic amino acid levels in infants with retinopathy of prematurity (ROP) and their effect on ROP, and to analyze the amino acid metabolic pathways that may be involved in the development of ROP.Methods:A retrospective cohort study. From January 2020 to December 2023, 65 premature infants with severe ROP (ROP group) who were hospitalized, born with gestational age <32 weeks in Children's Hospital Affiliated to Zhengzhou University were included in the study. Fifty premature infants with matched sex and gestational age and no ROP were selected as the control group. Urine amino acids and their derivatives were detected by gas chromatography-mass spectrometry. The two groups were compared by independent sample t test. The metabonomics of urinary amino acids was analyzed by orthogonal partial least squares discriminant analysis (OPLS-DA) model. The variable projection importance (VIP) score >1 suggested that the substance was two groups of differentially expressed amino acids. The predictive value of urinary amino acids for severe ROP was compared by using the receiver's operating characteristic (ROC) curve and the area under the curve. After t test and metabolomics analysis, the two groups of amino acids with large differences were normalized and compared by Pearson correlation analysis. The Kyoto Encyclopedia of Genes and Genomes database was used to analyze the metabolic pathways of differentially expressed amino acids involved in ROP. Results:Compared with the control group, the concentrations of oxalic acid -2 and thiodiacetic acid-2 in urine metabolites of children in ROP group were significantly decreased, while the concentrations of 4-hydroxybutyric acid-2, 3-methylpentadienoic acid-2(1), 2-ketoglutarate-ox-2(2) and 3, 6-epoxy-dodecanedioic acid-2 were significantly increased, with statistical differences ( t=0.036, 0.005, 0.038, 0.032, 0.022, 0.011; P<0.05). The results of OPLS-DA analysis showed that amino acids of urinary metabolites in ROP group and control group were distributed in the left and right regions of the scatter plot, and there was a satisfactory separation trend between the two groups (R 2Ycum=0.057 4, Q2cum=0.025 7, P<0.05). As shown in the S-Plot, the amino acids biased towards two stages are glycolic acid-2, phosphoric acid-3, oxalic acid-2, thiodiacetic acid-2, 4-hydroxybutyric acid-2, 3-methylcrotonylglycine-1, 3-methylpentadienoic acid-2(1), 2-ketoglutarate-ox-2(2) and 3, 6-epoxy- dodecanedioic acid-2, respectively. Eleven differentially expressed amino acids with VIP score >1 were screened, among which the highest VIP score was oxalate-2, glycerate-3, phosphoric acid-3, 3-methylcrotonylglycine-1, uranoic acid -3 and thiodiacetic acid-2. The difference of amino acid concentration between the two groups was the highest in 4-hydroxybutyric acid-2 and thiodiacetic acid-2. The correlation between oxalic acid-2 and glycerate-3 was the highest ( r=0.830, P<0.001), and most amino acids were positive correlated. ROC curve fitting analysis showed that the combined prediction of 11 differenly-expressed amino groups had the largest area under the curve (0.816), the cutoff value was 0.531, and the sensitivity and specificity were 83.1% and 70.0%, respectively. The enrichment analysis of these 11 amino acids with significant differences suggested that the main pathways involved included butyrate metabolism, glyoxylic acid and dicarboxylic acid metabolism and lipoic acid metabolism. Conclusion:Abnormal amino acid metabolism of 4-hydroxybutyrate-2, 3-methylpentadienoic acid-2(1), thiodiacetic acid-2, 2-ketoglutarate-ox-2(2), 3, 6-epoxy-dodecanedioic acid-2 may have a certain effect on the occurrence of ROP.

Objective:To analyze the clinical phynotypes of fetuses with 22q11.2 microduplications.Method:Eleven fetuses were diagnosed with 22q11.2 microduplications among 2 969 cases who underwent prenatal chromosomal microarray analysis from January 2016 to February 2020. The phenotypes, indications for invasive prenatal diagnosis, genetic results, pregnancy outcomes and postnatal clinical presentation were analyzed.Results:There were 6 cases diagnosed with classic 3.0 Mb microduplication (DiGeorge and velocardiofacial syndromes, DGS/VCFS) in the 22q11.2, 1 case with 1.5 Mb proximal microduplication and 4 cases with distal small segment microduplication (E-H). Out of 11 fetuses with 22q11.2 microduplications,7 cases were inherited, 2 cases was de novo and data were not available for 2 cases. Vicular septal defect and anencephalu were diagnosed by ultrasonography in 2 cases,fetal growth restriction was diagnosed in 2 cases,no any abnormalities were found in remaining 7 cases. Seven cases(3 cases of classic 3.0 Mb microduplication, 1 case of proximal microduplication and 3 cases of distal small segment microduplication) were delivered at full-term;and pregnancy was terminated in 4 cases. Seven infants were followed up after birth, 4 infants were normal, 3 showed abnormal phenotypes.Conclusion:The clinical phenotypes after birth of fetuses with 22q11.2 microduplication are diverse. Prenatal genetic counseling is necessary,so that pregnant women and their families can fully understand the possible clinical phenotypes and make informed choices.

OBJECTIVE: To explore strategies of prenatal genetic testing for fetuses featuring abnormal skeletal development. METHODS: Clinical data of 17 fetuses with skeletal dysplasia was collected. The results of genetic testing and outcome of pregnancy were analyzed. RESULTS: For 12 fetuses, the femur-to-foot length ratio was less than 0.9. Thirteen fetuses had a positive finding by genetic testing. One fetus was diagnosed with chromosomal aneuploidy, three were diagnosed with microdeletion/microduplications, and nine were diagnosed with hereditary bone diseases due to pathological variants of FGFR3, COL1A2, GPX4 or ALPL genes. CONCLUSION For fetuses with skeletal dysplasia characterized by short femur, in addition to chromosomal karyotyping and microarray analysis, sequencing of FGFR3 and other bone disease-related genes can improve the diagnostic rate.
Bone Diseases, Developmental/genetics* ; Female ; Fetus/diagnostic imaging* ; Genetic Testing ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Ultrasonography, Prenatal

Objective To evaluate endoscopic surgical treatment of synchronous esophageal squamous cell carcinoma and adenocarcinonm at the esophagogastric junction.Methods The clinical data of 17 patients with synchronous esophageal squamous cell carcinoma associated with adenocarcinoma of esophagogatric junction between Jan 2010 and Jan 2017 were analyzed retrospectively.Results Among these 17 patients,9 patients underwent thoracoscopy and laparoscopy with partial resection of esophagus and proximal stomach,and gastroesophageal and neck anastomosis.3 patients underwent thoracoscopy and laparoscopy with partial resection of esophagus and proximal stomach,gastroesophageal intrathoracic anastomosis.Laparoscopic radical total gastrectomy combined with radiotherapy for esophageal cancer was performed in 5 cases.There was not perioperative death or serious complications.The cumulative survival rates of 1,3 and 5 years after surgery were 100％,42％ and 24％,respectively.Conclusion Thoracolaparscopic surgery combined with local radiation therapy is a safe and effective treatment for patients with synchronous esophageal squamous cell carcinoma and adenocarcinoma at esophagogastric junction.

OBJECTIVE: To develop a fiber Raman endoscopic probe that can be integrated in a gastroscope and evaluate its value in the diagnosis of gastric cancer. METHODS: The Raman spectra of gastric cancer tissues and normal tissues were obtained using the fiber Raman endoscopic probe and confocal microRaman spectroscopy. After preprocessing with smoothing, baseline elimination and normalization, the spectroscopic data were analyzed by the principle component analyses combined with stechiometry. Based on the pathological results, the diagnostic accuracy, sensitiveness and specificity of Raman spectroscopy combined with stechiometry were evaluated. RESULTS: The fiber Raman endoscopic probe and microRaman spectroscopy revealed significantly different Raman spectra between gastric cancer tissues and normal tissues. The diagnostic accuracy, sensitiveness and specificity of the fiber Raman endoscopic probe was 80.56%, 88.89%, and 84.72% for gastric cancer, respectively. CONCLUSIONS The fiber Raman endoscopic probe combined with stechiometry provides an effective modality for the diagnosis of gastric cancer and can well distinguish gastric cancer tissue from normal gastric tissues.
Endoscopy ; Fiber Optic Technology ; Humans ; Sensitivity and Specificity ; Spectrum Analysis, Raman ; Stomach Neoplasms

Cancer is the most cause death of among adolescents and young adults (AYAs).Psychological distress caused by cancer affects AYAs' effective coping abilities of disease,physical symptoms and treatment.This paper mainly introduces the related concepts,screening tools and intervention progress of psychological distress of AYAs cancer patients to deepen the understanding of these among clinical professionals and provide reference for implement effective interventions to patients.

Objective To evaluate the accuracy of air column width difference (ACWD) between inflation and deflation of the cuff of the endotracheal tube (ETT) in predicting post-extubation stridor (PES).Methods A total of 102 intubated patients of both sexes and all ages,who were mechanically ventilated for ≥24 h in the intensive care unit,of American Society of Anesthesiologists physical status Ⅲ or Ⅳ,were enrolled in the study.After the patients were in a stable condition and recovered consciousness and myodynamia,they were weaned from the ventilator,and ultrasound examination of the larynx was performed to determine ACWD between ETT cuff inflation and deflation.PES was assessed using blinding nethod after extubation,and the patients were divided into 2 groups depending on whether or not the patients developed PES:PES group (group P) and non-PES group (group N).Results There were 94 patients in group N and 8 patients in group P.Compared with group N,ACWD was significantly decreased in group P (P＜ 0.05).The cut-off value of ACWD determined by the receiver operating characteristic curve was 1.65 mm,the sensitivity and specificity of ACWD were 0.830 and 0.750,respectively,and the area under the receiver operating characteristic curve was 0.801.Conclusion For the intubated patients who are mechanically ventilated for ≥24 h in an intensive care unit,ACWD between ETT cuff inflation and deflation＜ 1.65 mm can effectively predict PES.