Zinc finger protein 36 (ZFP36) was found to be downregulated in osteosarcoma (OS) tumor tissues. We aimed to investigate the roles and mechanisms of ZFP36 in ferroptosis regulation during OS development. Two Gene Expression Omnibus (GEO) datasets showed that ZFP36 was a differentially expressed gene (DEG) in OS. Western blot and immunohistochemistry results showed that ZFP36 was downregulated in OS tumors and cell lines. ZFP36 overexpression plasmids and small interfering RNAs (siRNAs) were respectively transfected into OS cells. ZFP36 overexpression restrained proliferation, migration, and invasion in MG63 and U2OS cells, while ZFP36 knockdown displayed the opposite results. Moreover, ZFP36 overexpression increased the levels of intracellular Fe²⁺, reactive oxygen species (ROS), and malondialdehyde (MDA), and decreased the levels of glutathione (GSH), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11). ZFP36 overexpression disturbed mitochondrial membrane potential (MMP) and mitochondrial morphology in OS cells. However, ZFP36 knockdown had the opposite results. Mechanistic studies indicated that ZFP36 promoted E2F transcription factor 1 (E2F1) messenger RNA (mRNA) degradation by binding to the AU-rich elements (AREs) within E2F1 3' untranslated region (3'UTR) in OS cells. E2F1 overexpression abrogated the effects of ZFP36 overexpression on malignant progression, ferroptosis, and mitochondrial dysfunction in OS cells. Furthermore, E2F1 promoted the transcription activation of activating transcription factor 4 (ATF4) by binding to ATF4 promoter. E2F1 knockdown inhibited malignant progression, and promoted ferroptosis and mitochondrial dysfunction in OS cells, which was abrogated by ATF4 overexpression. Additionally, MG63 cells transfected with lentivirus ZFP36 overexpression vector (Lv-ZFP36) were injected into nude mice and tumor growth was monitored. ZFP36 overexpression significantly suppressed OS tumor growth under in vivo settings. In conclusion, ZFP36 overexpression promoted ferroptosis and mitochondrial dysfunction and inhibited malignant progression in OS by regulating the E2F1/ATF4 axis. We may provide the promising ZFP36 target for OS treatment.

Objective:To describe the status and influencing factors of nurse-related empowerment perception in inpatients with chronic diseases.Methods:Totally 586 inpatients with chronic diseases from 6 class A hospitals in Shanghai from November 2019 to September 2020 were investigated by the Chinese version of Patient Perception of Patient-empowering Nurses Behaviors (PPPNBS), Self-Efficacy of Chronic Diseases (SECD6), Nurse-patient Trust Scale (NPTS), Chinese version of Chronic Illness Resource Survey (CV-CIRS) and a general information questionnaire which was designed by researchers.Results:The total score of PPPNBS was (134.98 ± 59.60) points, and the average score for each item was (6.14 ± 2.71) points. The total score of SECD6 was (38.81 ± 9.28) points. The total score of NPTS was (141.94 ± 11.42) points, and the total score of CV-CIRS was (57.90 ± 15.24) points, which were positively correlated with empowerment perception through Pearson correlation analysis. Multiple Linear Regression showed that the degree of education, the number of forms and compliance of health education, the times of admission, participation intention in medical decision-making, the dimension of Symptom Management in Self-efficacy, three dimensions of consistency, respect, and confidence in knowledge and technology in Nurse-Patient Trust degree and four dimensions of medical staff support, organization support, family and friends support, media and government support in Chronic Illness Resource were influencing factors of patients ′ empowerment perception (adjusted R 2 value was 0.636, F value was 79.441, P<0.01). Conclusions:Compared with the foreign level, the perception of nurses ′ empowerment of inpatients with chronic diseases is at a lower level, and self-efficacy, nurse-patient trust and chronic disease resource support are all at a medium level, which still need to be improved. Nurses should allow them to participate in their treatment, improve the control of life and reduce their anxiety.

OBJECTIVETo detect potential mutation of iduronate-2-sulfatase (IDS) gene in a family affected with mucopolysaccharidosis type Ⅱ (MPS Ⅱ).

METHODSFor the proband and his unaffected mother, the whole coding sequence of the IDS gene was analyzed with PCR and bidirectional Sanger sequencing.

RESULTSA novel splicing mutation, c.709-1G>A, was detected in the proband, for which his mother was heterozygous.

CONCLUSIONThe c.709-1G>A splicing mutation of the IDS gene is probably causative for the MSP Ⅱ in the proband. Prenatal diagnosis for the mutation may avoid birth of further child affected with this disease.

Base Sequence ; Child ; DNA Mutational Analysis ; methods ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Glycoproteins ; genetics ; metabolism ; Heterozygote ; Humans ; Iduronate Sulfatase ; genetics ; metabolism ; Male ; Mothers ; Mucopolysaccharidosis II ; diagnosis ; enzymology ; genetics ; Mutation

OBJECTIVETo analyze mutations of IDUA gene in two pedigrees affected with mucopolysaccharidosis type I and provide prenatal diagnosis for them.

METHODSThe 14 exons of the IDUA gene were subjected to PCR amplification and Sanger sequencing.

RESULTSFor pedigree 1, the proband was found to harbor compound heterozygous mutations c.46-57delTCGCTCCTGGCC (p.Ser16_Ala19del) of exon 1 and c.1147delC (p.Arg383Alafs*57) of exon 8 of the IDUA gene, which were inherited from his father and mother, respectively. The latter was unreported previously. Prenatal diagnosis suggested that the fetus has carried a heterozygous c.46-57delTCGCTCCTGGCC mutation. For family 2, the proband was also found to carry compound mutations of the IDUA gene, namely c.721T to C (p.Cys241Arg) of exon 6 and c.1491delG (p.Thr497fs27) of exon 8, which were inherited from her mother and father, respectively. Neither mutation was reported previously. Prenatal diagnosis suggested that the fetus has carried a heterozygous c.721T to C mutation.

CONCLUSIONMutations of the IDUA gene probably underlie the MPS-I in both pedigrees. Above results have enriched the spectrum of IDUA gene mutations and facilitated prenatal diagnosis for both families.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; China ; DNA Mutational Analysis ; Female ; Fetal Diseases ; diagnosis ; genetics ; Heterozygote ; Humans ; Iduronidase ; genetics ; Male ; Molecular Sequence Data ; Mucopolysaccharidosis I ; diagnosis ; embryology ; genetics ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Sequence Deletion

Objective: To analyze the treatment of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4, in order to improve the diagnosis and treatment of these patients. Methods: A total of 36 patients with advanced NSCLC with hypoxemia were reviewed. The clinical data of disease characteristics, etiology, complications, manifestation, therapy, progression, and secondary biopsy were collected. The clinical efficacy was graded according to the Response Evaluation Criteria In Solid Tumors (RECIST): complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD). Results: All patients had hypoxemia, of whom 86.1% (31 patients) had complications and 55.6% (20 patients) had noninvasive ventilator for respiratory support. 77.8% (28 cases) received broad-spectrum antibiotic treatment, and 78.6% of them got lung osmotic relief after the anti-infection treatment. 15 cases received bedside fiberoptic bronchoscopy suction, of whom two cases were treated with airway stent deposition due to airway obstruction, four cases with thoracic drainage, four cases with anticoagulation, and one with thrombolytic therapy. After these supportive treatment, the PS score of these patients decreased from 3.4±0.5 to 2.5±0.7, while SPO₂ improved from (89.0±5.2)% to (95.0±3.5)%. As first-ling anti-cancer treatment, nine patients were administrated with targeted medicine orally, 13 patients with a combined chemotherapy of pemetrexed plus bevacizumab or carboplatin, eight patients with paclitaxel plus carboplatin, four patients with gemcitabine plus carboplatin, and two patients with docetaxel plus gemcitabine. In the first response evaluation, there were one case of CR, 23 cases of PR, four cases of SD, and eight cases of PD, with a clinical benefit rate of 66.7% and a disease control rate of 77.8%. A total of 22 patients experienced disease progression, of whom eight cases had a secondary biopsy and six cases had gene sequencing. Of these 36 patients, 10 (27.8%) patients survived at the last follow-up, with a progression-free survival of (10.0±6.5) months. Conclusion Besides prompt anti-cancer treatment and best supportive treatment should be incorporated to improve PS and improve outcome.

Objective To investigate the effects of long chain non-coding RNA urothelial carcinoembryonic antigen 1(UCA1) on invasion, migration and proliferation abilities in oral squamous cell carcinoma cell lines SCC15 and CAL27.Methods Small interfering RNA of UCA1(UCA1-siRNA) was transfected into SCC15 and CAL27 cell lines by LipofectamineTM 3000 to silence UCA1, and transfected negtive control si-RNA served as a control.The effect of UCA 1-siRNA was detected by quantitative real time-polymerase chain reaction(qRT-PCR) to confirm the successful inhibition of UCA1 by siRNA.The matrix metalloproteinase 9(MMP-9) protein level was detected by Western blotting analysis.The effect of siRNA on cell proliferation and invasion was assessed by transwell migration assay and wound healing assay.Cell counting kit-8(CCK-8) assay was carried out to estimate the proliferation of two cell lines with different expression levels of UCA1.Results Expressions of UCA1 of SCC15 and CAL27 were successfully suppressed after transfected with siRNA which verified by qRT-PCR, and the efficiency of downregulation of SCC15 and CAL27 was 86.45％(P＜0.001)and 78.24％(P＜0.001), respectively.The migration, invasion and proliferation of SCC15 and CAL27 cell lines after transfected with siRNA were obviously restrained.The number of migration and invasion of CAL27 cells were 719.20±92.36 versus 208.00±25.58 (P=0.000 7) and 363.40±45.96 versus 164.80±24.68(P=0.005 2), respectively, the number of migration and invasion of SCC15 cells were 437.20±54.75 vs 145.80±23.31(P=0.001 1) and 249.80±38.41 vs 63.80± 11.11 (P=0.001 6), respectively (UCA1-si compare to negtive control), the relative proliferation rates of SCC 15 and CAL27 were SCC15:R24 h=0.870, R48 h=0.863, R72 h=0.64, R96 h=0.732;CAL27: R24 h=0.913, R48 h=0.829, R72 h=0.756, R96 h=0.705(P＜0.05), and MMP-9 expression level was decreased by UCA1-siRNA compared with negative control.Conclusions UCA1 could enhance the ability of invasion and migration of SCC15 and CAL27 cell lines via regulating MMP-9 protein expression, which suggests that UCA1 might play a pivotal role in oral squamous cell carcinoma invasion and progression.