As a novel form of cell death, ferroptosis is mainly regulated by the accumulation of soluble iron ions in the cytoplasm and the production of lipid peroxides and is closely associated with several diseases, including acute kidney injury, ischemic reperfusion injury, neurodegenerative diseases, and cancer. The term "immunosuppression" refers to various factors that can directly harm immune cells' structure and function and affect the synthesis, release, and biological activity of immune molecules, leading to the insufficient response of the immune system to antigen production, failure to successfully resist the invasion of foreign pathogens, and even organ damage and metabolic disorders. An immunosuppressive phase commonly occurs in the progression of many ferroptosis-related diseases, and ferroptosis can directly inhibit immune cell function. However, the relationship between ferroptosis and immunosuppression has not yet been published due to their complicated interactions in various diseases. Therefore, this review deeply discusses the contribution of ferroptosis to immunosuppression in specific cases. In addition to offering new therapeutic targets for ferroptosis-related diseases, the findings will help clarify the issues on how ferroptosis contributes to immunosuppression.
Ferroptosis/immunology* ; Humans ; Immune Tolerance/immunology* ; Animals ; Immunosuppression Therapy ; Iron/metabolism* ; Neoplasms/immunology*

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To investigate the value of pulse oxygen saturation (SpO 2) monitoring in predicting children with moderate-to-severe obstructive sleep apnea (OSA). Methods:It was a retrospective study involving 341 children with snoring during nighttime sleep who had visited the Children′s Hospital of Soochow University from June 2017 to November 2020 and monitored for polysomnography (PSG) and SpO 2.The SpO 2 parameters mainly included oxygen desaturation index (ODI), oxygen desaturation index ≥3% (ODI3), oxygen desaturation index ≥4% (ODI4), mean pulse blood oxygen saturation (MSpO 2), lowest pulse blood oxygen saturation (LSpO 2), cumulative time spent with blood oxygen saturation below 95%, 92% and 90%(T95, T92 and T90). According to obstructive sleep apnea hypopnea index (OAHI), patients were divided into the snoring and mild OSA group (OAHI≤5 times/h) and moderate-to-severe OSA group (OAHI>5 times/h). Differences in SpO 2 parameters were compared between groups using the Chi- square test and Mann- Whitney U test. Spearman correlation analysis was used to analyze the correlation between SpO 2 parameters and OAHI in all children.The SpO 2 parameters were included in the Logistic regression model.Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of SpO 2 parameters on moderate-to-severe OSA. Results:A total of 341 patients were recruited, including 206 male and 135 female patients with the mean age, body mass index (BMI) and OAHI of 6.0 (4.0, 7.5) years, 16.2 (15.1, 18.0) kg/m 2 and 0.6 (0.1, 3.0) times /h, respectively.There were 283(83.0%) and 58 (17.0%) patients in the snoring and mild OSA group and moderate-to-severe OSA group.The ODI3[0.7 (0.3, 1.4) times/h vs.7.7 (4.4, 12.8) times/h], ODI4[0.4 (0.1, 0.8) times/h vs.5.3 (2.7, 9.1) times/h], T95[1.4 (0.3, 5.3) min vs.13.7 (7.0, 33.5) min], T92[0.1 (0, 0.5) min vs.1.8 (0.9, 6.0) min] and T90[0 (0, 0.1) min vs.0.6 (0.2, 2.2) min] were significantly lower in the snoring and mild OSA group than those of moderate-to-severe group, while LSpO 2[91.0 (89.0, 93.0)% vs.86.5 (82.0, 88.0)%] and MSpO 2[ 97.0 (97.0, 98.0)% vs.96.0 (96.0, 97.0)%] were significantly higher(all P<0.001). All SpO 2 parameters were significantly correlated with OAHI (all P<0.001), and the correlation coefficient between ODI3 and OAHI was 0.660.ODI3 was an independent predictor of moderate-to-severe OSA ( OR=3.117, 95% CI: 1.635-5.945, P=0.001). The area under the ROC curve of ODI3 in predicting the moderate-to-severe OSA was 0.957, and the cut-off value of 3.45 times/h and specificity of 95.4%.MSpO 2 was an independent predictor of moderate-to-severe OSA ( OR=2.917, 95% CI: 1.589-5.354, P=0.001). Conclusions:ODI3 can be used to predict the moderate-to-severe OSA in children.

OBJECTIVE To investigate the pharmacokinetics and bioavailability of naproxen choline ionic liquid in rats after intragastric administration. METHODS Naproxen choline ionic liquid was given to rats by intragastric administration. Blood samples were collected at different time points after administration. The blood samples were precipitated by methanol and then centrifuged, and then an Extend-C18 column(4.6 mm×250 mm, 5 μm) was used. Methanol(A)-0.3% phosphoric acid aqueous solution(B) (74:26) was used as the mobile phase, the flow rate was 0.8 mL·min-1, and the detection wavelength was 230 nm. Indomethacin and naproxen were used as internal standard and tested object in determination of naproxen choline ionic liquid in rat plasma. Pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS After intragastric administration of naproxen suspension to rats, its t1/2α was 5.12 h, t1/2β was 10.13 h, Tmaxwas 2 h, Cmax was 112.92 mg·L-1, and AUC(0-t) was 1 091.01 mg·L-1·h. After intragastric administration of naproxen choline, its t1/2α was 5.64 h, t1/2β was 69.32 h, Tmax was 1 h, Cmax was 135.97 mg·L-1, AUC(0-t) was 1 305.79 mg·L-1·h, and the relative bioavailability was 119.686%. CONCLUSION After intragastric administration of naproxen choline to rats, the peak concentration and bioavailability of the naproxen in vivo are higher than those of the common suspension, and the peak time is earlier.

OBJECTIVE: To investigate the effect of hyperthermia on the expression of PANDAR, LncRNA-p21 and ST8SIA genes in the human lung adenocarcinoma A549 cells. METHODS: A549 cells were randomly divided into 4 groups. The A549 cells in control group were cultured at 37 ℃; the cells at experimental groups were cultured at 40, 42 or 44 ℃ respectively. The cells in these 4 groups were incubated for 1 hour, and the levels of PANDAR, LncRNA-p21 and ST8SIA genes were analyzed by real-time fluorescence quantitative polymerase chain reaction. RESULTS: In cells cultured at 40, 42 or 44 ℃ experimental groups, the relative expression of PANDAR gene was lower than that of control group(P<0.05). In cells cultured at 44 ℃ experimental group, the relative expression of PANDAR gene was lower than that of the 40 and 42 ℃ experimental groups(P<0.05). There was no significant change in the relative expression of LncRNA-p21 and ST8SIA genes among the four groups(P>0.05). CONCLUSION: Hyperthermia decrease the expression of PANDAR gene in A549 cells.

Objective To investigate the expression of miR?126, miR?355 and exportin?5 in lung cancer. Methods The cancer tissue and the tissue adjacent to carcinoma of 47 cases of patients with lung cancer was used to detect the expression of miR?126, miR?355 and Exportin?5 by the real?time fluorescence quantitative PCR. Results Significant difference of the expression of miR?126 (t=2.02,P=0.03) and exportin?5 (t=4.62,P<0.01) was observed in lung cancer tissue and tissue adjacent to carcinoma. Mature miR?126 and pri?miR?126 (R=0.309 , P = 0.044) had a negative correlation in the tissue adjacent to carcinoma. In the cancer tissue,miR?126 and MRP (R=0.432, P=0.019), miR?335 and k167 (R=0.410, P=0.033) were positively correlated, however, exportin?5 and TOPO (R=0.357, P=0.045), the pri?miR?126 and drinking (R=0.340, P=0.024), the pri?miR?126 and MRP (R=0.427, P=0.027) had a negative correlation relationship. Conclusion Expression of miR?126 and exportin?5 was decreased in lung cancer tissue, which may contribute to the occurrence and development of lung cancer.

OBJECTIVE: To explore the effect of arsenic on the homeobox D10( HOXD10) gene expression in peripheral blood lymphocytes and human lung adenocarcinoma cell A549. METHODS: ⅰ) A total of 59 workers exposed to arsenic from a arsenic factory were selected as the exposure group and 17 local people without arsenic exposure were chosen as controls by using judgment sampling method. Hydride generation-cold hydrazine trapping-atomic absorption spectrometry was used to detect arsenic levels in urine of these 2 groups. The expression of HOXD10 in peripheral blood lymphocytes was detected by real-time fluorescent quantitative polymerase chain reaction( qRT-PCR).ⅱ) The A549 cells were treated with arsenic trioxide( As_2O_3) with concentration of 0. 0,0. 1,0. 5,1. 0 and 2. 0 μmol/L,and the survival rate of cells was examined by colorimetric assay. The expression of HOXD10 was detected by qRT-PCR. RESULTS: ⅰ) The levels of inorganic arsenic,methylarsonic acid,dimethyl arsenate,total arsenic in the urine,and the relative expression of HOXD10 mRNA in peripheral blood lymphocyte in exposure group were higher than that of the control group( P < 0. 05).ⅱ) As_2O_3 decreased the survival rate of A549 cells in a dose-dependent manner( P < 0. 01) and lead to a dose-dependent increase of HOXD10 mRNA expression( P < 0. 01). A549 cell survival rate and relative expression of HOXD10 mRNA showed a negative correlation,the correlation coefficient was-0. 777( P < 0. 01). CONCLUSION: Arsenic can up-regulate HOXD10 expression in the peripheral blood of occupational arsenic exposure individuals. As_2O_3 can inhibit the proliferation of A549 cells,which may be related to the up-regulation of HOXD10 expression.

Objective To explore the MRI features of patients with multiple system atrophy (MSA) and Parkinson's disease (PD) for providing early evidence in differential diagnosis. Methods The MRI features of 24 patients with MSA, 30 patients with PD and 30 healthy people as controls were retrospectively analyzed. Abnormal intensity in MRI included the hot-cross bun sign and the slitlike changes. The atrophies of brain included cerebellar, middle cerebellar peduncles, medulla oblongata and pon. Cerebral ventricle dilatation included fourth ventricle and cisterna pontis. The midbrain area, pons area and middle cerebellar peduncles width were measured. Results All patients with MSA had at least one of the features observed on MR images, and there were some differences in the subtypes of MSA. The high sensitive features were the atrophies of middle cerebellar peduncles (79.2%), the atrophies of pons (79.2%) and the hot-cross bun sign (75.0%). The parameters with high specificity and high positive predictive value were hot-cross bun sign (both 100%), the slit-like sign (both 100%), the atrophies of middle cerebellar peduncles (93.3% and 90.1%), and the atrophies of pons (96.7% and 95.0%). MSA group had the statistically significantly decreased values of pons area, midbrain area and middle cerebellar peduncles width [(288. 7±75. 4) mm2, (127.8±25.8) mm2 and (10. 7±2.8) mm, respectively], as compared with PD group [(477. 5 ± 54. 3) mm2, (145.9±21.6) mm2 and (16.2±1.3) mm, respectively] and healthy group [(454. 5±36. 8) mm2 , (146.4±17.4) mm2 and (16.7±1.2) mm, respectively] (all P ＜0. 05). Conclusions The routine MRI is helpful in differential diagnosis between MSA and PD and has some values in diagnosing the subtypes of MSA.

Objective To explore the effect of inferior hypothermy treatment on serum TNF and IL-6 in patients with severe cerebral trauma.Methods 46 patients were randomly divided into two groups:inferior hypothermy group(24 C88e8)and normal group(22 cases).There are the same basic treatments within the two groups,in the inferior hypothermy group we also sive them hypothermy treatment rectal temperature:32～34℃ which need to last for nearly 4～5 days,at the same time we give patients the lyric cocktail.the TNF,IL-6 and GCS grades on the lst and 14th day were tested.Results TNF and IL-6 as compared with normal group are higher than the inferior hypothermy group,the differences between the two groups are of statistical significance(P＜0.01).The difference of GCS grades between the two groups are of stafictical significance(P＜0.05).Conclusion The inferior hypothermy tbempy which inhibits TNF and IL-6 releasing after severe cerebral trauma and the following damages plays a very important role in the cerebral trauma therapy.