Objective Methyltransferase 3(METTL3)mediated N6-methyladenosine(m6A)methylation modifica-tion of transient receptor potential cation channel subfamily M member 7(TRPM7)regulates ferroptosis and malig-nant progression in cervical cancer(CESC).Methods Totally 40 patients with cervical cancer were collected.Cer-vical cancer tissues and adjacent normal tissues(≥3 cm from the edge of the tumor tissue)were sampled at opera-tion and then divided into experimental group and control group,respectively.RT-qPCR and Western blot were used to detect the differences in TRPM7 mRNA and protein expression between the two groups.TRPM7-interfering cell lines were constructed to investigate the effects of TRPM7 on CESC cells.Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine(EdU)assay and flow cytometry,respectively.Transwell chamber assays were employed to evaluate cell invasion and migration capabilities.The levels of ferroptosis in CESC cells were measured using kits for reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),and Fe2+.Bioinformatics tools were utilized to predict methyltransferases associated with TRPM7.The interaction between METTL3 and TRPM7 was examined through RNA immunoprecipitation(RIP)and methylated RNA immunoprecip-itation quantitative PCR(Me-RIP qPCR).The effect of METTL3 on the stability of TRPM7 expression was assessed using actinomycin D assay.Results TRPM7 was highly expressed in CESC tissue and cells.Knockdown of TRPM7 significantly inhibited cell proliferation,promoted cell apoptosis,suppressed cell migration and invasion capabilities,and enhanced ferroptosis levels(P＜0.05).Bioinformatics predictions suggested that METTL3 might act as a methyltransferase for TRPM7.Interference with METTL3 gene expression significantly reduced TRPM7 pro-tein levels,decreased TRPM7 m6A modification levels,and impaired TRPM7 gene stability(P＜0.05).Conclusions METTL3 regulates CESC proliferation,apoptosis,migration,invasion,and ferroptosis by m6A meth-ylation modification of the TRPM7 gene.

Objective To investigate the effect and mechanism of remimazolam on circulatory function in septic shock rats.Methods Seventy-two SPF grade rats were randomly divided into the control group,the model group,the dexamethasone group,the low and high dose remimazolam groups and the high-dose remimazolam+Nrf2 inhibitor(ML385)group,with 12 rats in each group.The septic shock rat model was established by intravenous infusion of 10 mg/kg lipopolysaccharide(LPS).After 6 hours of modeling,the mean arterial pressure(MAP)and heart rate(HR)of rats were measured.Enzyme linked immunosorbent assay(ELISA)method was applied to measure serum levels of lactic acid(Lac),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,nitric oxide(NO),and endothelin-1(ET-1).Hematoxylin-eosin(HE)staining was applied to observe morphological changes in vascular tissue.TUNEL staining was applied to observe the apoptosis of vascular endothelial cells.DHE fluorescent probe was used to detect the level of ROS in vascular tissue.The colorimetric method was applied to detect the contents of MDA and the activity of SOD in vascular tissue.Western blot assay was applied to detect the protein expression of nuclear factor E2-related factor 2(Nrf2)and glutathione peroxidase 4(GPX4)in vascular tissue.Results Compared with the control group,MAP,SOD activity in vascular tissue,Nrf2 and GPX4 protein levels were lower in the model group,while HR,serum Lac,NO,ET-1,TNF-α,IL-1β,IL-6 levels,endothelial cell apoptosis rate,ROS level in vascular tissue and MDA content were higher(P＜0.05).Compared with the model group,MAP,SOD activity in vascular tissue,Nrf2 and GPX4 protein levels were higher in the dexamethasone group and in the low and high dose remimazolam groups,while HR,serum Lac,NO,ET-1,TNF-α,IL-1β,IL-6 levels,endothelial cell apoptosis rate,ROS level in vascular tissue and MDA content were lower(P＜0.05).Nrf2 inhibitor ML385 greatly reduced the protective effect of remimazolam on septic shock rats(P＜0.05).Conclusion Remimazolam may improve circulatory function in septic shock rats by activating the Nrf2/GPX4 pathway,inhibiting inflammatory response and oxidative stress,reducing endothelial cell damage.

Objective To investigate the effect and mechanism of remimazolam on circulatory function in septic shock rats.Methods Seventy-two SPF grade rats were randomly divided into the control group,the model group,the dexamethasone group,the low and high dose remimazolam groups and the high-dose remimazolam+Nrf2 inhibitor(ML385)group,with 12 rats in each group.The septic shock rat model was established by intravenous infusion of 10 mg/kg lipopolysaccharide(LPS).After 6 hours of modeling,the mean arterial pressure(MAP)and heart rate(HR)of rats were measured.Enzyme linked immunosorbent assay(ELISA)method was applied to measure serum levels of lactic acid(Lac),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,nitric oxide(NO),and endothelin-1(ET-1).Hematoxylin-eosin(HE)staining was applied to observe morphological changes in vascular tissue.TUNEL staining was applied to observe the apoptosis of vascular endothelial cells.DHE fluorescent probe was used to detect the level of ROS in vascular tissue.The colorimetric method was applied to detect the contents of MDA and the activity of SOD in vascular tissue.Western blot assay was applied to detect the protein expression of nuclear factor E2-related factor 2(Nrf2)and glutathione peroxidase 4(GPX4)in vascular tissue.Results Compared with the control group,MAP,SOD activity in vascular tissue,Nrf2 and GPX4 protein levels were lower in the model group,while HR,serum Lac,NO,ET-1,TNF-α,IL-1β,IL-6 levels,endothelial cell apoptosis rate,ROS level in vascular tissue and MDA content were higher(P＜0.05).Compared with the model group,MAP,SOD activity in vascular tissue,Nrf2 and GPX4 protein levels were higher in the dexamethasone group and in the low and high dose remimazolam groups,while HR,serum Lac,NO,ET-1,TNF-α,IL-1β,IL-6 levels,endothelial cell apoptosis rate,ROS level in vascular tissue and MDA content were lower(P＜0.05).Nrf2 inhibitor ML385 greatly reduced the protective effect of remimazolam on septic shock rats(P＜0.05).Conclusion Remimazolam may improve circulatory function in septic shock rats by activating the Nrf2/GPX4 pathway,inhibiting inflammatory response and oxidative stress,reducing endothelial cell damage.

Objective To explore some reasonable ways of anticoagulation for pregnant women with mechanical prosthetic valves.Methods Retrospective analysis was conducted for 27 women with mechanical prosthetic valves who have born children after their cardiac surgeries.Numbers of pregnancies,ages,ways of anticoagulation during pregnancy,ways of anticoagulation before pregnancy,valve thrombosis events,thromboembolism events,bleeding events,outcomes of pregnancy and ways of delivery were collected and studied.Comparing adverse events and outcomes of different ways of anticoagulation which those women used during their pregnancies.Results 27 women with mechanical prosthetic valves experienced 41 pregnancies,and bore 28 children.24 pregnancies used oral low does warfarin(＜ 5 mg/day) to anticoagulate,2 minor bleeding events and 10 early abortion occurred,no abnormal neonates were found,14 healthy neonates were born.6 pregnancies used low-molecularweight heparin to anticoagnlate from 6th week to 12th week,they used oral warfarin to anticoagulate in rest weeks of pregnancy.1 late abortion occurred,1 fetus with hydrocephalus was found at 20th week,then induced labour was conducted.4 healthy neonates were born.11 pregnancies used low-molecular-weight heparin to anticoagulate until delivery,1 early abortion,2 minor bleeding events and 1 valve thrombosis occurred.10 neonates were born,and 1 of them has hypoxic-ischemic encephalopathy,the other 9 neonates were healthy.Conclusion For pregnant women with mechanical prosthetic valves,using oral low does warfarin throughout pregnancy is a reasonable way of anicoagnlation with low risk of maternal and fetal adverse events except high risk of abortion.Low-molecular-weight heparin is hopeful anticoagulant agent for pregnant women with mechanical prosthetic valves,but more studies about its safety and effectiveness should be conducted.

OBJECTIVE To report on the phenotype of an infant with central hypoventilation syndrome (CCHS) and result of PHOX2B gene mutation analysis for the purpose of genetic counseling and prenatal diagnosis. METHODS Clinical data of an infant with CCHS was collected and analyzed. Potential mutation of PHOX2B gene was analyzed by amplified fragment length polymorphism (amp-FLP) and DNA sequencing. RESULTS The patient had typical clinical features of CCHS including frequent hypoventilation during sleeping, hypoxemia and hypercapnia which could be corrected by continuous ventilatory support. She also had repeated bruising and was difficult-to-wean, but without any cardiac, pulmonary, neuromuscular or brainstem lesions. DNA sequencing and amp-FLP of the PHOX2B gene showed that the patient has carried a polyalanine expansion repeat mutation (PARM) in exon 3. A 27 bp duplication was confirmed in the repeat sequence of 20 alanines by cloned and sequenced. This has led to an expansion of the repeat tract to 29 alanines. The genotype was therefore 20/29. CONCLUSION A patient with CCHS has been described. Mutation screening of PHOX2B gene can be used as an important support for diagnosis and genetic counseling for such patients.
Female ; Homeodomain Proteins ; genetics ; Humans ; Hypoventilation ; congenital ; genetics ; Infant, Newborn ; Mutation ; Sleep Apnea, Central ; genetics ; Transcription Factors ; genetics

Bcl-2 gene is the human homologous gene of anti-apoptotic gene Ced-9 in c-elegans, which can participate in regulations of cells apoptosis including suppression of neuronal apoptosis in cerebral ischemic penumbra.This review is about Bcl-2 anti-ischemic neuron injury, its possible mechanisms and the effects of anti-ischemic drugs on Bcl-2.