Objective To investigate the role of poly(rC)-binding protein 1(PCBP1)in cadmium(Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a(N2A)cells.Methods N2A cells were exposed to a concentration gradient of CdCl?(0,1,2,4 μmol/L)for 72 h.Cell viability was assessed by trypan blue staining.Western blotting was employed to detect the expression of ferroptosis-related proteins(GPX4,HMOX1,ACSL4)and PCBP1.Intracellular Fe2? level and lipid peroxidation were detected using FerroOrange and BODIPY581/591 C11 probes,respectively.Ferrostatin-1(Fer-1),a ferroptosis inhibitor,was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity.Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin,as well as the binding sites of Cd2?.PCBP1 overexpression plasmid was further constructed for functional validation.Results Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner(P<0.01),significantly down-regulated GPX4 expression(P<0.05),up-regulated HMOX1 expression(P<0.01),and induced Fe2? overload and lipid peroxidation(P<0.01).Molecular docking revealed that Cd2? directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain.Overexpression of PCBP1 markedly reversed Cd-induced Fe2? accumulation,GPX4 down-regulation,lipid peroxidation,and cell death.Conclusion Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions,and then synergistically drives Fe2? overload-triggered ferroptosis cascades,ultimately leading to neurotoxicity.Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity,and may serve as a novel therapeutic strategy.

Objective To investigate the application value of dual-layer spectral computed tomography(DLCT)45 keV single energy image in follow up after transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).Methods The DLCT images of 60 patients with HCC after TACE treatment were analyzed retrospectively.The CT value and standard deviation(SD)value of the lesion region of interest(ROI)and surrounding normal liver parenchyma on two kinds of images with 45 keV energy spectrum CT and 120 kVp conventional CT were measured respectively,then the contrast-to-noise ratio(CNR)between the lesions and surrounding normal liver parenchyma was calculated,and their differences were compared.The image quality of the two kinds of images was scored subjectively with the 3-point method,and the patients were divided into different groups according to the enhance-ment degree and tumor staining.The receiver operating characteristic(ROC)curve was also drawn.Results(1)There was no signif-icant difference in CNR between arterial phase,portal phase,and delayed phase of 120 kVp conventional CT(Hc=1.128,P>0.05).The CNR of 45 keV energy spectrum CT was higher than that of 120 kVp conventional CT,with a statistically significant difference(Z=5.060,P<0.05).(2)The subjective score of 45 keV energy spectrum CT was higher than that of 120 kVp conventional CT,and the difference was statistically significant(Z=5.335,P<0.05).ROC curve analysis showed that 45 keV energy spectrum CT had a larger area under the curve(AUC)than 120 kVp conventional CT,and the difference was statistically significant(Z=4.136,P<0.001).Conclusion 45 keV energy spectrum CT image can significantly improve the CNR between tumor and normal liver parenchyma,and it has the better image quality and higher diagnostic efficiency.

The typical manifestations of primary aldosteronism (PA) are hypertension with or without hypokalemia, high aldosterone, and low renal level. However, PA with normal blood pressure is rare in clinical practice. This article reported the diagnosis and treatment of a patient with subclinical PA, admitted for "adrenal accidental tumor" with normal blood pressure and serum potassium. We summarized and analyzed the clinical characteristics and treatment strategies, in order to provide some reference for clinicians.

OBJECTIVE To study the improvement effect and possible mechanism of N-butylphthalide on inflammatory injury of bone marrow mesenchymal stem cells （BMSCs） in rats. METHODS BMSCs of rats were divided into control group， model group， N-butylphthalide low-concentration， medium-concentration and high-concentration groups （10， 20， 50 μmol/L）. BMSCs were cultured in vitro and lipopolysaccharide （the final concentration of 10 mg/L） was used to establish the inflammatory injury model. After the intervention of N-butylphthalide， the survival rate， apoptotic rate， the contents of tumor necrosis factor α （TNF- α）， interleukin 1β （IL-1β） and IL-6 in cell culture medium， the mRNA expression of nuclear factor-κB（NF-κB） p65， and the protein expressions of caspase-3， B-cell lymphoma 2 （Bcl-2）， Bcl-2 related X protein （Bax） and NF-κB p65 in cells were detected. RESULTS Compared with control group， the survival rate and protein expression of Bcl-2 were decreased significantly in model group （P＜0.05）； the apoptotic rate， contents of TNF-α， IL-1β and IL-6， the mRNA expression of NF-κB p65， and the protein expressions of caspase-3， Bax and NF-κB p65 were increased significantly （P＜0.05）. Compared with model group， above indexes were significantly reversed in all concentration groups of N-butylphthalide （P＜0.05）， in concentration-dependent manner. CONCLUSIONS N-butylphthalide can ameliorate the inflammatory injury of BMSCs induced by lipopolysaccharide， and its mechanism may be related to the inhibition of NF-κB signaling pathway.

Entorhinal Cortex/physiology* ; Hippocampus/physiology* ; Neural Pathways/physiology*

Objective To investigate the effects on myocardial mitochondria-related indexes in rats after rapid elevation to 3 400 m altitude and myocardial protection effects with metoprolol.Methods Male Wistar rats were randomly divided into three groups with 12 rats in each group as follows,group A(normal group,55 m above sea level),group B(hypoxia group, 3 400 m above sea level),group C(metoprolol group,3 400 m above sea level).Heart rate and blood pressure were measured during the rapid transfer from the plain(Shanghai 55 m)to plateau of 3 400 m.Then,the rats were anesthetized with chloral hydrate.The blood was collected from the abdominal aorta and blood gas indexes were measured.The heart tissue was homog-enized.The oxidativee stress related parameters,such as superoxide dismutase(SOD),malondialdehyde(MDA)and nitric ox-ide(NO)were assayed.The mitochondrial function related parameters,such as complexes-Ⅰ,Ⅱ,Ⅲ,Ⅳ,succinate dehydro-genase(SDH),malate dehydrogenase(MDH)and adenosine triphosphate(ATP)were measured.Results After the rats were exposed to high altitude,the blood oxygen tension and oxygen saturation in the metoprolol group were increased in com-parison with the hypoxia group.Compared with the normal group,the content of MDA in the hypoxia group was increased sig-nificantly,while the content of SOD and NO were decreased significantly(P<0.01),the mitochondrial complex Ⅰ,Ⅱ,Ⅲand Ⅳ were also decreased 44.49%,32.38%,34.43% and 20.16%.Compared with hypoxia group,the MDA was decreased by 13.72%,while SOD and NO were increased by 25.73% and 168.55%,the activity of mitochondrial complexes were also increased by 44.92%,33.73%,37.11% and 10.09% for metoprolol group.The respiratory chain SDH and MDH in hypoxic group were decreased by 29.51% and 42.79% and the activity of Na+-K+-ATPase,Ca2+-Mg2+-ATPase and T-ATPase were decreased by 20.24%,27.56% and 33.32% in comparison with the normal group.After intervention with metoprolol,SDH and MDH were increased by 47.36% and 88.57% separately,the activities of Na+-K+-ATPase,Ca2+-Mg2+-ATPase and T-ATPase were also increased by 31.92%,26.95%,44.93% in comparison with hypoxia group.Those results indicated that metoprolol can increase ATPase activity.Conclusion Under the condition of acute hypoxia at 3 400 m above sea level,myocar-dial injury is related to the changes of oxidative stress and mitochondrial-related enzyme activity.Metoprolol helps to normalize the related indicators and provides the protection for myocardial injury caused by hypoxia.

Purpose To investigate the CT features of different pneumocystis pneumonia (PCP) types in AIDS as well as the relationship between different PCP types and CD4+ T lymphocyte count,in order to deepen the understanding and improve the diagnosis and treatment of PCP.Materials and Methods The CT examination data of 102 AIDS patients with PCP were retrospectively analyzed,the CT findings were divided into 6 types,and CD4+ T lymphocyte count of the 6 PCP types was statistically analyzed.Results ① The CT findings of PCP were divided into the following 6 types:transparent ground-glass type (42 cases,41.2％),muddy ground-glass type (17 cases,16.7％),solid variant (11 cases,10.8％),cystic variant (6 cases,5.9％),interstitial type (19 cases,18.6％),and mixed type (7 cases,6.9％).② The CD4+ T lymphocyte count of different PCP types was analyzed,and the difference was statistically significant (F=2.672,P＜0.05).Further pairwise comparison showed that the CD4+T lymphocyte count of transparent ground-glass type was higher than that of solid variant and cystic variant (P＜0.05),and there was no significant difference between the other groups (P＞0.05).Conclusion CT findings of AIDS with PCP have certain characteristics,and it is helpful to deepen the understanding of PCP through imaging classification.There is a certain correlation between different PCP types and CD4+T lymphocyte count,and it is helpful to improve the diagnosis and treatment of PCP by analyzing the correlation.

OBJECTIVE: To observe the effect of aminophylline on physiological and pathological changes in acute exposure to high altitude in rats. METHODS: A total of 21 male Wistar rats were randomly divided into a plain group (altitude 55 m), a high altitude hypoxia group (altitude 4 300 m), and a high altitude hypoxia plus aminophylline group. After 5 days, blood from orbital venous was collected for analyzing biochemical parameters. Blood from abdominal aorta was collected for analyzing the parameters of blood gas. The tissues of brain, lung, and kidney were dissected for pathological observation. RESULTS: Compared with the plain group, the parameters of LDH, ALP, Urea and cCl? in the hypoxia group or the aminophylline treatment group were significantly increased (P<0.01), while the parameters of ALB, Cr, SatO₂, Hb, Hct, PaCO₂, PaO₂2, BB and BE were significantly reduced (P<0.01). Compared with the hypoxia group, the parameters of Cr, pH, Hct, cNa⁺, cCl⁻ in the aminophylline treatment group were significantly increased (P<0.01), while AST, ALT, ALB, PaCO₂ and cK⁺ were significantly decreased (P<0.01 or P<0.05). Pathological results showed the brain, lung and liver tissues were obviously damaged in the hypoxia group compared with that in the plain group. These damages were significantly attenuated by aminophylline. CONCLUSION Aminophylline can improve blood gas and biochemical parameters in acute exposure to high altitude in rats. It can protect rat brain, lung and liver from the damage caused by acute high altitude, which may be related its effects on relaxation of bronchial smooth muscle and inhibition of inflammation.
Altitude ; Aminophylline ; pharmacology ; Animals ; Brain ; pathology ; Hypoxia ; blood ; physiopathology ; Liver ; pathology ; Lung ; pathology ; Male ; Rats ; Rats, Wistar

OBJECTIVETo investigate the influence of a sudden increase of altitudes (within 2500 m) in winter on cardiomyocyte functions in rats.

METHODSThirty male Wistar rats were randomly divided into groups A (55 m), B (1520 m), and C (2260 m) and subjected to simulated conditions at the indicated altitudes in winter for 3 days. Blood gas analysis, venous blood biochemistry, and measurements of SOD activity and myocardial concentrations of MDA and NO were performed. Histopathological changes in the left ventricle were observed with HE staining and electron microscopy.

RESULTSBlood pH and PCO2 did not differ significantly between the 3 groups, but PO2 and BE in groups B and C decreased significantly compared with those in group A (P<0.01). Compared with group A, the rats in group C showed obviously increased myocardial enzymes, MYB, Tn-I, and MDA contents (P<0.01) with significantly decreased SOD activity (P<0.05); both groups B and C showed significantly decreased NO content in the myocardium (P<0.01). Histopathologically, the myocardial fiber in group C showed irregular alignment, disruption, and mitochondrial expansion.

CONCLUSIONA sudden increase of altitude to 2260 m in winter can potentially cause hypoxic cardiomyocyte damage as a result of oxidative and environmental stresses.

Altitude ; Animals ; Hypoxia ; pathology ; Male ; Malondialdehyde ; metabolism ; Myocardium ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Oxidative Stress ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the changes in hepatic functions and activities of CYP1A2 and CYP3A4 in rats after acute exposure to high altitude.

METHODSTwelve healthy male Wistar rats were randomly divided into control group and exposure group for acute exposure to normal and high altitude (4010 m) environment. Blood samples were collected from the vena orbitalis posterior for detection of the hepatic function. Hepatic pathologies of the rats were examined microscopically with HE staining. Liver microsomes were extracted by differential centrifugation to assess the activities of CYP1A2 and 3A4 using P450-GloTM kit.

RESULTSIn rats with acute exposure to high altitude, AST, ALT, and ALP all increased significantly by 48.50%, 47.90%, and 103.02%, respectively, and TP decreased significantly by 17.80% as compared with those in rats maintained in normal altitude environment (P<0.05). Pathological examination of the liver revealed edema of the central vein of the liver and hepatocyte karyopyknosis in rats after acute exposure to high altitude, which also resulted in significantly lowered activities of CYP1A2 and 3A4 in the liver (by 96.56% and 43.53%, respectively).

CONCLUSIONAcute exposure to high altitude can cause obvious liver injuries and lowered activities of CYP1A2 and 3A4 in rats to severely affect drug metabolism in the liver and result in increased concentration, prolonged half-life and reduced clearance of drugs.

Altitude ; Animals ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 CYP3A ; metabolism ; Cytochromes ; metabolism ; Liver ; pathology ; Male ; Microsomes, Liver ; enzymology ; Rats ; Rats, Wistar