Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

ObjectiveTo explore the protective effect and mechanism of Zingiberis Rhizoma Recens alcohol extract on lipopolysaccharide （LPS）-induced acute lung injury in mice. MethodBalb/c mice were randomly divided into normal group， model group， dexamethasone group， and low- and high-dose Zingiberis Rhizoma Recens groups. Mice in the normal group were instilled with normal saline through the nose， and the other groups were instilled with normal saline containing LPS （50 μg）. After 30 minutes of modeling， the dexamethasone group was gavaged with 5 mg·kg^-1 of dexamethasone acetate solution， the low- and high-dose Zingiberis Rhizoma Recens groups were gavaged with different doses of （7， 14 g·kg^-1） of Zingiberis Rhizoma Recens alcohol extract， and the normal group and the model group were gavaged with the same volume of water. After 24 hours of modeling， the total number of white blood cells in bronchoalceolar lavage fluid （BALF） was detected by cell counter， and the levels of the inflammatory factors including tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and superoxide dismutase （SOD）， and myeloperoxidase （MPO） was detected by enzyme-linked immunosorbent assay （ELISA）. Haematoxylin-eosin （HE） staining method was used to observe the pathological changes of lung tissue in each group， and the Western blot was used to detect the protein expression of nuclear transcription factor （NF）-κB p65， phosphorylation （p）-NF-κB p65， and Toll-like receptor 4 （TLR4） in lung tissue. ResultCompared with the normal group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the model group was increased （P<0.01）， and the level of SOD was decreased （P<0.05）. Pathological damage of lung tissue was obvious， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was increased （P<0.01）. Compared with the model group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the treatment group was decreased （P<0.05，P<0.01）， and the level of SOD was increased （P<0.05，P<0.01）. Pathological damage of lung tissue was alleviated， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was decreased （P<0.01）. ConclusionZingiberis Rhizoma Recens alcohol extract may play a protective role in LPS-induced acute lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

Objective To construct Raji-Luc lymphoma cells with CD19 knockout using CRISPR/Cas9 technology and preliminarily validate their immune escape ability.Methods PB-CRISPR-CD19 small guide RNA(sgRNA)plasmids was constructed,the optimal sgRNA sequence was screened,and Raji-Luc cells with pCAG-PBase,PB-CD19 sgRNA,and PB-CRISPR-Cas9 were co-transfected.Stable knockout monoclonal cell lines were screened by flow sorting and limit dilution method and the knockout effect was verified through gene sequence testing.The expression of luciferase on the surface of the cell line was detected by microplate reader,CD19 CAR-T and CD38 CAR-T previously constructed in the laboratory were used as effector cells,and the immune escape ability of Raji-Luc CD19 KO cell line was verified by universal luciferase chemiluminescence method.Results The transfection efficiency of Raji-Luc CD19 KO cells prepared by electro transfection was high,and the knockout efficiency of the two monoclonal cells was more than 99%.There was no significant difference in luciferase expression compared to the original Raji-Luc cells,and CD19 CAR-T cells could not be activated to the kill them.Conclusion Successfully constructed Raji-Luc CD19 KO lymphoma cell line.

Traumatic spinal cord injury (TSCI) is a common nerve injury in the world, which has a high incidence and disability rate. Intraspinal pressure (ISP) monitoring is performed by placing a pressure sensing probe under the dura of the most severe part of the spinal cord injury after anterior/posterior laminectomy or vertebral body decompression. ISP value is monitored dynamically and objectively in real time by the pressure sensing system. Recent studies have found that ISP monitoring plays an important role in the clinical management and prognosis evaluation of TSCI. The author reviews the recent advance in ISP monitoring in TSCI in order to provide references for the improvement of clinical diagnosis and treatment of TSCI.

Traumatic spinal cord injury (TSCI) is a common nerve injury in the world, which has a high incidence and disability rate. Intraspinal pressure (ISP) monitoring is performed by placing a pressure sensing probe under the dura of the most severe part of the spinal cord injury after anterior/posterior laminectomy or vertebral body decompression. ISP value is monitored dynamically and objectively in real time by the pressure sensing system. Recent studies have found that ISP monitoring plays an important role in the clinical management and prognosis evaluation of TSCI. The author reviews the recent advance in ISP monitoring in TSCI in order to provide references for the improvement of clinical diagnosis and treatment of TSCI.

Objective:To compare the effects of dexmedetomidine combined with propofol on anesthesia and thromboelastography in patients undergoing radical gastrectomy.Methods:From September 2017 to December 2019, 120 patients undergoing radical gastrectomy in Chaoyang Central Hospital were prospectively selected and divided into control group and observation group according to random number table method, with 60 cases in each group.The two groups used the same drugs before induction and the same way of anesthesia induction. During the maintenance of anesthesia, remifentanil and propofol were injected intravenously in the control group, and dexmedetomidine was injected in the observation group on the basis of the control group. The indexes of thromboelastography, preoperative and postoperative cellular immune function, postoperative analgesic effect [Visual Analogue Scale (VAS)], Ramsay sedation score, and postoperative adverse reactions were compared between the two groups at different times.Results:The reaction time of coagulation factor (R) and fibrinogen (K) in the two groups decreased 3 hours after operation, and those in the observation group were lower than those in the control group (all P<0.05); The maximum thrombus amplitude (MA) of the two groups increased 3 hours after operation, and MA in the observation group was higher than that in the control group (all P<0.05). Compared with that before operation, the VAS scores and Ramsay sedation scores in the control group and the observation group at 24 h and 48 h after operation were significantly lower (all P<0.05), and the VAS scores and Ramsay sedation scores in the observation group at 24 h and 48 h after operation were significantly lower than those in the control group (all P<0.05). Compared with that before operation, the CD4 +, CD8 +, CD4 + /CD8 + in the control group and the observation group were improved at 6 h and 48 h after operation (all P<0.05), and the improvement in the observation group was significantly better than that in the control group at 6 h and 48 h after operation (all P<0.05). The incidence of adverse reactions in the control group was 6.67%(4/60), which was slightly higher than that in the observation group of 5.00%(3/60), but the difference was not statistically significant ( P>0.05). Conclusions:Compared with propofol and remifentanil alone, combined application of dexmedetomidine can help patients undergoing radical gastrectomy for gastric cancer to achieve better analgesic effect, improve the blood coagulation state of patients, and play a better regulatory role on cellular immune function, which is worthy of further promotion in clinic.

Objective: To understand the epidemic status and influencing factors of Mongolian children with ASD in central and eastern Inner Mongolia, so as to provide data support for formulating prevention and intervention strategies and improving the overall epidemiological investigation of ASD in Inner Mongolia. Methods: Sixteen kindergartens and primary schools were selected from Chifeng City, Ulanqab City, Tongliao City, Hulunbuir City and Xilingol League cities in Inner Mongolia by means of random cluster sampling. Firstly, 7 108 children aged 3-14 were initially screened with the Kirschner Autism Behavior Scale(CABS), and then the children with ASD positive were given the autism behavior test scale (ABC). According to the diagnostic criteria, the professionals, including chief physicians and associate chief physicians from the major of child psychiatry, diagnosed ASD with the total score of ABC scale ≥62. Univariate and Logistic regression multivariate analysis were carried out among Mongolian children to find out the influencing factors related to the occurrence of Mongolian ASD in Inner Mongolia. Results: The prevalence of Mongolian children was 0.37%. Mongolian ASD group and Mongolian normal children series in the household register, habitual twitch, hyperactivity, bite lips, families have extreme introverts, mothers age, father s cultural level, cultural degree of mother, father mother mild character, irritable, neonatal diseases, fetal gestational age distribution had statistical significance( χ 2/Z= 12.58 , 16.68, 14.93, 64.43, -3.76, -2.86, 4.57, 11.12, 12.33, 16.66, P <0.05). Conclusion Measures such as shaping a healthy growth environment, adjusting parental style, paying attention to the level of early childhood language development, and preventing neonatal diseases might lower the risk of ASD in children.

Objective: To understand the prevalence and influencing factors of children with ASD in central and eastern Inner Mongolia, and to provide theoretical basis for disease prevention and prevalence of ASD. Methods: Sixteen primary schools and kindergartens were selected from 5 cities in central and eastern Inner Mongolia through random cluster sampling. A total of 15 817 children aged 3-14 years were selected. Children who were positive using Clancy Autism Behavior Scale were further diagnosed according to the teacher s nomination form and the Autism Behavior Checklist, as well as the diagnostic criteria of the fifth edition of the American Diagnostic & Statistical Manual of Mental Disorders by 2 professionals. Results: The prevalence of ASD was 0.27% (42/15 817), with prevalence in urban areas (0.16%, 15/9 231) higher than that of rural areas (0.41%, 27/6 586) ( χ 2=8.89, P <0.01). Logistic regression analysis showed that maternal education and language development were negatively associated with ASD in urban children [ OR =0.29(95% CI =0.12-0.69) and 0.18(95% CI =0.05-0.60), P <0.05]. ASD in rural children were positively associated with enuresis and introverted family members [ OR =7.09(95% CI =1.60-32.27) and 8.63(95% CI =3.10- 24.01 ), P <0.05]. Conclusion High prevalence of ASD is found in urban area of central and eastern Inner Mongolia. Unhealthy habits, neonatal diseases, low parental education, delayed language development and poor exercise performance are primary factors associated with ASD in both urban and rural areas.

To screen the best genotypeⅠJapanese encephalitis virus subunit vaccine candidate antigens, the prMEIII gene, the polytope gene and the prMEIII-polytope fusion gene of the GenotypeⅠJapanese encephalitis virus GS strain were cloned into prokaryotic expression vector pET-30a. The recombinant proteins were obtained after the induction and purification. The prepared recombinant proteins were immunized to mice, and the immunogenicity of the subunit vaccine candidate antigens was evaluated through monitoring the humoral immune response by ELISA, detecting the neutralizing antibody titer by plaque reduction neutralization test, and testing the cell-mediated immune response by lymphocyte proliferation assay and cytokine profiling. The recombinant proteins with the molecular weights of 35 (prMEIII), 28 (polytope antigen) and 57 kDa (prMEIII-polytope) induced strong humoral and cellular immune responses in mice. Compared with prMEIII-polytope and polytope proteins, the prMEIII protein induced a significant expression of IL-2 and IFN-γ (P<0.05) and the significant lymphoproliferation of splenocytes (P<0.05). The neutralizing antibody titer induced by the prMEIII protein was close to that induced by the commercial attenuated vaccine SA14-14-2 (P>0.05). The study suggests that the prMEIII protein can be used for the development of the Japanese encephalitis virus subunit vaccine.
Animals ; Antibodies, Viral ; blood ; Antigens, Viral ; immunology ; Encephalitis Virus, Japanese ; immunology ; Encephalitis, Japanese ; immunology ; prevention & control ; Immunogenicity, Vaccine ; Mice ; Mice, Inbred BALB C ; Vaccines, Subunit ; immunology ; Viral Vaccines ; immunology