Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Objective:To explore the RH genotype for a female with RhD(-) blood type and its molecular basis. Methods:A 26-year-old female who had attended the outpatient clinic of the First Affiliated Hospital of Zhengzhou University in August 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents for Rh phenotyping with gel card method. PCR-sequence-based typing (PCR-SBT) and DNA sequencing were used to determine the RHD zygosity and RH genotype of the proband and her parents. Homology modeling of Rh proteins was performed with bioinformatic software, and protein structural alterations caused by the variant was simulated by molecular dynamics. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-0870-003). Results:Serological tests showed that the proband and her father both had weakened e antigen of the Rh phenotype. PCR-SBT and DNA sequencing showed that the genotypes of the proband and her parents were dce/ dCE, dce/ DcE and dCE/ DcE, respectively. And the genotypes of the RHD and RHCE of the proband were RHD*01N.01/ RHD*01N.16, RHCE*01.01/RHCE*04, respectively. Protein simulation and molecular dynamics analysis revealed that the ce_16C variant resulted from RHCE* ce (c.48G>C) may alter the structure of intracellular and extracellular loops, mainly affecting the mobility of extracellular loops 2, 6 and intracellular loops 3, 4. Conclusion:Variant of the RHCE* ce allele c. 48G>C probably underlay the weakened e antigen in this proband.

Purpose To explore the value of texture analysis in the diagnosis and course evaluation of Parkinson's disease(PD)by analyzing the texture features of gray matter nuclei and white matter on quantitative susceptibility mapping(QSM)sequences.Materials and Methods A total of 30 PD patients and 22 normal controls from July 2019 to November 2020 in Jiangyin People's Hospital were prospectively enrolled to perform enhanced gradient echo T2* weighted angiography(ESWAN)sequence scanning.All QSM images were obtained through post-processing.Region of interest was manually obtained,including bilateral caudate heads,globus pallidus,putamen,substantia nigra,red nucleus,cerebellar dentate nucleus and white matter at the center of the semicircle.The texture features of the region of interest were extracted.After dimension reduction and screening,a set of optimal texture parameters were obtained,and a random forest prediction model was constructed.The diagnostic efficiency of the model was analyzed and evaluated and the reliability of the model was evaluated.The correlation between the selected texture features and the clinical scale of PD patients was analyzed.Results A group(n=5)of the best texture feature parameters were obtained from QSM map.The area under curve range of independent prediction PD was 0.697-0.823,the area under curve of random forest model was 0.910,and the accuracy of cross validation was 0.888.Texture feature(r4_wavelet_LLL_firstorder_Energy)of PD group was negatively correlated with the scores of the mini mental state examination(r=-0.470,P=0.011).Conclusion The texture analysis based on QSM has a high diagnostic value for PD,and the texture features of the left putamen have a certain correlation with the cognitive function of PD patients.

Sepsis is a life-threatening organ dysfunction caused by the imbalance of host immune response to infection,which immune regulation mechanism is complex and has not been clarified.Programmed death receptor-1(PD-1)/programmed death recep-tor ligand-1(PD-L1)is a negative co-inhibitory molecule that has attracted much attention in recent years.Studies have shown that PD-1/PD-L1 signaling pathway plays an important immunosuppressive role in sepsis.There are differences in immune regulation mecha-nisms in heart,liver,spleen,lung and kidney,which has not been clarified.Immune regulation of PD-1/PD-L1 in different organs of sepsis is reviewied in this article,which could to provide a new direction for the study of sepsis.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Objective:To explore the expression of homologous recombination repair (HRR) deficiency related genes in endometrial cancer and their relationship with clinical pathological features and immune infiltration.Methods:A total of 53 patients with endometrial cancer (endometrial cancer group) who underwent surgical treatment at the Affiliated People′s Hospital of Shandong First Medical University from June 2018 to June 2020 were selected as the study subjects. Clinical data of the patients were retrospectively analyzed, and 50 healthy women who underwent physical examinations were selected as the control group. Clinical and pathological characteristics of 53 patients with endometrial cancer were collected, and real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed Methods The mRNA expressions of human breast cancer susceptibility gene 1 (BRCA1), tumor suppressor gene homologous loss phosphatase tensin gene (PTEN) on chromosome 10 in the peripheral blood of the subjects were detected, and the proportions of CD 4+ T cell subsets in peripheral blood monocytes were detected by flow cytometry; Pearson analysis of the correlation between peripheral blood BRCA1, PTEN mRNA expression and various subsets of CD 4+ T cell; Analysis of prognostic factors for endometrial cancer using COX risk regression model. Results:The peripheral blood BRCA1 and PTEN mRNA expression levels in patients with endometrial cancer were higher than those in the healthy control group: 2.87 ± 0.65 vs. 1.02 ± 0.13, 3.25 ± 0.74 vs. 1.01 ± 0.20, and the differences were statistically significant ( P<0.01). The proportion of peripheral blood helper T cell-2 (Th2), helper T cell-17 (Th17), regulatory T cell (Treg) and helper T cell-22 (Th22) in patients with endometrial cancer was significantly higher than that in the healthy control group: (10.72 ± 1.33)% vs. (5.43 ± 0.80)%, (9.78 ± 0.80)% vs. (3.31 ± 0.62)%, (10.81 ± 1.29)% vs. (5.74 ± 0.69)%, (6.09 ± 0.70)% vs. (3.09 ± 0.73)%, and the proportion of helper T cell-1 (Th1) was significantly lower than that in the healthy control group: (5.54 ± 0.90)% vs. (13.07 ± 2.55)%, the difference was statistically significant ( P<0.01). The peripheral blood BRCA1 and PTEN mRNA expression levels were significantly higher in patients with muscle infiltration depth ≥1/2, histological grade G 2 to G 3, lymph node metastasis, and International Federation of Obstetrics and Gynecology (FIGO) stage Ⅲ to Ⅳ than in patients with muscle infiltration depth<1/2, histological grade G 1, no lymph node metastasis, and FIGO stage Ⅰ to Ⅱ, with statistical significance ( P<0.01 or<0.05). Peripheral blood BRCA1 and PTEN mRNA were significantly positively correlated with Th2, Th17, Treg and Th22 ratios ( P<0.01), and negatively correlated with Th1 ratios ( P<0.01). COX risk regression analysis showed that histological grading, FIGO staging, depth of muscle infiltration, peripheral blood BRCA1 and PTEN mRNA expression with lymph node metastasis were all independent prognostic factors for endometrial cancer ( P<0.01 or<0.05). Conclusions:HRR deficiency related genes BRCA1 and PTEN mRNA exhibit high levels in patients with endometrial cancer, and are closely related to muscle infiltration depth, histological grading, lymph node metastasis, and FIGO staging. They can also affect the immune microenvironment of endometrial cancer patients, thereby affecting disease progression and prognosis.