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.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

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.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective To investigate the effects of clopidogrel on behavioral,content of inflamma-tory cytokines,and microglial in mice with comorbidity of pain and depression.Methods Twenty-four male pathogen-free C57BL/6J mice,aged 8 weeks,weighing 23-27 g,were selected.The mice were randomly divided into three groups:sham group(group C),spared nerve injury(SNI)group(group S),and SNI+clopidogrel group(group L),8 mice in each group.The surgical procedure in group C was consistent with the SNI model,but the nerve and maintained nerve integrity were not damaged.Group S was prepared with the SNI model,and group L was given clopidogrel 10 mg/kg since 21 days after the SNI model was prepared for 14 days continuously.Mechanical withdrawal threshold(MWT)was detected 1 day before surgery,7,14,21,28,and 35 days after surgery.The tail suspension test(TST)and forced swim test(FST)were performed 35 and 37 days after surgery,and the motionless time was calculated.Then the mice were killed,and the right hippocampal tissue was harvested to detect the concentration of IL-1β,IL-6,and TNF-α by enzyme-linked immunosorbent assay(ELISA),the expression of IL-1β,IL-6,and TNF-α mRNA by reverse transcription-polymerase chain reaction(RT-PCR),and the number of microglia by immunofluores-cence staining.Results Compared with group C,MWT were significantly decreased 7,14,21,28,and 35 days after operation,the immobility time of TST and FST were significantly prolonged,the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α were significantly increased,and the number of micro-glia were significantly increased in groups S and L(P＜0.05).Compared with group S,MWT were signifi-cantly increased 28 and 35 days after operation,the immobility time of TST and FST were significantly short-ened,the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α were significantly decreased,and the number of microglia was significantly reduced in group L(P＜0.05).Conclusion Clopidogrel can reduce the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α,inhibit the inflammatory reaction,reduce the number of activated microglia,and improve the and chronic neuropathic pain and de-pression in mice with comorbidity of pain and depression.

Objective:To investigate the effects and mechanisms of zinc ion-loaded composite hydrogel (hereinafter referred to as the zinc-containing hydrogel) on infected full-thickness skin defect wounds in diabetic mice.Methods:This study was an experimental study. A poly (glycerol sebacate)-co-poly(ethylene glycol)-g-catechol prepolymer/quaternized-chitosan hydrogel (hereinafter referred to as the simple hydrogel) and a solid-state zinc-containing hydrogel with porous and good adhesion by adding zinc ions to the simple hydrogel were prepared. The release rate of zinc ions from the zinc-containing hydrogel after immersion in phosphate buffer solution (PBS) for 14 days was calculated. The concentration of methicillin-resistant Staphylococcus aureus (MRSA) cultured for 2 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was measured. The scavenging ability of the simple hydrogel, zinc-containing hydrogel, and PBS for 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2, 4, 6-trinitrophenyl) hydrazyl (DPPH) was detected using microplate reader to reflect the ability of oxygen free radical removal. The length of vessels formed by human umbilical vein endothelial cells (HUVECs) cultured for 24 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was measured. The cell viability of L929 cells cultured for 24 hours with the simple hydrogel, zinc-containing hydrogel, and PBS was detected using the cell counting kit-8. The mouse red blood cell suspension was divided into blank control group treated with PBS, simple hydrogel group, zinc-containing hydrogel group, and Triton X-100 group treated with corresponding solution. Hemolysis was detected using microplate reader after 2 hours of treatment, and the hemolysis rate was calculated. All experiments had a sample size of 3. Twenty-one C57BL/6J mice aged 6-8 weeks were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back spine and infected with MRSA. Mice were divided into blank control group treated with PBS, simple hydrogel group, and zinc-containing hydrogel group treated with the corresponding hydrogel. Three days after injury, bacterial concentration in the wounds were measured in all groups of mice ( n=4). On day 0 (immediately), 3, 7, and 14 after injury, the wound infection status of mice was generally observed and the wound healing rate was calculated ( n=5). Hematoxylin-eosin staining and Masson staining were used to detect new epithelium and collagen formation in the wounds of mice on day 14 after injury. Immunofluorescence staining was used to detect neovascularization and distribution of M2 macrophages in the wounds of mice. Results:After immersion for 14 days, the release rate of zinc ions of the zinc-containing hydrogel was (70.5±4.6)%. Compared with the zinc-containing hydrogel, the bacterial concentration was significantly increased after 2 hours of culture with PBS and the simple hydrogel ( P<0.05). The DPPH scavenging rate of the zinc-containing hydrogel was significantly higher than that of PBS and the simple hydrogel (with P values all <0.05). The length of vessels formed by HUVECs cultured for 24 hours with the zinc-containing hydrogel was significantly longer than that cultured with PBS ( P<0.05). Compared with PBS and the simple hydrogel, the cell viability of L929 cells cultured for 24 hours with the zinc-containing hydrogel was significantly higher ( P<0.05). After 2 hours of incubation, compared with that in Triton X-100 group, the hemolysis rate of red blood cells in blank control, simple hydrogel, and zinc-containing hydrogel groups was significantly reduced ( P<0.05); and the hemolysis rate of red blood cells in the latter three groups was similar ( P>0.05). On day 3 after injury, the bacterial concentration in the wounds of mice in zinc-containing hydrogel group was significantly lower than that in blank control and simple hydrogel groups (with P values all <0.05). From day 3 to day 14 after injury, the wounds of mice in all the three groups were gradually healing, and on day 14 after injury, the wounds of mice in the zinc-containing hydrogel group were basically healed. On day 7 after injury, the wound healing rate of mice in zinc-containing hydrogel group was (72.4±8.4)%, which was significantly higher than that of blank control and simple hydrogel groups, being (31.6±6.7)% and (44.7±5.4)%, respectively(with P values all< 0.05). On day 14 after injury, the wound healing rate of mice in zinc-containing hydrogel group was (92.7±4.3)%, which was significantly higher than (73.5±7.4)% in blank control group ( P<0.05). On day 14 after injury, compared with that in blank control and simple hydrogel groups, the newly formed epidermis in mice wound of zinc-containing hydrogel group was longer and thicker, with more collagen deposition, and a more abundant distribution of new vessels and M2 macrophages. Conclusions:The zinc-containing hydrogel exhibits good biocompatibility, oxygen free radical scavenging capacity, and antimicrobial effects both in vitro and in vivo, as well as angiogenic promotion capability. It can provide sustained release of zinc ions to promote re-epithelialization and collagen synthesis, thus enhancing the healing of infected full-thickness skin defect wounds in diabetic mice.

Objective To explore the value of plaque-to-aorta CT value ratio(standardized CT value)in differentiating coronary lipid and fibrous plaques,and to preliminarily analyze the stability of the cutoff.Methods Patients who underwent coronary computed tomography angiography(CCTA)and intravascular ultrasound(IVUS)within 1 week were included.The plaque CT value was obtained by measuring the all,four and two short-axis planes,respectively.The CT value of the ascending aorta was measured and standardized(plaque-to-aorta CT value ratio).The receiver operating characteristic(ROC)curves of the standardized and the traditional CT values were drawn.Results A total of 60 patients with 74 plaques were included,35 lipid and 39 fibrous plaques were diagnosed by IVUS.The aorta CT value was significantly correlated with the plaque(r=0.420,P<0.01);the cutoffs for the CT value of all,four and two plaque slices were 55 HU,48 HU and 52 HU,respectively,and all there of the cutoffs of standardized CT value were 0.149;the sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of four-slice traditional and standardized CT values to differentiate lipid and fibrous plaques were 69%,87%,83%,76%and 91%,82%,82%,91%,respectively.Conclusion Compared with traditional CT value,the standardized CT value can greatly improve the sensitivity and NPV in differentiating coronary lipid and fibrous plaques,while maintaining modest to high specificity and PPV.Furthermore,the cutoff is stable.