Luminal surface of vascular endothelium is decorated with a variety of polysaccharide-protein complexes,which constitute the glycocalyx.It has been demonstrated that vascular endothelial glycocalyx plays an important role in modulation of selective permeability of vessels,mediation of the blood cell-endothelial cell interactions and the release of nitric oxide induced by fluid shear stress under physiological condition.In inflammation condition,sheding of glycocalyx due to inflammation mediator leads to its functional weakening in vessel protection.At the same time,heparan sulfate as a major constituent of vascular endothelial glycocalyx could be involved in regulating the evolution of inflammation.Heparan sulfate interacts with L-selectin to mediating leukocyte rolling,presents chemokines on luminal surfaces of endothelial cells to mediate leukocyte crawling and firm adhesion,participates in transcytosis of chemokines from tissue to luminal side of endothelial cells during inflammation.Various risk factors of atherosclerosis,as an inflammatory disease,are closely associated with vascular endothelial glycocalyx.This paper is aimed to review the role of vascular endothelial glycocalyx in inflammation and atherosclerosis.

To investigate the effects of curcumin on mitochondrial dysfunction induced by high glucose(40 mmol/L glucose, 24 h)in L6 cells, curcumin(10, 20, 40 μmol/L)was administered for 24 h after high glucose culture. The effects of curcumin on the mitochondrial dysfunction were evaluated by mitochondrial membrane potential, reactive oxygen species(ROS), ATP content and mtDNA copy number. The mRNA and protein expression of uncoupling protein 2(UCP2), PPARγ coactivator 1α(PGC-1α)and sirtuin-1(Sirt3)were also determined. As improvement of high glucose damage, curcumin significantly raised mitochondrial membrane potential and ATP content, and decreased ROS level. Curcumin significantly ameliorated the down regulation of UCP2 yet with little effect on mtDNA copy number and PGC-1α and Sirt3 expression. In conclusion, curcumin could significantly ameliorate mitochondrial dysfunction in L6 cells induced by high glucose, which involved the mechanism of multiple antioxidants.

Objective:To investigate the effects of Resolvin D1 (RvD1) on the inflammatory response and the expression of Nod-like receptor protein 3(NLRP3) inflammasomes in mice with acute lung injury.Methods:The 30 male BALB/c mice weighing 25-30 g were divided into 3 groups(each group with 10 mice). Mice in the normal control group were given normal saline by tail vein injection.Mice in the lipopolysaccharide (LPS) group were given the same volume of LPS (10 mg/kg) via tail vein injection.Mice in the RvD1 group were injected with RvD1 (5 μg/kg) through the tail vein 30 minutes prior to LPS administration.Mice were humanely sacrificed after 6 hours.Histopatholo-gical changes of lung tissue, the levels of pro-inflammatory cytokines interleukin(IL)-18 and IL-1β, and the expression of NLRP3 inflammasomes in lung tissue were measured.Results:After LPS administration, the lung of mice showed pathological damage.The levels of pro-inflammatory factors IL-18 and IL-1β as well as the expression of NLRP3, apoptosis-associated speck-like protein containing a card(ASC)and Caspase-1 in the LPS group were significantly higher than those in the normal control group (all P<0.05). After pretreatment with RvD1, the pathological damage of lung tissue was alleviated.The levels of pro-inflammatory factors IL-18 and IL-1β as well as the expression of NLRP3, ASC and Caspase-1 in the RvD1 group were significantly lower than those in the LPS group (all P<0.05). Conclusions:RvD1 can attenuate the pulmonary inflammation in acute lung injury and inhibit the release of pro-inflammatory factors, which is possibly related to the suppression of NLRP3.

Objective:To evaluate the immunogenicity and immune persistence of purified Vero cells rabies vaccine (PVRV) with Zagreb and Essen regimen.Methods:Prospective study: Patients with first Class II exposure to rabies were recruited from the Dog Injury Cinic of Guangxi Center for Disease Control and Prevention (Guangxi CDC) and randomly divided into the Zagreb (2-1-1) and Essen (1-1-1-1-1) regimen group. All patients were inoculated with the vaccines from the same manufacturer and batch, and 3 ml serum was collected at the 45th day and in 1-year, 2-year and 3-year after immunization. Rapid fluorescent inhibition test (RFFIT) was used to detect rabies virus neutralizing antibody (RVNA). The attenuation of RVNA positive rate and geometric mean titer (GMT) with time was analyzed. Retrospective study: The informed consents for rabies vaccine in the Dog Injury Clinic of Guangxi CDC were checked out. The patients who were injected with PVRV (same manufacturer but unlimited batch) but without passive immune agents for the first time within 3 years were selected and divided into 1-year, 2-year and 3-year group. Each group was further divided into Zagreb and Essen regimen group. The serum (3 ml) was collected at 1 year, 2 years and 3 years after immunization and detected the RVNA by RFFIT.Results:Prospective study: The RVNA positive rates on the 45th day and in 1-year, 2-year and 3-year after immunizationin in the Zagreb and Essen regimen group were 100%, 95%, 85%, 80% and 98.25%, 89.47%, 89.47%, 85.96%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT on the 45th day and in 1-year, 2-year, and 3-year in the Zagreb and Essen regimen group were 11.32 IU/ml, 1.69 IU/ml, 1.30 IU/ml, 1.30 IU/m and 13.18 IU/ml, 2.13 IU/ml, 1.87 IU/ml, 1.84 IU/m, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( F=1.971, P=0.164). The RVNA GMT levels in the two regimen groups had the same trend of attenuation over time (time*group F=0.702, P=0.435). Retrospective study: The RVNA positive rates in 1-year, 2-year and 3-year after immunization in the Zagreb and Essen regimen group were 100%, 95%, 91.43%和94.73%, 86.21%, 87.5%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT in 1-year, 2-year, and 3-year groups after immunization in the Zagreb and Essen regimen group were 2.65 IU/ml, 2.03 IU/ml, 1.57 IU/ml和3.2 IU/ml, 2.58 IU/ml, 2.45 IU/ml, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( P>0.05). Conclusions:The PVRV showed the same excellent immunogenicity and immune persistence after the vaccination with the Zagreb and Essen regimens.

OBJECTIVE To provide certain therapeutic ideas and references for the pharmaceutical care of severe Legionella pneumonia in anti-infection treatment. METHODS Clinical pharmacists participated in the entire treatment process of a patient with severe Legionella pneumonia， and assisted clinical physicians in evaluating the infecting pathogens using the WUH （Winthrop- University Hospital criteria） scoring system， based on the patient’s clinical symptoms， physical signs， and changes in pulmonary imaging. Leveraging their pharmaceutical expertise， clinical pharmacists recommended a combination of piperacillin sodium and tazobactam with moxifloxacin hydrochloride for anti-infection treatment， and closely monitored the patient’s clinical manifestations. They promptly identified delirium and abnormally elevated levels of lipase， amylase and liver enzymes， and successively suggested adjusting the treatment plan to a combination of piperacillin sodium and tazobactam with doxycycline or azithromycin for anti- infection after analyzing the causes， along with liver protection treatment， enteral nutrition， and parenteral nutrition. Additionally， clinical pharmacists closely monitor the patient’s medication adherence and provide her with medication education. RESULTS The clinical physicians accepted the recommendations of the clinical pharmacists， and the patient improved after treatment and was discharged. A follow-up examination one month later showed no recurrence. CONCLUSIONS Clinical pharmacists， when assisting clinicians in treating severe Legionella pneumonia， not only pay attention to changes in the patient’s clinical symptoms and physical signs， but also closely monitor the adverse reactions of fluoroquinolone， tetracycline， and macrolide antibiotics. They should promptly recognize adverse reactions and provide recommendations for adjusting treatment plans， as well as offer comprehensive pharmaceutical care throughout the patient’s treatment， to ensure the effectiveness and safety of clinical therapy.

Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC-δ-(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC-δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3β signaling via nuclear-export signal blockage independent of PKC-δ activation. By demonstrating independent modulation of PKC-δ and PKB/GSK-3β/Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo, further supporting the potential applicability of this rationale. Graphical abstract