Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Antibiotics exposure, risk factors, and outcomes with Candida albicans and non-Candida albicans candidemia. Results from a multi-center study

To define the differences in antibiotics exposure, risk factors, and outcome in hospitalized patients with Candida albicans [C. albicans] and non-C. albicans candidemia. This is a multi-center retrospective study of 132 patients with candidemia from 5 tertiary-care educational hospitals in Shandong, China conducted between January 2009 and June 2010. Fifty-six of 132 [42.4%] patients had candidemia due to C. albicans and 76/132 [57.6%] had non-C. albanians candidemia. Patients with non-C. albicans candidemia received anti-anaerobic agents more often [23.7% versus 8.9%; p=0.027] and beta-lactam/beta-lactamase inhibitors less often [34.2% versus 51.8%; p=0.043] than those with C. albicans candidemia. Independent risk factors of non-C. albicans candidemia were prior anti-anaerobic and antifungal therapies and central venous catheter placement. Overall, 30-day mortality was higher for patients with C. albicans than non-C. albicans candidemia [50% versus 31.6%; p=0.032]. Multivariate logistic regression analysis revealed that C. albicans candidemia, advanced age, and concomitant bacteremia were associated with death due to candidemia. Patients who received anti-anaerobic or antifungal agents were likely to develop non-C. albicans candidemia. Candida albicans infection was associated with poorer prognosis. An awareness of these factors is needed to guide therapy and decrease the high mortality of candidemia