Brain targeting efficacy of novel drug delivery system in the treatment of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group. MATERIALS AND METHODS: Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration. RESULTS: The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration. CONCLUSIONS: This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.

[Recommendations for diagnosis and treatment of systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complicated pathogenesis and diverse clinical manifestations. The current recommendations of the Chinese Rheumatology Association are based on a comprehensive investigation of evidence based medicine, domestic and international guidelines for SLE, and experts' proposals, and aim to provide a more scientific and authoritative reference for the diagnosis and management of SLE. The recommendations focus on four aspects; clinical manifestations, laboratory evaluation, diagnosis and disease assessment, and disease treatment and monitoring. The goal of the recommendations is to standardize the diagnosis and treatment of SLE in China so as to improve the prognosis of SLE patients.

Correlation research of serum substance P, CCK-8, and 5-HT values with depression levels in stroke survivors.

OBJECTIVE: This study aimed to investigate the correlation of serum octapeptide cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptryptamine (5-HT) values with depression levels in patients with post-stroke depression (PSD). It also aimed to explore the potential approach for the early diagnosis of PSD. PATIENTS AND METHODS: A correlation research between patients' biochemical indicators and depression levels was performed among 70 stroke patients during hospitalization from June 2021 to February 2022. The 70 stroke patients were selected and divided into post-stroke depression and non-depression groups according to the Hamilton Depression Scale (HAMD) score. The concentrations of CCK-8, SP, and 5-HT in both groups were measured, and the relationship between the values of CCK-8, SP, 5-HT and the depression levels was analyzed. RESULTS: Among the 70 stroke survivors, 35 were in the depression group and 35 were in the non-depression group. Significant differences were observed in the concentration of CCK-8, SP, and 5-HT between the patients in the depression and non-depression group (p < 0.05). Accompanied by an increase in the depression level, the SP value gradually increased, but the CCK-8 and 5-HT values gradually decreased. Spearman correlation analysis indicated that the order of the correlation between CCK-8, 5-HT, SP, and the depression levels was CCK-8 > SP > 5-HT. CONCLUSIONS: All the CCK-8, SP and 5-HT values were correlated with the depression levels in stroke survivors. Furthermore, the correlation between CCK-8, SP, and post-stroke depression levels was higher than that of 5-HT, suggesting that the early diagnosis of PSD may be reflected more precisely through the detection of CCK-8, and SP values, thus providing potential priority for biochemical detection in the diagnosis of PSD.

Phylogenetic analysis of the pathogenic genus Aeromonas spp. isolated from diseased eels in China.

Analyses of 16S rRNA and housekeeping genes (HKGs) were valuated as identification markers for pathogenic Aeromonas isolated from diseased eels. The interrelationships of 32 Aeromonas strains which had been verified as pathogens to eels were studied using phylogenetic analysis with 16S rRNA and HKG sequences (cpn60, gyrB, rpoB and dnaJ) and identified by Biolog automatic microbiology analysis system (gene III). From the analysis of 5 genes, the mean gene divergences of 16S rRNA, cpn60, gyrB, rpoB and dnaJ in 32 isolates were 1.4 ± 0.2%, 7.1 ± 0.7%, 5.2 ± 0.5%, 2.2 ± 0.4% and 6.8 ± 0.5%, respectively. The results of comparative phylogeny between nucleotide based analyses (excluding the third codon position) of four HKGs with the sequences from 55 strains of Aeromonas (including 23 referenced strains of Aeromonas) showed cpn60 and dnaJ have higher discriminate power than gyrB and rpoB comparing with the taxonomical identification by Biolog system. In addition, amino acid sequences of concatenated cpn60-rpoB-gyrB is a good method for Aeromonas pathogens identification. This study showed analysis of HKG sequences can be used as an alternative method for sound identification of bacterial pathogens isolated from diseased eels in China.

Protective effect of antagonist of high-mobility group box 1 on lipopolysaccharide-induced acute lung injury in mice.

We explored the effects of recombinant A-box (rA-box), a specific blockade for endogenous high mobility group box 1 (HMGB1) protein, on acute lung inflammation induced by lipopolysaccharide (LPS) in vivo. Acute lung injury (ALI) was produced successfully by intratracheal administration of LPS (10 microg/mouse) in male BALB/c mice. rA-box (0.3, 0.6 mg/mouse, i.p.) was administered 30 min prior to or 2 h after LPS exposure. Bronchoalveolar lavage fluid (BALF) was obtained to measure chemokines, proinflammatory cytokines, total cell counts and proteins at the indicated time points. It was found that rA-box caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and protein leakage at 24 h after LPS challenge. In addition, rA-box was also believed to have downregulated the expression of LPS-induced chemokines (keratinocyte-derived chemokine) and proinflammatory cytokines, including early mediator TNF-a and late mediator HMGB1. These findings confirm the significant protection of rA-box against LPS-induced ALI, and the effect mechanism of rA-box was associated with decreasing the expression of chemokines and proinflammatory cytokines.