Jiedu-Yizhi formula (JDYZF) is prescribed for the treatment of Alzheimer’s disease (AD) and was created by Jixue Ren, a master of traditional Chinese medicine, based on the “marrow deficiency and toxin damage” theory. In our clinic, this formula has been used for the treatment of AD for many years and has achieved good results. However, the mechanism by which JDYZF improves cognitive impairment has not been determined. In this study, we confirmed that orally administered JDYZF reversed the cognitive deficits in an Aβ25–35-induced rat model, increased the number of neurons in the hippocampal CA1 area, improved their structure, decreased the deposition of β-amyloid (Aβ), reduced the expression of proteins related to the NLRP3/Caspase-1/GSDMD and LPS/Caspase-11/GSDMD pyroptosis pathways, and reduced the levels of interleukin 1β (IL-1β) and IL-18, thereby inhibiting the inflammatory response. In addition, JDYZF exerted no hepatotoxicity in rats. In short, these results provide scientific support for the clinical use of JDYZF to improve the cognitive function of patients with AD.

ObjectivesDespite the improved survival of patients with AIDS and Kaposi's sarcoma (KS), competing events are a non‐negligible issue affecting the survival of such patients. In this study, we explored the prognostic factors of KS‐specific and non‐KS‐specific mortality in patients with AIDS‐related KS (AIDS‐KS), accounting for competing risk.MethodsWe identified 17 103 patients with AIDS‐KS aged 18–65 years between 1980 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) 18 registry database. Prognostic factors for KS‐specific and non‐KS‐specific mortality were determined by the Fine and Grey proportional subdistribution hazard model. We built competing risk nomograms and assessed their predictive performance based on the identified prognostic factors.ResultsIn total, 12 943 (75.68%) patients died, 1965 (15.50%) of whom died from competing events. The KS‐specific mortality rate was 14 835 per 100 000 person‐years, and the non‐KS specific mortality rate was 2719 per 100 000 person‐years. Specifically, age >44 years was associated with an 11% decrease in the subdistribution hazard of KS‐specific mortality compared with age <43 years but a 50% increase in the subdistribution hazard of non‐KS‐specific mortality. Being male was associated with a 26% increase in the subdistribution hazard of KS‐specific mortality compared with being female but a 32% decrease in the subdistribution hazard of non‐KS‐specific mortality. Notably, being in the antiretroviral therapy (ART) era consistently showed a decrease in the subdistribution hazard of both KS‐specific and non‐KS‐specific mortality than being in the pre‐ART era.ConclusionsCompeting events commonly occurred among patients with AIDS‐KS, which deserves further attention to improve the prognosis of these patients.

Objective The objective of this study was to explore the neuroprotective mechanism of JDYZF in treating AD from the perspective of inflammation and intestinal microflora. Methods A total of 24 APP/PS1 mice were randomly divided into four groups: model (n = 6), JDYZF low-dose (n = 6), JDYZF high-dose (n = 6), and positive drug (n = 6), six C57 mice were used as the control group. The body weights and diets of all mice were examined daily. After 8 weeks of administration, the learning and memory of mice were evaluated by the Morris water maze test. The histopathological changes of hippocampus, liver and kidney in mice were observed by HE staining after being euthanized. The expression of p-tau in hippocampus tissue was detected by immunohistochemistry. After that, 16S rDNA sequencing was used to investigate the relationship between JDYZF and intestinal microbiota. Finally, a comparison of TLR4, p65, p-p65, iκB, p-iκB, and IL-1β protein expression in the hippocampus tissue of mice in each group was measured by Western blot. Results The results showed that APP/PS1 mice taking JDYZF orally were generally in good condition. Compared with the control group, JDYZF significantly improved learning and memory ability in ethology. Histology showed that JDYZF improved the hippocampal structure of mice and inhibited the deposition of p-tau. JDYZF treatment could regulate the gut microbiota of APP/PS1 mice by increasing the richness of Lachnospiraceae, Ruminococcaceae , and Actinobacteria and reducing that of Alistipes and Muribaculaceae . It also significantly inhibited the activation of the TLR4/NF-κB signaling pathway in the brain. In addition, no obvious toxic reactions were found in the liver and kidney of APP/PS1 mice after taking JDYZF for 8 weeks. Conclusion The findings revealed that JDYZF improved cognitive ability and alleviated the TLR4/NF-κB signaling pathway in APP/PS1 mice, and the modulating the gut microbiota presented here may help illuminate its activation mechanism.

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