Early hyperbaric oxygen therapy through regulating the HIF-1α signaling pathway attenuates Neuroinflammation and behavioral deficits in a mouse model of Sepsis-associated encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) presents a significant clinical challenge, associated with increased mortality and healthcare expenses. Hyperbaric oxygen therapy (HBOT), involving inhaling pure or highly concentrated oxygen under pressures exceeding one atmosphere, has demonstrated neuroprotective effects in various conditions. However, the precise mechanisms underlying its protective actions against sepsis-associated brain injury remain unclear. This study aimed to determine whether HBOT protects against SAE and to elucidate the impact of the hypoxia-inducible factor-1α (HIF-1α) signaling pathway on SAE. METHODS: The experiment consisted of two parts. In the first part, C57BL/6 J male mice were divided into five groups using a random number table method: control group, sham surgery group, sepsis group, HBOT + sepsis group, and HBOT + sham surgery group. In the subsequent part, C57BL/6 J male mice were divided into four groups: sepsis group, HBOT + sepsis group, HIF-1α + HBOT + sepsis group, and HIF-1α + sepsis group. Sepsis was induced via cecal ligation and puncture (CLP). Hyperbaric oxygen therapy was administered at 1 h and 4 h post-CLP. After 24 h, blood and hippocampal tissue were collected for cytokine measurements. HIF-1α, TNF-α, IL-1ß, and IL-6 expression were assessed via ELISA and western blotting. Microglial expression was determined by immunofluorescence. Blood-brain barrier permeability was quantified using Evans Blue. Barnes maze and fear conditioning were conducted 14 days post-CLP to evaluate learning and memory. RESULTS: Our findings reveal that CLP-induced hippocampus-dependent cognitive deficits coincided with elevated HIF-1α and increased TNF-α, IL-1ß, and IL-6 levels in both blood and hippocampus. Observable activation of microglial cells in the hippocampus and increased blood-brain barrier (BBB) permeability were also evident. HBOT mitigated HIF-1α, TNF-α, IL-1ß, and IL-6 levels, attenuated microglial activation in the hippocampus, and significantly improved learning and memory deficits in CLP-exposed mice. Additionally, these outcomes were corroborated by injecting a lentivirus that overexpressed HIF-1α into the hippocampal region of the mice. CONCLUSION: HIF-1α escalation induced peripheral and central inflammatory factors, promoting microglial activation, BBB impairment, and cognitive dysfunction. However, HBOT ameliorated these effects by reducing HIF-1α levels in Sepsis-Associated Encephalopathy.

Mobile health-based remote interaction management intervention for patients with low anterior resection syndrome: study protocol for a randomised controlled trial.

INTRODUCTION: Low anterior resection syndrome (LARS) involves bowel dysfunction after sphincter-preserving surgery for rectal resection that significantly impacts patients' quality of life (QoL). The improvement of LARS largely depends on patient self-management behaviour; however, insufficient information about supportive care and weak awareness of self-management lead to poor self-management behaviour. Motivational interviewing (MIs) explore and change patients' ambivalence during the conversation, thereby changing and maintaining healthy behaviours to enhance effective participation. In recent years, mobile health has been widely used in clinical practice, providing continuous information support and remote interaction. However, current online information on LARS is suboptimal, websites are highly variable, important content is often lacking and the material is too complex for patients. Therefore, this study will evaluate the impacts of a remote LARS interaction management intervention based on a WeChat applet ('e-bowel safety') and MIs on patients with LARS. METHODS AND ANALYSIS: This study will be a single-blind, two-arm randomised controlled trial involving patients with LARS in three tertiary grade A general hospitals who will be randomised into two groups. The intervention group will use the 'e-bowel safety' applet and the intervention team will conduct a monthly MI about syndrome management. The control group will receive an information booklet that contains the same information as that provided in the 'e-bowel safety' informational module. The intervention will last for 3 months, followed by 3 months of follow-up. The primary outcome will be global QoL; the secondary outcomes will include bowel function, social support, self-management measured at the baseline, 3 months and 6 months for three times and patients' thinkings at the end of the intervention (at 3 months). ETHICS AND DISSEMINATION: Ethics approval was granted by the Clinical Medical Research Ethics Committee of the First Affiliated Hospital of Anhui Medical University (PJ2022-07-53). TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200061317).