Tectoridin alleviates caerulein-induced severe acute pancreatitis by targeting ERK2 to promote macrophage M2 polarization.

Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.

Anti-inflammatory effect of proanthocyanidins from blueberry through NF-κß/NLRP3 signaling pathway in vivo and in vitro.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is an uncontrolled systemic inflammatory response. Proanthocyanidins (PC) is a general term of polyphenol compounds widely existed in blueberry fruits and can treat inflammation-related diseases. This study aimed to explore the regulatory effect of PC on lipopolysaccharide (LPS)-induced systemic inflammation and its potential mechanism, providing effective strategies for the further development of PC. METHODS: Here, RAW264.7 macrophages were stimulated with LPS to establish an inflammation model in vitro, while endotoxin shock mouse models were constructed by LPS in vivo. The function of PC was investigated by MTT, ELISA kits, H&E staining, immunohistochemistry, and Western blot analysis. RESULTS: Functionally, PC could demonstrate the potential to mitigate mortality in mice with endotoxin shock, as well as attenuated the levels of inflammatory cytokines (IL-6, TNF-α) and biochemical indicators (AST, ALT, CRE and BUN). Moreover, it had a significant protective effect on lung and kidney tissues damage. Mechanistically, PC exerted anti-inflammatory effects by inhibiting the activation of the NF-κB/NLRP3 signaling pathway. CONCLUSION: PC might have the potential ability of anti-inflammatory effects via modulation of the NF-κB/NLRP3 signaling pathway.

Family caregivers' lived experience of caring for hospitalised patients with cancer during the COVID-19 lockdown: A descriptive phenomenological study.

AIMS: This study aimed to capture and explore family caregivers' lived experience of caring for hospitalised patients with cancer during the lockdown. BACKGROUND: The unprecedented lockdown episodes due to COVID-19 have brought significant changes in the hospital visiting policies and caregiving practices. As part of the precautionary measures for hospital visits, the bedside companion was restricted to one caregiver for patients with cancer in Shanghai hospitals. DESIGN: This study adopted a descriptive phenomenological approach. METHODS: Data were collected among 20 family caregivers recruited from the Oncology department of a tertiary hospital in Shanghai in May 2022, using purposive sampling method and followed by unstructured, open-ended interviews. Colaizzi's seven-step data analysis method was used to analyse the data to reveal the emergent themes and subthemes of the phenomenon. RESULTS: Four themes were generated on family caregivers' lived experience of caring for hospitalised patients with cancer during the lockdown, including (1) Feeling scared for the patient; (2) Living a life feeling trapped under COVID-19 surveillance; (3) Feeling neglected and unseen; (4) Growing resilience and appreciation. CONCLUSIONS: The lockdown exacerbated the burden of family caregivers when they cared for the hospitalised patients with cancer during the lockdown period. However, positive reframing of the lived experience facilitated their coping with the challenging situation. RELEVANCE TO CLINICAL PRACTICE: Findings from this study highlighted the potential proactive roles the healthcare providers could play in improving family caregivers' health and supporting them during and beyond the COVID-19 pandemic. REPORTING METHOD: The study adhered to relevant EQUATOR guidelines; the study was reported according to the COREQ checklist. PATIENT OR PUBLIC CONTRIBUTION: Family caregivers of patients with cancer were involved in data collection and member-checking of the transcripts and interpretations of their experiences.

Driving GABAergic neurons optogenetically improves learning, reduces amyloid load and enhances autophagy in a mouse model of Alzheimer's disease.

The changes of local field potentials (LFP, mainly gamma rhythm and theta rhythm) in the brain are closely related to learning and memory formation. Reduced gamma rhythm (20-50 Hz) and theta rhythm (4-10 Hz) has been observed in the progression of Alzheimer's disease (AD), but it is not clear whether it is related to cognition in AD. Here, we investigated behaviorally driven gamma rhythm and theta rhythm in APP/PS1 mice, and optogenetically stimulated GABAergic neurons in the brain to better understand the relationship between the changes of LFP, cognition, and cellular pathologies. Optogenetically driving GABAergic neurons rescued memory formation in a water maze task and normalized theta and gamma rhythm in the EEG. Furthermore, the optogenetic stimulation alleviated neuroinflammation and levels of amyloid-ß (Aß)1-42 fragments, and induced autophagy. GABA blockers also reversed the normalization of theta and gamma rhythms in the brain by optogenetic stimulation. The results demonstrate that stimulation of GABAergic interneurons not only rescues LFP rhythms and memory formation, but furthermore activates autophagy and reduces neuroinflammation, which have beneficial additional effects such as clearing amyloid. This is a proof of concept for a novel therapeutic approach to AD treatment.

Resveratrol alleviates temporomandibular joint inflammatory pain by recovering disturbed gut microbiota.

Patients with temporomandibular disorders (TMDs) often experience persistent facial pain. However, the treatment of TMD pain is still inadequate. In recent years, the disturbance of gut microbiota has been shown to play an important role in the pathogenesis of different neurological diseases including chronic pain. In the present study, we investigated the involvement of gut microbiota in the development of temporomandibular joint (TMJ) inflammation. Intra-temporomandibular joint injection of complete Freund's adjuvant (CFA) was employed to induce TMJ inflammation. Resveratrol (RSV), a natural bioactive compound with anti-inflammatory property, was used to treat the CFA-induced TMJ inflammation. We observed that CFA injection not only induces persistent joint pain, but also causes the reduction of short-chain fatty acids (SCFAs, including acetic acid, propionic acid and butyric acid) in the gut as well as decreases relevant gut bacteria Bacteroidetes and Lachnospiraceae. Interestingly, systemic administration of RSV (i.p.) dose-dependently inhibits CFA-induced TMJ inflammation, reverses CFA-caused reduction of SCFAs and these gut bacteria. Moreover, CFA injection causes blood-brain barrier (BBB) leakage, activates microglia and enhances tumor necrosis factor alpha (TNFα) release in the spinal trigeminal nucleus caudalis (Sp5C). The RSV treatment restores the BBB integrity, inhibits microglial activation and decreases the release of TNFα in the Sp5C. Furthermore, fecal microbiota transplantation with feces from RSV-treated mice significantly diminishes the CFA-induced TMJ inflammation. Taken together, our results suggest that gut microbiome perturbation is critical for the development of TMJ inflammation and that recovering gut microbiome to normal levels could be a new therapeutic approach for treating such pain.

The prognostic value of pretreatment neutrophil-to-lymphocyte ratio in breast cancer: Deleterious or advantageous?

Breast cancer is one of the leading malignant tumors that endanger women's health worldwide. Despite the rapid progress on the therapies, including chemotherapy, surgical resection, and other auxiliary methods, there were still numerous people died of breast cancer, which promoted the researchers to concentrate on the prognostic factor of breast cancer. In recent years, an increasing number of studies have been focused on the prognostic value of pretreatment neutrophil-to-lymphocyte ratio in breast cancer. This article is a brief review of the associations between neutrophil-to-lymphocyte ratio and the prognosis of breast cancer patients, which may give a greater insight into the development of breast cancer and enable clinicians to cure it completely.

Secure output consensus for multi-agent systems under edge-based event-trigger against denial-of-service.

This paper is concerned with the secure output consensus problem for the heterogeneous multi-agent systems under the event-triggered scheme in the presence of the denial-of-service attack. Without detecting the attack, the hold-input controller update strategy is adopted when some transmission data may be lost due to the effect of the attack. Based on the tolerable duration of the attack, a novel edge-based event-triggered scheme is developed. The scheme can avoid continuous communication and exclude Zeno behavior. With the aid of the switched system theory, output consensus is preserved. An example shows the effectiveness.

Approved drugs and natural products at clinical stages for treating Alzheimer's disease.

Alzheimer's disease (AD) remains the foremost cause of dementia and represents a significant unmet healthcare need globally. The complex pathogenesis of AD, characterized by various pathological and physiological events, has historically challenged the development of anti-AD drugs. However, recent breakthroughs in AD drug development, including the approvals of aducanumab, lecanemab, and sodium oligomannate (GV-971), have ended a nearly two-decade hiatus in the introduction of new AD drugs. These developments have addressed long-standing challenges in AD drug development, marking a substantial shift in the therapeutic landscape of AD. Moreover, natural products (NPs) have shown promise in AD drug research, with several currently under clinical investigation. Their distinct properties and mechanisms of action offer new avenues to complement and enhance existing AD treatment approaches. This review article aims to provide an overview of the recent advancements and prospects in AD therapeutics, focusing on both NPs and approved drugs.

Predictors of In-Stent Stenosis Following the Implantation of Pipeline Embolization Devices for the Treatment of Aneurysms Located at or beyond the Circle of Willis in the Anterior Circulation.

BACKGROUND AND PURPOSE: In-stent stenosis is commonly observed after stent implantation. There is no consensus on the contributing factors for in-stent stenosis, especially for aneurysms located at or beyond the circle of Willis in the anterior circulation. This study aimed to investigate the morbidity and determinants of in-stent stenosis in distal anterior circulation aneurysms following the implantation of Pipeline Embolization Devices. MATERIALS AND METHODS: Patients who underwent Pipeline Embolization Device treatment at our center between January 1, 2018, and June 15, 2023, were enrolled. Distal anterior circulation aneurysms were defined as those occurring at or beyond the circle of Willis, including anterior communicating artery aneurysms, anterior cerebral artery aneurysms, and MCA aneurysms. Baseline information, aneurysm characteristics, and follow-up data of patients were analyzed. Patients were divided into 2 groups: the in-stent stenosis group (patients with a loss of >25% of the lumen diameter of the parent artery) and the non-in-stent stenosis group. Binary logistic regression and restricted cubic spline curves were used to explore risk factors. RESULTS: We included 85 cases of 1213 patients treated with flow-diverter devices at our hospital. During an average follow-up period of 9.07 months, the complete occlusion rate was 77.64%. The overall incidence of in-stent stenosis was 36.47% (31/85), of which moderate stenosis accounted for 9.41% (8/85), and severe stenosis, 5.88% (5/85) (triglyceride-glucose index ≥ 8.95; OR = 6.883, P = .006). The difference in diameters between the stent and parent artery of ≥0.09 mm (OR = 6.534, P = .015) and 55 years of age or older (OR = 3.507, P = .036) were risk factors for in-stent stenosis. The restricted cubic spline curves indicated that the risk of in-stent stenosis increased as the difference in diameter between stent and parent artery and the triglyceride-glucose index increased. CONCLUSIONS: Compared with the on-label use of Pipeline Embolization Devices, the rate of in-stent stenosis did not obviously increase when treating distal anterior circulation aneurysms with these devices. The incidence of in-stent stenosis was 36.47% when defined as a lumen diameter loss of >25%, and 15.2% when defined as a lumen diameter loss of >50%. Stent-size selection and biochemical indicators can potentially impact the incidence of in-stent stenosis.

Value of difference in diameters between Pipeline embolization device and parent artery in assessing aneurysm outcome.

OBJECTIVE: In vitro trials have demonstrated that oversized stents are associated with reduced metal coverage and increased porosity. However, the relationship between stent selection and aneurysm outcome is inconclusive, and determination of this was the authors' purpose in conducting this study. METHODS: This was a single-center retrospective study. Patients who underwent Pipeline embolization device treatment at the authors' center between January 1, 2018, and June 15, 2023, were enrolled. The authors constructed multiple logistic regression models and restricted cubic spline plots to examine the effect of the difference in diameters between the stent and parent artery (Dd) on aneurysm outcome. The authors also performed stratified analyses. Then, Dd was included in the logistic regression analysis as a categorical variable. The cutoff value for Dd was determined according to the principle of the maximum Youden's index. RESULTS: In total, 302 patients were included in this study. The median Dd was 0.52 mm. With a median follow-up time of 7 months, the aneurysm occlusion rate was 80.1%. The restricted cubic spline plots showed a decreasing aneurysm occlusion rate as Dd increased. After stratification by age and adjunctive embolization, the restricted cubic splines aligned with the results of the main analysis. Compared with the group with a smaller Dd (Dd < 0.3625 mm), the group with a larger Dd showed an OR of 0.439 (p = 0.026). Additionally, patients with diabetes mellitus (OR 0.306, p = 0.018), age ≥ 65 years (OR 0.968, p = 0.03), aneurysm incorporation with a branch (OR 0.253, p < 0.001), and aneurysm neck ≥ 4 mm (OR 0.872, p = 0.003) were independent predictors of aneurysm persistence, whereas Pipeline embolization device plus coiling (OR 4.949, p < 0.001) and smoking history (OR 5.86, p = 0.025) were predictors of aneurysm occlusion. CONCLUSIONS: The authors' retrospective analysis demonstrated that the aneurysm occlusion rate declined when Dd increased within a certain range. The authors suggested that Dd with an interval of -0.25 to 0.5 mm may be proper in clinical practice.

Bletilla striata polysaccharide attenuated the progression of pulmonary fibrosis by inhibiting TGF-ß1/Smad signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bletilla striata, a traditional medicinal plant, has been utilized as a folk medicine for many years because of its superior biological activity in China. However, Bletilla striata polysaccharide (BSP) has received less attention, and its specific mechanism for ameliorating pulmonary fibrosis is completely unclear. AIMS OF THE STUDY: In this study, we aim to assess BSP on the treatment of PF and explore potential mechanisms. MATERIALS AND METHODS: BSP was successfully extracted and purified from Bletilla striata. The mechanisms were assessed in bleomycin-induced pulmonary fibrosis model and lung fibroblasts activated by transforming growth factor-ß1 (TGF-ß1). Histological analysis, immunofluorescence, Western blot and flow cytometry were used to explore the alterations after BSP intervention. RESULTS: The results in vivo showed an anti-PF effect of BSP treatment, which reduced pathogenic damages. Furthermore, TGF-ß1-induced abnormal migration and upregulated expression of collagen I (COL1A1), vimentin and α-smooth muscle actin (α-SMA) were suppressed by BSP in L929 cells. Moreover, the abnormal proliferation was retarded by inhibiting the cell cycle of G1 to S phase. Immunofluorescence assay showed that BSP activated autophagy and played an antifibrotic role by inhibiting the expression of p62 and phospho-mammalian target of rapamycin (p-mTOR). Last but not least, the suppression of TGF-ß1/Smad signaling pathway was critical for BSP to perform therapeutic effects in vitro and in vivo. CONCLUSION: The possible mechanisms were involved in improving ECM deposition, regulating cell migration and proliferation, and promoting cellular autophagy. Briefly, all of the above revealed that BSP might be a novel therapy for treating pulmonary fibrosis.

Specific Activation of Dopamine Receptor D1 Expressing Neurons in the PrL Alleviates CSDS-Induced Anxiety-Like Behavior Comorbidity with Postoperative Hyperalgesia in Male Mice.

Postoperative pain is a type of pain that occurs in clinical patients after surgery. Among the factors influencing the transition from acute postoperative pain to chronic postoperative pain, chronic stress has received much attention in recent years. Here, we investigated the role of dopamine receptor D1/D2 expressing pyramidal neurons in the prelimbic cortex (PrL) in modulating chronic social defeat stress (CSDS)-induced anxiety-like behavior comorbidity with postoperative hyperalgesia in male mice. Our results showed that preoperative CSDS induced anxiety-like behavior and significantly prolonged postoperative pain caused by plantar incision, but did not affect plantar wound recovery and inflammation. Reduced activation of dopamine receptor D1 or D2 expressing neurons in the PrL is a remarkable feature of male mice after CSDS, and chronic inhibition of dopamine receptor D1 or D2 expressing neurons in the PrL induced anxiety-like behavior and persistent postoperative pain. Further studies found that activation of D1 expressing but not D2 expressing neurons in the PrL ameliorated CSDS-induced anxiety-like behavior and postoperative hyperalgesia. Our results suggest that dopamine receptor D1 expressing neurons in the PrL play a crucial role in CSDS-induced anxiety-like behavior comorbidity with postoperative hyperalgesia in male mice.

Harmine ameliorates CCl4-induced acute liver injury through suppression of autophagy and inflammation.

CCl4-induced acute liver injury (ALI) is characterized by heightened autophagy, inflammation, and oxidative damage. Accumulating evidence suggests that harmine exerts beneficial effects in countering CCl4-induced ALI by mitigating inflammation and oxidative stress. However, the impact of autophagy on CCl4-induced ALI and the protective role of harmine remain unclear. This study aimed to investigate the potential protective effects of harmine against CCl4-induced ALI in mice by suppressing autophagy and inflammation. Male Kunming mice were orally administered harmine or bifendate for seven days. Subsequently, one hour after the final administration, the model group and treatment groups were intraperitoneally injected with CCl4 to induce ALI. The findings revealed that harmine significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, and ameliorated the liver histopathological changes induced by CCl4. Furthermore, harmine diminished the levels of TNF-α and IL-6, restored the levels of glutathione (GSH) and superoxide dismutase (SOD), and suppressed the production of nitric oxide (NO) and malondialdehyde (MDA) in the liver. Mechanistically, harmine down-regulated LC3B II/I, p38 MAPK, TLR4, and NF-κB levels, while upregulating p62, Bcl-2, Beclin1, ULK1, and p-mTOR expression. In conclusion, harmine mitigated CCl4-induced ALI by inhibiting autophagy and inflammation through the p38 MAPK/mTOR autophagy pathway, the Bcl-2/Beclin1 pathway, and the TLR4/NF-κB pathway.

ß-Cyclodextrin and Hyaluronic Acid-Modified Targeted Nanodelivery System for Atherosclerosis Prevention.

Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of ß-cyclodextrin (ß-CD), a nanoplatform encapsulating the unstable drug (-)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from ß-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE-/- mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.

(-)-Epicatechin gallate prevented atherosclerosis by reducing abnormal proliferation of VSMCs and oxidative stress of AML 12 cells.

(-)-Epicatechin gallate (ECG) is beneficial to the treatment of cardiovascular diseases (CVDs), especially atherosclerosis (AS) through antioxidant stress, but there is a lack of detailed mechanism research. In this study, the therapeutic target of ECG was determined by crossing the drug target and disease target of CVDs and AS. The combination ability of ECG with important targets was verified by Discovery Studio software. The abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by Ang-II and the oxidative damage of AML 12 induced by H2O2 were established to verify the reliability of ECG intervention on the target protein. A total of 120 ECG targets for the treatment of CVDs-AS were predicted by network pharmacology. The results of molecular docking showed that ECG has strong binding force with VEGFA, MMP-9, CASP3 and MMP-2 domains. In vitro experiments confirmed that ECG significantly reduced the expression of VEGFA, MMP-9, CASP3 and MMP-2 in Ang-II-induced VSMCs, and also blocked the abnormal proliferation, oxidative stress and inflammatory reaction of VSMCs by inhibiting the phosphorylation of PI3K signaling pathway. At the same time, ECG also interfered with H2O2-induced oxidative damage of AML 12 cells, decreased the expression of ROS and MDA and cell foaming, and increased the activities of antioxidant enzymes such as SOD, thus playing a protective role.

TRPA1 Ion Channel Mediates the Analgesic Effects of Acupuncture at the ST36 Acupoint in Mice Suffering from Arthritis.

Purpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia. Patients and Methods: We injected complete Freund's adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1-/- mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1. Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1-/- ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated. Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.

Mobilizing endogenous neuroprotection: the mechanism of the protective effect of acupuncture on the brain after stroke.

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.

Psychological experience of home-quarantined older women with COVID-19 in Hong Kong: A qualitative study.

BACKGROUND: The surge of positive COVID-19 cases taxed the local health care system and left many older adults initiating home self-care practices. The study aimed to explore the psychological experiences of home-quarantined older women diagnosed with COVID-19 in Hong Kong. METHODS: Ten semi-structured telephone interviews were held among older women from March to April 2022. Inductive thematic analysis was used to analyse the data. RESULTS: Older women experienced psychological distress, anxiety and depression after being infected with COVID-19. The source of their psychological difficulties included fear of losing control over one's health and dignity, feeling a burden to one's family, conflict in balancing risks and responsibilities, and being overwhelmed by the tragic news reported in media. Meanwhile, the participants demonstrated resilience following the infection and found meaning in their experiences, and grew mentally. CONCLUSIONS: The older women in this study have identified the negative impact having a diagnosis and being home-quarantine means to them and their family. Yet, they were also able to take some positives from this. Importantly, the older women report being able to build greater resilience, optimism and wisdom towards COVID-19 in general and feel better prepared for the potential of future positive diagnoses.

Safety and efficacy analysis of the off-label use of pipeline embolization devices for intracranial aneurysms: a propensity score matching study.

Background and objective: The safety and efficacy of on-label use of pipeline embolization devices (PEDs) are well established; however, there is much controversy over their off-label use. This study aimed to investigate the safety and efficacy of the off-label use of PEDs for treating intracranial aneurysms. Methods: This single-center study retrospectively included patients with digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography confirmed intracranial aneurysms treated with PEDs who were admitted to our institution between 1 January 2018 and 1 July 2022. Patients were divided into on- and off-label groups according to the Food and Drug Administration criteria published in 2021. Propensity score matching (PSM) was used to balance disparities in baseline information between the two groups. Safety outcomes included postoperative mortality and complication rates, whereas effectiveness outcomes included aneurysm occlusion rate (O'Kelly-Marotta grading system C + D grades), retreatment rate within 12 months, and postoperative functional score [modified Rankin scale (mRS) score]. The study was approved by the Ethics Committee of Scientific Research and Clinical Trial of the First Affiliated Hospital of Zhengzhou University (Ethics number: KY 2018-098-02). All patients provided informed consent. Results: A total of 242 patients with 261 aneurysms (160 on-label and 101 off-label aneurysms) were included in this study. PSM yielded 81 pairs of patients matched for baseline information. Postoperative hemorrhagic, ischemic, and procedure-related complication rates did not reach statistical significance. In addition, no statistically significant differences in the aneurysm occlusion rate, retreatment rate within 12 months, postoperative functional score (mRS score), or mRS score deterioration rate were observed between the two groups. A higher incidence of in-stent stenosis was observed in the off-label (4.9% vs. 21%, p = 0.002) group than in the on-label group; however, all patients were asymptomatic. Conclusion: Compared with on-label use, off-label use of PEDs for treating intracranial aneurysms did not increase the risk of complications, and the occlusion rates were comparable. Therefore, decisions regarding clinical management should not rely solely on on- or off-label indications.

Epigenetic Regulation of Neuroinflammation in Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease and clinically manifests with cognitive decline and behavioral disabilities. Over the past years, mounting studies have demonstrated that the inflammatory response plays a key role in the onset and development of AD, and neuroinflammation has been proposed as the third major pathological driving factor of AD, ranking after the two well-known core pathologies, amyloid ß (Aß) deposits and neurofibrillary tangles (NFTs). Epigenetic mechanisms, referring to heritable changes in gene expression independent of DNA sequence alterations, are crucial regulators of neuroinflammation which have emerged as potential therapeutic targets for AD. Upon regulation of transcriptional repression or activation, epigenetic modification profiles are closely involved in inflammatory gene expression and signaling pathways of neuronal differentiation and cognitive function in central nervous system disorders. In this review, we summarize the current knowledge about epigenetic control mechanisms with a focus on DNA and histone modifications involved in the regulation of inflammatory genes and signaling pathways in AD, and the inhibitors under clinical assessment are also discussed.