Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

OBJECTIVES: To investigate pharmacologically active components of Yiqi Zishen Formula (YZF) and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease (COPD). METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum. A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis. A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways. Fifty male C57BL/6J mice were randomized equally into control group, COPD model group, high- and low-dose YZF treatment groups, and N-acetylcysteine treatment group. Pulmonary function of the mice was assessed using whole-body plethysmography, and lung histopathology, alveolar structure, and airway remodeling were analyzed using HE staining. The levels of IL-1β, IL-6, and TNF‑α in bronchoalveolar lavage fluid (BALF) were determined with ELISA, and pulmonary expressions of PI3K, Akt, phosphorylated Akt (p-Akt), p65, and phosphorylated p65 (p-p65) were detected using immunohistochemistry. RESULTS: We identified a total of 156 chemical components (including 26 flavonoids or flavonoid glycosides, 27 alkaloids, and 11 saponins) in YZF and 43 prototype components in medicated rat serum. Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets. Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway. In mouse models of COPD, YZF treatment significantly increased mean alveolar number and peak expiratory flow (P<0.05), reduced mean linear intercept, bronchial wall thickness, lung coefficient, and BALF cytokine levels, and suppressed the expressions of PI3K, Akt, p-Akt, p65, and p-p65 in the lung tissues. CONCLUSIONS YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF‑κB pathway through its multiple components that interact with multiple targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Male ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; NF-kappa B/metabolism* ; Inflammation/drug therapy* ; Rats

Objective To investigate the effects of Duzhi Pills combined with MOTOmed training on limb function and activities of daily living in patients with cerebral infarction of qi deficiency and blood stasis type.Methods A prospective randomized controlled trial enrolled 98 cerebral infarction patients with qi deficiency and blood stasis treated at Qinhuangdao Hospital,Oriental Hospital of Beijing University of Chinese Medicine(Qinhuangdao Hospital of Traditional Chinese Medicine)from June 2022 to December 2024.Participants were randomized into control group(n=49,receiving conventional rehabilitation)and observation group(n=49,receiving additional Duzhi Pills+MOTOmed training)for 8 weeks.All patients received standard medication.Limb motor function and activities of daily living,and quality of life were assessed before and after treatment.Results(1)After treatment,both groups showed significant increases in Carroll Hand Function Test for Upper Extremity(CHFT-UE)scores,Fugl-Meyer Assessment Scale for Upper Extremity(FMA-UE)scores,and Simple Test for Evaluating Hand Function(STEF)scores compared to baseline(P＜0.05),with significantly greater improvements observed in the observation group(P＜0.01).(2)After treatment,both groups exhibited significant increases in Barthel Index scores for daily activity(P＜0.05),with the observation group demonstrating significantly greater improvement(P＜0.01).(3)After treatment,all subscale scores of the 36-Item Short-Form Health Survey(SF-36),including physical function,bodily pain,mental health,vitality,social functioning,emotional role,and general health,were significantly increased in both groups(P＜0.05),with significantly greater improvements in the observation group,the difference being statistically significant(P＜0.01).Conclusion The combined regimen of Duzhi Pills and MOTOmed training significantly enhances limb function,daily activity,and quality of life in cerebral infarction patients with qi deficiency and blood stasis syndrome,demonstrating clinical value for rehabilitation.

ObjectiveTo investigate the relationship between Jiaotai pill (JTP), its main component berberine (BBR), and the serotonin (5-HT) system in regulating islet hormone secretion and alleviating pancreatic β-cell dysfunction during type 2 diabetes mellitus (T2DM) progression.MethodsT2DM rat model was established using a high-fat diet and streptozotocin injection. JTP, BBR, and Metformin were intragastrically administered for 35 days. The analyzed indices included blood glucose, blood lipids, islet hormones, and proteins related to 5-HT synthesis, secretion, and transport. Additionally, an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1 (TPH1) inhibition.ResultsJTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats. Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion. However, the administration of JTP and BBR reversed these effects. Furthermore, JTP and BBR upregulated the expression of TPH1(P = .0194, P = .0413) transglutaminase 2 (TGase2; P = .0492, P = .0349), serotonin transporter (SERT, P = .0090), and 5- hydroxytryptamine 1F receptor (5-HT1FR) in the islet 5-HT pathway (P = .0194). In the cell model, the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition (P = .001), suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.ConclusionThe islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM. JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.

OBJECTIVE To investigate the mechanism of catalpol affecting the differentiation of helper T cell 17 （Th17） by interfering the expressions of pyruvate kinase M2 （PKM2） and lactate dehydrogenase A （LDHA）. METHODS The naive CD4+ T cells were selected from the spleen of C57BL/6 mice， and were differentiated into Th17 cells by adding directional differentiation stimulants for 72 hours. At the same time， the cells were treated with 0 （directed control）， 20， 40 and 80 μg/mL catalpol. The flow cytometry was used to detect the proportion of Th17 cell differentiation in cells； the colorimetric method was adopted to detect the levels of pyruvate and lactate in cell culture supernatant； mRNA expressions of retinoid-related orphan nuclear receptor gamma t （RORγt）， PKM2 and LDHA were detected by qRT-PCR method； Western blot was used to detect the expression levels of PKM2， LDHA， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated STAT3 （p-STAT3） proteins in cells. RESULTS Compared with the directed control group， after 72 hours of treatment with 20， 40， 80 μg/mL catalpol， the differentiation ratio of Th17 cells were decreased by 6.74%， 8.41%， 9.24%， and the levels of pyruvate and lactate in the cell culture supernatant， the mRNA expressions of PKM2， LDHA and RORγt as well as the protein expressions of PKM2 and LDHA and the phosphorylation of STAT3 were significantly reduced （P＜0.05）. CONCLUSIONS Catalpol can reduce the glycolysis level by down-regulating the expressions of PKM2 and LDHA， thereby inhibiting the differentiation of Th17 cells.

BACKGROUND:Medical hydrogels are new functional polymer materials with three-dimensional structural networks and excellent biocompatibility,which have been widely studied in the field of tissue engineering and drug carriers,but the research on the combination of medical hydrogels and Chinese medicine for the treatment of diseases based on tissue engineering is still in the early exploration stage.Therefore,through the analysis of the mechanism of the role of medical hydrogels,the integration of medical hydrogels and Chinese medicine in the research of the joint application of the article,can better provide ideas for scientific researchers,and the joint application of Chinese medicine and medical hydrogels is of great significance. OBJECTIVE:To explore the strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment based on tissue engineering research. METHODS:PubMed and CNKI were used to retrieve articles about the application of Chinese medicine combined with medical hydrogel in tissue engineering from January 2010 to November 2022,with the Chinese and English search terms"hydrogel,traditional Chinese medicine,drug carrier,tissue engineering".After the initial screening of all articles according to the inclusion and exclusion criteria,the 61 articles with high relevance were retained for review. RESULTS AND CONCLUSION:(1)Although the application of Chinese medicine combined with medical hydrogel is involved in intra-articular,intra-tissue organ,soft tissue wounds,tissue engineering,etc.,except for the clinical application of Chinese medicine combined with hydrogel dressing for soft tissue injury,other aspects are still in the experimental stage.(2)The development of Chinese medicine combined with medical hydrogel has great potential and development prospects,but there is a certain difficulty in the manufacture of the gel with high-performance requirements,and it is difficult to master the physical and chemical properties precisely.(3)At present,the comprehensive view of injectable hydrogel with the characteristics of easy to use,its joint use of Chinese medicine can be extended to a wider range,can be used for joint,organ,tissue engineering-related disease treatment.Smart hydrogel has high sensitivity and reversible transformation can also meet the use of the special environment.During the combined use of Chinese medicine,it also needs to understand the mechanism of action of Chinese medicine components.(4)The strategy of combining Chinese medicine with medical hydrogels for disease treatment should start with matching the therapeutic effects of Chinese medicine on organs,tissues and cells combined with appropriate types of medical hydrogels to make up for the shortcomings of traditional Chinese medicine delivery methods and frequent drug delivery.In tissue engineering,hydrogels can be loaded with stem cells after Chinese medicine intervention,or with both Chinese medicine and stem cells for disease treatment.(5)In future research of combined Chinese medicine and medical hydrogel application,we also need to consider:we should ensure that the biological properties of medical hydrogel can be quantified,and grasp the characteristics of hydrogel with different manufacturing processes of different materials to produce the required medical hydrogel that meets the application conditions.In Chinese medicine,we need to comprehensively understand and analyze the therapeutic effects and application mechanisms of known Chinese medicine monomer and Chinese medicine compound extracts,so as to achieve a more perfect combination between Chinese medicine and medical hydrogel under a more clear mechanism.With the continuous improvement of medical science and technology innovation,the medical hydrogel can be innovatively combined with other traditional treatment methods of Chinese medicine,such as acupuncture,massage,cupping and so on,to be used from multiple angles.

Objective:To investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.

Objective To understand the recognition and coping strategies of ICU nurses on post-ICU syndrome in family members of patients during hospitalisation so as to provide a reference for handling post-ICU syndrome of the family members of patients.Methods A phenomenological approach within qualitative research was adopted.Semi-structured in-depth interviews were conducted with 15 ICU nurses from 3 wards of the Second Affiliated Hospital of South China University.Colaizzi 7-step method was applied to analyse and refine the interview data themes.Results Three main themes and nine sub-themes were identified and they were insufficient cognition of post-ICU syndrome of the family members(limited understanding of post-ICU syndrome in family members,difficulty in recognising or ignoring symptoms,uncertainty about the impact of post-ICU syndrome),active coping with post-ICU syndrome of the family members(coping mainly through listening and explaining,coping mainly through verbal and physical actions,diligent patient care)and various factors hindering nurses'coping with post-ICU syndrome of the family members(compassion fatigue,high ICU work intensity,limited contact time with family members).Conclusion ICU nurses have insufficient understanding of post-ICU syndrome with the family members of patients during hospitalisation.It requires to enhance a comprehensive understanding in ICU nurses about post-ICU syndrome of the family members of patients and to optimise coping strategies to alleviate negative emotions of the family members.Additionally,efforts should be made to overcome factors that hinder nurses'coping with post-ICU syndrome of the family members of patients and to promote a harmonious relationship between medical staff and patients.

Osteoporosis can be induced by various factors including prolonged glucocorticoid usage, diminished estrogen levels, secondary hyperparathyroidism, and alterations in the microenvironment of bone tissue. The bone metabolism imbalance(osteogenic-lipogenic imbalance) plays a crucial role in the development of osteoporosis. This imbalance is primarily driven by an increase in the differentiation of bone marrow mesenchymal stem cells into adipocytes and a decrease in their differentiation into osteoblasts, thus forming the core of the osteogenic-lipogenic imbalance observed in osteoporosis. The bone morphogenesis protein(BMP) plays a crucial role in the regulation of the osteogenic-lipid balance in osteoporosis. This regulatory function is accomplished through both the Smad-dependent and Smad-independent pathways. This review centers on the Smad-dependent and Smad-independent pathways facilitated by BMP, offering a comprehensive overview of the potential mechanisms through which BMP-2, 4, 6, 7, and 9 contribute to the regulation of osteogenesis and lipid metabolism in osteoporosis via these pathways. In order to present novel insights for the identification of efficacious targets for clinical anti-osteoporosis medications.

Alzheimer's disease(AD),a common neurodegenerative disease,has been linked to periodontitis,espe-cially Porphyromonas gingivalis(P.gingivalis)infection.This review summarizes the potential mechanisms and path-ways through which P.gingivalis and its virulence factors are involved in AD pathogenesis,aiming to provide the scien-tific basis for the development of novel prevention and treatment strategies for AD.P.gingivalis can promote AD by ex-acerbating neuroinflammation,facilitating amyloid beta and Tau deposition,and disrupting the blood-brain barrier.Gin-gipains,secreted by P.gingivalis,serve as core effector molecules by increasing the blood-brain barrier permeability.The association between P.gingivalis and its effectors and AD pathology has been validated by metagenomic analysis and sample detection,indicating that P.gingivalis may be an environmental susceptibility factor or modifiable risk fac-tor for AD.However,the precise mechanisms by which P.gingivalis influences AD,and its interactions with other po-tential AD-related factors,remain unclear.Moreover,further research needs to be conducted on the therapeutic potential of P.gingvalis intervention in improving AD.