Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

Objective:To explore the experiences and needs of discharged patients with ischemic stroke during the implementation of home-based digital-intelligent blood pressure management.Methods:Using purposive sampling method, 13 acute ischemic stroke patients admitted to the Department of Neurology of Xuanwu Hospital of Capital Medical University and discharged to receive home-based digital-intelligent blood pressure management were selected for face-to-face semi-structured interviews between March and May 2024. Colaizzi 7-step analysis was used for the analysis.Results:A total of three themes and six sub-themes were extracted, namely, the double-edged effect under digital-intelligent empowerment (current situation of collision between technological novelty and cognitive generation gap, and contradiction between precision priority and lagging user experience), inertial resistance and behavioral reshaping in the process of digital-intelligent intervention (behavioral intervention exclusion under life inertia and self-efficacy enhancement driven by digital intelligence), and the "support disconnection" and the need for system reconstruction in home-based rehabilitation (professional guidance "vacuum" identity anxiety, and imbalance in the tension of family support networks) .Conclusions:Home-based blood pressure digital-intelligent management devices and programs for ischemic stroke patients need to be improved and developed. The role of multidisciplinary teams should be actively utilized, the digital divide should be emphasized, and post-disease family relationships should be reconstructed to further enhance patients' awareness of long-term blood pressure management.

Objective:To explore the experiences and needs of discharged patients with ischemic stroke during the implementation of home-based digital-intelligent blood pressure management.Methods:Using purposive sampling method, 13 acute ischemic stroke patients admitted to the Department of Neurology of Xuanwu Hospital of Capital Medical University and discharged to receive home-based digital-intelligent blood pressure management were selected for face-to-face semi-structured interviews between March and May 2024. Colaizzi 7-step analysis was used for the analysis.Results:A total of three themes and six sub-themes were extracted, namely, the double-edged effect under digital-intelligent empowerment (current situation of collision between technological novelty and cognitive generation gap, and contradiction between precision priority and lagging user experience), inertial resistance and behavioral reshaping in the process of digital-intelligent intervention (behavioral intervention exclusion under life inertia and self-efficacy enhancement driven by digital intelligence), and the "support disconnection" and the need for system reconstruction in home-based rehabilitation (professional guidance "vacuum" identity anxiety, and imbalance in the tension of family support networks) .Conclusions:Home-based blood pressure digital-intelligent management devices and programs for ischemic stroke patients need to be improved and developed. The role of multidisciplinary teams should be actively utilized, the digital divide should be emphasized, and post-disease family relationships should be reconstructed to further enhance patients' awareness of long-term blood pressure management.

Objective To analyze the cerebral blood flow changes in patients with newly diagnosed untreated early-onset depression(EOD),using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL),and to explore its relationship with clinical phenotypes.Methods The Hamilton Depression Scale(HAMD),Childhood Trauma Questionnaire(CTQ)scores,3D T1WI,and 3D-pCASL brain images of 65 untreated EOD patients and 55 healthy volunteers(HC group)were collected.SPM 12 and DPABI_V7.0 software were used to preprocess and analyze the whole brain images in two groups.Xjview software was used to analyze the value of cerebral blood flow(CBF)at the whole brain level of the two groups,and SPSS 25.0 software was used to evaluate the correlation of CBF values with HAMD scores and CTQ scores.Results Compared with the HC group,the CBF of the EOD group was reduced significantly[P＜0.05,cluster size＞50,false discovery rate(FDR)correction]in the right opercular inferior frontal gyrus(t=5.89),right temporo-parieto-occipital(TPO)region(t=6.49),and blood perfusion increased significantly(P＜0.05,cluster size＞50,FDR correction)in the left superior frontal gyrus(t=5.31)and left insular lobe(t=4.70).Conclusion The proportion of EOD patients with childhood trauma experience is relatively large.EOD patients have both reduced areas and increased areas in cerebral perfusion.The CBF value of the right TPO area is negatively correlated with HAMD scores;The CBF value of the left superior frontal gyrus is positively correlated with the total score of CTQ and the index of physical neglect score in CTQ,which is different from the result of studies that do not distinguish between early-onset and late-onset depression.

A 68-year-old patient with non-small cell lung squamous carcinoma who received 6 cycles of sintilimab combination chemotherapy and sintilimab 200 mg,ivd,monotherapy developed severe diarrhea,abdominal pain,blood in the stool and other discomforts,and ultrasound and colonoscopy demonstrated extensive congestion and inflammation in the intestinal tract,and the pathologic biopsy was comprehensively considered to be an acute immune enteritis.Immunotherapy was suspended,adequate glucocorticoids and symptomatic treatment were given,and the patient's diarrhea and blood in stool improved after 2 days,and the symptoms were relieved and returned to normal after 6 days.The association between the patient's immune enteritis and sintilimab was assessed as probably relerant.This article reviews the literature on the case of immune-associated enteritis caused by sintilimab,describes how to use experimental methods and enteroscopy to detect the pathological changes in the clinic;and combines them with the clinical manifestations of diarrhea and blood in the stools to make the diagnosis and differentiation;and then refers to the guideline grading for timely management;and discusses the case to improve the clinicians'ability to recognize and deal with the relevant scenarios.

Early and objective assessment, as well as early intervention, are of particular importance for autism spectrum disorder (ASD) to improve the long-term outcome. However, due to a lack of objective biomarkers, the current assessment of ASD depends mainly on limited behavioral observation. Recent advancements in software and hardware multimedia technologies provide new ways to identify ASD early. Evidence supports that the combination of machine learning with eye-tracking technology is expected to be a useful tool for the early and objective diagnosis of ASD. The current study reviewed the research on the combination of machine learning with eye-tracking technology for the identification of ASD. The limitations and future directions have also been proposed.

Early and objective assessment, as well as early intervention, are of particular importance for autism spectrum disorder (ASD) to improve the long-term outcome. However, due to a lack of objective biomarkers, the current assessment of ASD depends mainly on limited behavioral observation. Recent advancements in software and hardware multimedia technologies provide new ways to identify ASD early. Evidence supports that the combination of machine learning with eye-tracking technology is expected to be a useful tool for the early and objective diagnosis of ASD. The current study reviewed the research on the combination of machine learning with eye-tracking technology for the identification of ASD. The limitations and future directions have also been proposed.

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990^th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.
Female ; Humans ; Male ; Burns/surgery* ; Cicatrix ; Eosine Yellowish-(YS) ; Hyaluronic Acid/therapeutic use* ; Hyperplasia ; Ki-67 Antigen ; Prospective Studies ; Umbilical Cord ; Vimentin ; Young Adult ; Adult ; Middle Aged