ObjectiveTo investigate the effects of Huanglian Jiedutang （HLJDT） on cognitive function in mice with ischemic stroke （IS） and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB （NF-κB） signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion （MCAO）. Sixty C57BL/6J mice were randomly assigned to five groups （n =12 per group）， i.e.， sham operation， model， HLJDT low-dose （3.9 g·kg^-1·d^-1）， HLJDT high-dose （7.8 g·kg^-1·d^-1）， and Ginkgo biloba extract （GBE， 31.2 mg·kg^-1·d^-1）. Post-operatively， neurological deficit scores （Longa score）， cerebral infarct volume assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and brain water content were evaluated. Learning and memory were assessed using new object recognition （NOR） and fear conditioning （FC） tests. Hippocampal pathology was examined via hematoxylin and eosin （HE） staining. Immunofluorescence detected expression of glial fibrillary acidic protein （GFAP， astrocyte marker）， cellular oncogene Fos （c-Fos， neuronal activation marker）， and glutamate decarboxylase 65 （GAD65）. Western blot measured nuclear factor-κB inhibitor protein α （IκBα）， phosphorylated IκBα （p-IκBα）， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， ionic calcium binding adapter molecule 1 （Iba-1）， tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and apoptosis-related proteins， such as cleaved cysteinyl aspartate-specific protease 3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Real-time quantitative PCR （Real-time PCR） was used to assess mRNA levels of Iba-1， TNF-α， IL-1β， NF-κB p65， cleaved Caspase-3， Bax， and Bcl-2. ResultsCompared with the sham group， the model group exhibited significantly increased neurological deficit scores， brain water content， and cerebral infarct volume （P<0.01）. Hippocampal CA1 neurons were disorganized， showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced （P<0.01）. GFAP and c-Fos expression were increased， while GAD65 expression was decreased （P<0.01）. Cleaved Caspase-3 and Bax were upregulated， Bcl-2 was downregulated， and the Bax/Bcl-2 ratio was elevated （P<0.01）. Expression levels of p-IκBα， p-NF-κB p65， IL-1β， TNF-α， and Iba-1 were significantly increased （P<0.01）. Compared with the model group， HLJDT high-dose， low-dose， and GBE groups showed significant improvements in all parameters （P<0.01）. Among them， the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests （P<0.01）. In this group， GFAP and c-Fos decreased， GAD65 increased （P<0.01）， apoptosis-related protein expression was reversed， and NF-κB signaling and related inflammatory factor expression were suppressed （P<0.01）. ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS， potentially by inhibiting the NF-κB signaling pathway， thereby reducing neuroinflammation and hippocampal neuronal apoptosis.

The theory of "fire and primordial qi incompatibility" was proposed by LI Gao in Clarifying Doubts about Damage from Internal and External Causes, which has important guiding significance for explaining the pathogenesis, prognosis and treatment of immune-related adverse events (irAEs). "Fire" refers to yin fire, a type of deficient fire transformed from the deficiency of the spleen and stomach, reflecting the pathological state of coexisting deficiency and heat patterns in patients with tumor after immune checkpoint inhibitor (ICI) therapy. "Primordial qi" is the most fundamental essence of human life activities and serves as the source of all bodily qi. Based on the theory of "fire and primordial qi incompatibility" and Western medicine research, we found that excessive use of ICIs can damage the spleen and stomach, leading to excessive yin fire. When yin fire becomes excessive, it consumes and injures the primordial qi; when the primordial qi is depleted, it leads to more excessive yin fire and further deficiency of the spleen and stomach, forming a syndrome in which deficiency and excess coexist. Starting from the theory of "fire and primordial qi incompatibility, "combined with our team′s clinical practice and modern pharmacological research, this study explores the application characteristics of sweet-natured herbs for irAEs during ICIs therapy and interval periods, and summarizes the treatment principles, aiming to provide new perspectives and approaches for the prevention and treatment of tumor-related irAEs with traditional Chinese medicine.

Objective To explore the effect and mechanism of quercetin on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods BMSCs were divided into a blank control group(Control)and quercetin(Quercetin)low-dose group(4.8 mL/kg),medium-dose group(9.6 mL/kg),and high-dose group(19.2 mL/kg)intervened with drug-containing serum,while the positive control group was treated with osteogenic differentiation medium,respectively.The cell cycle was analysed by flow cytometry,cell proliferation was detected by MTT assay,cell activity was determined by Alkaline phosphatase(ALP)assay kit,and calcified nodule formation was observed by alizarin red staining.The expression of β-catenin and the key factors of osteogenic differentiation,runt-related transcription factor 2(RUNX2)and osteocalcin(OCN),were detected by qPCR and Western blot,respectively.Results Compared with the control group,quercetin-containing serum significantly promoted the proliferation of BMSCs(P=0.000205,P=0.000063)and enhanced the formation of calcium nodules,and increased osteogenic and ALP activity after osteogenic differentiation.The results of qPCR and Western blot showed that the quercetin group significantly up-regulated the mRNA and protein expression of β-catenin(P<0.0001),RUNX2(P<0.0001)and OCN(P<0.0001)during osteogenic differentiation.Conclusion Quercetin can effectively promote the osteogenic differentiation of BMSCs,and its mechanism is achieved by activating the Wnt/β-catenin signaling pathway and up-regulating the expression of the osteogenesis-related transcription factor RUNX2.

Real-time analysis of major element content in raw ore slurry represents a crucial part in mining extraction processes.A self-developed real-time online detection system based on laser-induced breakdown spectroscopy(LIBS)was applied for rapid detection of primary elements in raw ore slurry.Using 72 synchronized samples collected from mining enterprises,with 58 samples allocated for model construction and 14 for validation,this research focused on addressing the industrial requirements for real-time monitoring of sulfur(S),arsenic(As),and copper(Cu)elements.Multiple characteristic spectral lines were selected from LIBS detection system's spectral data.The analytical approach combined multiple linear regression(MLR)for initial model development with partial least squares(PLS)full-spectrum analysis for model refinement,ultimately establishing calibration and prediction models for the three target elements.The results demonstrated that the integrated MLR-PLS methodology achieved high precision,with calibration model determination coefficients(R2)of 0.95,0.97,and 0.99,and prediction model R2 values of 0.96,0.94,and 0.99 for S,As and Cu,respectively.The mean relative prediction errors were 1.65%,2.10%and 0.86%,respectively,which could meet the practical production requirements of mining operations.This approach provided an effective technical solution for real-time quality monitoring in mineral slurry processing.

Objective To investigate the levels of hypoxia-inducible factor 1α(HIF-1α)and lipopolysaccha-ride signal receptor(CD14)in gingival crevicular fluid of preschool children with dental caries and their clini-cal significance.Methods A total of 468 preschool children(aged 3-6 years)who underwent oral examina-tions in the hospital from April 2022 to May 2024 were selected as the research objects and were divided into the observation group(with dental caries,n=107)and the healthy group(without dental caries,n=361)based on the presence or absence of dental caries.The observation group was further divided into three sub-groups according to the degree of caries activity test(CAT)score:low activity group(n=29),moderate activ-ity group(n=46),and high activity group(n=32).The children in the observation group were followed up for 6 months,and then divided into the occurrence group(n=36)and the non-occurrence group(n=71)based on whether chronic apical periodontitis occurred during the follow-up period.The levels of HIF-1α and CD14 in gingival crevicular fluid in the research objects were detected.The relationship between the levels of HIF-1α and CD14 in gingival crevicular fluid of preschool children with dental caries and CAT score was ex-plored by Pearson correlation analysis.The predictive value of HIF-1α and CD14 levels in gingival crevicular fluid for chronic apical periodontitis in preschool children with dental caries was explored by receiver operating characteristic(ROC)curve.Results The levels of HIF-1α and CD14 in gingival crevicular fluid in the obser-vation group were higher than those in the healthy group(P＜0.05).With the increase of CAT score,the lev-els of HIF-1α and CD14 in gingival crevicular fluid gradually increased(high activity group＞moderate activi-ty group＞low activity group),and the differences were statistically significant(P＜0.05).The levels of HIF-1α and CD14 in gingival crevicular fluid of preschool children with dental caries were positively correlated with CAT score(r=0.526,0.634,P＜0.001).The levels of HIF-1α and CD14 in gingival crevicular fluid in the occurrence group were significantly higher than those in the non-occurrence group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of combined prediction of HIF-1α and CD14 levels in gingival crevicular fluid for chronic apical periodontitis in preschool children with dental caries was 0.902(95％CI:0.857-0.952),which was higher than 0.709(95％CI:0.664-0.759)and 0.825(95％CI:0.775-0.870)of individual prediction of HIF-1α and CD14 levels in gingival crevicular fluid.Conclusion HIF-1α and CD14 are highly expressed in gingival crevicular fluid of preschool children with dental caries,and their levels are related to the activity of dental caries and the occurrence of chronic apical periodontitis in preschool chil-dren with dental caries.The combined detection of the two can be used as effective indicators for predicting the occurrence of chronic apical periodontitis in preschool children with dental caries.

As a traditional nutritional and healthy cash crop in China, tea has certain significance in promoting human health and preventing and controlling chronic diseases. Studies have shown that the nutritional health effect of tea is due to its rich functional components, mainly including tea polyphenols, tea pigments, tea polysaccharides, theanine, alkaloids and other bioactive substances. At present, researchers from the academic circles have continuously carried out animal and human experiments on the health effects of various functional components of tea, which has accumulated abundant research data and materials. Based on this, this article reviews the literature on the nutritional and health effects of the main functional components of tea, and adopts the method of evidence-based research to screen and extract relevant data for qualitative and quantitative meta-analysis. Subsequently, the nutritional health effects of the five functional components of tea, namely tea polyphenols, tea pigments, tea polysaccharides, theanine, and alkaloids, are summarized and outlined. Studies have shown that tea polyphenols, tea pigments, tea polysaccharides, theanine and alkaloids have different health effects and are expected to play their unique roles in promoting human health and preventing and controlling diseases.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

This review examines strategies for the prevention and management of obesity, hypertension, type 2 diabetes mellitus and dyslipidaemia, conditions that are increasing in Singapore, as components of individualised health plans in 'Healthier SG' and beyond. We describe cardiometabolic disease prevention and management initiatives in Changi General Hospital (CGH), including collaborations with SingHealth Polyclinics, Active SG, Exercise is Medicine Singapore and community partners in the Eastern Community Health Outreach programme, and highlight advances in curable hypertension (e.g., primary hyperaldosteronism) and novel cardiovascular risk markers such as lipoprotein(a). We also outline technology-based interventions, notably the CGH Health Management Unit, which demonstrate the utility and convenience of telemedicine, and digital therapeutics in the form of apps that have been shown to improve treatment adherence and clinical outcomes. Individual empowerment, in partnership with community and healthcare providers and supported by research and innovation of care delivery, is key to building a healthier and stronger nation.
Humans ; Singapore ; Diabetes Mellitus, Type 2/therapy* ; Hypertension/therapy* ; Obesity/therapy* ; Dyslipidemias/therapy* ; Telemedicine ; Cardiovascular Diseases/prevention & control* ; Exercise ; Metabolic Diseases/prevention & control*

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.