This paper reviews research progress on a antibacterial-remineralization-infiltration synergistic strategy for the prevention and treatment of dental hard tissue diseases. Dental caries is a chronic infectious disease caused by cariogenic bacteria. Traditional fluoride prevention methods are unable to effectively halt the progression of deep caries due to limited antibacterial capacity and poor deep penetration. To address this, researchers have proposed an interruption of dental caries strategy that integrates antibacterial, remineralization, and infiltration functions. This approach utilizes antibacterial components, such as metal ions, antibacterial peptides, and nanoparticles, to suppress cariogenic bacterial activity. Bioactive glass and amorphous calcium phosphate materials induce in situ hydroxyapatite deposition to achieve dental hard tissue remineralization. Simultaneously, the materials penetrate deep into the micro-pores of a lesion via high permeability, forming a physical barrier that blocks acid erosion and plaque re-invasion. This strategy is applicable not only for minimally invasive intervention in early caries but also extends to treating non-carious conditions, such as dentine hypersensitivity, wedge-shaped defect, and tooth erosion. Multiple in vitro and animal studies demonstrate that multifunctional coatings and nanocomposite systems developed under this systemic approach significantly enhance treatment efficacy for dental hard tissue diseases. Future advancements in biomimetic materials and smart delivery systems hold promise for achieving higher levels of structure-function reconstruction, which will propel dental hard tissue disease treatment toward precision, minimally invasive, and intelligent approaches.

ObjectiveTo investigate the metabolic mechanisms of Limosilactobacillus reuteri （L. reuteri） in alleviating chemotherapy-induced intestinal mucosal injury （CIMI）. MethodsC57BL/6 mice were randomly divided into the Control group， Model group， and L. reuteri treatment group （n=8 per group）. Mice in the L. reuteri group were intragastrically administered L. reuteri （1 × 10⁹ CFU/mL） for 10 consecutive days. From day 5， mice in the Model and L. reuteri groups were intraperitoneally injected with 5-FU （65 mg/kg） for 6 consecutive days to establish a CIMI model. Body weight changes， colon length， and related indicators were recorded. Intestinal histopathological injury was assessed by HE staining with measurement of villus height and crypt depth. The expression levels of zonula occludens-1 （ZO-1）， Occludin， Claudin-4， Muc1， and Muc2 in ileal tissues were determined by RT-qPCR and immunohistochemistry to evaluate intestinal barrier function. In addition， untargeted metabolomics was performed on cecal contents from each group to analyze metabolic profiles and enrichment of differential metabolic pathways. ResultsL. reuteri intervention significantly alleviated body weight loss （P<0.001） and colon shortening （P<0.05） in CIMI mice， effectively reducing ileal tissue pathological damage， and upregulating the expression of ZO-1， Occludin， Claudin4， Muc1， and Muc2 （P<0.05）. Untargeted metabolomics analysis showed that L. reuteri treatment reversed the abnormal metabolic profile in the cecal contents of CIMI mice， bringing it closer to normal. Various differential metabolites， such as acylcarnitines and polyunsaturated fatty acids， might play an important role in L. reuteri-mediated alleviation of CIMI. These differential metabolites were primarily enriched in key pathways such as linoleic acid metabolism， tryptophan metabolism， and unsaturated fatty acid biosynthesis. ConclusionThis study reveals that L. reuteri improves intestinal barrier function and alleviates CIMI by regulating the intestinal metabolic profile， particularly lipid and amino acid metabolism. It provides a novel potential strategy for the prevention and treatment of CIMI.

ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs （mint and lily potted plants） combined with intradermal needling therapy for generalized anxiety disorder （GAD） of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy， and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups， horticultural therapy group， intradermal needling group， and horticultural therapy+intradermal needling group， with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment； the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment； the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy， following the same procedures and duration. Hamilton Anxiety Rating Scale （HAMA）， Self-Rating Anxiety Scale （SAS）， and Pittsburgh Sleep Quality Index （PSQI） scores were assessed at baseline and after 2， 4， 6， and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） were measured before treatment and after 8 weeks of treatment. Motor-evoked potential （MEP） baseline levels were recorded before treatment， and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels， MEP amplitude， and anxiety. ResultsIn the horticultural therapy group and intradermal needling group， HAMA， SAS and PSQI scores after 4， 6， and 8 weeks treatment were lower than baseline scores （P＜0.05）. In the horticultural therapy+intradermal needling group， these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment （P＜0.05）. The HAMA， SAS， and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2， 4， 6， and 8 weeks treatment （P＜0.05）. After 8 weeks of treatment， serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels （P＜0.05） and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point （P＜0.01）. When comparing the level after 8 weeks treatment to that after 1 week treatment， under PAS10 stimulation， the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes， while in the horticultural therapy+intradermal needling group， the MEP amplitude ratio decreased at all time points （P＜0.05 or P＜0.001）； under PAS25 stimulation， the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes， and in the intradermal needle group at 10 minutes （P＜0.05）. In the horticultural therapy+intradermal needling group， the MEP amplitude ratio increased significantly at all time points after treatment （P＜0.001）. The cure rate in the horticultural therapy+intradermal needling group （74.14%， 43/58） was significantly higher than that in the horticultural therapy group （30.00%， 18/60） and the intradermal needling group （48.28%， 28/58， P＜0.05）. Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores （r = 0.488， P＜0.01； r = 0.428， P＜0.01）. Following PAS10 intervention， the MEP amplitude ratio was positively correlated with HAMA scores （r = 0.458， P＜0.01）， whereas after PAS25 intervention， the MEP amplitude ratio was negatively correlated with HAMA scores （r = -0.562， P＜0.01）. ConclusionHorticultural therapy combined with intradermal needling treatment， under transcranial magnetic stimulation and basic psychological therapy， demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal （HPA） axis and the reduction of cortical excitability.

BACKGROUND: The epidemiological pattern and disease burden of type 2 diabetes have been shifting in China over the past decades. This analysis described the epidemiological transition of type 2 diabetes in the past three decades and projected the trend in the future three decades in China. METHODS: Age-, sex-, and year-specific incidence, prevalence, death, and disability-adjusted life years (DALYs) for people with 15 years or older and diabetes or high fasting glucose in China and related countries from 1990 to 2021 were obtained from the Global Burden of Disease. We obtained the trends of age-, sex-, and year-specific rates and absolute numbers of incidence, prevalence, deaths, and DALYs attributable to type 2 diabetes in China from 1990 to 2021. Using the Lee-Carter model, we projected the incidence, prevalence, death, and DALYs attributable to type 2 diabetes to 2050 stratified by age and sex. RESULTS: The age-standardized incidence of type 2 diabetes was 341.5 per 100,000 persons (1.6 times in 1990) and the age-standardized prevalence was 9.96% (9960.0 per 100,000 persons, 2.5 times in 1990) in China 2021. In 2021, there were 0.9 million deaths and 26.8 million DALYs due to type 2 diabetes or hyperglycemia, as 2.9 and 2.7 times the data in 1990, respectively. The age-standardized rates of type 2 diabetes and hyperglycemia were projected to raise to 449.5 per 100,000 persons for incidence, 18.17% for prevalence, 244.6 per 100,000 persons for death, and 4720.2 per 100,000 persons for DALYs by 2050. The incidence of type 2 diabetes kept growing among individuals under the age of 20 years in the past three decades (128.7 per 100,000 persons in 1990 and 439.9 per 100,000 persons in 2021) and estimating 1870.8 per 100,000 in 2050. CONCLUSIONS The incidence, prevalence, and disease burden of type 2 diabetes grew rapidly in China in the past three decades. The prevention of type 2 diabetes in young people and the care for elder adults will be the greatest challenge for the country.
Humans ; Diabetes Mellitus, Type 2/mortality* ; China/epidemiology* ; Prevalence ; Female ; Male ; Incidence ; Middle Aged ; Adult ; Aged ; Adolescent ; Young Adult ; Disability-Adjusted Life Years ; Aged, 80 and over

AIM: To assess the effectiveness of selective laser trabeculoplasty(SLT)in the treatment of primary open angle glaucoma(POAG).METHODS:Totally 24 patients(33 eyes)with POAG who had poor control of intraocular pressure(IOP)from June 2022 to December 2023 were included in this retrospective study, and all of them were treated with SLT. Furthermore, the IOP, mean deviation(MD), mean sensitivity(MS), and the thickness and vascular density(VD)of optic disc nerve layer were compared after treatment. RESULTS: There were significant reducion in IOP at 1, 3, 6, 12 mo after treatment(all P<0.001). There were no statistically significant differences in MD and MS before treatment and at 6 and 12 mo after treatment(all P>0.05), and there were no statistical significant differences in the thickness and VD of optic disc(all P>0.05).CONCLUSION: SLT can significantly reduce IOP in POAG patients in the short term, without damaging the visual field and optic disc nerves, while the effectiveness of SLT decreases over time.

Objective To investigate the potential core target and its mechanism of Simiao San(SMS)in the treatment of rheumatoid arthritis(RA)using network pharmacology and animal experiments.Methods Active components and corresponding SMS targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and cross-referenced with the Universal Protein(UniProt)database.RA-related targets were screened from The Human Gene Database(GeneCards),Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),DrugBank,and Disease Gene Network(DisGeNet).Protein-protein interaction(PPI)networks were constructed for shared targets between SMS and RA using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses via The Database for Annotation,Visualization and Integrated Discovery(DAVID).A"herb active component-disease target-signaling pathway"network was established to predict the mechanism of SMS in RA treatment.Molecular docking was performed between aryl hydrocarbon receptor(AHR)and the core active components of SMS to identify AHR-targeting constituents.For animal experiments,30 female SPF-grade C57/BL mice were randomly divided into normal,model,methotrexate(1.52 mg/kg,every 3 days),and SMS(12.48 g/kg,daily)groups with a 30-day intervention.Ankle diameter and arthritis index scores were measured.HE staining was used to assess joint inflammation,whereas immunohistochemistry(IHC)was used to measure cytochrome P450 1A1(CYP1A1),nuclear factor kappa B subunit p65(p65),and phosphorylated p65(p-p65)protein expression levels.Multiplex immunofluorescence(mIHC)was used to evaluate forkhead box protein P3(FOXP3)and interleukin-17A(IL-17A)protein expression.Results Forty-one active components and 228 targets of SMS were identified from TCMSP,whereas 1,207 RA-related targets were extracted from GeneCards,OMIM,TTD,DrugBank,and DisGeNet.Ninety-four overlapping targets were analyzed,yielding 612 GO terms and 143 KEGG pathways.Molecular docking of the ligand-binding domain of AHR with the top 10 Degree values of compounds of SMS(quercetin,stigmasterol,wogonin,beta-sitosterol,kaempferol,baicalein,et al.)revealed that stigmasterol,beta-sitosterol,(S)-canadine,and isocorypalmine was able to bind to AHR stably.In vivo,compared to the model group,the mice of the SMS and methotrexate groups joint swelling and arthritis index scores reduced(P<0.01).IHC indicated elevated CYP1A1 protein and decreased p65 and p-p65 protein levels in the SMS and methotrexate groups(P<0.05,P<0.01).mIHC demonstrated reduced IL-17A and increased FOXP3 protein expression in the SMS and methotrexate groups(P<0.05,P<0.01).Conclusion SMS alleviates joint inflammation in RA mice,potentially by targeting AHR,one of the core targets.SMS may suppress excessive inflammatory responses by activating AHR and inhibiting p65 phosphorylation.Additionally,SMS modulates the helper T cells 17/regulatory T cells balance by downregulating IL-17A and upregulating FOXP3.These results suggest that AHR is a key mediator in T-cell immune regulation.

Cancer represents a significant disease that profoundly impacts human health and longevity. Projections indicate a 47% increase in the global cancer burden by 2040 compared to 2020, accompanied by a further rise in the associated economic burden. Consequently, there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer. Natural products (NPs) play a crucial role in the identification and development of anticancer therapeutics. This study identified ustusolate E (UE) and its analog 11α-hydroxy-ustusolate E (HUE) from strain Aspergilluscalidoustus TJ403-EL05, and examined their antitumor activities and mechanisms of action. The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells), induced irreversible DNA damage, blocked the cell cycle at the G₂/M phase, and further induced apoptosis in tumor cells. To the best of the authors' knowledge, this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms. The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
Humans ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology* ; Sesquiterpenes/pharmacology* ; Aspergillus/chemistry*

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Bipolar disorder is a severe mental disorder characterized by mood fluctuations， with cognitive impairment being one of its key clinical features that seriously affects patients' social functions. In recent years， increasing evidence has indicated that oxidative stress imbalance may serve as a crucial pathophysiological basis for cognitive dysfunction in bipolar disorder. This review summarizes current research progress on oxidative stress-related biomarkers in cognitive impairment of patients with bipolar disorder， focusing on their roles in antioxidant defense， lipid peroxidation， neurotrophic factors， mitochondrial function， and telomere damage. Existing evidence suggests that oxidative stress is closely linked to processes such as neuroplasticity and cellular aging， potentially affecting cognition through multiple interacting pathways. This review also discusses the limitations in current studies， with the aim of informing future research on mechanism integration， longitudinal validation， and standardization of cognitive assessment methods.

ObjectiveTo explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch. (G. uralensis) and to improve the quality of cultivated G. uralensis for both medicine and food and aid in the increase in the content of effective components in G. uralensis.MethodsIn this study, whole G. uralensis plants were treated with exogenous chitosan, and comprehensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation, respectively. Effects of chitosan induction on endogenous hormones of G. uralensis were analyzed using an enzyme-linked immunosorbent assay. Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.ResultsChitosan induction significantly increased the levels of flavonoids in G. uralensis; however, the variation in triterpenoids was not substantial. Biological processes, including photosynthesis, secondary metabolism, and abiotic stress responses, were significantly enriched. Additionally, the photosynthetic pathway, photosynthesis-antenna protein pathway, and plant hormone signal transduction pathway were significantly enriched. In the flavonoid biosynthesis pathway, the upstream-related enzyme phenylalanine ammonia-lyase (PAL) and the downstream-related enzymes chalcone synthase (CHS), polyketide reductase (PKR), chalcone isomerase (CHI), and vestitone reductase (VR) were significantly upregulated.ConclusionsOur findings suggest that chitosan induction may promote the tricarboxylic acid (TCA) cycle, and the TCA cycle enhancement significantly upregulated PAL, CHS, PKR, CHI, and VR, the five key enzymes involved in flavonoid synthesis of G. uralensis, indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G. uralensis. Our findings provide a reference for improving the quality of cultivated G. uralensis from the perspective of pharmacodynamic components.