19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.

In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.

Root caries is a prevalent chronic oral disease with an average global prevalence of 41.5%, characterized by high incidence, low rate of treatment, and high rate of retreatment. Root caries is primarily caused by core microbiome-induced dysbiosis and has multiple risk factors, including gingival recession, root surface exposure, and salivary dysfunction. The traditional preventive measures and treatments such as fluoride, mineralizing agents, and restorative materials, are unable to restore or maintain oral microecological homeostasis. Recent studies have demonstrated that probiotics, prebiotics, synbiotics, and antimicrobial peptides may prevent and treat root caries by reversing dysbiosis. In addition, these biotherapeutics can reduce acid production by acidiferous bacteria, promote alkali production (hydrogen peroxide and ammonia) by alkali-producing bacteria, inhibit biofilm formation, decrease extracellular polysaccharide production, and suppress microbial adhesion and aggregation. It is expected to play an important role in the prevention and control of root caries. This article aims to review oral probiotics (Streptococcus oligofermentans, Streptococcus oralis subsp. dentisani, and Streptococcus salivarius), prebiotics (arginine, nitrates, and synthetic compounds), synbiotics, and antimicrobial peptides (gallic acid-polyphemusin I and LH12) to provide evidence and guidance for root caries management through microecological modulation.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique， and then to clarify the mechanism of the two， as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group（CG）， model group（MG）， Aconiti Coreani Radix group（RA） and Typhonii Rhizoma group（RT）. Except for the CG， ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG， rats in the other groups received whole powder suspension（0.586 mg·g^-1） was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0， 3， 7 and 14. After the end of administration， the serum， brain tissue and urine of gerbils in each group were collected， and the rate of cerebral infarction was detected by 2，3，5-triphenyltetrazolium chloride（TTC）， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， malondialdehyde（MDA）， superoxide dismutase（SOD）， glutathione（GSH）， and nitric oxide（NO） in serum and brain tissue were determined by enzyme-linked immunosorbent assay（ELISA）. The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， and the data were processed by multivariate statistical analysis， and differential metabolites were screened based on value of variable importance in the projection（VIP） of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG） database and Metaboanalyst 5.0. ResultCompared with the CG， the neurological deficit score was significantly increased in the MG（P<0.05）， compared with the MG， the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d（P<0.05）. Compared with the CG， the rate of cerebral infarction was significantly increased in the MG（P<0.05）， compared with the MG， the rates of cerebral infarction in the RA and RT were significantly reduced（P<0.05）. Compared with the CG， the levels of IL-6， TNF-α， and MDA in the serum and brain tissue of gerbils from the MG were significantly increased（P<0.05）， and the levels of SOD， GSH and NO were significantly reduced（P<0.05）. Compared with the MG， Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6， TNF-α and MDA， and up-regulated the levels of SOD， GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics， of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma， and could be used as potential biomarkers for both treatments in stroke gerbils， respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism， pyrimidine metabolism， and aminoacyl-tRNA biosynthesis. In addition， Aconiti Coreani Radix could also regulate riboflavin metabolism， Typhonii Rhizoma could also regulate purine metabolism， glycine， serine and threonine metabolism， arachidonic acid metabolism， biosynthesis of pantothenate and coenzyme A， and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke， with Aconiti Coreani Radix having stronger effects. From the metabolomics results， the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism， oxidative stress and so on， while Typhonii Rhizoma mainly involve amino acid metabolism， lipid metabolism， energy metabolism， etc.

AIM: To compare the changes in axial length of myopic patients of different ages after wearing orthokeratology lenses with increased compression factor(ICF)or conventional compression factor(CCF)for 2 a.METHODS: Retrospective study. A total of 141 myopia patients(141 right eyes)aged 8 to 15 years who fitted with orthokeratology lenses in the General Hospital of Foshan Aier Eye Hospital from July 2020 to July 2021 were continuously included. They were divided into the CCF group(70 cases, 70 eyes)and the ICF group(71 cases, 71 eyes). The patients in the CCF group were fitted with orthokeratology lens of 0.75 DS CCF, while patients in the ICF group were fitted with orthokeratology lens of 1.25 D ICF. Taking 12 years old as a boundary, these two groups were divided into 8-11 years old and 12-15 years old group. The uncorrected visual acuity(UCVA), horizontal corneal curvature(K1)and corneal staining were recorded for all subjects after wearing lenses for 1 d, 1 wk, 1, 6 mo, 1 and 2 a. The axial length(AL)was recorded after wearing lenses for 6 mo, 1 and 2 a, and the complication and corneal epithelial staining were observed during lens wearing.RESULTS:The improvement of UCVA in the ICF group was faster than that in the CCF group, which were statistical significant after wearing lenses for 1 d, 1 wk and 1 mo, respectively(all P<0.001); however, there was no statistical significance between the two groups after 6 mo, 1 and 2 a(all P>0.05); K1 of the ICF group decreased faster than that of the CCF group, and there were statistical significance at 1 d, 1 wk, and 1 mo after wearing lenses(all P<0.05); there was no statistical significance at 6 mo, 1 and 2 a(all P>0.05). The axial length growth of patients aged 8-11 years old in the ICF group and CCF group was 0.35±0.17 and 0.48±0.26 mm, respectively(P=0.010), after wearing lenses for 2 a, and the axial length growth of patients aged 12-15 years old in the ICF group and CCF group was 0.16±0.15 and 0.31±0.29 mm, respectively(P=0.011). During the follow-up period, corneal spotting occurred in 6 eyes(8.5%)in the ICF group, and 7 eyes(10%)in the CCF group(P>0.05), all of which were grade 1 spotting.CONCLUSION:Wearing ICF orthokeratology lens is more effective than wearing CCF lenses in controlling the growth of axial length, with faster shaping and more obvious improvement in UCVA, especially for the prevention of high myopia in children under 12 years. Therefore, young children can give priority to wearing lenses that increase the compression factor, and for children over 12 years old, the compression factor of the lens can be selectively increased according to the wearer's eye habits, health status of ocular surface and visual function.

Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L

Objective To explore the mechanism and effects of Basonuclin 1(BNC1)on the migration and invasion abilities of lung squamous cell carcinoma.Methods Bioinformatics technology was used to analyze the expression patterns and survival impact of BNC1 in patients with lung squamous cell carcinoma in online databases;Tissue microarrays were stained by immunohistochemistry assay and analyzed for BNC1 protein level.Cell lines for lung squamous cell carcinoma with high and low BNC1 expression were screened in the Cancer Cell Line Encyclopedia(CCLE)database.Wound healing experiment and transwell assay were performed on lung squamous cell carcinoma cell models with knockdown and overexpression of BNC1,and the migration and invasion rates of each cell line were detected;Quantitative reverse transcription PCR(RT-qPCR)was used to validate the migration and invasion of 10 highly related genes derived from literature.Western blotting was used to validate the selected regulatory genes.Results Bioinformatics technology found that BNC1 was highly expressed in lung squamous cell carcinoma tissues and was associated with lower survival rate(P=0.047).The expression of BNC1 in lung squamous cell carcinoma was higher than that in paracancerous tissues(P＜0.05).BNC1 had higher expression in the H226 cells and lower expression in the SK-MES1 cells.BNC1 knockdown inhibited the migration and invasion abilities of lung squamous cell carcinoma cells(P＜0.05),and BNC1 overexpression enhanced the migration and invasion abilities of lung squamous cell carcinoma cells(P＜0.05).Screening of BNC1 downstream regulatory molecules at the mRNA level showed that CDH1 was decreased when BNC1 was overexpressed(P＜0.05),and increased when BNC1 was knocked down(P＜0.05).The results of mRNA level were consistent with the results verified by Western blotting(P＜0.05).Conclusion BNC1 may be a gene predicting poor prognosis for lung squamous cell carcinoma patients,and BNC1 may likely to promote cell migration and invasion of lung squamous cell carcinoma by downregulating CDH1 expression.

Osteonecrosis of the femoral head(ONFH)is a common and intractable disease in orthopedics,and its occurrence is associated with lipid metabolism disorders,endothelial dysfunction,bone homeostasis imbalance,genetic polymorphism,etc.However,the specific mechanism has not been fully elucidated.ONFH has an insidious progression in the early stages,and in the later stages,it often requires hip replacement surgery,which imposes a heavy economic burden on patients and society.Non-coding RNA has been the hotspot of medical research in recent years,and increasing number of non-coding RNA has been found to regulate the occurrence and development of ONFH through various mechanisms.This article reviews the research progress on the role of non-coding RNA in the occurence,development and treatment of ONFH,in order to provide reference for the treatment of ONFH.