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 assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

Objective:To explore the prognostic value of MUC13 expression in gastric cancer(GC)patients and its impact on the biological behavior of GC cells.Methods:Comprehensive anal-ysis of the expression pattern of MUC genes in GC tissues based on the TCGA database to screen for differentially expressed genes.Spearman correlation analysis determined the correlation of ex-pression between MUC genes in GC tissues.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)enrichment analysis were used to explore the potential biological functions of MUC genes.Univariate COX regression analysis was performed to explore the relationship between all differentially expressed MUC genes and the prog-nosis of GC patients to screen out MUC genes that were significantly related to the prognosis of GC.Clinical GC tissue samples were used to further verify the expression of MUC13 through im-munofluorescence,and its relationship with the clinicopathological characteristics and prognosis of GC was analyzed.siRNA was used to silence the expression of MUC13 in GC cells,and the effect of MUC13 on cell proliferation,migration and invasion was analyzed through CCK-8,colony forma-tion and Transwell experiments.Results:Among all MUC members,the expression levels of MUC1,MUC2,MUC3A,MUC4,MCU5B,MUC12,and MUC13 were significantly upregulated in GC tissues(P＜0.05).There are certain interactions between these MUC genes,and they are mainly en-riched in pathways related to digestive system processes,epithelial structure maintenance,apical plasma membrane,saliva secretion,etc.Importantly,upregulation of MUC13 in GC tissues indicates poor patient prognosis(Log-rank P＜0.05).In addition,MUC13 expression was significantly correlat-ed with the age(P＜0.001)of GC patients and tumor size(P=0.035).Further cell function experiments showed that after silencing MUC13,the proliferation ability of GC cells was significantly reduced(P＜0.05),while their migration and invasion abilities were not significantly affected(P＞0.05).Con-clusions:Highly expressed MUC13 is closely related to the poor prognosis of gastric cancer,par-ticipates in the regulation of tumor progression and is a potential therapeutic target and prognostic marker for gastric cancer.

In recent years,the incidence and mortality rates of cancer have been rising steadily,with drug resistance becoming a major challenge in cancer treatment.Traditional monolithic treatment approaches have proven ineffective in addressing the heterogeneity of tumor cells and their multiple resistance mechanisms,leading to suboptimal therapeutic outcomes.Drug combination therapy,as a critical strategy,aims to enhance efficacy and delay the development of drug resistance through the synergistic action of multiple drugs.However,conventional methods for screening drug combinations are time-consuming and costly.With the accumulation of data and advances in computational methods,artificial intelligence,particularly deep learning,has demonstrated great potential in predicting synergistic drug combinations for cancer treatment.Artificial intelligence technologies allow researchers to efficiently predict whether drug combinations exhibit synergistic effects,reducing experimental costs and identifying novel potential synergistic combinations.Nevertheless,artificial intelligence models still face challenges such as poor interpretability,insufficient feature integration,and a lack of labeled data.This paper provided a comprehensive review of the advancements in artificial intelligence applications for predicting synergistic drug combinations in cancer therapy.First,it discussed the mechanisms of drug resistance and the challenges of combination therapy,highlighting the limitations of traditional drug combination screening methods.Then,it presented the advantages and disadvantages of various deep learning models used for predicting synergistic drug combinations,including feedforward neural networks,graph neural networks,autoencoders,visible neural networks,Transformer and their extended models.In response to the common issues in current deep learning models,this review proposed several solutions,such as leveraging multimodal data to enhance model generalization,employing transfer learning and multitask learning to address data scarcity,and designing more interpretable models to facilitate clinical application.In the future,the field of synergistic drug combination prediction is expected to benefit from the development of standardized synergy metrics,improvements in model interpretability,integration of multimodal data,and effective handling of data limitations,further advancing the transition of models from laboratory research to clinical practice,ultimately providing more effective solutions for cancer treatment.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

This study was aimed at exploring the epidemiological characteristics of plague,and the evolutionary relation-ships among the isolated plague strains in the Yunnan border area,to provide clues for further studying epidemic causes and ep-idemiological patterns.Plague epidemic data in the border area during the second epidemic period(1982-2007)were collected and analyzed with descriptive epidemiological methods.Whole genome sequences of 262 strains of Yersinia pestis in the border area were obtained for phylogenetic analysis.Plague outbreaks occurred in 17 counties(cities)among 25 border counties(cit-ies);a total of 552 epidemic foci and 123 human cases were identified.The 1.ORI2,1.ORI3,1.IN3,2.ANT and 2.MED geno-types were identified among Yersinia pestis isolated from the Yunnan border area,among which the 1.ORI2 population was dominant.A total of 258 strains of Yersinia pestis from the 1.OR12 population belonged to four subclusters.The Myanmar and Vietnam clade was embedded within the Yunnan clade in the overall phylogeny.The above results indicated that during the sec-ond period of the epidemic,the intensity of plague epidemics in Yunnan's border areas was high,showing a trend of devel-opment from west to south and east.Our findings indicated a risk of cross-border transmission of plague between Yunnan and neighboring countries;therefore,the surveillance,pre-vention,and control of plague in border areas should be strengthened.

Objective:To explore the effects of the intervention of ginger baixiao moxibustion combined with probiotics on immune function, liver and kidney function of colorectal cancer patients after surgery, so as to provide a theoretical basis for clinical intervention methods to promote postoperative rehabilitation of patients.Methods:This study was a randomized controlled trial, and 180 patients with colorectal cancer radical resection from the Cancer Hospital of Guangxi Medical University were randomly divided into 4 groups, namely control group, probiotic group, ginger baixiao moxibustion group, and combination group, with 45 cases in each group. The control group was given routine nursing before and after surgery. In the probiotic group, probiotics were used for 3 d in routine preoperative care and 4 d from the first day after surgery. The preoperative routine care of the ginger baixiao moxibustion group was supplemented by ginger baixiao moxibustion for 3 d, and the intervention was carried out on the first day after surgery for 4 d. The combined group was treated with probiotics before and after surgery, and the specific intervention methods were the same as those of the probiotics group and the ginger baixiao moxibustion group. The differences in postoperative immune function, liver and kidney function and and other indexes among the four groups were compared.Results:Forty-five cases were ultimately selected from each of the 4 groups. There were 31 males and 14 females, aged (56.67 ± 10.13) years old in the control group. There were 27 males and 18 females, aged (55.33 ± 13.02) years old in the probiotic group. There were 20 males and 25 females, aged (57.87 ± 12.43) years old in the ginger baixiao moxibustion group. There were 26 males and 19 females, aged (57.67 ± 11.63) years old in the combination group. The IgA at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were (1.46 ± 0.42), (1.71 ± 0.49), (1.72 ± 0.58), (1.97 ± 0.72) g/L, and the IgM were (0.96 ± 0.20), (1.13 ± 0.33), (1.11 ± 0.35), (1.18 ± 0.52) g/L, and the IgG were (8.45 ± 1.68), (9.57 ± 1.71), (9.41 ± 2.14), (10.40 ± 2.16) g/L, and the differences among the four groups were statistically significant ( F=6.20, 10.64, 7.69, all P<0.05). The CD3 + values at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were 0.616 ± 0.094, 0.671 ± 0.101, 0.653 ± 0.119, 0.723 ± 0.091, and CD4 + were 0.408 ± 0.060, 0.444 ± 0.063, 0.441 ± 0.103, 0.483 ± 0.069, and CD4 +/CD8 + were 2.173 ± 0.715, 2.367 ± 0.963, 2.204 ± 1.137, 2.803 ± 1.064, and the differences among the four groups were statistically significant ( F=8.58, 7.43, 3.93, all P<0.05). The alanine aminotransferases at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were (16.22 ± 11.56), (15.87 ± 10.69), (12.91 ± 7.45), (11.31 ± 8.31) U/L, and the aspartate aminotransferases were (26.13 ± 7.97), (25.84 ± 7.89), (25.67 ± 10.85), (21.84 ± 5.51) U/L, and the differences among the four groups were statistically significant ( F=2.71, 2.70, both P<0.05). Conclusions:The combination of ginger baixiao moxibustion and probiotics intervention can effectively improve the immune function of colorectal cancer patients after surgery, and improve the liver function and other indexes of patients to a certain extent, so as to benefit patients.

Background: We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. Methods: COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. Results: Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. Conclusion Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.