Alzheimer’s disease (AD) is a chronic, progressive, and irreversible neurodegenerative disorder that typically begins with a subtle onset and progresses slowly. Pathologically, it is characterized by two hallmark features: the extracellular accumulation of amyloid β-protein (Aβ), forming senile plaques, and the intracellular hyperphosphorylation of tau protein, resulting in neurofibrillary tangles (NFTs). These pathological changes are accompanied by substantial neuronal and synaptic loss, particularly in critical brain regions such as the cerebral cortex and hippocampus. Clinically, AD presents as a gradual decline in memory, language abilities, and spatial orientation, significantly impairing the quality of life of affected individuals. With the aging population steadily increasing in China, the incidence of AD is rising, making it a major public health concern that requires urgent attention. The growing societal and economic burden of AD underscores the pressing need to identify effective diagnostic biomarkers and develop novel therapeutic strategies. Among the various molecular signaling pathways involved in neurological disorders, the Notch signaling pathway is especially noteworthy due to its evolutionary conservation and regulatory roles in cell proliferation, differentiation, development, and apoptosis. In the central nervous system, Notch signaling is essential for neurodevelopment and synaptic plasticity and has been implicated in several neurodegenerative processes. Although some studies suggest that Notch signaling may influence AD-related pathology, its precise role in AD remains poorly understood. In particular, the interaction between Notch signaling and non-coding RNAs (ncRNAs)—key regulators of gene expression—has received limited attention. NcRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are known to exert extensive regulatory functions at both transcriptional and post-transcriptional levels. Dysregulation of these molecules has been widely associated with various diseases, including cancers, cardiovascular conditions, and neurodegenerative disorders. Notably, interactions between ncRNAs and major signaling pathways such as Notch can produce widespread biological effects. While such interactions have been increasingly reported in several disease models, comprehensive studies investigating the regulatory relationship between Notch signaling and ncRNAs in the context of AD remain scarce. Given the capacity of ncRNAs to modulate signaling cascades and form complex regulatory networks, a deeper understanding of their crosstalk with the Notch pathway could provide novel insights into AD pathogenesis and reveal potential targets for diagnosis and treatment. In this study, we investigated the regulatory landscape involving the Notch signaling pathway and associated ncRNAs in AD using bioinformatics approaches. By integrating data from multiple public databases, we systematically identified significantly dysregulated Notch pathway-related genes and their interacting ncRNAs in AD. Based on this analysis, we constructed a lncRNA-miRNA-mRNA regulatory network to elucidate the potential mechanisms linking Notch signaling to ncRNA-mediated gene regulation in AD pathogenesis. Furthermore, we explored the internal relationships and molecular mechanisms within this network and assessed the feasibility and clinical relevance of these molecules as early diagnostic biomarkers and potential therapeutic targets for AD. This study aims to deepen our understanding of the molecular basis of AD and offer novel strategies for its diagnosis and treatment.

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Objective:To compare the prognostic value of two predictive models based on C-reactive protein(CRP)and albumin(ALB),namely the CRP to ALB ratio(CAR)and the Glasgow prognostic score(GPS),in newly diagnosed patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed.A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical,laboratory data and follow-up information were included.The receiver operating characteristic(ROC)curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival.Furthermore,the association between CAR and baseline clinical,laboratory characteristics of patients was evaluated,and progression-free survival(PFS)and overall survival(OS)were compared between different CAR and GPS subgroups.Finally,the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes.Results:ROC curve showed that the area under the curve(AUC)of CAR predicting PFS and OS in DLBCL patients was 0.687(P=0.002)and 0.695(P=0.005),respectively,with the optimal cut-off value of 0.11 for both predicting PFS and OS.Compared with the lower CAR(＜0.11)group,the higher CAR(≥0.11)group had more clinical risk factors,including age＞60 years(P=0.025),ECOG score ≥2(P=0.004),Lugano stage Ⅲ-Ⅳ(P＜0.001),non-germinal center B-cell-like(non-GCB)subtype(P=0.035),elevated lactate dehydrogenase(LDH)(P＜0.001),extranodal involved site＞1(P=0.004)and IPI score＞2(P＜0.001).The interim response evaluation of patients showed that the overall response rate(ORR)and complete response rate(CRR)in the lower CAR group were both significantly better than those in the higher CAR group(ORR:96.9％vs 80.0％,P=0.035;CRR:63.6％vs 32.5％,P=0.008).With a median follow-up of 24 months,patients with lower CAR had significantly longer median PFS and OS than those with higher CAR(median PFS:not reached vs 67 months,P=0.0026;median OS:not reached vs 67 months,P=0.002),while there was no statistical difference in PFS(P=0.11)and OS(P=0.11)in patients with GPS of 0,1,and 2.Multivariate Cox regression analysis indicated that only sex(male)and IPI score＞2 were independent risk factors for both PFS and OS.Conclusion:CAR is significantly correlated with disease progression and survival in DLBCL patients;And compared with GPS,CAR has more advantages in predicting disease outcomes in DLBCL patients.

Objective:To compare the efficacy and safety of flumatinib (FM)and imatinib (IM)as first-line treatment in newly-diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP ) in real world. Methods:A total of 84 newly-diagnosed CP-CML patients in our center from December 2019 to December 2022 were retrospectively analyzed.Among them,32 cases received FM as first-line treatment,and 52 cases received IM. Molecular response (MR),disease progression,survival and incidence of adverse events (AEs)were compared between the two groups.Results:At 3 months of treatment,the incidences of early molecular response (EMR ),MR2.0 and MR3.0 were 96.7％,70.0％ and 20.0％ in FM group,respectively,which were significantly higher than 77.1％,29. 2％ and 0 in IM group (all P<0.05 ).At 6,9 and 12 months of treatment,the incidences of major molecular response (MMR)in FM group were 68.2％,85.7％ and 90.0％,respectively,which were significantly higher than 22.9％,34.0％ and 51.1％ in IM group (all P<0.01).The median time to achieve MMR in FM group was 6(6-9)months,which was significantly shorter than 18(12-22)months in IM group (P<0.001 ).The 3-year progression-free survival rate and 3-year event-free survival rate in FM group were 100％ and 68.8％,respectively,while in IM group were 98.1％ and 55.8％.There were no significant differences between the two groups (P>0.05). The incidence of grade 3-4 hematologic AEs in FM group was 21 .9％,which was slightly lower than 25.0％ in IM group,but the difference was not significant (P>0.05 ).Conclusion:In real clinical practice,FM as first-line treatment achieves MMR earlier than IM,and exhibits good safety profile in newly-diagnosed CML-CP patients,which potentially leads to improved long-term survival and treatment-free remission.

AIM To establish an LC-MS/MS method for the simultaneous content determination of forsythin,forsythoside A,chlorogenic acid,neochlorogenic acid,amygdalin,emodin,rhein and salidroside in Lianhua Qingwen Capsules.METHODS The analysis was performed on a 35℃thermostatic ACQUITY UPlC-HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Eight constituents showed good linear relationships within their own ranges(r≥0.999 5),whose average recoveries were 99.20%-100.96%with the RSDs of 0.62%-1.23%.CONCLUSION This simple,sensitive and reliable method can be used for the quality control of Lianhua Qingwen capsules.

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Protein phosphorylation modification is one of the key regulatory mechanisms in cellular signaling transduction and metabolic processes. The phosphorylation state of target proteins is regulated by specific protein kinases and phosphatases, which add or remove phosphate groups. Histidine phosphorylation (pHis) plays a crucial role in both prokaryotes and eukaryotes life activities and is linked to various pathological processes. Unlike the stable phosphorylation of proteins via phosphate ester bonds, histidine phosphorylation is linked through phosphoramide bonds, making it highly sensitive to high temperatures and low pH. This sensitivity has historically impeded progress in identifying and studying histidine phosphorylation. In recent years, the development of new techniques in phosphoproteomics and the emergence of pHis-specific antibodies have promoted the identification and functional research of pHis-modified substrates. For the first time, more than 700 pHis-modified proteins have been identified in mammalian cells, and pHis-modified substrates such as focal adhesion kinase (FAK) and phosphoglycerate mutase 1 (PGAM1) have been found to promote tumor development. This article mainly reviewed the key mechanisms and functions of histidine kinases and histidine phosphatases in regulating the histidine phosphorylation of specific substrates, and highlights their significant roles in human physiological and pathological processes, aiming to provide guidance for further research into the biological functions of histidine phosphorylation.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.