Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

Objective To investigate the value of flexible subtraction CE-Boost technique combined with low dosage contrast agents for CT pulmonary angiography(CTPA).Methods A total of 68 patients who would undergo CTPA examination due to suspected pulmonary embolism(PE)were prospectively enrolled and randomly divided into study group(n=34)and control group(n=34)using block randomization method.After injecting 25 ml contrast agents at a flow rate of 2.5 ml/s in study group or 50 ml contrast agents at a flow rate of 3.5 ml/s in control group,CTPA scanning were performed with identical parameters.For images in study group,hybrid iterative reconstruction was performed,followed by flexible subtraction CE-Boost post-processing to obtain CE-Boost CTPA.For images in control group,conventional CTPA was obtained with hybrid iterative reconstruction.Subjective and objective evaluations of image quality were compared between groups.Taken the final clinical diagnosis as standard,the accuracy rate of diagnosing PE were compared between groups.Results There were 7 cases of pulmonary artery main trunk PE and 15 cases of pulmonary lobe-level PE in study group,while in control group there were 8 cases and 17 cases.No statistical difference of subjective scores of CTPA was found between groups(P＞0.05).CT values of the main pulmonary artery,bilateral pulmonary artery trunks and lower lobes of both lungs,signal-to-noise ratio or contrast-to-noise ratio in CTPA were not significantly different between groups(all P＞0.05),while no significant difference of the accuracy rate of CTPA for diagnosing PE of pulmonary artery main trunk(100％[7/7]vs.100％[8/8])nor pulmonary lobe-level PE(86.67％[13/15]vs.88.24％[15/17])was detected between groups(all P＞0.05).Conclusion Flexible subtraction CE-Boost technique combined with low dosage contrast agents for CTPA could reduce contrast agent dosage without affecting image quality.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Objective:To analyze the effects of the disease and injury spectrum on health-adjusted life expectancy (HALE) among permanent residents aged 55 and above in Shenzhen from 2016 to 2030.Methods:Based on the mortality surveillance data and the permanent resident population data in Shenzhen from 2016 to 2022, the Sullivan method was used to calculate the HALE during 2016—2022. The Bayesian age-period-cohort model and the grey system model were used to predict the HALE during 2023—2030. The HALE changes in the two periods were decomposed into the contributions of 20 categories of diseases and injuries, respectively.Results:From 2016 to 2022, the HALE increased from 31.41 years (95% CI: 30.50-32.32) to 33.57 years (95% CI: 32.47-34.67). During this period, the mortality effect of neurological disorders slowed the increase of HALE, with a reduction of 0.27 years. By 2030, it is anticipated that the HALE will reach 36.40 years (95% CI: 34.78-38.01). This is expected to be influenced by the mortality effects of nutritional deficiencies (-0.40 years) and mental disorders (-0.29 years), as well as the disability effects of musculoskeletal disorders (-0.66 years), skin and subcutaneous diseases (-0.21 years) and nutritional deficiencies (-0.13 years). Conclusion:The HALE of permanent residents aged 55 years and above in Shenzhen demonstrated an increasing trend over time. Greater attention should be paid to the adverse effects of neurological disorders, nutritional deficiencies, mental disorders, musculoskeletal disorders, and skin and subcutaneous diseases on the continuous increase of HALE in this population.

Objective:To explore the effects of microRNA-221(miR-221)on inflammation and fibrosis induced by lipopoly-saccharide(LPS)in rat cardiomyocytes and the regulatory role of phosphatidylinositol 3-kinase(PI3K)/seronine/threonine protein kinase(AKT)signaling pathway.Methods:Cultured rat myocardial H9C2 cells in vitro,they were divided into control group(no inter-vention),LPS group(10 μg/ml LPS),experimental group(10 μg/ml LPS+10,20,40,80 μmol/L baicalin),mimics NC group(10 μg/ml LPS+mimics NC transfection),miR-221 mimics group(10 μg/ml LPS+transfection miR-221 mimics),inhibitor NC group(10 μg/ml LPS+transfection inhibitor NC),miR-221 inhibitor group(10 μg/ml LPS+transfection miR-221 inhibitor),10+miR-221 mimics group(10 μg/ml LPS+10 μmol/L baicalin+transfection miR-221 mimics)and 10+miR-221 inhibitor group(10 μg/ml LPS+10 μmol/L baicalin+transfection miR-221 inhibitor)were treated for 24 h.Real-time quantitative fluorescence PCR(RT-qPCR),ELISA,CCK-8,5-acetyne-2'-deoxyuracil nucleoside(EdU)and Transwell chamber methods were used to determine the expression level of miR-221,the expression levels of inflammatory factors,cell viability,cell proliferation and migration ability,Western blot was used to determine the expression levels of EMT-related proteins[E-cadherin,N-cadherin,Vimentin,fibronectin(FN)]and PI3K/AKT pathway related proteins.Results:Cell viability increased in LPS+10 group(P<0.05),so LPS+10 group was selected for follow-up experiment.The results of miR-221 level showed that miR-221 mimics group was higher than mimics NC group(P<0.05),miR-221 inhibitor group was lower than inhibitor NC group(P<0.05).Transfection of miR-221mimics group and miR-221 inhibitor group was successful.Compared with control group,cell proliferation rate and E-cadherin protein level in LPS group were decreased(P<0.05).The expression level of miR-221,cell migration number,IL-6 and TNF-α levels,and the protein levels of p-PI3K,p-AKT,N-cadherin,FN and Vimentin were increased(P<0.05).Compared with LPS group,LPS+10 group significantly reversed the changes of the above indexes(P<0.05).Compared with LPS+10 group,10+miR-221 mimics group reduced the above effect of baicalin in LPS-induced cells(P<0.05).However,miR-221 inhibitor of 10+miR-221 inhibitor group enhanced the above effect of baicalin in LPS-induced cells(P<0.05).Conclusion:Baicalin can inhibit the effects of LPS-induced myocyte H9C2 migration,inflammation and fibrosis and promote their proliferation by down-regulating the expression of miR-221,and its mechanism may be related to the inhibi-tion of PI3K/AKT signaling pathway.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

OBJECTIVES: To investigate the effect of Ching Shum Pills (CSP) for alleviating non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism. METHODS: In a mouse model of NAFLD, the therapeutic effect of CSP was evaluated by measuring serum glucose, lipid profiles (TC, TG, LDL-C, HDL-C), and hepatic function markers. Network pharmacology was employed to identify active compounds in CSP and their targets using TCMSP, HERB, SwissTargetPrediction, GeneCards, OMIM, and DisGeNET. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and KEGG pathway analyses were conducted. Molecular docking (AutoDock Vina) was used to assess the compound-target binding affinities. Quantitative real-time PCR (qRT-PCR) was used to validate the mRNA expressions of the core genes in the liver tissue of the mouse models. RESULTS: In the mouse model of NAFLD, treatment with CSP significantly reduced body weight gain and serum TG levels of the mice, and high-dose CSP treatment resulted in obvious reduction of ALT levels and hepatic fat accumulation. Network pharmacology analysis identified quercetin and 2-monolinolenin as the key bioactives in CSP, which target TNF, AKT1, IL6, TP53, and ALB. Docking simulations suggested strong binding between the two core compounds and their target proteins. The results of qRT-PCR showed that high-fat diet induced significant downregulation of Tp53, Cpt1, and Ppara expressions in mice, which was effectively reversed by CSP treatment. CONCLUSIONS CSP can improve lipid metabolism disorders in NAFLD mice through a regulatory mechanism involving multiple targets and pathways to reduce liver fat accumulation and protect liver function. The key components in CSP such as quercetin and linolenic acid monoacylglycerol may participate in the regulation of such metabolic processes as fatty acid oxidation by targeting TP53.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Lipid Metabolism/drug effects* ; Molecular Docking Simulation ; Disease Models, Animal ; Liver/metabolism* ; Male ; Lipid Metabolism Disorders/drug therapy* ; PPAR alpha/metabolism* ; Mice, Inbred C57BL ; Network Pharmacology

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins