Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Objective: To analyze the epidemilogical and seasonal characteristics of foodborne Salmonella-associated diarrhea among children aged 0-6 years in Guizhou Province from 2016 to 2023, so as to provide a basis for the prevention and control of foodborne diseases. Methods: Data were extracted from the Foodborne Disease Survellance System for cases reported between January 1, 2016, and December 31, 2023. The incidence, seasonal characteristics, and peak periods were analyzed by the method of concentration and circular distribution. Results: A total of 6 434 cases of diarrhea in children aged 0-6 years were collected, and 455 cases of Salmonella were detected, with a positive detection rate of 7.07%. Salmonella typhimurium was the main serotype causing diarrhea (59.34%). The peak of the disease was from May 3 to September 30, with certain seasonal characteristics. The highest detection rate was found in children aged 1-3 years (8.66%). Among food types, the positive detection rates of Salmonella were relatively high in other foods (17.39%), fruits and their products (10.22%), infant and toddler foods (10.09%), and aquatic animals and their products (9.80%). The processing and packaging methods of food were mainly home-made (9.38%) and bulk food (7.54%). Conclusions The detection rate of Salmonella in children aged 0-6 years is high in Guizhou Province, with strong seasonal characteristics. The detection rates of other foods, fruits and their products, infant and toddler foods, and aquatic animals and their products are high. Enhanced pathogen surveillance for susceptible populations and high-risk foods, coupled with public health education during summer/autumn, is recommended.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objective To compare the value of standard deviation(SD)method and root mean square(RMS)method for measuring signal-to-noise ratio(SNR)of MRI of American College of Radiology(ACR)phantom based on phased array coils.Methods ACR phantom was scanned with head coil(Head),abdominal coil(Anterior),dual piece flexible coil(Flex L)and abdominal coil+flexible coil(Anterior+Flex L)each for 6 times,respectively,with sequences of axial T 1W-spin echo(SE)and T2W-SE.And the scanning schemes were divided into 8 groups based on 4 types of coils and 2 sequences.SNR of 8 groups were measured with standard deviation method and root mean square method,respectively,and the differences between the above 2 methods were observed.Results For T1W-SE sequence,SNRsD of MRI based on Head,Anterior,Flex L and Anterior+Flex L was 1.25±0.07,0.56±0.02,1.15±0.10 and 1.04±0.11,respectively,while SNRRMs was 1.10±0.07,0.58±0.03,1.01±0.13 and 1.31±0.15,respectively.For T2W-SE sequence,SNRsD was 1.40±0.08,0.48±0.02,1.04±0.07 and 1.08±0.06,respectively,while SNRRMs was 1.29±0.09,0.53±0.03,0.84±0.08 and 1.35±0.12,respectively.Compared pairwise,significant difference of SNRsD was found in 9 pairs(all P＜0.05),while of SNRRMs was detected in 10 pairs(all P＜0.05).Conclusion Compared with standard deviation method,root mean square method was more suitable for measuring SNR of MRI of ACR phantom based on phased array coils.

Objectives:This study aims to establish a calcified aortic valve disease(CAVD)-related gene regulatory network,and clarify the impact of interactions between CAVD-related genes on CAVD.Methods:Differential expression gene method was used to screen candidate genes,and STRING software was used to construct protein-protein interaction networks for screened genes.The networks and genes with the highest scores were obtained.Monte Carlo method was used to rank the importance of genes in CAVD,and the top 1%genes were identified.Genes identified by these two methods are intersected to obtain the key genes.The correlation between the key genes and CAVD were confirmed by biological verification method.Then,key genes were used as query genes to establish CAVD gene regulatory module with a co-expression patterns-based gene regulatory network identifying method.Specifically,we first detected the underlying co-expression patterns of the seemingly uncorrelated genes,and then pieced the isolated gene pairs up into gene regulatory network with the help of the bridging genes.Finally,we verified the function of the established gene regulatory network through enrichment analysis and literature analysis.Results:We identified the CAVD gene regulatory network containing 211 genes from 18 084 candidate genes.Functional enrichment analysis indicate that the established gene regulatory network included genes with both known interactions and potential novel pathway interactions related to CAVD,serving as candidates for further experimental CAVD studies.Conclusions:Methodologically,the proposed method avoids the problem of complex computation,and relies only on available biological priors.It is also able to detect underlying co-expression patterns.The results will advance the understanding of the interactions of the CAVD-related genes and this method provides a novel way to identify underlying gene co-expression patterns in the setting of CAVD.

Objective To compare the value of standard deviation(SD)method and root mean square(RMS)method for measuring signal-to-noise ratio(SNR)of MRI of American College of Radiology(ACR)phantom based on phased array coils.Methods ACR phantom was scanned with head coil(Head),abdominal coil(Anterior),dual piece flexible coil(Flex L)and abdominal coil+flexible coil(Anterior+Flex L)each for 6 times,respectively,with sequences of axial T 1W-spin echo(SE)and T2W-SE.And the scanning schemes were divided into 8 groups based on 4 types of coils and 2 sequences.SNR of 8 groups were measured with standard deviation method and root mean square method,respectively,and the differences between the above 2 methods were observed.Results For T1W-SE sequence,SNRsD of MRI based on Head,Anterior,Flex L and Anterior+Flex L was 1.25±0.07,0.56±0.02,1.15±0.10 and 1.04±0.11,respectively,while SNRRMs was 1.10±0.07,0.58±0.03,1.01±0.13 and 1.31±0.15,respectively.For T2W-SE sequence,SNRsD was 1.40±0.08,0.48±0.02,1.04±0.07 and 1.08±0.06,respectively,while SNRRMs was 1.29±0.09,0.53±0.03,0.84±0.08 and 1.35±0.12,respectively.Compared pairwise,significant difference of SNRsD was found in 9 pairs(all P＜0.05),while of SNRRMs was detected in 10 pairs(all P＜0.05).Conclusion Compared with standard deviation method,root mean square method was more suitable for measuring SNR of MRI of ACR phantom based on phased array coils.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

Objectives:This study aims to establish a calcified aortic valve disease(CAVD)-related gene regulatory network,and clarify the impact of interactions between CAVD-related genes on CAVD.Methods:Differential expression gene method was used to screen candidate genes,and STRING software was used to construct protein-protein interaction networks for screened genes.The networks and genes with the highest scores were obtained.Monte Carlo method was used to rank the importance of genes in CAVD,and the top 1%genes were identified.Genes identified by these two methods are intersected to obtain the key genes.The correlation between the key genes and CAVD were confirmed by biological verification method.Then,key genes were used as query genes to establish CAVD gene regulatory module with a co-expression patterns-based gene regulatory network identifying method.Specifically,we first detected the underlying co-expression patterns of the seemingly uncorrelated genes,and then pieced the isolated gene pairs up into gene regulatory network with the help of the bridging genes.Finally,we verified the function of the established gene regulatory network through enrichment analysis and literature analysis.Results:We identified the CAVD gene regulatory network containing 211 genes from 18 084 candidate genes.Functional enrichment analysis indicate that the established gene regulatory network included genes with both known interactions and potential novel pathway interactions related to CAVD,serving as candidates for further experimental CAVD studies.Conclusions:Methodologically,the proposed method avoids the problem of complex computation,and relies only on available biological priors.It is also able to detect underlying co-expression patterns.The results will advance the understanding of the interactions of the CAVD-related genes and this method provides a novel way to identify underlying gene co-expression patterns in the setting of CAVD.

Objectives:To explore the dynamic changes of right ventricular global longitudinal strain (RVGLS) on echocardiography during the process of right ventricular fibrosis with right ventricular pressure overload.Methods:Animal models with RV pressure overload (n=5) were established by main pulmonary artery (PA) banding in piglets.The ratio of RV pressure to left ventricular (LV) pressure was greater than 60％ as assessed by the pressure measuring needle during the operation.Pre-and post-operative echocardiography were performed.Histopathological examination of RV tissues was performed at the end of the experiment.Results:During the establishment of the animal models,2 piglets died due to hemorrhagic shock,while 3 piglets survived and were included in the analysis.Systolic RV pressure,systolic PA pressure and mean PA pressure(measured at the proximal end of the constriction) were significantly increased immediately after PA banding,mean RV pressure and mean PA pressure were significantly inreased at 14 weeks postopseratively (all P<0.05).Tricuspid annulus plane systolic excursion and peak early diastolic velocity of tricuspid annulus (TV e') decreased immediately after operation (all P<0.05).They returned to the pre-operative level in the following three weeks.The absolute values of RVGLS were reduced after PA banding (all P>0.05).The RVGLS of the inner membrane layer began to recover after 3 weeks,and the RVGLS of the middle and outer membrane layers began to recover after 7 weeks.However,the time to peak RVGLS was significantly prolonged and could not be restored even untill the end of the experiment (14 weeks after surgery)(all P<0.05).At the end of the experiment,pathological examination revealed fibrous tissue hyperplasia in both the myocardial interstitium and endocardium.Conclusions:The measurement of intracardiac pressure and pathological results confirmed the success of the establishment of the animal model of increased right ventricular afterload.Both stress and strain cannot truly represent the intrinsic characteristics of the myocardium under pressure overload.The prolonged time to peak of longitudinal strain might indirectly reflect the progression of myocardial injury more persistently during the process of increased right ventricular afterload and myocardial injury.