AIM:To establish a physiological-based pharmacokinetic(PBPK)model of ertapen-em in elderly patients with chronic kidney disease,and to analyze the pharmacokinetic/pharmacody-namic index f％ T＞MIC at different doses.METH-ODS:The physicochemical properties and pharma-cokinetic characteristics of ertapenem were collect-ed by reviewing the literature and databases,and a healthy adult model was established in PKSim? software,and then extrapolated to the PBPK model of the elderly.The clinical pharmacokinetic re-search data were used to optimize and validate the model,and the mean folding error(MFE)was used as the index to evaluate the prediction perfor-mance of the model.The final model was used to simulate the in vivo exposure of elderly patients with chronic kidney disease after administration,and the pharmacokinetic/pharmacodynamic index of commonly used clinical dosing regimens was an-alyzed,and the recommended dosing regimens were given.RESULTS:The MFE of the area under the curve(AUC0-t),peak concentration(Cmax)and peak time(Tmmax)predicted by the established PBPK model of ertapenem in adults were 0.92,0.79 and 1.02,respectively,and the predicted value of the optimized PBPK model of ertapenem in the elderly was also consistent with the observed value of 0.5＜MFE＜2 standards,all of which have good predictive performance.With f％ T＞MIC greater than 40％as the drug efficacy target,the minimum inhibitory concentration(MIC)is 0.5-1 μg/mL for sensitive bacteria,and elderly patients with chronic kidney disease can consider reducing the drug dose as ap-propriate.CONCLUSION:The PBPK model of ertap-enem in elderly patients with renal insufficiency has been successfully established,and the model has good prediction performance and provides a reference for clinical personalized medication in el-derly patients with renal insufficiency.

Objective To observe the correlations of metabolite levels in medial prefrontal cortex(mPFC)and cancer-related depression(CRD)in patients with non-small cell lung cancer(NSCLC).Methods Totally 38 NSCLC patients were prospectively enrolled and divided into CRD group(n=23)and non CRD group(n=15)based on Hamilton depression scale(HAMD-17).Meanwhile,22 healthy individuals were taken as control group.1 H-MR spectroscopy was performed using Meshcher-Garwood point resolved spectroscopy sequence,then metabolite levels of mPFC were measured,and their correlations with HAMD-17 score were analyzed.Results Significant differences of gamma-aminobutyric acid(GABA)+/Water and glutamate/glutamine complex(Glx)/Water in mPFC were found among 3 groups.GABA+/Water in mPFC of CRD group was significantly lower than that of the other 2 groups(both P＜0.05),and Glx/Water in mPFC of CRD group was significantly lower than that of control group(P=0.034).In NSCLC patients,GABA+/Water in mPFC was negatively correlated with HAMD-17 score(r=-0.491,P=0.002).Conclusion GABA+/Water in mPFC was negatively correlated with HAMD-17 score in NSCLC patients.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

Objective To explore the role of ferroptosis in DIC through bioinformatics analysis of hub genes involved in ferroptosis in doxorubicin-induced cardiomyopathy(DIC),combined with in vitro experimental validation.Methods Divalent iron fluorescence staining confirms the occurrence of ferroptosis in myocardial cells of DIC.The GSE207737 dataset was retrieved from the Gene Expression Comprehensive Database(GEO)and intersected with the FerrDb database to identify ferroptosis-related genes.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the intersected genes and intersecting the genes obtained from LASSO regression analysis and SVM-SFR machine learning methods were used to obtain ferroptosis hub genes for DIC.Real-time PCR was used to validate H9C2 cells in the control and DIC model groups,and Western blotting was used to further validate those whose bioinformatics and real-time PCR results that did not match.Results Thirty-eight ferroptosis-related genes in DIC were identified,and GO and KEGG analyses showed that these genes mainly participate in cell metabolism.Five hub genes for ferroptosis in DIC were obtained using machine learning methods:Mpc1,Prdx1,Kdm4a,Alox 12b,and Tfrc.Through in vitro experiments,the mRNA expression levels of Mpc1,Prdx1,and Kdm4a were downregulated in the DIC model group compared to those in the control group(P＜0.001),whereas the mRNA expression level of Alox12b was upregulated(P＜0.001).There were no significant differences in the mRNA or protein expression levels of Tfrc(P＞0.05).Conclusion Mpc1,Prdx1,Kdm4a,and Alox12b are key genes involved in ferroptosis in doxorubicin-induced cardiomyopathy and potential targets for the prevention and treatment of doxorubicin-induced cardiomyopathy in ferroptosis.

In 2025,the International Association of Pancreatology(IAP),in collaboration with the American Pancreatic Association,European Pancreatic Club,Indian Pancreas Club,and Japan Pancreas Society,released the International Association of Pancreatology revised guidelines on acute pancreatitis 2025.This edition represents a comprehensive revision of the 2013 guidelines,based on high-quality evidence accumulated over the past decade,particularly randomized controlled trials.The guidelines encompass 18 key areas-including pain management,fluid therapy,nutritional support,management of infected necrosis,complication control,discharge and follow-up,and recurrence prevention-offering a total of 96 recommendations that emphasize individualized treatment.These updates provide important guidance for standardizing clinical practice and improving outcomes in acute pancreatitis,while also indicating future research directions such as the development of targeted therapies.However,some recommendations remain limited by lower evidence quality,uncertain applicability in specific clinical settings,and insufficient consideration of economic burden and cost-effectiveness.

In 2025,the International Association of Pancreatology(IAP),in collaboration with the American Pancreatic Association,European Pancreatic Club,Indian Pancreas Club,and Japan Pancreas Society,released the International Association of Pancreatology revised guidelines on acute pancreatitis 2025.This edition represents a comprehensive revision of the 2013 guidelines,based on high-quality evidence accumulated over the past decade,particularly randomized controlled trials.The guidelines encompass 18 key areas-including pain management,fluid therapy,nutritional support,management of infected necrosis,complication control,discharge and follow-up,and recurrence prevention-offering a total of 96 recommendations that emphasize individualized treatment.These updates provide important guidance for standardizing clinical practice and improving outcomes in acute pancreatitis,while also indicating future research directions such as the development of targeted therapies.However,some recommendations remain limited by lower evidence quality,uncertain applicability in specific clinical settings,and insufficient consideration of economic burden and cost-effectiveness.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Objective To establish a sensitive,accurate and rapid detection method for 10 drugs and metabolites in hair with triple quadrupole tandem mass spectrometry,addressing the identification of drugs in real hair samples.Methods After cryogenic grinding and ultrasonic extraction,hair was separated by Restek Allure PFPP column(100 mm × 2.1 mm,5 μm).The mobile phase A was 20 mmol/L ammonium acetate,0.1％formic acid and 5％acetonitrile aqueous solution.The mobile phase B was acetonitrile.An electrospray ionization source was used for data acquisition in scheduled MRM mode.Results The method showed good linearity for all analytes within the validated range(R2＞0.995),with the limits of detection ranging from 0.5 to 6 pg/mg,the limits of quantification ranging from 2.5 to 10 pg/mg.Accuracy ranged from 89.1％to 114.6％,with intra-day precision ranging from 0.2％to 11.7％,inter-day precision ranging from 4.0％to 15.8％.the matrix effects ranging from 89.4％to 118.4％,the recoveries ranging from 63.6％～112.1％.Totally 20 cases were detected positive in 196 actual hair samples.Conclusion The time-scheduled scanning method exhibits high stability and sensitivity,enabling high-throughput detection,and is suitable for forensic toxicology laboratories to identify drugs in hair.

[Purpose]To analyze cancer incidence and mortality in Anhui cancer registration areas in 2019 and the trends from 2015 to 2019.[Methods]Data from 42 cancer registration areas in Anhui Province in 2019 meeting quality control requirements were collected.The incidence,mor-tality,age-standardized rates by Chinese standard population and world standard population,age-specific rate,accumulation rate(0～74 years old)and the top 10 cancers of high incidence and mortality were calculated by urban and rural areas,sexes and age groups.The standard population of China in 2000 was used for age-standardized incidence or mortality rate(ASIRC or ASMRC),and the Segi world standard population was used for age-standardized incidence or mortality rate(ASIRW or ASMRW),respectively.Joinpoint was used to analyze the incidence and mortality trends from 2015 to 2019,and the annual percentage change(APC)was estimated.[Results]In 2019,the reported incidence rate(crude rate)in Anhui cancer registration areas was 282.87/105(313.24/105 for male,251.19/105 for female),ASIRC and ASIRW were 183.85/105 and 178.94/105,respectively,with the cumulative incidence rate of 20.35％.There was no significant change in the incidence of malignant tumors from 2015 to 2019(APC=-1.00％,P＞0.05).The reported mortality rate(crude rate)was 167.20/105(214.67/105 for male,117.67/105 for female),ASMRC and ASMRW were 98.41/105 and 97.15/105,and the cumulative mortality rate was 10.68％.There was no significant change in the mortality rate of malignant tumors from 2015 to 2019(APC=-3.44％,P＞0.05).The incidence and mortality rate of lung cancer ranked the first in urban and rural popu-lations of all genders.The incidence rate of female breast cancer ranked the third and the mortali-ty rate ranked the sixth of all malignancies.The incidence and mortality of malignant tumors in men were higher than those in women,and higher in rural areas than those in urban areas,and the main cancer types of rural and urban areas tended to be the same.[Conclusion]From 2015 to 2019,there was no significant change in the incidence and mortality of malignant tumors in the cancer registration areas of Anhui Province,but it is still necessary to prevent and treat lung can-cer and female breast cancer.

OBJECTIVE To provide references for ensuring the safety of prescription preparation， dispensing， and use of parenteral nutrition solution， as well as for expanding the scope of pharmaceutical services provided by pharmacists in the Pharmacy Intravenous Admixture Services （PIVAS）. METHODS Under the guidance of PIVAS pharmacists， the rules for reviewing medical orders of parenteral nutrition in the PIVAS system and the information displayed on the infusion labels of finished parenteral nutrition solutions were refined. The process management of dispensing parenteral nutrition solution was strengthened， and detailed quality control and inspection rules were formulated. Additionally， Clinical Safety Monitoring Form for Finished Parenteral Nutrition Infusions was designed to conduct clinical monitoring and inspections for abnormalities in the finished infusions， infusion operations， and complications that may arise during the use of finished parenteral nutrition infusions. The implementation effects of the aforementioned optimization/inspection measures were evaluated by comparing data on the efficiency of medical order review for parenteral nutrition， the rate of irrational medical orders， the compliance rate of vascular access selection and infusion rate standardization， the rate of dispensing error， as well as the abnormalities occurring during clinical use， before and after the optimization/inspection initiatives were put into place. RESULTS The optimized prescription review system achieved automatic review of medical orders for parenteral nutrition， enhancing the efficiency of order review. The average time taken to review one parenteral nutrition medical order was reduced from approximately 1 minute to 10 seconds. The irrational rate of parenteral nutrition orders decreased by 31.87%. The dispensing error rate of parenteral nutrition decreased by 56.55%. The standard rate of vascular access selection and standard rate of infusion speed were increased by 13.29% and 3.54%， respectively. The PIVAS pharmacists identified and intervened in 5 abnormal cases out of 298 cases examined for use of parenteral nutrition solutions. CONCLUSIONS By optimizing the prescription review system， improving labeling information， and strengthening quality control inspections during both preparation and administration processes， PIVAS pharmacists have enhanced the safety of compounded parenteral nutrition solutions. This initiative has expanded the scope and depth of pharmaceutical care provided by dispensing pharmacists.