OBJECTIVE To explore the changes and correlations of color， components and anti-tumor activity of Gelsemium elegans during sand-frying processing， so as to provide a reference for the toxicity-attenuating and efficacy-preserving processing as well as quality control of sand-fried G. elegans decoction pieces.METHODS Raw G.elegans and its processed products prepared by sand-frying for 15， 30， 75， 105 and 120 s were taken as test samples. The chromatic values， contents of total alkaloids and seven main active components （gelsemine， humantenine， koumine， gelsenicine， etc.） were determined. Their in vitro anti-tumor activity was investigated. The correlations between color and component contents， as well as between total alkaloid content and anti-tumor activity were analyzed.RESULTS The color of G.elegans samples generally darkened after sand-frying， and the total color difference （Δ E * ） of samples sand-fried for 75 s was greater than 20. At the initial stage of sand-frying （15-30 s）， the total alkaloid content in processed products decreased sharply compared with the raw material； at the later-stage of sand-frying （75-105 s）， the declining rate of total alkaloid content slowed down and tended to be stable. The contents of gelsenicine and humantenidine in processed products dropped drastically at 30 s of sand-frying， while the contents of koumine and sempervirine decreased substantially （by about 80%） after 75 s of sand-frying and then gradually tended to be stable. The anti-HepG2 cell proliferation activity of each processed product decreased with the extension of frying time. Correlation analysis demonstrated that color brightness and yellow-blue chromaticity were significantly positively correlated with the contents of total alkaloids and all determined active components except gelsemine （ P ＜0.05 or P ＜0.01）； red-green chromaticity was significantly positively correlated with the contents of koumine， sempervirine， gelsemivirine and humantenidine （ P ＜0.05 or P ＜0.01）； Δ E * was significantly negatively correlated with the contents of total alkaloids and all determined active components except gelsemine. Besides， total alkaloid content was significantly negatively correlated with the half maximal inhibitory concentration of the samples on HepG2 cells （ P ＜0.05 or P ＜0.01）.CONCLUSIONS With the prolongation of sand-frying time， the color of sand-fried G.elegans decoction pieces gradually turned brownish-brown， the contents of seven active components and total alkaloids decreased progressively， and its anti-HepG2 cell activity showed an overall downward trend. Sand-frying for 75 s serves as a critical turning-point for the above-mentioned changes.

Objective To investigate the correlation of serum levels of soluble programmed death ligand 1(sPD-L1),tumor necrosis factor-associated apoptosis-inducing ligand(TRAIL)and fibroblast growth factor 23(FGF-23)with risk stratification and death in patients with acute pulmonary embolism(APE).Methods A total of 113 pa-tients with APE admitted to the hospital from January 2022 to January 2024 were selected as APE group,and 50 healthy subjects were selected as control group.The 113 patients with APE were divided into high risk group(39 cases),medium risk group(45 cases)and low risk group(29 cases)by risk stratification.Accord-ing to the death of APE patients,they were divided into survival group(83 cases)and death group(30 cases).The levels of serum sPD-L1,TRAIL and FGF-23 were measured by enzyme-linked immunosorbent assay(ELISA).Multiple Logistic regression was used to analyze the risk factors affecting death of APE patients.Receiver operating characteristic(ROC)curve was drawn to analyze the value of serum sPD-L1,TRAIL and FGF-23 levels in evaluating mortality in APE patients.Pearson correlation analysis was used to investigate the correlation between serum sPD-L1,TRAIL and FGF-23 levels and cardiac function indicators in APE patients.Results The levels of serum sPD-L1,TRAILand FGF-23 in the APE group were significantly higher than those in the control group(P＜0.001).The serum sPD-L1,TRAIL and FGF-23 levels in the death group were significantly higher than those in the survival group(P＜0.001).The levels of serum sPD-L1,TRAIL and FGF-23 in the high-risk group were higher than those in the medium and low-risk groups,and the medium risk group was higher than the low-risk group,and the differences were statistically significant(P＜0.001).Multiple Logistic regression analysis showed that elevated levels of cardiac troponin Ⅰ(cTnⅠ),B type brain na-triuretic peptide(BNP),sPD-L1,TRAIL and FGF-23 were risk factors for mortality in APE patients(P＜0.05).ROC curve analysis showed that the combination of sPD-L1,TRAIL and FGF-23 had the largest area under curve for predicting death in APE patients,which was 0.924(95％CI:0.861-0.986),with a sensitivity of 96.8％and a specificity of 81.2％.Correlation analysis showed that the levels of serum sPD-L1,TRAIL and FGF-23 were positively correlated with cTnⅠ and BNP in APE patients(P＜0.001).Conclusion The lev-els of serum sPD-L1,TRAIL and FGF-23 are significantly elevated in APE patients,and their high expression is associated with high-risk stratification and mortality.The combination of these three indexes has good eval-uation value for APE patient mortality.

Objective To provide valuable references and insights for improving the excipient standard system of the Chinese Pharmacopeia and promoting its harmonization with ICH Q3D.By analyzing the harmonization strategies and implementation of excipient standards in the pharmacopoeias of Europe,the United States,and Japan.Methods Through a combination of literature review and case study analysis,this paper introduces the policies and strategies adopted by the pharmacopoeias of three major regions(Europe,the United States,and Japan)in implementing the ICH Q3D guidelines in the field of pharmaceutical excipients.Additionally,it reviews the updates on excipient standards in these regions and analyzes the characteristics of their alignment with ICH Q3D.Results The strategies for implementing ICH Q3D in pharmacopeial excipient standards vary across different regions,with each following distinct approaches and progressing at different rates.Notably,there are significant differences in the establishment of standards for elemental impurities.Conclusion Promoting the harmonization of pharmacopeial excipient standards with ICH Q3D is a challenging and long-term endeavor.It is essential to develop a harmonization strategy that is tailored to China's national context.

Objective To analyze the risk factors affecting the progression-free survival(PFS)of patients with intrahepatic cholangiocarcinoma(ICC)after surgical resection,and a predictive nomogram model was constructed based on blood test indicators.Methods A total of 99 ICC patients who received their first treatment at Hunan Provincial People's Hospital from January 2020 to December 2022 were selected as research subjects,they were divided into training group(n=70)and validation group(n=29).The independent risk factors for postoperative recurrence were identified using least absolute shrinkage and selection operator(LASSO)regression analysis and multivariate Cox risk regression analysis.The accuracy and clinical utility of the method were further tested by consistency index,receiver operating characteristic(ROC)curve,calibration graph,decision curve analysis,and progression-free survival curve.Results LASSO and multivariate Cox risk regression analysis showed that patient's gender,tumor-lymph node metastasis,differentiation grade,tumor diameter,aspartate aminotransferase,alpha-fetoprotein,total bile acid after surgery,and monocyte changes before and after surgery were independent factors affecting the PFS of ICC patients.The predictive model based on the risk factor showed that the consistency index of the training group was 0.884 and that of the validation group was 0.838.The area under ROC curve for training group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.965 and 0.923,respectively;for validation group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.821 and 0.923,respectively.The risk score calculated according to the nomogram divided ICC patients into high-risk group and low-risk group with high postoperative recurrence risk,and the median PFS in high-risk group was significantly shorter than that in low-risk group(P＜0.05).Conclusion The nomogram constructed by this study has good predictive effect and can be used as a supplementary evaluation for predicting PFS after ICC patients.

Objective To analyze and evaluate the differences between the standards for elemental impurities in pharmaceutical excipients in the"Chinese Pharmacopoeia"and ICH Q3D,and to explore strategies for harmonization between them.Methods This study summarizes and reviews the main differences between the general chapters and specific monographs of pharmaceutical excipients in the 2020 edition of the"Chinese Pharmacopoeia"and its first supplement,compared with ICH Q3D.Results By integrating the harmonization strategies for elemental impurities in foreign pharmacopoeias and the risk assessment results for pharmaceutical excipients,this study proposes harmonization strategies and pathways for the standards of pharmaceutical excipients in the"Chinese Pharmacopoeia."Conclusions A systematic risk assessment of elemental impurities in pharmaceutical excipients in the"Chinese Pharmacopoeia"should be conducted based on their risk levels.The revision methods should be determined and continuously updated according to the assessment results.

Objective To analyze the historical and current inclusion of heavy metals and specific elemental impurity tests in the monographs of pharmaceutical excipients in the Pharmacopeias of the US(USP),Europe(EP)and Japan(JP)pharmacopeias.By examining the characteristics and trends in these pharmacopeias,the study seeks to provide insights that can inform the strategy for incorporating elemental impurity tests in the Chinese Pharmacopoeia and offer guidance for the industry to enhance control over elemental impurities in drugs and excipients.Methods The study reviews the inclusion and revision processes of heavy metals and specific elemental impurity tests in the pharmacopeias of the US,Europe and Japan,focusing on aspects such as the number of excipient monographs,the proportion of heavy metal tests,professional categories,and treatment methods.A comparative analysis with the Chinese Pharmacopoeia was conducted to explore the reasons behind the observed differences and to identify potential future developments.Results The USP contains the largest number of excipient monographs,the EP has the fastest progress in the evaluation of elemental impurities in excipients,the JP relies most heavily on wet chemical methods for testing.Conclusion The strategies of the US,European,and Japanese pharmacopeias can serve as valuable references for the development of elemental impurity testing strategies in the Chinese Pharmacopoeia.It is recommended to classify pharmaceutical excipients by risk level,removing heavy metal tests for low-risk categories and conducting elemental impurity risk assessments for higher-risk mineral-based excipients.The inclusion of specific elemental impurity tests should be determined based on these risk assessments,with specific limits or methods established as needed according to excipient category or individual monographs.

Objective To provide valuable references and insights for improving the excipient standard system of the Chinese Pharmacopeia and promoting its harmonization with ICH Q3D.By analyzing the harmonization strategies and implementation of excipient standards in the pharmacopoeias of Europe,the United States,and Japan.Methods Through a combination of literature review and case study analysis,this paper introduces the policies and strategies adopted by the pharmacopoeias of three major regions(Europe,the United States,and Japan)in implementing the ICH Q3D guidelines in the field of pharmaceutical excipients.Additionally,it reviews the updates on excipient standards in these regions and analyzes the characteristics of their alignment with ICH Q3D.Results The strategies for implementing ICH Q3D in pharmacopeial excipient standards vary across different regions,with each following distinct approaches and progressing at different rates.Notably,there are significant differences in the establishment of standards for elemental impurities.Conclusion Promoting the harmonization of pharmacopeial excipient standards with ICH Q3D is a challenging and long-term endeavor.It is essential to develop a harmonization strategy that is tailored to China's national context.

Objective Analysing the risk factors for the occurrence of pre-frailty or frailty of the community elderly in Chengdu and constructing a risk prediction model.Methods The general information questionnaire,MNA-SF scale,Changsha version of the MoCA scale,PSQI scale,FRAIL scale,and Traditional Chinese Medicine Constitution Scale for the elderly were used in the cross-sectional survey.A total of 400 elderly people who completed community physical examinations in Chengdu from April 2022 to April 2023 were selected as the research objects.Based on multivariate Logistic regression analysis,the independent influencing factors were determined,and RStudio software was used to construct a risk prediction model nomogram.The physical examination data of 200 elderly people collected in Deyang City from June 2023 to October 2023 were used for external verification.The area under the ROC curve,Hosmer-Lemeshow test and calibration curve,and decision curve were used to evaluate the discrimination,calibration,and clinical practicability of the model.Results Age,abdominal circumference,number of chronic diseases,PSQI score,allergy history,and balanced constitution were independent influencing factors for pre-frailty/frailty in the elderly in the community(P<0.05),and the regression equation was as follows:Logit(P)=0.063×age+0.025×abdominal circumference-1.006×allergy history+0.300×number of chronic diseases+0.082×PSQI-1.013×balanced constitution-8.269.The area under the ROC curve of the modeling group was 0.779(95%CI:0.733-0.825),the sensitivity was 67.1%,the specificity was 76.3%,and the maximum Youden index was 0.434.The area under the ROC curve of the external validation group was 0.783(95%CI:0.709-0.856),the sensitivity was 62.0%,the specificity was 95.0%,and the maximum Youden index was 0.570.The Hosmer-Lemeshow goodness of fit test results of the two groups were χ2=3.285,P=0.915 and χ2=8.376,P=0.398,and the calibration curve fit was good.DCA showed that the threshold probability of clinical benefit was 5%-99%and 21%-98%.Conclusions The pre-frailty/frailty risk prediction model established in this study has good predictive efficacy for the elderly in the community,and the use of this model for screening and early intervention of high-risk populations can be clinically beneficial.

Objective To analyze the risk factors affecting the progression-free survival(PFS)of patients with intrahepatic cholangiocarcinoma(ICC)after surgical resection,and a predictive nomogram model was constructed based on blood test indicators.Methods A total of 99 ICC patients who received their first treatment at Hunan Provincial People's Hospital from January 2020 to December 2022 were selected as research subjects,they were divided into training group(n=70)and validation group(n=29).The independent risk factors for postoperative recurrence were identified using least absolute shrinkage and selection operator(LASSO)regression analysis and multivariate Cox risk regression analysis.The accuracy and clinical utility of the method were further tested by consistency index,receiver operating characteristic(ROC)curve,calibration graph,decision curve analysis,and progression-free survival curve.Results LASSO and multivariate Cox risk regression analysis showed that patient's gender,tumor-lymph node metastasis,differentiation grade,tumor diameter,aspartate aminotransferase,alpha-fetoprotein,total bile acid after surgery,and monocyte changes before and after surgery were independent factors affecting the PFS of ICC patients.The predictive model based on the risk factor showed that the consistency index of the training group was 0.884 and that of the validation group was 0.838.The area under ROC curve for training group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.965 and 0.923,respectively;for validation group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.821 and 0.923,respectively.The risk score calculated according to the nomogram divided ICC patients into high-risk group and low-risk group with high postoperative recurrence risk,and the median PFS in high-risk group was significantly shorter than that in low-risk group(P＜0.05).Conclusion The nomogram constructed by this study has good predictive effect and can be used as a supplementary evaluation for predicting PFS after ICC patients.