Trifluridine-tipiracil(TAS-102),as a novel fluorouracil-based chemotherapeutic agent,effectively overcomes fluorouracil resistance in colorectal cancer(CRC)through its unique pharmacological mechanisms,providing a critical treatment option for advanced CRC patients.Probiotics have shown unique value in CRC prevention and adjuvant therapy by regulating intestinal flora homeostasis and modulating host immune response.It is worth noting that the combination of chemotherapeutic drugs and probiotics not only enhances the anti-tumor activity through synergistic effects,but also reduces the adverse effects caused by chemotherapeutic drugs.Based on this,this paper systematically reviews the pharmacological properties of TAS-102 and describes its synergistic effects in combination with other antitumor drugs.It also summarizes the synergistic effect of fluorouracil drugs combined with probiotics to enhance the effectiveness and reduce the toxicity,and discusses the potential value of the combination of TAS-102 and probiotics,which provides a new research direction for optimizing the precision treatment of CRC and a scientific basis for improving the quality of life of patients.

Objective:To compare the differences among four routine lipid testing systems in detecting high triglyceride (TG) serum samples and evaluate the accuracy and consistency of the four homogeneous low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) reagents using vertical auto profile (VAP) as the reference method.Methods:A retrospective study was conducted on 249 serum samples with elevated TG levels collected from the Department of Laboratory Medicine at the Second Xiangya Hospital of Central South University between January and October 2024. TG, total cholesterol (TC), LDL-C, and HDL-C were measured using four homogeneous detection systems: Beckman Coulter (USA), Wako Pure Chemical Industries (Japan), Mindray (China), and Roche Diagnostics (Germany). VAP was used to analyze lipoprotein subfractions, including very-low-density lipoprotein cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), LDL-C, lipoprotein(a) cholesterol [Lp(a)-C], and HDL-C. The mean coefficient of variation ( CV) across the four systems was calculated for each parameter. Pearson correlation and ordinal logistic regression (OLR) were used to assess correlations between the four HDL-C/LDL-C systems and VAP. Bland-Altman plots were generated to evaluate biases, and deviations were calculated. For parameters with significant deviations, multivariate linear regression and standardized coefficients were used to analyze correlations between biases and lipoprotein subfractions. Based on the Chinese Guidelines for Lipid Management (2023), LDL-C and non-HDL-C treatment goals were categorized into five risk levels (ultra-high, high, moderate, high-risk, and low-risk). VAP results defined LDL-C/non-HDL-C intervals, and the four systems′ concordance in risk classification was evaluated. Samples were grouped into A, B, C, D ( n=63, 62, 62, 62) by TG concentration, and ANOVA, chi-square, and Fisher exact tests assessed intergroup differences. Results:The mean CVs across systems for TG, TC, LDL-C, HDL-C, and non-HDL-C were 2.98%, 1.76%, 18.10%, 5.60%, 2.58%, respectively. Pearson correlations between LDL-C results (Beckman, Wako, Mindray, Roche) and VAP were 0.889, 0.854, 0.899, and 0.973; mean relative deviations were 54.8%, 41.0%, 49.3%, and 3.6%; classification accuracies were 6.0% (15/249), 21.3% (53/249), 9.2% (23/249), and 76.7% (191/249). HDL-C deviations were 18.7%, 15.1%, 11.1%, and 8.7%, with correlations ( r) of 0.883, 0.911, 0.959, and 0.950 (all P<0.001). LDL-C means showed no intergroup differences (A-D), but CV increased with TG levels ( P<0.001). HDL-C means and CVs showed no significant intergroup differences. Beckman, Wako, and Mindray LDL-C results exhibited significant positive biases correlated with TG and VLDL-C (multivariate regression; P<0.05); VLDL-C had the strongest influence (standardized coefficients: 0.820, 0.394, 0.813; P<0.001). Non-HDL-C classifications matched VAP in 92.4% (Beckman), 85.9% (Wako), 94.0% (Mindray), and 93.2% (Roche), with no intergroup differences. Conclusion:For high-TG sera, Beckman, Wako, and Mindray LDL-C exhibited significant positive biases correlated with TG and VLDL-C, while Roche LDL-C showed minimal deviation. TG, TC, HDL-C, and non-HDL-C results showed minimal variation across the four systems. All systems demonstrated comparable accuracy for non-HDL-C compared to VAP. The non-HDL-C measured by the four detection systems demonstrates high accuracy and consistency in atherosclerotic cardiovascular disease risk stratification and lipid-lowering goal assessment, and it is unaffected by TG levels.

Purpose To investigate the differential expression of proteins secreted by diffuse-type gastric cancer-associated fibroblasts(DGC-CAFs)and intestinal-type gastric cancer-associated fibroblasts(IGC-CAFs)according to Lauren classification of gastric cancer.Methods Fresh surgery samples were acquired to extract primary cancer-asso-ciated fibroblasts(CAFs)to obtain the conditional medium,including three cases of diffuse-type gastric cancer(DGC)and three cases of intestinal-type gastric cancer(IGC).Then high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to detect the differences in secreted factors between DGC-CAFs and IGC-CAFs.Additionally,a total of 1 174 cases were collected from the GEO and TCGA databases,and the distribution of stromal cells was assessed via ESTIMATE to derive stromal scores for both DGC and GC.Furthermore,Kaplan-Meier survival analysis was performed to evaluate the relationship between high stromal scores,elevated CAFs proportions,and patient prognosis.Subsequently,GO enrichment analysis was performed to investigate associated genes and their bi-ological functions.Results HPLC-MS/MS analysis showed that only 10 proteins were identified to be expressed in both DGC-CAFs and IGC-CAFs,namely SPARC,COL6A1,COL1A2,COL1A1,COL3A1,FN1,DCN,ACTG1,TIMP1 and SHROOM3.There were 8 proteins expressed higher in DGC-CAFs than IGC-CAFs in all cases with ratio＞2,namely COL3A1(5.28),COL1A2(3.98),DCN(3.71),TIMP1(3.40),COL6A1(3.35),ACTG1(3.13),COL1A1(2.84)and SHROOM3(2.50).Two other proteins,TUBB and BASP1,were identified in all three cases of DGC-CAFs.The former was only identified in one case of IGC-CAFs,while the latter was not identified in all three cases of IGC-CAFs.The results of bioinformatics analysis showed that the stromal score of DGC was higher than IGC,which correlated with poor prognosis.Analysis of cell components revealed that the related genes were more enriched in ECM,collagen-containing extracellular matrix and cell-cell junction.Also,the biological process and molecular function was based on the components,which was consistent with HPLC-MS/MS analysis results.Conclusion There are differ-ences in secreted proteins of DGC-CAFs and IGC-CAFs,both on the types and the content.The differential proteins are mostly enriched in ECM-related signaling pathways.Presumably,the high content of CAFs in the stroma affects the prognosis of gastric cancer patients by influencing the gene expression and the function of receptor pathway of ECM.

Purpose To investigate the differential expression of proteins secreted by diffuse-type gastric cancer-associated fibroblasts(DGC-CAFs)and intestinal-type gastric cancer-associated fibroblasts(IGC-CAFs)according to Lauren classification of gastric cancer.Methods Fresh surgery samples were acquired to extract primary cancer-asso-ciated fibroblasts(CAFs)to obtain the conditional medium,including three cases of diffuse-type gastric cancer(DGC)and three cases of intestinal-type gastric cancer(IGC).Then high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to detect the differences in secreted factors between DGC-CAFs and IGC-CAFs.Additionally,a total of 1 174 cases were collected from the GEO and TCGA databases,and the distribution of stromal cells was assessed via ESTIMATE to derive stromal scores for both DGC and GC.Furthermore,Kaplan-Meier survival analysis was performed to evaluate the relationship between high stromal scores,elevated CAFs proportions,and patient prognosis.Subsequently,GO enrichment analysis was performed to investigate associated genes and their bi-ological functions.Results HPLC-MS/MS analysis showed that only 10 proteins were identified to be expressed in both DGC-CAFs and IGC-CAFs,namely SPARC,COL6A1,COL1A2,COL1A1,COL3A1,FN1,DCN,ACTG1,TIMP1 and SHROOM3.There were 8 proteins expressed higher in DGC-CAFs than IGC-CAFs in all cases with ratio＞2,namely COL3A1(5.28),COL1A2(3.98),DCN(3.71),TIMP1(3.40),COL6A1(3.35),ACTG1(3.13),COL1A1(2.84)and SHROOM3(2.50).Two other proteins,TUBB and BASP1,were identified in all three cases of DGC-CAFs.The former was only identified in one case of IGC-CAFs,while the latter was not identified in all three cases of IGC-CAFs.The results of bioinformatics analysis showed that the stromal score of DGC was higher than IGC,which correlated with poor prognosis.Analysis of cell components revealed that the related genes were more enriched in ECM,collagen-containing extracellular matrix and cell-cell junction.Also,the biological process and molecular function was based on the components,which was consistent with HPLC-MS/MS analysis results.Conclusion There are differ-ences in secreted proteins of DGC-CAFs and IGC-CAFs,both on the types and the content.The differential proteins are mostly enriched in ECM-related signaling pathways.Presumably,the high content of CAFs in the stroma affects the prognosis of gastric cancer patients by influencing the gene expression and the function of receptor pathway of ECM.

Trifluridine-tipiracil(TAS-102),as a novel fluorouracil-based chemotherapeutic agent,effectively overcomes fluorouracil resistance in colorectal cancer(CRC)through its unique pharmacological mechanisms,providing a critical treatment option for advanced CRC patients.Probiotics have shown unique value in CRC prevention and adjuvant therapy by regulating intestinal flora homeostasis and modulating host immune response.It is worth noting that the combination of chemotherapeutic drugs and probiotics not only enhances the anti-tumor activity through synergistic effects,but also reduces the adverse effects caused by chemotherapeutic drugs.Based on this,this paper systematically reviews the pharmacological properties of TAS-102 and describes its synergistic effects in combination with other antitumor drugs.It also summarizes the synergistic effect of fluorouracil drugs combined with probiotics to enhance the effectiveness and reduce the toxicity,and discusses the potential value of the combination of TAS-102 and probiotics,which provides a new research direction for optimizing the precision treatment of CRC and a scientific basis for improving the quality of life of patients.

Objective:To compare the differences among four routine lipid testing systems in detecting high triglyceride (TG) serum samples and evaluate the accuracy and consistency of the four homogeneous low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) reagents using vertical auto profile (VAP) as the reference method.Methods:A retrospective study was conducted on 249 serum samples with elevated TG levels collected from the Department of Laboratory Medicine at the Second Xiangya Hospital of Central South University between January and October 2024. TG, total cholesterol (TC), LDL-C, and HDL-C were measured using four homogeneous detection systems: Beckman Coulter (USA), Wako Pure Chemical Industries (Japan), Mindray (China), and Roche Diagnostics (Germany). VAP was used to analyze lipoprotein subfractions, including very-low-density lipoprotein cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), LDL-C, lipoprotein(a) cholesterol [Lp(a)-C], and HDL-C. The mean coefficient of variation ( CV) across the four systems was calculated for each parameter. Pearson correlation and ordinal logistic regression (OLR) were used to assess correlations between the four HDL-C/LDL-C systems and VAP. Bland-Altman plots were generated to evaluate biases, and deviations were calculated. For parameters with significant deviations, multivariate linear regression and standardized coefficients were used to analyze correlations between biases and lipoprotein subfractions. Based on the Chinese Guidelines for Lipid Management (2023), LDL-C and non-HDL-C treatment goals were categorized into five risk levels (ultra-high, high, moderate, high-risk, and low-risk). VAP results defined LDL-C/non-HDL-C intervals, and the four systems′ concordance in risk classification was evaluated. Samples were grouped into A, B, C, D ( n=63, 62, 62, 62) by TG concentration, and ANOVA, chi-square, and Fisher exact tests assessed intergroup differences. Results:The mean CVs across systems for TG, TC, LDL-C, HDL-C, and non-HDL-C were 2.98%, 1.76%, 18.10%, 5.60%, 2.58%, respectively. Pearson correlations between LDL-C results (Beckman, Wako, Mindray, Roche) and VAP were 0.889, 0.854, 0.899, and 0.973; mean relative deviations were 54.8%, 41.0%, 49.3%, and 3.6%; classification accuracies were 6.0% (15/249), 21.3% (53/249), 9.2% (23/249), and 76.7% (191/249). HDL-C deviations were 18.7%, 15.1%, 11.1%, and 8.7%, with correlations ( r) of 0.883, 0.911, 0.959, and 0.950 (all P<0.001). LDL-C means showed no intergroup differences (A-D), but CV increased with TG levels ( P<0.001). HDL-C means and CVs showed no significant intergroup differences. Beckman, Wako, and Mindray LDL-C results exhibited significant positive biases correlated with TG and VLDL-C (multivariate regression; P<0.05); VLDL-C had the strongest influence (standardized coefficients: 0.820, 0.394, 0.813; P<0.001). Non-HDL-C classifications matched VAP in 92.4% (Beckman), 85.9% (Wako), 94.0% (Mindray), and 93.2% (Roche), with no intergroup differences. Conclusion:For high-TG sera, Beckman, Wako, and Mindray LDL-C exhibited significant positive biases correlated with TG and VLDL-C, while Roche LDL-C showed minimal deviation. TG, TC, HDL-C, and non-HDL-C results showed minimal variation across the four systems. All systems demonstrated comparable accuracy for non-HDL-C compared to VAP. The non-HDL-C measured by the four detection systems demonstrates high accuracy and consistency in atherosclerotic cardiovascular disease risk stratification and lipid-lowering goal assessment, and it is unaffected by TG levels.

A 50-year-old male patient diagnosed with extensive stage small cell lung cancer was treated with pamiparib in combination with temozolomide.Five days later,the patient developed fever with fatigue.After 10 days,the patient stopped taking the drug due to worsening symptoms and was diagnosed with chemotherapy-induced myelosuppression(grade 4).The clinicist evaluated the patient's condition and assessed the association of adverse reactions using the Naranjo's evaluation scale,and concluded that myelosuppression may be induced by the combination of pamiparib and temozolomide.After symptomatic treatment,the patient's myelosuppression recovered completely.This article discusses the correlation between myelosuppression and the combination of the two drugs,provides treatment measures for this situation,briefly describes the risk factors of myelosuppression,treatment and prevention,and guides medical personnel to adjust the treatment plan in time according to different individuals in the process of using similar programs,and strengthens the monitoring and education of adverse drug reactions,so as to provide references for safe drug use.

AIM:This study is aimed to investigate the impact of 3,5,6,7,8,3',4'-heptamethoxyflavone(HMF)on the proliferation,invasion,and migration of human colorectal cancer(CRC)cell lines(SW480 and HCT116)and preliminarily explore the underlying molecular mechanisms.METHODS:Human colorectal cancer cells(SW480 and HCT116)cultured in vitro were subjected to various concentrations of HMF(0,12.5,25 and 50 μmol/L)for 48 h.Proliferation levels were assessed using the CCK-8 assay,invasion abilities were examined via the Transwell assay,migra-tion rates were measured using the scratch assay,and oxidative stress levels were determined by the DCF-DA reactive oxy-genation assay.The mRNA expression levels of heme oxygenase-1(HO-1)mRNA and NAD(P)H:quinone oxidoreduc-tase-1(NQO-1)were quantified using RT-qPCR.RESULTS:Treatment with varying concentrations of HMF resulted in a significant reduction in the proliferative capacity of SW480 and HCT116 cancer cells,as was indicated by CCK-8 experi-ments(P<0.05).Transwell assays demonstrated a pronounced attenuation in the invasive potential of SW480 and HCT116 following HMF treatment(P<0.05).Scratch assays highlighted a notable constraint on the migratory capabilities of SW480 and HCT116 after HMF treatment(P<0.05).DCF-DA staining revealed a substantial increase in reactive oxy-gen species(ROS)levels within SW480 and HCT116 cells after HMF treatment(P<0.05).Furthermore,RT-qPCR ex-periments elucidated that HMF markedly suppressed the mRNA expression of antioxidant genes HO-1 and NQO-1.CON-CLUSION:HMF induces oxidative stress response in SW480 and HCT116 cells,consequently inhibiting their prolifera-tion,invasion and migration.

With the continuous progress of research methodology in the real world and the growing maturity of artificial intelligence technology， a method for conducting “quantitative” research to guide clinical practice based on traditional Chinese medicine （TCM） diagnosis and treatment data was gradually developed. However， there is still a need for further improvements in the overall design of studies and the transformation of findings into clinical practice. Based on this， we put forward a comprehensive overall design concept and application approach for real-world study and artificial intelligence research based on clinical diagnosis and treatment data of TCM. This approach consists of five steps： Constructing a research-based database with a large sample size and high data quality； Mining and classification of core prescriptions； Conducting cohort studies to evaluate the effectiveness of core prescriptions； Utilizing case-control studies to clarify the dominant population； Establishing predictive models to achieve precision medicine. Additionally， it is imperative for researchers to establish a standardized system for collecting TCM variables and processing data， optimize the determination and measurement methods of confounding factors， further improve and promote methodologies， and strengthen the training of interdisciplinary talents. By following this research method， we anticipate that the clinical translation of research findings will be facilitated， leading to advancements in TCM precision medicine. Real-world study and artificial intelligence research share similar research foundations， and clinical applications complement each other. In the future， the two will merge together.

Objective:To explore the relationship between the maternal dietary patterns during pregnancy and the early childhood BMI change trajectory.Methods:The subjects were 1 241 pairs of pregnant women and their children in Ma'anshan maternal and infant health cohort. The food frequency questionnaire was used to collect the maternal diet data during pregnancy. The cohort children were followed up at birth, month 3, 6, 12, 18 and 24, respectively. The body height and weight data of the cohort children were collected. The principal component analysis was used to determine the categories of maternal dietary patterns during pregnancy, group-based multi-trajectory modeling was used to fit the early childhood BMI change trajectory, and the multiple classification logistic regression model was used to evaluate the relationship between the maternal dietary patterns during pregnancy and the early childhood BMI change trajectory.Results:The maternal dietary patterns during pregnancy included protein type, healthy type, vegetarian type, processing type and beverage type, which could explain 50.04% of the total dietary variation. Among them, the protein type, main dietary pattern, could explain 21.34% of the total dietary variation. The early childhood BMI change trajectory was from thinnish stature to average stature, then to mild obesity, accounting for 42.9%, 45.6% and 11.5% respectively. After controlling the potential confounding factors, it was found that there was a statistical correlation between healthy type and beverage type of maternal dietary patterns during pregnancy and early childhood BMI change trajectory ( P<0.05). Comparison of change trajectories between thinnish type and average stature type, children in the low-level group of healthy diet pattern tended to have a thinnish type change trajectory in early life ( OR=1.286, 95% CI: 1.002-1.651). Comparison of change trajectories between mild obesity type and average stature type, children in the high-level group of beverage diet pattern tended to have a mild obesity type change trajectory in early life ( OR=0.565, 95% CI: 0.342-0.935). The other dietary patterns had no statistical correlation with the early childhood BMI change trajectory. Conclusions:Maternal dietary patterns during pregnancy can affect the early childhood BMI change trajectory, and the low-level healthy type diet is an independent risk factor for thinnish type change trajectory, and the high-level beverage type diet is an independent risk factor for the mild obesity type change trajectory.