Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

AIM:To explore the role and mechanism of calcium-sensing receptor(CaSR)in regulating macro-phage polarization in hypertensive rats.METHODS:Male spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats were categorized into WKY group,SHR group,SHR+R568(CaSR agonist)group,and SHR+NPS2143(CaSR inhibitor)group.The thoracic aorta was isolated,and the expression of CaSR and macrophage polarization markers in the aorta was observed through immunofluorescence staining.The primary peritoneal macrophages of SHR and WKY rats were aseptically extracted following anesthesia.After intervention with R568 and NPS2143,the expression levels of M1 and M2 markers of peritoneal macrophages were observed by Western blot and immunofluorescence staining.The levels of interleukin(IL)-1β and IL-10 were measured by ELISA.The concentration of Ca2+in peritoneal macrophages was mea-sured by immunofluorescence.Western blot was employed to identify the expression of CaSR and nucleotide-binding oligo-merization domain-like receptor protein 3(NLRP3)inflammasome components.Following anesthesia,vascular smooth muscle cells(VSMCs)were isolated from SHR using an adherent method.Subsequently,a co-culture system was estab-lished with macrophage supernatant.The optimal action time for this co-culture system was determined through CCK-8 as-say.RESULTS:Compared with SHR group,activation of CaSR resulted in a significant decrease in the protein expres-sion of M1 polarization markers(P<0.05)and a concomitant increase in the protein expression of M2 polarization markers in the aorta(P<0.05).Compared with SHR group,administration of R568 led to a significant decrease in the protein ex-pression of M1 polarization markers(P<0.05)and a concomitant increase in the protein expression of M2 polarization markers(P<0.05)in peritoneal macrophages.Additionally,there was a notable reduction in the protein levels of NLRP3 inflammasome components(P<0.05).Furthermore,the fluorescence intensity of intracellular Ca2+was significantly en-hanced following R568 treatment(P<0.05).After administration of MCC950,an NLRP3 inflammasome inhibitor,the re-sults were consistent with those observed following R568 treatment,demonstrating statistical significance(P<0.05).This effect was reversed by the combined intervention of U73122,a phospholipase C(PLC)inhibitor(P<0.05).Compared with the control(0 h),the 24-h peritoneal macrophage supernatant exhibited the strongest capacity to enhance the viabili-ty of VSMCs after 24 h of culture(P<0.05).CONCLUSION:In hypertensive rats,the CaSR inhibits NLRP3 inflamma-some activation via the PLC-Ca2+signaling pathway,thereby mediating an increase in macrophage polarization towards the M2 phenotype and a decrease towards the M1 phenotype.

AIM:To explore the role and mechanism of calcium-sensing receptor(CaSR)in regulating macro-phage polarization in hypertensive rats.METHODS:Male spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats were categorized into WKY group,SHR group,SHR+R568(CaSR agonist)group,and SHR+NPS2143(CaSR inhibitor)group.The thoracic aorta was isolated,and the expression of CaSR and macrophage polarization markers in the aorta was observed through immunofluorescence staining.The primary peritoneal macrophages of SHR and WKY rats were aseptically extracted following anesthesia.After intervention with R568 and NPS2143,the expression levels of M1 and M2 markers of peritoneal macrophages were observed by Western blot and immunofluorescence staining.The levels of interleukin(IL)-1β and IL-10 were measured by ELISA.The concentration of Ca2+in peritoneal macrophages was mea-sured by immunofluorescence.Western blot was employed to identify the expression of CaSR and nucleotide-binding oligo-merization domain-like receptor protein 3(NLRP3)inflammasome components.Following anesthesia,vascular smooth muscle cells(VSMCs)were isolated from SHR using an adherent method.Subsequently,a co-culture system was estab-lished with macrophage supernatant.The optimal action time for this co-culture system was determined through CCK-8 as-say.RESULTS:Compared with SHR group,activation of CaSR resulted in a significant decrease in the protein expres-sion of M1 polarization markers(P<0.05)and a concomitant increase in the protein expression of M2 polarization markers in the aorta(P<0.05).Compared with SHR group,administration of R568 led to a significant decrease in the protein ex-pression of M1 polarization markers(P<0.05)and a concomitant increase in the protein expression of M2 polarization markers(P<0.05)in peritoneal macrophages.Additionally,there was a notable reduction in the protein levels of NLRP3 inflammasome components(P<0.05).Furthermore,the fluorescence intensity of intracellular Ca2+was significantly en-hanced following R568 treatment(P<0.05).After administration of MCC950,an NLRP3 inflammasome inhibitor,the re-sults were consistent with those observed following R568 treatment,demonstrating statistical significance(P<0.05).This effect was reversed by the combined intervention of U73122,a phospholipase C(PLC)inhibitor(P<0.05).Compared with the control(0 h),the 24-h peritoneal macrophage supernatant exhibited the strongest capacity to enhance the viabili-ty of VSMCs after 24 h of culture(P<0.05).CONCLUSION:In hypertensive rats,the CaSR inhibits NLRP3 inflamma-some activation via the PLC-Ca2+signaling pathway,thereby mediating an increase in macrophage polarization towards the M2 phenotype and a decrease towards the M1 phenotype.

Objective Analyzes the grouping effect and its influencing factors under DRG payment,provides reference for the reform of DRG payment.Methods Evaluates the effectiveness of DRG grouping using Coefficient of Variation(CV)and Reduction in Variance;using Value of Structure of Variation and Degree of Structure Variation,analyzes hospitalization costs structure changes of different DRG groups,and calculates the degree of correlation between average hospitalization costs through grey relational analysis;using non parametric tests and multiple regression to analyze the influencing factors of hospitalization cost.Results DRG grouping effect was not good,inter-group heterogeneity was not obvious;the structure of hospitalization expenses is unreasonable,and the proportion of consumables expenses is too high,ranking first in the grey correlation degree of hospitalization expenses,comprehensive medical service fees and treatment fees rank third and fifth respectively;the main factors affecting hospitalization costs are treatment methods,length of stay,presence of complications,and first hospitalization,the difference is statistically significant(P＜0.05).Conclusion More grouping nodes or higher CV value standards should be added to enhance the grouping effect of gastric cancer DRG;optimize the structure of hospitalization costs to reflect the labor and technical value of medical personnel;strengthen internal management and control the unreasonable use of drugs and consumables.

Objective:To analyze the genetic and clinical characteristics, treatment and prognosis of patients diagnosed with maturity onset of diabetes of the young (MODY) 12 subtype.Methods:This retrospective study collected and analyzed data from 5 children with MODY12 subtype caused by ABCC8 gene variants who underwent inpatient and outpatient genetic testing at Beijing Children′s Hospital from January 2016 to December 2023. Their clinical and genetic features, treatment, and follow-up results were analyzed.Results:Among the 5 patients with MODY12 subtype, 4 were male and 1 was female, with an age of 13.4 (5.5, 14.6) years. Four of the patients were born large for gestational age, while one was born small for gestational age. Two patients were overweight or obese. Three patients exhibited typical symptoms of diabetes, while 2 were incidentally found to have elevated blood glucose level. One patient was found to have diabetic ketoacidosis at onset, who was diagnosed with congenital hyperinsulinism during the neonatal period and received diazoxide treatment, and experienced intellectual developmental delay. All 5 patients had autosomal dominant inherited diabetes within 3 generations. The fasting blood glucose at onset was 7.5 (6.5, 10.0) mmol/L, the haemoglobin A1c (HbA1c) was 11.8% (7.5%, 13.5%), and the fasting C-peptide was 1.2 (1.1, 2.2) μg/L. The duration of follow-up was 15 (9, 32) months. One patient underwent lifestyle intervention, 2 received metformin orally, 1 received insulin therapy, and the other received subcutaneous injection of insulin combined with sulfonylurea orally. At the last follow-up, the median fasting blood glucose was 6.1 (5.1, 7.0) mmol/L, the HbA1c was 5.9% (5.7%, 7.1%), and the fasting C-peptide was 1.7 (0.9, 2.9) μg/L. One patient developed diabetic retinopathy. There were 4 missense variations in ABCC8 gene and one in-frame deletion, all of which were maternally inherited heterozygotes.Conclusions:MODY12 subtype is a heterogeneous disorder with the age of onset from infancy to adolescence. It can present as mild hyperglycemia or diabetic ketoacidosis, and has a high incidence of obesity. Definitive diagnosis can be achieved through genetic test, and individualized treatment is recommended based on glucose levels.

Objective Analyzes the grouping effect and its influencing factors under DRG payment,provides reference for the reform of DRG payment.Methods Evaluates the effectiveness of DRG grouping using Coefficient of Variation(CV)and Reduction in Variance;using Value of Structure of Variation and Degree of Structure Variation,analyzes hospitalization costs structure changes of different DRG groups,and calculates the degree of correlation between average hospitalization costs through grey relational analysis;using non parametric tests and multiple regression to analyze the influencing factors of hospitalization cost.Results DRG grouping effect was not good,inter-group heterogeneity was not obvious;the structure of hospitalization expenses is unreasonable,and the proportion of consumables expenses is too high,ranking first in the grey correlation degree of hospitalization expenses,comprehensive medical service fees and treatment fees rank third and fifth respectively;the main factors affecting hospitalization costs are treatment methods,length of stay,presence of complications,and first hospitalization,the difference is statistically significant(P＜0.05).Conclusion More grouping nodes or higher CV value standards should be added to enhance the grouping effect of gastric cancer DRG;optimize the structure of hospitalization costs to reflect the labor and technical value of medical personnel;strengthen internal management and control the unreasonable use of drugs and consumables.

Objective Analyzes the grouping effect and its influencing factors under DRG payment,provides reference for the reform of DRG payment.Methods Evaluates the effectiveness of DRG grouping using Coefficient of Variation(CV)and Reduction in Variance;using Value of Structure of Variation and Degree of Structure Variation,analyzes hospitalization costs structure changes of different DRG groups,and calculates the degree of correlation between average hospitalization costs through grey relational analysis;using non parametric tests and multiple regression to analyze the influencing factors of hospitalization cost.Results DRG grouping effect was not good,inter-group heterogeneity was not obvious;the structure of hospitalization expenses is unreasonable,and the proportion of consumables expenses is too high,ranking first in the grey correlation degree of hospitalization expenses,comprehensive medical service fees and treatment fees rank third and fifth respectively;the main factors affecting hospitalization costs are treatment methods,length of stay,presence of complications,and first hospitalization,the difference is statistically significant(P＜0.05).Conclusion More grouping nodes or higher CV value standards should be added to enhance the grouping effect of gastric cancer DRG;optimize the structure of hospitalization costs to reflect the labor and technical value of medical personnel;strengthen internal management and control the unreasonable use of drugs and consumables.

Objective Analyzes the grouping effect and its influencing factors under DRG payment,provides reference for the reform of DRG payment.Methods Evaluates the effectiveness of DRG grouping using Coefficient of Variation(CV)and Reduction in Variance;using Value of Structure of Variation and Degree of Structure Variation,analyzes hospitalization costs structure changes of different DRG groups,and calculates the degree of correlation between average hospitalization costs through grey relational analysis;using non parametric tests and multiple regression to analyze the influencing factors of hospitalization cost.Results DRG grouping effect was not good,inter-group heterogeneity was not obvious;the structure of hospitalization expenses is unreasonable,and the proportion of consumables expenses is too high,ranking first in the grey correlation degree of hospitalization expenses,comprehensive medical service fees and treatment fees rank third and fifth respectively;the main factors affecting hospitalization costs are treatment methods,length of stay,presence of complications,and first hospitalization,the difference is statistically significant(P＜0.05).Conclusion More grouping nodes or higher CV value standards should be added to enhance the grouping effect of gastric cancer DRG;optimize the structure of hospitalization costs to reflect the labor and technical value of medical personnel;strengthen internal management and control the unreasonable use of drugs and consumables.

Objective Analyzes the grouping effect and its influencing factors under DRG payment,provides reference for the reform of DRG payment.Methods Evaluates the effectiveness of DRG grouping using Coefficient of Variation(CV)and Reduction in Variance;using Value of Structure of Variation and Degree of Structure Variation,analyzes hospitalization costs structure changes of different DRG groups,and calculates the degree of correlation between average hospitalization costs through grey relational analysis;using non parametric tests and multiple regression to analyze the influencing factors of hospitalization cost.Results DRG grouping effect was not good,inter-group heterogeneity was not obvious;the structure of hospitalization expenses is unreasonable,and the proportion of consumables expenses is too high,ranking first in the grey correlation degree of hospitalization expenses,comprehensive medical service fees and treatment fees rank third and fifth respectively;the main factors affecting hospitalization costs are treatment methods,length of stay,presence of complications,and first hospitalization,the difference is statistically significant(P＜0.05).Conclusion More grouping nodes or higher CV value standards should be added to enhance the grouping effect of gastric cancer DRG;optimize the structure of hospitalization costs to reflect the labor and technical value of medical personnel;strengthen internal management and control the unreasonable use of drugs and consumables.