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.

The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.

Objective To explore the application value of serum Syndecan-1 and endocan-1 combined with rapid sequential organ failure(qSOFA)score in the diagnosis and prognosis of sepsis.Methods The severity of 118 patients with sepsis was divided into the general sepsis group(48 cases),the severe sepsis group(42 cases)and the septic shock group(28 cases).According to the prognosis,patients were divided into the death group(n=32)and the survival group(n=86).A total of 118 healthy volunteers were selected as the control group.Serum Syndecan-1 and endocan-1 levels were detected by enzyme-linked immunosorbent assay(ELISA).The value of serum Syndecan-1,endocan-1 and qSOFA scores in the early diagnosis and prognosis of sepsis was analyzed by receiver operating characteristic(ROC)curve,and the area under the curve(AUC)was compared.Results Compared with the control group,levels of Syndecan-1,endocan-1 and qSOFA scores were increased in the study group(P＜0.05).The serum Syndecan-1,endocan-1 and qSOFA score in the general sepsis group,the severe sepsis group and the septic shock group were significantly increased in sequence(P＜0.05).ROC curve analysis showed that the AUC of serum Syndecan-1,endocan-1 and qSOFA score in the diagnosis of sepsis(0.967)were higher than that of Syndecan-1(AUC=0.868),endocan-1(AUC=0.798)and qSOFA score(AUC=0.873)alone(Z=6.541,5.495 and 6.395,P＜0.001).Compared with the survival group,the levels of Syndecan-1,endocan-1 and qSOFA scores were significantly increased in the death group(P＜0.05).The combined prediction of AUC(0.983)was higher than that of Syndecan-1(AUC=0.814),endocan-1(AUC=0.834)and qSOFA score(AUC=0.924)alone(Z=6.596,9.268 and 6.904,P＜0.001).Conclusion Serum levels of Syndecan-1,endocan-1 and qSOFA are increased in patients with sepsis,and the combination of the three has higher clinical value in the diagnosis and prognosis evaluation of sepsis.

Objective To explore the application value of serum Syndecan-1 and endocan-1 combined with rapid sequential organ failure(qSOFA)score in the diagnosis and prognosis of sepsis.Methods The severity of 118 patients with sepsis was divided into the general sepsis group(48 cases),the severe sepsis group(42 cases)and the septic shock group(28 cases).According to the prognosis,patients were divided into the death group(n=32)and the survival group(n=86).A total of 118 healthy volunteers were selected as the control group.Serum Syndecan-1 and endocan-1 levels were detected by enzyme-linked immunosorbent assay(ELISA).The value of serum Syndecan-1,endocan-1 and qSOFA scores in the early diagnosis and prognosis of sepsis was analyzed by receiver operating characteristic(ROC)curve,and the area under the curve(AUC)was compared.Results Compared with the control group,levels of Syndecan-1,endocan-1 and qSOFA scores were increased in the study group(P＜0.05).The serum Syndecan-1,endocan-1 and qSOFA score in the general sepsis group,the severe sepsis group and the septic shock group were significantly increased in sequence(P＜0.05).ROC curve analysis showed that the AUC of serum Syndecan-1,endocan-1 and qSOFA score in the diagnosis of sepsis(0.967)were higher than that of Syndecan-1(AUC=0.868),endocan-1(AUC=0.798)and qSOFA score(AUC=0.873)alone(Z=6.541,5.495 and 6.395,P＜0.001).Compared with the survival group,the levels of Syndecan-1,endocan-1 and qSOFA scores were significantly increased in the death group(P＜0.05).The combined prediction of AUC(0.983)was higher than that of Syndecan-1(AUC=0.814),endocan-1(AUC=0.834)and qSOFA score(AUC=0.924)alone(Z=6.596,9.268 and 6.904,P＜0.001).Conclusion Serum levels of Syndecan-1,endocan-1 and qSOFA are increased in patients with sepsis,and the combination of the three has higher clinical value in the diagnosis and prognosis evaluation of sepsis.

The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.

Objective To investigate the characteristics of the gut microbiota of patients with non-alcoholic fatty liver(NAFLD)damp-heat accumulation syndrome and its correlation with serum metabolites.Methods 40 NAFLD patients with damp-heat accumulation,19 NAFLD patients with depressed liver and deficient spleen and 32 healthy people were selected,using 16 SrRNA amplicon sequencing technology and LC-MS/MS technology to test gut microbiota and serum metabolites.The correlation between gut microbiota and serum metabolites was analyzed using Spearman rank correlation.Results Compared with the healthy control group,the relative abundance of Shigella and Collinsella in the NAFLD with damp-heat accumulation group was higher,and the relative abundance of Bifidobacterium was lower,there was no difference between NAFLD with damp-heat accumulation group and depressed liver and deficient spleen group.Compared with the healthy group and NAFLD with depressed liver and deficient spleen group,the level of L-Tryptophan in NAFLD with damp-heat accumulation group was significantly higher;compared with healthy people,the level of Xanthurenic acid in NAFLD with damp-heat accumulation group increased.L-Tryptophan is negatively correlated with Agrobacterium,and Xanthurenic acid is positively correlated with Acinetobacter,Leuconostoc,and Collinsella.Compared with the healthy group and NAFLD with depressed liver and deficient spleen group,the level of L-Thyroxine in NAFLD with damp-heat accumulation group was significantly lower;compared with healthy people,the level of L-phenylalanine in NAFLD with damp-heat accumulation group was increased,and compared with NAFLD with depressed liver and deficient spleen group,its level was significant decline.L-Thyroxine is negatively correlated with Megamonas,Acinetobacter,and Subdoligranulum.Compared with the healthy control group,the levels of Glycochenodeoxycholate,Deoxycholic Acid,and Glycocholate in the NAFLD with damp-heat accumulation group were significantly higher.Compared with the NAFLD depressed liver and deficient spleen group,the above metabolites were not significantly different.Glycochenodeoxycholate is positively correlated with Collinsella and Agrobacterium,and Glycocholate is positively correlated with Acinetobacter,Leuconostoc,and Shigella.Compared with the healthy control group and NAFLD with depressed liver and deficient spleen group,the levels of Inosine 5'-Monophosphate and guanine nucleoside in NAFLD with damp-heat accumulation group were significantly increased;compared with the healthy control group,the level of uric acid was significantly increased,and there was no significant difference compared with the NAFLD with damp-heat accumulation group.Inosine 5'-Monophosphate was positively correlated with Leuconostoc,negatively correlated with Bifidobacterium,and guanosine was positively correlated with Leuconostoc.Conclusion NAFLD patients with damp-heat accumulation syndrome have gut microbiota imbalance and metabolic disorders.The gut microbiota imbalance of NAFLD with damp-heat accumulation syndrome is closely related to the host tryptophan,phenylalanine,and purine metabolism disorder.

Mechanical allodynia (MA), including punctate and dynamic forms, is a common and debilitating symptom suffered by millions of chronic pain patients. Some peripheral injuries result in the development of bilateral MA, while most injuries usually led to unilateral MA. To date, the control of such laterality remains poorly understood. Here, to study the role of microglia in the control of MA laterality, we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice. Surprisingly, the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA. Moreover, in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons. Consistent with behavioral results, microglial depletion did not prevent the opening of bilateral gates for Aβ pathways in the superficial dorsal horn. This study challenges the role of microglia in the control of MA laterality in mice. Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.
Mice ; Animals ; Hyperalgesia/metabolism* ; Microglia/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Spinal Cord Dorsal Horn/metabolism* ; Ganglia, Spinal/metabolism*

Objective: To evaluate the changes of oral health status and oral health behavior among 12 year old children in Hainan province during 2005-2015, to provide basis for child oral disease prevention. Methods: Through the third and fourth national oral health epidemiology survey, changes in dental caries prevalence rate, dietary habit, oral health behavior, medical care in 12 year old chirdren were analyzed. Results: The percentage of dental caries in permanent, gingival blleeding, dental calculus of 12 year old chirdren in 2005 was 49.9%, 63.2%, 31.5% respectively, which 57.0%, 46.8%, 39.5% respectively in 2015( χ 2=6.78, 36.78, 9.45, P<0.05). The percentage of sugary snacks,drink and milk consumption every day in 2005 was 31.0%, 13.1%, 21.8% respectively, which increased to 40.3%, 27.5%, 30.8% in 2015(χ2=11.53, 38.76, 12.73, P<0.05). 49.3% children had a toothache in 2005, which increased 58.8% in 2015(χ2=23.43, P<0.05). Conclusion The prevalence of dental caries in permanent teeth of 12 year old children in Hainan was high, while eating habits was poor and oral health behavior was showed significant improvement. Oral health education for 12 year old should be strengthened.