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.

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 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.

Objective:To explore the association between vitamin A, E and recurrent respiratory tract infections (RRTIs) in children.Methods:1 853 children with RRTIs and 2 695 health children were separately selected as cases and controls. Propensity score matching (PSM) analysis were conducted to reducing confounding bias between groups. Blood samples were collected to measure serum levels of vitamins A and E by high performance liquid chromatographie (HPLC). Paired logistic regression was used to determine odds ratios ( OR) and 95% confidence intervals ( CI) to evaluate the association of RRTIs with the serum levels of vitamin A and E. Results:After propensity score estimation and 1∶1 matching, the study cohort included 1 507 cases with RRTIs and 1 507 health children as controls. The main characteristics between the two groups were all not significantly different after matching ( P>0.05). The average levels of vitamin A in two groups were different ( P<0.05). Paired logistic regression analysis showed that greater serum levels of vitamin A had a lower risk of RRTIs ( OR=0.46, 95% CI: 0.22-0.98), similarly, deficiency of vitamin A would also increase the risk of RRTIs ( OR=1.18, 95% CI: 1.00-1.38). The statistical difference was not found between VitE and RRTIs ( P>0.05). Conclusions:The serum levels of vitamin E didn′t have a statistically significant association with RRTIs. However, we observed an obvious association between vitamin A and RRTIs. Hence vitamin A clinical monitoring and supplementation are vital for preventing and treating RRTIs.

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.

Objective: To evaluate ten year changes in deciduous teeth health and oral health behavior aged 5 year old children in Hainan province (during the year of 2005-2015), to provide basis for oral health promotion among 5 year old children in Hainan province. Methods: Through the comparison and analysis of the third and the fourth national oral health epidemiology survey,changes of dental caries prevalence rate, dietary habit, oral health behavior, and health seeking behavior were analyzed. Results: The prevalence of dental caries in 2005 was 76.1%, 2015 was 82.3% which had significant difference(χ2=6.23，P<0.05), the percentage of consuming sugary food and sweet drinks every day in 2005 was 13.4% and 6.1%, which increased to 30.0% and 7.4% respectively in 2015. The percentage of drinking milk and yoghurt with sugar was 47.6%, which decreased 36.5% in 2015 (χ2=12.76，P<0.05), the percentage of consuming sugary food and sweet drinks before going to bed in 2005 was17.8%, which decreased to 13.3% in 2015 (χ2=32.27，P<0.05). The percentage of brushing the teeth two or more times a day was 16.9%, which increased to 24.2% in 2015(χ2=20.50，P<0.05). The percentage of using fluoridated toothpaste decreased from 31.7% (2005) to 7.4% (2015) (χ2=229.13，P<0.05). No need to treatment for baby teeth and afraid of pain among children were the main reason for no health-seeking among parents which children of dental health problems,which deffered significantly between 2005 and 2015(χ2=6.05，9.34，P<0.05). Conclusion Children’s oral health behavior improved, while eating habits fluoridated toothpaste usage and health seeking behavior remain poor.Health education on child oral health should be strengthened.

OBJECTIVE： To study the effects of ADRB2 （rs1042713） gene polymorphism on therapeutic efficacy of anticholinergic drug in the treatment for refractory asthma pediatric patients. METHODS： 171 children with refractory asthma were selected from outpatient department of Kunming Children’s Hospital during Nov. 2016 to Jul. 2019. The distribution of ADRB2 （rs1042713） genotype， the clinical efficacy [asthma control test （C-ACT） score， FEV1， FVC， PEF， maximal mid-expiratory flow （MMEF）] of anticholinergic drug were analyzed statistically； the response of different genotypes to the use of anticholinergic drug were also analyzed statistically. RESULTS： 148 of 171 refractory asthmatics pediatric patients were administered anticholinergic drug， among them 50 of the 71 AA genotype and 36 of the 77 GA genotype responded to anticholinergic drug treatment. Statistical analysis showed that 71 children with AA refractory asthma had improved C-ACT score， FEV1， FVC， PEF and MMEF， there was statistical significance， compared with GA genotype （P＜0.05）； the response rate of the AA genotype to anticholinergic drugs was 2.71 times that of the GA genotype [OR＝2.71， 95％CI （1.38， 5.34）， P＝0.005]. CONCLUSIONS： The detection of ADRB2 （rs1042713） gene polymorphism has some guiding significance in the treatment of refractory asthma with anticholinergic drugs， and the response of AA genotype is better.

Objective To evaluate the relationship between the degree of brain injury during the perioperative period of liver transplantation and postoperative cognitive dysfunction (POCD).Methods Thirtythree patients,undergoing elective liver transplantation,were enrolled in this study.Before induction of anesthesia (T0),at 5 min before blocking the portal vein (T1),5 min after opening the portal vein (T2),5 min after opening the hepatic artery (T3),and at 24 h after surgery (T4),blood samples were collected from the central vein for determination of the serum concentrations of S1O0β protein and neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay.Patients were divided into POCD group and control group (group C) according to whether POCD happened within 7 days after surgery.Results Compared with the baseline value at T0,the serum concentrations of S100β protein were significantly increased at T2 and T3,and the serum concentrations of NSE was increased at T3 (P＜0.05).There was no significant difference in serum concentrations of S100β and NSE at each time point between group POCD and group C (P＞0.05).Conclusion The degree of brain injury during the perioperative period of liver transplantation is not the dominant factor for the development of POCD in the patients.

Objective To investigate the level of caregivers′burden and the coping style among parents of cancer children. Methods Totally, 229 parents of cancer children participated in the investigation by Chinese version of zarit burden interview (ZBI), Chinese version of coping health inventory for parents (CHIP) and self-designed general information questionnaire. The associations between caregivers′burden and coping styles were tested by Spearman correlation analysis. Results The caregiver′s burden on the parents was in the middle level with a total score of (30.50 ± 12.24). The coping style the parents took most frequently was to unite the family and keep a positive attitude and regard it as most effective. The caregiver′s burden was negatively associated with the positive coping style . Conclusion The parents of cancerous children suffer from middle level of burden . Nurses should assess the caregiver′s burden, provide targeted interventions to relieve it, help the to establish effective coping style and change their psychological and mental state and ultimately improve their quality of life.