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.

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Objective:To investigate the impact and interaction of Toll like receptor 2 (TLR2) and interferon regulatory factor 5 (IRF-5) gene polymorphisms on the susceptibility to neonatal sepsis.Methods:A total of 78 cases of neonatal septicemia patients admitted to Baoding Children′s Hospital from July 2018 to August 2021 were prospectively selected as the study group, and 78 cases of healthy newborns in the same period were selected as the control group. The TLR2 and IRF-5 gene polymorphisms and the levels of inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in different genotypes of infants were compared between the two groups. We evaluated the relationship between TLR2 and IRF-5 genotypes, inflammatory markers, and susceptibility to neonatal sepsis, and analyzed the interaction between their gene polymorphisms and susceptibility to neonatal sepsis.Results:There were significant differences in the distribution of TLR2 (rs3804099) and IRF-5 (rs2004640) loci genotype and Allele frequency between the two groups (all P<0.05); The serum CRP, TNF-α, and IL-6 levels in children with TLR2 (rs3804099) genotype TT genotype [(111.12±30.87)mg/L, (77.50±20.02)pg/ml, (40.27±11.31)pg/ml] were higher than those in children with CC/CT genotype [(72.46±24.51)mg/L, (54.18±17.65)pg/ml, (28.34±9.05)pg/ml], and the differences were statistically significant (all P<0.05). The serum CRP, TNF-α, and IL-6 levels [(113.90±28.94)mg/L, TNF-α (79.84±19.82)pg/ml, IL-6 (41.05±11.49)pg/ml] in children with the IRF-5 (rs2004640) TT genotype were higher than those in children with the GG/GT genotype [(70.88±22.16)mg/L, (52.27±16.73)pg/ml, (27.96±9.75)pg/ml], and the differences were statistically significant (all P<0.05). The TT genotypes at TLR2 (rs3804099) and IRF-5 (rs2004640) loci were positively correlated with serum CRP, TNF-α, and IL-6 levels (all P<0.05); The TT genotypes at TLR2 (rs3804099) and IRF-5 (rs2004640) loci were independent risk factors for susceptibility to neonatal sepsis (all P<0.05); The TT genotype at the TLR2 (rs3804099) locus and the TT genotype at the IRF-5 (rs2004640) locus exhibited a positive interaction in susceptibility to neonatal sepsis ( OR=7.467, γ=1.728). Conclusions:TLR2 (rs3804099) TT genotype and IRF-5 (rs2004640) TT genotype significantly increase the susceptibility to neonatal sepsis, and there is a positive interaction between the two.

Objective: To investigate the nutritional status and associated factors of vitamin D among children aged 0 to 12 years old in Chongqing. Methods: From January 2019 to December 2021, 1 877 children aged 0-6 years who received regular child health care were randomly selected from Chongqing maternal and child health hospital, and 707 school age children were also selected from three primary school in Chongqing for investigation. The serum sample were collected for detecting serum 25 (OH) D level by chemiluminescence method, and the possible influencing factors of vitamin D deficiency (VDD) were analyzed. Results: The average serum 25 (OH) D concentration of children was (39.9±9.1) ng/mL with the positive rate of VDD was 14.59%. There were significant differences of VDD positive rate in different age, visiting time, visiting season, body shape, outdoor activity time and vitamin D supplementation (0-3 years old vs 4-6 years old vs 7-12 years old: 14.73% vs 22.19% vs 10.47%; visiting season: spring vs summer vs autumn vs winter: 12.97% vs 10.65% vs 14.86% vs 21.33%; pre COVID 19 epidemic vs post COVID-19 epidemic: 11.18% vs 17.08%; underweight or normal vs overweight or obesity: 12.34% vs 26.13%; adequate outdoor activity time vs inadequate:11.84% vs 16.27%; regular vitamin D supplementation vs irregular vitamin D supplementation: 11.71% vs 15.62% )( χ 2=26.17, 17.59, 30.98, 53.74, 9.60, 6.17, P <0.05). Underweight or normal body weight, sufficient outdoor activities and regular vitamin D supplementation were associated with less vitamin D deficiency with OR(OR95%CI ) at 0.68(0.55-0.84), 0.57 (0.25-0.77) and 0.62(0.44-0.85)( P <0.05). Conclusion The prevalence of VDD among preschool and school age children is high in Chongqing. Integrated prevention and control strategies incluing overweight or obesity control, increasing outdoor activities and oral vitamin D supplements should be taken.

Objective To investigate the clinical characteristics,antibiotic susceptibilities and serotypes of Group B Streptococcus(GBS)isolated from neonatal meningitis to provide references for the prevention and treatment of neonatal GBS meningitis. Methods From June 2013 to June 2016,we surveyed the GBS strains iso-lated from purulent meningitis of < 90 days infants from Guangzhou Women and Children′s Medical Center. The GBS isolates were identified and the minimum inhibitory concentration of the antibiotics was determined by Vitek 2 Compact automatic bacterial identification system.GBS serotyping was performed using Strep-B-Latex?rapid latex agglutination test kit. Results A total of 46 cases of neonatal GBS meningitis,15 cases of early-onset infection and 31 cases of late-onset infection were diagnosed. 78.3% of GBS meningitis with varying degrees of complica-tions.Among 41 survivors with 3~24 months follow-up,50% of the early-onset and 44.8% of the late-onset GBS meningitis with varying degrees of neurological sequelae.Four capsular types were identified among the 46 isolates, serotype-Ⅲwas the most prevalent(73.9%),followed by Ib(19.6%),V(4.3%)and Ia(2.2%).All the isolates were susceptible to penicillins,cephalosporins,linezolid and vancomycin. Conclusion The highly pathogenic serotype-Ⅲ was the predominant serotype among neonatal GBS meningitis in Guangzhou,Therefore,it is neces-sary to strengthen the epidemiological surveillance of GBS invasive infection and the effective implementation of pre-ventive measures.

ABSTRACT:In the present study ,we aimed to identify differentially expressed proteins between induced worms (the infec‐ted mice were treated intragastrically with ED50 PZQ) and uninduced worms (control group) for clarifying the mechanism of PZQ .ED50 PZQ was used to administrate mice that were infected with S .japonicum via intragastric incubation for consecutive‐ly 30 days .Twenty‐one days later ,mice were sacrificed after treatment with 200 mg/kg PZQ for continuously five days ,and the male worms were obtained and some of them were subjected in DMEM medium with different concentrations of PZQ in vitro for 16 hours .Then the worms were washed twice and incubated in PZQ‐free medium for 72 hours .Compared with control group ,the induced worms had lesser sensitivity to PZQ .The survival rate of induced worms was 75 .6% in vitro when the con‐centration of PZQ was 112 mol/L (the concentration was 8 times of uninduced worms Lethal Concentration ) ,significantly higher than that in the uninduced worms (11 .1% ,P<0 .05) ,showing obviously tolerance .The other induced and uninduced worms were acquired and collected for 2D‐DIGE and MALDI‐TOF‐MS ,and combined with bioinformatics to analyse the func‐tion of the identified protein .Thirty differential expression proteins were confirmed between induced and uninduced worms ,in‐cluding 12 proteins up‐regulated and 18 proteins down‐regulated .These proteins respectively ascribed to cytoskeleton‐associat‐ed protein ,glucose and energy metabolism enzymes ,stress proteins ,thioredoxin peroxidase enzymes ,and other protease .Up‐or down‐regulation of these differential proteins indicated that PZQ promote or inhibit the expression of some specific genes . These findings may help to clarify the mechanism of PZQ ,simultaneously ,providing a scientific basis for exploring new vaccine candidate antigens and targets for drug therapy .