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.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To investigate human factors underlying radiotherapy planning safety incidents and quantitatively explore their interrelationships.Methods:A total of 1 619 safety incidents recorded in the automated plan checking system developed by West China Hospital of Sichuan University were utilized. Human factors were identified and statistically analyzed using the Human Factors Analysis and Classification System (HFACS). A Bayesian network model was developed and combined with sensitivity analysis for quantitative assessment.Results:Key contributing factors included organizational processes (12.89%), inadequate supervision (11.85%), and personnel factors (13.50%). Utilizing the established HFACS Bayesian network hybrid model in conjunction with sensitivity analysis, it has been found that the most significant influences on skill‐based errors and decision errors were condition of operators and environmental factors, with corresponding indices of 0.96 and 0.76. Additionally, personnel factors had the greatest impact on routine, with an index of 3.51.Conclusions:Key contributing factors span all HFACS levels, with organizational processes, supervision, personnel, and condition of operators each playing a significant role. Upstream factors — such as organizational climate, environment factors, and personnel factors — strongly influence downstream risks. These offer actionable insights for developing targeted safety protocols.

Objective:To analyze the application of antitoxin therapy in severe infant botulism.Methods:A retrospective analysis was conducted on 14 cases of severe infant botulism treated at 3 pediatric medical centers from July 2020 to August 2024. This study investigated antitoxin dosage, treatment duration, discontinuation criteria and adverse reactions.Results:A total of 14 cases (12 males and 2 females) were included, with an age of 5.0 (3.8, 7.0) months. Botulinum toxin typing revealed 10 cases of Type B, 2 cases of Type A and 2 untyped cases. The interval from symptom onset to antitoxin administration was 9.0 (6.0, 11.5) d. The initial dosage of type A antitoxin was 12 500 (10 000, 22 500) U, while type B was 5 000 (5 000, 5 000) U. The dosage was tapered in some cases after symptom improvement, the duration of treatment was 16.5 (9.8, 25.3) d. In total, 11 infants discontinued medications after improvement in muscle strength, while 3 infants discontinued treatment after obtaining negative results from fecal mouse bioassays. Adverse events were reported in 2 cases, both of which resulted in rash, and 1 case was complicated with anaphylactic shock. All the patients survived upon discharge with a follow-up period of 11 d to 3 years and 8 months. Totally 12 infants had fully recovered, while 2 infants were still recovering after discharge.Conclusion:Antitoxin therapy is a feasible and safe approach which showed favorable prognosis in severe infant botulism.

OBJECTIVES: The major histocompatibility complex class I chain-related gene A (MICA), a component of the human leukocyte antigen (HLA) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among MICA gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism. METHODS: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. MICA genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of MICA alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined. RESULTS: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified MICA alleles. The most common alleles in the rosacea group were MICA*010:01, MICA*008:04, and MICA*019:01. The frequencies of MICA*002:01 and MICA*027 were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and MICA*010:01 were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all P<0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of MICA-A4 and MICA-A9 were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas MICA-A6 was higher (10.12% vs 4.03%; all P<0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C₃₆+M₁₂₉+K₁₇₃+G₂₀₆+W₂₁₀+S₂₁₅) and Type II (Y₃₆+V₁₂₉+E₁₇₃+S₂₀₆+R₂₁₀+T₂₁₅). Type I MICA variants were significantly associated with rosacea susceptibility. CONCLUSIONS MICA gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the MICA gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans ; Polymorphism, Single Nucleotide ; Histocompatibility Antigens Class I/genetics* ; Rosacea/genetics* ; Genetic Predisposition to Disease/genetics* ; Female ; Male ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Haplotypes ; Case-Control Studies ; Aged ; High-Throughput Nucleotide Sequencing

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

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.

Objective To investigate the differences in BMD,T-scores,lumbar HU values,and modified VBQ scores in patients with thoracolumbar fractures,analyze their correlations,and evaluate their predictive efficacy for thoracolumbar fractures.Methods Patients with thoracolumbar fragility fractures and hospitalized in the Department of Orthopedics at the Second Affiliated Hospital of Kunming Medical University from January 2022 to March 2025 were retrospectively enrolled.Among them,132 eligible patients were divided into the fracture group(n=63)and the non-fracture group(n=69).BMD and T-scores of L1～L4 vertebrae were measured via DEXA,lumbar HU values were obtained from CT scans,and modified VBQ scores were calculated using lumbar MRI.Intergroup comparisons were performed using independent samples t-tests.Pearson's correlation analysis was used to assess the relationships among BMD,T-scores,HU values,and modified VBQ scores.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate their predictive performance for thoracolumbar fractures.Results The fracture group exhibited significantly lower mean BMD,T-scores,and HU values in L1～L4 compared to the non-fracture group,while modified VBQ scores were significantly higher(P<0.001).Correlation analysis revealed a significant positive correlation between BMD,T-scores,and HU values in L1～L4,whereas all three parameters showed a significant negative correlation with modified VBQ scores(P<0.001).The AUC values for predicting thoracolumbar fractures were 0.826(T-score),0.836(BMD),0.759(HU value),and 0.875(modified VBQ score),with optimal cutoff thresholds of-1.65(T-score),0.836 g/cm2(BMD),68.4(HU value),and 3.01(modified VBQ score),respectively.Conclusion BMD,T-scores,HU values,and modified VBQ scores in L1～L4 vertebrae are significantly correlated and can serve as the predictive indicators for thoracolumbar fractures.Among them,the modified VBQ score demonstrates the best predictive performance,making it a valuable auxiliary tool for assessing the vertebral bone quality.

OBJECTIVE To summarize the current situation of pharmaceutical clinic service in our hospital over the past five years， and explore sustainable development strategies for service models of pharmaceutical clinics. METHODS A retrospective analysis was conducted on the consultation records of patients who registered and established files at the pharmaceutical clinic in our hospital from January 2019 to December 2023. Statistical analysis was performed on patients’ general information， medication- related problems， and types of pharmaceutical services provided by pharmacists. RESULTS A total of 963 consultation records were included， among which females aged 20-39 years accounted for the highest proportion （66.04%）； obstetrics and gynecology- related consultations accounted for the largest number of cases. Additionally， 80 patients attended follow-up visits at our hospital’s pharmaceutical clinic. A total of 1 029 medication-related issues were resolved， including 538 cases of drug consultations （52.28%）， 453 medication recommendations （44.02%）， 22 medication restructuring（2.14%）， and 16 medication education （1.55%）； the most common types of medication-related problems identified were adverse drug events（70.07%）. CONCLUSIONS Although the pharmaceutical clinic has achieved recognition from clinicians and patients， challenges such as low awareness among healthcare providers and the public persist. Future efforts should focus on strengthening information technology construction， enhancing pharmacist training， and establishing various forms of outpatient pharmaceutical service models.