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 current status of clinical practice of optical surface guided radiation therapy (SGRT) technology in China.Methods:A survey questionnaire was designed based on a similar investigation conducted by the European Society for Radiotherapy and Oncology in collaboration with the American Association of Physicists in Medicine on SGRT. The questionnaire covered aspects such as the installation, implementation, commissioning, quality assurance, clinical application, challenges, and cost considerations of SGRT systems. An online questionnaire was distributed to 49 institutions in China that have installed or are in the process of installing SGRT systems. Data were summarized and analyzed using Excel and SPSS 29 software.Results:Among the 49 institutions, 96% had at least one SGRT system. In terms of commissioning, quality assurance and implementation, it was mainly operated by physicists (94%) and technicians (82%), the cycle of test items for quality assurance was only achieved by the highest percentage of units with end-to-end test items for the annual inspection (50%). Eighty-six percent of the institutions used phantoms provided by suppliers, and 53% followed supplier recommendations or guidelines. For the installation of the first SGRT system, 37% of the institutions reported that initial staff training required more than 48 hours, while 73% found the training content easy to understand. Regarding the clinical application of SGRT technology, the majority of the institutions (53%) had used it for 1-3 years, with breast radiotherapy being the most commonly used treatment site. The primary scenario of SGRT application was intra-fraction motion monitoring / patient monitoring (69%). Furthermore, 47% of the institutions combined SGRT with open-face masks, and 71% used visual feedback devices for breath-hold or free-breathing gating. In terms of treatment thresholds, the median thresholds for monitoring and positioning were the same for breast, abdominopelvic (non- stereotactic body radiation therapy), and head-and-neck (non-brain stereotactic radiosurgery) treatments but varied for other sites.Conclusions:Although SGRT technology requires a relatively long initial training period, it is generally well accepted in terms of training and operation. Clinically, SGRT has been widely applied in breast radiotherapy, playing a crucial role in patient monitoring and intra-fraction motion management. However, most institutions have had limited clinical experience with the technology, highlighting the need for continuous technical supervision and improvement. The establishment of standardized protocols is necessary to ensure broader clinical adoption and long-term effectiveness.

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

OBJECTIVE: To investigate the association between long-term exposure to ambient fine particulate matter (PM _2.5) and its constituents and the risk of incident type 2 diabetes mellitus (T2DM), and to examine the modification roles of overweight status. METHODS: This prospective study included 27,507 adults living in rural China. The annual mean residential exposure to PM _2.5 and its constituents was estimated using a satellite-based statistical model. Cox models were used to estimate the risk of T2DM associated with PM _2.5 and its constituents. Stratified analysis quantified the role of overweight status in the association between PM _2.5 constituents and T2DM. RESULTS: Over a median follow-up of 9.4 years, 3,001 new T2DM cases were identified. The hazard ratio ( HR) for a 10 μg/m ³ increase in ambient PM _2.5 was 1.30 (95% confidence interval [ CI]: 1.17, 1.45). Among the constituents, the strongest association was observed with black carbon. Being overweight significantly modified the association between certain constituents and the risk of T2DM. Participants who were overweight and exposed to the highest quartile of PM _2.5 constituents had the highest risk of T2DM ( HR: 2.46, 95% CI: 2.04, 2.97). CONCLUSIONS Our findings indicate that PM _2.5 was associated with an increased risk of T2DM, with black carbon potentially being the primary contributor. Being overweight appeared to enhance the association between PM _2.5 and T2DM. This suggests that controlling both PM _2.5 exposure and overweight status may reduce the burden of T2DM.
Humans ; Diabetes Mellitus, Type 2/chemically induced* ; China/epidemiology* ; Particulate Matter/analysis* ; Overweight/epidemiology* ; Female ; Male ; Middle Aged ; Rural Population ; Air Pollutants/analysis* ; Adult ; Prospective Studies ; Environmental Exposure/adverse effects* ; Aged ; Risk Factors

Objective:To explore the protective effect of sesquiterpene lactones of Eupatorium lindleyanum DC.(SLEL)on lipopolysac-charide(LPS)-induced acute lung injury(ALI)in rats using metabolomics.Methods:Forty-eight male SD rats were randomly divided into a blank control group(CG),a model control group(MG),low-,medium-,and high-dose SLEL groups(50,100,and 200 mg/kg),and a positive control group(dexamethasone acetate tablets,5 mg/kg).CG and MG groups were given phosphate-buffered saline.All groups received intragastric administration at a dose volume of 10 mL/kg once a day for 7 consecutive days.One hour after the last ad-ministration,LPS(5 mg/kg)was instilled into the trachea of all groups except the CG group to establish the ALI rat model.Twenty-four hours after model establishment,blood was collected from the abdominal aorta and bronchoalveolar lavage fluid(BALF)was col-lected from the left lung.The total number of inflammatory cells,neutrophils,lymphocytes,and eosinophils in BALF was counted by Wright-Giemsa staining.The levels of interleukin-18(IL-18)and interferon-γ(IFN-γ)in serum and BALF were measured by enzyme-linked immunosorbent assay.The pathological changes of lung tissue were observed using hematoxylin-eosin staining.The ex-pression levels of tight junction protein-1(ZO-1)and occludin in lung tissue were determined by Western blot.The mRNA expression levels of IL-18,IFN-γ,ZO-1,and occludin in the lung were measured by real-time fluorescence quantitative PCR.Non-targeted me-tabolomics analysis of serum and lung tissue was performed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.Results:Compared with the MG group,all SLEL groups had significantly reduced wet/dry weight ratio of lung tissue,lung coefficient,and total number of inflammatory cells,neutrophils,lymphocytes,and eosinophils in BALF.SLEL signifi-cantly decreased the levels of IL-18 and IFN-γ in serum and BALF and the mRNA expression of IL-18 and IFN-γ in lung tissue,and significantly promoted the protein and mRNA expression of ZO-1 and occludin.Under light microscopy,the degree of lung tissue edema,alveolar hemorrhage,and inflammatory cell infiltration were significantly reduced,indicating a certain protective effect on ALI rats.The results of non-targeted metabolomics studies showed that there were 91 and 33 significantly different metabolites in the serum and lung tissue of rats treated with SLEL,respectively.Among them,the main differential metabolites in the serum were sphingosine,L-lactic acid,nicotinic acid,D-nucleotide,and mevalonate-5P,while the main differential metabolites in the lung tissue were tauro-cholic acid.This suggests that SLEL may mainly affect the metabolic pathways of sphingolipids,pyruvate,nicotinic acid,nicotinamide,and tryptophan in the serum and the metabolic pathways of taurine and hypotaurine in the lung tissue to improve ALI.Conclusion:SLEL has a significant protective effect on rats against LPS-induced ALI,and its mechanism of action may be related to the inhibition of inflammatory factors,improvement of lung barrier function,and regulation of related metabolic pathways.

Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.

Objective To explore the evaluation value of serum follistatin like protein 1(FSTL1)and glu-cose regulatory protein 78(GRP78)on disease severity and readmission in elderly patients with chronic ob-structive pulmonary disease(COPD).Methods A total of 100 elderly COPD patients(COPD group)treated in this hospital from March 2020 to May 2023 were selected as COPD group,and were divided into grade Ⅰ(35 cases),grade Ⅱ(46 cases)and grade Ⅲ(19 cases)according to the severity of the disease.Another 100 elderly volunteers who underwent physical examination during the same period were selected as the control group.Serum FSTL1 and GRP78 levels were detected by enzyme-linked immunosorbent assay(ELISA).Spearman and Pearson correlation were used to analyze the correlation between serum FSTL1 and GRP78 lev-els and general data.The evaluation value of serum FSTL1 and GRP78 levels in COPD patients on disease se-verity and readmission was analyzed by receiver operating characteristics(ROC)curve.Results Compared with the control group,serum levels of FSTL1 and GRP78 in COPD group were significantly increased(P＜0.05).Serum levels of FSTL1 and GRP78 in COPD patients increased with the severity of the disease(P＜0.05).Compared with non-readmission group,the serum levels of FSTL1 and GRP78 in readmission group were significantly increased(P＜0.05).Spearman correlation analysis showed that serum FSTL1 and GRP78 levels were positively correlated with smoking history,hypertension history and disease severity(P＜0.05).Pearson correlation analysis showed that serum FSTL1 and GRP78 levels were negatively correlated with arte-rial oxygen pressure(PaO2),the ratio of forced expiratory volume in the first second to forced vital capacity(FEV1/FVC),and the percentage of forced expiratory volume in the first second to expected value(FEV1％pred),with significance(P＜0.05),while it was positively correlated with the partial pressure of carbon diox-ide(PaCO2),with significance(P＜0.05).ROC curve analysis showed that serum FSTL1,GRP78 and their combined assessment of disease severity and readmitted area under the curve(AUC)were higher in COPD pa-tients,and the combination was significantly better than the single assessment(P＜0.05).Conclusion Serum levels of FSTL1 and GRP78 are significantly increased in COPD patients,which are correlated with the severi-ty of the disease and have a high value in evaluating the severity of the disease and readmission.

Hematologic malignancies,such as lymphoma,myeloma,and myeloid neoplasms,can occur in extramedullary tissues.Traditional histopathological morphology and immunohistochemical staining have lim-itations,including time-consuming specimen processing,prolonged reporting cycles,and relatively low sensi-tivity in cases of limited cell numbers.Flow cytometry offers significant advantages in detecting tissue sam-ples,such as rapid processing,shorter reporting cycles,and high accuracy and sensitivity,making it an effective complement to histopathological and immunohistochemical methods.However,the application of flow cytome-try in tissue sample detection currently lacks standardized protocols for sample collection and preservation,single-cell suspension preparation,antibody panel design for limited samples,data analysis,and result repor-ting.To promote the standardized application of flow cytometry in detecting hematologic tumor cells in tissue samples,the Cell Analysis Professional Committee of the Chinese Society of Biotechnology organized experts to develop the Chinese Expert Consensus on Flow Cytometry for Detecting Hematologic Tumor Cells in Tis-sue Samples(hereinafter referred to as the Consensus).This Consensus elaborates on the technical aspects of flow cytometry for tissue sample detection,covering sample processing,antibody panel design,data analysis,reporting content,and quality management.It particularly emphasizes recommended antibody panels and data analysis methods for flow cytometry when tissue sample cell counts are low.This article aims to interpret the key points of the Consensus to facilitate its better application in clinical practice.