Objective To investigate the levels of gross α and gross β activities in different water types within a 40-kilometer radius around the Zhangzhou Nuclear Power Plant prior to its operation. Methods In 2018, drinking water samples were collected from the area surrounding the nuclear power plant during both the wet and dry seasons, including source water, treated water, tap water, and well water. The gross α and gross β activity concentrations were measured using a low-background α/β counter, followed by statistical analysis. Results A total of 80 water samples from different sources around the Zhangzhou Nuclear Power Plant were collected. The average gross α and gross β activity concentrations during the wet season were (0.110 ± 0.036) Bq/L and (0.643 ± 0.028) Bq/L, respectively, while those during the dry season were (0.124 ± 0.032) Bq/L and (0.624 ± 0.026) Bq/L, respectively. There were no significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for the overall sample set (P > 0.05). However, there were statistically significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for source water and well water (Z_wet = −2.005, −2.123; Z_dry = −1.943, −3.090; P < 0.05). Conclusion The radioactivity levels in different water types within various ranges around the Zhangzhou Nuclear Power Plant before its operation were determined. The measured activity concentrations were at the same level as those from previous investigations in other regions of Fujian Province.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To analyze the clinical efficacy and safety of carglumic acid in the treatment of neonatal hyperammonemia caused by organic acidemia.Methods:A case summary was made.Six cases of neonatal hyperammonemia caused by organic acidemia treated at the Neonatal Intensive Care Unit of Henan Children′s Hospital from March to September in 2024 were included.They received comprehensive ammonia-lowering treatment in combination with oral carglumic acid dispersible tablets.The clinical data of the children were collected and analyzed retrospectively.Changes in blood ammonia levels, blood gas parameters, and complete blood count before and after treatment with carglumic acid were analyzed using the Wilcoxon test.The incidence of adverse reactions and clinical regression during the treatment with carglumic acid was observed.Results:There were 2 females and 4 males in the 6 patients included.Four children suffered from isolated methylmalonic acidemia caused by MUT gene mutations, and the other 2 had propionic acidemia.The clinical manifestations were poor breastfeeding in 6 cases, vomiting in 2 cases, poor response in 6 cases, weight loss in 6 cases, and convulsions in 3 cases.Acute metabolic decompensation abnormalities were presented in all children, such as metabolic acidosis, hyperammonemia, leukopenia and thrombocytopenia.The first dose of carglumic acid was 62-255 mg/kg, the second dose was 75-172 mg/kg.The blood ammonia level decreased from 411.7 (339.7, 623.8) μmol/L before treatment to 108.1 (35.5, 229.1) μmol/L after 48 hours of treatment, showing a statistically significant reduction ( Z=2.20, P<0.05).Three cases with a blood ammonia level higher than 400 μmol/L, it was effectively reduced after treatment with carglumic acid.Two cases did not undergo hemodialysis or peritoneal dialysis.One case underwent hemodialysis but died after withdrawing the treatment.After administration of carglumic acid, metabolic acidosis was corrected in all children, and 2 patients ultimately died after discontinuing the treatment.No causal relationship was identified between adverse events and carglumic acid treatment.The examinations at discharge and during the follow-up period (2-7 months) showed that most laboratory abnormalities (including leukopenia, anemia, thrombocytopenia, hyperlactatemia, hyponatremia, hyperkalemia, elevated myocardial enzymes, and hyperbilirubinemia) returned to normal. Conclusions:Carglumic acid can effectively reduce neonatal hyperammonemia caused by organic academia, improve metabolic disorders, and reduce the need for blood purification or peritoneal dialysis, with good safety.

Objective To establish a method for the simultaneous determination of 16 cephalosporin antibiotics of the fourth generation in whole blood by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),including representative drugs such as cefalexin,cefuroxime axetil,cefetamet pivoxil,ceftizoxime,cefodizime,cefteram pivoxil,cefpodoxime proxetil,cefditoren pivoxil,cefminox sodium,cefoperazone,cefpirome,cefoxitin,cefamandole nafate,cefquinome sulfate,cefpiramide,and ceftiofur.Methods Whole blood was pretreated with acetonitrile for protein precipitation and then determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry.The liquid phase used a Hypersil GOLD? C18 column(2.1 mm ×100 mm,1.9 μm).The organic phase was 0.1％formic acid methanol solution,and the aqueous phase was 0.1％formic acid aqueous solution(containing 10 mmol/mL ammonium formate)for gradient elution.Detection was performed in electrospray positive ionization mode with selected reaction monitoring(SRM).Results The 16 drugs showed good linearity within their respective concentration ranges,with R2 values all greater than 0.99.Limits of detection for cefminox sodium and cefpiramide were 50 and 20 ng/mL,respectively,and for the remaining 14 drugs were all lower than 5 ng/mL.The relative standard deviations(RSDs)of intra-day and inter-day precisions at four spiked concentrations for the 16 drugs were all no higher than 10％(n=5).Accuracy ranged within±15％for mosg drugs,except for cefamandole nafate,ceftiofur,and cefetamet pivoxil at the lower limit of quantification,which showed accuracy within±20％.Extraction recoveries exceeded 80％for all compounds.Conclusion This method has high detection sensitivity,rapid speed,and good repeatability for the simultaneously determination of 16 cephalosporin antibiotics in whole blood.

Objective:To explore the value of N-terminal brain natriuretic peptide precursor (NT-proBNP), CHA2DS2-VASc score combined with echocardiography in predicting the prognosis of patients with atrial fibrillation (AF).Methods:A retrospective analysis was performed on 320 AF patients admitted to the First People′s Hospital of Chuzhou from January 2022 to June 2024. All patients completed echocardiography, NT-proBNP blood sample testing, and CHA2DS2-VASc assessment. They were followed up for 6 months or until the occurrence of endpoint events (stroke or all-cause death). According to the prognosis, patients were divided into the endpoint event group and the good prognosis group. The clinical data of the two groups were compared. Multivariate logistic regression analysis was used to screen the influencing factors of endpoint events in AF patients. Receiver operating characteristic (ROC) curve was applied to analyze the predictive value of NT-proBNP, CHA2DS2-VASc score and echocardiography for the prognosis of AF patients.Results:By the end of follow-up, among 320 AF patients, 64 cases (20.00%) had endpoint events, including 33 cases (10.31%) of stroke and 31 cases (9.69%) of all-cause death; 256 cases (80.00%) had no endpoint events. The age, CHA2DS2-VASc score, proportion of New York Heart Association (NYHA) cardiac function grade Ⅳ, proportion of complicated type 2 diabetes, proportion of complicated peripheral vascular disease, left atrial diameter (LAD), left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), logarithm of NT-proBNP, and C-reactive protein (CRP) level in the endpoint event group were all higher than those in the good prognosis group (all P<0.05). The hemoglobin (Hb) level, left ventricular ejection fraction (LVEF), and proportions of lipid-lowering and anticoagulant drug treatments were lower than those in the good prognosis group (all P<0.05). Multivariate logistic regression analysis showed that CHA2DS2-VASc score and NT-proBNP were independent risk factors for poor prognosis in AF patients (all P<0.05), and anticoagulant and lipid-lowering drug treatments were independent protective factors (all P<0.05). The sensitivity, specificity, and area under the ROC curve (AUC) of NT-proBNP, CHA2DS2-VASc score combined with echocardiography in predicting the prognosis of AF patients were 90.63%, 95.31%, and 0.927, respectively. The specificity and AUC of the combined prediction were higher than those of single assessment (all P<0.05), and there was no significant difference in sensitivity compared with single prediction (all P>0.05). Conclusions:NT-proBNP, CHA2DS2-VASc score, and echocardiography all have certain predictive value for the prognosis of AF patients, but the combined prediction value of the three is higher.

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 The aim of this study was to explore the effects of changes in the estrogen receptor alpha 36(ER-α36)expression on the proliferation and membrane-initiated estrogen signaling in glioblastoma U251 cells.Methods The expression and localization of ER-α36 and EGFR glioblastoma U87 cells and U251 cells were determined by immunofluorescence,qRT-PCR and Western blot.The effect of upregulating ER-α 36 on U251 cell proliferation and estrogen signaling pathway activity by low con-centrations of 100 pmol/L icariin isomer(SNG162)was detected by MTT assay and Western blot.Results ER-α36 and EGFR were co-expressed in the cell membrane of glioblastoma.Compared with DMSO(control group),the expression ER-α36(P<0.01)and EG-FR increased in U251 cells treated with SNG162(P<0.05);Further experments also found that low concentrations of SNG162 in-creased the expression of cycle related proteins-cyclin D1,cyclin B,cyclin E and CDK4(P<0.01),and enhanced the proliferative a-bility of U251 cells(P<0.05).Conclusion The low concentration of SNG162 upregulates the expression of ER-α36,activates the estrogen-mediated ERK1/2 MAPK,p38 MAPK,and EGFR/Src signaling pathways,promotes glioblastoma proliferation,and activates the membrane initialized estrogen signaling pathway.

Objective To investigate the status of feeding intolerance in patients with enteral nutrition after lung transplantation and analyze its influencing factors,to provide a reference for formulating a reasonable enteral nutrition plan and improving patients'nutritional status.Methods Convenient sampling method was used to retrospectively collect the clinical data of 115 patients who received enteral nutrition support after lung transplantation and were hospitalized in the ICU of a tertiary hospital in Guangdong Province from August 2022 to November 2023.According to the occurrence of feeding intolerance during ICU hospitalization,the patients were divided into a feeding tolerance group and a feeding intolerance group.Univariate and logistic regression analysis were used to analyze the influencing factors of feeding intolerance patients with enteral nutrition after lung transplantation.Results Within 7 days of initiating enteral nutrition,a total of 63 patients developed feeding intolerance,with an incidence of 54.78％.Among them,the incidence of feeding intolerance was relatively high within 1 to 3 days after initiating enteral feeding.The clinical manifestations of feeding intolerance were diarrhea,bloating,gastric retention,vomiting/regurgitation,among which the diarrhea was the highest incidence(87.30％).Logi-stic regression analysis showed that intraoperative net balance volume(OR=0.999),intraoperative blood transfusion(OR=1.001)volume and diabetes history(OR=0.170)were independent influencing factors for feeding intolerance in patients with enteral nutrition after lung transplantation(P＜0.05).Conclusion There was a high incidence of feed-ing intolerance in patients with enteral nutrition after lung transplantation.Patients undergoing lung transplantation who have a high net intraoperative fluid balance,receive a low volume of intraoperative blood transfusions,and have a history of diabetes are at a lower risk of developing feeding intolerance when receiving postoperative enteral nutrition.When starting enteral nutrition,medical staff should dynamically evaluate the risk factors of feeding intolerance,screen high-risk patients as early as possible,and formulate reasonable enteral nutrition programs to improve the nutritional status of patients and promote their rehabilitation.