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.

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.

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*

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 separation efficiency of three physical separation methods for gaseous ¹⁴C, namely membrane separation, adsorption separation, and low-temperature separation, to screen for the optimal separation method, and to provide a reference for the separation and enrichment of ¹⁴CO₂ in online monitoring of ¹⁴C. Methods The experimental plan was designed, and three devices were constructed for separation and purification experiments. The purity, recovery rate, and separation time of CO₂ separated by the three methods were analyzed. Results All the three methods achieved the separation of CO₂. Under certain conditions, 20 mL of sample gas was obtained. The separation time of membrane separation method was 0.5 hour, CO₂ gas with a sample purity of 0.0486%-0.0488%VOL was obtained, and the recovery rate was only 2.5%−12.7%. The separation time of MOF material adsorption separation method was 24−30 hours, CO₂ gas with a sample purity of 20.2%−47.5%VOL was obtained, and the recovery rate was 57.3%−63.2%. The separation time of low-temperature separation method was 3 hours, CO₂ gas with a sample purity of 96.0%−99.8%VOL was obtained, and the recovery rate was 81.5%−92.5%. Conclusion The purity and recovery rate of CO₂ with low-temperature separation method were higher compared to membrane separation method and MOF material adsorption separation method. The separation time of low-temperature separation method was moderate. The low-temperature separation method can provide a reference for the enrichment technology of ¹⁴C in the rapid measurement of gaseous ¹⁴C effluent.

Objective:To investigate the regulative effects of Streptococcus mutans (Sm) antisense vicK RNA (ASvicK) on the multi-species biofilm formed by three common oral streptococci (Sm, Streptococcus sanguinis, and Streptococcus gordonii) (Sm+Ss+Sg). Methods:ASvicK over-expression strain was constructed by using a recombinant plasmid, and three-species biofilm UA159+Ss+Sg and ASvicK+Ss+Sg were cultured. The phenotypes of biofilms were detected by scanning electron microscopy (SEM). Crystal violet (CV) assay was used to detect biofilm biomass. Lactate kit and anthrone-sulfuric acid colorimetric assay were used to determine the abilities of lactic acid and exopolysaccharides production, respectively. The proportions of three-species and expression levels of the cariogenic-related genes in biofilms were detected by TaqMan fluorescence quantitative PCR and real-time fluorescence quantitative PCR. A biofilm demineralization model of human enamel slabs was further constructed, and the hardness of enamel surface was detected.Results:Compared to UA159+Ss+Sg, over-expression of ASvicK could inhibit biofilm formation and lactic acid production in ASvicK+Ss+Sg biofilm significantly decreased by 78.93% ( P<0.001) and 62.23% ( P<0.001), respectively. With ASvicK over-expression, the amounts of water-insoluble and-soluble glucoses in ASvicK+Ss+Sg biofilm were reduced respectively by 39.13% ( P<0.001) and 68.00% ( P<0.001). Compared to the UA159+Ss+Sg Group, the proportion of Sm, the cariogenic bacteria, showed 33.00% reduction ( P<0.01) in Sm+Ss+Sg biofilm, and the gene expressions of cariogenic-relative genes vicK/X, gtfB/C/D, and ftf significantly decreased ( P<0.05). The micro-hardness value of enamel slabs after demineralization by ASvicK+Ss+Sg biofilm was significantly increased to 183.84% ( P<0.001). Conclusions:ASvicK over-expression could reduce the Sm proportion and weaken the cariogenicity of oral Streptococcus biofilm, thereby possibly slowing down the progression of caries.

Objective To screen items of the Clinical Aided Decision Scheme for Stroke Simultaneous Treatment of Disease,Pulse and Syndrome;To provide reference for the formulation and improvement of the scheme.Methods The Delphi method was used to distribute two rounds of questionnaires to 60 experts in cerebropathy or neurology across the country.Statistical analysis was performed on the questionnaire results of the scheme's items,including the disease names,etiology and pathogenesis,syndrome characteristics,rules and regulations,representative prescriptions,acupuncture and other therapies,and preventive care.Results Totally 42 and 50 valid questionnaires were collected.The experts reached the consensus for the importance of etiology and pathogenesis,rules and regulations,acupuncture and other therapies,and preventive care.In the section on syndrome characteristics,items with low relevance or causing ambiguity were removed.Items that were no longer used in modern times and different prescriptions with the same name were removed from the representative prescriptions.The names of syndromes,rules and regulations were unified.Conclusion The experts generally reached the consensus for the importance of the Clinical Aided Decision Scheme for Stroke Simultaneous Treatment of Disease,Pulse and Syndrome.However,there are still some limitations that require further study and discussion.

Objective:To construct a three-dimensional time-dose-response model for dose estimation and validate its feasibility.Methods:Based on a random number table, mice were divided into 0, 2, 4, 6, and 8 Gy groups for whole-body X-ray irradiation, with each group consisting of three mice. Hair follicle cells of whiskers were sampled at 1, 6, and 24 h after the irradiation. After immunofluorescence staining, the numbers of γ-H2AX foci at different time points from 1 to 24 h post-irradiation were observed using a confocal laser scanning microscope. The average numbers of γ-H2AX foci observed were corrected using the Dolphin’s model, followed by the fitting of dose-response curves. Using the R software, the equations and surfaces of the three-dimensional model for partial-body irradiation were established using the irradiation doses, post-irradiation time, and the corrected average numbers of γ-H2AX foci.Results:The average number of γ-H2AX foci increased with dose at fixed time points 1, 6, and 24 h but decreased with irradiation time at fixed doses 2, 4, 6, and 8 Gy. The dose-response curve equations of partial-body irradiation were fitted as follows: YF = 2.853+ 3.775 D, R2= 0.928, at 1 h after the irradiation; YF = 0.144+ 2.775 D, R2= 0.903, at 6 h after the irradiation; YF = 0.066+ 2.472 D, R2= 0.85, at 24 h after the irradiation. The three-dimensional model equation fitted was YF = 6.837 t-1.728+ 3.113 t-0.071D, R2=0.897. Substituting different post-irradiation time points into the three-dimensional surface model appeared as a two-dimensional linear model. By substituting the number of γ-H2AX foci and irradiation time into the linear and the three-dimensional models, both models yielded relative deviations between the estimated and actual radiation doses of 30% or less. Conclusions:The three-dimensional time-dose-response model, established by using the number of γ-H2AX foci to estimate partial-body irradiation doses, can be preliminarily applied for dose estimation at all time points 1-24 h after irradiation.

Radiation-induced damage to vascular endothelium is a major complication of radiotherapy and a primary cause of morbidity and mortality in the population exposed to radiation. Ionizing radiation-induced cellular senescence serves as a critical factor in damage to vascular endothelial cells. Therefore, understanding the mechanisms of cellular senescence caused by senescence-associated secretory phenotype (SASP), as well as its role in ionizing radiation-induced damage to vascular endothelial cells, is significant for preventing and treating ionizing radiation-induced damage to vascular endothelial cells. In this study, the relationship between SASP-related premature senescence and this ionizing radiation-induced damage was explored from the following aspects: the mechanisms behind ionizing radiation-induced damage to vascular endothelial cells, ionizing radiation-induced cellular senescence, and the role of SASP-related premature senescence in the ionizing radiation-induced damage to vascular endothelial cells, as well as potential targets.