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 explore the clinical and genetic characteristics of three children with Leguis syndrome.Methods:Three children suspected as Legius syndrome at the Henan Children′s Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c. 751C>T (p.Arg251Ter194) in child 1, c. 229A>T (p.Lys77Ter368) in child 2, and c. 1044_1046delinsC (p.R349fs *11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants. Conclusion:All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.

To monitor and analyze the molecular variation of the H3N2 influenza virus in Guangzhou during the COVID-19 pandemic, respiratory samples of influenza-like cases from influenza monitoring sentinel hospitals were collected from influenza monitoring sentinel hospitals for virus isolation and whole genome sequencing. The results showed that during COVID-19, there was only one peak of H3N2 influenza in the second quarter of 2022 in Guangzhou (the positive rate was 52.23%), and the epidemic intensity and duration were both higher than those in 2019. The HA gene and NA gene of the epidemic strain in Guangzhou in 2022 belonged to the 3C.2a1b. 2a. 1a. 1 branch, which had a good antigenic site matching with the vaccine strain (A/Cambodia/e0826360/2020) from 2021 to 2022 and had no antigen drift. In 2022 strains, the variation of antigen determinant mainly occurred in the I48T of C region, while no variation occurred in the A, B, D, and E regions. The binding site of the HA protein receptor was consistent with the vaccine strain (A/Cambodia/e0826360/2020). Most of the strains in 2022 carried 13 glycosylation sites on the HA protein, but an outbreak of strains caused a loss of glycosylation sites at 24-NST. In conclusion, the strains that caused the epidemic of H3N2 influenza in Guangzhou in 2022 were not evolved or transmitted from the local strains in 2019 during the COVID-19 pandemic.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Objective:To explore the effects of Undaria pinnatifida polysaccharides(UPPs)on depressive-like behavior,neurotransmitter content,oxidative stress,and the hypothalamus-pituitary-adrenal(HPA)axis in rats treated with chronic unpredictable mild stress(CUMS).Methods:A rat model of depression was prepared using the CUMS method,and rats were treated with normal saline(NS)or different doses of UPPs by gavage.The general condition of the rats was observed,and depressive-like behavior was detected by the open field test(OFT),sucrose preference test(SPT),and forced swimming test(FST).The activity or levels of 5-hydroxytryptamine(5-HT),dopamine(DA)and norepinephrine(NE),malondialdehyde(MDA),superoxide disidase(SOD)and catalase(CAT),adrenocorticotrop-ic hormore(ACTH),corticosterone(CORT)in the hippocampus or serum of rats were detected using commercial kits.Western Blot was used to detect the expression level of hippocampal glucocorticoid receptor(GR)protein,and hema-toxylin-eosin(HE)staining was used to observe the tissue structure of hippocampus of rats.Results:The depressive-like behavior of rats in the UPPs medium and high dose groups was significantly improved(P＜0.05).In the UPPs high dose group,the contents of 5-HT,DA,and NE in the hippocampus of rats increased(P＜0.05),while the con-tents of MDA in both serum and hippocampus decreased(P＜0.05),and the activities of SOD and CAT increased(P＜0.05).The contents of ACTH and CORT in serum decreased(P＜0.05).In the UPPs medium dose group,the levels of hippocampal MDA and CAT,as well as serum SOD,ACTH,and CORT were improved(P＜0.05).The expression level of GR protein in the hippocampus increased(P＜0.05),and the pathological changes in the hipp-ocampal dentate gyrus were significantly improved.Conclusion:UPPs can alleviate depressive-like behavior in CUMS rats,and its mechanism may be related to increasing the content of monoamine neurotransmitters in the hippocampus,reducing oxidative stress damage,and HPA axis hyperfunction.

Objective:To analyze the influence of midwifeled accompanyon the psychological status and delivery outcomes of gestational diabetes patients, and to provide reference for the implementation of clinical intervention programs for gestational diabetes patients.Methods:A semi-randomized controlled trial was adopted.Convenience sampling method was used to select 120 gestational diabetes patients admitted to Langfang People′s Hospital from March 2021 to September 2023, and they were divided into control group and experimental group according to the admission order. Both groups were given intraspinal delivery analgesia, while the control group was combined with routine midwifery management, and the experimental group was combined with a midwife led accompany. Intervention lasted until 2 h postpartum in both groups, and follow-up for 1 month. The delivery indicators, psychological status, delivery outcome and satisfaction of the two groups were compared.Results:Finally, 120 gestational diabetes patients were included, 60 patients in the control group, aged (28.73 ± 2.79) years, and 60 patients in the experimental group, aged (27.98 ± 1.09) years. The first and second stages of labor in the experimental group were (416.35 ± 29.87) and (60.95 ± 7.44) min, respectively, which were shorter than (501.33 ± 37.59) and (80.28 ± 8.95) min in the control group, and the differences were statistically significant ( t = 13.71, 12.87, both P<0.05). The blood glucose during delivery and 2 h postpartum hemorrhage was (6.81 ± 0.10) mmol/L and (236.18 ± 37.58) ml, respectively, lower than (7.48 ± 0.45) mmol/L and (325.70 ± 59.88) ml in the control group, the differences were statistically significant ( t = 11.26, 9.81, both P<0.05). After 1 month of follow-up, the scores of Self-rating Anxiety Scale and Self-rating Depression Scale of the experimental group were (30.86 ± 2.55) and (21.45 ± 2.67) points, which were lower than (42.19 ± 3.86) and (42.97 ± 3.15) points in the control group, and the scores of Psychological Resilience Scale were (71.22 ± 6.54) points, which was higher than that of the control group (55.38 ± 6.06) points, the differences were statistically significant ( t = 18.97, 40.37, 13.76, all P<0.05). After intervention, the incidence rates of lateral resection and postpartum hemorrhage in the experimental group were 28.3%(17/60) and 5.0%(3/60), respectively, lower than 48.3%(29/60) and 18.3%(11/60) in the control group, and the total satisfaction rate of the experimental group was 93.3%(56/60), higher than 80.0% (48/60) of the control group. The differences were statistically significant ( χ2 = 5.08, 5.18, 4.62, all P<0.05). Conclusions:The midwife led accompany could shorten the labor process of gestational diabetes patients, reduce their blood glucose during delivery and the amount of blood 2 h postpartum, and improve their psychological status and delivery outcomes, which was conducive to improving patient satisfaction.