OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease （ASCVD） following percutaneous coronary intervention （PCI）. METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1， 2023 and December 31， 2024. According to the lipid-lowering regimen， the patients were categorized into evolocumab group （ n ＝86） and probucol group （ n ＝70）. Changes in lipid parameters [total cholesterol （TC）， low-density lipoprot ein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， triglycerides， lipoprotein （a）， and lipid goal achievement rate ] ， inflammatory markers [interleukin-6 （IL-6） and C-reactive protein （CRP） ] ， and cardiac function indices （left ventricular ejection fraction， left ventricular end-systolic diameter， left ventricular end-diastolic diameter， and N-terminal pro-B-type natriuretic peptide） were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment， including acute myocardial infarction， in-stent restenosis， acute heart failure， cerebral hemorrhage， and stroke， was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline （ P ＞0.05）. After 6 months of treatment， both groups demonstrated significant improvements in lipid profiles （except HDL-C） and inflammatory markers compared to those at baseline （ P ＜0.05）. The evolocumab group exhibited greater reductions in TC， LDL-C， IL-6， and CRP， along with a higher lipid target achievement rate， compared with the probucol group （ P ＜0.05）. There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups， nor in the incidence of adverse events during the treatment （ P ＞0.05）. CONCLUSIONS For ultra-high-risk ASCVD patients after PCI， both of the above treatment options are associated with improvements in blood lipid and inflammatory response， with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC， LDL-C and inflammatory markers reduction and lipid target achievement， compared to probucol.

Background 900 MHz radiofrequency radiation (RF) is a commonly used frequency in modern wireless communication devices, and its potential health effects have drawn much attention, especially its impact on bone metabolism, which has not been fully clarified. Objective To investigate the effects of 900 MHz RF on the bone tissue and osteoblast senescence of mice, as well as the dose-effect relationship. Methods In vivo, 3-month-old female C57BL/6 mice were divided into five groups (n=10): sham exposure, low-dose RF (50 μW·cm⁻²), medium-dose RF (150 μW·cm⁻²), high-dose RF (450 μW·cm⁻²), and D-galactose positive control (D-gal). Treatments were administered for 4 h per day for 28 d. Bone mineral density (BMD) and microstructure, including bone volume (BV), tissue volume (TV), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular separation (Tb.Sp), and trabecular thickness (Tb.Th), were assessed by Micro-CT; bone morphology was examined after hematoxylin and eosin (HE) staining; osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-κΒ ligand (RANKL) expression was detected by immunohistochemistry; serum OPG, tartrate-resistant acid phosphatase 5b (TRACP-5b), plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), and C-X-C motif chemokine ligand 15 (CXCL15) levels were measured by enzyme-linked immunosorbent assay (ELISA); mRNA expression of Tp53, Cdkn1a, and Cdkn2a in bone tissue was analyzed by reverse transcription polymerase chain reaction (RT-PCR). In vitro, MC3T3-E1 pre-osteoblasts were grouped into sham, low-dose RF (50 μW·cm⁻²), medium-dose RF (150 μW·cm⁻²), high-dose RF (450 μW·cm⁻²), and H₂O₂ control, groups, and were exposed for 4 h per day for 5 d. Cell morphology was observed by microscopy; viability was tested by cell counting kit-8 (CCK-8); senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining; P53 and P21 protein expression was detected by Western blot; Tp53 and Cdkn1a mRNA levels were measured by RT-PCR. Results In vivo, RF at each dose significantly reduced the BMD of the mice's femurs and the bone microstructure parameters, such as BV/TV, Tb.N, and Tb.Th (P<0.05). Among them, Tb.Sp only increased in the 150 μW·cm⁻² RF group (P<0.05), with a looser bone network; fewer, sparser trabeculae and increased marrow fat were observed after HE staining; down-regulated OPG and up-regulated RANKL expression levels were observed by immunohistochemistry; the ELISA test revealed that the serum OPG levels in the 150 μW·cm⁻² RF group and the 450 μW·cm⁻² RF group of mice were significantly decreased (P<0.05), while the indicator in the 50 μW·cm⁻² RF group showed a decreasing trend but the difference was not statistically significant (P>0.05), TRACP-5b rose, and PAI-1, IL-6, and CXCL15 levels increased (P<0.05); the RT-PCR results showed thatTp53, Cdkn1a, and Cdkn2a mRNA expression was upregulated (P<0.05). In vitro, radiofrequency radiation induced cell flattening, reduced viability (P<0.05), increased SA-β-gal-positive cells (P<0.05), and upregulated P53, P21, Tp53, and Cdkn1a expression (P<0.05). Conclusion 900 MHz RF disrupts bone metabolism in mice by inhibiting bone formation, promoting resorption, and inducing osteoblast senescence, accelerating bone aging. The 150 μW·cm⁻² RF dose exhibits the most pronounced effect, reflecting a nonlinear “window effect,” highlighting potential health risks.

Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.

Background Noise-induced hearing loss (NIHL) is a prevalent occupational health problem in workplace settings, with non-steady noise exposure being particularly widespread. Although kurtosis-adjusted equivalent sound level (\begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}) methods based on linear regression are available to assess hearing damage, the complexity of kurtosis effects necessitates introducing new metrics through nonlinear regression to improve predictive accuracy for hearing loss from non-steady noise exposure. Objective To examine the adjustment terms [\begin{document}$ \mathrm{lg}(\beta _{N}/{\beta }_{G}) $\end{document}] and coefficients (λ) of \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} using nonlinear regression and evaluate the method’s effectiveness in assessing occupational hearing loss associated with non-steady noise exposure. Methods A cross-sectional study design was employed, enrolling 1034 manufacturing workers and evaluating noise exposure to estimate hearing loss metrics. Quantile regression analysis quantified the proportional contributions of influencing factors for noise-induced permanent threshold shift at 3, 4, and 6 kHz frequencies (NIPTS₃₄₆). \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} was computed using multiple linear regression and nonlinear least squares optimization. Paired t-tests analyzed predictive efficacy before and after kurtosis adjustment to evaluate its impact on ISO 1999 NIPTS₃₄₆ predictions. Chow tests compared the similarity of logistic regression curves for high-frequency noise-induced hearing loss (HFNIHL) incidence between non-steady noise (\begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}) and steady noise (\begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document}), thereby validating the effectiveness of \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}. Results The quantile regression analysis showed that kurtosis was a significant indicator of occupational hearing loss risk from non-steady noise (contribution rate was 27.5%, P<0.05). The linear regression and nonlinear least squares methods obtained six different combinations of coefficients (λ) and adjustment terms [\begin{document}$ \mathrm{lg}(\beta _{N}/{\beta }_{G}) $\end{document}]. Incorporating these \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} adjustments into the ISO 1999 predictive model significantly reduced NIPTS underestimation (from 14.2 dB HL with \begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document} to 11.5–5.6 dB HL with \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document}, P < 0.001). The model \begin{document}$ {{{L'}}_{\text{EX,}\text{8}\text{ h}\text{,6}}=L}_{\mathrm{E}\mathrm{X},8\;\mathrm{h}}+7.9\mathrm{lg}({{\beta }_{N}}/{10}) $\end{document} achieved the most significant improvement, reducing underestimation by 8.7 dB HL. The logistic curve analysis further demonstrated that all \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} dose-response relationships for non-steady noise aligned more closely with the steady noise group than \begin{document}$ {{L}}_{\text{EX,}\text{8}\text{ h}} $\end{document}, with \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}\text{,6}} $\end{document} showing the smallest divergence (difference: 4.1%). Conclusions \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} demonstrates superior efficacy in assessing the risk of occupational hearing loss induced by non-steady noise exposure. The \begin{document}$ {{L'}}_{\text{EX,}\text{8}\text{ h}} $\end{document} metric, constructed by calculating adjustment terms and coefficients through nonlinear regression analysis, exhibits greater effectiveness than linear regression methods in evaluating occupational hearing loss associated with non-steady noise exposure.

Background Temporal kurtosis (without frequency weighting, i.e., Z-weighted kurtosis) can evaluate noise-induced hearing loss (NIHL). However, few studies have considered the function of frequency weighting (A- or C-weighted) kurtosis on NIHL. Objective To study the significance of A- and C-weighted kurtosis adjustment for equivalent sound level (L'_{EX,8 h}) in evaluating occupational hearing loss. Methods A cross-sectional survey was used to select 973 noise-exposed workers in seven industries as the subjects. The noise exposure of all workers was assessed by distributions of A-, C-, and Z-weighted kurtosis (e.g., K_A, K_C, and K_Z) and respective adjusted equivalent sound level (e.g., L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z). The significance of A- and C-weighted kurtosis in evaluating NIHL was evaluated by correlations between three types of L'_{EX,8 h} and NIHL, and improvement of noise-induced permanent threshold shift (NIPTS) underestimation predicted by the ISO prediction model (Acoustics—Estimation of noise-induced hearing loss, ISO 1999-2013). Results The median K_A, K_C, and K_Z were 68.33, 28.22, and 19.82, respectively. The binary logistic regression showed that L_{EX, 8 h}-K_A, L_{EX, 8 h}-K_C, and L'_{EX, 8 h}-K_Z were risk factors for NIHL (OR>1, P<0.001). The receiver operating characteristic (ROC) curve showed that when the outcome variable was noise-induced hearing impairment (NIHI), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX,8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.625, 0.628, and 0.625, respectively. When the outcome variable was high-frequency noise-induced hearing loss (HFNIHL), the areas under the curves corresponding to L'_{EX,8 h}-K_A, L'_{EX, 8 h}-K_C, and L'_{EX,8 h}-K_Z were 0.624, 0.623, and 0.622, respectively (P<0.05). The order of underestimation improvement values predicted by L'_{EX,8 h} for NIPTS₁₂₃₄ was: L'_{EX,8 h}-K_A (4.68 dB HL)>L'_{EX,8 h}-K_C (4.38 dB HL)>L'_{EX,8 h}-K_Z (4.28 dB HL) (P<0.001). The order of underestimation improvement values predicted by L'_{EX,8 h}-K for NIPTS₃₄₆ was: L'_{EX,8 h}-K_A (7.20 dB HL)>L'_{EX,8 h}-K_C (6.83 dB HL)>L'_{EX,8 h}-K_Z (6.71 dB HL) (P<0.001). Conclusion The adjustment of A- and C-weighted kurtosis to equivalent sound level L_{EX,8 h} can effectively improve the accuracy of the ISO 1999 prediction model in NIPTS prediction, and compared with the C-weighted, the A-weighted kurtosis can improve the result of the ISO 1999 prediction model in terms of underestimating NIPTS.

background Current assessment of noise-induced hearing loss relies on the hearing threshold statistical distribution table of ISO 7029-2017 standard (ISO 7029), which is based on foreign population data and lacks a hearing threshold distribution table derived from pure-tone audiometry data of the Chinese population, hindering accurate evaluation of hearing loss in this group. Objective To establish a statistical distribution table of hearing threshold level (HTL) for otologically normal Chinese adults and to provide a scientific basis for revising the diagnostic criteria of occupational noise-induced deafness in China. Methods A total of 1271 otologically normal Chinese adults aged 18-60 years were divided into four groups with 10-year age intervals. Based on the pure tone audiometry data and power function operation formula, the relevant parameters of the median and percentile calculation formula of ISO 7029 were adjusted. Based on the adjusted parameters, a statistical distribution table of HTL of normal Chinese adults in otology was preliminarily constructed according to the calculation formula of ISO 7029. A nonparametric rank sum test was used to compare the difference between the adjusted median deviation value and the ISO 7029 calculation. Results Except for a few frequencies (2000, 3000, and 8000 Hz), the value of parameter α adjusted for the auditory threshold deviation of the Chinese population (α_CHN-md) increased with the increase of frequency, while the value of parameter β adjusted for the auditory threshold deviation of the Chinese population (β_CHN-md) decreased with the increase of frequency. The preliminary distribution table of otologically normal Chinese adults' median hearing threshold deviation (ΔH_CHN-md) showed that the hearing threshold deviation increased with age and frequency. At 8000 Hz, the increase in ΔH_CHN-md with age was the greatest for both men and women, from 0 dB to 23 dB and 21 dB respectively. The minimal threshold elevation was noted at 500, 1000, and 2000 Hz, which increased from 0 dB to 2 dB. In otologically normal Chinese adults, the maximum increase of ΔH_CHN-md with frequency was observed at age of 50 years, which increased from 2 dB at 500 Hz to 23 dB at 8000 Hz in men and from 2 dB at 500 Hz to 21 dB at 8000 Hz in women. The comparison results with the ISO 7029 calculation showed that the trend was consistent. The median hearing threshold deviation value of the adjusted Chinese population was lower than that of the ISO 7029 calculation (ΔH_md). However, they had no significant statistical difference (P>0.05). For otologically normal normal Chinese men and women, the maximum difference of ΔH_md between the 50-year-old group and the ISO calculation at 8000 Hz was 7 dB and 9 dB, respectively. Conclusion This preliminary analysis of hearing threshold deviations in otologically normal Chinese adults suggests that current standards may potentially underestimate hearing loss at frequencies below 8000 Hz while possibly overestimating it at 8000 Hz. These findings require further validation through expanded sample sizes to more accurately assess the characteristics of hearing thresholds in the Chinese population and their discrepancies with existing standards.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Objective To investigate the bone protective effects and underlying mechanisms of 900MHz radiofrequency radiation (RF) at different power densities (50, 150, and 450 μW/cm²) on an ovariectomy-induced osteoporosis mouse model. Methods Sixty 3-month-old C57BL/6 female mice were randomly divided into Sham group (sham exposure), OVX group (ovariectomy), OVX + LRF group (OVX + 50 μW/cm² RF), OVX + MRF group (OVX + 150 μW/cm² RF), OVX + HRF group (OVX + 450 μW/cm² RF), and OVX + E2 group (OVX + estradiol). Ovariectomized mice in the OVX + RF groups were exposed to RF of varying power densities for 4 hours daily. Ovariectomized mice in the OVX + E2 group received intramuscular injections of estradiol (0.04 mg/kg) every two days. After four weeks of intervention, Micro-CT, ELISA, RT-PCR, and immunohistochemistry were employed to analyze bone density, bone microstructure, serum bone metabolic markers, and the expression of related genes and proteins. Results Compared with the Sham group, the OVX group showed significantly decreased bone mineral density (BMD) and bone microstructure indicators such as BV, BV/TV, Tb.Th, and Tb.N, significantly increased bone microstructure indicator Tb.Sp, significantly decreased serum estradiol, significantly increased serum CTX-I, TRACP-5b, BGP, and OPG, significantly increased Nfatc1 and Runx2 mRNAs, and significantly increased OPG and RANKL. Compared with the OVX group, the OVX + MRF group and OVX + E2 group exhibited significantly increased BMD, BV, BV/TV, Tb.Th, and Tb.N, significantly decreased Tb.Sp, significantly increased serum OPG, Runx2 mRNA, and OPG, and significantly decreased serum CTX-I, TRACP-5b, Nfatc1 mRNA, and RANKL. Compared with the OVX group, the OVX + LRF group showed significantly increased cortical bone BMD and Tb.Th, the OVX + HRF group showed significantly increased cortical bone BMD and serum CTX-I and TRACP-5b, and the OVX + MRF group showed significantly increased serum BGP. Among the three power densities, the 150 μW/cm² RF showed the most significant effect. Conclusion The 150 μw/cm² 900 MHz RF can counteract the abnormalities in serum bone metabolism biomarkers, the decrease in BMD, the degeneration of bone microstructure, and the increase in bone resorption caused by ovariectomy in mice.

ObjectiveTo find out whether there is any difference in the monitoring results of mosq-ovitraps placed in different orientations in multi-storey residential areas, so as to provide a scientific basis for routine and emergency monitoring of Aedes albopictus with mosq-ovitraps in residential areas. MethodsFrom July 6th to October 26th 2023, one mosquito ovitrap was set up in each of the 4 orientations of east, south, west and north around the buildings in a multi-storey residential area in Jinhui Town, Fengxian District, Shanghai. Data was collected and recorded 72 hours after placement. The chi-square test was used to compare the mosquito ovitrap indices (MOIs) of two independent samples, and the Kruskal⁃Wallis H test was used to compare the MOIs of multiple independent samples. ResultsAfter 16 weeks of surveillance, 997 mosquito ovitraps were recovered, of which 211 were positive, with the mosquito ovitrap index (MOI) of 21.16% and the Aedes albopictus density index of 1.03 mosquitoes·ovitrap^-1. The MOIs were higher in September (24.22%) and October (23.96%), and the MOIs in the west, south and north within the two months were all above 20.00%. From July to October, the MOIs in the east, west, south and north were 20.70%, 22.20%, 25.50% and 16.20%, respectively, and the difference in MOIs among the 4 orientations was not statistically significant (χ²=6.647, P=0.084). Stratified analysis by month showed that in August, the south side of the multi-storey residential areas had the highest MOI (31.30%), the north side had the lowest MOI (1.30%), and there was a statistically significant difference in MOI in the east, west, south and north (χ²=25.986, P<0.001). In October, the MOI in the west was the highest (33.30%) and the MOI in the east was the lowest (6.30%), the difference in MOIs of the 4 orientations was statistically significant (χ²=12.007, P=0.007). The MOIs in the south side of the building in the outskirts of the residential area from the 1st week in July to the 4th week in October was lower (19.20%) than that in the south side of the inner building (31.70%), and the difference in MOI was statistically significant (χ²=5.118, P=0.024). ConclusionThe study of MOI in different orientations in a multi-storey residential area is a preliminary exploration based on field work, and the results show that there is a difference in MOIs in different orientations during the peak breeding period of mosquitoes. Further indicators such as temperature, humidity and wind speed in different orientations can be collected to explore the influencing factors of MOIs.