Objective To analyze the characteristics of hearing loss at different frequencies among noise-exposed workers in a lithium battery manufacturing enterprise. Methods A total of 1 954 noise-exposed workers from a large lithium battery manufacturing enterprise were selected as the study subjects using the judgmental sampling method. Pure-tone audiometry, individual noise exposure level monitoring, and workplace noise intensity measurement were conducted. Results The overall detection rate of hearing loss among the study subjects was 39.0%. The detection rates of unilateral and bilateral hearing loss were 21.0% (410/1 954) and 18.0% (352/1 954), respectively. The detection rate of hearing loss in the right ear was higher than that in the left ear (30.1% vs 26.9%, P<0.05). The detection rates of elevated hearing thresholds at high frequencies and speech frequencies were 38.8% and 1.1%, respectively. Comparisons of the detection rates of elevated hearing thresholds across different frequencies between the left and right ears showed significant differences (all P<0.01); specifically, the detection rate at 4.0 kHz in the right ear was higher than that in the left ear (P<0.01). The detection rates of elevated hearing thresholds at 2.0, 4.0, and 6.0 kHz increased with longer duration of noise exposure (all P<0.05). Except at 1.0 kHz, the detection rates of elevated hearing thresholds at 0.5, 2.0, 3.0, 4.0, and 6.0 kHz showed increasing trends with age (all P<0.05). Conclusion Hearing loss among noise-exposed workers in the lithium battery manufacturing industry is predominant in the high-frequency type, with the highest sensitivity at 4.0 kHz and greater susceptibility in the right ear. The detection rate of high frequency hearing loss increases with longer noise exposure duration and advacing age. Health surveillance should focus on workers with longer noise exposure duration and older age. Noise control measures should be strengthened.

Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Background Di(2-ethylhexyl) phthalate (DEHP) is the most prevalent environmental endocrine disruptor among phthalate acid esters (PAEs) worldwide. Previous studies have indicated that exposure to DEHP may disrupt glucose metabolism. Objective To investigate the impact of DEHP on glucose homeostasis in rats, focusing on oxidative stress-induced impairment of autophagy in islet β cells. Methods Forty male SD rats were randomly assigned to four groups, receiving DEHP doses of 0, 187, 375, and 750 mg·kg⁻¹ for 12 weeks. Oral glucose tolerance (OGTT) and insulin tolerance tests (ITT) were conducted 24 h after the final exposure. Pancreatic microstructural alterations were assessed using hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Commercial ELISA kits were employed to quantify the levels of insulin, adenosine triphosphate (ATP), and adenosine monophosphate (AMP) in rat serum, as well as the protein expression level of activated caspase-3 in pancreatic tissue. Additionally, commercial microplate kits were utilized to measure the concentration of reduced glutathione (GSH) in serum, the activity of superoxide dismutase (SOD) using water-soluble tetrazolium salt-1, the content of malondialdehyde (MDA) by thiobarbituric acid method, and the level of reactive oxygen species (ROS) in pancreatic tissue by chemical fluorescence method. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure sequestosome1 (SQSTM1/p62), Beclin1, microtubule-associated protein 1 light chain 3 (LC3), and cysteinyl aspartate specific proteinase-8 (Caspase-8) mRNA levels. Western blot analysis was applied to detect the protein relative expression levels of p62, Beclin-1, LC3-I, LC3 II, AMPK, p-AMPK, mTOR, p-mTOR, ULK1, and Caspase-8. Results Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited a significant increase in fasting blood glucose levels at 2, 4, 6, and 12 weeks (P<0.05). The OGTT showed that, following high-glucose gavage, the 187 mg·kg⁻¹ DEHP group had elevated blood glucose at 30 min (P<0.05), the 375 mg·kg⁻¹ DEHP group showed increased glucose levels at 15, 30, and 180 min (P<0.05), and the 750 mg·kg⁻¹ DEHP group exhibited elevated levels at 15, 30, 60, and 180 min (P<0.05). The 375 and 750 mg·kg⁻¹ DEHP groups demonstrated significantly increased OGTT area under the curve (AUC) values (P<0.05). In contrast, ITT results indicated no significant differences in blood glucose levels or AUC among the DEHP exposure groups at all time points (P>0.05). Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited significantly higher HOMA-IR levels and markedly lower HOMA-ISI values (P<0.05). HE and TEM showed that in each DEHP exposure group, the number of islet cells decreased, the islet area reduced, and chromatin condensation occurred. The endocrine granules in the cytoplasm of islet β cells decreased, and there were varying degrees of widening of the nuclear membrane gap, flattening and expansion of the Golgi complex, and expansion of the endoplasmic reticulum. Ribosome separation was observed, and autophagosomes were visible. In the 375 and 750 mg·kg⁻¹ DEHP groups, the mitochondria were deformed to varying degrees, and some cristae structures disappeared, presenting vacuolization. Moreover, the chromatin condensation in the nuclei was more severe in the 750 mg·kg⁻¹ DEHP group. The serum SOD activity was significantly elevated in the 750 mg·kg⁻¹ DEHP group (P<0.05). Both the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP groups exhibited a significant increase in the relative ROS content in pancreatic tissue (P<0.05). In DEHP-treated groups, the MDA content increased (P<0.05), while the GSH content decreased (P<0.05). Additionally, in the 750 mg·kg⁻¹ DEHP group, the AMP/ATP ratio in serum was significantly raised (P<0.05), and the expression of cleaved Caspase-3 protein in pancreatic tissue was also significantly increased (P<0.05). The relative mRNA levels of p62, Beclin-1, LC3, and Caspase-8 in the pancreatic tissue of rats exposed to DEHP were significantly elevated (P<0.05). The relative expression levels of p-AMPK/AMPK, p-ULK1/ULK1, and Beclin-1 proteins in the DEHP-treated groups were significantly increased (P<0.05). In the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP treatment groups, the relative expression levels of p62, LC3 II/LC1, and Caspase-8 proteins were significantly increased (P<0.05), while the relative expression level of p-mTOR/mTOR was significantly decreased (P<0.05). Conclusion DEHP can disrupt glucose homeostasis by inducing oxidative stress, which subsequently activates autophagy via the ROS/AMPK/ULK1 pathway, impairing autophagic flux and promoting apoptosis of islet β cells, ultimately decreasing their function and number.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment, memory decline and emotional loss, which is more common in middle-aged and elderly people. In recent years, studies have shown that chronic neuroinflammation is an important factor leading to AD development. As the core participant in neuroinflammation, microglia play a dual role in the pathological process of AD: on one hand, through M1 polarization, they exert a pro-inflammatory effect and exacerbate the neurotoxic response; on the other hand, through M2 polarization, they enhance the phagocytic ability of amyloid β-protein and exert a neuroprotective effect. Metabolic reprogramming is the key in determining the polarization of microglia M1/M2 type and exerting neurotoxicity/protection. Therefore, this article reviews the recent advance in role of metabolism reprogramming of microglia in AD, in order to provide new idea and direction for studing AD pathogenesis and treatment in the future.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment, memory decline and emotional loss, which is more common in middle-aged and elderly people. In recent years, studies have shown that chronic neuroinflammation is an important factor leading to AD development. As the core participant in neuroinflammation, microglia play a dual role in the pathological process of AD: on one hand, through M1 polarization, they exert a pro-inflammatory effect and exacerbate the neurotoxic response; on the other hand, through M2 polarization, they enhance the phagocytic ability of amyloid β-protein and exert a neuroprotective effect. Metabolic reprogramming is the key in determining the polarization of microglia M1/M2 type and exerting neurotoxicity/protection. Therefore, this article reviews the recent advance in role of metabolism reprogramming of microglia in AD, in order to provide new idea and direction for studing AD pathogenesis and treatment in the future.

Objective To explore the application value of lymphocyte subsets combined with various cytokines in the disease progression of elderly patients with corona virus disease 2019(COVID-19).Methods From December 2022 to January 2023,146 elderly patients with COVID-19 diagnosed in the emergency ward of the Eighth Medical Center of PLA General Hospital were selected and divided into two groups according to the prognosis:127 cases in the COVID-19 survival group,19 cases in the COVID-19 death group.In addition,51 osteoporosis patients in geriatric medicine department were collected as control group.The proportion and absolute count of lymphocyte subsets(including T,B and NK cells),and 12 cytokines in plasma(including IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,TNF-α and IFN-γ)were compared between the control group and COVID-19 group,survival group and death group.The receiver operating characteristic(ROC)curve was used to evaluate its prognostic value in elderly patients with COVID-19 infection.Results Compared with the control group:① The proportion of NK cells in COVID-19 group was decreased,while the proportion of B cells was increased,and the differences were statistically significant(Z=-3.386,-4.140,all P<0.01).There was no significant difference in the proportion of T,CD8+T and CD4+T cells,and the differences were not statistically significant(Z=-1.244,-1.770,-0.951,all P>0.05).② The absolute numbers of T,CD8+T,CD4+T,NK and B cells in COVID-19 group were decreased,and the differences were statistically significant(Z=-9.418～-6.539,all P<0.01).③ The concentrations of IL-2,IL-6,IL-1β,IFN-γ,IL-8,IL-17,IL-12P70 and IL-10 in COVID-19 group were all increased,and the differences were statistically significant(Z=-8.851～-1.986,all P<0.05).There was no significant difference in the concentrations of IL-5,IFN-α,TNF-α and IL-4,and the differences were not statistically significant(Z=-0.460～-0.217,all P>0.05).Compared with the survival group:① There was no significant difference in the proportion of T,CD8+T,CD4+T,NK and B cells in the death group(Z=-1.873～-0.422,all P>0.05).② The absolute numbers of T,CD8+T and CD4+T cells in the death group were all decreased,and the differences were statistically significant(Z=-2.667,-2.287,-2.556,all P<0.05),while there was no significant difference in absolute numbers of NK and B cellsm and the differences were not statistically significant(Z=-1.934,-0.532,all P>0.05).③ The concentrations of IL-6,IFN-γ,IL-8,IL-17 and IL-10 in the death group were all increased,and the differences were not statistically significant(Z=-4.211～-2.655,all P<0.05),and there was no significant difference in the concentrations of IL-5,IFN-α,IL-2,IL-1β,IL-12p70,TNF-α and IL-4 the differences were not statistically significant(Z=-1.329～-0.279,all P>0.05).ROC curve analysis for the prognostic value of lymphocyte subsets combined with cytokines in elderly patients with COVID-19 showed that:the areas of total T cells,B cells and NK cells under ROC curve for predicting the prognosis of COVID-19 infection were 0.94,0.80 and 0.93,respectively.The areas of CD4+T cells and CD8+T cells under ROC curve for predicting the prognosis of COVID-19 infection were 0.93 and 0.90,respectively.The areas of IL-6,IFN-γ,IL-8,IL-17 and IL-10 in cytokines under the ROC curve for predicting the prognosis of COVID-19 infection were 0.91,0.71,0.87,0.74 and 0.90,respectively.However,the area of combined lymphocyte subsets and cytokines under ROC curve for predicting the prognosis of COVID-19 infection reached 0.99.Conclusion The immune status of elderly patients with COVID-19 was generally low.Evaluation of immune status has important clinical guidance significance in disease diagnosis,disease observation and prognosis.

Objective To investigate the effect of erythroid differentiation associated gene(EDAG)on hematopoietic stem/progenitor cells(HSPCs)under chronic inflammation.Methods In this study,EDAG-/-and wild type(WT)mice were divided into the experiment group and control group.An infectious chronic inflammation model was established via multiple intraperitoneal injections of Listeria monocytogenes(LM),while a sterile chronic inflammation model was generated via multiple intraperitoneal injections of polyinosinic-polycytidylic acid[Poly(I∶C)].The effect of EDAG on HSPCs was explored under chronic inflammation conditions.Results In the LM repeated infection model,EDAG deletion led to a decrease in HSPCs and long-term hematopoietic stem cells(LT-HSCs)in mice as well as a significant bias towards myeloid differentiation in peripheral blood.Similarly,EDAG knockout also resulted in reduced numbers of HSPCs and decreased colony-forming ability in aseptic chronic inflammation models.Conclusion EDAG deficiency accelerates HSPC depletion in young mice under chronic inflammation,indicating strong protection of EDAG against HSPC damage induced by chronic inflammation.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.