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.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

A middle-aged patient presented with persistent purulent discharge from a scalp incision five years after undergoing craniotomy with artificial dura mater implantation. The wound showed no significant improvement despite a month of systemic antibiotic therapy and local debridement. Subsequent superficial ultrasonography revealed complete separation of the artificial dura mater implant area from the surrounding flap tissue, with a loss of local blood supply. Based on these findings, the artificial dura mater was surgically removed, and a free skin flap transplantation was performed to successfully cover the wound. The wound was well-healed at the 10-month postoperative follow-up.
Humans ; Scalp/diagnostic imaging* ; Middle Aged ; Male ; Epidural Abscess/etiology* ; Ultrasonography ; Surgical Flaps ; Surgical Wound Infection/surgery* ; Dura Mater/surgery*

Background Di(2-ethylhexyl) phthalate (DEHP) is the highest consumed and the most widely used phthalic acid ester, their effects on lipid metabolism have attracted the attention of many scholars. However, the associated mechanism is still unclear. Objective To observe the effect of DEHP on lipid metabolism in rats, probe its possible mechanism, and provide a research basis for the effect of DEHP on human lipid metabolism. Methods Forty healthy male SD rats were randomly divided into 4 groups: solvent control (0 mg·kg⁻¹ DEHP), low DEHP (187 mg·kg⁻¹), medium DEHP (375 mg·kg⁻¹), and high DEHP (750 mg·kg⁻¹) groups. DEHP was administered by oral gavage for 6 d per week, consecutively 8 weeks. The rats were weighed once a week during the exposure period. At 24 h after the last exposure, the rats were anesthetized with 20% urethane and sacrificed by apical puncture. Rat livers were harvested and weighed before hematoxylin-eosin (HE) histopathological observation. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of lipid metabolism-related genes Janus kinase 3 (JAK3), signal transducer and activator of transcription 5b (STAT5b), and peroxisome proliferator-activated receptor γ (PPARγ) in liver, and Western blot was used to detect the expression levels of lipid metabolism-related proteins JAK3, STAT5b, and PPARγ in liver. Results Compared with the control group, there was no significant difference in the body weight gain of the rats in each group (P>0.05). The liver organ coefficients of the DEHP exposure groups were higher than that of the control group (P<0.001), and increased with higher DEHP dosages. The level of high-density lipoprotein cholesterol (HDL-C) in serum decreased in all DEHP exposure groups (P<0.05), and the level of low-density lipoprotein cholesterol (LDL-C) in serum increased in the high DEHP group (P<0.05). The results of liver histopathological morphology showed that the hepatocytes of each DEHP group were enlarged and edematous in varying degrees, with loose stroma and irregular arrangement of cells, which were manifested as inflammatory cell infiltration and fatty degeneration of liver cells. Compared to the control group, the mRNA levels of JAK3, STAT5b, and PPARγ in liver tissues of rats in each DEHP group decreased (P<0.001). Compared to the control group, the relative expression levels of JAK3 in each DEHP group decreased (P<0.05), and the relative expression levels of STAT5b and PPARγ in the medium and high DEHP groups decreased (P<0.05). Conclusion DEHP exposure can induce abnormal lipid metabolism in rats, and the mechanism may be related to DEHP inhibiting the activation of JAK3/STAT5b/PPARγ signaling pathway.

Bruton's tyrosine kinase(BTK)inhibitors are novel drugs targeted for the treatment of B-cell lymphoma.BTK inhibitors have pro-duced strong curative effects,especially for mantle cell lymphoma(MCL),chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SSL),and Waldenstr?m's macroglobulinemia(WM).However,the adverse effect of bleeding has gradually been noted with the wide-spread use of BTK inhibitors in clinical practice.Bleeding events are caused by the off-target effects of BTK inhibitors,which affect platelet function through multiple signaling pathways during use.Bleeding affects patient treatment and threatens their quality of life.As such,the clinical management of bleeding should be strengthened.This paper provides a review of the mechanisms of action and clinical manage-ment of bleeding caused by BTK inhibitors.

Objective To observe the effect of edaravone (ED) on cognition function and expression of Nogo-A in prefrontal cortex neuron of rats with serious intermittent hypoxia.Methods Ninety-six adult male Wistar rats were randomly divided into normal control group, chronic intermittent hypoxia (CIH) model group and ED group, 32 rats in each group. The rat model of CIH was reproduced in a low oxygen box at 08:00-15:00 every day: alternatively, different flow rates of nitrogen and compressed air were given, 120 seconds being one cycle, maintaining the oxygen concentration at 5%-21% in the low oxygen chamber; the normalcontrol group was continuously under the circumstance fulfilled with compressed air. The rat in ED group was given intravenous injection of 3 mg/kg ED in a tail vein at 07:00 daily. After modeling for 7, 14, 21, 28 days, the learning and memory functions of rats were assessed with the Morris water maze test, and the reactive oxygen species (ROS) content in the rat prefrontal lobe tissue was detected; the level of Nogo-A protein expression in the rat prefrontal cortex was examined by immunohistochemical method .Results ① Rat learning results: in CIH model group, with the time prolongation escaping latency period was gradually longer, since 14 days after the modeling, the difference was statistically significant compared with that in normal control group, while the learning time in ED group was obviously shorter than that in the CIH model group (seconds: 14 days was 26.97±3.35 vs. 34.95±3.36, 21 days was 32.78±4.59 vs. 46.72±4.11, 28 days was 41.39±3.84 vs. 57.35±3.72, allP < 0.05). ② Rat memory results: the rats in CIH model group, with the time prolongation crossing the target quadrant time was gradually shorter, since 14 days after the modeling, the difference was statistically significant compared with that of the normal control group, while the memory time in the ED group was obviously longer than that of the model group (seconds: 14 days was 42.72±3.35 vs. 39.88±3.56, 21 days was 40.48±4.62 vs. 28.72±3.93, 28 days was 31.13±3.46 vs. 22.79±3.24, allP < 0.05). ③ ROS content: with the time prolongation, ROS content was gradually increased in CIH model group, but the ROS content in ED group was significantly lower than that in CIH model group at various time points (MU/L: 7 days was 13.27±0.23 vs. 17.68±0.51, 14 days was 15.51±0.28 vs. 20.41±0.65, 21 days was 20.29±0.44 vs. 23.86±0.35, 28 days was 24.46±0.53 vs. 30.43±0.85, allP < 0.05). ④ Protein expression of Nogo-A: with the time prolongation, the protein expression of Nogo-A was gradually increased in CIH model group, they reached the peak on the 14th day, the expression of Nogo-A [absorbance (A) value] in ED group were significantly lower than that in CIH model group at each time point (×103: 7 days was 4.80±0.70 vs. 5.99±0.62, 14 days was 5.89±0.90 vs. 7.42±0.66, 21 days was 4.92±0.64 vs. 5.90±0.37, 28 days was 3.59±0.59 vs. 4.27±0.40, allP < 0.05).Conclusions The mechanism of ED has a valid therapeutic effect on the cognitive dysfunction induced by serious intermittent hypoxia in rats, ED can remove oxygen free radicals and inhibit the protein expression of Nogo-A in the prefrontal cortex, so ED can alleviate the damage of cognitive function in rats with CIH.

Objective To analyze the relationship between internal carotid artery (ICA) stenosis and ipsilateral retinal vascular calibers,and to investigate the feasibility and accuracy of changes of retinal vascular calibers for assessment of ICA stenosis.Methods Unilateral ICA and ipsilateral retinal vascular of 243 patients were enrolled based on CTA and fundus imaging.Patients were divided into 4 groups according to the highest ICA stenosis rate (Rmax),i.e.no stenosis group,mild stenosis group,moderate stenosis group and severe stenosis group.The differences of retinal vascular calibers among four groups and correlation between retinal vascular calibers and ICA stenosis were analyzed.Results The average central retinal vein equivalents (CRVE) in moderate ICA stenosis group and severe stenosis group were significantly wider than those in the other two groups (all P＜0.05).There was no statistical significance of central retinal artery equivalent (CRAE) nor retinal arteriolar-to-venular ratio (AVR) among groups (both P＞0.05).Rmax was positively correlated with CRVE (r=0.27,P＜0.01) and negatively correlated with AVR (r=-0.16,P＜0.05),whereas Rmax had no correlation with CRAE (P＞0.05).CRVE was the impact factor of ipsilateral Rmax (B=0.243,P＜0.01),but the adjusted R2 of the model was weak (0.173).Area under the ROC curve of CRVE was 0.619 in assessing ICA moderate and severe stenosis,and taking threshold as 229.5μm,the sensitivity and specificity was 80.3％ and 40.1％,respectively.Conclusion CRVE can assess and predict ICA stenosis to some extent,but the diagnosis efficacy is limited.

Objective:To investigate the correlation between IL-10 and I1-17 expression levels in Mycoplasma pneumoniae pneumonia (MPP) and lung function.Methods:70 patients were included in this study.According to wheezing or not,they were divided into wheezing group and non-wheezing group.Another 30 healthy children were taken as a control group.After taking fasting blood 5ml,the serum IL-10 and IL-17 expression levels were detected by ELISA.The forced expiratory volume in one second (PEV1),peak expiratory flow (PEF) and forced vital capacity (FEV1 / FVC) of all subjects were detected.Results:The IL-10 expression level of the wheezing group were significantly different with that of the control group (P＜0.05) and that of the non-wheezing group (P＜0.05).The 1L-17 expression level of the wheezing group also had significant difference (P＜0.05) with that of the control group and non-wheezing group (P＜0.05).The IL-10 expression levels of wheezing and non-wheezing group all were lower than that of the control group.Whereas the IL-17 expression levels of wheezing and non-wheezing group all were higher than that in the control group.In addition,patients in wheezing group had higher PEV1,PEF,PVE1/FVC values than those in non-wheezing group,with significant difference (P＜0.05).The serum level of IL-10 expression of Mycoplasma pneumonia patients was positively correlated with PEV1,PEF and PVE1/FVC,while the serum level of IL-17 expression of Mycoplasma pneumonia patients was negatively correlated with PEV1,PEF and PVE1/FVC.Conclusion:The serum levels of IL-17 and IL-10 expression of Mycoplasma pneumonia children had close correlation with their pulmonary function.

Objective To explore the expression changes of C/EBP homologous binding protein (CHOP)in intermittent hypoxic rats with cognitive function decline and clinical significance.Methods We randomly divided 75 adult male Wistar rats into normal group (NC group),5% intermittent hypoxia group (5% CIH group)and 10%intermittent hypoxia group (10% CIH group),with 25 rats in each.Then the three groups were further divided into 3 d,7 d,14 d,21 d and 28 d subgroups,and each time a subgroup had 5 rats.The control group was exposed to the air while 10% CIH group and 5% CIH group were exposed to CIH for eight hours from 8:00 to 1 6:00 each day. After exposure for 3 d,7 d,14 d,21 d and 28 d,the cognitive function of rats was assessed with Morris water maze, the expression of CHOP in the hippocampus was assayed qualitatively by immunohistochemical technique,and the apoptosis of neurons was detected by TUNEL method.Results ① With prolonged hypoxia,the time of escape latency obviously prolonged,the time spent crossing the target quadrant shortened (P < 0.05 ),and the apoptosis index of hippocampal neurons in the CIH groups was increased gradually compared with those in control group (P <0.05).The above-mentioned indexes changed more significantly in 5% CIH group than in 10% CIH group (P <0.05).②.The expression of CHOP protein at each time point was increased (P <0.05 ).In 10% CIH group it reached the peak at 28 d while in 5% CIH group it decreased after it peaked at 21 d.③ The expression of CHOP in the two CIH groups was positively correlated with apoptosis index and animal escape latency time,but negatively correlated with the target quadrant time.Conclusion Intermittent hypoxia,which is likely to induce the high expression of CHOP and activation of neural CHOP mediated apoptosis,causes cognitive impairment of various degrees.

OBJECTIVE: To explore the effect and clinical significance of serum S100β and NSE on moderate and severe obstructive sleep apnea syndrome (OSAHS) after the continuous positive airway pressure (CPAP). METHOD: A total of 60 cases with obstructive sleep apnea were choosed with PSG in our hospital in June 2009 to June 2009. According to apnea hypoventilation index and at night the lowest oxygen saturation, divided into severe group (n=60) and moderate group (n=60), selecting 60 cases of healthy physical examination for a control over the same period. According to the length of the course of the disease in patients with each group can be divided into <5 years group, 5-10 years and > 10 years group, severe and moderate groups were recruited to undergo an CPAP treatment,both before and after treatment for 3 months, the lowest oxygen saturation, average blood oxygen saturation and apnea hypoventilation index were determined in moderate and severe groups with PSG, at the same time, serum S100β and NSE were determined with immune enzyme-linked adsorption testing before and after patients in different course of treatment and control group. RESULT: Compared with pretherapy of severe and moderate groups, the lowest oxygen saturation, average blood oxygen saturation and apnea hypoventilation index were ower after treatment (P<0. 05), serum S100β and NSE in severe and moderate groups before and after treatment were significantly higher than control group (P<0. 05), and two groups > 10 years before and after treatment in patients with serum according to beta and NSE levels higher than 5-10 patients, 5-10 patients before and after treatment according to beta and NSE serum levels higher than <5 years group of patients, the relation between the two groups of patients before and after treatment according to beta and NSE serum levels with the extension of history time increased. Before the treatment serum according to beta and NSE in patients with severe group were higher than moderate group before treatment (P< 0.05). Relation between the two groups after treatment according to beta and serum NSE was significantly decreased the (P<0. 05), the relation between the two groups after treatment according to beta and serum NSE, there was no statistically significant difference (p>0. 05), the relation between two groups according to beta, NSE serum are positively correlated with AHI (P < 0. 01). CONCLUTION CPAP significantly reduced serum S100β and NSE levels in patients with OSAHS, both may be important index which evaluated nervous system protection of CPAP in patients with OSAHS.
Continuous Positive Airway Pressure ; Humans ; Phosphopyruvate Hydratase ; blood ; S100 Calcium Binding Protein beta Subunit ; blood ; Sleep Apnea, Obstructive ; blood ; therapy