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

OBJECTIVE: To investigate the effectiveness of the suture anchor technique without knots for reconstruction of the anterior talofibular ligament (ATFL) combined with the reinforcement of the inferior extensor retinaculum in treating chronic lateral ankle instability (CLAI). METHODS: The clinical data of 31 patients with CLAI who were admitted between August 2017 and December 2023 and met the selection criteria were retrospectively analyzed. There were 18 males and 13 females, with an age range from 20 to 48 years (mean, 34.6 years). All patients had a history of repeated ankle sprain, with a disease duration of 6-18 months (mean, 9.65 months). The anterior drawer test and inversion stress test were positive, and tenderness was present in the ligament area. Stress X-ray films of the ankle joint showed a talar tilt angle of (10.00±2.78)° and an anterior talar displacement of (9.48±1.96) mm on the affected side. MRI revealed discontinuity, tortuosity, or disappearance of the ATFL structure. Preoperatively, the visual analogue scale (VAS) score was 5.2±2.1, and the American Orthopaedic Foot and Ankle Society (AOFAS) score was 62.9±7.1. All patients underwent arthroscopic debridement of the ankle joint followed by reconstruction of the ATFL using the suture anchor technique without knots combined with reinforcement of the inferior extensor retinaculum. Postoperatively, pain and function were assessed using the VAS and AOFAS scores. Stress X-ray films were taken to measure the talar tilt angle and anterior talar displacement to evaluate changes in ankle joint stability. Patient satisfaction was assessed according to the Insall criteria. RESULTS: All 31 surgeries were successfully completed. One case had wound exudation, while the remaining surgical incisions healed by first intention. Two cases experienced numbness on the lateral aspect of the foot, which disappeared within 1 month after operation. All patients were followed up 15-84 months (mean, 47.2 months). No complication such as anchor loosening, recurrent lateral ankle instability, superficial peroneal nerve injury, rejection reaction, or wound infection occurred postoperatively. The anterior drawer test and inversion stress test were negative at 3 months after operation. Stress X-ray films taken at 3 months after operation showed the talar tilt angle of (2.86±1.72)° and the anterior talar displacement of (2.97±1.32) mm, both of which were significantly different from the preoperative values ( t=12.218, P<0.001; t=15.367, P<0.001). At last follow-up, 2 patients had ankle swelling after exercise, which resolved spontaneously with rest; all 31 patients returned to their pre-injury level of sports or had no significant discomfort in daily activities. At last follow-up, 25 patients were pain-free, 4 had mild pain after exercise, and 2 had mild pain after walking more than 2 000 meters. The VAS score was 0.8±0.9 and the AOFAS score was 91.6±4.1, both of which were significantly different from the preoperative scores ( t=10.851, P<0.001; t=-19.514, P<0.001). According to the Insall criteria, 24 patients were rated as excellent, 4 as good, and 3 as fair, with a satisfaction rate of 90.3%. CONCLUSION The suture anchor technique without knots for reconstruction of the ATFL combined with reinforcement of the inferior extensor retinaculum provides satisfactory short- and mid-term effectiveness in treating CLAI.
Humans ; Male ; Adult ; Female ; Joint Instability/surgery* ; Lateral Ligament, Ankle/surgery* ; Retrospective Studies ; Middle Aged ; Ankle Joint/diagnostic imaging* ; Young Adult ; Suture Anchors ; Treatment Outcome ; Suture Techniques ; Plastic Surgery Procedures/methods* ; Chronic Disease ; Ankle Injuries/surgery*

Objective:To investigate the clinical characteristics and treatment outcomes of patients with blast-induced hearing loss（BIHL）. Methods:The clinical features, laboratory parameters, audiometric profiles, and treatment efficacy of patients with blast induced hearing loss and those with idiopathic sudden hearing loss（ISHL） were analyzed using t-tests, Wilcoxon rank-sum tests, and chi-square tests, with a significance level set at P<0.05. Results:A total of 59 patients in the BIHL group and 117 patients in the ISHL group were included in this study. The mean age of the BIHL group was（39.07±14.49） years, comprising 45 males and 14 females. After the blast, 21 patients went to the hospital within the initial 14-day period, and an additional 38 patients seeking admission thereafter. In the BIHL group, 33 patients had unilateral hearing loss with PTA of （50.30±28.85） dB HL, while 26 had bilateral hearing loss with a PTA of（44.54±26.22） dB HL. In comparison, among the ISHL group, 112 patients had unilateral hearing loss with a PTA of（56.28±14.19） dB HL, and 5 had bilateral involvement with a PTA of（56.25±35.14） dB HL. The effective treatment rate within 14 days for the BIHL group was 31.8%, while for the ISHL group, the effective rate within 14 days was 77.0%. Conclusion:Blast-induced hearing loss is caused by exposure to high-intensity noise. The overall treatment effectiveness during hospitalization is lower compared to idiopathic sudden hearing loss, and the treatment window is shorter. Therefore, greater emphasis should be placed on prevention.
Humans ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; Blast Injuries/therapy* ; Treatment Outcome ; Hearing Loss, Sudden/etiology* ; Adolescent ; Hearing Loss, Noise-Induced/diagnosis*

OBJECTIVES: To compare the efficacy of toric implantable collamer lens (Toric-ICL) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction in patients with moderate to high myopia complicated with astigmatism. METHODS: We retrospectively collected data from 64 patients (aged 18-42 years) with moderate to high myopia complicated with astigmatism (128 eyes) undergoing either Toric-ICL (28 patients/56 eyes) or FS-LASIK (36 patients/72 eyes) at our department between January, 2019 and December, 2020. The changes of uncorrected distance visual acuity (UCVA), spherical equivalent (SE), mean astigmatism correction index (CI), corneal endothelial cell density (ECD) and intraocular pressure (IOP) following the procedures were compared between the two groups. RESULTS: In FS-LASIK group, all the eyes (72/72) achieved an UCVA≥1.0, similar to the rate in Toric-ICL group (55/56 eyes; P=0.2374). The postoperative SE was also comparable between FS-LASIK and Toric-ICL groups [0.43±0.06 D (range: -1.0 to 1.50 D) vs 0.38±0.05 D (range: -0.75 to 1.00 D); P=0.56]. The mean astigmatism CI was significantly higher in FS-LASIK group than in Toric-ICL group (0.8561 vs 0.7176; P<0.0001), and 88.89% of the eyes in FS-LASIK group and 69.64% in Toric-ICL group had postoperative astigmatism ≤0.50 D. No significant changes were observed in postoperative corneal ECD in FS-LASIK group, whereas ECD decreased significantly after the procedure in Toric-ICL group (P=0.0057). The patients undergoing Toric-ICL exhibited no significant changes of postoperative IOP, but the patients receiving FS-LASIK had significantly reduced IOP after the procedure (P<0.001). CONCLUSIONS Although the patients included in Toric-ICL group had higher myopia and astigmatism, Toric-ICL still showed better predictability and efficacy for astigmatic correction in Toric-ICL group. Toric-ICL is an effective and safe equivalent of FS-LASIK for correcting moderate myopia but can be more advantageous for correcting high myopia with astigmatism.
Humans ; Astigmatism/complications* ; Myopia/complications* ; Keratomileusis, Laser In Situ/methods* ; Retrospective Studies ; Adult ; Visual Acuity ; Adolescent ; Young Adult ; Treatment Outcome ; Male ; Lens Implantation, Intraocular/methods* ; Female ; Phakic Intraocular Lenses ; Intraocular Pressure

Objectives To analyze the spatial and temporal aggregation of multidrug resistant pulmonary tuberculosis (MDR-TB) incidence in Nanning at the township / street scale from 2017 to 2021, to explore the spatial and temporal characteristics of the spread of MDR-TB in Nanning, and to provide a scientific reference basis for the health administrative departments to achieve the precise implementation of MDR-TB prevention and control. Methods Based on the data of MDR-TB cases in Nanning from 2017 to 2021, the spatial-temporal scanning analysis software SaTScan v9.7 was used to retrospectively detect and analyze the areas where MDR-TB cases gathered. Results Through simple spatial scanning analysis, it was found that there were three first-class aggregation areas (the aggregation center was Fujiayuan Street, Jiangnan District, 2017, Xinyang Street, Xixiangtang District, 2019, and Zhonghe Town, Yongning District, 2020), and one second-class aggregation area (the aggregation center was Jinchai Town, Mashan County, 2020). Simple time scanning showed that the clustering occurred from May 2019 to December 2020. Temporal and spatial aggregation analysis showed that Xinyang Street in Xixiangtang District was the center of the first-class aggregation area, Zhonghe Town in Yongning District was the center of the second-class aggregation area, and Jinchai Town in Mashan County was the center of the third-class aggregation area. Conclusion The multidrug resistant pulmonary tuberculosis epidemic in Nanning is distributed in an aggregated manner, especially in Xinyang Street, Xixiangtang District, which has the highest spatial and temporal aggregation. It is necessary to focus on and take regional prevention and control measures to control the epidemic.

Objective:To investigate possible neuromodulatory mechanisms involved in the involvement of parvalbu-min(PV)expression in the basal ganglia output nuclei,entopeduncular nucleus(EPN)and substantia nigra pars etic-ulata(SNr),in exercise-induced chronic fatigue impairs working memory capacity.Methods:Male SD rats were divid-ed into control group and Fatigue group by random number method,and a three-stage incremental load treadmill training program was selected to establish a chronic exhaustion exercise-induced fatigue rat model.The working memory ability of rats was assessed by the Y-maze autonomous alternation experiment.Immunohistochemical staining was used to ob-serve the expression of parvalbumin(PV)positive neurons and cysteine aspartate-specific protease-3(caspase-3)in EPN and SNr of rats.Results:The accuracy of voluntary alternation in the fatigue group was obviously lower than that in control group(P＜0.05).The results of immunohistochemical staining showed that the density of PV positive neu-rons and the degree of positive fiber staining in EPN and SNr in the fatigue group were obviously lower than those in the control group(P＜0.05,P＜0.01).The number of caspase-3 positive cells per unit area of EPN and SNr in the fa-tigue group was obviously higher than that in the control group(P＜0.05,P＜0.01).Conclusion:The mechanism of impairing working memory in rats caused by exercise-induced chronic fatigue may be related to the apoptosis of PV posi-tive neurons in EPN and SNr.

Objective:To investigate the protective mechanism of TRPV4 channel inhibitor on blood-brain barrier(BBB)damage after traumatic brain injury(TBI).Methods:The TBI rat model was established.TRPV4 channel inhibitor HC067047 or PKC-δ inhibitor Rottlerin was used to detect changes in BBB permeability,neurological function score,and the expression of microvascular endothelial tight junction proteins ZO-1 and ZO-2 in brain injury areas after TBI.Results:Compared with the Sham group,BBB permeability significantly increased,brain neurological function score significantly decreased,and the expression of ZO-1 and ZO-2 significantly decreased in TBI group(P＜0.05).Compared with the TBI group,after administration of HC067047 or Rottlerin,changes in BBB permeability,brain neurological function score,the expression of ZO-1 and ZO-2 were partially reversed(P＜0.05).Conclusions:TBI-induced BBB injury may be mediated by TRPV4 channel regulating PKC-δ signaling pathway to affect the expression of tight junction proteins ZO-1 and ZO-2.Inhibition of TRPV4 channel function or PKC-δ signal molecule can partially alleviate BBB damage induced by TBI.This study may provide new ideas for the treatment of clinical TBI.

BACKGROUND:Hyperhomocysteinemia is closely related to the function of islet β cells,but its specific molecular mechanism is not fully understood. OBJECTIVE:To investigate the role of N6 methyltransferase-like 3(METTL3)in homocysteine(Hcy)-induced autophagy of mouse islet β cells. METHODS:The 3rd and 4th generation mouse islet β cells were taken for the experiment.(1)Cell modeling and grouping:cells in control group were not treated with Hcy,while those in homocysteine group were treated with 100 μmol/L Hcy for 48 hours.(2)The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000.Three different interfering fragments were designed,and the one with the best interfering efficiency was verified and screened by PCR.(3)After transfection,the cells were divided into control group,Hcy group,Ad-NC(negative control)+Hcy group,Ad-METTL3+Hcy group,si-NC(negative control)+Hcy group and si-METTL3+Hcy group.(4)qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3Ⅱ/Ⅰ and p62 in cells.Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells.Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION:Compared with the control group,the expression level of LC3Ⅱ/Ⅰ was increased(P＜0.05),the expression of p62 was significantly reduced(P＜0.05),and the insulin secretion capacity was significantly decreased(P＜0.05)in the Hcy group.Compared with the control group,the protein and mRNA levels of METTL3 were reduced in the Hcy group(P＜0.05).After METTL3 silencing in islet β cells,Hcy further upregulated the expression of LC3Ⅱ/Ⅰ(P＜0.05),significantly dowregulated the expression of p62(P＜0.05),and increased the insulin level(P＜0.05).After overexpression of METTL3,Hcy significantly decreased the LC3Ⅱ/Ⅰ expression and increased the p62 expression in islet β cells(P＜0.05).To conclude,METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion.

Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data（including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography）, imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.
Humans ; Connexins/genetics* ; Connexin 26/genetics* ; Hearing Loss, Central/genetics* ; Deafness/genetics* ; Mutation