Vitamin E protects dopaminergic neurons against manganese-induced neurotoxicity through stimulation of CHRM1 and KCNJ4.

BACKGROUND: Manganese (Mn) overexposure can induce neurotoxicity and lead to manganism. Vitamin E (Vit E) has neuroprotective effects by acting as an ROS scavenger, preventing mitochondrial dysfunction and neuronal apoptosis. However, the effects of Vit E on Mn-induced nigrostriatal system lesions remains unknown. OBJECTIVES: We aim to investigate whether Vit E has protective effects on Mn-induced nigrostriatal system lesions and mRNA expression profiles in the SN of mice. METHODS: Sixty 8-week-old C57BL/6 male mice were randomly divided into the Control, MnCl2, MnCl2 +Vit E, and Vit E group. Twenty-four hours after the last injection, the behaviour test was performed. The numbers of dopaminergic neurons in Substantia nigra (SN), the contents of dopamine and its metabolite levels in striatium, and the morphology of mitochondria and nuclei in the dopaminergic neurons in SN were detected by immunofluorescence staining, high-performance liquid chromatography, and transmission electron microscopy. Transcriptome analysis was used to analyze the signaling pathways and RT-PCR was used to verify the mRNA levels. RESULTS: Vit E ameliorates behavioral disorders and attenuates the loss of nigral dopaminergic neurons in the Mn-induced mouse model. In addition, Vit E antagonized Mn-induced toxicity by restoring mitochondrial function. The results of transcriptome sequencing and RTPCR show that the protective effect of Vit E was related to the upregulation of CHRM1 and KCNJ4 mRNA in the SN. CONCLUSIONS: Vit E has neuroprotective effects on Mn-induced neurodegeneration in the nigrostriatal system. This effect may be related to the upregulation of CHRM1 and KCNJ4 mRNA stimulated by Vit E in the SN.

Correlation between dietary theobromine intake and low cognitive performance in older adults in the United States: A cross-sectional study based on the National Health and Nutrition Examination Survey.

BACKGROUND AND OBJECTIVES: Few studies have investigated the effects of dietary theobromine intake on the cognitive performance of older adults. Therefore, we investigated these effects in older adults in the United States. METHODS AND STUDY DESIGN: In this cross-sectional study, we used data (2011-2014) from the National Health and Nutrition Examination Survey. Intake of theobromine intake was obtained through two 24-h dietary recall interviews and was adjusted by energy. Cognitive performance was assessed using the animal fluency test, Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD), and Digit Symbol Substitution Test (DSST). Logistic regression and restricted cubic spline models were constructed to evaluate the correlation between the dietary intake of theobromine from different sources and the likelihood of low cognitive performance. RESULTS: The fully adjusted model revealed that compared with the lowest quintile, the odds ratios (with 95% confidence intervals) of cognitive performance in the CERAD test were 0.42 (0.28-0.64), 0.34 (0.14-0.83), 0.25 (0.07-0.87), and 0.35 (0.13-0.95) for the highest quintile of total theobromine intake and that from chocolate, coffee, and cream, respectively. Dose-response relationship analysis indicated nonlinear correlations between the likelihood of low cognitive performance and die-tary theobromine (total intake and that from chocolate, coffee, and cream). An L-shaped relationship was ob-served between total theobromine intake and cognitive performance in the CERAD test. CONCLUSIONS: The dietary intakes of theobromine (total and that from chocolate, coffee, and cream) may protect older adults, particularly men, against low cognitive performance.

Association between urinary phthalate metabolites and hyperuricemia in US adults.

Phthalate metabolites have been detected from urine in most of the US population and have become a public health problem. However, the association between phthalate metabolites and hyperuricemia has been scarcely studied so far. We aimed to evaluate if phthalate metabolites were associated with hyperuricemia in US adults. A total of 8816 participants of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were included in our study. We used multivariable logistic regression models and restricted cubic spline (RCS) models to explore the association between urinary phthalate metabolites and hyperuricemia. Then, stratified analyses were conducted by sex and age. The prevalence of hyperuricemia in the study sample was 20.35%. Compared to the lowest quantile, the odds ratios (ORs) and 95% confidence intervals (CIs) for hyperuricemia were all statistically significant in following phthalate metabolites: 1.34 (1.13-1.58) for the second quartile in Mono-isobutyl phthalate (MiBP), 1.21 (1.01-1.46) for the highest quartile in Mono-(carboxyoctyl) phthalate (MCOP), 0.66 (0.56-0.76) for the second quartile in Mono-(2-ethyl)-hexyl phthalate (MEHP), 1.22 (1.05-1.43) for quartile 2 in Benzyl butyl phthalate (ΣBBP), and 1.43 (1.22-1.66) for the third quartile in high molecular-weight phthalate (ΣHigh MWP), respectively. Our results indicate that several urinary phthalate metabolites are positively associated with the odds of hyperuricemia.

Association between mixed dioxin exposure and hyperuricemia in U.S. adults: A comparison of three statistical models.

BACKGROUND: Previous studies on the relationship between dioxin exposures and hyperuricemia have usually been based on multi-chemical linear models. However, the complex nonlinear relationship and interaction between mixed dioxin exposures and hyperuricemia have seldom been studied. In this study, we applied three different statistical models to assess the joint effect of 12 dioxins on hyperuricemia. METHODS: A total of 7 dioxin-like polychlorinated biphenyls (DL-PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 2 polychlorinated dibenzofurans (PCDFs) were measured in the serum of adults by the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004. We fitted multivariable logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association of individual and mixed dioxin exposures with hyperuricemia. RESULTS: Among the 1008 individuals included in our analysis, 20.04% had hyperuricemia. In the multivariable logistic regression established for each single dioxin, PCB28, PCB74, PCB105, PCB118, and 1,2,3,4,6,7,8-HPCDD were positively associated with hyperuricemia. With including all dioxins in the multivariable logistic regression model simultaneously, only PCB28 and 1,2,3,4,6,7,8-HPCDD were positively associated with hyperuricemia. In the WQS regression model, the WQS index was significantly associated (OR (95% CI): 2.32 (1.26, 4.28)) with hyperuricemia, and 1,2,3,4,6,7,8-HPCDD (weighted 0.22) had the largest contribution. In BKMR analysis, a significant positive association was found between mixed dioxin exposure and hyperuricemia when all dioxins were at their 60th percentile or above, compared to their 50th percentile. The univariate exposure-response function showed that PCB105 and PCB118 were positively associated with hyperuricemia. CONCLUSION: By comparing the three statistical models, we concluded that the whole-body burden of 12 dioxins was significantly positively associated with hyperuricemia. PCB105, PCB118, and 1,2,3,4,6,7,8-HPCDD played the most important roles in hyperuricemia.

Temporal Associations between Tri-Ponderal Mass Index and Blood Pressure in Chinese Children: A Cross-Lag Analysis.

Background: No longitudinal studies have explored the relationship between tri-ponderal mass index (TMI) and blood pressure (BP) in children. This study is aimed to investigate the temporal associations between TMI and BP among children in China. Methods: A longitudinal study was carried out with Chinese children from 2014 to 2019. Data of the anthropometric examination and blood pressure were collected annually. TMI was calculated by dividing weight by the cube of height. BP was measured using a standard mercury sphygmomanometer. We investigated temporal associations between TMI and BP with a cross-lagged panel model using repeated measure data from 2014 (Wave 1), 2016 (Wave 2), and 2018 (Wave 3). Results: Results of the cross-lagged panel model showed that TMI was associated with subsequent BP. Participants with higher levels of TMI presented higher levels of BP (Wave 1: ß = 0.737 for systolic blood pressure (SBP) and ß = 0.308 for diastolic blood pressure (DBP), Wave 2: ß = 0.422 for SBP and ß = 0.165 for DBP, p < 0.01). In addition, children with higher BP could also present higher TMI (Wave 1: ß = 0.004 for SBP and ß = 0.006 for DBP, Wave 2: ß = 0.003 for SBP and ß = 0.005 for DBP, p < 0.01), but the cross-lag path coefficient indicated that the influence of TMI on BP was stronger than the influence of BP on TMI. Conclusions: There was a temporal association between TMI and BP in Chinese children. Higher TMI predicted higher subsequent BP rather than the reverse relationship.

Expression and prognostic analysis of BGN in head and neck squamous cell carcinoma.

OBJECTIVE: BGN belongs to class of small leucine rich proteoglycans, which is high expression in plenty of human cancers. However, the detailed role of BGN remains unclear in Head and neck squamous cell carcinoma (HNSC). MATERIALS AND METHODS: In this study, we assessed the transcriptional expression, protein expression, prognosis, co-expressed genes, functional enrichment, and hub genes in HNSC patients based on the data published in the following databases: ONCOMINE, GEPIA, GEO, LinkedOmics, and HPA databases. Data from the TCGA database was used to analyze the correlations between BGN expression and different clinicopathological features, as well as prognostic analysis. RESULTS: We found that the expression of BGN is higher in patients with HNSC than in control tissues. Pathologically, high BGN expression was significantly correlated with T3 and T4 stage. Besides, high expression of BGN is a poor prognostic factor for overall surviva, not disease free survival. The co-expression genes associated with BGN expression exhibited enriched in various function and pathway, such as extracellular matrix, mitochondrion, PI3K-Akt signaling pathway. A total of 10 hub genes were identified from the co-expressed genes, within which five genes, including FSTL1, LAMB1, SDC2, VCAN, and IGFBP7, were significantly increased in patient's with HNSC. BGN exhibited weak correlations with tumor-infiltrating CD4+ T, macrophages cell, and dendritic cells. Futhermore, many markers of infiltrating immune cells, such as Treg, showed different BGN-related immune infiltration patterns. BGN expression showed strong correlations with diverse immune marker sets in COAD and STAD. CONCLUSIONS: Our results demonstrated that BGN is high expression in HNSC and is a poor prognostic factor for clinical outcome in patients with HNSC. It could serve as a potential prognostic biomarker for patients survival in HNSC.

[Clinical characteristics analysis of patients with Meniere's disease and vestibular migraine].

Objective:To analyze the clinical characteristics of patients with Meniere's disease and vestibular migraine, improve the understanding of such diseases for accurate treatment. Method:Eighteen patients with MD and VM were reviewed and the clinical characteristics of the patients were evaluated. Result:There were 4 males and 14 females whose average age was 55.2 years old. The average onset age was 36.5 years meanwhile the headache occured 7.5 years earlier than the vertigo. The average time of vertigo attacks was 30 min-24 h; The mainly kind of headache was unilateral pulsatile headache with or without vertigo attacks; All patients showed the characteristics of photophobia or phonophobia, 7 of them showed visual aura and 9 of them experienced vertigo attacks with headache but without auditory symptoms; 11 patients experienced motion sickness and 10 patients had a related family history. Electrocochleogram abnormal was 11 ears; c-VEMP abnormal was 11 cases; Caloric test abnormal was 13 cases; Velocity step test abnormal was 4 cases. Conclusion:MD and VM shows recurrent vertigo, There are evidences of hearing loss and abnormal changes of electrocochleogram、c-VEMP and lateral semicircular canal function in MD; VM experienced migraine attacks with the characteristics of photophobia、phonophobia and visual aura; The patients can be diagnosed with overlap syndrome when they fulfill the diagnostic criteria of MD and VM at the same time and the two diseases should be treated at the same time.

[Efficacy of semicircular canal occlusion in the treatment of fifteen pateints with Meniere's disease].

Objective:To investigate the long-term efficacy of semicircular canal occlusion in the treatment of refractory Meniere's disease. Method:Fifteen patients with Meniere's disease who underwent semicircular canal occlusion were reviewed. The preoperative and postoperative frequency of vertigo ,quality of life, hearing and tinnitus level were compared. All patients were followed for more than 24 months. Result:Postoperatively, vertigo was controlled effectively in all 15 cases, and the control rate was 100%, of which 11 cases were completely controlled（Grade A） and 4 cases were basically controlled（Grade B）. The improvement rate of quality of life was 100%. The hearing worse in 4 cases（26.7%） and stabilized in 11 cases（73.3%）. The tinnitus was relieved in 7 cases（46.7%）, unchanged in 7 cases（46.7%） and aggravated in 1 case（6.7%）. Conclusion:Semicircular canal occlusion can effectively control the vertigo symptoms of refractory Meniere's disease and improve the quality of life. The long-term efficacy of semicircular canal occlusion is definite, but there is a risk of hearing loss.

[Anatomical measurements and clinical applications through facial recess approach].

OBJECTIVE: To provide the anatomic data for the correlated otologic microsurgery by the microdissection of temporal bone through facial recess approach. METHOD: Sixteen human temporal bones of eight adult cadaveric heads were dissected under surgical microscope through facial recess approach, and the relative anatomic structures were observed and measured, such as the bony entrance of facial recess approach, facial nerve, stapes, round window, round window niche, pyramidal eminence, cochleariform process, etc. The data were analyzed statistically. RESULT: The width of the bony entrance of facial recess approach was (2.94 +/- 0.32) mm, the height was (8.83 +/- 0.84) mm, the depth was (3.51 +/- 0.17) mm. The distances from stapes to tympanic segment of facial nerve, mastoid segment of facial nerve, round window, cochleariform process and anterior ligament of malleus were (1.38 +/- 0.21) mm, (6.94 +/- 0.47) mm, (3.60 +/- 0.55)mm, (2.23 +/- 0.33)mm, (4.93 +/- 0.61) mm, respectively. The distances from pyramidal eminence to tympanic segment of facial nerve, mastoid segment of facial nerve, round window, round window niche and cochleariform process were (1.05 +/- 0.09) mm, (5.63 +/- 0.41) mm, (3.01 +/- 0.34) mm, (3.29 +/- 0.44) mm, (4.13 +/- 0.51) mm, respectively. The distances from round window to cochleariform process and tympanic segment of facial nerve were (5.11 +/- 0.61) mm and (3.97 +/- 0.61) mm. The distances from round window niche to tympanic segment of facial nerve and mastoid segment of facial nerve were (4.13 +/- 0.38) mm and (7.28 +/- 0.29) mm. CONCLUSION: The facial recess approach played an important role in modern otologic microsurgery. The position of anatomical structure was constant relatively, including short crus of incus, stapes, pyramidal eminence and cochleariform process, etc. These could be used as reference marks for otologic microsurgery.

[Clinical characteristics and surgical management of extensive cholesteatoma of external auditory canal].

OBJECTIVE: To classify the external auditory canal cholesteatoma(EACC) by high-resolution temporal bone CT scans and the clinical findings of the patients, and to discuss the clinical and imaging characteristics and the surgical management of the extensive EACC. METHOD: A retrospective study was carried out among 56 patients (58 ears) with EACC and their clinical data were carefully analyzed. We classified EACC as the extensive type and the localized type. The operation strategy depended on the extent of lesion. All cases were followed up for 1 to 6 years after surgery. RESULT: There were 31 patients with localized EACC, 2 with no bone erosion and 29 (31 ears) with bone erosion within external auditory canal, and 25 patients with extensive EACC, 16 with bone erosion of intra temporal bone and 9 with bone erosion of extra temporal bone. Among all the 25 patients with the extensive type, the most common symptoms were otorrhea, otalgia and hearing loss, with 25, 23, 22 cases, respectively. The tympanic membrane (TM) was intact in 23 patients and perforated in two. The mastoid air cells in 23 patients were involved by the lesion, as well as tympanic antrum in eight, tympanic cavity in two, sigmoid sinus bony wall in five, mastoid segment of facial canal in four, and temporomandibular joint in two patients. Twenty patients underwent modified radical mastoidectomy, only one underwent reconstruction of ossicular chain, and four underwent canaloplasty. The average time of ear dry after surgery was 29 days. The postoperative hearing was improved by an average of 15 dB. No recurrence except for one patient was found during the follow-up period. CONCLUSION: It was of important clinical significance to classify EACC as the extensive type and the localized type. The extensive EACC was misdiagnosed easily because of the complicated clinical manifestations. The classification was helpful for the diagnosis and the selection of surgery strategy of EACC.

[Clinical analysis of bilateral same-day myringoplasty for 22 cases with bilateral tympanic membrane perforation].

OBJECTIVE: To investigate the feasibility of bilateral same-day myringoplasty and the indications for myringoplasty for patients with bilateral tympanic membrane perforation, and to summarize relevant experience. METHODS: Twenty-two patients underwent bilateral same-day underlay myringoplasty, and all cases were consistent with the indications for myringoplasty. The preoperative hearing and postoperative hearing at three months were compared, and the postoperative symptoms and complications were observed. Forty patients underwent monaural myringoplasty as the control group over the same period. All cases were followed up for 1 - 3 years. RESULTS: The postoperative hearing was increased by an average of 18 dB, and the rate of closure of tympanic membrane perforation was 93.2% (41/44). There were seven patients with ear fullness after operation in the bilateral myringoplasty group and two patients in the control group (χ(2) = 4.5374, P = 0.0332). There were no differences in the postoperative hearing improvement, the rate of closure and the rates of other discomfort symptoms except for ear fullness between the two groups (P > 0.05). CONCLUSION: It was feasible and safe to perform bilateral same-day myringoplasty for bilateral tympanic membrane perforation, but the postoperative temporary discomfort of bilateral ear fullness should be informed the patients in advance.