High Dietary Zinc Intake Is Associated with Shorter Leukocyte Telomere Length, Mediated by Tumor Necrosis Factor-α: A Study of China Adults.

OBJECTIVES: Diet can influence peripheral leukocyte telomere length (LTL), and various micronutrients have been reported to correlate with it. Zinc is known for its antioxidant properties and immunomodulatory effects. However, there are few epidemiological investigations on the relationship between dietary zinc intake and LTL. This study analyzed the association between dietary zinc and LTL and the potential role of inflammation and oxidative stress among them. DESIGN: Cross-sectional and community-based study. SETTING AND PARTICIPANTS: 599 participants from rural communities in the Changping suburb of Beijing, China, were recruited. MEASUREMENTS: Serum lipid profile, glycosylated hemoglobin (HbA1c), oxidative stress marker, and inflammatory cytokines levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Spearman analysis, restricted cubic splines (RCS), and general linear regression models were used to determine the association between dietary zinc intake and LTL. Simple regulatory models were also applied to analyze the role of inflammation and oxidative stress among them. RESULTS: A total of 482 subjects were ultimately included in this analysis. Spearman analysis showed that dietary zinc intake and zinc intake under energy density were negatively correlated with LTL (r=-0.142 and -0.126, all P <0.05) and positively correlated with tumor necrosis factor-α (TNF-α) (r=0.138 and 0.202, all P <0.05) while only dietary zinc without energy adjustment had a positive correlation with superoxide dismutase (SOD). RCS (P for non-linearity=0.933) and multiple linear regression (B=-0.084, P=0.009) indicated a negative linear association between dietary zinc and LTL. The adjustment of TNF-α rather than SOD could abolish the relationship. The mediation model suggested that the unfavorable effect of dietary zinc on LTL was mediated by TNF-α. CONCLUSIONS: High dietary zinc may correlate with telomere attrition, and TNF-α can act as a mediator in this relationship. In the future, more extensive cohort studies are needed to further explore the relationship between dietary zinc and cellular aging and the specific mechanisms.

Isotopic Resolution of Protein Complexes up to 466 kDa Using Individual Ion Mass Spectrometry.

Native mass spectrometry involves transferring large biomolecular complexes into the gas phase, enabling the characterization of their composition and stoichiometry. However, the overlap in distributions created by residual solvation, ionic adducts, and post-translational modifications creates a high degree of complexity that typically goes unresolved at masses above ∼150 kDa. Therefore, native mass spectrometry would greatly benefit from higher resolution approaches for intact proteins and their complexes. By recording mass spectra of individual ions via charge detection mass spectrometry, we report isotopic resolution for pyruvate kinase (232 kDa) and ß-galactosidase (466 kDa), extending the limits of isotopic resolution for high mass and high m/z by >2.5-fold and >1.6-fold, respectively.

Iron deficiency plays essential roles in the trigger, treatment, and prognosis of autosomal dominant hypophosphatemic rickets.

By analyzing iron status of 14 ADHR patients, we found that iron deficiency was an important trigger of ADHR. Correcting iron deficiency significantly improved patients' symptoms. Meanwhile, patients' serum phosphate showed positive correlations with iron metabolism parameters and hemoglobin-related parameters, suggesting the necessity of monitoring and correcting the iron status in ADHR. INTRODUCTION: Autosomal dominant hypophosphatemic rickets (ADHR) is unique for its incomplete penetrance, variety of disease onsets, and waxing and waning phenotypes. Iron deficiency is a trigger of ADHR. This study aimed to clarify the role of iron deficiency in ADHR. METHODS: Data of clinical manifestations and laboratory examinations were collected from patients among eight kindreds with ADHR. Multiple regression and Pearson's correlation tests were performed to test the relationships of serum phosphate levels and other laboratory variables during the patients' follow-ups. RESULTS: Among 23 ADHR patients with fibroblast growth factor 23 (FGF23) mutations, 14 patients presented with obvious symptoms. Ten patients had iron deficiency at the onset of ADHR, coinciding with menarche, menorrhagia, pregnancy, and chronic gastrointestinal bleeding. Two patients who did not have their iron status tested presented with symptoms after abortion and pregnancy in one patient each, which suggested that they also had iron deficiency at onset. Patients were treated with ferrous succinate tablets, vitamin C, and neutral phosphate and calcitriol. With correction of the iron status, the patients' symptoms showed notable improvement, with increased serum phosphate levels. Two patients' FGF23 levels also declined to the normal range. There were strong correlations between serum phosphate and serum iron levels (r = 0.7689, p < 0.0001), serum ferritin levels (r = 0.5312, p = 0.002), iron saturation (r = 0.7907, p < 0.0001), and transferrin saturation (r = 0.7875, p < 0.001). We also examined the relationships between serum phosphate levels and hemoglobin-related indices, which were significant (hemoglobin: r = 0.71, p < 0.0001; MCV: r = 0.7589, p < 0.0001; MCH: r = 0.8218, p < 0.0001; and MCHC: r = 0.7751, p < 0.0001). Longitudinal data of six patients' follow-up also showed synchronous changes in serum phosphate with serum iron levels. CONCLUSIONS: Iron deficiency plays an important role in triggering ADHR. Monitoring and correcting the iron status are helpful for diagnosing and treating ADHR. Iron metabolism parameters and hemoglobin-related parameters are positively correlated with serum phosphate levels in patients with ADHR and iron deficiency, and these might serve as good indicators of prognosis of ADHR.

[A three-year follow-up observation of a pedigree of maturity onset diabetes of the young caused by a novel mutation of glucokinase and literature review].

Objective: To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK). Methods: The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. The proband and her father were followed up for 3 years. Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD. Results: Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T (p. Ala450Thr). The proband was treated with diet and exercise control only. At the end of the follow-up, her fasting plasma glucose (FPG, 6.8 mmol/L), 2 h postprandial plasma glucose (2hPG, 7.4 mmol/L), and glycated hemoglobin (HbA1c, 6.3%) were all within the control targets. Additionally, the levels homeostasis model assessment of insulin resistance (HOMA-IR) tended to improved comparing to that at baseline (4.09 to 2.32), and glucose disposition index (DI) was improved compared with baseline (16.22 to 20.05). As to the proband's father, the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy. His FPG and 2hPG mostly were within the target range, and the levels of HbA1c were significantly reduced by 0.5%-0.7% when compared to that at baseline. The HOMA-IR or islet beta cell function was comparable to those at baseline. Conclusions: Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY, so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.

Multiplexed mass spectrometry of individual ions improves measurement of proteoforms and their complexes.

An Orbitrap-based ion analysis procedure determines the direct charge for numerous individual protein ions to generate true mass spectra. This individual ion mass spectrometry (I2MS) method for charge detection enables the characterization of highly complicated mixtures of proteoforms and their complexes in both denatured and native modes of operation, revealing information not obtainable by typical measurements of ensembles of ions.

Long non-coding RNA MIR503HG serves as a tumor suppressor in non-small cell lung cancer mediated by wnt1.

OBJECTIVE: The incidence and death rate of lung cancer has been rising year by year. Non-small cell lung cancer (NSCLC) seriously affects people's health and quality of life. This study was designed to explore the functional role of long-chain non-coding RNA (LncRNA) MIR503HG in the development of NSCLC. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was conducted to access the expression level of MIR503HG in NSCLC cell lines and tissues. The Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometric analysis were performed to assess the ability of MIR503HG in regulating cell proliferation and apoptosis in NSCLC. Subsequently, Western blotting was used to detect the expression level of Wnt1 in NSCLC. Besides, in vivo tumorigenesis assay was performed in nude mice to examine the ability of MIR503HG in tumor formation. RESULTS: MIR503HG was downregulated in NSCLC. CCK-8 assay and colony formation assay revealed that MIR503HG negatively regulated cell proliferation in NSLCL progression. In addition, MIR503HG promoted cell apoptosis and suppressed cell cycle progression in NSCLC in vitro. MIR503HG inhibited tumor formation in nude mice bearing NSCLC in vivo. MIR503HG downregulated Wnt1 expression in NSCLC. CONCLUSIONS: Lon non-coding RNA MIR503HG was downregulated in NSCLC. The over-expression of MIR503HG suppressed cell proliferation and promoted cell apoptosis in vitro and repressed tumorigenesis in vivo. MIR503HG suppressed NSCLC progression via negatively regulating Wnt1 expression.

STORI Plots Enable Accurate Tracking of Individual Ion Signals.

Charge detection mass spectrometry (CDMS) of low-level signals is currently limited to the analysis of individual ions that generate a persistent signal during the entire observation period. Ions that disintegrate during the observation period produce reduced frequency domain signal amplitudes, which lead to an underestimation of the ion charge state, and thus the ion mass. The charge assignment can only be corrected through an accurate determination of the time of ion disintegration. The traditional mechanisms for temporal signal analysis have severe limitations for temporal resolution, spectral resolution, and signal-to-noise ratios. Selective Temporal Overview of Resonant Ions (STORI) plots provide a new framework to accurately analyze low-level time domain signals of individual ions. STORI plots allow for complete correction of intermittent signals, the differentiation of single and multiple ions at the same frequency, and the association of signals that spontaneously change frequency.

Negative Association of Serum URIC Acid with Peripheral Blood Cellular Aging Markers.

OBJECTIVES: We aimed to explore the association between serum UA and cellular aging markers. DESIGN: The current cross-sectional analysis was based on data collected within a type 2 diabetes project. SETTINGS: Serum uric acid (UA), which has both antioxidant and pro-oxidant properties, is thought to be involved in cellular aging processes. PARTICIPANTS: There are 536 participants included in total, 65.3% of which are women. The average serum UA in women was 267.8 umol/l, lower than in men of 337.7 umol/l (P<0.001). MEASUREMENTS: Serum UA, blood lipid profile, HbA1c, plasma glucose and insulin were determined. The peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) were assessed using a real-time PCR assay. Logistic regressions were used to analyze the associations between serum UA and cellular aging markers. RESULTS: In Spearman's correlation analysis, there were significantly negative correlations between serum UA and LTL in both women and men (r=-0.162, P=0.006; and r=-0.232, P=0.004, respectively). The logistic regression adjusted for age, BMI, WC, daily energy intake, HbA1c, TG, and LDL-C revealed that the ORs of shorter LTL comparing the extreme serum UA quintiles was 5.52 (95% CI 1.69-18.02; P for trend =0.025) in women and 6.49 (95% CI 1.38-30.45; P for trend =0.108) in men. Furthermore, the OR (95% CI) for shorter LTL per 1 SD increment in serum UA was 1.51(1.10-2.07) in women and 1.64(1.01-2.65) in men. In regard to mtDNAcn, the association between elevated serum UA and lower mtDNAcn only reached significance in men when comparing the second and fifth quintiles with reference quintile (OR=3.73(1.07-13.04) and 3.76(1.01-14.09) , separately, and P for trend=0.066). CONCLUSIONS: Our results indicate a significant negative association between serum UA and peripheral blood cellular aging markers. Serum UA might play a role in promoting cellular aging.

[Research hotspot in IgG4-related sialadenitis].

IgG4-related disease is a novel clinical entity which can affect single or multiple organs. IgG4-related sialadenitis is referred to the salivary gland involvement of IgG4-related disease, with or without other organ involvement. IgG4-related sialadenitis is characterized by painless swelling or enlargement of salivary glands, high serum IgG4 level, abundant IgG4+ plasma cells infiltration with fibrosis histologically, and good response to glucocorticoids. With review of related articles, highlight and provide an overview of the most recent and focused findings and concepts of this disease, including the most significant pathogenic process based on kinds of immunocytes, cytokines, as well as participation of epithelial-mesenchymal transition, the clinical value of elevated serum IgG4 concentration and pathological role of infiltrated IgG4+ plasma cells, the potential relationship with salivary gland malignant tumor, the applying and usefulness of positron emission tomography-CT, the diagnostic utility of lip biopsy, treatment, prognosis, and also future perspectives.

Tuning dissimilarity explains short distance decline of spontaneous spike correlation in macaque V1.

Fast spike correlation is a signature of neural ensemble activity thought to underlie perception, cognition, and action. To relate spike correlation to tuning and other factors, we focused on spontaneous activity because it is the common 'baseline' across studies that test different stimuli, and because variations in correlation strength are much larger across cell pairs than across stimuli. Is the probability of spike correlation between two neurons a graded function of lateral cortical separation, independent of functional tuning (e.g. orientation preferences)? Although previous studies found a steep decline in fast spike correlation with horizontal cortical distance, we hypothesized that, at short distances, this decline is better explained by a decline in receptive field tuning similarity. Here we measured macaque V1 tuning via parametric stimuli and spike-triggered analysis, and we developed a generalized linear model (GLM) to examine how different combinations of factors predict spontaneous spike correlation. Spike correlation was predicted by multiple factors including color, spatiotemporal receptive field, spatial frequency, phase and orientation but not ocular dominance beyond layer 4. Including these factors in the model mostly eliminated the contribution of cortical distance to fast spike correlation (up to our recording limit of 1.4mm), in terms of both 'correlation probability' (the incidence of pairs that have significant fast spike correlation) and 'correlation strength' (each pair's likelihood of fast spike correlation). We suggest that, at short distances and non-input layers, V1 fast spike correlation is determined more by tuning similarity than by cortical distance or ocular dominance.

Mandible reconstruction with transport-disc distraction osteogenesis in children of deciduous dentition.

Reconstructing segmental mandibular defects in children of deciduous dentition is a challenge. The authors treated a 23-month-old girl with a segmental mandibular defect secondary to tumour resection. Considering the unpredictable negative impacts of the autogenous bone grafting method on the musculoskeletal system of the donor sites, which was growing rapidly at this age, the authors applied transport disc distraction osteogenesis (TDDO) to reconstruct the mandible discontinuity. To the best of the authors' knowledge, this is the first time TDDO has been used for mandible reconstruction in such a young patient with deciduous dentition. Aesthetics and function were restored satisfactorily at the end of treatment. The facial appearance and occlusion were stable through the 35 month follow-up, possibly due to the growth of the regenerated bone parallel with the rest of the maxillofacial skeleton. The satisfactory reconstruction also contributed to the patient's physical and psychological development. The success of mandible reconstruction with TDDO in this study casts new light on the management of segmental mandibular defect in children with deciduous dentition.

Double-step transport distraction osteogenesis in the reconstruction of unilateral large mandibular defects after tumour resection using internal distraction devices.

One-step transport disc distraction osteogenesis (TDDO) is an effective method for the restoration of mandibular defects. This study aimed to investigate the feasibility of double-step TDDO in the reconstruction of unilateral mandibular segmental defects after tumour resection using internal distraction devices. Six patients with unilateral mandibular segmental defects were reconstructed successfully with this technique. In the double-step TDDO procedure, the mandibular body was lengthened first and then the mandibular ramus was restored. The distraction movement was set at a rate of 0.4mm twice per day. Dental rehabilitation followed distractor removal. The maximal amount of lengthening was 55 mm in the mandibular body and 42 mm in the mandibular ramus. The average amount of lengthening was 52 mm in the mandibular body and 34 mm in the mandibular ramus. The aesthetic and functional results were excellent in all patients. The implants were integrated successfully and dental restoration was satisfactory. In this study, double-step TDDO is a reliable method for reconstruction of mandibular defects after tumour resection, especially for large mandibular defects. This technique is an ideal method for dental rehabilitation, despite the long overall treatment time.

Two-step transport-disk distraction osteogenesis in reconstruction of mandibular defect involving body and ramus.

One-step transport-disk distraction osteogenesis (TDDO) is effective for repairing segmental mandibular defects. The authors studied whether it was effective for reconstructing angled large mandibular defects using a two-step TDDO procedure in seven patients suffering from neoplasm. In the two-step TDDO procedure, the first distraction (horizontal distraction) was initiated immediately after mandibulectomy, aimed at restoring the mandibular body. It was followed by the second distraction, which was obliquely vertical and aimed at restoring the height of the ramus. The distraction rate was set at twice 0.4mm/day. The treatment lasted for 14-18 months. The horizontal distraction length ranged from 48 to 55mm, and the vertical one from 33 to 43mm, with full ossification in the distraction area. No obvious shift of mandible, malocclusion or mouth opening limitation was observed. Patients had a regular diet and spoke clearly. In conclusion, the two-step TDDO is still an option for the reconstruction of large angled mandibular defects when patients are prudently selected, despite the long treatment period required.

A method for assessing and maintaining the reproducibility of mass spectrometric analyses of complex samples.

Direct injection mass spectrometric analysis of biological samples is potentially an attractive approach to the discovery of diagnostic patterns for specific pathophysiological conditions because of its speed and simplicity. Despite the possible benefits offered by such a method, its extensive application has been limited so far by several factors, including the inadequate reproducibility of the analytical results. We describe a method for monitoring and optimizing the performance of mass spectrometers used for biomarker discovery studies, based on the analysis of patterns of standardized spectral features. The method was successfully applied to maintaining spectral reproducibility during a multi-day analysis of hundreds of serum samples despite an ion source failure, which necessitated minor maintenance. The monitoring method allowed the early detection of that failure and the restoration of the spectral profiles after the system was restarted.

A randomized controlled trial of high-permeability haemodialysis against conventional haemodialysis in the treatment of uraemic pruritus.

BACKGROUND: Uraemic pruritus (UP) is one of the most common problems in patients with chronic renal failure. Owing to the complexity of UP, no specific treatment is currently available. Recently, the accumulated toxins of mid and macro molecules in advanced renal failure have been proposed to play an important role in the mediation of pruritus. AIM: To evaluate the effect of high permeability haemodialysis (HPHD) against conventional haemodialysis (CHD) on UP. METHODS: A randomized, prospective, double-blind study was performed to compare the efficacy of HPHD against CHD in the treatment of UP. In total, 116 patients with chronic renal failure and UP were enrolled in the trial. A visual analogue scale (VAS) was used to assess the severity of itch. The toxins of mid and macro molecules [beta2-microglobulin (beta2-MG), parathyroid hormone (PTH), respectively] were measured, and the solute clearance rate (SCR) and urea clearance index (Kt/V) were also determined. RESULTS: The pruritus scores in the HPHD group were significantly lower (2.23 +/- 1.05) than those in the CHD group (5.45 +/- 1.91, P = 0.012), although the SCR and Kt/V showed no significance between the two groups (SCR P = 0.075; Kt/V P = 0.082). It was found that HPHD and CHD achieved a reasonable clearance rate of blood urea nitrogen and creatinine. However, the toxins of mid and macro molecules were markedly reduced in the blood of patients treated with HPHD, compared with those treated with CHD. The concentrations of PTH and beta2-MG were significantly reduced by HPHD in comparison with CHD (PTH 119.27 +/- 8.41 vs. 165.18 +/- 9.37 pmol/L, P = 0.01; beta2-MG 3.39 +/- 0.76 vs. 5.92+/- 1.58 g/mL, P = 0.012). CONCLUSIONS: These data indicate that HPHD can efficiently relieve UP through clearance of accumulated mid and macro molecules in vivo. This further supports the hypothesis that these molecules are involved in UP.

A method for monitoring and controlling reproducibility of intensity data in complex electrospray mass spectra: a thermometer ion-based strategy.

Reproducibility in mass spectral data is important in both biomarker discovery and spectral database searching. We report a strategy, employing a series of substituted benzylpyridinium thermometer ions that can be used to monitor changes in performance of multiple aspects of an electrospray ionization source that impact the intensity axis of a spectrum. Performance attributes, which could confound even isotope-based quantification strategies, are readily assessed using a mixture of thermometer ions. Based on the observed behavior of the ions, a procedure is proposed for monitoring instrument performance and compensating for factors that affect reproducibility across both time and instruments.

Detection of telomerase activity in saliva from oral squamous cell carcinoma patients.

Tumor markers have been detected in saliva from patients with oral cancers. In order to investigate the expression of telomerase in saliva and its clinical significance. Sixty-two saliva specimens were collected from 32 patients with oral squamous cell carcinoma and 30 normal persons, the telomerase activity was assayed by telomerase PCR-ELISA method. It was detected positively in 75.0% (24/32) of patients with oral squamous cell carcinoma, while it was positive in 6.67% (2/30) of normal persons, the statistical difference was significant with P < 0.001. But the difference of expression of telomerase activity between the patients in clinical early and late stage was not significant with P > 0.05, the same to that between the patients with and without lymph nodes metastasis with P > 0.05. The results suggest that the telomerase in saliva could be used as an assistant marker for oral squamous cell carcinoma, however, a larger study is encouraged to confirm the value of judgement on clinical stage and lymph nodes metastasis.