Expert Consensus on Prevention and Treatment of Aging-Related Gonadal Dysfunction.

Aging-related hypogonadism involves complex mechanisms in humans, predominantly relating to the decline of multiple hormones and senile gonads. Late-onset hypogonadism (LOH) and erectile dysfunction (ED) are the main manifestations in men, while premature ovarian insufficiency (POI) and menopause are the main forms in women. Anti-aging measures include lifestyle modification and resistance training, hormonal supplementation, stem cell therapy, metformin, and rapamycin. In this expert consensus, the mechanisms, efficacy, and side effects of stem cell therapy on aging gonadal function are reviewed. Furthermore, various methods of stem cell therapy, administered intravenously, intracavernously, and intra-ovarially, are exemplified in detail. More clinical trials on aging-related gonadal dysfunction are required to solidify the foundation of this topic.

Relationship among α­synuclein, aging and inflammation in Parkinson's disease (Review).

Parkinson's disease (PD) is a common neurodegenerative pathology whose major clinical symptoms are movement disorders. The main pathological characteristics of PD are the selective death of dopaminergic (DA) neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein (α-Syn) within these neurons. PD is associated with numerous risk factors, including environmental factors, genetic mutations and aging. In many cases, the complex interplay of numerous risk factors leads to the onset of PD. The mutated α-Syn gene, which expresses pathologicalα-Syn protein, can cause PD. Another important feature of PD is neuroinflammation, which is conducive to neuronal death. α-Syn is able to interact with certain cell types in the brain, including through phagocytosis and degradation of α-Syn by glial cells, activation of inflammatory pathways by α-Syn in glial cells, transmission of α-Syn between glial cells and neurons, and interactions between peripheral immune cells and α-Syn. In addition to the aforementioned risk factors, PD may also be associated with aging, as the prevalence of PD increases with advancing age. The aging process impairs the cellular clearance mechanism, which leads to chronic inflammation and the accumulation of intracellular α-Syn, which results in DA neuronal death. In the present review, the age-associated α-Syn pathogenicity and the interactions between α-Syn and certain types of cells within the brain are discussed to facilitate understanding of the mechanisms of PD pathogenesis, which may potentially provide insight for the future clinical treatment of PD.

Clinical Characteristics and Gene Mutations of Two Families with MODY 3 in Inner Mongolia.

Objective: This study aimed to analyze the clinical characteristics and gene mutations of two families with maturity-onset diabetes of the young 3 (MODY 3) in Inner Mongolia. Methods: Fifty-three patients in Inner Mongolia suspected of having MODY 3 were enrolled in this study according to clinical manifestations. Blood samples were collected, and all exons of the HNF1α gene were analyzed; the second-generation DNA of the splicing regions of the gene was determined by direct sequencing. Results: In Family 1, the proband, mother, and uncle all carried the missense heterozygous mutation on exon 2 of the HNF1α gene (c.512G>A, p.Arg171Gln), and both the proband and uncle had MODY 3. In Family 2, the proband, grandfather, father, uncle I, and uncle II all carried a missense mutation on exon 2 (c.391C>t, p.Arg131Trp), and all had MODY 3. The blood glucose control in these patients was stable while they were being treated with oral sulfonylurea hypoglycemic drugs alone or with insulin. Uncle II had serious macrovascular and microvascular complications. Conclusion: Maturity-onset diabetes of the young 3 gene mutations (c.512G>A, p.Arg171Gln) and (c.391C>T, p.Arg131Trp) may be the main pathogenic genes of the two families with MODY 3. The two gene mutations found in this study have not been reported previously in China.

Synthesis and Characterization of Single-Phase α-Cordierite Glass-Ceramics for LTCC Substrates from Tuff.

Single-phase α-cordierite glass-ceramics for a low-temperature co-fired ceramic (LTCC) substrate were fabricated from tuff as the main raw material, using the non-stoichiometric formula of α-cordierite with excess MgO without adding any sintering additives. The sintering/crystallization behavior and the various performances of dielectric properties, thermal expansion, and flexural strength of the glass-ceramics were detected. The results indicated that only single-phase α-cordierite crystal was precipitated from the basic glass sintered at the range 875-950 °C, and µ-cordierite crystal was not observed during the whole sintering-crystallization process. The properties of glass-ceramics were first improved and then deteriorated with the increase in tuff content and sintering temperature. Fortunately, the glass-ceramics sintered at 900 °C with 45 wt.% tuff content possessed excellent properties: high densify (2.62 g∙cm-3), applicable flexural strength (136 MPa), low dielectric loss (0.010, at 10 MHz), low dielectric constant (5.12, at 10 MHz, close to α-cordierite), and suitable coefficients of thermal expansion (CTE, 3.89 × 10-6 K-1).

Supramolecular Precursor Strategy to Construct g-C3N4/Silica Hybrid Nanosheets for Photocatalytic Degradation of Dye and Antibiotic Pollutants.

To construct a highly active g-C3N4 (CN)/silica hybrid nanosystem, the supramolecular precursor strategy of introducing melamine-cyanuric acid (MCA) by synergistically using micromolecular melamine (m) and urea (u) for CN nanostructure construction on the silica nanosheets (SiNSs) surface was researched. The results showed that the introduction of MCA supramolecular aggregates promoted the generation of ordered CN nanostructures attached to SiNSs, and the morphology of the CN nanostructure could be regulated through the m/u mass ratio. When the ratio is equal to 1/30, a typical g-C3N4/silica hybrid nanosheet (mu-CN/SiNSs-3) was successfully prepared, which showed the ultra-high photocatalytic activity for Rhodamine B dye degradation within 25 min with an apparent rate constant of 0.186 min-1, owing to the large surface area of highly dispersed and ordered CN nanosheets, a strong interaction between CN and SiNSs, high photogenerated carriers separation efficiency, and the more negative conduction band potential offering more active species of 1O2 and •O2-. Unexpectedly, the mu-CN/SiNSs-2 composite (m/u = 1/10) exhibited the highest activity for tetracycline antibiotic degradation, mainly due to the morphological advantage of a certain number of nanotubes generated on the CN/SiNSs hybrid nanosheets. It indicates that the supramolecular precursor strategy by synergistically using melamine and urea is highly efficient for the nanostructure construction of the CN/SiNSs hybrid system, enabling an appropriate nanostructure for the photodegradation of various pollutants.

Functional annotation and enrichment analysis of differentially expressed serum proteins in patients with type 2 diabetes after dapagliflozin.

BACKGROUND: Only 50% of patients with type 2 diabetes mellitus (T2DM) can control their blood glucose levels. Dapagliflozin is a selective inhibitor of sodium-glucose co-transporter 2 (SGLT-2) that improves the insulin sensitivity of the liver and peripheral tissues. Many studies confirmed that SGLT2 inhibitors reduce blood glucose and have multiple beneficial effects such as weight loss, lipid regulation, and kidney protection. Nevertheless, the mechanisms of the renal and cardiovascular protective effects of dapagliflozin from the perspective of differentially expressed proteins in the serum of T2DM patients have not been intensively explored so far. AIM: To identify differentially expressed proteins associated with dapagliflozin treatment in patients with T2DM. METHODS: Twenty T2DM patients [hemoglobin A1c (HbA1c) 7.0%-10.0%] were enrolled at The Affiliated Hospital of Inner Mongolia Medical University between January 1, 2017 and December 1, 2018. They received dapagliflozin (10 mg/d) for 3 mo, and the HbA1c < 7.0% target was achieved. The changes in clinical indexes were compared before and after treatments. Label-free quantitative proteomics was used to identify differentially expressed proteins using the serum samples of five patients. The identified differentially expressed proteins were analyzed using various bioinformatics tools. RESULTS: Dapagliflozin significantly improved the clinical manifestation of the patients. There were 18 downregulated proteins and one upregulated protein in the serum samples of patients after dapagliflozin administration. Bioinformatics analyses, including subcellular localization, EuKaryotic Orthologous Groups, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes annotations, were used to profile the biological characteristics of the 19 differentially expressed proteins. Based on the literature and function enrichment analysis, two downregulated proteins, myeloperoxidase (MPO) and alpha II B integrin (ITGA2B), and one upregulated protein, podocalyxin (PCX), were selected for enzyme linked immunosorbent assay validation. These validated differentially expressed proteins had multiple correlations with clinical indexes, including HbAc1 and fasting C-peptide. CONCLUSION: Dapagliflozin has hypoglycemic effects and regulates the serum expressions of MPO, ITGA2B, and PCX, possibly contributing to the effects of dapagliflozin on oxidative stress, insulin resistance, and lipid metabolism.

The Positive Association between Subclinical Hypothyroidism and Newly-Diagnosed Hypertension Is More Explicit in Female Individuals Younger than 65.

BACKGROUND: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. METHODS: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. RESULTS: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. CONCLUSION: The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Association Between Lipoprotein (A) and Diabetic Nephropathy in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis.

Background: Lipoprotein (a) [Lp (a)] has been well recognized as a risk factor of cardiovascular disease. However, the association between serum Lp (a) and diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM) remains unknown. We performed a meta-analysis to comprehensively evaluate the above association. Methods: Observational studies aiming to evaluate the independent association between serum Lp (a) and diabetic nephropathy in T2DM patients were identified by systematic search of PubMed and Embase databases. A random-effect model which incorporated the potential intra-study heterogeneity was used for the meta-analysis. Results: Eleven observational studies with 9304 T2DM patients were included. Results showed that compared to those with the lowest Lp (a), patients with the highest Lp (a) level had higher odds of diabetic nephropathy (adjusted odds ratio [OR]: 1.63, 95% confidence interval [CI]: 1.25-2.14, I2 = 54%, P < 0.001). Meta-analysis of studies in which Lp (a) was presented as continuous variables showed consistent result (adjusted OR: 1.13 for 1 mg/dl increment of Lp (a), 95% CI: 1.03-1.24, I2 = 36%, P = 0.008). Subgroup analyses showed that study characteristics such as definitions of diabetic nephropathy and study design did not significantly affect the association (P for subgroup difference all > 0.05). Conclusions: Higher serum Lp (a) in patients with T2DM is independently associated with higher odds of diabetic nephropathy. Large scale prospective cohort studies are needed to validate this finding. Moreover, the potential influence of Lp (a) lowering on renal function in T2DM patients may be further investigated.

The Relationship between Erythrocytes and Diabetes Mellitus.

High blood glucose level (hyperglycemia) is a leading indicator of diabetes mellitus (DM). Erythrocytes are the most abundant cells in the circulation and the first to perceive changes in plasma composition. Long-lasting hyperglycemia affects the structure and function of erythrocytes. The detection of erythrocyte-related indicators can provide a valuable reference for the prevention, diagnosis, and treatment of DM and its complications. This paper reviews the normal structure and function of erythrocytes, the changes in erythrocytes in patients with diabetes, and the role of erythrocytes in the development of diabetic complications to provide more indicators for the early prevention of DM complications and to monitor the therapeutic effect of DM.

Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomized, double-blind, phase 3 trial (CMAS).

Chiglitazar (Carfloglitazar) is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes. In this randomized phase 3 trial, we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen. Eligible patients were randomized (1:1:1) to receive chiglitazar 32 mg (n = 245), chiglitazar 48 mg (n = 246), or sitagliptin 100 mg (n = 248) once daily for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin A1C (HbA1c) from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin. Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of -1.40%, -1.47%, and -1.39% for chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg, respectively. Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg, with mean differences of -0.04% (95% confidential interval (CI) -0.22 to 0.15) and -0.08% (95% CI -0.27 to 0.10), respectively. Compared with sitagliptin, greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar. Overall adverse event rates were similar between the groups. A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported. The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions, thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

Role of microporous Janus silica nanosheets in the assembly of ultra-small Ag nanoparticles with high catalytic activity.

As an emerging nano-silica material, two-dimensional (2D) silica nanosheets (SiNSs) have been derived from natural layered kaolinite and applied as a substrate for the highly efficient and dispersed assembly of functional materials, such as noble metal nanoparticles (NPs). In this work, the nature of SiNSs and its particular role in the assembly of ultra-small AgNPs via the reduction-growth method using a Sn(ii) reductant were further researched. By adjusting the Sn(ii) content x (1.2-6.0 wt%), it was found that the surface areas of the Sn(ii)-activated SiNSs (xSn-SiNSs) had almost no change, and their reducibility did not fully increase with the increased x values, due to the saturated adsorption of the Sn(ii) reductant by the surface hydroxyls of the SiNSs, which subsequently caused the decrease of the adsorbed Ag(i) precursor by the hydroxyls on the xSn-SiNSs (x≥ 4.8 wt%). Accordingly, the sizes and loading amounts of the resultant AgNPs mainly showed a similar trend of increase before decrease. Furthermore, the regulated AgNPs with diverse mean sizes ranging from 1.71 to 2.16 nm were all ultra-small (more than half were nanoclusters < 2 nm) and highly dispersed, owing to the high electrostatic attraction of the negatively charged hydroxyls and the anchoring effect of the micropores on the hydroxylated surface of the Janus SiNSs. Therefore, the Ag/xSn-SiNSs nanocomposites displayed better catalytic properties for 4-nitrophenol reduction than most Ag-based supported catalysts, and the optimal Ag/2.4Sn-SiNSs catalyst exhibited quick reaction within 80 s and turnover frequency (TOF) of 3.34 min-1. It reveals the key role of negatively charged surface hydroxyls and micropores of Janus SiNSs in the highly efficient and dispersed assembly of functional materials.

Clinical and laboratory features of female Gitelman syndrome and the pregnancy outcomes in a Chinese cohort.

AIM: Gitelman syndrome (GS) is a rare inherited salt-losing renal tubulopathy. Data on clinical features and the pregnancy outcome for female GS patients in a large cohort are lacking. The study was aimed to explore the phenotype and pregnant issue for female GS patients. METHODS: GS cases from the National Rare Diseases Registry System of China (NRSC) were collected, and detailed clinical, laboratory and genetic data were analysed. Articles on pregnancy in GS were also systemically reviewed. RESULTS: A total of 101 GS patients were included; among them, 42.6% were female and 79.2% showed hypomagnesaemia. A lower proportion of female patients presented before 18 years of age, with less frequently reported polyuria, higher serum potassium and less urine sodium and chloride excretions. There was no gender difference in the sodium-chloride cotransporter (NCC) dysfunction evaluated by hydrochlorothiazide test. Twelve of the 43 female GS patients delivered after disease symptom onset, and their pregnancies were generally uneventful. As a group, pregnant GS patients had lower potassium levels in the first-trimester (P = .002) requiring higher potassium supplementation. After delivery, serum potassium (P = .02) and magnesium (P = .03) increased significantly. Both caesarean section and vaginal delivery were safe. CONCLUSION: Female GS patients may have a less severe phenotype with generally favourable outcomes of pregnancy. Intensive monitoring and increased potassium supplementation are necessary during pregnancy, especially in the first-trimester.

Primary aldosteronism complicated by hyperparathyroidism: report of one case and literature review.

Primary aldosteronism (PA) is a category of secondary hypertension induced by inhibition of the renin-angiotensin system due to increased aldosterone secretion. Aldosterone-producing adenoma (APA) is the most common hypotype of PA. Primary hyperparathyroidism (PHPT) refers to the symptoms of increased bone resorption and increased calcium reabsorption of kidney tubules caused by parathyroid secretion and excessive synthesis of parathyroid hormone. APA, complicated with PHPT has been extremely rare in clinical practice. In this study, the diagnosis and treatment of one case of APA complicated by PHPT was reported. Relevant literature review was performed.

Amino-functionalized hierarchical porous SiO2-AlOOH composite nanosheets with enhanced adsorption performance.

Hierarchical porous SiO2-AlOOH composite nanosheets (HPSA) with a three-dimensional (3D) structure were prepared from two-dimensional (2D) layered mineral kaolinite (A12Si2O5(OH)4) via a template-free structural reorganization method. The obtained material was subjected to homogeneous and effective amino-functionalization by grafting it with (3-aminopropyl) triethoxysilane. Owing to the enhanced 3D hierarchical meso-macroporous structure containing highly dispersed protonated amino groups (NH3+), the as-prepared amino-functionalized HPSA (NH2-HPSA) showed unique adsorption performance towards the congo red anionic dye. It provides feasibilities to fabricate other functional hierarchical porous materials from clay minerals, which can offer potential applications in adsorption, separation, catalysis and other environmental remediation fields.

An Intelligent Monitoring Network for Detection of Cracks in Anvils of High-Press Apparatus.

Due to the endurance of alternating high pressure and temperature, the carbide anvils of the high-press apparatus, which are widely used in the synthetic diamond industry, are prone to crack. In this paper, an acoustic method is used to monitor the crack events, and the intelligent monitoring network is proposed to classify the sound samples. The pulse sound signals produced by such cracking are first extracted based on a short-time energy threshold. Then, the signals are processed with the proposed intelligent monitoring network to identify the operation condition of the anvil of the high-pressure apparatus. The monitoring network is an improved convolutional neural network that solves the problems that may occur in practice. The length of pulse sound excited by the crack growth is variable, so a spatial pyramid pooling layer is adopted to solve the variable-length input problem. An adaptive weighted algorithm for loss function is proposed in this method to handle the class imbalance problem. The good performance regarding the accuracy and balance of the proposed intelligent monitoring network is validated through the experiments finally.

Smoking increases the risk of diabetic foot amputation: A meta-analysis.

Accumulating evidence suggests that smoking is associated with diabetic foot amputation. However, the currently available results are inconsistent and controversial. Therefore, the present study performed a meta-analysis to systematically review the association between smoking and diabetic foot amputation and to investigate the risk factors of diabetic foot amputation. Public databases, including PubMed and Embase, were searched prior to 29th February 2016. The heterogeneity was assessed using the Cochran's Q statistic and the I2 statistic, and odds ratio (OR) and 95% confidence interval (CI) were calculated and pooled appropriately. Sensitivity analysis was performed to evaluate the stability of the results. In addition, Egger's test was applied to assess any potential publication bias. Based on the research, a total of eight studies, including five cohort studies and three case control studies were included. The data indicated that smoking significantly increased the risk of diabetic foot amputation (OR=1.65; 95% CI, 1.09-2.50; P<0.0001) compared with non-smoking. Sensitivity analysis demonstrated that the pooled analysis did not vary substantially following the exclusion of any one study. Additionally, there was no evidence of publication bias (Egger's test, t=0.1378; P=0.8958). Furthermore, no significant difference was observed between the minor and major amputation groups in patients who smoked (OR=0.79; 95% CI, 0.24-2.58). The results of the present meta-analysis suggested that smoking is a notable risk factor for diabetic foot amputation. Smoking cessation appears to reduce the risk of diabetic foot amputation.

Use of Acoustic Emission and Pattern Recognition for Crack Detection of a Large Carbide Anvil.

Large-volume cubic high-pressure apparatus is commonly used to produce synthetic diamond. Due to the high pressure, high temperature and alternative stresses in practical production, cracks often occur in the carbide anvil, thereby resulting in significant economic losses or even casualties. Conventional methods are unsuitable for crack detection of the carbide anvil. This paper is concerned with acoustic emission-based crack detection of carbide anvils, regarded as a pattern recognition problem; this is achieved using a microphone, with methods including sound pulse detection, feature extraction, feature optimization and classifier design. Through analyzing the characteristics of background noise, the cracked sound pulses are separated accurately from the originally continuous signal. Subsequently, three different kinds of features including a zero-crossing rate, sound pressure levels, and linear prediction cepstrum coefficients are presented for characterizing the cracked sound pulses. The original high-dimensional features are adaptively optimized using principal component analysis. A hybrid framework of a support vector machine with k nearest neighbors is designed to recognize the cracked sound pulses. Finally, experiments are conducted in a practical diamond workshop to validate the feasibility and efficiency of the proposed method.

Association between consumption of soy and risk of cardiovascular disease: A meta-analysis of observational studies.

Background The relationships between dietary intake of soy foods and risk of cardiovascular disease are uncertain. The aims of this study were to evaluate and summarize the evidence on the association between consumption of soy and risk of cardiovascular disease (including stroke and coronary heart disease). Methods We systematically searched the MEDLINE and EMBASE databases from their inception up to 22 February 2016. We included only observational studies, and used random-effects models to calculate summary relative risks (SRRs) and 95% confidence intervals (CIs). Results A total of 10 prospective cohort and seven case-control studies met the inclusion criteria. There were a total of 17,269 cardiovascular disease events, including 6265 stroke events, 10,806 coronary heart disease events, and 198 other cardiovascular disease events. A significant negative association was shown between soy intake and risk of cardiovascular disease (SRR = 0.84 95% CI: 0.75-0.94; pheterogeneity<0.001, I2 = 71.4%). Subgroup meta-analyses indicated that a statistically significant protective effect was primarily observed in case-control studies and in Asian populations. There was a borderline significant association between intake of tofu and the risk of cardiovascular disease (SRR = 0.80, 95% CI: 0.64-1.00). A significant negative association was shown for the association between soy intake and risk of stroke (SRR = 0.82, 95% CI: 0.68-0.99) and coronary heart disease (SRR = 0.83, 95% CI: 0.72-0.95). There were no associations between soy isoflavones consumption and risk of cardiovascular disease, stroke, and coronary heart disease. Conclusion Overall evidence indicated that consumption of soy was negatively associated with the risk of cardiovascular disease, stroke, and coronary heart disease risk.