VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.

BACKGROUND: Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se. METHODS: VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis. RESULTS: VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis. CONCLUSIONS: VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.

Experimental and Numerical Simulation Research on Controllable Shock Wave-Induced Shale Fracturing under Repeated Action.

Low permeability is a key geological factor constraining the development of shale gas, and reservoir modification to improve its permeability is a prerequisite. Controlled shock wave fracturing can induce the formation of complex fractures in reservoirs and is expected to become an important means of reservoir modification. However, the mechanism of controlled shock wave fracturing in shale and the geological engineering control factors are unclear. Therefore, this article reveals the mechanism and effect of shock wave modification through small-scale experiments and large-scale numerical simulations. Results show that as the impact number increases, a significant increase in large fractures and fracture connectivity within the shale samples is observed, while the correlation between the geometric parameters of the fractures and the number of impacts is weak. High-energy input in the model will cause a larger range of damage to the rock, accompanied by a smaller attenuation index, indicating that the speed of energy attenuation plays a decisive role in rock damage. The influence of crustal stress is greater than the speed of energy attenuation, and higher crustal stress will inhibit the formation of fractures. A moderate increase in the number of controllable shock waves is beneficial for the fracturing effect; however, further increasing the loading number of controllable shock waves will weaken the strengthening effect of the fracturing effect.

A Gender-, Age-, and Weight Status-Specific Analysis of the High Prevalence of Hyperuricemia Among Chinese Children and Adolescents with Obesity.

Objective: To explore the gender-, age-, and weight status-specific prevalence of hyperuricemia (HUA) and its associated risk factors among Chinese children and adolescents with obesity. Methods: A total of 1329 children aged 2-17 years, who were diagnosed with obesity and hospitalized in our center from January 2016 to December 2022 were recruited. They were divided into mild obesity, moderate obesity, and severe obesity groups. HUA was defined as fasting serum uric acid level >420 µmol/L for boys and >360 µmol/L for girls. Multivariate logistic regression analyses were performed to identify risk factors for HUA. Results: The highest proportion of hospitalized obese children was aged 10-13 years comprising 677 (50.9%) followed by those aged 6-9 years comprising 348 (26.2%) whereas the least proportion was aged 2-5 years comprising 76 (5.7%). The above differences in age distribution were still present in subgroup analyses according to weight status. Most hospitalized obese children were boys (64.7%), especially in the severe obesity group (75.0%). The overall estimated prevalence of HUA in obese children was 54.8%. It presented a gradual increase trend over the last 7 years, with more rapidly in boys than in girls. Subgroup analysis by weight status showed that the prevalence of HUA was higher in children with moderate obesity (64.3%) and severe obesity (64.2%) when compared with mild obesity (48.2%) (P all<0.01). Boys reached a relatively high HUA incidence level (≥60%) at age 12, which occurred about 2 years later than in girls (age 10). With 12 years as the cut-off point, a high prevalence of HUA (≥60%) was observed in both genders. Multivariable logistic regression analyses showed that boy (OR=2.844, 95% CI 2.024-3.998), age (OR=1.253, 95% CI 1.155-1.360), BMI-Z score (OR=2.132, 95% CI 1.438-3.162), fasting blood glucose (OR=0.907, 95% CI 0.860-0.956), phosphorus (OR=4.123, 95% CI 2.349-7.239), alkaline phosphatase (OR=1.002, 95% CI 1.001-1.004), creatinine (OR=1.067, 95% CI 1.037-1.098), urea nitrogen (OR=1.193, 95% CI 1.032-1.378), aspartate aminotransferase (OR=1.016, 95% CI 1.002-1.030), triglycerides (OR=1.339, 95% CI 1.075-1.667), and high-density lipoprotein cholesterol (OR=0.381, 95% CI 0.160-0.910) were independently associated with odds of HUA (P all<0.05). Conclusion: The prevalence of HUA in Chinese obese children and adolescents is unexpectedly high. Childhood HUA was significantly associated with obesity. Gender and age differences were observed in the association between childhood obesity and HUA. Obese children aged ≥12 years should be focused on screening the risk of HUA.

Homogeneous and Label-Free Detection and Monitoring of Protein Kinase Activity Using the Impact Electrochemistry of Silver Nanoparticles.

Protein kinase activity correlates closely with that of many human diseases. However, the existing methods for quantifying protein kinase activity often suffer from limitations such as low sensitivity, harmful radioactive labels, high cost, and sophisticated detection procedures, underscoring the urgent need for sensitive and rapid detection methods. Herein, we present a simple and sensitive approach for the homogeneous detection of protein kinase activity based on nanoimpact electrochemistry to probe the degree of aggregation of silver nanoparticles (AgNPs) before and after phosphorylation. Phosphorylation, catalyzed by protein kinases, introduces two negative charges into the substrate peptide, leading to alterations in electrostatic interactions between the phosphorylated peptide and the negatively charged AgNPs, which, in turn, affects the aggregation status of AgNPs. Via direct electro-oxidation of AgNPs in nanoimpact electrochemistry experiments, protein kinase activity can be quantified by assessing the impact frequency. The present sensor demonstrates a broad detection range and a low detection limit for protein kinase A (PKA), along with remarkable selectivity. Additionally, it enables monitoring of PKA-catalyzed phosphorylation processes. In contrast to conventional electrochemical sensing methods, this approach avoids the requirement of complex labeling and washing procedures.

Exceptional and long-time economic development: CO2 emission reduction and adoption of green marketing in China.

This study aims to boost green bond China's adoption of green marketing; the current research focuses on green defaults as demand-side strategies. This paper panel data collected from 2002 to 2021 used econometric methods. Purposive sampling was used to collect information from respondents. The empirical findings show that the link between income and Green Business Initiatives (GBI) increases emissions of carbon dioxide. Moreover, trade openness raises carbon dioxide emission, but human capital reduces them. This article also makes some predictions about how monetary policies will affect the economy. A policy of open market operations in which the government discounts less for second-hand debt, lowering the market value of money, credit, and interest rates. Results (2) show that the descriptive statistics for the dependent and independent variables of the global market's first-layer model. Green bonds are priced 0.12% more in ask yield than its conventional counterparts on average. The 0.09% point mean of GBI demonstrates that the bid-ask yields of green bonds are somewhat lower on average than those of conventional bonds. The econometric findings of robustness checks reveal that GDP volatility is low and growth rates are higher in economies with GB marketing. Excellent and long-term financial development, as well as strong gross fixed capital formation, are hallmarks China region, which indicate higher levels of economic investment than their control counterparts.

High-intensity first near-infrared emission through energy migration in multilayered upconversion nanoparticles.

The development of Tm3+ 807 nm first near-infrared (NIR-I, 700-1000 nm) emission with second near-infrared (NIR-II, 1000-1700 nm) excitation is urgently needed, due to its potential application in biomedicine. In this work, a range of NaErF4:Yb@NaYF4:Yb@NaYF4:Yb,Tm@NaYF4 multilayer core-shell structure upconversion nanoparticles (UCNPs) were successfully prepared by a co-precipitation method. The strongest UC emissions can be obtained by changing the concentration of Yb3+ in the core and the first shell, and the proposed UC process was discussed in detail. The analysis shows that high-intensity NIR-I emission (807 nm) from Tm3+ and visible light from Er3+ were achieved through the energy migration among Yb3+ and the energy back transfer from Yb3+ to Er3+ under 1532 nm excitation. Besides, compared to bilayer UCNPs, multilayer core-shell UCNPs display superior optical performance. The high-intensity NIR-I emission at 807 nm (Tm3+:3H4 → 3H6) under 1532 nm NIR-II excitation demonstrates huge advantages in bioimaging.

Therapeutic potential of melatonin in the intervertebral disc degeneration through inhibiting the ferroptosis of nucleus pulpous cells.

Ferroptosis, a novel type of cell death mediated by the iron-dependent lipid peroxidation, contributes to the pathogenesis of the intervertebral disc degeneration (IDD). Increasing evidence demonstrated that melatonin (MLT) displayed the therapeutic potential to prevent the development of IDD. Current mechanistic study aims to explore whether the downregulation of ferroptosis contributes to the therapeutic capability of MLT in IDD. Current studies demonstrated that conditioned medium (CM) from the lipopolysaccharide (LPS)-stimulated macrophages caused a series of changes about IDD, including increased intracellular oxidative stress (increased reactive oxygen species and malondialdehyde levels, but decreased glutathione levels), upregulated expression of inflammation-associated factors (IL-1ß, COX-2 and iNOS), increased expression of key matrix catabolic molecules (MMP-13, ADAMTS4 and ADAMTS5), reduced the expression of major matrix anabolic molecules (COL2A1 and ACAN), and increased ferroptosis (downregulated GPX4 and SLC7A11 levels, but upregulated ACSL4 and LPCAT3 levels) in nucleus pulposus (NP) cells. MLT could alleviate CM-induced NP cell injury in a dose-dependent manner. Moreover, the data substantiated that intercellular iron overload was involved in CM-induced ferroptosis in NP cells, and MLT treatment alleviated intercellular iron overload and protected NP cells against ferroptosis, and those protective effects of MLT in NP cells further attenuated with erastin and enhanced with ferrostatin-1(Fer-1). This study demonstrated that CM from the LPS-stimulated RAW264.7 macrophages promoted the NP cell injury. MLT alleviated the CM-induced NP cell injury partly through inhibiting ferroptosis. The findings support the role of ferroptosis in the pathogenesis of IDD, and suggest that MLT may serve as a potential therapeutic approach for clinical treatment of IDD.

Medical Prospect of Melatonin in the Intervertebral Disc Degeneration through Inhibiting M1-Type Macrophage Polarization via SIRT1/Notch Signaling Pathway.

The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate Mφ polarization and the inflammatory reaction of Mφs with or without MLT were detected. Conditioned medium (CM) collected from these activated Mφs with or without MLT treatment were further used to incubate NP cells. The oxidative stress, inflammation and extracellular matrix (ECM) metabolism in NP cells were determined. Then, the changes in SIRT1/Notch signaling were detected. The agonist (SRT1720) and inhibitor (EX527) of SIRT1 were used to further explore the association among MLT. The interaction between SIRT1 and NICD was detected by immunoprecipitation (IP). Finally, puncture-induced rat IDD models were established and IDD degrees were clarified by X-ray, MRI, H&E staining and immunofluorescence (IF). The results of flow cytometry and inflammation detection indicated that LPS could induce M1-type Mφ polarization with pro-inflammatory properties. MLT significantly inhibited the aforementioned process and inhibited M1-type Mφ polarization, accompanied by the alleviation of inflammation. Compared with those without MLT, the levels of oxidative stress, pro-inflammatory cytokines and ECM catabolism in NP cells exposed to CM with MLT were markedly downregulated in a dose-dependent manner. The inhibition of SIRT1 and the enhancement of Notch were observed in activated Mφs and they can be reversed after MLT treatment. This prediction was further confirmed by using the SRT1720 and EX527 to activate or inhibit the signaling. The interaction between SIRT1 and NICD was verified by IP. In vivo study, the results of MRI, Pfirrmann grade scores and H&E staining demonstrated the degree of disc degeneration was significantly lower in the MLT-treated groups when compared with the IDD control group. The IF data showed M1-type Mφ polarization decreased after MLT treatment. MLT could inhibit M1-type Mφ polarization and ameliorate the NP cell injury caused by inflammation in vitro and vivo, which is of great significance for the remission of IDD. The SIRT1/Notch signaling pathway is a promising target for MLT to mediate Mφ polarization.

The diagnostic value of shear-wave elastography in the salivary glands of patients with primary Sjögren syndrome.

OBJECTIVE: We aimed to quantify the extent of salivary gland fibrosis using shear-wave elastography (SWE) to assess its diagnostic value for primary Sjögren syndrome (pSS). METHODS: A total of 58 pSS patients and 44 controls underwent SWE ultrasound evaluation of the parotid and submandibular glands. We measured the degree of salivary gland fibrosis in all participants and investigated the diagnostic accuracy of SWE for pSS and its relationship to disease progression. RESULTS: The diagnostic sensitivity, specificity, and accuracy of pSS were highest when the critical Young's modulus values of the parotid and submandibular glands were 18.4 and 15.9 kPa, respectively, effectively improving the diagnostic value of pSS. The area under the SWE curve of the submandibular gland was higher than that of the parotid gland (z = 2.292, P = 0.02), suggesting that the submandibular gland was damaged earlier. The mean parotid gland thickness of pSS patients was thicker than in healthy controls (mean ± standard deviation 2.5 ± 0.3 vs 2.4 ± 0.2, P = 0.013]. SWE had a 70.3% sensitivity for diagnosing pSS patients with a disease duration of 5 years, but this did not differ significantly from pSS patients with a longer disease duration. CONCLUSIONS: SWE is a valid diagnostic method for pSS. The degree of salivary gland fibrosis related to secretory function and pathological progression, and quantitative measurements of tissue elasticity provide objective criteria for predicting damage in pSS.

How do vertical fiscal imbalances affect energy efficiency? The role of government spending on science and technology.

How to improve energy efficiency is a practical issue of common concern around the world. In China, vertical fiscal imbalances (VFIs) generated under the existing fiscal system may have a significant impact on energy efficiency through government spending on science and technology (S&T). However, this potential relationship has not been explored in the literature. In this work, we aim to address this gap. Using Chinese provincial panel data from 2001 to 2017, this study empirically examines the relationship between VFIs and energy efficiency through a mediation model. The results show that VFIs greatly suppress energy efficiency. We further find that VFIs indirectly affect energy efficiency by reducing government spending on S&T. The results show significant regional heterogeneity. The intermediary role of government S&T expenditure is more significant in inland areas than in coastal areas. Therefore, to improve energy efficiency and achieve sustainable development, the Chinese government should focus on innovative reform of the existing fiscal system and reduce VFIs. In addition, the government should focus on fiscal spending in the field of S&T to promote technological innovation to guarantee the improvement of energy efficiency. Inland areas should pay particular attention to this issue.

Homogeneous Electrochemical Immunoassay Using an Aggregation-Collision Strategy for Alpha-Fetoprotein Detection.

Homogeneous immunoassays represent an attractive alternative to traditional heterogeneous assays due to their simplicity and high efficiency. Homogeneous electrochemical assays, however, are not commonly accessed due to the requirement of electrode immobilization of the recognition elements. Herein, we demonstrate a new homogeneous electrochemical immunoassay based on the aggregation-collision strategy for the quantification of tumor protein biomarker alpha-fetoprotein (AFP). The detection principle relies on the aggregation of AgNPs induced by the molecular biorecognition between AFP and AgNPs-anti-AFP probes, which leads to an increased AgNP size and decreased AgNP concentration, allowing an accurate self-validated dual-mode immunoassay by performing nanoimpact electrochemistry (NIE) of the oxidation of AgNPs. The intrinsic one-by-one analytical capability of NIE as well as the participation of all of the atoms of the AgNPs in signal transduction greatly elevates the detection sensitivity. Accordingly, the current sensor enables a limit of detection (LOD) of 5 pg/mL for AFP analysis with high specificity and efficiency. More importantly, reliable detection of AFP in diluted human sera of hepatocellular carcinoma (HCC) patients is successfully achieved, indicating that the NIE-based homogeneous immunoassay shows great potential in HCC liquid biopsy.

Advanced Ann Arbor stage and age over 60 years as prognostic predictors in patients with primary cervical lymphoma: a retrospective cohort study and systematic review.

OBJECTIVE: To evaluate the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) for primary cervical lymphoma (PCL), an extremely rare disease without treatment consensus. METHODS: We conducted a retrospective study included 177 patients, including 169 cases identified from literature review. The Kaplan-Meier methods and Cox regression were used to determine the OS, DSS, RFS, and relevant risk factors. RESULTS: The 5-year OS and 5-year DSS rates were 85.8 and 87.2%, respectively, while the 5-year RFS rate was 85.5%. Diffuse large B-cell lymphoma (DLBCL) was the predominant subtype that comprised 63.8% (113 cases) in this cohort. Multivariate analysis in the DLBCL subgroup revealed that age ≥ 60 years (Odds ratio [OR]: 26.324, 95% Confidence Interval [CI]: 5.090-136.144, P < 0.001) or stage IIIE-IVE (advanced stage) (OR: 4.219, 95%CI: 1.314-13.551, P = 0.016) were the risk factors for OS, while patients with age ≥ 60 years (OR:23.015, 95%CI: 3.857-137.324, P = 0.001), and stage IIIE-IVE (OR: 4.056, 95% CI: 1.137-14.469, P = 0.031) suffered a poor DSS. Chemotherapy and/or radiotherapy improved the OS (P = 0.008), DSS (P = 0.049), and RFS (P = 0.003). However, cancer-directed surgery did not improve the OS, DSS, and RFS. The risk factor was unavailable in other subtypes of PCL due to limited cases. CONCLUSION: The survival outcomes in patients with PCL at early stage were satisfactory, while the advanced disease stage and age ≥ 60 years were the two major factors predicting poor prognosis in DLBCL subtype.

Spatial-temporal characteristics and influencing factors of county-level carbon emissions in Zhejiang Province, China.

Zhejiang Province is a "demonstration area for high-quality development and construction of common prosperity" in China. Moreover, the county is the basic unit and power source for the economic development of Zhejiang Province. Therefore, the research on the spatial-temporal characteristics and influencing factors of county-level carbon emissions is of great significance for Zhejiang Province to achieve the strategic goal of carbon peak and carbon neutrality. Based on the carbon emissions and socio-economic data of 62 counties in Zhejiang Province from 2014 to 2020, the spatial dependence and agglomeration of county-level carbon emissions are analyzed through the spatial autocorrelation test and local spatial autocorrelation test respectively. According to the spatial-temporal characteristics of county-level carbon emissions revealed by the index of Moran's I and local Moran's I, the spatial error STIRPAT model is used to study the influencing factors of county-level carbon emissions in Zhejiang Province, China. The main results are as follows: (1) The total amount of county-level carbon emissions of 62 counties fluctuates from 259.69 to 326.28 million tons and shows a growth trend. (2) Moran's I index is between 0.369 and 0.399. The county-level carbon emissions have a significant spatial correlation, and the spatial agglomeration trend is relatively stable, which is consistent with the hypothesis of the geographical polarization effect. (3) High-high agglomeration counties are concentrated in the northeast of Zhejiang Province, while low-low agglomeration counties are mainly in the southwest. (4) The relationship between county per capita GDP and carbon emissions has not been "decoupled," because when other variables remain unchanged, the county's total carbon emissions will increase by 2.866% for every 1% increase in the county's per capita GDP; the increase of the proportion of secondary industry contributes to the decline of carbon emissions, and the low-carbon effect brought by large-scale industrial development as well as scientific and technological innovation has not yet appeared. (5) The estimate of the spatial coefficient λ was 0.324, which illustrates that the carbon emission of a single county is positively affected by the carbon emission of the neighboring counties, and other socio-economic factors affecting carbon emission among counties also have a spatial correlation. Therefore, the policy of realizing regional coordinated development as well as the carbon peaking and carbon neutrality goals should not only focus on industrial layout, but also take a dynamic and comprehensive consideration from a spatial perspective.

An effective preselection criterion for MODY with an increasingly positive genetic testing rate by NGS: results from two cohorts of Chinese children.

The purpose of this study was to determine the frequency of maturity-onset diabetes of the young (MODY) in two selected cohorts of Chinese children with diabetes and clinically suspected MODY, using next-generation sequencing (NGS). Ninety-three children who met the comprehensive criteria of suspected MODY were enrolled in two cohorts. A custom NGS panel or a whole exon group was used for sequencing. We identified 55/93 (59.1%) children with pathogenic and likely pathogenic MODY variants. Forty-two (76.3%) were confirmed to have the GCK (MODY2) mutation. Additionally, five had the HNF1A (MODY3), two the HNF1B (MODY5), one the 17q12 microdeletion (MODY5), two the HNF4A (MODY1), two the ABCC8 (MODY12), and one the PDX1 mutation (MODY4). Of these, 13 novel variants were detected in different genes. By comparing the gene-positive with gene-negative children, we found that discriminatory factors for MODY at diagnosis included lower HbA1c [7.4% vs. 10.2% (53 vs. 86 mmol/mol); P = 0.002], lower body mass index z score (0.2 vs. 1.0; P = 0.01), lower onset age (8.1 vs. 11.2 years; P = 0.001), and lower C-peptide (1.4 vs. 2.5 ng/mL; P = 0.02). In conclusion, the criteria used in this study for screening MODY are effective, and MODY2 is the most common subtype (76%), followed by MODY3 and MODY5. Some rare MODY subtypes have been reported in Chinese children.NEW & NOTEWORTHY We proved the clinical suspicion of maturity-onset diabetes of the young (MODY) according to the comprehensive criterion for next-generation sequencing testing, which helps to identify both common and rare MODYs, leading to accurate diagnosis and personalized treatment.

The critical BMI hypothesis for puberty initiation and the gender prevalence difference: Evidence from an epidemiological survey in Beijing, China.

Background: Although previous studies suggested that there is a certain level of body fat mass before puberty can be initiated, most studies have focused on girls. Objective: To investigate the relationship between precocious puberty and physical growth in school-aged children in Beijing, China. Methods: 7590 Chinese children (3591 girls and 3999 boys) aged 6-11 years were recruited in Beijing, China. Body mass index (BMI) categories were defined by WHO Child Growth Standards and central obesity were defined by sex-specific waist-to-height ratio cut-offs (≥0.46 for girls, ≥0.48 for boys). Sexual development was assessed using Tanner criteria. Results: The prevalence of general obesity and central obesity among boys was higher than that in girls. Girls had a significantly higher precocious puberty rate than boys (5.93% vs. 0.87%), particularly in those aged 7 years old (9.20%). Children in the general obesity and central obesity groups have a higher prevalence of precocious puberty and earlier median ages for the attainment of Tanner B2/T2. For girls with Tanner stages≥II at 6-year-old and 7-year-old, the mean BMI was equivalent to the 50th centile of a normal 9.9-year-old and 11.9-year-old girl, respectively. The mean BMI of boys with Tanner stages≥II at 7-year-old and 8-year-old was correspondent to the 50th centile of a normal 14-year-old and 15.3-year-old boy, respectively. For girls, general obesity appears to contribute to the risk of the development of precocious puberty to a greater extent than central obesity does. For boys, central obesity, but not general obesity, was an independent risk factor for precocious puberty. Conclusions: The prevalence of childhood obesity and precocious puberty was high in China. Precocious puberty was correlated with a large BMI. Boys had a higher threshold of BMI for puberty development than girls. Children with precocious puberty, particularly those with central obesity, should be aware of adverse cardiovascular events.

Associations between body mass index and pubertal development based on the outcomes of girls with early breast development.

Objective: To investigate the associations between physical and pubertal development based on the breast development outcomes in girls. Methods: This was a retrospective study. A total of 452 girls aged 6~8 years were included. Based on their breast development outcomes, the patients were divided into an idiopathic central precocious puberty (ICPP) group and a premature thelarche (PT) group. Anthropometry included measurements of height, weight, and BMI. ICPP was diagnosed when five diagnostic criteria from the current guidelines were met. Results: The girls with breast development at initial evaluation had a median age of 6.9 years. In total, 31.4% of patients were diagnosed with ICPP, and ICPP was rare in girls <7 years old (19%). Patients who presented with recurrence of breast development in the PT group accounted for 38.4%. At initial evaluation, the height, weight, BMI and bone age (BA) of the girls in the PT group corresponded to those of a normally developing girl at ages 7.8 years, 8.2 years, 8.6 years and 7.6 years, respectively. The girls in the ICPP group had a mean age of 7.3 years, and their mean height, weight, and BMI were 129.6 cm, 28.4 kg, and 17.0 kg/m2, which corresponded to the mean of a normally developing girl at ages 8.5 years, 9.1 years, and 10.5 years, respectively; these patients had BA of 9.2 years. Additionally, based on receiver operating characteristic (ROC) curve analysis, when the basal luteinizing hormone (LH) level was 0.32 IU/L and BMI reached 16.4 kg/m2, CPP was diagnosed in patients meeting all five diagnostic criteria for CPP, and the specificity and sensitivity were 71.9% and 88.2%, respectively. Conclusions: Girls with breast development before 8 years old had a high proportion of recurrence of breast development. The physical development of these girls at the time of breast development preceded that of normally developing girls by 1-2 years. BMI is an independent risk factor for early pubertal development, and is a simple and clear predictor of ICPP. In addition to the five classic diagnostic criteria, CPP is diagnosed when physical development corresponds to the mean for a 10.5 years old girl.

Clinically Applicable Homogeneous Assay for Serological Diagnosis of Alpha-Fetoprotein by Impact Electrochemistry.

Tumor protein quantification with high specificity, sensitivity, and efficiency is of great significance to enable early diagnosis and effective treatment. The existing methods for protein analysis usually suffer from high cost, time-consuming operation, and insufficient sensitivity, making them not clinically friendly. In this work, a label-free homogeneous sensor based on the nano-impact electroanalytic (NIE) technique was proposed for the detection of tumor protein marker alpha-fetoprotein (AFP). The detection principle is based on the recovery of current of single PtNP catalyzed hydrazine oxidation due to the release of the pre-adsorbed passivating aptamers on PtNPs from the competition of the stronger binding between the specific interaction of the AFP aptamer and AFP. The intrinsic one-by-one analytical ability of NIE allows highly sensitive detection, which can be further improved by reducing the reaction/incubation volume. Meanwhile, the current sensor avoids a laborious labeling procedure as well as the separation and washing steps due to the in situ characteristic of NIE. Accordingly, the current sensor enables efficient, highly sensitive, and specific AFP analysis. More importantly, the reliable detection of AFP in diluted real sera from hepatocellular carcinoma (HCC) patients is successfully achieved, indicating that the impact electrochemistry-based sensing platform has great potential to be applied in point-of-care devices for HCC liquid biopsy.

Chronic oral mucocutaneous candidiasis, recurrent respiratory infection, hepatosplenomegaly, and autoimmune diabetes mellitus: A case report of a gain-of-function mutation of STAT1 in a Chinese boy.

Background: Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations are characterized by chronic mucocutaneous candidiasis and autoimmune diseases. Type 1 diabetes mellitus is one of the well-characterized autoimmune conditions. Case presentation: We reported a 5-year-old boy who presented with polydipsia and polyuria, with a medical history of chronic oral mucocutaneous candidiasis, recurrent respiratory infection, hepatosplenomegaly, and abnormal liver function. Genetic analysis identified a heterozygous GOF mutation (c.866A > G, p.Y289C) in STAT1. Results: Various medicines were given to the boy during the follow-up, including insulin to keep blood glucose stable, intravenous immunoglobulin and antifungal agents for recurrent infections, and antituberculosis drugs (isoniazid, rifampicin) to combat tuberculosis infection. He did not show recurrent infection, but chronic oral mucocutaneous candidiasis still occurred twice per month. The blood glucose level was well controlled. Conclusion: This article illustrates that early diagnosis and identification of STAT1 mutation are essential for assessing the severity of the disease and determining reasonable treatment options.

Synthesis of morphology-controlled N-doped porous carbon for simultaneous electrochemical sensing of dihydroxybenzene isomers.

Different morphology of N-doped carbon materials, including three-dimensional interconnected N-doped hierarchically porous carbon networks (3D-NC), two-dimensional ultrathin porous carbon nanosheets (2D-NC), and bulk N-doped carbon with micron size (bulk-NC), was easily prepared by using NaCl crystal templates-assisted strategy. Compared with bare glassy carbon, bulk-NC, and 2D-NC, the as-synthesized 3D-NC exhibits excellent electrochemical activity toward the oxidation and sensing of three kinds of common environmental pollutants dihydroxybenzene isomers (hydroquinone (HQ), catechol (CC), and resorcinol (RS)). The impressive electrochemical activity of 3D-NC can be interpreted by its large specific surface area, continuous network-like morphology, superior electro-catalytic ability, and strong accumulation efficiency. Differential pulse voltammetry (DPV) test showed the 3D-NC-modified electrode exhibited three well-separated oxidation peaks at 0.05 V, 0.14 V, and 0.45 V vs. saturated calomel electrode (SCE) for HQ, CC, and RS, and their detection limits were evaluated to be as low as 0.0044, 0.012, and 0.016 mg L-1, respectively. Finally, a novel electrochemical analytical platform is successfully fabricated for the simultaneous monitoring of hydroquinone, catechol, and resorcinol with high sensitivity. When used for real wastewater samples analysis, recovery ratio ranging from 94 to 108% with lower than 5% of relative standard deviation (RSD) values was achieved. This work proves a facile strategy to prepare morphology-controlled N-doped carbon-based material and demonstrates its high application potential for environmental monitoring and electrochemical analysis.

Effect of low-dose lidocaine on MEPs in patients undergoing intracranial tumor resection with propofol anesthesia: A randomized controlled trial.

OBJECTIVE: To investigate the effect of low-dose lidocaine on motor evoked potentials (MEPs) in patients undergoing intracranial tumor resection with propofol anesthesia. METHODS: Forty patients who underwent intracranial tumor resection and required MEP monitoring were selected. They were randomly divided into the lidocaine group (group L, n = 20) and the control group (group C, n = 20) by computer-generated randomization. All patients were given propofol anesthesia under the guidance of the bispectral index. In group L, 1 mg/kg of lidocaine was injected intravenously during anesthesia induction. Then, lidocaine was continuously pumped at a speed of 1 mg/kg/h until the operation started. Group C was given an equal volume of normal saline. Heart rate (HR), mean artery pressure (MAP), and bispectral index were recorded before anesthesia induction (T0), 2 minutes after tracheal intubation (T1), and 35 minutes (T2), and 50 minutes (T3) after anesthesia induction. The amplitude and latency of MEP at T2 and T3, the total dosage of propofol after anesthesia induction, and adverse events before T3 were recorded. RESULTS: Compared with those in group C, HR and MAP were significantly decreased at T1 in group L. No significant differences were observed in HR and MAP at T0, T2, and T3 between group L and group C. The total dosage of propofol and the incidence of adverse events were significantly lower in group L than in group C before T3. There were no significant differences in the amplitude and latency of MEP between the 2 groups at each time point. CONCLUSIONS: Low-dose lidocaine has no obvious effect on MEP in patients undergoing intracranial tumor resection. However, it increased hemodynamic stability, reduced propofol use, and decreased the incidence of adverse events.