[Application of metagenomic next-generation sequencing of bronchoalveolar lavage fluid in the diagnosis and treatment of refractory pneumonia in children]. / æ”¯æ°”ç®¡è‚ºæ³¡çŒæ´—æ¶²å®åŸºå› ç»„äºŒä»£æµ‹åºåœ¨å„¿ç«¥éš¾æ²»æ€§è‚ºç‚Žè¯Šæ²»ä¸­çš„åº”ç”¨.

OBJECTIVES: To investigate the clinical application of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the etiological diagnosis and treatment of refractory pneumonia (RTP) in children. METHODS: A retrospective analysis was performed on 160 children with RTP who were admitted to the Department of Pediatric Internal Medicine, Maternal and Child Health Hospital of Inner Mongolia Autonomous Region, from January 2020 to March 2023. According to whether mNGS was performed, they were divided into two groups: mNGS (n=80) and traditional testing (n=80). All children received the tests of inflammatory markers and pathogen tests after admission. Traditional pathogenicity tests included microbial culture (sputum specimen collected by suction tube), nucleic acid detection of respiratory pathogens, and serological test (mycoplasma, tuberculosis, and fungi). For the mNGS group, BALF specimens were collected after bronchoscopy and were sent to the laboratory for mNGS and microbial culture. The two groups were analyzed and compared in terms of the detection of pathogens and treatment. RESULTS: Compared with the traditional testing group, the mNGS group had a significantly higher detection rate of pathogens (92% vs 58%, P<0.05), with more types of pathogens and a higher diagnostic rate of mixed infections. Compared with the traditional testing group, the mNGS group had a significantly higher treatment response rate and a significantly lower incidence rate of complications during hospitalization (P<0.05). Treatment was adjusted for 68 children in the mNGS group according to the results of mNGS, with a treatment response rate of 96% (65/68) after adjustment. CONCLUSIONS: Compared with traditional pathogen tests, BALF mNGS can significantly improve the detection rate of pathogens and find some rare pathogens. In clinical practice, when encountering bottlenecks during the diagnosis and treatment of children with RTP, it is advisable to promptly perform the mNGS to identify the pathogens.

Antibiotics prescription for targeted therapy of pediatric invasive pneumococcal diseases in China: a multicenter retrospective study.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

Portable Interactive Pulse Tactile Recorder and Player System.

Pulse palpation is an effective method for diagnosing arterial diseases. However, most pulse measurement devices use preconfigured pressures to collect pulse signals, and most pulse tactile simulators can only display standard or predefined pulse waveforms. Here, a portable interactive human pulse measurement and reproduction system was developed that allows users to take arbitrary pulses and experience realistic simulated pulse tactile feedback in real time by using their natural pulse-taking behaviors. The system includes a pulse tactile recorder and a pulse tactile player. Pulse palpation forces and vibrations can be recorded and realistically replayed for later tactile exploration and examination. To retain subtle but vital pulse information, empirical mode decomposition was used to decompose pulse waveforms into several intrinsic mode functions. Artificial neural networks were then trained based on intrinsic mode functions to determine the relationship between the driving signals of the pulse tactile player and the resulting vibration waveforms. Experimental results indicate that the average normalized root mean square error and the average R-squared values between the reproduced and original pulses were 0.0654 and 0.958 respectively, which indicate that the system can reproduce high-fidelity pulse tactile vibrations.

Analysis of circulating non-coding RNAs in a non-invasive and cost-effective manner.

Non-coding RNAs (ncRNAs) participate in regulation of gene expression, and are highly relevant to pathological development. They are found to be stably present in diverse body fluids, including those in the circulatory system, which can be sampled non-invasively for clinical tests. Thus, circulating ncRNAs have great potential to be disease biomarkers. However, tremendous efforts are desired to discover and utilize ncRNAs as biomarkers in clinical diagnosis, calling for technological advancement in analysis of circulating ncRNAs in biospecimens. Hence, this review summarizes the recent developments in this area, highlighting the works devoted to cancer diagnosis and prognosis. Three main directions are focused: 1) Extraction and purification of ncRNAs from body fluids; 2) Quantification of the purified circulating ncRNAs; and 3) Microfluidic platforms for integration of both steps to enable point-of-care diagnostics. These technologies have laid a solid foundation to move forward the applications of circulating ncRNAs in disease diagnosis and cure.

Laser-cooling with an intermediate electronic state: Theoretical prediction on bismuth hydride.

The possibility of laser cooling of bismuth hydride (BiH) molecules has been investigated based on high-level ab initio calculations by considering the core-valence and the spin-orbit coupling (SOC) effects. The potential energy curves of the 12 Λ-S states as well as the 25 Ω states that split from them via SOC are obtained by multireference configuration interaction plus the Davidson correction. The properties of b-X transition are investigated. Based on our calculations, we show that the transition between Ω states b0+-X10+ of BiH is a possible candidate for laser cooling, with consideration of the intermediate Ω state X21. An optical cycling scheme is proposed by utilizing four lasers at wavelengths around 471 and 601 nm with 5400 cycles for photon absorption/emission and a sub-microkelvin temperature. Our study should shed some light on searching for possible molecular candidates for laser cooling with the existence of an intermediate electronic state.

Tumor-Targeted Graphitic Carbon Nitride Nanoassembly for Activatable Two-Photon Fluorescence Imaging.

Unique physicochemical characteristics of graphitic carbon nitride (g-CN) nanosheets suit them to be a useful tool for two-photon fluorescence bioimaging. Current g-CN nanosheets based imaging probes typically use the "always-on" design strategies, which may suffer from increased fluorescence background and limited contrast. To advance corresponding applications, g-CN nanosheets based activatable two-photon fluorescence probes remain to be explored. For the first time, we developed an activatable two-photon fluorescence probe, constructed from a nanoassembly of g-CN nanosheets and hyaluronic acid (HA)-gold nanoparticles (HA-AuNPs), for detection and imaging of hyaluronidase (HAase) in cancer cells. The deliberately introduced HA in our design not only functions as the buffering layer for stabilizing AuNPs and inducing corresponding self-assembly on g-CN nanosheets but also as a pilot for targeting HA receptors overexpressed on cancer cell surfaces. Our results show that the developed nanoassembly enables specific detection and activatable imaging of HAase in cancer cells and deep tissues, with superb signal-to-background ratio and high sensitivity. This nanoassembly can afford a promising platform for highly specific and sensitive imaging of HAase and for related cancer diagnosis.

A multiplex paper-based nanobiocatalytic system for simultaneous determination of glucose and uric acid in whole blood.

In this work, a versatile point-of-care assay platform based on a microfluidic paper-based analytic device (µPAD) was developed for the simultaneous detection of multiple targets. The µPAD with a central zone and six test zones is fabricated by a simple and inexpensive wax printing method. A flower-like hybrid nanocomplex synthesized with specific dual enzymes and Cu3(PO4)2 inorganic nanocrystals is spotted in the test zones on the µPAD, followed by the introduction of assay targets. Using dual-enzyme inorganic hybrid nanoflowers in the µPAD as nanobiocatalysts, which preserve the activity and enhance the stability of the enzymes, based on the H2O2-mediated catalytic oxidizing chromogenic reaction produced by glucose/uric acid, the developed multiplex paper-based nanobiocatalytic system is demonstrated to enable simultaneous and sensitive detection of glucose and uric acid with a detection limit of 60 and 25 µM, respectively. More importantly, it has been successfully used for detecting glucose and uric acid levels in human whole blood samples. The developed multiplex paper-based nanobiocatalytic system features very easy fabrication and operation, low cost, and high sensitivity and has promising prospects for a clinical multianalyte point-of-care test.

Enhancement of the Intrinsic Peroxidase-Like Activity of Graphitic Carbon Nitride Nanosheets by ssDNAs and Its Application for Detection of Exosomes.

The present work investigates the capability of single-stranded DNA (ssDNA) in enhancing the intrinsic peroxidase-like activity of the g-C3N4 nanosheets (NSs). We found that ssDNA adsorbed on g-C3N4 NSs could improve the catalytic activity of the nanosheets. The maximum reaction rate of the H2O2-mediated TMB oxidation catalyzed by the ssDNA-NSs hybrid was at least 4 times faster than that obtained with unmodified NSs. The activity enhancement could be attributed to the strong interaction between TMB and ssDNA mediated by electrostatic attraction and aromatic stacking and by both the length and base composition of the ssDNA. The high catalytic activity of the ssDNA-NSs hybrid permitted sensitive colorimetric detection of exosomes if the aptamer against CD63, a surface marker of exosome, was employed in hybrid construction. The sensor recognized the differential expression of CD63 between the exosomes produced by a breast cancer cell line (MCF-7) and a control cell line (MCF-10A). Moreover, a similar trend was detected in the circulating exosomes isolated from the sera samples collected from breast cancer patients and healthy controls. Our work sheds lights on the possibility of using ssDNA to enhance the peroxidase-like activity of nanomaterials and demonstrates the high potential of the ssDNA-NSs hybrid in clinical diagnosis using liquid biopsy.

Cobalt oxyhydroxide nanoflakes with intrinsic peroxidase catalytic activity and their application to serum glucose detection.

Cobalt oxyhydroxide (CoOOH) nanoflakes, an emerging type of two-dimensional nanomaterial, show great potential for use in molecular detection. Previous assays utilizing such materials have largely been based on their outstanding fluorescence quenching ability and oxidizing power. Herein, we report the intrinsic peroxidase-like activity of cobalt oxyhydroxide (CoOOH) nanoflakes, and we show how this activity can be employed for glucose detection. We found that, in the presence of hydrogen peroxide (H2O2), the nanoflakes accelerated the conversion of peroxidase substrates such as 3,3',5,5'-tetramethylbenzidine (TMB) into colored products. By combining the CoOOH nanoflakes with the biological enzyme glucose oxidase (GOx), we developed a colorimetric method for the detection of glucose within the concentration range 5.3-500 µM. The proposed method was applied to detect elevated blood glucose levels in diabetic patients, and the intense color change induced by elevated glucose levels was found to be readily apparent to the naked eye, proving the utility of our assay for point-of-care testing. Graphical abstract The intrinsic peroxidase-like activity of cobalt oxyhydroxide (CoOOH) nanoflakes was exploited to enable the direct visualization of elevated glucose levels in sera from diabetic patients.

[Dynamic changes of reproductive hormone levels and related factors in old and middleaged men in health examination].

OBJECTIVE: To investigate the dynamic changes of serum reproductive hormone levels in old and middleaged males in health examination and their correlation with age and lipid profile. METHODS: This study included 4 333 men in health examination from January 2011 to December 2014. The men were aged from 40 to 85 years old and divided into seven fiveyearspan age groups. We determined the levels of serum testosterone (T), luteinizing hormone (LH), folliclestimulating hormone (FSH), estradiol (E2), progesterone (P), prolactin (PRL), total cholesterol (TC), triglyceride (TG), lowdensity lipoprotein cholesterol (LDLC), highdensity lipoprotein cholesterol (HDLC), and the testosterone secretion index (TSI = T/LH). We analyzed the obtained data using SPSS Pram, KruskalWallis H test, MannWhitney U test, exponential regression, and Spearman correlation analysis. RESULTS: Statistically significant differences were found in LH, FSH, E2 and TSI among the seven age groups (P< 0.05). The levels of serum LH, FSH and E2 were significantly higher (P< 0.05) while TSI remarkably lower (P< 0.05) in the ≥70 yr group than in the other six groups. The serum T and E2 levels and TSI were markedly lower in the 40－44, 45－49 and 50－54 yr groups in 2014 than in the other three years (P< 0.05), and so were the levels of serum T and TSI in the 55－59 yr group (P< 0.05). The levels of serum LH, FSH and E2 were correlated positively while those of P, PRL and TSI negatively with age. The serum T level was correlated positively with HDLC but negatively with TC, TG and LDLC. The levels of serum LH, FSH and E2 showed a yearly average increase of 1.9%, 2.7% and 0.5%, respectively, while TSI an annual mean decline of 2.0% in the 40－85 yr group. CONCLUSIONS: LH, FSH and E2 were increased while TSI decreased with age in the >40 years old males. T and TSI were reduced in the 40－59 years old men from 2011 to 2014, and so was E2 in the 40－54 yr group. Lowlevel testosterone is closely related to dyslipidemia.

Melanin-Like Nanoquencher on Graphitic Carbon Nitride Nanosheets for Tyrosinase Activity and Inhibitor Assay.

Graphitic C3N4 (g-C3N4) nanosheets are a type of emerging graphene-like carbon-based nanomaterials with high fluorescence and large specific surface areas that hold great potential for biosensor applications. However, current g-C3N4 based biosensors have prevailingly been limited to coordination with metal ions, and it is of great significance to develop new designs for g-C3N4 nanosheets based biosensors toward biomarkers of general interest. We report the development of a novel g-C3N4 nanosheet-based nanosensor strategy for highly sensitive, single-step and label-free detection of tyrosinase (TYR) activity and its inhibitor. This strategy relies on the catalytic oxidation of tyrosine by TYR into melanin-like polymers, which form a nanoassembly on the g-C3N4 nanosheets and quench their fluorescence. This strategy was demonstrated to provide excellent selectivity and superior sensitivity and to enable rapid screening for TYR inhibitors. Therefore, the developed approach might create a useful platform for diagnostics and drugs screening for TYR-based diseases including melanoma cancer.

Structure-Switching Aptamer Triggering Hybridization Chain Reaction on the Cell Surface for Activatable Theranostics.

The ability to probe low-abundance biomolecules or transport a high-load drug in target cells is essential for biology and theranostics. We develop a novel activatable theranostic approach by using a structure-switching aptamer triggered hybridization chain reaction (HCR) on the cell surface, which for the first time creates an aptamer platform enabling real-time activation and amplification for fluorescence imaging and targeting therapy. The aptamer probe is designed not to initiate HCR in its free state but trigger HCR on binding to the target cell via structure switching. The HCR not only amplifies fluorescence signals from a fluorescence-quenched probe for activatable tumor imaging but also accumulates high-load prodrugs from a drug-labeled probe and induces its uptake and conversion into cisplatin in cells for selective tumor therapy. An in vitro assay shows that this approach affords efficient signal amplification for fluorescence detection of target protein tyrosine kinase-7 (PTK7) with a detection limit of 1 pM. Live cell studies reveal that it provides high-contrast fluorescence imaging and highly sensitive detection of tumor cells, while renders high-efficiency drug delivery into tumor cells via an endocytosis pathway. The results imply the potential of the developed approach as a promising platform for early stage diagnosis and precise therapy of tumors.

The variation of riverbed material due to tropical storms in Shi-Wen River, Taiwan.

Taiwan, because of its location, is a flood prone region and is characterised by typhoons which brings about two-thirds to three quarters of the annual rainfall amount. Consequently, enormous flows result in rivers and entrain some fractions of the grains that constitute the riverbed. Hence, the purpose of the study is to quantify the impacts of these enormous flows on the distribution of grain size in riverbeds. The characteristics of riverbed material prior to and after the typhoon season are compared in Shi-Wen River located at southern Taiwan. These include grain size variation, bimodality, and roughness coefficient. A decrease (65%) and increase (50%) in geometric mean size of grains were observed for subsurface and surface bed material, respectively. Geometric standard deviation decreased in all sites after typhoon. Subsurface material was bimodal prior to typhoons and polymodal after. For surface material, modal class is in the gravel class, while after typhoons it shifts towards cobble class. The reduction in geometric mean resulted to a decrease in roughness coefficient by up to 30%. Finally, the relationship of Shields and Froude numbers are studied and a change in the bed form to antidunes and transition form is observed, respectively.

Reducing statistics anxiety and enhancing statistics learning achievement: effectiveness of a one-minute strategy.

Statistical knowledge is widely used in academia; however, statistics teachers struggle with the issue of how to reduce students' statistics anxiety and enhance students' statistics learning. This study assesses the effectiveness of a "one-minute paper strategy" in reducing students' statistics-related anxiety and in improving students' statistics-related achievement. Participants were 77 undergraduates from two classes enrolled in applied statistics courses. An experiment was implemented according to a pretest/posttest comparison group design. The quasi-experimental design showed that the one-minute paper strategy significantly reduced students' statistics anxiety and improved students' statistics learning achievement. The strategy was a better instructional tool than the textbook exercise for reducing students' statistics anxiety and improving students' statistics achievement.

A Finite Element Model for Simulating Stress Responses of Permeable Road Pavement.

Permeable road pavements, due to their open-graded design, suffer from low structural strength, restricting their use in areas with light traffic volume and low bearing capacity. To expand application of permeable road pavements, accurate simulation of stress parameters used in pavement design is essential. A 3D finite element (3D FE) model was developed using ABAQUS/CAE 2021 to simulate pavement stress responses. Utilizing a 53 cm thick permeable road pavement and a 315/80 R22.5 wheel as prototypes, the model was calibrated and validated, with its accuracy confirmed through t-test statistical analysis. Simulations of wheel speeds at 11, 15, and 22 m/s revealed significant impact on pavement depths of 3 cm and 8 cm, while minimal effects were observed at depths of 13 cm and 33 cm. Notably, stress values at a depth of 3 cm with 15 m/s speed in the open-graded asphalt concrete (OGFC) surface layer exceeded those at the speed of 11 m/s, while at a depth of 8 cm in the porous asphalt concrete (PAC) base layer, an opposite performance was observed. This may be attributed to the higher elastic modulus of the OGFC surface layer, which results in different response trends to velocity changes. Overall, lower speeds increase stress responses and prolong action times for both layers, negatively affecting pavement performance. Increasing the moduli of layers is recommended for new permeable road pavements for low-speed traffic. Furthermore, considering the effects of heavy loads and changes in wheel speed, the recommended design depth for permeable road pavement is 30 cm. These conclusions provide a reference for the design of permeable road pavements to address climate change and improve performance.

Recent Advances in Engineering Carriers for siRNA Delivery.

RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical are hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, the recent advances in siRNA carriers consisting of lipids, polymers, and polymer-modified inorganic particles for cancer therapy are summarized. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. It is believed that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.

Prediction of missing flow records using multilayer perceptron and coactive neurofuzzy inference system.

Hydrological data are often missing due to natural disasters, improper operation, limited equipment life, and other factors, which limit hydrological analysis. Therefore, missing data recovery is an essential process in hydrology. This paper investigates the accuracy of artificial neural networks (ANN) in estimating missing flow records. The purpose is to develop and apply neural networks models to estimate missing flow records in a station when data from adjacent stations is available. Multilayer perceptron neural networks model (MLP) and coactive neurofuzzy inference system model (CANFISM) are used to estimate daily flow records for Li-Lin station using daily flow data for the period 1997 to 2009 from three adjacent stations (Nan-Feng, Lao-Nung and San-Lin) in southern Taiwan. The performance of MLP is slightly better than CANFISM, having R (2) of 0.98 and 0.97, respectively. We conclude that accurate estimations of missing flow records under the complex hydrological conditions of Taiwan could be attained by intelligent methods such as MLP and CANFISM.

A case report of Williams syndrome with main clinical manifestation of hypercalcemia and gastrointestinal bleeding as the main clinical manifestations, and with an accompanying literature review.

BACKGROUND: Williams syndrome is an autosomal dominant multisystem disorder caused by a 1.5-1.8 Mb deletion on chromosome 7q11.23. It is characterized by facial deformations, cardiovascular abnormalities, developmental delays, gastrointestinal manifestations, and endocrine disorders. CASE DESCRIPTION: A 1-year-old child presenting with developmental delays, special facial features, gastrointestinal bleeding, renal calcium deposition, and hypotonia was admitted to the hospital for "hypercalcemia and gastrointestinal bleeding." Genetic testing showed a deletion mutation in the 7q11.23 region. Currently, the child receiving treatment to promote calcium excretion and rehabilitation training, but hypercalcemia has recurred. CONCLUSION: The clinical phenotype of Williams syndrome is complex, and different severities, characterized by developmental delays, facial deformities, cardiovascular abnormalities, gastrointestinal symptoms and endocrine disorders, should be considered in children. The syndrome may require thorough genetic testing for diagnosis and early intervention treatment to improve patient quality of life.

Changes to Material Phase and Morphology Due to High-Level Molybdenum Doping of ZnO Nanorods: Influence on Luminescence and Defects.

The influence of Mo on the electronic states and crystalline structure, as well as morphology, phase composition, luminescence, and defects in ZnO rods grown as free-standing nanoparticles, was studied using a variety of experimental techniques. Mo has almost no influence on the luminescence of the grown ZnO particles, whereas shallow donors are strongly affected in ZnO rods. Annealing in air causes exciton and defect-related bands to drop upon Mo doping level. The increase of the Mo doping level from 20 to 30% leads to the creation of dominating molybdates. This leads to a concomitant drop in the number of formed ZnO nanorods.

A survey of urolithiasis in young children fed infant formula contaminated with melamine in two townships of Gansu, China.

OBJECTIVE: To determine the prevalence of urolithiasis in young children fed infant formula (IF) contaminated with melamine, and the association between IF consumption and urolithiasis. DESIGN: A total of 2 733 children < or = 3 years of age on September 1, 2008 in two townships of Gansu Province, China were studied. Cases of urolithiasis were diagnosed by ultrasonography. Milk product consumption was determined by their caregivers. Remaining IF samples were tested for melamine and cyanuric acid. RESULTS: Of 2 733 eligible children in the two townships, 2 186 (80%) were enrolled in our study. Overall, 16.6% (362) of 2 186 children had urolithiasis. The prevalence was 24.6% in children exclusively fed Sanlu brand IF, 9.7% in those fed other IF, and 8.5% in those fed exclusively on other milk products. For children exclusively breast-fed, no urolithiasis was found (P < 0.05). The prevalence of urolithiasis was 11.4% in children fed 400 g of Sanlu IF, rising to 37.5% in children fed over 25 600 g. Of 48 Sanlu IF samples, 91.7% contained melamine (median = 1 800 ppm; range = 45-4 700) and 66.7% contained cyanuric acid (median = 1.2 ppm; range = 0.4-6.3). Melamine was also detected in 22.2% of 36 other brand IF (median = 27.5 ppm, range = 4-50). CONCLUSIONS: Urolithiasis was associated with melamine-contaminated IF. Although one product caused most morbidity, other milk products may have also contributed to the outbreak.