Engineering Versatile Nanomedicines for Ultrasonic Tumor Immunotherapy.

Due to the specific advantages of ultrasound (US) in therapeutic disease treatments, the unique therapeutic US technology has emerged. In addition to featuring a low-invasive targeted cancer-cell killing effect, the therapeutic US technology has been demonstrated to modulate the tumor immune landscape, amplify the therapeutic effect of other antitumor therapies, and induce immunosensitization of tumors to immunotherapy, shedding new light on the cancer treatment. Tremendous advances in nanotechnology are also expected to bring unprecedented benefits to enhancing the antitumor efficiency and immunological effects of therapeutic US, as well as therapeutic US-derived bimodal and multimodal synergistic therapies. This comprehensive review summarizes the immunological effects induced by different therapeutic US technologies, including ultrasound-mediated micro-/nanobubble destruction (UTMD/UTND), sonodynamic therapy (SDT), and focused ultrasound (FUS), as well as the main underlying mechanisms involved. It is also discussed that the recent research progress of engineering intelligent nanoplatform in improving the antitumor efficiency of therapeutic US technologies. Finally, focusing on clinical translation, the key issues and challenges currently faced are summarized, and the prospects for promoting the clinical translation of these emerging nanomaterials and ultrasonic immunotherapy in the future are proposed.

Modeling the Formation of Organic Compounds across Full Volatility Ranges and Their Contribution to Nanoparticle Growth in a Polluted Atmosphere.

Nanoparticle growth influences atmospheric particles' climatic effects, and it is largely driven by low-volatility organic vapors. However, the magnitude and mechanism of organics' contribution to nanoparticle growth in polluted environments remain unclear because current observations and models cannot capture organics across full volatility ranges or track their formation chemistry. Here, we develop a mechanistic model that characterizes the full volatility spectrum of organic vapors and their contributions to nanoparticle growth by coupling advanced organic oxidation modeling and kinetic gas-particle partitioning. The model is applied to Nanjing, a typical polluted city, and it effectively captures the volatility distribution of low-volatility organics (with saturation vapor concentrations <0.3 µg/m3), thus accurately reproducing growth rates (GRs), with a 4.91% normalized mean bias. Simulations indicate that as particles grow from 4 to 40 nm, the relative fractions of GRs attributable to organics increase from 59 to 86%, with the remaining contribution from H2SO4 and its clusters. Aromatics contribute much to condensable organic vapors (∼37%), especially low-volatility vapors (∼61%), thus contributing the most to GRs (32-46%) as 4-40 nm particles grow. Alkanes also contribute 19-35% of GRs, while biogenic volatile organic compounds contribute minimally (<13%). Our model helps assess the climatic impacts of particles and predict future changes.

Ultrasound-activated nanosonosensitizer for oxygen/sulfate dual-radical nanotherapy.

An all-in-one therapy for cooperatively fighting cancer, infection and boosting wound repair is exceedingly demanded for patients with advanced superficial cancers or after surgical intervention to avoid multiple drug abuse and resultant adverse effects. Here, the ultrasound-activated nanosonosensitizer PHMP that integrated peroxymonosulfate (PMS) into the Pd-catalyzed hydrogenated mesoporous titanium dioxide (PHM) was dexterously designed for combined therapy of cancer and infected wound based on oxygen/sulfate dual-radical nanotherapy. Firstly, the PHM with single crystal structure and abundant oxygen deficiencies exhibited excellent ultrasound-excited reactive oxygen species (ROS) production for enhanced sonodynamic therapy (SDT) under the support of Pd nanozyme-mediated O2 supply. Simultaneously, the physically targeted ultrasound irradiation effectively transformed PMS loaded in the hollow cavities into distinct sulfate radical (•SO4-) with longer half-life and stronger oxidation, which remarkably enhanced the therapeutic efficacy of PHM-mediated SDT for cancer and bacteria. In addition, by embedding PHMP into the hydrogel, the enrichment of PHMP in the focal site was guaranteed, and meanwhile a moist and ventilated environment was created to speed up wound repair. The study broadens the potential of •SO4- in the therapeutic fields and contributes a simple and appealing tactic for the comprehensive treatment of cancer, infection and wound repair.

Molecular Characterization of Oxygenated Organic Molecules and Their Dominating Roles in Particle Growth in Hong Kong.

Oxygenated organic molecules (OOMs) are critical intermediates linking volatile organic compound oxidation and secondary organic aerosol (SOA) formation. Yet, the understanding of OOM components, formation mechanism, and impacts are still limited, especially for urbanized regions with a cocktail of anthropogenic emissions. Herein, ambient measurements of OOMs were conducted at a regional background site in South China in 2018. The molecular characteristics of OOMs revealed dominant nitrogen-containing products, and the influences of different factors on OOM composition and oxidation state were elucidated. Positive matrix factorization analysis resolved the complex OOM species to factors featured with fingerprint species from different oxidation pathways. A new method was developed to identify the key functional groups of OOMs, which successfully classified the majority species into carbonyls (8%), hydroperoxides (7%), nitrates (17%), peroxyl nitrates (10%), dinitrates (13%), aromatic ring-retaining species (6%), and terpenes (7%). The volatility estimation of OOMs was improved based on their identified functional groups and was used to simulate the aerosol growth process contributed by the condensation of those low-volatile OOMs. The results demonstrate the predominant role of OOMs in contributing sub-100 nm particle growth and SOA formation and highlight the importance of dinitrates and anthropogenic products from multistep oxidation.

Enigma of Urban Gaseous Oxygenated Organic Molecules: Precursor Type, Role of NOx, and Degree of Oxygenation.

Oxidation of volatile organic compounds (VOCs) forms oxygenated organic molecules (OOMs), which contribute to secondary pollution. Herein, we present measurement results of OOMs using chemical ionization mass spectrometry with nitrate as the reagent ion in Shanghai. Compared to those in forests and laboratory studies, OOMs detected at this urban site were of relatively lower degree of oxygenation. This was attributed to the high NOx concentrations (∼44 ppb), which overall showed a suppression on the propagation reactions. As another result, a large fraction of nitrogenous OOMs (75%) was observed, and this fraction further increased to 84% under a high NO/VOC ratio. By applying a novel framework on OOM categorization and supported by VOC measurements, 50 and 32% OOMs were attributed to aromatic and aliphatic precursors, respectively. Furthermore, aromatic OOMs are more oxygenated (effective oxygen number, nOeff = 4-6) than aliphatic ones (nOeff = 3-4), which can be partly explained by the difference in initiation mechanisms and points to possible discrimination in termination reactions. This study highlights the roles of NOx in OOM formation in urban areas, as well as the formation of nitrogenous products that might show discrimination between aromatic and aliphatic VOCs.

High-density volatile organic compound monitoring network for identifying pollution sources.

The elusive sources of air pollution have hampered effective control across all sectors, with long-term consequences for the greenhouse effect and human health. Multiple monitoring systems have been highly desired for locating the sources. However, when faced with extensive sources, diverse air environments and meteorological conditions, the low spatiotemporal resolution, poor reliability and high cost of existing monitors were significant obstacles to their applications. Extending our previous demonstration of sensitive and reliable electrochemical sensors, we here present a machine-learning-assisted sensor arrays for monitoring typical volatile organic compounds (VOCs), which shows the consistent response with gas chromatography-mass spectrometry in the actual air environment. As a proof-of-concept, a low-cost and high-resolution VOC network of 152 sets of monitors across ~55 km2 of mixed-used land is established in southwest Beijing. Benefiting from the strong reliability, the pollution sources are revealed by the VOC network and supported by the joint mobile sampling of a vehicle-mounted gas chromatography-mass spectrometry system. With the sustained help of the network, the sources polluted by the local industrial facilities, traffic, and restaurants are effectively site-specific abatement by the local authorities and enterprises during the next half-year. Our findings open up a promising path toward more effective tracing of regional pollution sources, as well as accelerate the long-term transformation of industry and cities.

The interaction between cellular senescence and chronic kidney disease as a therapeutic opportunity.

Chronic kidney disease (CKD) is an increasingly serious public health problem in the world, but the effective therapeutic approach is quite limited at present. Cellular senescence is characterized by the irreversible cell cycle arrest, senescence-associated secretory phenotype (SASP) and senescent cell anti-apoptotic pathways (SCAPs). Renal senescence shares many similarities with CKD, including etiology, mechanism, pathological change, phenotype and outcome, however, it is difficult to judge whether renal senescence is a trigger or a consequence of CKD, since there is a complex correlation between them. A variety of cellular signaling mechanisms are involved in their interactive association, which provides new potential targets for the intervention of CKD, and then extends the researches on senotherapy. Our review summarizes the common features of renal senescence and CKD, the interaction between them, the strategies of senotherapy, and the open questions for future research.

Insufficient Condensable Organic Vapors Lead to Slow Growth of New Particles in an Urban Environment.

Atmospheric new particle formation significantly affects global climate and air quality after newly formed particles grow above ∼50 nm. In polluted urban atmospheres with 1-3 orders of magnitude higher new particle formation rates than those in clean atmospheres, particle growth rates are comparable or even lower for reasons that were previously unclear. Here, we address the slow growth in urban Beijing with advanced measurements of the size-resolved molecular composition of nanoparticles using the thermal desorption chemical ionization mass spectrometer and the gas precursors using the nitrate CI-APi-ToF. A particle growth model combining condensational growth and particle-phase acid-base chemistry was developed to explore the growth mechanisms. The composition of 8-40 nm particles during new particle formation events in urban Beijing is dominated by organics (∼80%) and sulfate (∼13%), and the remainder is from base compounds, nitrate, and chloride. With the increase in particle sizes, the fraction of sulfate decreases, while that of the slow-desorbed organics, organic acids, and nitrate increases. The simulated size-resolved composition and growth rates are consistent with the measured results in most cases, and they both indicate that the condensational growth of organic vapors and H2SO4 is the major growth pathway and the particle-phase acid-base reactions play a minor role. In comparison to the high concentrations of gaseous sulfuric acid and amines that cause high formation rates, the concentration of condensable organic vapors is comparably lower under the high NOx levels, while those of the relatively high-volatility nitrogen-containing oxidation products are higher. The insufficient condensable organic vapors lead to slow growth, which further causes low survival of the newly formed particles in urban environments. Thus, the low growth rates, to some extent, counteract the impact of the high formation rates on air quality and global climate in urban environments.

Description of the Molecular and Phenotypic Spectrum of Lesch-Nyhan Disease in Eight Chinese Patients.

Background: Lesch-Nyhan disease (LND) is a rare disorder involving pathogenic variants in the HPRT1 gene encoding the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) that result in hyperuricemia, intellectual disability, dystonic movement disorder, and compulsive self-mutilation. The purpose of the present study was to characterize the genetic basis of LND and describe its phenotypic heterogeneity by identifying the variation in the HPRT1 gene in a cohort of Chinese LND patients. Results: The median age at diagnosis was 31 mo (interquartile range (IQR): 7-76 mo), and the initial manifestations were mainly head control weakness and motor development delay. The median age of self-mutilation behavior onset was 19 mo (IQR: 17-24 mo), and all patients were required to travel in a wheelchair and fall into the predicament of compulsive self-harm behavior. There were two patients whose blood uric acid levels were normal for their high urinary acid excretion fraction without taking uric acid-lowering drugs. Seven different pathogenic variants of the HPRT1 gene were identified among eight independent pedigrees, including four novel mutations [c.299 (exon 3) T > A; loss (exon: 6) 84 bp; c.277_281delATTGC; c.468_470delGAT]. The pathogenic variant sites were mainly concentrated in exon 3, and truncating mutations (including frameshift mutations and nonsense mutations) were the most common genetic variant types (5/7, 71.4%). Conclusion: The present study described the phenotypic and molecular spectrum of LND in eight Chinese families, including four novel mutations, which expands our understanding of LND.

Engineering defected 2D Pd/H-TiO2 nanosonosensitizers for hypoxia alleviation and enhanced sono-chemodynamic cancer nanotherapy.

BACKGROUND: Sonodynamic therapy (SDT) is a burgeoning modality for cancer therapy owing to its high tissue-penetrating capability, controllability and safety. Whereas, the undesirable reactive oxygen species (ROS) yield of sonosensitizers and tumor hypoxia are two vulnerable spots of SDT. Therefore, it is an advisable strategy to augment ROS level and simultaneously relieve hypoxia for SDT to arrive its full potential in cancer treatment. RESULTS: In this work, the defected two-dimensional (2D) Pd/H-TiO2 nanosheets (NSs) with triple antineoplastic properties were dexterously elaborated and engineered using a facile one-pot Pd-catalyzed hydrogenation tactic by loading a tiny amount of Pd and then inletting hydrogen flow at atmospheric pressure and temperature. The 2D black Pd/H-TiO2 NSs with oxygen defects exerted eximious SDT effect based on the decreased bandgap that made it easier for the separation of electrons and holes when triggered by ultrasound as theoretically guided by density functional theory calculations. Additionally, Pd/H-TiO2 NSs could serve as Fenton-like agents because of the presence of oxygen defects, facilitating the conversion of hydrogen peroxide into hydroxyl radicals for exerting the chemodynamic therapy (CDT). Simultaneously, the introduced tiny Pd component possessed catalase-like activity responsible for oxygen production to ameliorate hypoxic condition and thus contributed to improving SDT and CDT efficacies. Both in vitro and in vivo results provided compelling evidences of high ROS yield and aggrandized sono-chemodynamic effect of Pd/H-TiO2 nanosonosensitizers with the detailed underlying mechanism investigation by RNA sequencing. CONCLUSION: This work delves the profound potential of Pd-catalyzed hydrogenated TiO2 on oncotherapy, and the effective antineoplastic performance and ignorable therapeutic toxicity make it a powerful competitor among a cornucopia of nanosonosensitizers.

SMAD1 Loss-of-Function Variant Responsible for Congenital Heart Disease.

As the most common form of developmental malformation affecting the heart and endothoracic great vessels, congenital heart disease (CHD) confers substantial morbidity and mortality as well as socioeconomic burden on humans globally. Aggregating convincing evidence highlights the genetic origin of CHD, and damaging variations in over 100 genes have been implicated with CHD. Nevertheless, the genetic basis underpinning CHD remains largely elusive. In this study, via whole-exosome sequencing analysis of a four-generation family inflicted with autosomal-dominant CHD, a heterozygous SMAD1 variation, NM_005900.3: c.264C > A; p.(Tyr88∗), was detected and validated by Sanger sequencing analysis to be in cosegregation with CHD in the whole family. The truncating variation was not observed in 362 unrelated healthy volunteers employed as control persons. Dual-luciferase reporter gene assay in cultured COS7 cells demonstrated that Tyr88∗-mutant SMAD1 failed to transactivate the genes TBX20 and NKX2.5, two already well-established CHD-causative genes. Additionally, the variation nullified the synergistic transcriptional activation between SMAD1 and MYOCD, another recognized CHD-causative gene. These data indicate SMAD1 as a new gene responsible for CHD, which provides new insight into the genetic mechanism underlying CHD, suggesting certain significance for genetic risk assessment and precise antenatal prevention of the family members inflicted with CHD.

Contribution of Atmospheric Oxygenated Organic Compounds to Particle Growth in an Urban Environment.

Gas-phase oxygenated organic molecules (OOMs) can contribute substantially to the growth of newly formed particles. However, the characteristics of OOMs and their contributions to particle growth rate are not well understood in urban areas, which have complex anthropogenic emissions and atmospheric conditions. We performed long-term measurement of gas-phase OOMs in urban Beijing during 2018-2019 using nitrate-based chemical ionization mass spectrometry. OOM concentrations showed clear seasonal variations, with the highest in the summer and the lowest in the winter. Correspondingly, calculated particle growth rates due to OOM condensation were highest in summer, followed by spring, autumn, and winter. One prominent feature of OOMs in this urban environment was a high fraction (∼75%) of nitrogen-containing OOMs. These nitrogen-containing OOMs contributed only 50-60% of the total growth rate led by OOM condensation, owing to their slightly higher volatility than non-nitrate OOMs. By comparing the calculated condensation growth rates and the observed particle growth rates, we showed that sulfuric acid and its clusters are the main contributors to the growth of sub-3 nm particles, with OOMs significantly promoting the growth of 3-25 nm particles. In wintertime Beijing, however, there are missing contributors to the growth of particles above 3 nm, which remain to be further investigated.

SOX17 Loss-of-Function Mutation Underlying Familial Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) refers to a rare, progressive disorder that is characterized by occlusive pulmonary vascular remodeling, resulting in increased pulmonary arterial pressure, right-sided heart failure, and eventual death. Emerging evidence from genetic investigations of pediatric-onset PAH highlights the strong genetic basis underpinning PAH, and deleterious variants in multiple genes have been found to cause PAH. Nevertheless, PAH is of substantial genetic heterogeneity, and the genetic defects underlying PAH in the overwhelming majority of cases remain elusive. In this investigation, a consanguineous family suffering from PAH transmitted as an autosomal-dominant trait was identified. Through whole-exome sequencing and bioinformatic analyses as well as Sanger sequencing analyses of the PAH family, a novel heterozygous SOX17 mutation, NM_022454.4: c.379C>T; p. (Gln127*), was found to co-segregate with the disease in the family, with complete penetrance. The nonsense mutation was neither observed in 612 unrelated healthy volunteers nor retrieved in the population genetic databases encompassing the Genome Aggregation Database, the Exome Aggregation Consortium database, and the Single Nucleotide Polymorphism database. Biological analyses using a dual-luciferase reporter assay system revealed that the Gln127*-mutant SOX17 protein lost the ability to transcriptionally activate its target gene NOTCH1. Moreover, the Gln127*-mutant SOX17 protein exhibited no inhibitory effect on the function of CTNNB1-encode ß-catenin, which is a key player in vascular morphogenesis. This research firstly links SOX17 loss-of-function mutation to familial PAH, which provides novel insight into the molecular pathogenesis of PAH, suggesting potential implications for genetic and prognostic risk evaluation as well as personalized prophylaxis of the family members affected with PAH.

Immunopathogenesis of idiopathic nephrotic syndrome in children: two sides of the coin.

BACKGROUND: Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children, with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities. The etiological factors and mechanisms of childhood idiopathic nephrotic syndrome have not yet been fully elucidated. This review summarizes the progress of the immunopathogenesis of idiopathic nephrotic syndrome in children. DATA SOURCES: We review the literature on the immunopathogenesis of idiopathic nephrotic syndrome in children. Databases including Medline, Scopus, and Web of Science were searched for studies published in any language with the terms "children", "idiopathic nephrotic syndrome", "immunopathogenesis", "T cells", "circulating permeability factors", and "B cells". RESULTS: Dysfunction in T lymphocytes and pathogenic circulatory factors were indicated to play key roles in the pathogenesis of idiopathic nephrotic syndrome. Recently, some studies have shown that cellular immune dysfunction may also be involved in the pathogenesis of idiopathic nephrotic syndrome. CONCLUSIONS: Both T- and B-cell dysfunction may play significant roles in the pathogenesis of idiopathic nephrotic syndrome, like two sides of one coin, but the role of B cell seems more important than T cells.

Improving data reliability: A quality control practice for low-cost PM2.5 sensor network.

Low-cost air quality sensor networks have been increasingly used for high spatial resolution air quality monitoring in recent years. Ensuring data reliability during continuous operation is critical for these sensor networks. Using particulate matter sensor as an example, this study reports a data quality control method, including sensor selection, pre-calibration, and online inspection. It was used in developing and operating the dense low-cost particle sensor networks in two Chinese cities. Firstly, seven mainstream sensors were tested and one model of particle sensor was selected due to its better linearity and stability. For a batch of sensors of the same model, although they were calibrated after manufactured, there are differences in response toward the same concentration of pollutants. The systematical variation of sensors was corrected and unified through pre-calibration. After deploying them in the field, a data analysis method is established for online inspecting their working status. Using data from these sensors, it evaluates parameters such as intraclass correlation coefficients and normalized root mean square error. These two metrics help to construct a two-dimensional coordinate system and to classify sensors into four status, including normal, fluctuation, hotspots, and malfunction. During a one-month operation in the two cities, 8 (out of 82) and 10 (out of 59) sensors with suspected malfunctions were screened out for further on-site inspection. Moreover, the sensor networks show potential in identifying illegal emission sources that cannot be typically detected by sparse regulatory air quality monitoring stations.

Quantifying the Deposition of Airborne Particulate Matter Pollution on Skin Using Elemental Markers.

Airborne particulate matter (PM) pollution is an environmental and health concern. The health impact of PM pollution has typically focused on the respiratory system. The impact of PM pollution on skin has been largely understudied due to the lack of a quantitative method to measure the deposition on skin. This manuscript presents a method to quantify PM pollution on skin using elemental markers as a proxy for PM. Skin tape strips were collected from forehead and buttock of 100 outdoor workers in Beijing, China. Skin samples were analyzed for 19 elemental markers using inductively coupled plasma mass spectrometry. To determine the specific elemental signature of PM for the region, air samples were collected over 7 days for PM < 2.5 µm (PM2.5) and analyzed for the same 19 elements as the skin samples. An enrichment factor was calculated for each element and the potential source was evaluated. Using the elemental markers unique to PM pollution for the region, the PM concentration deposited on skin was determined to be 0.621-2.53 µg PM2.5 /cm2. This method can be re-applied in different regions and the PM concentration on skin can inform future studies on the health impact of air pollution on skin.

Seasonal Characteristics of New Particle Formation and Growth in Urban Beijing.

Understanding the atmospheric new particle formation (NPF) process within the global range is important for revealing the budget of atmospheric aerosols and their impacts. We investigated the seasonal characteristics of NPF in the urban environment of Beijing. Aerosol size distributions down to ∼1 nm and H2SO4 concentration were measured during 2018-2019. The observed formation rate of 1.5 nm particles (J1.5) is significantly higher than those in the clean environment, e.g., Hyytiälä, whereas the growth rate is not significantly different. Both J1.5 and NPF frequency in urban Beijing show a clear seasonal variation with maxima in winter and minima in summer, while the observed growth rates are generally within the same range around the year. We show that ambient temperature is a governing factor driving the seasonal variation of J1.5. In contrast, the condensation sink and the daily maximum H2SO4 concentration show no significant seasonal variation during the NPF periods. In all four seasons, condensation of H2SO4 and (H2SO4)n(amine)n clusters contributes significantly to the growth rates in the sub-3 nm size range, whereas it is less important for the observed growth rates of particles above 3 nm. Therefore, other species are always needed for the growth of larger particles.

Responses of gaseous sulfuric acid and particulate sulfate to reduced SO2 concentration: A perspective from long-term measurements in Beijing.

SO2 concentration decreased rapidly in recent years in China due to the implementation of strict control policies by the government. Particulate sulfate (pSO42-) and gaseous H2SO4 (SA) are two major products of SO2 and they play important roles in the haze formation and new particle formation (NPF), respectively. We examined the change in pSO42- and SA concentrations in response to reduced SO2 concentration using long-term measurement data in Beijing. Simulations from the Community Multiscale Air Quality model with a 2-D Volatility Basis Set (CMAQ/2D-VBS) were used for comparison. From 2013 to 2018, SO2 concentration in Beijing decreased by ~81% (from 9.1 ppb to 1.7 ppb). pSO42- concentration in submicrometer particles decreased by ~60% from 2012-2013 (monthly average of ~10 µg·m-3) to 2018-2019 (monthly average of ~4 µg·m-3). Accordingly, the fraction of pSO42- in these particles decreased from 20-30% to <10%. Increased sulfur oxidation ratio was observed both in the measurements and the CMAQ/2D-VBS simulations. Despite the reduction in SO2 concentration, there was no obvious decrease in SA concentration based on data from several measuring periods from 2008 to 2019. This was supported by the increased SA:SO2 ratio with reduced SO2 concentration and condensation sink. NPF frequency in Beijing between 2004 and 2019 remains relatively constant. This constant NPF frequency is consistent with the relatively stable SA concentration in Beijing, while different from some other cities where NPF frequency was reported to decrease with decreased SO2 concentrations.

Multiple bladder diverticula with Williams-Beuren syndrome: a case report.

Williams-Beuren syndrome (WBS) is an autosomal dominant disorder caused by a gene deletion on chromosome 7q11.23. Patients with WBS usually show a group of features such as developmental delay, cardiovascular anomalies, mental retardation, and characteristic facial appearance. It occurs in 1:7,500 live births and affects males and females equally. Recent studies showed that lower urinary tract symptoms were also frequent in WBS patients. However, there is extremely rare study report non-monosymptomatic nocturnal enuresis as the main manifestation of Williams syndrome in children. We reported a child with non-monosymptomatic nocturnal enuresis and multiple bladder diverticula as the main implications of Williams syndrome. A 7.6-year-old girl was admitted to our hospital due to frequent micturition, urgency, and nocturnal enuresis for 4 years, and B ultrasound of urinary system revealed multiple bladder diverticula. The patient was found to have 7q11.23 deletion that involves the elastin gene for WBS. Multiple bladder diverticula in WBS patients can lead to many lower urinary tract symptoms. The treatment for the lower urinary tract symptoms in WBS patients with multiple bladder diverticula is lacking. Lower urinary tract symptoms should be considered as a significant indicator of the clinical diagnosis of WBS and have a significant negative impact on patient's quality of life.

Combination of Maximum Shear Wave Elasticity Modulus and TIRADS Improves the Diagnostic Specificity in Characterizing Thyroid Nodules: A Retrospective Study.

OBJECTIVES: The present study is aimed at evaluating the diagnostic value of combining shear wave elastography (SWE) parameters and the thyroid imaging reporting and data system (TIRADS) for differentiating between benign and malignant thyroid nodules. METHODS: Patients who underwent conventional ultrasonography (US) and SWE before surgery were enrolled in the current study. Each nodule was given a TIRADS risk score. The effectiveness of the SWE parameters was assessed by odds ratios (ORs). The SWE scoring risk stratification was proposed beyond 95% probability, and the desired values were obtained according to the log-normal distribution. The area under the receiver-operating characteristic (AUC) was used to compare the diagnostic performance between TIRADS-alone and TIRADS + SWE. RESULTS: A total of 262 patients with 298 thyroid nodules were enrolled in our study. The pathological analyses were conducted on 121 benign and 177 malignant nodules. The AUC values for TIRADS-alone and TIRADS + SWE were 0.896 (accuracy 83.2%) and 0.917 (accuracy 84.2%), respectively. However, the TIRADS + SWE scores showed a higher specificity (88.4%) and positive predictive value (91.2%) as compared with the TIRADS-alone of 73.6% and 83.2%, respectively. CONCLUSIONS: Combining SWE and TIRADS improves the specificity of TIRADS-alone in differentiating between benign and malignant thyroid nodules.