Lymphadenectomy After Melanoma-A National Analysis of Recurrence Rates and Risk of Lymphedema.

INTRODUCTION: Treatment for melanoma after a positive sentinel lymph node biopsy includes nodal observation or lymphadenectomy. Important considerations for management, however, involve balancing the risk of recurrence and the risk of lymphedema after lymphadenectomy. METHODS: From the Merative MarketScan Research Databases, adult patients were queried from 2007 to 2021. International Classification of Disease, Ninth (ICD-9) and Tenth (ICD-10) Editions, diagnosis codes and Current Procedural Terminology codes were used to identify patients with melanoma diagnoses who underwent an index melanoma excision with a positive sentinel lymph node biopsy (SLNB). Main outcomes were completion lymph node dissection (CLND) utilization after a positive SLNB, developing lymphedema with or without CLND, and nodal basin recurrence 3 months or more after index excision. Subanalyses stratified by index excision year (2007-2017 and 2018-2021) and propensity score matched were additionally conducted. Demographics and comorbidities (measured by Elixhauser index) were recorded. RESULTS: A total of 153,085,453 patients were identified. Of those, 359,298 had a diagnosis of melanoma, and 202,456 patients underwent an excision procedure. The study cohort comprised 3717 patients with a melanoma diagnosis who underwent an excision procedure and had a positive SLNB. The mean age of the study cohort was 49 years, 57% were male, 41% were geographically located in the South, and 24% had an Elixhauser index of 4+. Among the 350 patients who did not undergo CLND, 10% experienced recurrence and 22% developed lymphedema. A total of 3367 patients underwent CLND, of which 8% experienced recurrence and 20% developed lymphedema. Completion lymph node dissection did not significantly affect risk of recurrence [odds ratio (OR), 1.370, P = 0.090] or lymphedema (OR, 1.114, P = 0.438). After stratification and propensity score matching, odds of experiencing lymphedema (OR, 1.604, P = 0.058) and recurrence (OR, 1.825, P = 0.058) after CLND were not significantly affected. Rates of CLND had significantly decreased (P < 0.001) overtime, without change in recurrence rate (P = 0.063). CONCLUSIONS: Electing for nodal observation does not increase the risk of recurrence or reduce risk of lymphedema. Just as CLND does not confer survival benefit, its decreased utilization has not increased recurrence rate.

Replicator-mutator dynamics with evolutionary public goods game-environmental feedbacks.

Feedback loops between strategies and the environment are commonly observed in socio-ecological, evolution-ecological, and psychology-economic systems. However, the impact of mutations in these feedback processes is often overlooked. This study proposes a novel model that integrates the public goods game with environmental feedback, considering the presence of mutations. In our model, the enhancement factor of the public goods game combines positive and negative incentives from the environment. By employing replicator-mutator (RM) equations, we provide an objective understanding of the system's evolutionary state, focusing on identifying conditions that foster cooperation and prevent the tragedy of the commons. Specifically, mutations play a crucial role in the RM dynamics, leading to the emergence of an oscillatory tragedy of the commons. By verifying the Hopf bifurcation condition, we establish the existence of a stable limit cycle, providing valuable insights into sustained oscillation strategies. Moreover, the feedback mechanism inherent in the public goods game model offers a fresh perspective on effectively addressing the classic dilemma of the tragedy of the commons.

The Prevalence of Difficult Airway and Associated Risk Factors in Pediatric Patients: A Cross-sessional Observational Study.

BACKGROUND: Difficult airway remains a great challenge in pediatric anesthesia practice. Previously published data show the prevalence of difficult airways in pediatric population varies in a wide range. However, there is a lack of studies in the Asian region. METHODS: This cross-sectional single-center study was conducted in a tertiary pediatric hospital in China from October 2022 to October 2023. The patients who underwent elective surgery under general anesthesia with tracheal intubation were recruited consecutively. Data on patient characteristics, airway assessment, and airway management information were collected. Multivariable logistic regression analysis was performed to detect the independent variables of difficult airway in pediatric patients. RESULTS: A total of 18,491 pediatric patients were included in this study. The overall incidence of difficult airways was 0.22%, 39% of whom were unanticipated. Very few previous airway management information was available in the patients presented with a known difficult airway. Patients with younger age, higher American Society of Anesthesiologists (ASA) physical status classification grade, and presented for craniofacial and thoracic surgery were associated with higher incidence of difficult airway. Further multivariable logistic regression analysis revealed that age ≤28 days (OR=50.48), age between 28days and 1 year (OR=6.053), craniofacial surgery (OR=1.81), and thoracic surgery (OR=0.2465) were independent risk factors of increased incidence of difficult airway. CONCLUSIONS: Our study showed the prevalence of difficult airways in pediatric surgical patients. Patient characteristics, age, and type of surgery were identified as the independent factors associated with increased occurrence of difficult airways. Unanticipated difficult airway was not unusual in our study population, even for the patients with previous surgical history.

Anisotropic Semicrystalline Homopolymer Dielectrics for High-temperature Capacitive Energy Storage.

High-temperature dielectric polymers are in high demand for powering applications in extreme environments. Here, we have developed high-temperature homopolymer dielectrics with anisotropy by leveraging the hierarchical structure in semicrystalline polymers. The lamellae have been aligned parallel to the surface in the dielectric films. This structural arrangement resembles the horizontal alignment of nanosheet fillers in polymer nanocomposites and nanosheet-like lamellae in block copolymers, which has been proven to provide the optimal topological structure for electrical energy storage. The unique ordering of lamellae in our dielectric films endue a significantly increased breakdown strength and a reduced leakage current compared to amorphous films. This novel approach of enhancing the capacitive energy storage properties by controlled orientation of lamellae in homopolymer offers a new perspective for the design of high-temperature polymer dielectrics.

A wideband, high-resolution vector spectrum analyzer for integrated photonics.

The analysis of optical spectra-emission or absorption-has been arguably the most powerful approach for discovering and understanding matter. The invention and development of many kinds of spectrometers have equipped us with versatile yet ultra-sensitive diagnostic tools for trace gas detection, isotope analysis, and resolving hyperfine structures of atoms and molecules. With proliferating data and information, urgent and demanding requirements have been placed today on spectrum analysis with ever-increasing spectral bandwidth and frequency resolution. These requirements are especially stringent for broadband laser sources that carry massive information and for dispersive devices used in information processing systems. In addition, spectrum analyzers are expected to probe the device's phase response where extra information is encoded. Here we demonstrate a novel vector spectrum analyzer (VSA) that is capable of characterizing passive devices and active laser sources in one setup. Such a dual-mode VSA can measure loss, phase response, and dispersion properties of passive devices. It also can coherently map a broadband laser spectrum into the RF domain. The VSA features a bandwidth of 55.1 THz (1260-1640 nm), a frequency resolution of 471 kHz, and a dynamic range of 56 dB. Meanwhile, our fiber-based VSA is compact and robust. It requires neither high-speed modulators and photodetectors nor any active feedback control. Finally, we employ our VSA for applications including characterization of integrated dispersive waveguides, mapping frequency comb spectra, and coherent light detection and ranging (LiDAR). Our VSA presents an innovative approach for device analysis and laser spectroscopy, and can play a critical role in future photonic systems and applications for sensing, communication, imaging, and quantum information processing.

Thermal Transport in Pentagonal CX2 (X = N, P, As, and Sb).

Two-dimensional (2D) materials with a pentagonal structure have many unique physical properties and great potential for applications in electrical, thermal, and optical fields. In this paper, the intrinsic thermal transport properties of 2D pentagonal CX2 (X = N, P, As, and Sb) are comparatively investigated. The results show that penta-CN2 has a high thermal conductivity (302.7 W/mK), while penta-CP2, penta-CAs2, and penta-CSb2 have relatively low thermal conductivities of 60.0, 36.9, and 11.8 W/mK, respectively. The main reason for the high thermal conductivity of penta-CN2 is that the small atomic mass of the N atom is comparable to that of the C atom, resulting in a preferable pentagonal structure with stronger bonds and thus a higher phonon group velocity. The reduction in the thermal conductivity of the other three materials is mainly due to the gradually increased atomic mass from P to Sb, which reduces the phonon group velocity. In addition, the large atomic mass difference does not result in a huge enhancement of the anharmonicity or weakening of the phonon relaxation time. The present work is expected to deepen the understanding of the thermal transport of main group V 2D pentagonal carbons and pave the way for their future applications, also, providing ideas for finding potential thermal management materials.

Bibliometric analysis of global performance and trends of research on combined sewer overflows (CSOs) from 1990 to 2022.

Combined sewer overflows (CSOs) are one of the main sources of pollution in urban water systems and significantly impede the restoration of water body functionalities within urban rivers and lakes. To understand the research and frontier trends of CSOs comprehensively and systematically, a visual statistical analysis of the literature related to CSOs in the Web of Science core database from 1990 to 2022 was conducted using the bibliometric method using HistCite Pro and VOSviewer. The results reveal a total of 1,209 pertinent publications related to CSOs from 1990 to 2022, and the quantity of CSOs-related publications indicated an increasing trend. Investigations of the distribution and fate of typical pollutants in CSOs and their ecological effects on receiving waters and studies on pollution control technologies (source reduction, process control, and end-of-pipe treatment) are the current focus of CSOs research. CSOs pollution control technologies based on source reduction and the monitoring and control of emerging contaminants are at the forefront of scientific investigations on CSOs. This study systematically and comprehensively summarized current research topics and future research directions of CSOs, thus providing a reference for CSOs control and water environment management research.

Single-cell transcriptome analysis profiling lymphatic invasion-related TME in colorectal cancer.

Lymphatic invasion (LI) is extremely aggressive and induces worse prognosis among patients with colorectal cancer (CRC). Thus, it is critical to characterize the cellular and molecular mechanisms underlying LI in order to establish novel and efficacious therapeutic targets that enhance the prognosis of CRC patients. RNA-seq data, clinical and survival information of colon adenocarcinoma (COAD) patients were obtained from the TCGA database. In addition, three scRNA-seq datasets of CRC patients were acquired from the GEO database. Data analyses were conducted with the R packages. We assessed the tumor microenvironment (TME) differences between LI+ and LI- based scRNA-seq data, LI+ cells exhibited augmented abundance of immunosuppression and invasive subset. Marked extracellular matrix network activation was also observed in LI+ cells within SPP1+ macrophages. We revealed that an immunosuppressive and pro-angiogenic TME strongly enhanced LI, as was evidenced by the CD4+ Tregs, CD8+ GZMK+, SPP1+ macrophages, e-myCAFs, and w-myCAFs subcluster infiltrations. Furthermore, we identified potential LI targets that influenced tumor development, metastasis, and immunotherapeutic response. Finally, a novel LIRS model was established based on the expression of 14 LI-related signatures, and in the two testing cohorts, LIRS was also proved to have accurate prognostic predictive ability. In this report, we provided a valuable resource and extensive insights into the LI of CRC. Our conclusions can potentially benefit the establishment of highly efficacious therapeutic targets as well as diagnostic biomarkers that improve patient outcomes.

Evaluation of reference genes for quantitative expression analysis in Mylabris sibirica (Coleoptera, Meloidae).

Mylabris sibirica is a hypermetamorphic insect whose adults feed on oilseed rape. However, due to a shortage of effective and appropriate endogenous references, studies on molecular functional genes in Mylabris sibirica, have been tremendously limited. In this study, ten internal reference genes (ACT, ARF1, AK, EF1α, GAPDH, α-TUB, RPL6, RPL13, RPS3 and RPS18) were tested and assessed under four selected treatments including adult ages, adult tissues, temperatures, and sex by RT-qPCR based on five methods (Ct value, geNorm, NormFinder, BestKeeper and RefFinder). Our findings showed that RPL6 and RPL13 were the most optimal internal reference gene combination for gene expression during various adult ages and under diverse temperatures; The combination of RPL6 and RPS18 was recommended to test gene transcription levels under different adult tissues. AK and RPL6 were the best reference genes in male and female adults. RPL6 and RPL13 were the most appropriate reference gene pair to estimate gene expression levels under four different tested backgrounds. The relative transcript levels of a uridine diphosphate (UDP)-N-acetylglucosamine-pyrophosphorylase (MsUAP), varied greatly according to normalization with the two most- and least-suited reference genes. This study will lay the basis for further molecular physiology and biochemistry studies in M. sibirica, such as development, reproduction, sex differentiation, cold and heat resistance.

Direct visualization of stacking-selective self-intercalation in epitaxial Nb1+xSe2 films.

Two-dimensional (2D) van der Waals (vdW) materials offer rich tuning opportunities generated by different stacking configurations or by introducing intercalants into the vdW gaps. Current knowledge of the interplay between stacking polytypes and intercalation often relies on macroscopically averaged probes, which fail to pinpoint the exact atomic position and chemical state of the intercalants in real space. Here, by using atomic-resolution electron energy-loss spectroscopy in a scanning transmission electron microscope, we visualize a stacking-selective self-intercalation phenomenon in thin films of the transition-metal dichalcogenide (TMDC) Nb1+xSe2. We observe robust contrasts between 180°-stacked layers with large amounts of Nb intercalants inside their vdW gaps and 0°-stacked layers with little detectable intercalants inside their vdW gaps, coexisting on the atomic scale. First-principles calculations suggest that the films lie at the boundary of a phase transition from 0° to 180° stacking when the intercalant concentration x exceeds ~0.25, which we could attain in our films due to specific kinetic pathways. Our results offer not only renewed mechanistic insights into stacking and intercalation, but also open up prospects for engineering the functionality of TMDCs via stacking-selective self-intercalation.

Epidemiology of tuberculosis among children in Beijing, China, 2012-2021.

Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children's Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1-4 years exhibited higher risk of PTB and TB meningitis, and children aged 5-12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.

Anatomical attention can help to segment the dilated pancreatic duct in abdominal CT.

PURPOSE: Pancreatic duct dilation is associated with an increased risk of pancreatic cancer, the most lethal malignancy with the lowest 5-year relative survival rate. Automatic segmentation of the dilated pancreatic duct from contrast-enhanced CT scans would facilitate early diagnosis. However, pancreatic duct segmentation poses challenges due to its small anatomical structure and poor contrast in abdominal CT. In this work, we investigate an anatomical attention strategy to address this issue. METHODS: Our proposed anatomical attention strategy consists of two steps: pancreas localization and pancreatic duct segmentation. The coarse pancreatic mask segmentation is used to guide the fully convolutional networks (FCNs) to concentrate on the pancreas' anatomy and disregard unnecessary features. We further apply a multi-scale aggregation scheme to leverage the information from different scales. Moreover, we integrate the tubular structure enhancement as an additional input channel of FCN. RESULTS: We performed extensive experiments on 30 cases of contrast-enhanced abdominal CT volumes. To evaluate the pancreatic duct segmentation performance, we employed four measurements, including the Dice similarity coefficient (DSC), sensitivity, normalized surface distance, and 95 percentile Hausdorff distance. The average DSC achieves 55.7%, surpassing other pancreatic duct segmentation methods on single-phase CT scans only. CONCLUSIONS: We proposed an anatomical attention-based strategy for the dilated pancreatic duct segmentation. Our proposed strategy significantly outperforms earlier approaches. The attention mechanism helps to focus on the pancreas region, while the enhancement of the tubular structure enables FCNs to capture the vessel-like structure. The proposed technique might be applied to other tube-like structure segmentation tasks within targeted anatomies.

Evolution of volatile compounds of baked dried tofu during catalytic infrared baking process and their correlation with relevant physicochemical properties.

BACKGROUND: Energy-saving and low-carbon baking processes, as well as the need to determine the flavor-forming mechanisms of baked dried tofu, are becoming increasingly necessary. The application of emerging catalytic infrared radiation (CIR) technology in baking of dried tofu is considered of high interest due to the low energy consumption and high baking efficiency compared to traditional baking methods. Hence, this study aimed to investigate the evolution of aroma compounds in baked dried tofu during the CIR baking process and reveal relevant relationships between physical qualities, potential flavor precursors and key volatile compounds. RESULTS: The results showed that the surface color of dried tofu gradually turned an appetizing golden yellow color during the rapid heating process, caused by the uniform infrared radiation from the radiant emitters. Meanwhile, the moisture of dried tofu experienced minimal reduction and the hardness of dried tofu gradually increased with the formation of crust on the surface. In addition, 49 volatile compounds were identified by headspace solid-phase microextraction-gas chromatography-mass spectrometry and 13 substances - 1-hexanol, 1-octen-3-ol, 1-pentanol, heptanal, nonanal, hexanal, (E,E)-2,4-decadienal, (E,Z)-2,4-decadienal, octanal, (E)-2-octenal, (E)-2-nonenal, 2-heptanone and 2-pentylfuran - were confirmed as key aroma compounds. Moreover, the amino acids aspartic acid, glutamic acid, isoleucine, lysine and arginine, and the fatty acids butyric, caprylic, capric, tridecanoic, stearic, oleic and linolenic were responsible for the unique flavor of CIR-baked dried tofu. CONCLUSION: Consequently, the findings can provide a scientific basis for manufacturers to achieve precise quality control and large-scale production of CIR-baked dried tofu products. © 2024 Society of Chemical Industry.

Dupilumab therapy improves gut microbiome dysbiosis and tryptophan metabolism in Chinese patients with atopic dermatitis.

BACKGROUND: Dupilumab has demonstrate its potential to orchestrate inflammatory skin microenvironment, enhance skin barrier and shift skin microbiome dysbiosis, collectively contributing to clinical improvement in patients with atopic dermatitis (AD). As the second genome of human body, growing evidence suggests that the gut microbiome might relate to the host response to treatments. Little is known about the association between dupilumab treatment and gut microbiome in AD patients. OBJECTIVE: We aimed to characterize the gut microbiome among Chinese subjects with or without AD and determine the potential effect of dupilumab on the gut microbiome. RESULTS: The 16 s rRNA gene sequencing was conducted on 48 healthy controls (HC), 44 AD patients and 27 AD patients who received dupilumab for 16 weeks. Prior to treatment, we identified the changed beta-diversity, increased Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium and expanded Faecalibacterium among the AD patients compared to HC. After 16 weeks of dupilumab treatment, gut microbiome dysbiosis of the AD patients improved with reversed beta-diversity, closer bacterial connections, increased colonization of Bifidobacterium, Ruminococcus gnavus, and Coprococcus, which were negatively correlated with disease severity indicators. This shift was largely independent of the degree of clinical improvement. Bacterial function analysis revealed further metabolic alterations following dupilumab treatment, including up-regulated expression of genes involved in the indole pathway of tryptophan metabolism, corroborated by quantitative UHPLC-MS/MS analysis. CONCLUSION: Dupilumab treatment tends to help shift the gut microbial dysbiosis in AD patients to a healthier state, along with improved intestinal tryptophan metabolism, suggesting the gut flora and its metabolites may mediate part of the synergistic therapeutic effects on the host.

Experimental demonstration of rainbow trapping of elastic waves in two-dimensional axisymmetric phononic crystal platesa).

Structures with specific graded geometries or properties can cause spatial separation and local field enhancement of wave energy. This phenomenon is called rainbow trapping, which manifests itself as stopping the propagation of waves at different locations according to their frequencies. In acoustics, most research on rainbow trapping has focused on wave propagation in one dimension. This research examined the elastic wave trapping performance of a two-dimensional (2D) axisymmetric grooved phononic crystal plate structure. The performance of the proposed structure is validated using numerical simulations based on finite element analysis and experimental measurements using a laser Doppler vibrometer. It is found that rainbow trapping within the frequency range of 165-205 kHz is achieved, where elastic waves are trapped at different radial distances in the plate. The results demonstrate that the proposed design is capable of effectively capturing elastic waves across a broad frequency range of interest. This concept could be useful in applications such as filtering and energy harvesting by concentrating wave energy at different locations in the structure.

In vitro assessment of cytotoxicity of spent fluid catalytic cracking refinery catalysts on cell lines and identification of critical toxic metals.

The Purpose of the present study was to quantify the responses of ten cell lines (HeLa, HepG2, HEK293, MDA-MB-231, A498, A549, A357, 3 T3, BALB-C3 T3, and NIH-3 T3) to spent fluid catalytic cracking catalysts (SFCCCs) from different petroleum refineries, and relate these responses to metal concentrations of SFCCC leachates (SFCCCLs). Cytotoxicity of SFCCCs were significantly different depending on cell lines. A357 and 3 T3 cell were the most sensitive, and A498 and HeLa cells were the least sensitive. HEK293 cells showed the least fluctuation in toxic response to different SFCCCLs among all cells. Cytotoxic IC50 values of SFCCCs to 7 kinds of cells were the most correlated with vanadium (V) concentration in SFCCCLs. V is the most critical toxic factor of SFCCC. Glutathione synthesis was induced in HepG2 cells exposed to higher concentrations of SFCCCLs. SFCCCLs with low concentration of V can induce the decrease of GSH/GSSG ratio in HepG2 cells, suggesting that high concentration of V inhibits the detoxification of glutathione.

Discovery of novel peptide-dehydroepiandrosterone hybrids inducing endoplasmic reticulum stress with effective in vitro and in vivo anti-melanoma activities.

Steroid hybrids have emerged as a type of advantageous compound as they could offer improved pharmacological and pharmaceutical properties. Here, we report a series of novel peptide-dehydroepiandrosterone hybrids, which would effectively induce endoplasmic reticulum stress (ERS) and lead to apoptosis with outstanding in vitro and in vivo anti-melanoma effects. The lead compound IId among various steroids conjugated with peptides and pyridines showed effective in vivo activity in B16 xenograft mice: in medium- and high-dose treatment groups (60 and 80 mg/kg), compound IId would significantly inhibit the growth of tumours by 98%-99% compared to the control group, with the highest survival rate as well. Further mechanism studies showed that compound IId would damage the endoplasmic reticulum and upregulate the ERS markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), which could further regulate caspase and Bcl-2 family proteins and lead to cell apoptosis. The compound IId was also proven to be effective in inhibiting B16 cell migration and invasion.

Prosocial punishment bots breed social punishment in human players.

Prosocial punishment, an important factor to stabilize cooperation in social dilemma games, often faces challenges like second-order free-riders-who cooperate but avoid punishing to save costs-and antisocial punishers, who defect and retaliate against cooperators. Addressing these challenges, our study introduces prosocial punishment bots that consistently cooperate and punish free-riders. Our findings reveal that these bots significantly promote the emergence of prosocial punishment among normal players due to their 'sticky effect'-an unwavering commitment to cooperation and punishment that magnetically attracts their opponents to emulate this strategy. Additionally, we observe that the prevalence of prosocial punishment is greatly enhanced when normal players exhibit a tendency to follow a 'copying the majority' strategy, or when bots are strategically placed in high-degree nodes within scale-free networks. Conversely, bots designed for defection or antisocial punishment diminish overall cooperation levels. This stark contrast underscores the critical role of strategic bot design in enhancing cooperative behaviours in human/AI interactions. Our findings open new avenues in evolutionary game theory, demonstrating the potential of human-machine collaboration in solving the conundrum of punishment.

Plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.

BACKGROUND: Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine. METHODS: Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis. RESULTS: A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05). CONCLUSIONS: The levels of choline-related metabolites and glutamate-related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.