Combined untargeted metabolomics and network pharmacology approaches to reveal the therapeutic role of withanolide B in psoriasis.

Psoriasis is a refractory inflammatory skin disorder in which keratinocyte hyperproliferation is a crucial pathogenic factor. Up to now, it is commonly acknowledged that psoriasis has a tight connection with metabolic disorders. Withanolides from Datura metel L. (DML) have been proved to possess anti-inflammatory and anti-proliferative properties in multiple diseases including psoriasis. Withanolide B (WB) is one of the abundant molecular components in DML. However, existing experimental studies regarding the potential effects and mechanisms of WB on psoriasis still remain lacking. Present study aimed to integrate network pharmacology and untargeted metabolomics strategies to investigate the therapeutic effects and mechanisms of WB on metabolic disorders in psoriasis. In our study, we observed that WB might effectively improve the symptoms of psoriasis and alleviate the epidermal hyperplasia in imiquimod (IMQ)-induced psoriasis-like mice. Both network pharmacology and untargeted metabolomics results suggested that arachidonic acid metabolism and arginine and proline metabolism pathways were linked to the treatment of psoriasis with WB. Meanwhile, we also found that WB may affect the expression of regulated enzymes 5-lipoxygenase (5-LOX), 12-LOX, ornithine decarboxylase 1 (ODC1) and arginase 1 (ARG1) in the arachidonic acid metabolism and arginine and proline metabolism pathways. In summary, this paper showed the potential metabolic mechanisms of WB against psoriasis and suggested that WB would have greater potential in psoriasis treatment.

On the way to the azygos vein: a road of return rather than ruined.

BACKGROUND: The malposition of central venous catheters (CVCs) may lead to vascular damage, perforation, and even mediastinal injury. The malposition of CVC from the right subclavian vein into the azygos vein is extremely rare. Here, we report a patient with CVC malposition into the azygos vein via the right subclavian vein. We conduct a comprehensive review of the anatomical structure of the azygos vein and the manifestations associated with azygos vein malposition. Additionally, we explore the resolution of repositioning the catheter into the superior vena cava by carefully withdrawing a specific length of the catheter. CASE PRESENTATION: A 79-year-old female presented to our department with symptoms of complete intestinal obstruction. A double-lumen CVC was inserted via the right subclavian vein to facilitate total parenteral nutrition. Due to the slow onset of sedative medications during surgery, the anesthetist erroneously believed that the CVC had penetrated the superior vena cava, leading to the premature removal of the CVC. Postoperative contrast-enhanced computed tomography of the chest confirmed that the central venous catheter had not penetrated the superior vena cava but malpositioned into the azygos vein. The patient was discharged 15 days after surgery without any complications. CONCLUSIONS: CVC malposition into the azygos vein is extremely rare. Clinical practitioners should be vigilant regarding this form of catheter misplacement. Ensuring the accurate positioning of the CVC before each infusion is crucial. Utilizing chest X-rays in both frontal and lateral views, as well as chest computed tomography, can aid in confirming the presence of catheter misplacement.

Device for Measuring Contact Reaction Forces during Animal Adhesion Landing/Takeoff from Leaf-like Compliant Substrates.

A precise measurement of animal behavior and reaction forces from their surroundings can help elucidate the fundamental principle of animal locomotion, such as landing and takeoff. Compared with stiff substrates, compliant substrates, like leaves, readily yield to loads, presenting grand challenges in measuring the reaction forces on the substrates involving compliance. To gain insight into the kinematic mechanisms and structural-functional evolution associated with arboreal animal locomotion, this study introduces an innovative device that facilitates the quantification of the reaction forces on compliant substrates, like leaves. By utilizing the stiffness-damping characteristics of servomotors and the adjustable length of a cantilever structure, the substrate compliance of the device can be accurately controlled. The substrate was further connected to a force sensor and an acceleration sensor. With the cooperation of these sensors, the measured interaction force between the animal and the compliant substrate prevented the effects of inertial force coupling. The device was calibrated under preset conditions, and its force measurement accuracy was validated, with the error between the actual measured and theoretical values being no greater than 10%. Force curves were measured, and frictional adhesion coefficients were calculated from comparative experiments on the landing/takeoff of adherent animals (tree frogs and geckos) on this device. Analysis revealed that the adhesion force limits were significantly lower than previously reported values (0.2~0.4 times those estimated in previous research). This apparatus provides mechanical evidence for elucidating structural-functional relationships exhibited by animals during locomotion and can serve as an experimental platform for optimizing the locomotion of bioinspired robots on compliant substrates.

Aquatic photolysis of high-risk fluorinated liquid crystal monomers: Kinetics, toxicity evaluation, and mechanisms.

Despite the frequent detection of fluorinated liquid-crystal monomers (FLCMs) in the environment, the level of understanding of their fate, toxicity, and transformation remains insufficient. Herein, we investigated the degradation kinetics and mechanism of an FLCM (4-cyano-3-fluorophenyl 4-ethylbenzoate, CEB-F) under ultraviolet (UV) photolysis in aquatic environment. Our findings demonstrated that the UV photolysis of CEB-F followed first-order kinetics. Photodegradation products were identified using liquid chromatography with mass spectrometry, and detailed reaction pathways were proposed. It is postulated that through the attack of reactive oxygen species, hydroxylation, and CO/C-F bond cleavage, CEB-F gradually degraded into small molecular compounds, releasing fluorine ions. Acute immobilization tests with Daphnia magna (D. magna) revealed significant acute toxicity of CEB-F, with LC50 values ranging from 1.023 to 0.0536 µM over 24 to 96 h, emphasizing the potential high risk of FLCMs in aquatic ecosystems if inadvertently discharged. Interestingly, we found that the toxicity of CEB-F photolysis reaction solutions was effectively reduced. Through catalase and acetylcholinesterase activities analysis along with molecular docking simulation, we proposed differences in the underlying toxicity mechanisms of CEB-F and its photolysis products to D. magna. These findings highlight the potential harmful effects of FLCMs on aquatic ecosystems and enrich our understanding of the photolysis behavior of FLCMs.

Modification effects of long-term air pollution levels on the relationship between short-term exposure to meteorological factors and hand, foot, and mouth disease: A distributed lag non-linear model-based study in Shandong Province, China.

The occurrence of hand, foot, and mouth disease (HFMD) is closely related to meteorological factors. However, location-specific characteristics, such as persistent air pollution, may increase the complexity of the impact of meteorological factors on HFMD, and studies across different areas and populations are largely lacking. In this study, a two-stage multisite time-series analysis was conducted using data from 16 cities in Shandong Province from 2015 to 2019. In the first stage, we obtained the cumulative exposure-response curves of meteorological factors and the number of HFMD cases for each city. In the second stage, we merged the estimations from the first stage and included city-specific air pollution variables to identify significant effect modifiers and how they modified the short-term relationship between HFMD and meteorological factors. High concentrations of air pollutants may reduce the risk effects of high average temperature on HFMD and lead to a distinct peak in the cumulative exposure-response curve, while lower concentrations may increase the risk effects of high relative humidity. Furthermore, the effects of average wind speed on HFMD were different at different levels of air pollution. The differences in modification effects between subgroups were mainly manifested in the diversity and quantity of significant modifiers. The modification effects of long-term air pollution levels on the relationship between sunshine hours and HFMD may vary significantly depending on geographical location. The people in age＜3 and male groups were more susceptible to long-term air pollution. These findings contribute to a deepening understanding of the relationship between meteorological factors and HFMD and provide evidence for relevant public health decision-making.

Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery.

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed.

Leaching of triphenyl phosphate and tri-n-butyl phosphate from polystyrene microplastics: influence of plastic properties and simulated digestive fluids.

Microplastics have gained considerable attention as a growing environmental problem owing to their potential to serve as vectors for harmful chemicals. However, the leaching of these chemicals from microplastics is unclear. In this study, we investigated the leaching of two organophosphate flame retardants, triphenyl phosphate and tri-n-butyl phosphate, from polystyrene microplastics in simulated digestive fluids and water, and polypropylene microplastics were simultaneously used for comparison with polystyrene microplastics. The results indicated that the first-order kinetic model best explained the leaching process, suggesting that leaching was related to the release of organophosphate flame retardant molecules at the polymer surface. Additionally, the size and crystalline state of the microplastics had a significant effect on the leaching, whereas organophosphate flame retardant content had a minimal impact. Simulated digestive fluids facilitated the leaching to a different extent, and under these influencing conditions, leaching percentages from polystyrene microplastics did not exceed 0.51%. Therefore, leaching from PS microplastics may not be an important source of OPFRs in the environment. However, the release of organophosphate flame retardants can be considerably enhanced with the breakdown of polystyrene microplastics to polystyrene nanoplastics.

Efficient degradation and detoxification of antibiotic Fosfomycin by UV irradiation in the presence of persulfate.

Fosfomycin (FOS) as a widely used antibiotic has been found in abundance throughout the environment, but little effort has been devoted to its treatment. In this study, we systemically looked into the degradation of FOS by ultraviolet-activated persulfate (UV/PS) in aqueous solutions. Our findings demonstrated that FOS can be degraded efficiently under the UV/PS, e.g., >90 % of FOS was degraded with 19,200 mJ cm-2 of UV irradiance and 20 µM of PS. HO was the dominant radical responsible for FOS degradation. FOS degradation increased as PS dosage increased, and higher degradation efficiency was observed at neutral pH. Natural water constitutes either promoted (e.g., Cu2+, Fe3+, and SO42-) or inhibited (e.g., humic acid, HCO3-, and CO32-) FOS degradation to varying degrees. Hydroxyl substitution, CP bond cleavage, and coupling reactions were the major degradation pathways for FOS degradation. Finally, the toxicity evaluation revealed that FOS was toxic to E. coli and S. aureus, but the toxicity of the intermediate products of FOS to E. coli and S. aureus rapidly decreased over time after UV/PS treatment. Therefore, these findings provided a fundamental understanding of the transformation process of FOS and supplied useful information for the environmental elimination of FOS contamination and its toxicity.

Mechanistic Insights into the Biodegradation of Carbon Dots by Fungal Laccase.

While carbon dots (CDs) have the potential to support the agricultural revolution, it remains obscure about their environmental fate and bioavailability by plants. Fungal laccase-mediated biotransformation of carbon nanomaterials has received little attention despite its known capacity to eliminate recalcitrant contaminants. Herein, we presented the initial investigation into the transformation of CDs by fungal laccase. The degradation rates of CDs were determined to be first-order in both substrate and enzyme. Computational docking studies showed that CDs preferentially bonded to the pocket of laccase on the basal plane rather than the edge through hydrogen bonds and hydrophobic interactions. Electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry (ESI-FT-ICR MS) and other characterizations revealed that the phenolic/amino lignins and tannins portions in CDs are susceptible to laccase transformation, resulting in graphitic structure damage and smaller-sized fragments. By using the 13C stable isotope labeling technique, we quantified the uptake and translocation of 13C-CDs by mung bean plants. 13C-CDs (10 mg L-1) accumulated in the root, stem, and leaf were estimated to be 291, 239, and 152 µg g-1 at day 5. We also evidenced that laccase treatment alters the particle size and surface chemistry of CDs, which could facilitate the uptake of CDs by plants and reduce their nanotoxicity to plants.

The elevation of salinity above 1% deteriorated nitrification performance and reshaped nitrifier community of an MBR: An often overlooked factor in the treatment of high-strength ammonium wastewater.

The effects of synchronous variations of influent salinity with the elevation of NH4+-N concentration on nitrification performance and microbial community structure of bioreactor are often ignored. In this study, we investigated the dynamic response of nitrifying activated sludge to synchronously increased salinity and ammonia loading rate (ALR) in a nitrification membrane bioreactor (MBR). We found that the increase in influent salinity above 1% (from 0.91 to 1.32%) led to the deterioration of the nitrification performance of the MBR. The combined inhibition effect of salinity (1.32%), free ammonia (FA, an average of 1.37 mg/L), and free nitrous acid (FNA, an average of 0.155 mg/L) on nitrite-oxidizing bacteria (NOB) resulted in long-term (35 days) nitrite accumulation. The further increase of salinity and ALR exhibited little influence on the nitrification performance of MBR after the activated sludge had adapted to high salinity (>1%), effective nitrification performance was achieved at high ALR up to 1.71 kg NH4+-N/m3·d and high salinity (2.13%). The microbial analysis showed that the elevated salinity and accumulation of FNA reshaped the microbial community structure of ammonia-oxidizing bacteria (AOB) and NOB. The dominant species of AOB and NOB shifted from the salinity-resistant species Nitrosomonas aestuarii to the species Nitrosomonas mobilis with dual resistant to salinity and FNA, and from non-salinity-resistant species Candidatus Nitrospira defluvii to salinity-resistant species Nitrobacter winogradskyi and Nitrospira marina, respectively. Therefore, the salinity of 1% may be a critical level for the nitrification performance and the shift in the nitrifier community of activated sludge without salinity acclimation.

Recent Advancements on Long COVID in China: A Narrative Review.

The COVID-19 pandemic is a huge public health crisis in the 21st century. In addition to the acute symptoms, a considerable proportion of patients worldwide have suffered from post-COVID-19 syndrome, commonly known as Long COVID. The impact of Long COVID on individual and public health burden cannot be ignored. According to recent researches, Long COVID has been affecting multiple organ systems throughout the body, with respiratory, mental, nervous and digestive symptoms often seen in Chinese population. Clinical studies have proved that symptoms were alleviated by a variety of treatments, such as physical therapy, rehabilitation training, psychological support, behavioral cognitive therapy, stem cell therapy, etc. Based on the current clinical evidence, it is recommended to strengthen the scientific research on Long COVID and actively carry out early monitoring and intervention in the future, so as to effectively prevent the long-term disease burden and economic pressure.

Removal of tetracycline in nitrification membrane bioreactors with different ammonia loading rates: Performance, metabolic pathway, and key contributors.

Membrane bioreactors (MBRs) have been widely applied for the treatment of wastewater that contains high concentrations of both ammonium and antibiotics. Nonetheless, information about tetracycline (TC) removal in nitrification MBRs with high ammonium loading rates (ALRs) is still very limited. Herein, the fate of TC at four different concentrations of 1, 5, 20, and 50 mg/L in three parallel lab-scale nitrification MBRs with different ALRs (named AN50, AN500, and AN1000) were investigated in this study. Excellent nitrification performance and high TC removal efficiency (90.46%) were achieved in AN1000 at influent TC concentration of 50 mg/L. Higher ALRs promoted the removal of TC at lower influent TC concentration (≤5 mg/L), while no significant difference was observed in TC removal efficiencies among different ALRs MBRs at higher influent TC concentration (≥20 mg/L), implying that the heterotrophic degradation could be strengthened after long-term exposure to high concentration of TC. Batch tests demonstrated that adsorption and biodegradation were the primary TC removal routes by nitrification sludge, of which both autotrophic ammonia oxidizers and heterotrophic microorganisms played an important role in the biodegradation of TC. FT-IR spectroscopy confirmed that amide groups on the sludge biomass contributed to the adsorption of TC. Mass balance analyses indicated that biodegradation (63.4-88.6% for AN50, 74.5-88.4% for AN500 and 74.4-91.4% for AN1000) was the major mechanism responsible for the removal of TC in nitrification MBRs, and its contribution increased with influent TC concentration, while only 1.1%-15.0% of TC removal was due to biosorption. TC was progressively degraded to small molecules and the presence of TC had no notable effect on membrane permeability. These jointly confirmed TC could be effectively removed via initial adsorption and subsequent biodegradation, while biodegradation was the primary mechanism in this study.

Cytotoxicity and hemolysis of rare earth ions and nanoscale/bulk oxides (La, Gd, and Yb): Interaction with lipid membranes and protein corona formation.

The widespread application of rare earth elements (REEs) has raised concerns about their potential release into the environment and subsequent ingestion by humans. Therefore, it is essential to evaluate the cytotoxicity of REEs. Here, we investigated the interactions between three typical REEs (La, Gd, and Yb) ions as well as their nanometer/µm-sized oxides and red blood cells (RBCs), a plausible contact target for nanoparticles when they enter the bloodstream. Hemolysis of REEs at 50-2000 µmol L-1 was examined to simulate their cytotoxicity under medical or occupational exposure. We found that the hemolysis due to the exposure of REEs was highly dependent on their concentration, and the cytotoxicity followed the order of La3+ > Gd3+ > Yb3+. The cytotoxicity of REE ions (REIs) is higher than REE oxides (REOs), while nanometer-sized REO caused more hemolysis than that µm-sized REO. The production of reactive oxygen species (ROS), ROS quenching experiment, as well as the detection of lipid peroxidation, confirmed that REEs causes cell membrane rupture by ROS-related chemical oxidation. In addition, we found that the formation of a protein corona on REEs increased the steric repulsion between REEs and cell membranes, hence mitigating the cytotoxicity of REEs. The theoretical simulation indicated the favorable interaction of REEs with phospholipids and proteins. Therefore, our findings provide a mechanistic explanation for the cytotoxicity of REEs to RBCs once they have entered the blood circulation system of organisms.

Biochar Facilitated Direct Interspecies Electron Transfer in Anaerobic Digestion to Alleviate Antibiotics Inhibition and Enhance Methanogenesis: A Review.

Efficient conversion of organic waste into low-carbon biofuels such as methane through anaerobic digestion (AD) is a promising technology to alleviate energy shortages. However, issues such as inefficient methane production and poor system stability remain for AD technology. Biochar-facilitated direct interspecies electron transfer (DIET) has recently been recognized as an important strategy to improve AD performance. Nonetheless, the underlying mechanisms of biochar-facilitated DIET are still largely unknown. For this reason, this review evaluated the role of biochar-facilitated DIET mechanism in enhancing AD performance. First, the evolution of DIET was introduced. Then, applications of biochar-facilitated DIET for alleviating antibiotic inhibition and enhancing methanogenesis were summarized. Next, the electrochemical mechanism of biochar-facilitated DIET including electrical conductivity, redox-active characteristics, and electron transfer system activity was discussed. It can be concluded that biochar increased the abundance of potential DIET microorganisms, facilitated microbial aggregation, and regulated DIET-associated gene expression as a microbial mechanism. Finally, we also discussed the challenges of biochar in practical application. This review elucidated the role of DIET facilitated by biochar in the AD system, which would advance our understanding of the DIET mechanism underpinning the interaction of biochar and anaerobic microorganisms. However, direct evidence for the occurrence of biochar-facilitated DIET still requires further investigation.

Longitudinal trajectories of depressive symptoms: the role of multimorbidity, mobility and subjective memory.

BACKGROUND: The high prevalence of depression among older people in China places a heavy burden on the health system. Multimorbidity, mobility limitation and subjective memory impairment are found to be risk indicators for depression. However, most studies on this topic focused on depression at a single point in time, ignoring the dynamic changes in depressive symptoms and the relationship between the trajectories and these three conditions. Therefore, we aimed to identify distinct trajectories of depressive symptoms in older people and investigate their associations with multimorbidity, mobility limitation and subjective memory impairment. METHODS: Data was drawn from China Health and Retirement Longitudinal Study conducted during 2011-2018. A total of 5196 participants who completed 4 visits, conducted every 2-3 years were included in this study. Group-based trajectory modeling was conducted to identify distinct trajectories of depressive symptoms z-scores. Multinomial logistic regression was used to investigate the relationships. RESULTS: Four distinct trajectories of depressive symptoms z-scores were identified, labeled as persistently low symptoms (68.69%, n = 3569), increasing symptoms (12.14%, n = 631), decreasing symptoms (14.05%, n = 730) and persistently high symptoms (5.12%, n = 266). Participants with multimorbidity had unfavorable trajectories of depressive symptoms compared with those without multimorbidity, with adjusted odds ratios (95% CIs) of 1.40 (1.15, 1.70), 1.59 (1.33, 1.90) and 2.19 (1.65, 2.90) for the increasing symptoms, decreasing symptoms and persistently high symptoms, respectively. We also observed a similar trend among participants with mobility limitations. Compared with participants who had poor subjective memory, participants with excellent/very good/good subjective memory had a lower risk of developing unfavorable trajectories of depressive symptoms. The adjusted odds ratios (95% CIs) of the increasing symptoms, decreasing symptoms and persistently high symptoms were 0.54 (0.40, 0.72), 0.50 (0.38, 0.65) and 0.48 (0.31, 0.73), respectively. CONCLUSIONS: Multimorbidity, mobility limitation and subjective memory impairment were found to be potential risk factors for unfavorable depression trajectories.

P-Type 2D Semiconductors for Future Electronics.

2D semiconductors represent one of the best candidates to extend Moore's law for their superiorities, such as keeping high carrier mobility and remarkable gate-control capability at atomic thickness. Complementary transistors and van der Waals junctions are critical in realizing 2D semiconductors-based integrated circuits suitable for future electronics. N-type 2D semiconductors have been reported predominantly for the strong electron doping caused by interfacial charge impurities and internal structural defects. By contrast, superior and reliable p-type 2D semiconductors with holes as majority carriers are still scarce. Not only that, but some critical issues have not been adequately addressed, including their controlled synthesis in wafer size and high quality, defect and carrier modulation, optimization of interface and contact, and application in high-speed and low-power integrated devices. Here the material toolkit, synthesis strategies, device basics, and digital electronics closely related to p-type 2D semiconductors are reviewed. Their opportunities, challenges, and prospects for future electronic applications are also discussed, which would be promising or even shining in the post-Moore era.

Interaction of Graphitic Carbon Nitride with Cell Membranes: Probing Phospholipid Extraction and Lipid Bilayer Destruction.

Understanding how nanomaterials interact with cell membranes has important implications for ecotoxicology and human health. Here, we investigated the interactions between graphitic carbon nitride (g-C3N4, CN) and red blood cells, a plausible contact target for nanoparticles when they enter the bloodstream. Through a hemolysis assay, the cytotoxicity of CN derived from different precursors was quantitatively assessed, which is highly related to the surface area of CN. Reactive oxygen species (ROS) generation and lipid peroxidation detection confirmed that CN causes rapid cell membrane rupture by a physical interaction mechanism rather than ROS-related chemical oxidation. Dye leakage assay and theoretical simulation indicated that the less-layered CN is prone to folding inward to wrap and extract lipid molecules from cell membranes. The electron-rich inherent pores of CN play a dominant role in capturing the headgroups of phospholipids, whereas the hydrophobic interaction is critical for the anchoring of lipid tails. Our further experimental evidence demonstrated that the destructive extraction of phospholipids from cell membranes by CN occurs primarily in the outer leaflet, and phosphatidylcholine is the most easily extracted lipid. Moreover, the formation of protein corona on CN was found to decrease the nonspecific interactions but increase steric repulsion, thus mitigating CN cytotoxicity. Overall, our data provide a molecular basis for CN's cytotoxicity.

Anlotinib combined with temozolomide for the treatment of patients with diffuse midline glioma: a case report and literature review.

Background: Diffuse midline glioma with a histone H3-K27M mutation is a brand-new tumor entity according to the 2016 edition of World Health Organization (WHO) classification. As diffuse midline gliomas are aggressive and incurable brain tumors, characterized by high levels of intrinsic and acquired resistance to therapy, as well as conventional treatment can hardly work due to an intact blood-brain barrier, leading to very poor outcomes for patients. Anlotinib is a multitarget tyrosine kinase inhibitor and has been used for the treatment of multiple tumor species, with satisfying outcomes. However, anlotinib has not been reported for the treatment of patients with diffuse midline glioma. Case Description: This is a case report about a 51-year-old man suffering from diffuse midline glioma with a histone H3-K27M mutation. After surgery, the patient underwent chemoradiation treatment and then adjuvant temozolomide (TMZ). After 7 months, the tumor had enlarged with severe peritumor edema and hydrocephalus. Bevacizumab was treated for 3 cycles, and then the treatment was changed to anlotinib combined with TMZ. After 8 months, magnetic resonance imaging (MRI) scans showed that the mass was significantly reduced compared with before targeted therapy. Until the present time, the patient has survived for 20 months. Conclusions: Therapy combining anlotinib with TMZ is potential therapeutic option for the patients with diffuse midline glioma.

Comparative efficacy and safety of glucose-lowering drugs in children and adolescents with type 2 diabetes: A systematic review and network meta-analysis.

Objective: Type 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical management for children and adolescents with type 2 diabetes by assessing the efficacy and safety of several glucose-lowering drugs. Methods: Searches were performed in PubMed, Medline, Ovid, Cochrane Controlled Register of Trials (CENTRAL), and ClinicalTrials.gov that reported the efficacy and safety of drugs for children and adolescents with type 2 diabetes. Pooled effects were calculated by frequentist fixed effects network meta-analyses and additive network meta-analyses. Results: A total of 12 trials assessing eight glucose-lowering drugs were included, which compose of seven trials with monotherapy and five trials with combination therapies. Network meta-analysis results showed compared to placebo, saxagliptin+metformin (mean difference (MD) -1.91% [-2.85%, -0.97%]), liraglutide+metformin (MD -1.45% [-1.65%, -1.26%]), and liraglutide (MD -0.90% [-1.35%, -0.45%]) were the top 3 drugs that significantly reduced hemoglobin A1c (HbA1c). Sitagliptin+metformin, dapagliflozin, exenatide-2mcg, linagliptin-5mg, metformin, exenatide-5/10mcg, glimepiride, and sitagliptin also showed significant reduction in HbA1c. There were no significant differences between treatments in the incidence of adverse events, except that liraglutide+metformin had significant adverse effect such as abdominal pain. In addition, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy compared with FDA-approved drugs. Conclusions: The top 10 treatments of type 2 diabetes in children and adolescents aged 10-17 years were saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide-2 mcg, sitagliptin+metformin, linagliptin-5 mg, linagliptin-1 mg, metformin, and exenatide-5/10 mcg. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284897, identifier CRD42021284897.