Heteryunine A, an amidated tryptophan-catechin-spiroketal hybrid with antifibrotic activity from Heterosmilax yunnanensis.

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).

[Application of automatic slide-dropping instrument in bone marrow chromosomal karyotyping].

OBJECTIVE: To explore the application of an automatic slide-dropping instrument in bone marrow chromosomal karyotyping. METHODS: The effects of manual and automatic dropping methods under different environmental humidity were retrospectively analyzed, and the repeatability of the automatic dropping method was analyzed. RESULTS: No statistical difference was found between the results of automatic and manual dropping methods under the optimum ambient humidity and high humidity (P > 0.05). At low humidity, there was a statistical difference between the two methods (P < 0.05). With regard to the repeatability, the coefficient of variations of the automatic dropping method for the number of split phases, the rate of good dispersion and the rate of overlap were all lower than those of the manual dropping method. A statistical difference was also found in the number of split phases (P < 0.05) but not in the discrete excellent rate and overlapping rate between the two methods (P > 0.05). CONCLUSION: Better effect can be obtained by the automatic dropping instrument. It is suggested to gradually replace manual work with machine.

Optimizing treatment administration strategies using negative mNGS results in corticosteroid-sensitive diffuse parenchymal lung diseases.

Timely adjustments of antibiotic and corticosteroid treatments are vital for patients with diffuse parenchymal lung diseases (DPLDs). In this study, 41 DPLD patients with negative metagenomic next-generation sequencing (mNGS) results who were responsive to corticosteroids were enrolled. Among these patients, about 26.8% suffered from drug-induced DPLD, while 9.8% presented autoimmune-related DPLD. Following the report of the negative mNGS results, in 34 patients with complete antibiotics administration profiles, 79.4% (27/34) patients discontinued antibiotics after receiving negative mNGS results. Moreover, 70.7% (29/41) patients began or increased the administration of corticosteroid upon receipt of negative mNGS results. In the microbiota analysis, Staphylococcus and Stenotrophomonas showed higher detection rates in patients with oxygenation index (OI) below 300, while Escherichia and Stenotrophomonas had higher abundance in patients with pleural effusion. In summary, our findings demonstrated the clinical significance of mNGS in assisting the antibiotic and corticosteroid treatment adjustments in corticosteroid-responsive DPLD. Lung microbiota may imply the severity of the disease.

Emerging probing perspective of two-dimensional materials physics: terahertz emission spectroscopy.

Terahertz (THz) emission spectroscopy (TES) has emerged as a highly effective and versatile technique for investigating the photoelectric properties of diverse materials and nonlinear physical processes in the past few decades. Concurrently, research on two-dimensional (2D) materials has experienced substantial growth due to their atomically thin structures, exceptional mechanical and optoelectronic properties, and the potential for applications in flexible electronics, sensing, and nanoelectronics. Specifically, these materials offer advantages such as tunable bandgap, high carrier mobility, wideband optical absorption, and relatively short carrier lifetime. By applying TES to investigate the 2D materials, their interfaces and heterostructures, rich information about the interplay among photons, charges, phonons and spins can be unfolded, which provides fundamental understanding for future applications. Thus it is timely to review the nonlinear processes underlying THz emission in 2D materials including optical rectification, photon-drag, high-order harmonic generation and spin-to-charge conversion, showcasing the rich diversity of the TES employed to unravel the complex nature of these materials. Typical applications based on THz emissions, such as THz lasers, ultrafast imaging and biosensors, are also discussed. Step further, we analyzed the unique advantages of spintronic terahertz emitters and the future technological advancements in the development of new THz generation mechanisms leading to advanced THz sources characterized by wide bandwidth, high power and integration, suitable for industrial and commercial applications. The continuous advancement and integration of TES with the study of 2D materials and heterostructures promise to revolutionize research in different areas, including basic materials physics, novel optoelectronic devices, and chips for post-Moore's era.

Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery.

Objective: The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery. Methods: Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, n = 140), the control cohort (NCLNM, n = 128), and the external verification cohort (CLNM, n = 50; NCLNM, n = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography. Results: A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), p = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), p = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), p = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), p = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), p < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), p < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels. Conclusion: We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.

Electrical switching of Ising-superconducting nonreciprocity for quantum neuronal transistor.

Nonreciprocal quantum transport effect is mainly governed by the symmetry breaking of the material systems and is gaining extensive attention in condensed matter physics. Realizing electrical switching of the polarity of the nonreciprocal transport without external magnetic field is essential to the development of nonreciprocal quantum devices. However, electrical switching of superconducting nonreciprocity remains yet to be achieved. Here, we report the observation of field-free electrical switching of nonreciprocal Ising superconductivity in Fe3GeTe2/NbSe2 van der Waals (vdW) heterostructure. By taking advantage of this electrically switchable superconducting nonreciprocity, we demonstrate a proof-of-concept nonreciprocal quantum neuronal transistor, which allows for implementing the XOR logic gate and faithfully emulating biological functionality of a cortical neuron in the brain. Our work provides a promising pathway to realize field-free and electrically switchable nonreciprocity of quantum transport and demonstrate its potential in exploring neuromorphic quantum devices with both functionality and performance beyond the traditional devices.

Histidine-Rich Glycoprotein Modulates the Toxic Effects of High-Dose Polyphosphate in Mice.

BACKGROUND: Polyphosphate (polyP), a procoagulant released from platelets, activates coagulation via the contact system and modulates cardiomyocyte viability. High-dose intravenous polyP is lethal in mice, presumably because of thrombosis. Previously, we showed that HRG (histidine-rich glycoprotein) binds polyP and attenuates its procoagulant effects. In this study, we investigated the mechanisms responsible for the lethality of intravenous polyP in mice and the impact of HRG on this process. METHODS: The survival of wild-type or HRG-deficient mice given intravenous synthetic or platelet-derived polyP in doses up to 50 mg/kg or saline was compared. To determine the contribution of thrombosis, the effect of FXII (factor XII) knockdown or enoxaparin on polyP-induced fibrin deposition in the lungs was examined. To assess cardiotoxicity, the ECG was continuously monitored, the levels of troponin I and the myocardial band of creatine kinase were quantified, and the viability of a cultured murine cardiomyocyte cell line exposed to polyP in the absence or presence of HRG was determined. RESULTS: In HRG-deficient mice, polyP was lethal at 30 mg/kg, whereas it was lethal in wild-type mice at 50 mg/kg. Although FXII knockdown or enoxaparin administration attenuated polyP-induced fibrin deposition in the lungs, neither affected mortality. PolyP induced dose-dependent ECG abnormalities, including heart block and ST-segment changes, and increased the levels of troponin and myocardial band of creatine kinase, effects that were more pronounced in HRG-deficient mice than in wild-type mice and were attenuated when HRG-deficient mice were given supplemental HRG. Consistent with its cardiotoxicity, polyP reduced the viability of cultured cardiomyocytes in a dose-dependent manner, an effect attenuated with supplemental HRG. CONCLUSIONS: High-dose intravenous polyP is cardiotoxic in mice, and HRG modulates this effect.

Endoplasmic reticulum-resident selenoproteins and their roles in glucose and lipid metabolic disorders.

Glucose and lipid metabolic disorders (GLMDs), such as diabetes, dyslipidemia, metabolic syndrome, nonalcoholic fatty liver disease, and obesity, are significant public health issues that negatively impact human health. The endoplasmic reticulum (ER) plays a crucial role at the cellular level for lipid and sterol biosynthesis, intracellular calcium storage, and protein post-translational modifications. Imbalance and dysfunction of the ER can affect glucose and lipid metabolism. As an essential trace element, selenium contributes to various human physiological functions mainly through 25 types of selenoproteins (SELENOs). At least 10 SELENOs, with experimental and/or computational evidence, are predominantly found on the ER membrane or within its lumen. Two iodothyronine deiodinases (DIOs), DIO1 and DIO2, regulate the thyroid hormone deiodination in the thyroid and some external thyroid tissues, influencing glucose and lipid metabolism. Most of the other eight members maintain redox homeostasis in the ER. Especially, SELENOF, SELENOM, and SELENOS are involved in unfolded protein responses; SELENOI catalyzes phosphatidylethanolamine synthesis; SELENOK, SELENON, and SELENOT participate in calcium homeostasis regulation; and the biological significance of thioredoxin reductase 3 in the ER remains unexplored despite its established function in the thioredoxin system. This review examines recent research advances regarding ER SELENOs in GLMDs and aims to provide insights on ER-related pathology through SELENOs regulation.

Electrical acupoint stimulation for the treatment of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

Background: Chemotherapy-induced nausea and vomiting (CINV) is the most common adverse effect of chemotherapy and affects the continuation of chemotherapy in cancer patients. Electrical acupoint stimulation (EAS), which includes electroacupuncture and transcutaneous electrical stimulation (TES), has been used to treat CINV. This meta-analysis aimed to evaluate the efficacy of EAS in the treatment of CINV. Methods: Randomized controlled trials (RCTs) of EAS for CINV retrieved form five key databases. Two researchers independently performed article screening, data extraction and data integration. The Cochrane Collaboration's tool for assessing risk of bias was used to assesse the methodological quality according to Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.4 was used to perform analyses. Results: 10 RCTs with a total of 950 participants were included. The results showed that there was no significant difference between EAS compared to sham EAS in terms of increasing the rate of complete control of CINV and decreasing the overall incidence of CINV [RR = 1.26, 95 % CI (0.96, 1.66), P = 0.95; RR = 1.16, 95 % CI (0.97, 1.40), p = 0.71]. In terms of CINV severity, EAS reduced the occurrence of moderate-to-severe CINV [RR = 0.60, 95 % CI (0.38, 0.94), P = 0.03; RR = 0.50, 95 % CI (0.33, 0.76), P = 0.001]. Conclusion: EAS could improve moderate-to-severe CINV. However, EAS did not show a significant difference in reducing overall incidence and improving complete control rates compared with sham EAS. Due to limitations in the quality of the included articles, the available studies are insufficient to have sufficient evidence to confirm the efficacy of EAS for CINV. Validation with rigorously designed, large-sample, high-quality clinical trial studies may also be needed.

Enhanced electrochemical nitrate reduction on copper nitride with moderate intermediates adsorption.

Nitrate in surface and underground water caused systematic risk to the ecological environment. The electrochemically reduction of nitrate into ammonia (NO3RR), offering a sustainable route for nitrate containing wastewater treatment and ammonia fertilizer conversion. Exploration of catalyst with improved catalytic activity with lower energy barriers is still challenging. Here, we report a copper nitride (Cu3N) catalyst with moderate *NOx and *H2O intermediates adsorptions showed enhanced NO3RR performance. Density functional theory calculations reveals that the unique electronic structure of Cu3N provides efficient active sites for NO3RR, thus enabled balanced adsorption of *NO3 and *H2O (ΔE descriptor), sufficient active hydrogen, and moderate intermediate (*NO3 â†’ HNO3, *NH2→*NH3) adsorption energy. Notably, the in-situ analysis technology revealed potential-driven reconstruction and rehabilitation of Cu3N, forming possible nitrogen vacancy, thus implied for better mechanism understanding. The NO3RR activity of Cu3N surpasses that of most recent catalysts and demonstrates superior stability and implies the application for NH4+ fertilizer recovery, which maintaining an NH3 Faradaic efficiency of 93.1 % and high yield rate of 2.9 mg cm2h-1 at -0.6 V versus RHE. These findings broaden the application scenarios of Cu3N catalyst for ammonia synthesis and provide strategy on improving NO3RR performance.

Sound attenuation at low to mid frequencies in low velocity seabottoms.

Attenuation is the most difficult seafloor acoustic property to get, particularly at low to mid frequencies. For low velocity bottoms (LVB), it becomes even more challenging, due to its small attenuation and lower velocity (relative to the velocity of the adjacent water). The latter one causes a fatal "seafloor velocity-attenuation couplings" in geo-acoustic inversions. Thus, attenuation inversions for the LVB require an accurate seafloor velocity profile, especially the velocity in the LVB layer. The propagation of explosive sound in the Yellow Sea with a strong thermocline and a top LVB layer exhibits many prominent characteristics: modal dispersion (the ground wave, water wave, Airy phase), two groups of water waves at high frequencies, and the siphon effect which causes abnormally large sound transmission loss at selected frequencies, etc. These observations are used to precisely measure the critical frequency, the Airy frequency, Airy wave velocity, 1st mode group velocity, and to derive the velocities in the LVB layer and in the basement. Using inverted seafloor parameters, the source level-normalized transmission loss and the first mode decay rate in ranges up to 27.66 km, the sound attenuations in the LVB are derived for a frequency range of 13-5000 Hz.

Effect of schooling on flow generated sounds from carangiform swimmers.

Computational models are used to examine the effect of schooling on flow generated noise from fish swimming using their caudal fins. We simulate the flow as well as the far-field hydrodynamic sound generated by the time-varying pressure loading on these carangiform swimmers. The effect of the number of swimmers in the school, the relative phase of fin flapping of the swimmers, and their spatial arrangement is examined. The simulations indicate that the phase of the fin flapping is a dominant factor in the total sound radiated into the far-field by a group of swimmers. For small schools, a suitable choice of relative phase between the swimmers can significantly reduce the overall intensity of the sound radiated to the far-field. The relative positioning of the swimmers is also shown to have an impact on the total radiated noise. For a larger school, even highly uncorrelated phases of fin movement between the swimmers in the school are very effective in significantly reducing the overall intensity of sound radiated into the far-field. The implications of these findings for fish ethology as well as the design and operation of bioinspired vehicles are discussed.

Insomnia-related rodent models in drug discovery.

Despite the widespread prevalence and important medical impact of insomnia, effective agents with few side effects are lacking in clinics. This is most likely due to relatively poor understanding of the etiology and pathophysiology of insomnia, and the lack of appropriate animal models for screening new compounds. As the main homeostatic, circadian, and neurochemical modulations of sleep remain essentially similar between humans and rodents, rodent models are often used to elucidate the mechanisms of insomnia and to develop novel therapeutic targets. In this article, we focus on several rodent models of insomnia induced by stress, diseases, drugs, disruption of the circadian clock, and other means such as genetic manipulation of specific neuronal activity, respectively, which could be used to screen for novel hypnotics. Moreover, important advantages and constraints of some animal models are discussed. Finally, this review highlights that the rodent models of insomnia may play a crucial role in novel drug development to optimize the management of insomnia.

[Baicalin induces ferroptosis in HepG2 cells by inhibiting ROS-mediated PI3K/Akt/FoxO3a signaling pathway].

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.

Vitamin D3 exacerbates steatosis while calcipotriol inhibits inflammation in non-alcoholic fatty liver disease in Sod1 knockout mice: a comparative study of two forms of vitamin D.

The role of vitamin D (VD) in non-alcoholic fatty liver disease (NAFLD) remains controversial, possibly due to the differential effects of various forms of VD. In our study, Sod1 gene knockout (SKO) mice were utilized as lean NAFLD models, which were administered 15 000 IU VD3 per kg diet, or intraperitoneally injected with the active VD analog calcipotriol for 12 weeks. We found that VD3 exacerbated hepatic steatosis in SKO mice, with an increase in the levels of Cd36, Fatp2, Dgat2, and CEBPA. However, calcipotriol exerted no significant effect on hepatic steatosis. Calcipotriol inhibited the expression of Il-1a, Il-1b, Il-6, Adgre1, and TNF, with a reduction of NFκB phosphorylation in SKO mice. No effect was observed by either VD3 or calcipotriol on hepatocyte injury and hepatic fibrosis. Co-immunofluorescence stains of CD68, a liver macrophage marker, and VDR showed that calcipotriol reduced CD68 positive cells, and increased the colocalization of VDR with CD68. However, VD3 elevated hepatocyte VDR expression, with no substantial effect on the colocalization of VDR with CD68. Finally, we found that VD3 increased the levels of serum 25(OH)D3 and 24,25(OH)2D3, whereas calcipotriol decreased both. Both VD3 and calcipotriol did not disturb serum calcium and phosphate levels. In summary, our study found that VD3 accentuated hepatic steatosis, while calcipotriol diminished inflammation levels in SKO mice, and the difference might stem from their distinct cellular selectivity in activating VDR. This study provides a reference for the application of VD in the treatment of lean NAFLD.

Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 􀁐g/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 􀁐g/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Ultrafast polarization characterization with Mueller matrix based on optical time-stretch and spectral encoding.

High-speed optical polarization characterization is highly desirable for a wide range of applications, including remote sensing, telecommunication, and medical diagnosis. The utilization of the Mueller matrix provides a superior systematic and comprehensive approach to represent polarization attributes when matter interacts with optical beams. However, the current measurement speed of Mueller matrix is limited to only seconds or milliseconds. In this study, we present an ultrafast Mueller matrix polarimetry (MMP) technique based on optical time-stretch and spectral encoding that enables us to achieve an impressive temporal resolution of 4.83 nanoseconds for accurate Mueller matrix measurements. The unique feature of optical time-stretch technology enables continuous, ultrafast single-shot spectroscopy, resulting in a remarkable speed of up to 207 MHz for spectral encoding Mueller matrix measurement. We have employed an effective Mueller linear reconstruction algorithm based on the measured modulation matrix, accounting for all potential non-ideal effects of polarization components like retardance error and azimuth error. To ensure high precision, prior to the actual measurement, high-order dispersion induced by time-stretch requires adjustment through proper modulation matrix design. Upon such correction, both the results of static and rapid dynamic samples measurements exhibit exceptional accuracy with root-mean-square error (RMSE) approximately equal to 0.04 and 0.07 respectively. This presented ultrafast MMP provides a significant advance over preceding endeavors, enabling superior accuracy and increased speed concurrently.

Clinical Presentation, Management, and Diagnostic Performance of 2021 Criteria for Paraneoplastic Neurologic Syndromes in Childhood.

BACKGROUND AND OBJECTIVES: Paraneoplastic neurologic syndromes (PNSs) are remote neurologic immune-related effects of tumors. The clinical characteristics of pediatric PNSs remain unclear. We retrospectively examined the clinical characteristics of cases of pediatric PNSs and assessed the performance of the 2021 diagnostic criteria in children. METHODS: Patients hospitalized in the Beijing Children's Hospital between June 2015 and June 2023 and fulfilling the description of definite by 2004 diagnostic criteria of PNSs were included. A retrospective analysis of clinical characteristics was conducted, and the 2021 diagnostic criteria were applied to rediagnostic stratification. RESULTS: Among the 42 patients included, the most common neurologic syndrome was opsoclonus-myoclonus syndrome (OMS) (62%), followed by rapidly progressive cerebellar syndrome (26%). Most tumors were neuroblastomas (88%), with few being ovarian teratomas (10%). Approximately 71% (30/42) of patients were classified as definite and 24% (10/42) as probable according to the 2021 criteria. All cases judged as probable exhibited rapidly progressive cerebellar ataxia with neuroblastoma. For OMS, chemotherapy was administered based on the tumor's risk stage, accompanied by regular infusion of IV gamma globulin and oral steroids following tumor diagnosis. Twenty-one patients underwent regular follow-ups over 4.92 (0.58-7.58) years. The initial hospitalization recorded a median score of 12 (7-14) on the Mitchell and Pike OMS rating scale, decreasing to 0 (0-5) at the final follow-up. In cases of rapidly progressive cerebellar syndrome, a similar therapeutic regimen was used. Nine patients underwent regular follow-ups over 4.42 (1.17-7.50) years. The mean modified Rankin scale score at first hospitalization was 4 (3-4), reducing to 1 (0-4) at the final follow-up. Only 17% (5/30) of patients across both groups exhibited poor response to this regimen. Among these 5 patients, 4 belonged to the low-risk group (without chemotherapy). DISCUSSION: OMS followed by rapidly progressive cerebellar ataxia are the most common forms of PNSs in children and are associated with neuroblastoma. An aggressive approach with multiple immunotherapies may improve the prognosis of neuroblastoma-associated PNSs. The 2021 criteria perform well in pediatric PNSs. However, we propose upgrading the classification of antibody-negative rapidly progressive cerebellar ataxia with neuroblastoma to definite diagnosis. This adjustment aims to further improve the diagnostic efficacy of this diagnostic criterion in childhood.

Sugar-sweetened beverage intake and long-term mortality in individuals with metabolic dysfunction-associated steatotic liver disease: a longitudinal analysis of the National Health and Nutrition Examination Survey database.

BACKGROUND: Consuming sugar-sweetened beverages (SSBs) has been linked to the development of various adverse health conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluated associations between SSB intake and long-term mortality among individuals with MASLD using a nationally representative database. METHODS: This population-based, longitudinal study extracted data of adults aged 20-79 years with MASLD from the USA (US) National Health and Nutrition Examination Survey database 2003-2014. Associations between the amount of SSB intake and all-cause, cancer and cardiovascular disease mortality until the end of 2019 were determined using Cox proportional hazards regression analyses. RESULTS: A total of 12 965 individuals aged 20-79 years who had MASLD were identified in the database. After exclusion, 5630 participants remained for the analyses. This cohort can be extrapolated to 43 420 321 individuals in the entire US after proper weighting. The mean age of the study cohort was 44.1 years. After adjusting for confounders, no significant association was observed between SSB intake (tertile 3 vs. tertile 1) and all-cause [adjusted hazard ratio (aHR): 1.03, 95% confidence interval (CI), 0.60-1.76) or cancer mortality (aHR, 0.41; 95% CI, 0.15-1.16). However, higher SSB intake (tertile 3 vs. tertile 1) was significantly associated with elevated cardiovascular disease mortality risk (aHR = 2.83; 95% CI, 1.01-7.91). CONCLUSION: In US adults with MASLD, high SSB intake is associated with nearly three-fold increased cardiovascular disease mortality risk. The findings underscore the critical need for concerted action on the part of healthcare providers and policymakers.