The Mevalonate Pathway Is a Druggable Target for Vaccine Adjuvant Discovery.

Motivated by the clinical observation that interruption of the mevalonate pathway stimulates immune responses, we hypothesized that this pathway may function as a druggable target for vaccine adjuvant discovery. We found that lipophilic statin drugs and rationally designed bisphosphonates that target three distinct enzymes in the mevalonate pathway have potent adjuvant activities in mice and cynomolgus monkeys. These inhibitors function independently of conventional "danger sensing." Instead, they inhibit the geranylgeranylation of small GTPases, including Rab5 in antigen-presenting cells, resulting in arrested endosomal maturation, prolonged antigen retention, enhanced antigen presentation, and T cell activation. Additionally, inhibiting the mevalonate pathway enhances antigen-specific anti-tumor immunity, inducing both Th1 and cytolytic T cell responses. As demonstrated in multiple mouse cancer models, the mevalonate pathway inhibitors are robust for cancer vaccinations and synergize with anti-PD-1 antibodies. Our research thus defines the mevalonate pathway as a druggable target for vaccine adjuvants and cancer immunotherapies.

Chimeric Antigen Receptor Designed to Prevent Ubiquitination and Downregulation Showed Durable Antitumor Efficacy.

Clinical evidence suggests that poor persistence of chimeric antigen receptor-T cells (CAR-T) in patients limits therapeutic efficacy. Here, we designed a CAR with recyclable capability to promote in vivo persistence and to sustain antitumor activity. We showed that the engagement of tumor antigens induced rapid ubiquitination of CARs, causing CAR downmodulation followed by lysosomal degradation. Blocking CAR ubiquitination by mutating all lysines in the CAR cytoplasmic domain (CARKR) markedly repressed CAR downmodulation by inhibiting lysosomal degradation while enhancing recycling of internalized CARs back to the cell surface. Upon encountering tumor antigens, CARKR-T cells ameliorated the loss of surface CARs, which promoted their long-term killing capacity. Moreover, CARKR-T cells containing 4-1BB signaling domains displayed elevated endosomal 4-1BB signaling that enhanced oxidative phosphorylation and promoted memory T cell differentiation, leading to superior persistence in vivo. Collectively, our study provides a straightforward strategy to optimize CAR-T antitumor efficacy by redirecting CAR trafficking.

O-GlcNAcylation promotes cerebellum development and medulloblastoma oncogenesis via SHH signaling.

Sonic hedgehog (Shh) signaling plays a critical role in regulating cerebellum development by maintaining the physiological proliferation of granule neuron precursors (GNPs), and its dysregulation leads to the oncogenesis of medulloblastoma. O-GlcNAcylation (O-GlcNAc) of proteins is an emerging regulator of brain function that maintains normal development and neuronal circuitry. Here, we demonstrate that O-GlcNAc transferase (OGT) in GNPs mediate the cerebellum development, and the progression of the Shh subgroup of medulloblastoma. Specifically, OGT regulates the neurogenesis of GNPs by activating the Shh signaling pathway via O-GlcNAcylation at S355 of GLI family zinc finger 2 (Gli2), which in turn promotes its deacetylation and transcriptional activity via dissociation from p300, a histone acetyltransferases. Inhibition of OGT via genetic ablation or chemical inhibition improves survival in a medulloblastoma mouse model. These data uncover a critical role for O-GlcNAc signaling in cerebellar development, and pinpoint a potential therapeutic target for Shh-associated medulloblastoma.

Miniature two-photon microscopy for enlarged field-of-view, multi-plane and long-term brain imaging.

We have developed a miniature two-photon microscope equipped with an axial scanning mechanism and a long-working-distance miniature objective to enable multi-plane imaging over a volume of 420 × 420 × 180 µm3 at a lateral resolution of ~1 µm. Together with the detachable design that permits long-term recurring imaging, our miniature two-photon microscope can help decipher neuronal mechanisms in freely behaving animals.

Dynamic phase-differencing profilometry with number-theoretical phase unwrapping and interleaved projection.

High-speed 3D measurement is receiving increasing attention. However, simultaneously achieving high computational efficiency, algorithmic robustness, and reconstructing ratio is challenging. Therefore, a dynamic phase-differencing profilometry (DPDP) is proposed. By capturing the minimum three phase-shifting sinusoidal deformed patterns and establishing a brand-new model, the phase difference between the object on the reference plane and the reference plane is directly resolved to effectively improve computational efficiency. Although it is wrapped, by using only two auxiliary complementary gratings with a purposely designed lower frequency, a DPDP-based number-theoretical temporal phase unwrapping (NT-TPU) algorithm is also proposed to unwrap the wrapped phase difference rather than the phase itself with high robustness. Furthermore, compared to existing PSP-based NT-TPU, the proposed NT-TPU can normally work under more relaxed restrictions. In order to accomplish a high reconstructing ratio, a pentabasic interleaved projection (PIP) strategy based on time division multiplexing is proposed. It can improve the reconstructing ratio from one reconstruction per every five patterns to an equivalent of one reconstruction per every 1.67 patterns. Experimental results demonstrate that the proposed method achieves high computational efficiency, high algorithmic robustness, and high reconstructing ratio simultaneously and has prospective application in high-speed 3D measurement.

Unveiling out-of-loop attosecond timing jitter precision in Ti:sapphire mode-locked lasers with an optical heterodyne technique.

The out-of-loop timing jitter exhibited in free-running Ti:sapphire mode-locked lasers with attosecond resolution is demonstrated using an optical heterodyne technique. To assess the feasibility of the experiment and discrimination signal properties, numerical simulations were conducted for Ti:sapphire mode-locked lasers. For accurately characterizing the genuine phase noise exhibited by Ti:sapphire mode-locked lasers, out-of-loop measurements were conducted, and a straightforward yet improved optical heterodyne setup was employed, allowing simultaneous low-bandwidth locking and out-of-loop timing jitter measurements with two Ti:sapphire mode-locked lasers. The out-of-loop phase noise floor for a single mode-locked laser reaches -203.47 d B c/H z, assuming a 10 GHz carrier frequency. Additionally, the out-of-loop integrated timing jitter is 11.9 a s from 10 kHz to the Nyquist frequency (50 M H z).

Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia.

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.

Global profiling of protein lactylation in microglia in experimental high-altitude cerebral edema.

BACKGROUND: High-altitude cerebral edema (HACE) is considered an end-stage acute mountain sickness (AMS) that typically occurs in people after rapid ascent to 2500 m or more. While hypoxia is a fundamental feature of the pathophysiological mechanism of HACE, emerging evidence suggests that inflammation serves as a key risk factor in the occurrence and development of this disease. However, little is known about the molecular mechanism underlying their crosstalk. METHODS: A mouse HACE model was established by combination treatment with hypobaric hypoxia exposure and lipopolysaccharides (LPS) stimulation. Lactylated-proteomic analysis of microglia was performed to reveal the global profile of protein lactylation. Molecular modeling was applied to evaluate the 3-D modeling structures. A combination of experimental approaches, including western blotting, quantitative real-time reverse transcriptionpolymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and RNA interference, were used to explore the underlying molecular mechanisms. RESULTS: We found that hypoxia exposure increased the lactate concentration and lactylation in mouse HACE model. Moreover, hypoxia aggravated the microglial neuroinflammatory response in a lactate-dependent manner. Global profiling of protein lactylation has shown that a large quantity of lysine-lactylated proteins are induced by hypoxia and preferentially occur in protein complexes, such as the NuRD complex, ribosome biogenesis complex, spliceosome complex, and DNA replication complex. The molecular modeling data indicated that lactylation could affect the 3-D theoretical structure and increase the solvent accessible surface area of HDAC1, MTA1 and Gatad2b, the core members of the NuRD complex. Further analysis by knockdown or selectively inhibition indicated that the NuRD complex is involved in hypoxia-mediated aggravation of inflammation. CONCLUSIONS: These results revealed a comprehensive profile of protein lactylation in microglia and suggested that protein lysine lactylation plays an important role in the regulation of protein function and subsequently contributes to the neuroinflammatory response under hypoxic conditions.

Comprehensive Characterization of Immune Cell Infiltration Characteristics and Drug Sensitivity Analysis in Inflammatory Breast Cancer Based on Bioinformatic Strategy.

Inflammatory breast cancer (IBC) is a rare and highly invasive form of breast cancer, renowned for its aggressive behavior, malignant capacity, and unfavorable prognosis. Despite considerable advancements in comprehending the underlying biology of IBC, the immune cell infiltration (ICI) profile in IBC remains inadequately elucidated. The current work endeavors to investigate the ICI characteristics of IBC and ascertain the pivotal immune cell subtypes and genes that impact its prognosis. The present study employed microarray data from the GEO database to demonstrate that IBC exhibited a lower abundance of activated mast cells (AMC) in comparison to non-inflammatory breast cancer (nIBC) or normal breast tissue (NBT). Additionally, the mRNA expression level of the gene polo-like kinase 5 (PLK5), which was correlated with AMC, was found to be lower in IBC relative to nIBC or NBT. Furthermore, this investigation provided compelling evidence indicating a potential association between a decreased mRNA expression level of PLK5 and a shorter progression-free survival in patients with breast cancer. The gene set enrichment analysis performed on PLK5 revealed that the gene expression in IBC was closely associated with diverse immune functions and pathways. Besides, a negative correlation has been established between PLK5 mRNA expression level and a majority of immune checkpoint-related genes, thereby suggesting the potential suitability of immunotherapy treatment for IBC. In summary, this study offers valuable insights into the ICI profile of IBC and identifies potential target PLK5 for improving its clinical management.

GNSS Receiver Fingerprinting Based on Time Skew of Embedded CSAC Clock.

GNSS spoofing has become a significant security vulnerability threatening remote sensing systems. Hardware fingerprint-based GNSS receiver identification is one of the solutions to address this security issue. However, existing research has not provided a solution for distinguishing GNSS receivers of the same specification. This paper first theoretically proves that the CSACs (Chip-Scale Atomic Clocks) used in GNSS receivers have unique hardware noise and then proposes a fingerprinting scheme based on this hardware noise. Experiments based on the neural network method demonstrate that this fingerprint achieved an identification accuracy of 94.60% for commercial GNSS receivers of the same specification and performed excellently in anomaly detection, confirming the robustness of the fingerprinting method. This method shows a new real-time GNSS security monitoring method based on CSACs and can be easily used with any commercial GNSS receivers.

Identification and scoring of conservation gaps in wetlands of China's coastal provinces: Implications for extending protected areas.

Wetlands in China's coastal provinces are strategically positioned along migratory flyways for waterbirds, serving as essential habitats and stopover sites due to the expansive land area and abundant wetland resources they offer. This study aimed to introduce a simplified index system to enable rapid assessment and prioritization of unprotected areas for wetlands in China's coastal provinces. A spatial analysis was conducted, combining wetland distribution and existing protected areas data and spatial extent of wetlands extracted by remote sensing data. Results indicate substantial gaps in coverage, covering an area of 108.33 × 104 ha, with 76% being natural wetlands. Over half of these gaps are identified as high-value wetlands with significant ecological functions. The uneven distribution of unprotected wetlands reflects a tension between economic development and wetland conservation. Our findings support the expansion of the existing coastal wetland protected areas' coverage, as well as protecting critical habitats in conservation gaps, and establishing of a network-based waterbird protection system. This research contributes to informed decision-making and policy in wetlands' conservation planning.

Factors governing the dynamics of soil organic carbon and nitrogen in wetlands undergoing management changes in a semi-arid region.

Soil organic carbon and nitrogen play pivotal roles as indicators of soil quality and ecological functioning in wetlands. The escalating impact of human activities and climate change has led to a severe degradation of wetland soils, particularly in semi-arid regions. However, an understanding of the factors governing the dynamics of total soil organic carbon (TSOC) and total soil nitrogen (TSN) in semi-arid areas remains elusive, impeding a comprehensive understanding of wetland ecological functions. The present study investigated variations in TSOC and TSN content as well as vegetation and soil physicochemical properties under five different land management practices (mowed wetlands, mowed and slightly grazed wetlands, moderately grazed wetlands, heavily grazed wetlands, and natural wetlands unaffected by human interference) in the semi-arid Songnen Plain region of China. The results revealed significant decreases in TSOC and TSN content within managed wetlands compared to natural wetlands. Moreover, positive correlations were observed between pairs of SOC-TN or their storage values for SOC (TSOC)-TN (TSN). Furthermore, TSOC and TSN exhibited significant positive associations with aboveground and belowground biomass levels, stem C:N, stem C:P, soil C:P, and soil N:P. Additionally, redundancy analysis indicated that species diversity accounted for 37.4% of the variations in TSOC-TSN while belowground biomass accounted for 8.5% of the variations. Furthermore, nutrient content within stems (particularly N content and C:P) contributed to a 37.2% variation in TSOC and TSN whereas root nutrient content (especially N:P, C:N, and C:P) contributed to a 15.3% variation. Soil C:P, C:N, and total phosphorous (TP) content accounted for 65.7%, 9.6%, and 7.5% of variations of TSOC and TSN, respectively. Besides, variation partitioning analysis revealed that plant community characteristics, community nutrient content, and soil physicochemical properties collectively influenced the dynamics of TSOC and TSN. Among these factors, soil physicochemical properties emerged as the primary drivers of carbon and nitrogen dynamics in degraded wetlands in semi-arid regions. The impact on TSN was more pronounced than that of TSOC. This study provides valuable insights for understanding the processes and mechanisms underlying carbon and nitrogen accumulation in degraded wetlands, facilitating the development of regionally adaptive management plans under different management practices.

Effect of black wolfberry anthocyanin and maltitol on the gelation and microstructural properties of curdlan/gellan gum hybrid gels.

BACKGROUND: Laboratory scale experiments have shown that curdlan and gellan gum gelled together as curdlan/gellan gum (CG) hybrid gels showed better gel properties than the individual curdlan and gellan gum. In this study, CG and black wolfberry anthocyanin (BWA), CG and maltitol (ML) hybrid gels were constructed using CG hybrid gel as matrix. The effects of BWA or ML on the gel properties and microstructure of CG hybrid gels were investigated and a confectionery gel was developed. RESULTS: The presence of BWA increased the storage modulus (G') value of CG at 0.1 Hz, whereas ML had little effect on the G' value of CG. The addition of BWA (5 g L-1 ) and ML (0.3 mol L-1 ) increased the melting and gelling temperatures of CG hybrid gels to 42.4 °C and 34.1 °C and 44.2 °C and 33.2 °C, respectively. Meanwhile, the relaxation time T22 in CG-ML and CG-BWA hybrid gels was reduced to 91.96 and 410.27 ms, indicating the strong binding between BWA and CG, ML and CG. The hydrogen bond interaction between BWA or ML and CG was confirmed by the shift in the hydroxyl stretching vibration peak. Moreover, the microstructures of CG-ML and CG-BWA hybrid gels were denser than that of CG. In addition, confectionery gel containing CG-BWA-ML has good chewing properties. CONCLUSION: These results indicated that the incorporation of BWA or ML could improve the structure of CG hybrid gels and assign a sustainability potential for the development of confectionery gels based on CG complex. © 2024 Society of Chemical Industry.

Ultra-Fast-Healing Glassy Hyperbranched Plastics Capable of Restoring 26.4†MPa Tensile Strength within One Minute at Room Temperature.

The growing concern regarding widespread plastic pollution has propelled the development of sustainable self-healing plastics. Although considerable efforts have been dedicated to fabricating self-healing plastics, achieving rapid healing at room temperature is extremely challenging. Herein, we have developed an ultra-fast-healing glassy polyurethane (UGPU) by designing a hyperbranched molecular structure with a high density of multiple hydrogen bonds (H-bonds) on compliant acyclic heterochains and introducing trace water to form water bridge across the fractured surfaces. The compliant acyclic heterochains allow the dense multiple hydrogen bonds to form a frozen network, enabling tensile strength of up to 70 MPa and storage modulus of 2.5 GPa. The hyperbranched structure can drive the reorganization of the H-bonding network through the high mobility of the branched chains and terminals, thereby leading to self-healing ability at room temperature. Intriguingly, the presence of trace water vapor facilitates the formation of activated layers and the rearrangement of networks across the fractured UGPU sections, thereby enabling ultra-fast self-healing at room temperature. Consequently, the restored tensile strength after healing for 1 minute achieves a historic-record of 26.4 MPa. Furthermore, the high transparency (>90 %) and ultra-fast healing property of UGPU make it an excellent candidate for advanced optical and structural materials.

Absolute phase retrieval based on fringe amplitude encoding without any additional auxiliary pattern.

An absolute phase retrieval method based on fringe amplitude encoding is proposed. Different from the conventional intensity coding methods which are based on time division multiplexing with multiple additional auxiliary patterns, the proposed fringe order encoding strategy is codeword overlapping interaction based on space division multiplexing. It just directly encodes different fringe amplitudes for different periods in corresponding sinusoidal phase-shifting patterns to generate space division multiplexing composite sinusoidal phase-shifting patterns and quantifies the fringe amplitudes into four levels as encoding strategy, so it can retrieve absolute phase without any additional auxiliary patterns. To improve the anti-interference capability of the proposed method, a codeword extraction method based on image morphological processing is proposed to segment the grayscale. Consequently, both the phase-shifting sinusoidal deformed patterns and the single frame space division multiplexing four gray-level codewords for fringe order recognition can be extracted respectively from the captured composite deformed patterns. Then, a half-period single-connected domain correction method is also proposed to correct the codewords. Moreover, in order to suppress the effect of jump errors, the phase zero points are constructed to segment the positive and negative ranges of the phase, making the phase unwrapping process segmented. The experimental results demonstrate the feasibility and effectivity of the proposed method.

Ultra-fast 3D imaging by a big codewords space division multiplexing binary coding.

Patternless binary coding strategies have been a challenge for ultra-fast 3D imaging with structured light. This Letter proposes a big codewords space division multiplexing binary coding method. From the third to the multiple order, a special spatial binary coding instead of the Gray code is created for the first time, to the best of our knowledge, to achieve an ultra-wide unambiguous range with only one auxiliary pattern. Advantageously, a connection domain segmentation technique with anomaly detection is proposed to achieve decoding of the fringe order, which cleverly avoids the misalignment problem. Additionally, a center of gravity method is applied to compensate for the codewords of the residual connected domain. The robustness and effectiveness of the proposed method for complex, isolated, and non-uniform reflectivity objects, as well as the ultra-fast 3D imaging of dynamic measurements, are experimentally verified.

Ternary Organic Solar Cells with Power Conversion Efficiency Approaching 15% by Fine-Selecting the Third Component.

Nonfullerene acceptors with mediate bandgap play a crucial role in ternary devices as the third component, further boosting the performance of organic solar cells (OSCs). Herein, three F-series acceptors (F-H, F-Cl, and F-2Cl) with mediate bandgap are selected and introduced into the PM6:BDT-Br binary system as third component to find the detailed influence of end groups with chlorine (Cl) atom substitution on the performance of ternary organic solar cells. Due to the increased substitution of Cl atoms on the end groups, F-Cl and F-2Cl as guest acceptors reveal a superior ability to regulate the morphology of blend films, contributing to the ordered packing properties and high crystallinity. As a result, F-Cl and F-2Cl based ternary OSCs achieve significantly improved PCEs of 13.89% and 14.67%, respectively, compared with the binary devices (12.70%). On the contrary, F-H without Cl atom displays a poor compatibility with the host system, resulting in an inferior ternary device with a low PCE of 10.79%. This work indicates that F-series acceptors with mediate bandgap are a promising class of third component for high-performance ternary OSCs. And introducing more Cl atoms substitution on the end groups, especially F-2Cl, will own a broad applicability for other binary devices.

Establishment and characterization of immortalized human vocal fold fibroblast cell lines.

PURPOSE: Vocal fold scarring is abnormal scar tissue in the lamina propria layer of the vocal fold. To facilitate investigation of vocal fold scarring, we established and characterized immortalized human vocal fold fibroblast (iHVFF) cell lines. METHODS: Human vocal fold fibroblasts were immortalized by introducing Simian virus 40 large T antigen (SV40TAg) by transfection. Successfully transfected fibroblasts were sorted using flow cytometry. Immunofluorescence cytochemistry and western blot were applied to analyze the expression of fibronectin, vimentin, alpha-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). Cell proliferation rate was measured by CCK-8 assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the mRNA expression level. RESULTS: The iHVFFs continued to proliferate for more than 30 generations and appeared spindle-shaped. The expression of Vimentin and α-SMA were detected in both iHVFFs and primary fibroblasts, and enhanced expression of FAP was observed in iHVFFs. Furthermore, iHVFFs exhibited an increased proliferative capability compared with the primary fibroblasts. RT-qPCR results suggested that collagen type III alpha 1 chain (COL3A1), interleukin-6, cyclooxygenase 2 (COX2), hyaluronan synthase 2 (HAS2), hepatocyte growth factor (HGF) in the iHVFFs significantly increased, whereas transforming growth factor-ß1 (TGF-ß1), elastin and matrix metallopeptidase-1 (MMP-1) expression significantly downregulated. No differences in mRNA expression of α-SMA, fibronectin and collagen type I alpha 2 chain (COL1A2) were noted between iHVFFs and primary fibroblasts. CONCLUSION: iHVFFs can be used as a novel tool cell for future researches on the mechanisms of pathogenesis and treatment of vocal fold scarring.

Morphology-guided treatment of adult laryngeal and hypopharyngeal hemangioma: FD-EENT experience.

OBJECTIVES: To investigate the clinical outcomes of morphology-guided surgical treatment for adult laryngeal and hypopharyngeal hemangioma. MATERIALS AND METHODS: Patients diagnosed with adult laryngeal and hypopharyngeal hemangioma by outpatient laryngoscopy and received surgical treatments were retrospectively included. Size and morphology were classified to guide the choose of surgical procedures including CO2 laser excision, CO2 coagulation + bleomycin injection and potassium-titanyl-phosphate (KTP) laser + bleomycin injection. The baseline information and pre-, postoperative laryngoscopies were collected, the outcomes were followed up and analyzed. RESULTS: A total of 68 patients were included, 7 cases with exophytic and non-bulky hemangioma received CO2 laser excision, 20 cases received CO2 laser coagulation + bleomycin injection and 25 cases with KTP + bleomycin injection, another 16 cases with pure bleomycin injection were included as comparison. There was no difference of baseline analysis among the groups (P > = 0.05). Positive outcomes were achieved in most cases of CO2 excision (100%), CO2 coagulation + bleomycin (90.0%) and KTP + bleomycin (84.0%) groups, which were better than pure bleomycin (56.3%, p = 0.001). CO2 or KTP, associated to Bleomycin, gave same results on same lesions (P = 0.132). CONCLUSIONS AND SIGNIFICANCE: Morphology of hemangioma may help in the selection of surgical procedures. CO2 coagulation can be used as a potential substitute for KTP in the treatment of adult laryngeal and hypopharyngeal hemangioma.

Clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease, RDD).

PURPOSE: To investigate the clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal RDD. METHODS: A retrospective analysis was performed on 16 patients who were initially diagnosed and treated with otolaryngological extranodal RDD in our hospital from January 2013 to January 2019. RESULTS: There were 9 females and 7 males. The mean diagnostic age was 45.35. Nasal, laryngeal and otic RDD were, respectively, accounting for 56.25%, 31.25% and 12.5%. The median interval diagnostic time was individually 1, 0.5 and 0.2 year for nasal, laryngeal and otic RDD. The most common symptoms were separately progressive nasal congestion, dyspnea, otorrhea in nasal, laryngeal and otic RDD. 13 had cervical lymph node swelling on MRI. Surgery or postoperative radiotherapy were conformed. In the end, 14 patients with RDD survived. The survival rate is as high as 87.5%. One of them died of RDD in the fifth year. One case was lost to follow-up 2 years after treatment. Patients survive for at least 2 years and up to 9 years. There was no significant difference in life expectancy of extranodal RDD among different parts of ENT (P = 0.508 > 0.05). The average ages of laryngeal and nasal RDD were similar (P = 0.898 > 0.05). However, the age of both was significantly higher than ear RDD (P = 0.023 and 0.019 < 0.05). CONCLUSIONS: The average diagnostic age was more than 20 years. Nasal RDD was the most common in this area. All laryngeal RDD had infiltrated subglottis. Functional surgery and postoperative radiotherapy can be used to achieve long-term remission and survival.