Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis.

The heterogeneous cellular microenvironment of human airway chronic inflammatory diseases, including chronic rhinosinusitis (CRS) and asthma, is still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on the nasal mucosa of healthy individuals and patients with three subtypes of CRS and identified disease-specific cell subsets and molecules that specifically contribute to the pathogenesis of CRS subtypes. As such, ALOX15+ macrophages contributed to the type 2 immunity-driven pathogenesis of one subtype of CRS, eosinophilic CRS with nasal polyps (eCRSwNP), by secreting chemokines that recruited eosinophils, monocytes and T helper 2 (TH2) cells. An inhibitor of ALOX15 reduced the release of proinflammatory chemokines in human macrophages and inhibited the overactivation of type 2 immunity in a mouse model of eosinophilic rhinosinusitis. Our findings advance the understanding of the heterogeneous immune microenvironment and the pathogenesis of CRS subtypes and identify potential therapeutic approaches for the treatment of CRS and potentially other type 2 immunity-mediated diseases.

MdNAC5: a key regulator of fructose accumulation in apple fruit.

The sweetness of apple fruit is a key factor in the improvement of apple varieties, with fructose being the sweetest of the soluble sugars, playing a crucial role in determining the overall sweetness of the apple. Therefore, uncovering the key genes controlling fructose accumulation and deciphering the regulatory mechanisms of fructose are vitally important for the improvement of apple varieties. In this study, through BSA-seq and transcriptome analysis of the 'Changfu 2' × 'Golden Delicious' F1 hybrid population, MdNAC5 was identified as a key regulatory gene for fructose content. MdNAC5 was shown to significantly influence fructose accumulation in both apples and tomatoes. Furthermore, we conducted a detailed identification of sugar transporters and metabolic enzymes in apples, discovering that MdNAC5 can enhance fructose accumulation in vacuoles and the conversion of sucrose to fructose by binding to and activating the promoters of the vacuolar sugar transporter MdTST2 and the neutral invertase MdNINV6. Additionally, MdNAC5 regulated the MdEIN3.4-MdSWEET15a module, strengthening the unloading of sucrose in the phloem of the fruit. Our results reveal a new mechanism by which MdNAC5 regulates fructose accumulation in apples and provide theoretical foundations for improving apple sweetness through genetic modification.

Development and validation of a nomogram for predicting overall survival in patients with sinonasal mucosal melanoma.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a relatively rare malignant tumour with a poor prognosis. This study was designed to identify prognostic factors and establish a nomogram model to predict the overall survival (OS) of patients with SNMM. METHODS: A total of 459 patients with SNMM were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort. Univariate and multivariate Cox regression analyses were used to screen for independent factors associated with patient prognosis and develop the nomogram model. In addition, external validation was performed to evaluate the effectiveness of the nomogram with a cohort of 34 patients with SNMM from Peking Union Medical College Hospital. RESULTS: The median OS in the cohort from the SEER database was 28 months. The 1-year, 3-year and 5-year OS rates were 69.8%, 40.4%, and 30.0%, respectively. Multivariate Cox regression analysis indicated that age, T stage, N stage, surgery and radiotherapy were independent variables associated with OS. The areas under the receiver operating characteristic curves (AUCs) of the nomograms for predicting 1-, 3- and 5-year OS were 0.78, 0.71 and 0.71, respectively, in the training cohort. In the validation cohort, the area under the curve (AUC) of the nomogram for predicting 1-, 3- and 5-year OS were 0.90, 0.75 and 0.78, respectively. Patients were classified into low- and high-risk groups based on the total score of the nomogram. Patients in the low-risk group had a significantly better survival prognosis than patients in the high-risk group in both the training cohort (P < 0.0001) and the validation cohort (P = 0.0016). CONCLUSION: We established and validated a novel nomogram model to predict the OS of SNMM patients stratified by age, T stage, N stage, surgery and radiotherapy. This predictive tool is of potential importance in the realms of patient counselling and clinical decision-making.

Discovery and preclinical profile of YK-2168, a differentiated selective CDK9 inhibitor in clinical development.

Emerging clinical evidence indicates that selective CDK9 inhibition may provide clinical benefits in the management of certain cancers. Many CDK9 selective inhibitors have entered clinical developments, and are being investigated. No clear winner has emerged because of unforeseen toxicity often observed in clinic with these agents. Therefore, a novel agent with differentiated profiles is still desirable. Herein, we report our design, syntheses of a novel azaindole series of selective CDK9 inhibitors. SAR studies led to a preclinical candidate YK-2168. YK2168 exhibited improved CDK9 selectivity over AZD4573 and BAY1251152; also showed differentiated intravenous PK profile and remarkable solid tumor efficacy in a mouse gastric cancer SNU16 CDX model in preclinical studies. YK-2168 is currently in clinical development in China (CTR20212900).

Ambient air pollution and risk of allergic respiratory diseases in European and East Asian populations: A Mendelian randomization study.

BACKGROUND: Ambient air pollution has become a challenging global health issue since industrialization, especially affecting respiratory diseases. However, the causal link between air pollution and allergic respiratory diseases (ARDs) remains unclear due to confounding factors in conventional epidemiological studies across different populations. Thus, we aimed to clarify the causal associations between air pollution and ARDs in European and East Asian populations using Mendelian randomization (MR). METHODS: MR utilizes genetic variants and provides a satisfactory level of causal evidence. Genetic data for exposures (PM2.5, PM2.5 absorbance, PM10, PMcoarse, NO2 and NOx) and outcomes (allergic rhinitis, chronic rhinosinusitis, asthma, and obesity related asthma) were obtained from genome-wide association studies. Instrumental variables were strictly filtered based on core assumptions. Two-sample MR and sensitivity analyses were conducted separately for European and East Asian populations. RESULTS: PMcoarse was causally associated with an increased risk of chronic rhinosinusitis (OR = 1.588 [1.002-2.518]; p = 0.049) and obesity related asthma (OR = 1.956 [1.012-3.780]; p = 0.046) in European population, and PM10 was associated with a decreased risk of allergic rhinitis in East Asian population (OR = 0.882 [0.798-0.974]; p = 0.013). No heterogeneity or pleiotropy was detected in any significant causal association. CONCLUSION: Our findings indicate that ambient air pollution has opposite impacts on the etiology of ARDs in European and East Asian populations, which provides evidence for decisions on public policies and suggests that different responses to environmental factors such as air pollution may contribute to racial heterogeneity of ARDs.

Ambient Phosphor with High Efficiency and Long Lifetime in Poly(Methyl Methacrylate) Through Charge-Transfer-Mediated Triplet Exciton Formation for Photolithography Applications.

Currently, purely organic compounds showing ambient phosphorescence with high efficiency (ΦP ) and ultra-long lifetime (τP ) are quite rare and often need to be achieved in hydrophilic poly(vinyl alcohol)-based hosts. This severely limits their applications. Here, we provide a solution to this issue by constructing an ortho-linked donor-acceptor (D-A) dyad whose D moiety has not only a long-lived T1 state to achieve a long τP , but also a Tn state that is close to the S1 state of the dyad to trigger effective spin-orbit charge transfer intersystem crossing (SOCT-ISC). The rationality of this strategy was validated by a new phosphor OF-BCz that is able to show a τP of 1.92 s and a ΦP of 30 % even in a less rigid matrix of poly(methyl methacrylate) (PMMA). Excitingly, OF-BCz exhibited its potential as both a photocuring initiator and an in situ quality indicator, allowing for the visual detection of defects in photolithographic patterning.

Multiplex immunohistochemistry defines two cholesterol metabolism patterns predicting immunotherapeutic outcomes in gastric cancer.

BACKGROUND: The role of cholesterol metabolism in gastric cancer (GC) and its implications for tumor characteristics and immunotherapy response remain poorly understood. In this study, our aim was to investigate this role, identify associated metabolic subtypes, and assess their clinical implications in GC. METHODS: We conducted a comprehensive analysis of cholesterol metabolism genes (CMGs) using transcriptomic data from TCGA and GEO. Based on 23 representative CMGs, we classified GC into metabolic subtypes. We evaluated clinical features and immune cell infiltration between these subtypes. Additionally, we identified a CMG signature and assessed its clinical relevance in GC. We retrospectively enrolled thirty-five GC patients receiving chemotherapy plus a PD-1 inhibitor to assess the CMG signature using multiplex immunohistochemistry. RESULTS: Our analysis revealed two cholesterol metabolism subtypes in GC: Cholesterol Metabolism Type 1 (CMT1) and Cholesterol Metabolism Type 2 (CMT2). These subtypes exhibited distinct patterns: CMT1 indicated heightened cholesterol biosynthesis, while CMT2 showed abnormal cholesterol transport. CMT2 was associated with unfavorable clinical features, enriched malignant pathways, and a pro-tumor immune microenvironment. Furthermore, we developed a five-CMG prognostic signature (ABCA1, NR1H3, TSPO, NCEH1, and HMGCR) that effectively predicted the prognosis of patients with GC and their response to chemotherapy plus a PD-1 inhibitor. This signature was validated in a clinical cohort using multiplex immunohistochemistry. CONCLUSION: Our results highlight the effectiveness of cholesterol metabolism patterns as biomarkers for predicting the prognosis and immunotherapy response in GC. The expression of cholesterol metabolism genes and the assessment of cholesterol metabolism patterns have the potential to predict the outcome of immunotherapy and guide treatment strategies.

Discovery of novel bicyclic[3.3.0]proline peptidyl α-ketoamides as potent 3CL-protease inhibitors for SARS-CoV-2.

The outbreak of SARS-CoV-2 has caused global crisis on health and economics. The multiple drug-drug interaction risk associated with ritonavir warrants specialized assessment before using Paxlovid. Here we report a multiple-round SAR study to provide a novel bicyclic[3.3.0]proline peptidyl α-ketoamide compound 4a, which is endowed with excellent antiviral activities and pharmacokinetic properties. Also, in vivo HCoV-OC43 neonatal mice model demonstrated compound 4a has good in vivo efficacy. Based on these properties, compound 4a worth further SAR optimization with the goal to develop compounds with better pharmacokinetic properties and finally to realize single agent efficacy in human.

2-Aminopyrimidine derivatives as selective dual inhibitors of JAK2 and FLT3 for the treatment of acute myeloid leukemia.

Dual inhibitors of JAK2 and FLT3 can synergistically control the development of acute myeloid leukemia (AML), and overcome secondary drug resistance of AML that is associated with FLT3 inhibition. We therefore designed and synthesized a series of 4-piperazinyl-2-aminopyrimidines as dual inhibitors of JAK2 and FLT3, and improved their selectivity for JAK2. Screening cascades revealed that compound 11r exhibited inhibitory activity with IC50 values of 2.01, 0.51, and 104.40 nM against JAK2, FLT3, and JAK3, respectively. Compound 11r achieved a high selectivity for JAK2 at a ratio of 51.94, and also showed potent antiproliferative activity in HEL (IC50 = 1.10 µM) and MV4-11 (IC50 = 9.43 nM) cell lines. In an in vitro metabolism assay, 11r exhibited moderate stability in human liver microsomes (HLMs), with a half-life time of 44.4 min, and in rat liver microsomes (RLMs), with a half-life of 143 min. In pharmacokinetic studies, compound 11r showed moderate absorption (Tmax = 5.33 h), with a peak concentration of 38.7 ng/mL and an AUC of 522 ng h/mL in rats, and an oral bioavailability of 25.2%. In addition, 11r induced MV4-11 cell apoptosis in a dose-dependent manner. These results indicate that 11r is a promising selective JAK2/FLT3 dual inhibitor.

The MdBBX22-miR858-MdMYB9/11/12 module regulates proanthocyanidin biosynthesis in apple peel.

Proanthocyanidins (PAs) have antioxidant properties and are beneficial to human health. The fruit of apple (Malus × domestica Borkh.), especially the peel, is rich in various flavonoids, such as PAs, and thus is an important source of dietary antioxidants. Previous research on the regulation of PAs in apple has mainly focussed on the transcription level, whereas studies conducted at the post-transcriptional level are relatively rare. In this study, we investigated the function of mdm-miR858, a miRNA with multiple functions in plant development, in the peel of apple fruit. We showed that mdm-miR858 negatively regulated PA accumulation by targeting MdMYB9/11/12 in the peel. During fruit development, mdm-miR858 expression was negatively correlated with MdMYB9/11/12 expression and PA accumulation. A 5'-RACE experiment, GUS staining assays and transient luminescent assays indicated that mdm-miR858 cleaved and inhibited the expression of MdMYB9/11/12. Overexpression of mdm-miR858 in apple calli, tobacco and Arabidopsis reduced the accumulation of PAs induced by overexpression of MdMYB9/11/12. Furthermore, we found that MdBBX22 bound to the mdm-miR858 promoter and induced its expression. Overexpression of MdBBX22 induced the expression of mdm-miR858 to inhibit the accumulation of PAs in apple calli overexpressing MdMYB9/11/12. Under light stress, MdBBX22 induced mdm-miR858 expression to inhibit PA accumulation and thereby indirectly enhanced anthocyanin synthesis in the peel. The present results revealed that the MdBBX22-miR858-MdMYB9/11/12 module regulates PA accumulation in apple. The findings provide a reference for further studies of the regulatory mechanism of PA accumulation and the relationship between PAs and anthocyanins.

Profile of Tissue Immunoglobulin E in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) exhibits a poorer prognosis than noneCRSwNP. The aim of this study was to analyze the potential of total immunoglobulin E (tIgE) and specific IgE (sIgE) levels in tissues for distinguishing and assessing eCRSwNP. METHODS: We enrolled 10 control and 88 CRSwNP patients. The clinical data of patients were collected before surgery. Nasal mucosa tissues were taken during surgery for measurements of tIgE, sIgE (weed pollen, epidermal and animal protein, mold, house dust, tree pollen), and subepithelial eosinophil (EOS) counts. The predictive significance of the potential predictors for eCRSwNP was assessed with receiver operating characteristic (ROC) curves. RESULTS: Nasal polyps tIgE and mold-sIgE were positively correlated with blood and tissue EOSs, comorbid allergic rhinitis and asthma, ethmoid score/total maxillary score ratio, visual analog scale, and CT score. The ROC curve analysis showed that tissue tIgE (p = 0.0004), mold-sIgE (p = 0.0030), blood EOS percentage (p = 0.0003), and absolute blood EOS count (p = 0.0010) acted as predictive factors for eCRSwNP. According to the cutoff value of tissue tIgE of 34.55 ku/L, patients with a high level were more likely to suffer from asthma (p = 0.016) and showed a significantly higher EOS count (p = 0.022), EOS percentage (p = 0.029), and tIgE (p = 0.002) in blood. CONCLUSION: Tissue tIgE and mold-sIgE had a significant relationship with the clinical and pathological characteristics of CRSwNP patients and might be reliable for distinguishing and assessing eCRSwNP.

Discovery and preclinical evaluations of WX-0593, a novel ALK inhibitor targeting crizotinib-resistant mutations.

ALK gene rearrangements are oncogenic drivers in approximately 5% of NSCLC. Crizotinib, a first generation ALK inhibitor, is widely prescribed for ALK-positive NSCLC in clinic. Resistance to crizotinib and other ALK inhibitors has been problematic. Addressing resistance, here we describe discovery and development of a novel, proprietary spirocyclic diamine-substituted aryl phosphine oxide series of inhibitors, which led to the identification of WX-0593 (16a) as a potent ALK inhibitor. WX-0593 inhibited the activity of both wild type and resistant mutants of ALK in vitro, showed strong antitumor activity in a crizotinib-resistant mouse PDX model. WX-0593 is currently under development in phase II/III clinical trials.

Patient-reported outcome measures of edentulous patients restored with single-implant mandibular overdentures: A systematic review.

AIM: To review the literatures concerning the effect of the single-implant mandibular overdenture (SIMO) on patient-reported outcome measures (PROMs) and masticatory function in the fully edentulous patients. MATERIALS AND METHODS: Electronic databases (PubMed, Cochrane Library, EMBASE and Web of Science) were searched, complemented with manual resources. Prospective studies published in English up to February 2020 reporting the effect of SIMO on PROMs and masticatory function in the edentulous patients were included. This review focused on oral health-related quality of life (OHRQoL), satisfaction and masticatory function outcomes. RESULTS: Of 1157 initially screened articles, 9 randomised controlled trials (RCTs) and 8 prospective studies involving 551 subjects fulfilled the inclusion criteria. Two RCTs were graded as high risk of bias or some concern, while others were low risk. All prospective studies had adequate representativeness and assessment, but only one study had a controlled cohort. In general, the edentulous patients restored with SIMOs had improved OHRQoL and general satisfaction compared to those with conventional complete dentures (CCDs), but the outcome of masticatory function was controversial. Compared with two-implant mandibular overdenture (TIMO), SIMO showed no significant differences regarding general satisfaction and satisfaction with speech, comfort, chewing ability, aesthetics and social life. Conflicting results were observed in OHRQoL and satisfaction with retention and stability. Better masticatory performance was observed in TIMO group than SIMO group. CONCLUSION: Within the limitation of this review, SIMO is featured with better OHRQoL and satisfaction than CCD. SIMO and TIMO rendered similar patient satisfaction, but TIMO had better masticatory performance.

Impact of sequencing depth and technology on de novo RNA-Seq assembly.

BACKGROUND: RNA-Seq data is inherently nonuniform for different transcripts because of differences in gene expression. This makes it challenging to decide how much data should be generated from each sample. How much should one spend to recover the less expressed transcripts? The sequencing technology used is another consideration, as there are inevitably always biases against certain sequences. To investigate these effects, we first looked at high-depth libraries from a set of well-annotated organisms to ascertain the impact of sequencing depth on de novo assembly. We then looked at libraries sequenced from the Universal Human Reference RNA (UHRR) to compare the performance of Illumina HiSeq and MGI DNBseq™ technologies. RESULTS: On the issue of sequencing depth, the amount of exomic sequence assembled plateaued using data sets of approximately 2 to 8 Gbp. However, the amount of genomic sequence assembled did not plateau for many of the analyzed organisms. Most of the unannotated genomic sequences are single-exon transcripts whose biological significance will be questionable for some users. On the issue of sequencing technology, both of the analyzed platforms recovered a similar number of full-length transcripts. The missing "gap" regions in the HiSeq assemblies were often attributed to higher GC contents, but this may be an artefact of library preparation and not of sequencing technology. CONCLUSIONS: Increasing sequencing depth beyond modest data sets of less than 10 Gbp recovers a plethora of single-exon transcripts undocumented in genome annotations. DNBseq™ is a viable alternative to HiSeq for de novo RNA-Seq assembly.

The gut microbiota: a new perspective on the toxicity of malachite green (MG).

Gut microbiome critically contributes to host health status. Thus, investigating the relationship between the gut microbiome and toxic chemicals is a hot topic in toxicology research. Exposure to malachite green (MG) has been linked to various health disorders. Thus, exploring the gut microbiota changes in response to MG would provide a new perspective on the toxicity effects of this chemical substance. MG exposure resulted in the significantly lower alpha diversity (Mann-Whitney U test, z = - 6.83, p = 0.00) but higher beta diversity (Mann-Whitney U test, z = - 1.98, p = 0.04) of gut microbiota, and significantly decreased ecosystem stability (alpha and beta variability; Mann-Whitney U test, all p < 0.05) of gut microbial communities. Gut bacterial networks showed that the interactions became more complex and stronger after MG exposure, which could decrease the stability of the network. Changes in gut microbiota composition were mainly reflected in the enrichment of opportunistic bacteria (i.e., Aeromonas and Vibrio) and the depression of fermentative bacteria (i.e., Bacteroides and Paludibacter). MG exposure leads to a significantly increased gut permeability (lipopolysaccharide-binding protein; Mann-Whitney U test, z = - 6.92, p = 0.00), which could reduce the host selective pressures on particular bacterial species (such as members in Aeromonas and Vibrio). This result was further supported by the weakened importance of a deterministic microbial assembly after MG exposure. All these findings indicated that MG exposed fishes might have more possibilities to be infected, as demonstrated by the enrichment of opportunistic pathogenic bacteria, high-level immune responses, and increased gut permeability. These findings greatly improve our understanding of the toxicity effects of MG.

Transcriptomic analyses of human bronchial epithelial cells BEAS-2B exposed to brominated flame retardant (tetrabromobisphenol A).

Brominated flame retardants (BFRs) are supposed to act as disruptors of cell signaling, but the underlying mechanisms remain less clear. Human bronchial epithelial cells (BEAS-2B) were used to investigate the toxic effect and gene expression changes induced by tetrabromobisphenol A (TBBPA). By genome-wide approaches with Illumina RNA-seq, 87 genes were identified to exhibit ≥1.5-fold changes in expression after treatment by TBBPA for 48 h, among which, 79 were upregulated and 8 were downregulated. Gene ontology (GO) annotation enriched unigenes were divided into three clusters: biological process (BP), cellular component (CC) and molecular function (MF). Pathway analysis showed that NF-κB, TNF signaling, toll-like receptor, MAPK signaling and B-cell receptor were the most prominent pathways affected by TBBPA, which play key roles in regulating cell proliferation and cell differentiation, inflammatory response. Finally, for verifying the accuracy of microarray analysis, qRT-PCR was used to analyze the transcription level of key genes in the above signaling pathways, and ELISA assay confirmed the effect of TBBPA on the levels of CXCL-2, CCL-3, CCL-4, IL-1ß, TNF-α, and IL-6. These findings provided important information for further exploitation of the mechanisms under-lying BFR-induced adverse health effects.

Identification of balanced chromosomal rearrangements previously unknown among participants in the 1000 Genomes Project: implications for interpretation of structural variation in genomes and the future of clinical cytogenetics.

PURPOSE: Recent studies demonstrate that whole-genome sequencing enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in the 1000 Genomes Project without knowing which bands were affected. METHODS: The 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparent BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold). RESULTS: With this approach, we detected four reciprocal balanced translocations and four inversions, ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and polymerase chain reaction studies. One of these DNAs has a subtle translocation that is not readily identified by chromosome analysis because of the similarity of the banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene. CONCLUSION: Our study demonstrates the extension of utilizing low-pass whole-genome sequencing for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project.

The Streptococcus suis transcriptional landscape reveals adaptation mechanisms in pig blood and cerebrospinal fluid.

Streptococcus suis (SS) is an important pathogen of pigs, and it is also recognized as a zoonotic agent for humans. SS infection may result in septicemia or meningitis in the host. However, little is known about genes that contribute to the virulence process and survival within host blood or cerebrospinal fluid (CSF). Small RNAs (sRNA) have emerged as key regulators of virulence in several bacteria, but they have not been investigated in SS. Here, using a differential RNA-sequencing approach and RNAs from SS strain P1/7 grown in rich medium, pig blood, or CSF, we present the SS genome-wide map of 793 transcriptional start sites and 370 operons. In addition to identifying 29 sRNAs, we show that five sRNA deletion mutants attenuate SS virulence in a zebrafish infection model. Homology searches revealed that 10 sRNAs were predicted to be present in other pathogenic Streptococcus species. Compared with wild-type strain P1/7, sRNAs rss03, rss05, and rss06 deletion mutants were significantly more sensitive to killing by pig blood. It is possible that rss06 contributes to SS virulence by indirectly activating expression of SSU0308, a virulence gene encoding a zinc-binding lipoprotein. In blood, genes involved in the synthesis of capsular polysaccharide (CPS) and subversion of host defenses were up-regulated. In contrast, in CSF, genes for CPS synthesis were down-regulated. Our study is the first analysis of SS sRNAs involved in virulence and has both improved our understanding of SS pathogenesis and increased the number of sRNAs known to play definitive roles in bacterial virulence.

Infratemporal Fossa Metastasis of Non-Small-Cell Lung Adenocarcinoma: A Case Report and Literature Review.

Neoplasms in the infratemporal fossa (ITF) are rare and insidious lesions that cause various symptoms due to involvement of the temporomandibular joint (TMJ), paranasal sinuses, and orbit. Here, we report a case of metastatic non-small cell lung adenocarcinoma in the ITF. The patient presented with facial pain and limited mouth opening, which did not respond to treatment for TMJ disorder, and a neoplasm was discovered in the ITF through medical imaging. With an open biopsy, the diagnosis was finalized. This report suggested that the physician should consider lesions in the ITF when facial pain and limited mouth opening failed local treatment, and distant metastasis of malignant tumor should be alerted. We also reviewed the literature regarding metastatic cancer to the ITF.