Endoscopic endonasal transsphenoidal surgery for unusual sellar lesions: eight cases and review of the literature.

Background: Preoperative imaging for some unusual lesions in the sellar region can pose challenges in establishing a definitive diagnosis, impacting treatment strategies. Methods: This study is a retrospective analysis of eight cases involving unusual sellar region lesions, all treated with endoscopic endonasal transsphenoidal surgery (EETS). We present the clinical, endocrine, and radiological characteristics, along with the outcomes of these cases. Results: Among the eight cases, the lesions were identified as follows: Solitary fibrous tumor (SFT) in one case, Lymphocytic hypophysitis (LYH) in one case, Cavernous sinus hemangiomas (CSH) in one case, Ossifying fibroma (OF) in two cases; Sphenoid sinus mucocele (SSM) in one case, Pituitary abscess (PA) in two cases. All patients underwent successful EETS, and their diagnoses were confirmed through pathological examination. Postoperatively, all patients had uneventful recoveries without occurrences of diabetes insipidus or visual impairment. Conclusion: Our study retrospectively analyzed eight unusual lesions of the sellar region. Some lesions exhibit specific imaging characteristics and clinical details that can aid in preoperative diagnosis and inform treatment strategies for these unusual sellar diseases.

Solitary fibrous tumor in the saddle area treated with neuroendoscopic surgery and proton therapy: A case report and literature review.

Solitary fibrous tumor (SFT) of the central nervous system is a rare fibroblastic tumor of mesenchymal origin. SFTs in the saddle area are much less common. In January 2022, a 43-year-old female patient was admitted with SFT 3 months following partial resection of a microscopic transsphenoidal saddle area tumor at a different hospital. Magnetic resonance imaging indicated that the unresected part of the tumor was significantly enhanced on T1 enhancement, which strongly indicated a recurrence. Subsequently, the patient underwent transnasal endoscopic saddle area tumor resection at our hospital and the tumor was successfully removed. By using postoperative pathology examination, immunohistochemical analysis of Bcl-2, cluster of differentiation 99, STAT6 and vimentin, and a fusion gene test performed by high-throughput sequencing technology, the SFT was definitively diagnosed. Following 3 months of follow-up, the patient was found to have tumor recurrence in the cavernous sinus and absence of tumor growth in the pituitary fossa. Therefore, the patient received proton therapy and tumor growth was controlled effectively.

How does the recurrence-related morphology characteristics of the Pcom aneurysms correlated with hemodynamics?

Introduction: Posterior communicating artery (Pcom) aneurysm has unique morphological characteristics and a high recurrence risk after coil embolization. This study aimed to evaluate the relationship between the recurrence-related morphology characteristics and hemodynamics. Method: A total of 20 patients with 22 Pcom aneurysms from 2019 to 2022 were retrospectively enrolled. The recurrence-related morphology parameters were measured. The hemodynamic parameters were simulated based on finite element analysis and computational fluid dynamics. The hemodynamic differences before and after treatment caused by different morphological features and the correlation between these parameters were analyzed. Result: Significant greater postoperative inflow rate at the neck (Qinflow), relative Qinflow, inflow concentration index (ICI), and residual flow volume (RFV) were reported in the aneurysms with wide neck (>4 mm). Significant greater postoperative RFV were reported in the aneurysms with large size (>7 mm). Significant greater postoperative Qinflow, relative Qinflow, and ICI were reported in the aneurysms located on the larteral side of the curve. The bending angle of the internal carotid artery at the initiation of Pcom (αICA@PCOM) and neck diameter had moderate positive correlations with Qinflow, relative Qinflow, ICI, and RFV. Conclusion: The morphological factors, including aneurysm size, neck diameter, and αICA@PCOM, are correlated with the recurrence-inducing hemodynamic characteristics even after fully packing. This provides a theoretical basis for evaluating the risk of aneurysm recurrence and a reference for selecting a surgical plan.

LRP1B mutation is associated with tumor immune microenvironment and progression-free survival in lung adenocarcinoma treated with immune checkpoint inhibitors.

Background: Only a fraction of lung adenocarcinoma (LUAD) patients are eligible for immunotherapy. The identification of biomarkers for immunotherapy is crucial to improve patient outcomes. This study aims to systemically analyze LRP1B mutation and its association with the tumor immune microenvironment (TIME) and immunotherapy. Methods: A cohort of immune checkpoint inhibitors (ICIs)-treated LUAD patients was analyzed to assess the association of LRP1B mutation with immunotherapy prognosis. Another cohort of LUAD patients with genetic and transcriptomic data was also obtained from The Cancer Genome Atlas (TCGA). By investigating the ICIs and the TCGA-LUAD cohorts, we compared the differences in mutation profiles, immunogenicity, TIME, and DNA damage repair (DDR) mutations between the LRP1B-mutated and LRP1B wild-type groups. Additionally, we performed multiplex immunohistochemistry (mIHC) to validate the differences in the tumor microenvironment. Results: Our results revealed that LRP1B mutation is associated with multiple immune-related pathways. Analysis of TIME indicated that LUAD patients with LRP1B mutation expressed significant levels of genes involved in antigen presentation, cytotoxicity, chemokines, and pro-inflammatory mediators, whereas a few immune checkpoint genes were highly expressed in the LRP1B-mutated group as well. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis indicated that LRP1B-mutated LUAD patients had higher infiltration of active immune cells. Multiplex IHC analysis showed that LRP1B-mutated LUAD patients had elevated programmed death ligand-1 (PD-L1) expression and immune cell infiltration. Patients with LRP1B mutation had higher tumor mutation burden, neoantigens, as well as more mutated genes in the DDR-related pathways. Finally, LRP1B-mutated LUAD patients showed a significant prolongation of progression-free survival (PFS) in the ICIs cohort and could be effectively predicted by our constructed nomogram. Conclusions: Our study suggests that LRP1B mutation is associated with higher immune cell infiltration and elevated immune gene expression in TIME and potentially serves as a prognostic biomarker for LUAD patients treated with ICIs.

Bead-Based Immunocomplex Entrapment Assays for Rapid, Sensitive, and Multiplexed Detection of Disease Biomarkers with Minimal User Intervention.

Current interest in at-home diagnostic devices derives from their potential to disrupt expensive and time-consuming hospital-based diagnostic practices. Conventional immunoassays are often touted for use in at-home diagnostic devices, although in practice they are slow, labor-intensive and require expensive equipment. Here, we introduce bead-based sensors as alternative biomarker detection platforms for at-home diagnostic devices. The immunocomplex entrapment assay (ICEA), and the related enzyme-linked ICEA (ELICEA) offer enhancements over conventional immunoassays in terms of their speed, and minimal requirements for user intervention and instrumentation. In particular, we designed bead-based sensors to entrap large molecular weight complexes between target molecules and signal-generating immunoconjugates while allowing any unbound conjugates to escape from the bead. Confocal fluorescence microscopy was used to demonstrate the sensitivity, robustness, and reproducibility of the ICEA and ELICEA platforms. For example, we showed the intensity of signals generated by entrapped immunoconjugate complexes correlate linearly with the concentration of target molecule in the sample. We employed ICEA, and ELICEA platforms to detect human forms of immunoglobulins, albumin, and κ light chain (KLC). For example, we used ICEA to detect KLC at 5 µg·mL-1 in urine, which would allow for earlier diagnosis of Bence-Jones disease compared to conventional assays. In addition, we showed bead-entrapped phosphatases (AP) in immunocomplexes generate insoluble, blue-colored dyes from AP-substrates that accumulate in beads and allow for visual and cellphone camera-based detection of IgG to 10 ng·mL-1 within 20 min. Finally, we described ICEA and ELICEA platforms to analyze multiple target proteins within individual beads.

Ultra-sub-stoichiometric "Dynamic" Bioconjugation Reduces Viscosity by Disrupting Immunoglobulin Oligomerization.

Monoclonal antibodies (mAb) are a major focus of the pharmaceutical industry, and polyclonal immunoglobulin G (IgG) therapy is used to treat a wide variety of health conditions. As some individuals require mAb/IgG therapy their entire life, there is currently a great desire to formulate antibodies for bolus injection rather than infusion. However, to achieve the required doses, very concentrated antibody solutions may be required. Unfortunately, mAb/IgG self-assembly at high concentration can produce an unacceptably high viscosity for injection. To address this challenge, this study expands the concept of "dynamic covalent chemistry" to "dynamic bioconjugation" in order to reduce viscosity by interfering with antibody-antibody interactions. Ultra-sub-stoichiometric amounts of dynamic PEGylation agents (down to the nanomolar) significantly reduced the viscosity of concentrated antibody solutions by interfering with oligomerization.

Releasable Conjugation of Polymers to Proteins.

Many synthetic strategies are available for preparing well-defined conjugates of peptides/proteins and polymers. Most reports on this topic involve coupling methoxy poly(ethylene glycol) to therapeutic proteins, a process referred to as PEGylation, to increase their circulation lifetime and reduce their immunogenicity. Unfortunately, the major dissuading dogma of PEGylation is that, in many cases, polymer modification leads to significant (or total) loss of activity/function. One approach that is gaining momentum to address this challenge is to release the native protein from the polymer with time in the body (releasable PEGylation). This contribution will present the state-of-the-art of this rapidly evolving field, with emphasis on the chemistry behind the release of the peptide/protein and the means for altering the rate of release in biological fluids. Linkers discussed include those based on the following: substituted maleic anhydride and succinates, disulfides, 1,6-benzyl-elimination, host-guest interactions, bicin, ß-elimination, biodegradable polymers, E1cb elimination, ß-alanine, photoimmolation, coordination chemistry, zymogen activation, proteolysis, and thioesters.

PEGylated peptide based reductive polycations as efficient nonviral gene vectors.

To overcome the critical barriers in gene delivery, a series of reducible polycations (RPCs) based on low molecular weight (LMW) peptides, i.e. PolyHK6 H, PolyHK6 H-mPEG1 , PolyHK6 H-mPEG2 , and PolyHK6 H-mPEG3 , with different poly(ethylene glycol) (PEG) contents, are synthesized and evaluated as nonviral gene vectors. All the RPCs exhibit lower cytotoxicity compared with 25 kDa polyethyleneimine (PEI) and PEGylated PEI (PEI-mPEG: PEI-mPEG1 , PEI-mPEG2 , and PEI-mPEG3 ). PolyHK6 H-mPEG1 and PolyHK6 H-mPEG2 can bind and condense plasmid deoxyribonucleic acid (pDNA) efficiently with a particle size of about 200 nm. Moreover, they display much higher transfection efficiency than that of 25 kDa PEI especially in serum-supplemented medium. Moreover, PolyHK6 H-mPEG1 has equal transfection efficiency with PEI-mPEG1 which is optimal in the PEI-mPEG, but PolyHK6 H-mPEG1 exhibits significantly lower cytotoxicity than PEI-mPEG1 . This is attributed to the fact that inter-peptide disulfide bonds can increase the stability of RPCs/pDNA complexes in extracellular environment and thereafter cleave in cytoplasm to facilitate the release of pDNA in intracellular environment. The PEGylated RPCs demonstrate here improved intracellular gene transfer performance and will have great potential applications in vivo.

Photoresponsive smart template for reversible cell micropatterning.

A novel micropatterned smart template based on transparency photolithography allows the spatial control of cell micropatterning. By utilizing the photoinduced reaction of azobenzene ligands and cyclodextrin-terminated alkanesilane via host-guest recognitions, cells can be easily controlled to adhere reversibly in well defined areas.

Encapsulation of an adamantane-doxorubicin prodrug in pH-responsive polysaccharide capsules for controlled release.

Supramolecular microcapsules (SMCs) with the drug-loaded wall layers for pH-controlled drug delivery were designed and prepared. By using layer-by-layer (LbL) technique, the SMCs were constructed based on the self-assembly between polyaldenhyde dextran-graft-adamantane (PAD-g-AD) and carboxymethyl dextran-graft-ß-CD (CMD-g-ß-CD) on CaCO(3) particles via host-guest interaction. Simultaneously, adamantine-modified doxorubicin (AD-Dox) was also loaded on the LbL wall via host-guest interaction. The in vitro drug release study was carried out at different pHs. Because the AD groups were linked with PAD (PAD-g-AD) or Dox (AD-Dox) by pH-cleavable hydrazone bonds, AD moieties can be removed under the weak acidic condition, leading to destruction of SMCs and release of Dox. The pH-controlled drug release can enhance the uptake by tumor cells and thus achieve improved cancer therapy efficiency.