A rare condition similar to inguinal hernia in pregnancy: A case of bilateral varicose veins of round ligament of uterus.

Round ligament varicosities (RLV) are a very rare cause of an inguinal mass, which is very similar to an inguinal hernia, and should be taken seriously by women, especially in mid-pregnancy. Ultrasound can confirm the diagnosis of the RLV and can prevent unnecessary interventions. We report a case of a patient with bilateral RLV: the primigravida was 31 years old, G1P0, gestation 30+2w. The patient presented to the clinic 1 month ago due to the discovery of bilateral inguinal masses. After the diagnosis was confirmed by ultrasound, this patient received regular reviews during labor and delivery and is currently in good maternal condition. The patient came to the clinic 1 month after the discovery of bilateral inguinal area masses for 1 month.

Molecular-level insights into the brewing-dependent chemical diversity, properties, and formation mechanism of Moutai Base baijiu using Fourier transform ion cyclotron resonance mass spectrometry.

The brewing-dependent molecular diversity, properties, and formation mechanism of Moutai (a typical sauce-flavor Baijiu) base Baijiu, were explored using FT-ICR MS combined with various visualization methods. Seven-round Moutai base Baijiu exhibited significant diversity and heterogeneity, containing more unsaturated/saturated reduced molecules. The increased brewing round increased the molecular unsaturation/aromaticity and enhanced the transformation between saturated/oxidized and unsaturated/reduced molecules. Moreover, lignin-/aliphatic-/peptide-/lipid-like molecules dominated the molecular characteristics of Moutai base Baijiu. The basic and acidic components contained more reduced carbohydrate-/lipid-like molecules and oxidized tannin-like/condensed aromatic molecules, respectively, contributing to the molecular stability and diversity, respectively. More unique lipid-like and lignin-like molecules newly formed in the early and late brewing rounds, respectively, and the increased brewing shifted the chemical reaction from a single dominant to a multi-dimensional balance. More unique N-containing molecules (>450 Da) significantly contributed the specific brewing characteristics. These new findings help to understand the molecular-level formation mechanism of Moutai base Baijiu.

Latent Reciprocal Engagement and Accuracy Variables in Social Relations Structural Equation Modeling.

The social relations model (SRM) is the standard approach for analyzing dyadic data stemming from round-robin designs. The model can be used to estimate correlation-coefficients that reflect the overall reciprocity or accuracy of judgements for individual and dyads on the sample- or population level. Within the social relations structural equation modeling framework and on the statistical grounding of stochastic measurement and classical test theory, we show how the multiple indicator SRM can be modified to capture inter-individual and inter-dyadic differences in reciprocal engagement or inter-individual differences in reciprocal accuracy. All models are illustrated on an open-access round-robin data set containing measures of mimicry, liking, and meta-liking (the belief to be liked). Results suggest that people who engage more strongly in reciprocal mimicry are liked more after an interaction with someone and that overestimating one's own popularity is strongly associated with being liked less. Further applications, advantages and limitations of the models are discussed.

Histopathological Patterns of Otosclerosis Progression: Exploring Otic Capsule and Round Window Involvement.

OBJECTIVES: Obliteration of the round window (RW) in cases of otosclerosis presents a significant clinical challenge due to its association with more severe hearing loss and a poorer prognosis for functional recovery after stapes surgery. The objective is to assess and characterize the occurrence of RW involvement in otosclerosis cases and to identify patterns of disease progression that may indicate a potential for RW obliteration. METHODS: We selected archival temporal bones from donors with otosclerosis. We evaluated the degree of RW obliteration using a semi-quantitative scale and the location of the foci within the temporal bone, and whether the foci were continuous or isolated. RESULTS: Most of the foci were located anteriorly to the oval window (89.2%), while RW area involvement was seen in 26.9% of the ears. In cases with fenestral foci, 68.1% directly involved and/or fixed the footplate. Among donors with bilateral otosclerosis, foci affected both ears in a similar pattern in 64.2%. Among donors with RW involvement, ones with continuous, large lesions that extended from the oval window associated with complete RW obliteration, while ones with smaller degrees of obliteration had solitary foci scattered within the otic capsule. CONCLUSION: Our results demonstrate a high rate of RW involvement in cases of otosclerosis. Ears with continuous lesions extending from the oval window region to the RW area were more likely to present with complete RW obliteration. These results provide insights that could lead to better prognostic assessment of patients with otosclerosis in the future. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Wireless electrocochleography in awake chinchillas: A model to study crossmodal modulations at the peripheral level.

The discovery and development of electrocochleography (ECochG) in animal models has been fundamental for its implementation in clinical audiology and neurotology. In our laboratory, the use of round-window ECochG recordings in chinchillas has allowed a better understanding of auditory efferent functioning. In previous works, we gave evidence of the corticofugal modulation of auditory-nerve and cochlear responses during visual attention and working memory. However, whether these cognitive top-down mechanisms to the most peripheral structures of the auditory pathway are also active during audiovisual crossmodal stimulation is unknown. Here, we introduce a new technique, wireless ECochG to record compound-action potentials of the auditory nerve (CAP), cochlear microphonics (CM), and round-window noise (RWN) in awake chinchillas during a paradigm of crossmodal (visual and auditory) stimulation. We compared ECochG data obtained from four awake chinchillas recorded with a wireless ECochG system with wired ECochG recordings from six anesthetized animals. Although ECochG experiments with the wireless system had a lower signal-to-noise ratio than wired recordings, their quality was sufficient to compare ECochG potentials in awake crossmodal conditions. We found non-significant differences in CAP and CM amplitudes in response to audiovisual stimulation compared to auditory stimulation alone (clicks and tones). On the other hand, spontaneous auditory-nerve activity (RWN) was modulated by visual crossmodal stimulation, suggesting that visual crossmodal simulation can modulate spontaneous but not evoked auditory-nerve activity. However, given the limited sample of 10 animals (4 wireless and 6 wired), these results should be interpreted cautiously. Future experiments are required to substantiate these conclusions. In addition, we introduce the use of wireless ECochG in animal models as a useful tool for translational research.

Objective evaluation, using computed tomography, of round window access for cochlear implantation.

OBJECTIVE: The aim of this study was to determine optimal radiological parameters for assessment of the round window approach in cochlear implantation surgery. MATERIALS AND METHODS: Patients undergoing cochlear implantation at the Department of Otolaryngology in Szczecin, between 2015 and 2022 inclusive, were eligible for the study. Radiological assessments were performed according to eight parameters (seven proposed in the literature) and visibility clinical assessments were made intra-operatively on a scale of 1 to 5 (1 - not visible, 5 - fully visible). Visibility assessments of the round window niche (RWN) and round window membrane (RWM) allowed the difference (RWN minus RWM) to be used as a clinical assessment of the size of the overhang over the round window. RESULTS: Computed tomography images of 57 ears from 52 patients were analyzed in terms of round window access. The study group included 26 females and 26 males, ranging in age from 1 year to 80 years, with a median age of 41 years. In clinical assessment, round window visibility was rated as 5, after removal of the bone overhang, in 69% of patients. Cochlear access through the round window was achieved in 39 (68%) cases, extended access through the round window in 13 (23%) cases and cochleostomy was performed in 5 (9%) cases. Statistically significant ordinal correlations with round-window access were found using one parameter from the literature (Chen_Angle) and from our proposal (RWM_prediction). From parameters describing the bone overhang of the round window, positive correlations (using Kendall rank tests) were found using parameters from the literature (Sarafraz_OH and Mehanna_OH). CONCLUSIONS: Radiological measurements describing access to the round window which determine the angle based on the anatomy of the posterior wall of the auditory canal and the position of the facial nerve were found to be of the highest value. CLINICAL RELEVANCE STATEMENT: In the future, the use of algorithms for computed tomography evaluation and robot-assisted surgery will require parameters for assessing round window access, for surgery planning and choice of electrode. The parameters proposed by various authors are summarized, allowing researchers to assess their usefulness in further clinical practice.

Peer-to-peer validation of Ki-67 scoring in a pathology quality circle as a tool to assess interobserver variability: are we better than we thought?

Ki-67, a nuclear protein expressed in all stages of cellular proliferation, is a valuable tool to assess tumor proliferation and has been linked to more aggressive tumor behavior. However, interlaboratory staining heterogeneity and inter-observer variability challenge its reproducibility. Round Robin tests are a suitable tool to standardize and harmonize immunohistochemical and molecular analyses in histopathology. The study investigates the interrater and interlaboratory reproducibility of Ki-67-scoring using both manual and automated approaches. Unstained TMA slides comprising diverse tumor types (breast cancer, neuroendocrine tumors, lymphomas, and head and neck squamous cell carcinoma) were distributed to six pathology laboratories, each employing their routine staining protocols. Manual and automated scoring methods were applied, and interrater and interlaboratory agreement assessed using intraclass correlation coefficients (ICC). The results highlight good-to-excellent reliability overall, with automated scoring demonstrating higher consistency (ICC 0.955) than manual scoring (ICC 0.871). Results were more variable when looking at the individual entities. Reliability remained good for lymphomas (ICC 0.878) and breast cancer (ICC 0.784) and was poor in well-differentiated neuroendocrine tumors (ICC 0.354). This study clearly advocates standardized practices and training to ensure consistency in Ki-67-assessment, and it demonstrates that this can be achieved in a peer-to-peer approach in local quality-circles.

Desmoplastic Small Round Cell Tumor as a Rare Cause of an Incarcerated Epigastric Linea Alba Hernia: A Case Report and Literature Review.

Desmoplastic small round cell tumor is a very rare soft tissue sarcoma with a bleak prognosis and short patient survival. The most common occurrence is in 20-30-year-old men. Our study presents the case report of a 40-year-old patient who was diagnosed with this sarcoma. The first symptom of the illness was an incarcerated epigastric hernia with sarcoma metastasis resembling an intestinal loop in an ultrasound image. The fluorescence in situ hybridization (FISH) method showed a fusion of the EWS and WT1 genes. Systemic palliative chemotherapy using the VDC-IE (vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide) regimen was chosen instead of further surgery due to the disease's generalization. However, the therapy failed to halt the disease progression and was thus terminated after 18 months. The patient's overall survival was 19 months. The rare character of this disease complicates the diagnostics in clinical practice. Nevertheless, rare sarcomas should be considered in patients with non-specific abdominal symptoms, including patients with incarcerated ventral hernia.

Practicality of multilayer round window reinforcement in the surgical management of superior semicircular canal dehiscence syndrome: a case report of long-term follow-up.

Several surgical techniques have been documented for approaching and repairing superior semicircular canal dehiscence syndrome (SCDS). These techniques encompass the trans-middle cranial fossa, transmastoid, endoscopic approaches, and round window reinforcement (RWR). RWR entails the placement of connective tissue with or without cartilage and around the round window niche, restricting the round window's movement to minimize the 3rd window effect and restore the bony labyrinth closer to its normal state. We employed the multilayer RWR technique, resulting in significant postoperative improvement and long-lasting effects for 3.7 years in 2 cases. Here, we present the clinical findings, surgical procedures, and the effectiveness of multilayer RWR. This technique can be the initial choice for surgical treatments of SCDS due to its high effectiveness, longer-lasting effect, and minimal risk of surgical complications.

Alike but genetically divergent: The resurrection of Urotrygon asterias (Jordan & Gilbert, 1883) from its closest relatives, the Munda and the Blotched stingray.

The genus Urotrygon comprises small- to medium-sized endemic round rays on the American continent and has undergone several synonymization processes. Here, we used an integrative taxonomic approach, including meristic, morphometric, and mtDNA analyses, to resolve the particularly intricate relationship among Urotrygon munda Gill, 1863, Urotrygon chilensis (Günther, 1872), and Urotrygon asterias (Jordan & Gilbert, 1883). The latter species is currently a synonym of U. munda but is also considered the U. chilensis "northern morphotype." These taxonomic entities have historically been confounded, mainly due to their phenotypical resemblance along their geographic distribution in the eastern Pacific. We assessed 78 specimens (43 "northern" and 30 "southern morphotypes" of U. chilensis, as well as 5 U. munda) using 19 external variables for taxonomic and morphometric analysis. Distinct meristic patterns, including pectoral and pelvic ceratotrichia, vertebrae number, and thorn distribution along the dorsal midline, were observed in the series-type specimens of the three taxonomic entities. Our multivariate morphometric analyses consistently differentiated the three groups as distinct taxonomic entities, with an overall classification accuracy of 66.7%. The meristic results also provided reliable information distinguishing the three entities. Based on the nicotinamide adenine dinucleotide (NADH2) and cytochrome oxidase subunit I (COI) genes, our phylogenetic analysis were consistent with the morphometric and meristic data, supporting these three entities as distinct species having their own evolutionary lineages. Our comprehensive approach confidently demonstrated that the northern U. chilensis morphotype matched and corresponded to the description of the Starry round ray, U. asterias, confirming its taxonomic resurrection as a valid species distinct from U. chilensis and U. munda. The geographic distribution of U. asterias spans from the tropical west coast of Mexico (including the Gulf of California) to Costa Rica, revealing that microevolutionary processes have well-defined population clades within this range. Furthermore, U. chilensis is unequivocally established as the sole Urotrygon species occurring south of the Guayaquil marine ecoregion. In addition, the public COI and NADH2 sequences available for Urotrygon hosted in the ad hoc online databases were found to be misidentified, emphasizing the need for rigorous taxonomic scrutiny in this group. Finally, our research underscores the significance of an integrative approach that combines morphometric, meristic, and molecular techniques with historical data to disentangle the complexities of closely related taxa.

A case of giant labia majora lipoma in an adult.

Lipomas are common benign adipose tissue tumors but are infrequently found in the labia majora, especially at a large size. We report a case of a giant lipoma of the labia majora in a 37-year-old woman diagnosed by imaging methods and successfully treated by surgery. This case highlights the importance of considering lipoma in the differential diagnosis of labial masses and underscores the role of imaging in diagnosis. They need to be differentiated from liposarcoma or omental herniation into Nuck's canal. It also demonstrates the effectiveness of surgical management for large lipomas in sensitive areas, with attention to both medical and aesthetic outcomes.

Case report: Metastatic refractory undifferentiated small round-cell sarcoma successfully treated with surufatinib and camrelizumab.

Background: Undifferentiated small round-cell sarcomas (uSRCSs) are a subgroup of sarcomas that are difficult to diagnose. Some uSRCSs have specific gene re-arrangements, but others do not. Currently, there is no specific treatments for advanced uSRCSs, and its treatment is largely based on general experience with sarcomas, which includes chemotherapy, targeted therapy, and immunotherapy. In this article, we report a patient with uSRCS who responded to treatment with anti-VEGF inhibitor surufatinib and anti-PD-1 inhibitor camrelizumab after progression on first-line chemotherapy, second-line anlotinib combined with immunotherapy, and third-line chemotherapy. Case description: In July 2020, a 37-year-old female patient was diagnosed with advanced uSRCS. Results for the Ewing sarcoma RNA binding protein 1 and Wilms tumor suppressor (EWSR1/WT1) fusion gene were negative. The patient was also negative with BCOR (BCL6 co-repressor) and CIC (capicua transcriptional repressor) fusion gene. The next-generation sequencing results revealed point mutations on Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB), Transcription Factor Binding To IGHM Enhancer 3 (TFE3), Mucin 16 (MUC16), and AXL (Axl, also called UFO, ARK, and Tyro7, is part of a family of receptor tyrosine kinases). The patient received 4 cycles of the Ifosfamide and epirubicin hydrochloride regimen, and her best objective response was stable disease. On November 3, 2020, a computed tomography (CT) scan revealed progressive disease (PD). Two cycles of camrelizumab (a programmed death-1 inhibitor) plus anlotinib (an anti- vascular endothelial growth factor drug) were administered, but PD was again observed. Thus, a regimen of gemcitabine plus docetaxel was adopted. Unfortunately, the disease progressed once again after two cycles of the treatment. On February 4, 2021, the patient began to receive targeted therapy with surufatinib combined with camrelizumab. A CT scan showed that the tumor achieved a partial response. As of April 2023, the patient had a progression-free survival time of 26 months. Conclusions: Surufatinib in combination with camrelizumab could be effective in the treatment of advanced uSRCSs.

Laparoscopic surgery for endometriosis of the round ligament: A case of a patient with right-sided inguinal pain.

Round ligament endometriosis is a rare phenomenon reported in approximately 0.3% to 0.6% of endometriosis cases. Presurgical diagnosis is carried out for about 50% of the cases. The association of the right-sided inguinal hernia, nonspecific pain in the organs, and no history of surgery or labor make the diagnosis intricate. We report a case of endometriosis of the round ligament in a 39-year-old woman who complained of intense pain in the right groin during the menstrual period for about 4 years, with no complaints of bulging or change in the size of the mentioned area. The clinical suspicion of inguinal endometriosis, supported by sonography and magnetic resonance imaging, was confirmed by histological examination of the surgical specimen after laparoscopic surgery, which included the mass and the extraperitoneal segment of the round ligament. After surgery, the patient's pain disappeared completely. The round ligament endometriosis or endometriosis of the inguinal region could be considered an important differential diagnosis in women of reproductive age without a history of surgery who presented with inguinal region pain during menstruation but no clear mass was palpable in the physical exam.

Laparoscopic cholecystectomy for a gallbladder with a right sided round ligament using indocyanine green fluorescence imaging: A case report.

INTRODUCTION: The gallbladder with a right sided round ligament is a rare anomaly. It is frequently associated with various biliary, vascular, and other anomalies. Herein, we present a case of a gallbladder with a right-sided round ligament treated with laparoscopic cholecystectomy using indocyanine green fluorescence imaging. PRESENTATION OF CASE: A 50-year-old woman had right upper quadrant discomfort. Gallbladder stones, a polyp, and a right-sided round ligament were found on preoperative computed tomography. Laparoscopic cholecystectomy with indocyanine green fluorescence imaging was decided. During surgery, "fundus first technique" was performed and the biliary anatomy was confirmed with the aid of indocyanine green fluorescence guidance. The gallbladder was attached to segment 4 of the liver which was the left side of the round ligament. Cystic artery and cystic duct were ligated safely. The patient had no postoperative complication. DISCUSSION: Although there are various anomalies in patients having a gallbladder with a rights-sided round ligament, ICG fluorescence imaging can show the anatomy of the extrahepatic biliary tree. It can enable surgeons to recognize concomitant vascular and biliary anomalies. CONCLUSION: Laparoscopic cholecystectomy for gallbladder with a right-sided round ligament can be safely performed by identifying biliary anatomy with indocyanine green fluorescence imaging.

Heat stress induced piRNA alterations in pachytene spermatocytes and round spermatids.

BACKGROUND: Spermatogenesis is a temperature-sensitive process, and elevation in temperature hampers this process quickly and significantly. We studied the molecular effects of testicular heating on piRNAs and gene expression in rat testicular germ cells. METHODS: We generated a cryptorchid rat model by displacing the testis from the scrotal sac (34 °C) to the abdominal area (37 °C) and sacrificed animals after 1 day, 3 days, and 5 days. Pachytene spermatocytes and round spermatids were purified using elutriation centrifugation and percoll gradient methods. We performed transcriptome sequencing in pachytene spermatocytes and round spermatids to identify differentially expressed piRNAs and their probable targets, i.e., TE transcripts and mRNAs. RESULTS: As a result of heat stress, we observed significant upregulation of piRNAs and TE transcripts in testicular germ cells. In addition to this, piRNA biogenesis machinery and heat shock proteins (Hsp70 and Hsp90 family members) were upregulated. mRNAs have also been proposed as targets for piRNAs; therefore, we shortlisted certain piRNA-mRNA pairs with an inverse relationship of expression. We observed that in testicular heat stress, the heat shock proteins go hand-in-hand with the upregulation of piRNA biogenesis machinery. The dysregulation of piRNAs in heat-stressed germ cells, increased ping-pong activity, and disturbed expression of piRNA target transcripts suggest a connection between piRNAs, mRNAs, and TE transcripts. CONCLUSIONS: In heat stress, piRNAs, piRNA machinery, and heat shock proteins are activated to deal with low levels of stress, which is followed by a rescue approach in prolonged stressaccompained by high TE activity to allow genetic mutations, perhaps for survival and adaptability.

Undifferentiated Round Cell Sarcoma With CRTC1::SS18 Fusion: Expanding Clinicopathologic Features of a Rare Translocation Sarcoma With Prominent Desmoplastic Stroma.

Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS-non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range, 12-42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round-to-epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor. Immunohistochemical results were nonspecific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exons 1 to 2 of CRTC1 (the 5' partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3' partner gene) on chromosome 18. The clinical course was variable. Although 1 previously reported case demonstrated aggressive behavior with a fatal outcome, 2 others had a relatively indolent course with gradual growth for 6 to 7 years prior to resection. Two cases developed metastatic disease, including 1 case with bilateral lung metastasis and 1 with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aimed to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.

Metagenomic analysis of core differential microbes between traditional starter and Round-Koji-mechanical starter of Chi-flavor Baijiu.

Xiaoqu starter serves as the saccharifying and fermenting agent in the production of Cantonese soybean-flavor (Chi-flavor) Baijiu, and the complex microbial communities determine the flavor and quality of the product. Round-Koji-mechanical starter (produced by using an automated starter-making disk machine) is advantageous as it decreases operator influence, labor costs, and fermentation time, but the product quality is lower compared to traditional starter. Thus, two types of starters (traditional and Round-Koji-mechanical starter) from a Cantonese Baijiu factory were compared in a metagenomic analysis to investigate the differences in microbial community composition and core microbes. The results showed that several core microbes related to carbohydrate metabolism, amino acid metabolism and lipid metabolism, were differentially enriched in the traditional starter. Mucor lusitanicus and Rhizopus delemar were significantly positively correlated with the three key metabolic pathways. Saccharomyces cerevisiae, Cyberlindnera fabianii, Kluyveromyces marxianus, Lactobacillus fermentum, Mucor ambiguous, Rhizopus microspores, Rhizopus azygosporus, Mucor circinelloides, and Ascoidea rubescens were significantly positively correlated with two of the three key metabolic pathways. The results of this study provide a basis for understanding the differential core microbes in traditional and Round-Koji-mechanical starters of Chi-flavor Baijiu, and they also provide guidance for improving Round-Koji-mechanical starter.

CD34-Negative Malignant Renal Solitary Fibrous Tumor: Case Report and Diagnostic Insights.

Solitary fibrous tumors (SFTs) are rare fibroblastic neoplasms with diverse biological behaviors and widespread distribution. Primary renal SFTs are uncommon, and their malignant variants, especially those that are CD34 negative, are even rarer. This study presents a case of malignant renal SFT in a 57-year-old female, focusing on its immunomorphological features. On gross examination, the tumor's large size (11.5 cm) was remarkable. Microscopic analysis showed high cellularity, diffuse sheets of moderately pleomorphic ovoid cells, prominent staghorn vessels, tumor cell necrosis, and a high mitotic count. Immunohistochemistry revealed strong positivity for STAT6, vimentin, and Bcl-2 and, notably, negativity for CD34. The presence of the NAB2::STAT6 gene fusion was confirmed through fluorescence in situ hybridization. This case emphasizes the need to consider SFT in the differential diagnosis of unusual renal tumors, even when CD34 is negative. The infrequency, morphological diversity, and resemblance to other tumors make diagnosing renal SFTs challenging. Accurate identification and classification as benign or malignant are crucial for proper clinical management and prognosis.

Magnetic/Acoustic Dual-Controlled Microrobot Overcoming Oto-Biological Barrier for On-Demand Multidrug Delivery against Hearing Loss.

Multidrug combination therapy in the inner ear faces diverse challenges due to the distinct physicochemical properties of drugs and the difficulties of overcoming the oto-biologic barrier. Although nanomedicine platforms offer potential solutions to multidrug delivery, the access of drugs to the inner ear remains limited. Micro/nanomachines, capable of delivering cargo actively, are promising tools for overcoming bio-barriers. Herein, a novel microrobot-based strategy to penetrate the round window membrane (RWM) is presented and multidrug in on-demand manner is delivered. The tube-type microrobot (TTMR) is constructed using the template-assisted layer-by-layer (LbL) assembly of chitosan/ferroferric oxide/silicon dioxide (CS/Fe3O4/SiO2) and loaded with anti-ototoxic drugs (curcumin, CUR and tanshinone IIA, TSA) and perfluorohexane (PFH). Fe3O4 provides magnetic actuation, while PFH ensures acoustic propulsion. Upon ultrasound stimulation, the vaporization of PFH enables a microshotgun-like behavior, propelling the drugs through barriers and driving them into the inner ear. Notably, the proportion of drugs entering the inner ear can be precisely controlled by varying the feeding ratios. Furthermore, in vivo studies demonstrate that the drug-loaded microrobot exhibits superior protective effects and excellent biosafety toward cisplatin (CDDP)-induced hearing loss. Overall, the microrobot-based strategy provides a promising direction for on-demand multidrug delivery for ear diseases.