This article reports a 14-year-old boy who presented with "a nearly 7-year history of a right upper arm mass and a more than 1-year history of cervical lymphadenopathy". His main clinical manifestations included a subcutaneous mass in the right upper arm, bilateral eyelid and submandibular masses, and multiple enlarged cervical lymph nodes, accompanied by persistent peripheral blood eosinophilia. Biopsies of the right upper arm lesion and a left submandibular lymph node showed lymphoid hyperplasia with prominent eosinophilic infiltration, vascular and fibrous tissue proliferation, and eosinophilic microabscess formation in the left submandibular lymph node, confirming the diagnosis of Kimura′s disease. The lesions regressed markedly after glucocorticoid therapy but recurred after treatment discontinuation. Because the patient and his family were concerned about long-term glucocorticoid therapy, mepolizumab was subsequently administered. Peripheral eosinophil counts normalized, whereas the local tissue lesions showed limited improvement. A multidisciplinary team comprehensively evaluated the diagnosis, the need for repeat biopsy of atypical lymph nodes on imaging, the possible association between the cardiac valve abnormalities and the underlying disease, and subsequent treatment options. The patient is currently receiving methotrexate with folic acid supplementation and remains under regular follow-up. This case indicates that the diagnosis of Kimura′s disease relies on clinical manifestations and histopathological findings. Once diagnosed, comprehensive evaluation, individualized treatment, and long-term management should be implemented.

Atherosclerosis, a chronic inflammatory disease, is markedly influenced by both immune and inflammatory reactions throughout its progression. Dendritic cells, as pivotal antigen-presenting entities, play a crucial role in the initiation of immune responses and the preservation of immunological homeostasis. Accumulating data indicates that dendritic cells are present in healthy arteries and accumulate significantly in atherosclerotic plaques. Novel immunotherapeutic approaches and vaccination protocols have yielded substantial clinical advancements in managing chronic inflammatory diseases, with dendritic cell-centric modalities emerging for atherosclerotic management. In this review, we delineate the essential functions and underlying mechanisms of dendritic cells and their subsets in the modulation of atherosclerotic inflammation and immune responses. We underscore the immense promise of dendritic cell-based immunotherapeutic strategies, including vaccines and innovative combinations with nanotechnological drug delivery platforms for atherosclerosis treatment. We also discuss the challenges associated with dendritic cell immunotherapy and provide perspectives on the future direction of this field.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

This article explores the technological innovations and clinical prospects of robot-assisted hiatal hernia repair (RAHHR). RAHHR demonstrates outstanding performance in hiatal hernia repair, particularly for complex hernias, owing to its advantages such as 3D visualization and 7-degree-of-freedom robotic arms, which contribute to reduced recurrence rates and accelerated recovery. However, challenges remain, including high costs and limited operative space. Future directions include the development of single-port robotic systems, force feedback technology, and AI-powered surgical navigation. Standardized training and technological innovations are expected to promote its widespread application.

Objective:To investigate the clinical features of patients with congenital atresia of the oval window (CAOW).Methods:A retrospective analysis was conducted on 7 cases (8 ears) of surgically confirmed CAOW treated at our department from July 2018 to July 2024. Among the cases, 1 patient had bilateral CAOW, and 4 patients had unilateral CAOW combined with other types of ossicular chain malformations in the contralateral ear. We collected and analyzed the clinical data, audiological features, and temporal bone HRCT results of all patients.Results:The 7 patients were diagnosed at ages ranging from 8 to 19 years, with a mean age of (13.2±6.9) years. None of the patients exhibited significant auricular deformities. All presented with conductive hearing loss or mixed hearing loss predominantly of the conductive type, with an intact tympanic membrane. The diagnosis of CAOW was confirmed via endoscopic tympanotomy, revealing a concave oval window area on the medial wall of the tympanic cavity, sealed by a bony plate. All 8 ears exhibited additional ossicular chain deformities. Stapes absence was present in all 8 ears. Partial absence of the incus long process was observed in 3 ears, while, abnormal bony connections between the incus long process and the promontory were seen in 4 ears, 1 ear had a short malleolar handle, 1 ear had a smaller than normal malleus volume. In addition, facial nerve deformities were found in 6 ears, with 4 ears showing bifurcation of the facial nerve and 2 ears showing facial nerve obscuration of the oval window. Pure-tone audiometry revealed that 62.5% (5/8 ears) of patients had air conduction (AC) thresholds≥60 dB preoperatively, with a mean pure-tone average (PTA) of (69.0±11.8) dB HL and a mean air-bone gap (ABG) of (52.0±7.0) dB. The mean AC threshold and ABG were higher in the low-frequency (125-1 000 Hz) range compared to the high-frequency (2 000-8 000 Hz) range (both P<0.05). Preoperative HRCT showed abnormalities in all patients, with 7 ears being diagnosable as CAOW. Although the remaining 1 ear could not be diagnosed as CAOW, stapes and incus long process absence were detected. Conclusion:CAOW is rare in clinical, as the patients with non-progressive conductive hearing loss (AC≥60 dB, ABG≥50 dB) since childhood, intact tympanic membrane without malformations of auricle and external auditory canal, and thick bony plate covered the oval window of the HRCT imaging, CAOW should be highly suspected, which could be confirmed by the exploratory tympanotomy.

Objective:To investigate the long-term outcomes of using 3D-printed preformed titanium meshes in repair and reconstruction of orbital region.Methods:A retrospective analysis was conducted on patients with tumors invading the naso-orbito-maxillary region who underwent surgical resection and repair/reconstruction with 3D-printed preformed titanium meshes. The patients were collected at three medical centers (the Third Affiliated Hospital of Sun Yat-sen University, Xijing Hospital of Air Force Military Medical University, and Shenzhen Longgang District Ear, Nose and Throat Hospital) from 2016 to 2023. Tumor extent was evaluated radiologically, and the surgical approaches, reconstruction outcomes, surgical complications, and long-term follow-up results were analyzed.Results:A total of 46 patients from the three centers were included in this study, comprising 27 males and 19 females, with an average age of 51 years (range: from 13 to 86 years). Among them, 4 patients had benign tumors, while the remaining 42 had malignant tumors. The median follow-up duration was 60.7 months (range: from 19.0 to 75.0 months). Postoperatively, symmetrical globe position was achieved in 38 cases without significant diplopia; 4 cases exhibited enophthalmos without diplopia, and 4 cases had enophthalmos with diplopia. Twelve patients received preoperative radiotherapy, and 30 patients received postoperative radiotherapy. Six patients developed enophthalmos, and 6 experienced titanium mesh exposure after radiotherapy. Following treatment completion, 3 patients underwent repair using frontal flaps, 1 using a superficial temporal artery island flap, and 2 using free flaps. All remaining patients showed no postoperative infections, and their wounds healed normally.Conclusion:The application of 3D-printed preformed titanium mesh enables precise repair of postoperative defects in patients with naso-orbital tumors, facilitating reliable reconstruction of the orbital and facial contours with straightforward operation and dependable outcomes.

Objective To investigate the effect of bone metastasis on the efficacy of immune check-point inhibitors(ICI)in treatment of advanced non-small cell lung cancer(NSCLC).Methods A retro-spective analysis was conducted in 248 patients with advanced NSCLC who received ICI therapy.The patients were divided into bone metastasis group(110 cases)and non-bone metastasis group(138 ca-ses)based on the presence of bone metastasis.Clinical characteristics,objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.The correlations of factors such as bone metastasis with the survival prognosis of NSCLC patients were analyzed using the Cox proportional hazards regression mod-el.A total of 60 treatment-naive NSCLC patients with bone metastasis were selected from research ob-jects,with 30 patients receiving ICI combined with conventional chemotherapy(combination group)and 30 patients receiving conventional chemotherapy alone(chemotherapy group).The therapeutic effects and incidence of treatment emergent adverse events(TEAE)were compared between the two groups.Results There were no statistically significant differences in ORR and DCR between the bone metastasis and non-bone metastasis groups(P＞0.05).The PFS of the bone metastasis group(5.53 months)was shorter than that of the non-bone metastasis group(7.72 months)(x2=3.674,P=0.045).However,there was no statistically significant difference in OS between the bone me-tastasis group and the non-bone metastasis group(16.98 versus 17.56 months,x2=1.333,P=0.248).Multivariate Cox regression analysis showed that bone metastasis was an independent prog-nostic factor for PFS in NSCLC patients(HR=1.52,95％CI,1.10 to 1.98,P=0.003),but not a prognostic factor for OS(P＞0.05).The ORR and DCR in the combination group were 43.33％and 93.33％,respectively,which were higher than 26.67％and 76.67％in the chemotherapy group(P＜0.05).The PFS in the combination group was longer than that in the chemotherapy group(x2=4.023,P=0.036).However,there was no statistically significant difference in OS be-tween the two groups(x2=1.235,P=0.267).There were no statistically significant differences in the overall incidence of TEAEs or the incidence of≥grade 3 TEAE between the two groups(P＞0.05).Conclusion Although the occurrence of bone metastasis has an adverse effect on the effica-cy of ICI therapy in advanced NSCLC,patients with bone metastasis can still achieve better thera-peutic effects through ICI combined with chemotherapy compared with chemotherapy alone.