Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To analyze the diagnosis, treatment and clinical characteristics of a patient with parotid gland metastasis of clear cell renal cell carcinoma(ccRCC)following radical nephrectomy. Methods The clinical data and diagnostic/therapeutic course of the patient were reported, and the metastasis time and treatment methods of patients with parotid metastasis of renal cancer were summarized in combination with literature. Results The 63-year-old male patient sought medical help due to a mass behind the right ear persisting for 3 months. He had undergone a right radical nephrectomy for a renal tumor 10 years ago. Preoperative computed tomography(CT)with contrast of the parotid region revealed an approximately 2.5 cm×2.1 cm round soft-tissue density lesion in the right parotid gland with slightly irregular margins. Positron emission tomography/computed tomography(PET/CT)showed an enlarged left kidney with an irregular shape and multiple round, slightly hyperdense lesion(SUVmax=7.2), suggestive of malignancy. A round, slightly hyperdense lesion(diameter 2.6 cm, SUVmax=4.2)with well-defined borders and increased radiotracer uptake was noted in the right parotid gland, indicating a hypermetabolic mass where malignancy could not be excluded. The patient subsequently underwent partial parotidectomy, advancement flap transplantation, and facial nerve dissection. Postoperative pathology revealed tumor cells with clear/eosinophilic cytoplasm and nuclear atypia, exhibiting ill-defined borders with salivary gland tissue. Immunohistochemistry was positive for PAX-8, CAⅨ, and Ki-67. During the 12-month follow-up, the patient was in good condition with no evidence of tumor recurrence or metastasis. Conclusion Parotid gland metastasis following radical nephrectomy is exceedingly rare, with no specific imaging features and clinical manifestations, and definitive diagnosis relies on pathological examination. Currently, there is no standardized treatment protocol, but complete surgical excision remains the primary therapeutic option.

Objective To initially explore the possibility of applying the fluorescence micro-optical sectioning tomography(fMOST)high-resolution 3D reconstruction system to the morphological study of the intestinal nervous system and to preliminarily establish a method for studying the morphology of the intestinal nervous system using this system.Methods fMOST high-resolution 3D reconstruction system was used to study the intestinal nervous system of C57BL/6 mice in detail.Based on this method,a new morphological method of the visceral nervous system of small animal models was explored at the single-cell level.Results Compared with the large intestine,the small intestine lacked the typical myenteric plexus(Auerbach),deep mucosal plexus(Henley),and submucosal superficial plexus(Meissner).Conclusion The result of this paper provide a clearer and systematic display of the anatomical structure of the enteric nervous system in C57BL/6 mice,and further clarify the similarities and differences between the enteric nervous system of mice and human,and provide a theoretical basis for its rational application in the study of digestive system diseases.The morphological study of fMOST high-resolution 3D reconstruction system is not limited to the central nervous system,but can be extended to the morphological study of multiple visceral nervous systems.

Objective To explore the indication, surgical technique, and clinical efficacy of the cross bar based on the Nuss procedure in pectus excavatum. Methods The clinical data of patients who underwent cross bar based on the Nuss procedure from August 2023 to August 2024 in Guangdong Provincial People's Hospital were retrospectively analyzed. Results A total of 88 patients including 85 males and 3 females with a mean age of (17.56±5.20) years were enrolled. All operations were performed successfully without intraoperative cardiac injury, pericardial injury or diaphragmatic injury. The mean operation time was (147.65±47.75) min. The mean blood loss was (13.30±9.06) mL. The mean postoperative hospitalization stay was (4.81±1.55) days, without perioperative death. Six (6.82%) patients developed early postoperative complications, including 3 patients of pleural effusion, 1 patient of subcutaneous hematoma, 1 patient of suffocation and 1 patient of bar rotation. The postoperative outcomes were excellent in 71 (80.68%) patients, good in 16 (18.18%) patients and moderate in 1 (1.13%) patient. The excellent and good rate was 98.86%. Conclusion The cross bar technique is safe and convenient, with satisfactory results. It is worth promoting in clinical application.

Imaging examination is a crucial part in diagnosis and treatment of central nervous system infection(CNSI),involving complex imaging sequences and parameters.This consensus was jointly written by multiple CNSI imaging experts in China,aimed to standardize imaging examination of CNSI.

Objective To investigate the efficacy and safety of Linggui Qihua No.2 Prescription(LGQH2)in patients with heart failure with preserved ejection fraction(HFpEF).Methods Totally 60 HFpEF patients were randomly divided into experimental group and control group according to random number table method,with 30 patients in each group.On the basis of standardized treatment for heart failure,the experimental group was given LGQH2 granules,13 g/time,twice a day,orally;the control group was given placebo granules of LGQH2,with the same administration method as the experimental group.The treatment course for both groups was 4 weeks.6-minute walking distance(6MWD),Kansas City Cardiomyopathy Questionnaire(KCCQ)score,TCM syndrome score and serum NT-proBNP levels.Echocardiography was used to detect the ratio of early diastolic blood flow velocity(E)at the mitral valve to early diastolic myocardial motion velocity(e')at the mitral annulus,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD)and interventricular septal thickness(IVST).Adverse reactions and events were also recorded.Results Compared with before treatment,both groups showed significant improvement in 6MWD,KCCQ score,TCM syndrome score,serum NT proBNP,and E/e'after treatment(P<0.05),and there was no statistical significance in LAD,LVEDD and IVST between the two groups(P>0.05);after treatment,the experimental group showed better improvement in 6MWD,KCCQ score,TCM syndrome score and E/e'compared to the control group(P<0.05).During the research process,neither group of patients experienced any adverse reactions or events.Conclusion LGQH2 Prescription can effectively enhance exercise tolerance and cardiac function of HFpEF patients,alleviate symptoms,improve quality of life,and inhibit diastolic dysfunction of the heart,without notable adverse reactions.

This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

Objective:To analyze the clinical characteristics and treatment of eosinophilic angiocentric fibrosis (EAF) involving the orbit.Methods:We described a case and review the literature of EAF involving the orbit.Results:The literature review has shown 34 similar cases. Nineteen patients combined with other site involvement (17 cases had nasal involvement), whereas 15 had primary orbital involvement. Ocular swelling (18 cases) and epiphora (4 cases) were the most common initial presenting symptoms. The typical histopathologic findings include a perivascular, eosinophil-rich infiltrate and a "onion-skin" type of fibrosis concentrated around small vessels and all cases in this group conformed the above typical characteristics. In this series, 20 patients provided immunohistochemical results for IgG4, among them, 16 cases were positive while 4 cases were negative. No manifestations of obliterative phlebitis and storiform fibrosis were observed. The age, gender, and lesion locations (single or multiple) of the IgG4 staining positive group and the negative group were analyzed. There was no statistically significant difference in the age of onset, gender ratio and lesion the two groups ( P>0.05). Conclusion:For patients presented with ocular swelling, epiphora, with or without nasal lesions, EAF should be considered. The diagnosis of EAF is based largely on histopathologic findings. Although some cases were positive for IgG4 by immunohistochemistry, storiform fibrosis and obliterative phlebitis is not seen in our series, which aid in distinguishing EAF from IgG4-related disease.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.