Objective:To explore the clinical manifestations, diagnosis, treatment, pathological types and prognosis of primary cervical neuroblastoma in children. Methods:The clinical data of 11 children with primary cervical neuroblastoma admitted to the Department of Otolaryngology and Head and Neck Surgery at Shanghai Children's Hospital from April 2015 to April 2022 were retrospectively analyzed. The clinical characteristics, imaging findings, pathological types, treatment methods, and outcomes of these 11 patients were examined in conjunction with a review of the literature. Results:The cohort of 11 neuroblastoma patients ranged in age from 28 days to 88 months （median age: 24 months）, including 3 males and 8 females. Among the 11 patients, 4 had tumors located in the carotid sheath area, 4 in the cervical space, and 3 in the parapharyngeal and retropharyngeal spaces. The clinical manifestations primarily included painless cervical masses and laryngeal stridor. There were 3 cases of primary cervical tumors with cervical lymph node metastasis and 1 case with bone marrow metastasis. Pathological findings revealed neuroblastoma in 8 cases and ganglionic neuroblastoma in 3 cases. In this group, 7 patients underwent surgery combined with chemotherapy, 2 patients received surgery combined with chemoradiotherapy, and 2 patients underwent surgery alone. Surgical resection was performed via a cervical approach in 7 cases, while 3 cases were treated using a transoral endoscopic approach. Additionally, one patient underwent a transoral endoscopic approach initially and a cervical approach subsequently. All patients completed their treatment and were followed up regularly, with follow-up durations ranging from 6 to 79 months （median: 34 months）. Nine patients achieved complete remission, 2 patients achieved partial remission, and none experienced disease progression. Conclusion:Primary cervical neuroblastoma exhibits a high degree of heterogeneity and presents at a younger age, primarily with cervical masses. Compared to external approaches, endoscopy-assisted transoral resection of parapharyngeal tumors offers advantages such as reduced damage to surrounding tissue and no visible neck scars, providing a new method for clinical treatment. Regular follow-up is essential for children with neuroblastoma, along with the establishment of specific disease management protocols and comprehensive care to improve survival quality.
Humans ; Female ; Male ; Neuroblastoma/surgery* ; Child, Preschool ; Infant ; Retrospective Studies ; Child ; Head and Neck Neoplasms/pathology* ; Prognosis

By various chromatographic techniques and extensive spectroscopic methods, 17 abietane diterpenoids were isolated from the dichloromethane fraction of the 95% ethanol cold-soak extracts of the seeds of Pseudolarix amabilis, namely pseudoamaol A(1), 12α-hydroxyabietic acid(2), 12-methoxy-7,13-abietadien-18-oic acid(3), 13-hydroxy-8,11,13-podocarpatrien-18-oic acid(4), 15-hydroxy-7,13-abietadien-12-on-18-oic acid(5), 8(14)-podocarpen-13-on-18-oic acid(6), holophyllin K(7), metaglyptin B(8), 7α-hydroxydehydroabietinsaure-methylester(9), 7-oxodehydroabietic acid(10), 15-hydroxy-7-oxodehydroabietinsaure-methy-lester(11), 15-methoxydidehydroabietic acid(12), 7-oxo-15-hydroxy-dehydroabietic acid(13), 15-hydroxydehydroabietic acid(14), 8,11,13-abietatriene-15,18-diol(15), 8,11,13-abietatriene-15-hydroxy-18-succinic acid(16), and 7β-hydroxydehydroabie-tic acid(17). Compound 1 was a new compound. The isolated compounds were evaluated for their antitumor activities(HepG2, SH-SY5Y, K562), and compounds 8 and 17 showed potential cytotoxic activity against K562 cells, with IC_(50) values of 26.77 and 37.35 μmol·L~(-1), respectively.
Humans ; Molecular Structure ; Neuroblastoma ; Diterpenes/chemistry* ; Antineoplastic Agents

To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.
Humans ; Rhododendron/chemistry* ; Neuroblastoma ; Oxidative Stress ; Magnetic Resonance Spectroscopy ; Stereoisomerism ; Molecular Structure

Humans ; Tumor-Associated Macrophages/pathology* ; Neuroblastoma/pathology*

OBJECTIVES: To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB). METHODS: A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed. RESULTS: Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05). CONCLUSIONS Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.
Child, Preschool ; Female ; Humans ; Male ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bone Marrow Neoplasms/drug therapy* ; China ; Combined Modality Therapy ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Neuroblastoma/pathology* ; Prognosis ; Retrospective Studies ; Stem Cell Transplantation ; Transplantation, Autologous

INTRODUCTION: In Europe and North America, the majority of children with high-risk neuroblastoma survive the disease. Elsewhere, the treatment outcomes are poor. METHODS: A retrospective review of children treated for high-risk neuroblastoma in a single institution in Singapore from 2007 to 2019 was carried out. Treatment consisted of intensive chemotherapy, surgery aimed at gross total resection of residual disease after chemotherapy, consolidation with high-dose therapy followed by autologous stem cell rescue, and radiotherapy to the primary and metastatic sites followed by maintenance treatment with either cis-retinoic acid or anti-disialoganglioside monoclonal antibody therapy. Survival data were examined on certain clinical and laboratory factors. RESULTS: There were 57 children (32 male) treated for high-risk neuroblastoma. Their mean age was 3.9 (range 0.7-14.9) years. The median follow-up time was 5.5 (range 1.8-13.0) years for the surviving patients. There were 31 survivors, with 27 patients surviving in first remission, and the five-year overall survival and event-free survival rates were 52.5% and 47.4%, respectively. On log-rank testing, only the group of 17 patients who were exclusively treated at our centre had a survival advantage. Their five-year overall survival rate compared to patients whose initial chemotherapy was done elsewhere was 81.6% versus 41.1% (P = 0.011), and that of event-free survival was 69.7% versus 36.1% (P = 0.032). Published treatment results were obtained from four countries in Southeast Asia with five-year overall survival rates from 13.5% to 28.2%. CONCLUSION Intensified medical and surgical treatment for high-risk neuroblastoma proved to be effective, with superior survival rates compared to previous data from Southeast Asia.
Child ; Humans ; Male ; Infant ; Child, Preschool ; Adolescent ; Disease-Free Survival ; Neuroblastoma/pathology* ; Hematopoietic Stem Cell Transplantation/methods* ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Asia, Southeastern/epidemiology* ; Combined Modality Therapy

Five undescribed sesquiterpenoids (1-5), and nine known sesquiterpenoids (6-14) were obtained from the fruits of Litsea lancilimba Merr. by LC-MS/MS molecular networking strategies. Litsemene A (1) possessed a unique 8-member ring through unexpected cyclization of the methyl group on C-10 of guaiane. Their structures were elucidated by spectroscopic techniques including IR, UV, NMR, HR-ESI-MS, and their absolute configurations were assigned by ECD calculations. All isolated sesquiterpenoids were analyzed by bioinformatics and evaluated for their neuroprotective effects against H₂O₂-induced injury in human neuroblastoma SH-SY5Y cells.
Chromatography, Liquid ; Humans ; Hydrogen Peroxide/toxicity* ; Litsea ; Molecular Structure ; Neuroblastoma/drug therapy* ; Neuroprotective Agents/pharmacology* ; Sesquiterpenes/chemistry* ; Tandem Mass Spectrometry

Objective: To investigate the expression of Ki-67 and CD34 in the differential diagnosis of ductal carcinoma in situ (DCIS) and DCIS-like invasive breast cancer (DLIBC). Methods: A total of 100 cases of DCIS and 150 cases of DLIBC diagnosed pathologically in Yantai Yuhuangding Hospital from January 2019 to March 2022 were collected. The expression of p63, CK5/6, Ki-67 and CD34 in both groups were detected by immunohistochemical (IHC) staining and evaluated. Results: The 100 cases of DCIS included 11 cases of low-grade DCIS, 28 cases of intermediate-grade DCIS and 61 cases of high-grade DCIS. IHC staining of p63 and CK5/6 showed the myoepithelial cells around cancerous duct were complete or partial absence. Ki-67 expression showed two patterns: high expression in the basal layers and scattered expression within the tumor. Most cases showed mainly high basal expression (77/100, 77%), and the proportion of this pattern was significantly different between low grade and high grade DCIS (P<0.05). All cases showed complete CD34 expression surrounding the cancerous duct with different proportion (vascular necklace) suggested small vessels proliferation. The 150 cases of DLIBC included 142 cases of invasive ductal carcinoma (IDC) (three cases of basal-like breast cancer was included), two cases of secretory carcinoma, three cases of solid papillary carcinoma, two cases of adenoid cystic carcinoma and one case of acinar cell carcinoma. Among 142 cases of IDC, 13 cases were grade Ⅰ, 77 were grade Ⅱ and 52 were grade Ⅲ. IHC staining of p63 showed complete absence of myoepithelium. CK5/6 was negative in most cases and only positively expressed within the tumor in 3 cases of basal-like breast cancer. Ki-67 indicated a scattered expression pattern within the tumor. In most cases, CD34 immunostaining showed scattered positive blood vessels within the tumor while only two cases showed incomplete expression of CD34 around the tumor (2/150, 1.3%). The different expression patterns of Ki-67 and CD34 in DCIS and DLIBC was statistically significant (P<0.05). Conclusions: The different expression patterns of Ki-67 and CD34 are helpful to distinguish DLIBC from DCIS. The appearance of "vascular necklace" with CD34 and the high expression of Ki-67 around the cancerous duct highly support the diagnosis of DCIS, and the scattered expression pattern of CD34 supports DLIBC.
Antigens, CD34 ; Breast Neoplasms/pathology* ; Carcinoma, Ductal, Breast/pathology* ; Carcinoma, Intraductal, Noninfiltrating/pathology* ; Cell Adhesion Molecules ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Neuroblastoma

OBJECTIVE: To investigate the role of long non-coding RNA ZEB1-AS1 in cerebral ischemia/reperfusion injury (CI/RI). METHODS: We detected the temporal changes of ZEB1-AS1 and HMGB1 expression using qPCR and Western blotting in SD rats following CI/RI induced by middle cerebral artery occlusion (MCAO). The rat models of CI/RI were subjected to injections of vectors for ZEB1-AS1 overexpression or knockdown into the lateral ventricle, and the changes in cognitive function, brain water content, blood-brain barrier integrity, and IL-1β and TNF-α levels in the cerebrospinal fluid (CSF) and serum were observed. Neuronal loss and cell apoptosis in the cortex of the rat models were detected by FJC and TUNEL methods, and HMGB1 and TLR-4 expressions were analyzed with Western blotting. We also examined the effects of ZEB1-AS1 knockdown on apoptosis and expressions of HMGB1 and TLR-4 in SH-SY5Y cells with oxygen-glucose deprivation/reoxygenation (OGD/R). RESULTS: In CI/RI rats, the expressions of ZEB1-AS1 and HMGB1 in the brain tissue increased progressively with the extension of reperfusion time, reaching the peak levels at 24 h followed by a gradual decline. ZEB1-AS1 overexpression significantly aggravated icognitive impairment and increased brain water content, albumin content in the CSF, and IL-1β and TNF-α levels in the CSF and serum in CI/RI rats (P < 0.05), while ZEB1-AS1 knockdown produced the opposite effects (P < 0.05 or 0.01). ZEB1-AS1 overexpression obviously increased the number of FJC-positive neurons in the cortex and enhanced the expressions of HMGB1 and TLR-4 in the rat models (P < 0.01); ZEB1-AS1 knockdown significantly reduced the number of FJC-positive neurons and lowered HMGB1 and TLR-4 expressions (P < 0.01). In SH-SY5Y cells with OGD/R, ZEB1-AS1 knockdown significantly suppressed cell apoptosis and lowered the expressions of HMGB1 and TLR-4 (P < 0.01). CONCLUSION ZEB1-AS1 overexpression aggravates CI/RI in rats through the HMGB1/TLR-4 signaling axis.
Animals ; Cell Line, Tumor ; Cell Proliferation/genetics* ; HMGB1 Protein/metabolism* ; Humans ; Infarction, Middle Cerebral Artery ; Neuroblastoma ; RNA, Long Noncoding/metabolism* ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha ; Water

Arrhythmias, Cardiac ; Genetic Diseases, X-Linked/genetics* ; Gigantism/genetics* ; Heart Defects, Congenital/genetics* ; Humans ; Intellectual Disability/genetics* ; Male ; Neuroblastoma