Objective:To investigate the clinical characteristics and prognostic factors of extracranial malignant rhabdoid tumors (eMRTs) in children.Methods:In this retrospective case series study, a retrospective analysis was conducted on clinical data of 21 eMRT patients admitted to Children′s Hospital of Nanjing Medical University from April 2018 to January 2023 and followed up until October 30, 2023.Patients were grouped according to their gender, age, tumor origin site, clinical staging, initial lactate dehydrogenase (LDH) level, extent of tumor resection, chemotherapy regimen, and radiotherapy.The Kaplan-Meier method was used to calculate the 2-year progression-free survival rate (PFS) and overall survival rate (OS) of the patients, and the Cox regression model was used to analyze the prognostic factors.Results:Among the 21 patients with eMRTs, there were 7 males and 14 females, with the age of onset of 24 (3-138) months.Immunohistochemistry showed that all tumor tissues of the patients did not secrete integrase interactor 1 (INI-1).Among them, 13 cases originated from the kidney, and 8 cases originated from extrarenal non-central sites.At the time of diagnosis, there were 4 cases in clinical stages Ⅰ-Ⅱ, 17 cases in stage Ⅲ-Ⅳ.Thirteen patients underwent complete tumor resection surgery, 7 underwent partial resection, and 1 only underwent biopsy.Among the 13 cases of renal rhabdoid tumors, 8 cases were treated with the AVDC (Epirubicin, Vincristine, Actinomycin D, Cyclophosphamide)/ICE (Ifosfamide, Carboplatin, Etoposide) regimen, and 5 cases were treated with the protocol for nephroblastoma; among the 8 cases of extrarenal non-central rhabdoid tumors, 5 cases were treated with the AVDC/ICE regimen, and 3 cases were treated with the commonly used protocol for soft tissue sarcoma.Thirteen patients received radiotherapy.One patient received consolidation therapy with autologous stem cell transplantation following chemotherapy and radiotherapy.As of October 2023, there were 14 survivors and 7 deaths.The overall 2-year PFS and OS were 56%(95% CI: 35.7%-88.5%) and 62%(95% CI: 43.2%-89.4%), respectively.Among the patients who received the AVDC/ICE alternating chemotherapy regimen, the 2-year PFS and OS were 73%(95% CI: 47.0%-100.0%) and 79% (95% CI: 56.4%-100.0%), respectively.Univariate Cox regression analysis showed that complete tumor resection, the AVDC/ICE alternating chemotherapy, and radiotherapy were associated with a better prognosis in children (all P≤0.05).Multivariate Cox regression analysis showed that whether to receive radiotherapy was an independent risk factor affecting the overall survival in children. Conclusions:eMRTs are more common in infants and young children, with high malignancy and invasiveness.There is currently no standard treatment.Complete tumor resection combined with the AVDC/ICE alternating chemotherapy and radiotherapy may improve the prognosis of children with eMRTs.

Objective:To explore the molecular basis for a Chinese pedigree affected with Achromatopsia (ACHM).Methods:A pedigree with ACHM which was admitted to the Women and Children′s Hospital of Ningbo University on April 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. Related literature was reviewed, and clinical and genetic features of Chinese patients with ACHM due to variants of CNGA3 gene were summarized. This study was approved by the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048). Results:WES revealed that the proband and his younger brother had both harbored compound heterozygous variants of the CNGA3 gene, namely c. 1190G>T (p.Gly397Val) and c. 2013del (p.Gly672ValfsTer69), which were respectively inherited from their mother and father. The c. 1190G>T was a known pathogenic variant, while the c.2013del was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2013del variant was predicted to be likely pathogenic (PM2_Supporting+ PVS1_Moderate+ PM3+ PP4). Literature review has identified 41 CNGA3 gene variants among 43 patients from 38 pedigrees, most of which were missense variants and had located in exon 8. Most patients were males, with nystagmus, photophobia, amblyopia and other symptoms during infancy/childhood as the main clinical manifestations, and there was a lack of genotype-phenotype correlation. Conclusion:The c. 1190G>T (p.Gly397Val) and c. 2013del (p.Gly672ValfsTer69) variants of the CNGA3 gene probably underlay the ACHM in the proband. Discovery of the c. 2013del variant has enriched the mutational spectrum of the CNGA3 gene and provided a basis for genetic counseling and reproduction guidance for this pedigree.

With the advances in understanding the relationships among biomaterials, the immune system and the skeletal system, the host responses elicited by implanted biomaterials can be balanced by properly designing material characteristics from the perspective of osteoimmunology. The immunoregulatory properties of bone tissue engineering scaffolds provide advantages for inducing macrophages from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype and promoting osseointegration. Hydrogels are increasingly a focus in bone tissue engineering, and the immune response can be affected by different compositions of hydrogels, such as the sources, concentration, molecular weight, coupling with fibronectin, and the addition of cross-linking agents. Different physicochemical properties of modified hydrogels can trigger different host immune responses, modified by using soft photolithography to fabricate micropatterned hydrogels, adding enzyme-sensitive sequences, ester bonds and dynamic covalent chemistry to prevent rapid or slow degradation of the hydrogels, and adding porogens and 3D printing to modify the hydrogels with macroporous interconnective pore structures, soft and injectable hydrogels, etc. These optimized hydrogels can reduce proinflammatory factors, promote M2 macrophage polarization, and minimize foreign body reactions to evoke bone regeneration. However, the mechanism underlying the bone immune response is still poorly understood, and further study of the effects of hydrogels with different physicochemical properties on immune regulation is needed.

OBJECTIVE: To explore the types of NF1 gene variants and clinical characteristics among patients with Neurofibromatosis type I (NF1). METHODS: Clinical data of 12 patients diagnosed at Ningbo Women and Children's Hospital between December 2019 and May 2022 were retrospectively analyzed. The probands and their family members were subjected to high-throughput sequencing, and candidate variants were verified by Sanger sequencing and chromosome microarray analysis. RESULTS: The 12 patients had ranged from 4 months to 27 years old, with a male-to-female ratio of 2 : 1. Cafè-au-lait spots were found in all patients. 83.3% of them also had axillary and/or inguinal freckling, 58.3% had neurofibromas, and 16.7% had congenital pseudarthrosis of the tibia. Five types of NF1 gene variants were identified in the patients, including 5 nonsense variants, 4 frameshift variants, 1 missense variant, 1 splice variant, 1 large deletion involving the whole gene. Six patients were found to harbor de novo variants, 2 had inherited the variants from their parents, and 4 were not verified for their parental origin. The c.3379del (p.Thr1127Glnfs*15) and c.6628_6629del (p.Glu2210Thrfs*10) variants were unreported in literature and databases. CONCLUSION Most NF1 patients may present with Cafè-au-lait spots initially and are due to pathogenic variant of the NF1 gene. High-throughput sequencing can efficiently identify such variants among the patients and enable the definite diagnosis.
Child ; Humans ; Female ; Male ; Neurofibromatosis 1/diagnosis* ; Cafe-au-Lait Spots/diagnosis* ; Genes, Neurofibromatosis 1 ; Retrospective Studies ; Frameshift Mutation

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Triple-negative breast cancer (TNBC) represents a distinct subtype of breast cancer, characterized by unique clinical traits including early lung metastasis, elevated recurrence rates, and diminished survival prospects. Owing to the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, concrete therapeutic targets remain elusive, thereby confining available clinical treatment methods. In the context of advanced TNBC, chemotherapy remains the predominant therapeutic approach. In recent years, with the in-depth study of tumor microenvironment, new immunotherapy targets have been discovered one after another. Thus, immunotherapy-based combined therapy strategies have brought new hope in patients with advanced TNBC.

Objective:To investigate the clinical characteristics and short-term and long-term outcomes of preterm infants under two diagnostic criteria of bronchopulmonary dysplasia (BPD).Methods:A retrospective observational cohort study was conducted of infants admitted to the Department of Neonatology of Guangdong Women and Children's Hospital from January 2019 to June 2021. Infants who were born at <32 weeks gestational age and met the 2001 National Institute of Child Health and Human Development (NICHD) BPD definition were included. The 2019 Jenson BPD diagnostic criteria was then used to re-grade the enrolled population. Comparisons of clinical characteristics, neonatal morbidities, respiratory morbidities and growth status at follow-up between the two definition groups were conducted with t-test, nonparametric test, or Chi‐square test. Results:A total of 392 patients were included. The number of patients with BPD classified as mild, moderate, severe, and unclassifiable according to the 2001 definition was 129, 134, 114, and 15, respectively. According to the 2019 definition, there were 134 cases in the Class Ⅰ group, 89 cases in the Class Ⅱ group, 25 cases in the Class Ⅲ group, and 144 cases of non BPD. Patients with grade Ⅰ and Ⅱ BPD from the 2019 definition had an higher incidence of post-discharge home oxygen therapy, older age at discharge, and longer length of stay, compared to those with mild and moderate BPD from the 2001 definition (all P<0.05). Under both criteria, mortality increased as severity of BPD increased. Patients with grade Ⅲ BPD from the 2019 definition had higher mortality than those with severe BPD from the 2001 definition, the difference was statistically significant (48.0% vs. 14.0%, P<0.01). A total of 138 infants were followed up at 12 months of corrected age. There were no significant differences in the majority of physical development indicators and the rates of respiratory disease, readmission, and severe neurological injury, between the two definition groups at follow-up. Conclusions:The 2001 definition leads to higher BPD diagnosis rate and higher incidence of classification into the severest category within the definition. But mortality in the severe BPD group from 2001 definition was lower than that in the grade Ⅲ group from the 2019 definition. The 2019 definition is more stringent, more reasonable, more practical, and more capable of identifying patients with poor outcomes.

Objective:To observe the distribution characteristics of fungi, bacteria and Demodex in the eyelid margin of patients with blepharitis and without blepharitis at different ages. Methods:A cross-sectional study was conducted.A total of 98 patients diagnosed with anterior blepharitis and 99 patients diagnosed with posterior blepharitis in Henan Eye Hospital from March 2021 to June 2022 were enrolled as anterior blepharitis group and posterior blepharitis, respectively.Additionally, 100 patients with an initial diagnosis of refractive error and 200 patients with vitreous opacity were enrolled during the same period as a non-blepharitis group.All patients underwent examinations for lid margin fungi, bacteria and eyelash Demodex, as well as fungal spores and ciliary Demodex count.The differences in the positive rate and load of palpebral fungi, bacteria and eyelash Demodex were compared between anterior and posterior blepharitis groups, as well as across different ages in non-blepharitis group.This study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[18]).All patients were informed about the purpose and methods of the study.Written informed consent was obtained from each patient. Results:There were significant differences in the positive rates of bacteria, fungi and Demodex and the load of Demodex in the non-blepharitis group at different ages ( χ2=28.34, 10.36, 51.57, H=35.66; all at P<0.01).The positive rates of palpebral bacteria and ciliary Demodex and the load of Demodex were significantly higher and the palpebral fungi positive rate was significantly lower in the ≥60 years old than in the <60 years old (all at P<0.05).There were significant differences in the positive rates of bacteria and fungi among anterior blepharitis, posterior blepharitis and non-blepharitis groups ( χ2=18.99, 6.36; all at P<0.01).The palpebral bacteria positive rate was significantly higher in anterior blepharitis group than in posterior blepharitis and non-blepharitis groups, and the palpebral fungi positive rate was significantly higher in anterior blepharitis and posterior blepharitis groups than in non-blepharitis group (all at P<0.05).There was no significant difference in the ciliary Demodex detection rate among the three groups ( χ2=0.16, P=0.74).The number of palpebral fungi spores and eyelash Demodex counts were higher in anterior and posterior blepharitis groups than in non-blepharitis group, and the differences were statistically significant (all at P<0.05).The positive rate of palpebral margin bacteria in ciliary Demodex-positive group was 45.7%(156/341), which was significantly higher than 25.6%(40/156) in ciliary Demodex-negative group ( χ2=17.20, P<0.01), and there was no significant difference in the positive rate of palpebral margin fungi between them ( χ2=0.11, P=0.70). Conclusions:In the population with normal eyelid margin, the infection of Demodex and bacteria in lid margin increases and fungal infection decreases in the ≥60 years old.Fungal and bacterial infections are the main sources of palpebral infection in patients with blepharitis, and positive detection of Demodex increases the chance of bacterial infection.

OBJECTIVE: To analyze the clinical manifestation and genetic basis for four children with delayed onset Ornithine transcarbamylase deficiency (OTCD). METHODS: Clinical data of four children with OTCD admitted to the Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2021 were reviewed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Bioinformatic analysis and Sanger sequencing verification were carried out to verify the candidate variants. Impact of the candidate variants on the protein structure was also predicted. RESULTS: The clinical manifestations of the four children included vomiting, convulsion and disturbance of consciousness. WES revealed that the child 1 was heterozygous for a c.421C>T (p.R141X) variant in exon 5, children 2 and 3 were hemizygous for a c.119G>A (p.R40H) variant in exon 2, and child 4 was hemizygous for a c.607T>A (p.S203T) variant in exon 5 of the OTC gene. Among these, the c.607T>A variant was unreported previously and predicted to be pathogenic (PM1+PM2_Supporting+PP3+PP4). Bioinformatic analysis has predicted that the variant may result in breakage of hydrogen bonds and alter the protein structure and function. Sanger sequencing confirmed that the variants in children 2 to 4 have derived from their mothers. CONCLUSION The pathogenic variants of the OTC gene probably underlay the delayed OTCD in 4 children. The discovery of the c.607T>A variant has enriched the mutational spectrum of the OTC gene.
Child ; Humans ; Ornithine Carbamoyltransferase Deficiency Disease/genetics* ; Exons ; Seizures ; Computational Biology ; Heterozygote

OBJECTIVE: To compare and analyze the effect of unplanned versus planned admission to the intensive care unit (ICU) on the prognosis of high-risk patients after surgery, so as to provide a clinical evidence for clinical medical staff to evaluate whether the postoperative patients should be transferred to ICU or not after surgery. METHODS: The clinical data of patients who were transferred to ICU after surgery admitted to the Affiliated Hospital of Guizhou Medical University from January to December in 2021 were retrospectively analyzed, including gender, age, body mass index, past history (whether combined with hypertension, diabetes, pulmonary disease, cardiac disease, renal failure, liver failure, hematologic disorders, tumor, etc.), acute physiology and chronic health evaluation II (APACHE II), elective surgery, pre-operative hospital consultation, length of surgery, worst value of laboratory parameters within 24 hours of ICU admission, need for invasive mechanical ventilation (IMV), duration of IMV, length of ICU stay, total length of hospital stay, ICU mortality, in-hospital mortality, and survival status at 30th day postoperative. The unplanned patients were further divided into the immediate transfer group and delayed transfer group according to the timing of their ICU entrance after surgery, and the prognosis was compared between the two groups. Cox regression analysis was used to find the independent risk factors of 30-day mortality in patients transferred to ICU after surgery. RESULTS: Finally, 377 patients were included in the post-operative admission to the ICU, including 232 in the planned transfer group and 145 in the unplanned transfer group (42 immediate transfers and 103 delayed transfers). Compared to the planned transfer group, patients in the unplanned transfer group had higher peripheral blood white blood cell count (WBC) at the time of transfer to the ICU [×10⁹/L: 10.86 (7.09, 16.68) vs. 10.11 (6.56, 13.27)], longer total length of hospital stay [days: 23.00 (14.00, 34.00) vs. 19.00 (12.00, 29.00)], and 30-day post-operative mortality was higher [29.66% (43/145) vs. 17.24% (40/232)], but haemoglobin (Hb), arterial partial pressure of carbon dioxide (PaCO₂), oxygenation index (PaO₂/FiO₂), and IMV requirement rate were lower [Hb (g/L): 95.00 (78.00, 113.50) vs. 98.00 (85.00, 123.00), PaCO₂ (mmHg, 1 mmHg ≈ 0.133 kPa): 36.00 (29.00, 41.50) vs. 39.00 (33.00, 43.00), PaO₂/FiO₂ (mmHg): 197.00 (137.50, 283.50) vs. 238.00 (178.00, 350.25), IMV requirement rate: 82.76% (120/145) vs. 93.97% (218/232)], all differences were statistically significant (all P < 0.05). Kaplan-Meier survival curve showed that the 30-day cumulative survival rate after surgery was significantly lower in the unplanned transfer group than in the planned transfer group (Log-Rank test: χ² = 7.659, P = 0.006). Univariate Cox regression analysis showed that unplanned transfer, APACHE II score, whether deeded IMV at transfer, total length of hospital stay, WBC, blood K⁺, and blood lactic acid (Lac) were associated with 30-day mortality after operation (all P < 0.05). Multifactorial Cox analysis showed that unplanned transfer [hazard ratio (HR) = 2.45, 95% confidence interval (95%CI) was 1.54-3.89, P < 0.001], APACHE II score (HR = 1.03, 95%CI was 1.00-1.07, P = 0.031), the total length of hospital stay (HR = 0.86, 95%CI was 0.83-0.89, P < 0.001), the need for IMV on admission (HR = 4.31, 95%CI was 1.27-14.63, P = 0.019), highest Lac value within 24 hours of transfer to the ICU (HR = 1.17, 95%CI was 1.10-1.24, P < 0.001), and tumor history (HR = 3.12, 95%CI was 1.36-7.13, P = 0.007) were independent risk factors for patient death at 30 days post-operative, and the risk of death was 2.45 times higher in patients unplanned transferred than in those planned transferred. Subgroup analysis showed that patients in the delayed transfer group had significantly longer IMV times than those in the immediate transfer group [hours: 43.00 (11.00, 121.00) vs. 17.50 (2.75, 73.00), P < 0.05]. CONCLUSIONS The 30-day mortality, WBC and total length of hospital stay were higher in patients who were transferred to ICU after surgery, and PaO₂/FiO₂ was lower. Unplanned transfer, oncology history, use of IMV, APACHE II score, total length of hospital stay, and Lac were independent risk factors for patient death at 30 days postoperatively, and patients with delayed transfer to ICU had longer IMV time.
Humans ; Retrospective Studies ; Respiration, Artificial ; Hospitalization ; Prognosis ; Intensive Care Units