The inflammatory factor IL6 secreted by bone marrow mesenchymal stem cells (BMSCs) in the tumor microenvironment (TME) facilitates the survival and therapeutic resistance of neuroblastoma (NB). Here, we found that IL6 expression in primary tumor tissues or bone marrow (BM) metastases was closely associated with the disease risk and prognosis of NB patients. IL6 secretion from immortalized BMSC (iBMSC) was directly regulated by NB cells and is involved in promoting the proliferation and metastasis of NB cells. Beta-Lapachone (ARQ-501, LPC), an ortho-naphthoquinone natural product, significantly prevented the iBMSC-induced malignant transformation effect on NB cells through suppressing the expression and secretion of IL6 from iBMSC in vitro and in vivo. Mechanistically, LPC disrupted the crosstalk between NB cells and iBMSC in an NQO1-dependent manner through blocking the Gal-3/Gal-3BP/IL6 axis. Our results reveal the effect of iBMSC-derived IL6 on TME-induced malignant transformation of NB cells, and provide theoretical basis for the clinical application of LPC as a potential IL6 inhibitor in high-risk refractory NB patients.

ObjectiveThis study aimed to examine the prevalence and the related risk factors of congenital heart disease (CHD) in children with different birth weights in China and the relationship between the subtypes of CHD and birth weight (BW).MethodsThis study conducted a cross-sectional survey on the data collected in the children’s congenital heart disease database (CHDD) established in China. This database contained data from one Grade A, Level III Children’s Public Hospital in Zhengzhou, Henan. The study included all the children and their parents in the database from 2014 to 2020 as the study subjects, and the missing data were processed by means of imputation. Diagnoses of CHD were coded using the International Classification of Diseases version 10 (ICD-10), and subtypes were classified by the codes Q20 to Q26. We reported the prevalence of CHD based on birth weight and gestational age and analyzed the related risk factors for children with CHD in different birth weight groups and factors for children of the same birth weight groups between the CHD groups and the non-CHD groups. The generalized linear model was used to assess the association between the subtypes of CHD and BW by establishing three adjusting models, and the data were stratified for further analysis by urban-rural and infant gender.ResultsA total of 42,814 children were identified as having CHD among 5,071,799 live children; the overall prevalence of CHD was 8.44 per 1,000 live births during 2014–2020; and the three subtypes with the highest prevalence of CHD were atrial septal defect (ASD) (2.75‰), ventricular septal defect (VSD) (2.57‰), and patent foramen ovale (PFO) (1.12‰). The prevalence of CHD was 18.87‰ in the group with BW <1,500 g, 12.84‰ in the group with BW 1,500–2,500 g, 8.24‰ in the group with BW 2,500–4,000 g, and 4.80‰ in the group with BW ≥4,000 g. The prevalence of CHD was 16.62‰ in the small for gestational age (SGA) group, 6.99‰ in the appropriate for gestational age (AGA) group, and 6.40‰ in the larger for gestational age (LGA) group. Parental factors such as drinking, smoking, viral infections, peri-pregnancy exposure to radioactive substances, low family monthly expenditure, and low Apgar scores at 1 and 5 min were related to the increased risk of CHD in the offspring. Parental supplementation of folic acid and exercise during the peri-pregnancy period could reduce the risk of CHD in the offspring. The results of Model 3 adjusting for confounding variables showed that infants with ASD had a birth weight 461 g lower (95% CI: −1,085, –128), infants with VSD had a birth weight 426 g lower (95% CI: –932, –120), infants with tetralogy of Fallot (TOF) had a birth weight 532 g lower (95% CI: –987, –168), and without classification, infants with CHD had a birth weight 973 g lower (95% CI: –1,502, –204).ConclusionIn very low birth weight (VLBW) and low birth weight (LBW) infants, CHDs are more prevalent than in the general live-born population. Moreover, some peri-pregnancy factors of parents are closely related to the occurrence of CHD in offspring; different types of heart defects can lead to LBW. Therefore, if the fetus is found to have a heart defect during the prenatal examination, the mother should pay more attention to maintaining weight and ensuring that the fetus is within the normal weight range, thereby increasing the postpartum survival rate, reducing complications, and promoting children’s health.

Sewing needles, albeit rare in the case of penetrating cardiac injury, are highly lethal; especially in children, because the injury is difficult to diagnose and treat. We herein present the case of a 13-month-old girl who was injured by a sewing needle inserted in the myocardium; it is the first report of its kind from mainland China. The 13-month-old girl was referred to our hospital with a range of symptoms, including convulsions, diarrhea, and cough. Chest X-ray and echocardiogram revealed a needle located below the aortic valve, passing through the ventricular septum and aortic root. Surgical removal of the needle was performed under extracorporeal circulation. No hemorrhage or arrhythmia was seen, so the operation was ended, and the patient was discharged 8 days after the surgery. An early diagnosis and intervention proved to be lifesaving for this patient with a penetrating cardiac injury. We hope this case can provide a reference for the treatment of similar situations.Key words: Cardiac function -Foreign body -Pediatric -Patient safety -Surgery A needle in the heart is a comparatively rare event. It is typically considered to be life threatening as it may induce adverse events such as cardiac tamponade, infection, mural thrombus, peripheral embolism, and valve dysfunction. Especially in children, a sharp needle in the heart poses a serious hazard requiring immediate intervention. However, because of the limited communication skills of children, it is difficult to make a timely and accurate diagnosis, which adds complexity to the treatment. To date, no similar cases have been reported from China. In this report, we present a case of a child who had a sewing needle inserted in the myocardium. The needle was successfully extracted under extracorporeal circulation. Case Report A 13-month-old girl with the manifestation of diarrhea was admitted to a local hospital, and the symptoms of diarrhea were relieved after taking some medications, which are unknown. Two days later, she suffered from diarrhea again and was prescribed some traditional Chinese medicine (TCM), the components of which were also unknown. However, the child went into convulsions 12 hours after intake of the TCM, and the convulsions lasted for approximately 2 minutes. Four hours later, the patient developed fever, accompanied with a nonprojectile vomiting. Emergency examination revealed elevated serum myocardial enzymes and bradycardia. Vitamin C, cephalosporins, mannitol, and cimetidine were prescribed for treatment. Although bradycardia was relieved, the rest of the above symptoms remained after a week of treatment. A productive cough also appeared subsequently. The child was then transferred to our institution for further management.On examination, her vital signs were stable. Results of routine blood and urine analyses as well as serum cardiac enzymes were normal. The respiratory sound of the patient was rough, and there were rales as well as expiratory wheeze during lung auscultation. A routine chest X-ray and cranial computed tomography...

Sewing needles, albeit rare in the case of penetrating cardiac injury, are highly lethal; especially in children, because the injury is difficult to diagnose and treat. We herein present the case of a 13-month-old girl who was injured by a sewing needle inserted in the myocardium; it is the first report of its kind from mainland China. The 13-month-old girl was referred to our hospital with a range of symptoms, including convulsions, diarrhea, and cough. Chest X-ray and echocardiogram revealed a needle located below the aortic valve, passing through the ventricular septum and aortic root. Surgical removal of the needle was performed under extracorporeal circulation. No hemorrhage or arrhythmia was seen, so the operation was ended, and the patient was discharged 8 days after the surgery. An early diagnosis and intervention proved to be lifesaving for this patient with a penetrating cardiac injury. We hope this case can provide a reference for the treatment of similar situations.

No abstract

A previously healthy 7-year-old had 1 week of fevers, productive cough, and lethargy, which did not improve after 3 days of oral cefuroxime. He lived in a rural area and had close contact with dogs, cattle, and sheep. White blood cell count was 8000/μL, with 25.8% eosinophils; computed tomography showed a ruptured right upper lobe pulmonary cyst and 3 liver cysts. What is the diagnosis and what would you do next?

Background MYCN amplification as a common genetic alteration that correlates with a poor prognosis for neuroblastoma (NB) patients. However, given the challenge of directly targeting MYCN, indirect strategies to modulate MYCN by interfering with its cofactors are attractive in NB treatment. Although cyclin B1 interacting protein 1 (CCNB1IP1) has been found to be upregulated in MYCN‐driven mouse NB tissues, its regulation with MYCN and collaboration in driving the biological behaviour of NB remains unknown. Methods To evaluate the expression and clinical significance of CCNB1IP1 in NB patients, public datasets, clinical NB samples and cell lines were explored. MTT, EdU incorporation, colony and tumour sphere formation assays, and a mouse xenograft tumour model were utilized to examine the biological function of CCNB1IP1. The reciprocal manipulation of CCNB1IP1 and MYCN and the underlying mechanisms involved were investigated by gain‐ and loss‐of‐function approaches, dual‐luciferase assay, chromatin immunoprecipitation (CHIP) and co‐immunoprecipitation (Co‐IP) experiments. Results CCNB1IP1 was upregulated in MYCN‐amplified (MYCN‐AM) NB cell lines and patients‐derived tumour tissues, which was associated with poor prognosis. Phenotypic studies revealed that CCNB1IP1 facilitated the proliferation and tumourigenicity of NB cells in cooperation with MYCN in vitro and in vivo. Mechanistically, MYCN directly mediates the transcription of CCNB1IP1, which in turn attenuated the ubiquitination and degradation of MYCN protein, thus enhancing CCNB1IP1‐MYCN cooperativity. Moreover, CCNB1IP1 competed with F box/WD‐40 domain protein 7 (FBXW7) for MYCN binding and enabled MYCN‐mediated tumourigenesis in a C‐terminal domain‐dependent manner. Conclusions Our study revealed a previously uncharacterized mechanism of CCNB1IP1‐mediated MYCN protein stability and will provide new prospects for precise treatment of MYCN‐AM NB based on MYCN‐CCNB1IP1 interaction.

This study aimed to investigate the effect of video-assisted thoracoscopic surgery (VATS) on pain stress indicators nitric oxide (NO), interleukin-1β (IL-1β) and IL-6 in the treatment of mediastinal tumor in children, so as to explore the clinical application value of this surgery. A retrospective analysis was performed on 82 children with mediastinal tumor undergoing operation in Children's Hospital Affiliated to Zhengzhou University from January 2012 to January 2016. Among them, 48 children undergoing VATS were enrolled as an observation group, and 34 children undergoing conventional thoracotomy were enrolled as a control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the preoperative and postoperative expression levels of NO, IL-1β and IL-6. The intraoperative clinical data, postoperative pain degree and infection rate were observed and recorded in real time, and then compared between the two groups. Before operation (T 0), there were no statistically significant differences between the two groups in serum NO, IL-1β and IL-6 expression levels, which were lower in the observation group than those in the control group at 12 h (T 1) and 24 h (T 2) after operation (P<0.05). The visual analog scale (VAS) score in the observation group was lower than that in the control group at T 1 (P<0.05). Compared with the control group, the largest blade opening, intraoperative blood loss, drainage duration and postoperative pain degree were significantly improved in the observation group. The postoperative infection rate was 4.17% in the observation group, significantly lower than 17.64% in the control group. VATS is effective for postoperative pain stress indicators and infection control in children with mediastinal tumor, which is therefore more suitable for children with the disease and has a higher clinical value.