Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Objective:To examine the impact of sleep quality on cognitive function in older adults with mild cognitive impairment(MCI)and explore the potential mediating role of depression.Methods:Using a cross-sectional design, we conducted an on-site questionnaire survey among 310 elderly individuals with MCI in Haishu District, Ningbo City from April to June 2021.Out of the 310 questionnaires collected, 299 were deemed valid.The survey encompassed gathering basic demographic information of the participants, as well as administering the Montreal Cognitive Assessment Scale, Patient Health Questionnaire Depression Scale, and Pittsburgh Sleep Quality Index Scale.Results:The cognitive functions of patients with MCI were found to be positively related to their education level( F=3.89, P<0.05).The correlation analysis indicated that sleep quality was positively correlated with depression( r=0.40, P<0.01)and negatively correlated with cognitive function( r=-0.22, P<0.01).Furthermore, a significant negative correlation was observed between depression and cognitive function( r=-0.20, P<0.01).The mediation analysis revealed that depression played a role in mediating the influence of sleep quality on cognitive function, with a mediation effect of -0.02(95% CI: -0.03--0.01). Conclusions:The cognitive function of elderly individuals with MCI can be significantly affected by sleep quality, with depression playing a mediating role.

Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8⁺ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

Purpose: This study explored the performance of prenatal ultrasonography in the differential diagnosis of cystic biliary atresia (CBA) and choledochal cyst (CC). Methods: Fetuses diagnosed with hepatic hilar cyst in the second trimester were included in this study. A series of prenatal ultrasound examinations were performed in the second and third trimesters. The diameter of the gallbladder (GB) and hepatic cyst were measured, as well as the wall thickness of the GB. The GB-cyst connection, visibility of the right hepatic artery (RHA), and other concomitant abnormalities were carefully evaluated. A neonatal transabdominal ultrasound examination was performed within 1 week after birth, and clinical data were followed up to 6 months after birth. Results: Between January 1, 2016 and January 31, 2020, 53 fetuses diagnosed with hepatic hilar cyst were recruited. Eight were excluded because they were lost to follow-up. Among the 45 cases included in this study, 10 were diagnosed with CBA and 35 with CC after birth. Statistically significant differences were found in GB width, wall thickness, change in GB width, change in cyst length, GB-cyst connection, and RHA visibility between the CBA and CC groups. GB width showed the best diagnostic performance with an area under the curve (AUC) of 0.899. The combination of GB width, GB wall thickness, and GB-cyst connection yielded a comparable AUC of 0.971. Conclusion The GB should be carefully evaluated in fetuses with hepatic hilar cyst. Prenatal ultrasound findings could provide suggestive parameters for the differential diagnosis of CBA from CC.

Objective:To investigate the expression of miR-151a-3p in peripheral blood mononuclear cells (PBMCs) of children with lupus nephritis (LN) and its correlation with activity and vascular damage.Methods:A total of 87 children with LN admitted in Hainan Women and Children′s Medical Center from January 2016 to March 2019 were enrolled, including 16 cases of type Ⅱ, 14 cases of type Ⅲ, 34 cases of type Ⅳ, 17 cases of type Ⅴ and 6 cases of type Ⅵ.Besides, additional 40 children with normal physical examination were selected as the healthy control group.The 87 children with LN were divided into the LN stable group (31 cases) and LN active group (56 cases) by using systemic lupus erythematosus disease activity index (SLEDAI) scores.According to different proportions of the medium membrane, the patients were classified into the mild group (25 cases), moderate group (34 cases) and severe group (28 cases). Real time quantitative PCR (qPCR) was used to detect the expression level of miR-151a-3p in PBMCs of each group.The correlation of the expression level of miR-151a-3p in PBMCs of LN children with the SLEDAI score and renal interstitial damage score was studied by Pearson correlation analysis. Results:The expression levels of miR-151a-3p in the LN group, LN active group and LN stable group (0.47 ± 0.06, 0.30 ± 0.04, and 0.75±0.12, respectively) were significantly lower than that in the healthy control group (1.62±0.35) (all P<0.01), and the expression level of miR-151a-3p in the LN active group (0.30±0.04) was significantly lower than that in the LN stable group (0.75±0.12) ( P< 0.01). The SLEDAI score [(14.35±4.60) points vs.(8.25±2.24) points] and renal interstitial damage score [(52.70±6.30) points vs.(34.80±4.10) points] in the LN active group were significantly higher than those in the LN stable group (all P<0.01). The expression levels of miR-151a-3p (0.18±0.02, 0.41±0.05 vs.0.83±0.16) in type Ⅴ-Ⅵ and type Ⅳ groups were significantly lower than that in the type Ⅱ-Ⅲ group (all P<0.01). The SLEDAI scores [(16.50±5.28) points, (12.36±3.74) points vs.(6.40±1.70) points] and renal interstitial damage scores [(62.70±7.40) points, (47.20±5.80) points vs.(25.80±3.50) points] in type Ⅴ-Ⅵ and type Ⅳ groups were significantly higher than those in the type Ⅱ-Ⅲ group (all P< 0.01). The expression levels of miR-151a-3p (0.20±0.02, 0.39±0.04, 0.86±0.18 vs.1.62±0.35) in severe, moderate and mild groups were significantly lower than that in the healthy control group (all P<0.01), and the expression level of miR-151a-3p decreased with the aggravation of vascular damage.The SLEDAI scores [(15.20±5.10) points, (12.85±3.90) points vs.(6.70±1.82) points] and renal interstitial damage scores [(57.30±6.80) points, (51.60±6.30) points vs.(27.20±3.60) points] in the severe and moderate groups were significantly higher than those in the mild group (all P<0.01). The expression level of miR-151a-3p in LN children was negatively correlated with the SLEDAI score and renal interstitial damage score ( r=-0.682, -0.627, all P<0.001). Conclusions:The expression level of miR-151a-3p in PBMCs of LN children is significantly decreased.The declined miR-151a-3p level is closely related to disease activity and vascular damage, and may be involved in the occurrence and development of LN.

Objective To study the molecular genetic mechanism of congenital central hypoventilation syndrome ( CCHS).Method The clinical data and molecular genetics results of CCHS diagnosed in neonatology department from 2014 to 2016 were analyzed retrospectively.The relationship between genotypes and clinical phenotypes in patients of CCHS was analyzed , and the diagnostic thinkings , follow－up and prognosis were summarized.Result A total of 4 infants with CCHS were included in this study.Among them, 2 were boys and the other 2 were girls.They were all full－term neonates without asphyxia at birth , but they soon sufferd from dyspnea and cyanosis , required assisted ventilation.One case had difficult defecation. All 4 cases had difficulty in weaning.The respiratory rhythm became weak developed apnea and carbon dioxide retention was detected in blood gas analysis.All the 4 cases died after withdrawal of treatment.The results of molecular genetic testing were as follows.There was a 38bp heterozygous deletion mutation in exon 3 of gene PHOX2B ( e.756＿776 del21bp).Three cases were found small fragment insertion in exon 3 of gene PHOX2B, which attributed to polyalanine repeat expansion mutations (PARMs).One case belonged to type 20/27 and another 2 cases belonged to type 20/26.Conclusion The main manifestation of CCHS in the neonatal period is ventilator dependant , which can combined with megacolon and atypical autonomic nerve disorder.According to the literature, more than 95%of CCHS are caused by the PHOX2B mutation. The symptom is severe when it got a non－PARMs mutation.It′s useful to make a definite diagnosis with genetic diagnosis results , which could be helpful for treating and predicting.Only effective respiratory support and standardized follow－up system can improve the quality of life in patients of CCHS.

Objective To explore the perception of clinical learning environment,career maturity,and professional identity as well as their associations among 3+2 nursing undergraduates.Method Totally 198 3+2 nursing undergraduate students from two provincial medical colleges in Shandong province were enrolled.Results Mean scores for clinical learning environment,career maturity and professional identity were (3.44 ± 0.54),(3.31 ± 0.37) and (3.63 ± 0.62),respectively.Clinical learning environment and career maturity (P＜0.001) were positivelyassociated with 3+2 nursing undergraduates' professional identity.Conclusions Clinical learning environment,career maturity and professional identity of 3 +2 nursing undergraduates areat a moderate level.Interventions to facilitate clinical learning environments and career maturity will foster the growth of professional identity.

OBJECTIVETo explore the genetic cause for two children with omphalocele.

METHODSThe patients were examined, and the medical history of their families was collected. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to detect potential mutation in the patients.

RESULTSLoss of methylation of imprinting center 2 (IC2) at the 11p15.5 region of the maternal chromosome was detected in both children.

CONCLUSIONThe two patients were diagnosed with Beckwith-Wiedemann syndrome by MS-MLPA. The loss of methylation of IC2 probably underlies the disease in both patients.

Beckwith-Wiedemann Syndrome ; genetics ; Chromosomes, Human, Pair 11 ; DNA Methylation ; Female ; Genomic Imprinting ; Humans ; Infant ; Infant, Newborn ; Male ; Multiplex Polymerase Chain Reaction

Objective: To investigate the genetic cause for a family with multiorgan dysplasia and "molar tooth sign" on MRI image. Method: The patient, a 3 months and 21 days old boy, was clinically examined and the medical history of his family was collected. Next generation sequencing was performed to analyze his clinical and genetic causes. Result: Clinical manifestation of the child displayed multiorgan dysplasia, such as six finger deformity, short limbs, coloboma of optic disc and choroid, situs inversus.Cranial MRI showed "molar tooth sign" . The gene sequencing confirmed that the child carried a de novo deletion of c. 2843_2844 delAA in OFD1 gene. Conclusion The child has typical clinical features of Joubert syndrome, such as MRI "molar syndrome" , developmental abnormalities of ocular tissue and limb, visceral inversion, and so on.The OFD1 gene had a novel deletion mutation through gene detection. Combined clinical features with gene detection, it was clear that the child was a rare case of Joubert syndrome type 10 which was the first case of Joubert syndrome caused by OFD1 gene mutation in China.