Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

OBJECTIVE To investigate the inhibitory effect of human β defensin-3(HBD3)on the replication of in-fluenza A virus(IAV)[A/PR/8/34(H1N1)virus strain]in human bronchial epithelial cells(BEAS-2B)via the mitochondrial autophagy pathway.METHODS BAS-2B cells were infected with IAV,and cell condition observa-tion:plaque assay and light microscopy.Drug treatment:HBD3,autophagy agonist rapamycin(Rapa),autoph-agy inhibitor LY294002;The expression levels of TUFM、MAVS、NP、M2 and PB1-F2 genes were detected by real-time fluorescence quantitative polymerase chain reaction(qPCR).Western blot was used to detect the protein expression levels of P62、LC3Ⅱ and LC3Ⅰ.RESULTS Plaque formation experiments showed that the number of plaques increased with the increase of viral titer.With the increase of viral titer or the prolongation of infection time,the expres-sion levels of TUFM,MAVS,NP,M2 and PB1-F2 genes in BEAS-2 B cells gradually increased,the expression levels of P62 protein decreased,and the protein expression levels of LC3Ⅱ/LC3Ⅰ increased(P＜0.05).Forty-eight hpi of BE-AS-2B cells with IAV,the number of cells in the IAV group was significantly lower than that in the IAV+HBD3 group,the intercellular space was enlarged,and the cells shrunk significantly.Compared with the IAV group,the expression lev-els of TUFM,MAVS,NP,M2 and PB1-F2 genes in BEAS-2B cells in the IAV+HBD3 group decreased,the expres-sion levels of P62 protein increased,and the protein levels of LC3Ⅱ/LC3Ⅰ decreased(P＜0.05).Gene expression levels of TUFM,MAVS,NP,M2 and PB1-F2 were in the IAV+Rapa+HBD3 group were lower than those in the IAV+Ra-pa group(P＜0.05).The protein expression level of P62 in the IAV+Rapa+HBD3 group was higher than that in the IAV+Rapa group(P＜0.05).The protein expression levels of LC3Ⅱ/LC3Ⅰ were lower in the IAV+Rapa+HBD3 group than in the IAV+Rapa group(P＜0.05).CONCLUSION With the increase of viral titer or the prolongation of in-fection time,the proliferation of IAV in BEAS-2B cells increases,and the cell damage exacerbates.HBD3 can inhibit the replication of IAV after its entry into the cells;HBD3 can protect host cells and inhibit IAV replication by inhibiting MA-VS,TUFM-mediated mitophagy pathways.

OBJECTIVE To investigate the inhibitory effect of human β defensin-3(HBD3)on the replication of in-fluenza A virus(IAV)[A/PR/8/34(H1N1)virus strain]in human bronchial epithelial cells(BEAS-2B)via the mitochondrial autophagy pathway.METHODS BAS-2B cells were infected with IAV,and cell condition observa-tion:plaque assay and light microscopy.Drug treatment:HBD3,autophagy agonist rapamycin(Rapa),autoph-agy inhibitor LY294002;The expression levels of TUFM、MAVS、NP、M2 and PB1-F2 genes were detected by real-time fluorescence quantitative polymerase chain reaction(qPCR).Western blot was used to detect the protein expression levels of P62、LC3Ⅱ and LC3Ⅰ.RESULTS Plaque formation experiments showed that the number of plaques increased with the increase of viral titer.With the increase of viral titer or the prolongation of infection time,the expres-sion levels of TUFM,MAVS,NP,M2 and PB1-F2 genes in BEAS-2 B cells gradually increased,the expression levels of P62 protein decreased,and the protein expression levels of LC3Ⅱ/LC3Ⅰ increased(P＜0.05).Forty-eight hpi of BE-AS-2B cells with IAV,the number of cells in the IAV group was significantly lower than that in the IAV+HBD3 group,the intercellular space was enlarged,and the cells shrunk significantly.Compared with the IAV group,the expression lev-els of TUFM,MAVS,NP,M2 and PB1-F2 genes in BEAS-2B cells in the IAV+HBD3 group decreased,the expres-sion levels of P62 protein increased,and the protein levels of LC3Ⅱ/LC3Ⅰ decreased(P＜0.05).Gene expression levels of TUFM,MAVS,NP,M2 and PB1-F2 were in the IAV+Rapa+HBD3 group were lower than those in the IAV+Ra-pa group(P＜0.05).The protein expression level of P62 in the IAV+Rapa+HBD3 group was higher than that in the IAV+Rapa group(P＜0.05).The protein expression levels of LC3Ⅱ/LC3Ⅰ were lower in the IAV+Rapa+HBD3 group than in the IAV+Rapa group(P＜0.05).CONCLUSION With the increase of viral titer or the prolongation of in-fection time,the proliferation of IAV in BEAS-2B cells increases,and the cell damage exacerbates.HBD3 can inhibit the replication of IAV after its entry into the cells;HBD3 can protect host cells and inhibit IAV replication by inhibiting MA-VS,TUFM-mediated mitophagy pathways.

Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Neuroblastoma(NB)is the most common extracranial solid tumor in children.It is notable for highly heterogeneous and associated with tumor histologic classification and differentiation status, with ganglioneuroma representing fully mature and differentiated NB.Differentiation therapy reduces the adverse reactions caused by treatment without affecting normal cells and tissues by inducing the redifferentiation of NB cells, and has a good development prospect in the maintenance treatment of high-risk NB patients.Therefore, studying the key molecules and signaling pathways affecting NB differentiation is significant to further clarify the pathogenesis and improve the prognosis of neuroblastoma.This article reviews the important molecules related to NB cell differentiation, signaling pathways and the research progress of differentiation induction therapy.

Different microorganisms can cause intraperitoneal infection. This study was to distinguish different microbial infections by urine analysis. Rats were intraperitoneally injected with Escherichia coli, Staphylococcus aureus, and Candida albicans, separately. Urine samples were collected from rats at 0, 12, 36 and 72 h after infection. Urinary proteins were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with the control (without infection), a total of 69 differential proteins were identified in rats injected with E. coli. A total of 31 differences proteins were identified in rats injected with S. aureus. A total of 38 differential proteins were identified in rats injected with C. albicans. Urine proteome was different when rats were infected by different microorganisms, suggesting that urine may have the potential for differential diagnosis of different intraperitoneal infections.
Animals ; Chromatography, Liquid ; Escherichia coli ; Proteome ; Rats ; Staphylococcus aureus ; Tandem Mass Spectrometry

Objective:To assess the impact of integrated curriculum (vertically integrated curriculum system) and traditional curriculum system on the perceptions of post competency of undergraduate medical students.Methods:Bibliographic retrieval method and expert consultation were used to compile the questionnaire of perceptions on the post competency of undergraduate medical students. The questionnaire was conducted online to survey the undergraduate medical students from Shanghai Jiao Tong University School of Medicine during March to April, 2019. SPSS 20.0 software was applied for data analysis, chi-square test was used to analyze the classroom teaching forms of medical undergraduates who received different curriculum systems, and their cognition of the doctor post competency and cognitive pathways, and finally the top 10 important competencies were compared.Results:A total of 200 questionnaires were distributed and 167 were recovered, with a recovery rate of 83.5%. Workshop learning was more common in the vertically integrated undergraduate curriculum. Compared with Chinese traditional curriculum, the medical students taught by the vertically integrated undergraduate curriculum were much better informed about competency ( P<0.05). The access to knowledge of competency was also statistically different between two groups of students ( P<0.05). Conclusion:The vertically integrated curriculum is more efficient in helping undergraduate medical students to acquire knowledge about competency.

Objective To investigate the peripherally inserted central catheter (PICC) to improve the accuracy of three valve PICC head end position of the fortune with endocardial mapping method.Methods 204 patients with PICC were randomly divided into observation group and control group according to the digital table,102 cases in each group.The observation group used saline infusion method by three valve PICC guided endocardial mapping catheter tip location.The control group received conventional positioning surface positioning method.The accurate rate of end position of the two groups was compared.Results The head position accuracy of the observation group was significantly higher than that of the control group (100.00％ vs.93.14％,x2 =3.003,P =0.004).Conclusion The use of saline drip instillation to guide intracardiac electrogram during PICC catheter placement can reduce ectopia and improve the accuracy of the head end position of the catheter,and it is worthy of promotion.

Currently,the undergraduate teaching of pediatrics in China is still the science-based curriculum,having a big gap with international medical teaching idea and mode.Medical colleges of the University of Ottawa and Shanghai Jiao Tong University co-established the 0ttawa-Shanghai Joint School of Medicine (OSJSM) in October 2014.By enriching the curriculum content (including theory,skill and professionalism),adding "active" teaching,introducing clinical pediatricians to the students-management group,and applying formative evaluation method,the OSJSM started transforming to the competency-based cultivation,improving the teaching quality.