Owing to physical and mental immaturity， children require special protection in medical research. With the rise of real-world research， ethical issues such as informed consent， privacy protection， and risk-benefit assessment have become particularly prominent in pediatric studies due to diverse data sources and complex study designs. Although institutional review boards constitute the primary safeguard for research ethics， journal editors play an irreplaceable role in pre-publication ethical gatekeeping. From the perspective of journal editors， this paper reviewed common ethical risks in pediatric real-world research， including the lack of scientific value in research topics， unjust control groups， inadequate privacy protection， and other issues. Based on the four principles of biomedical ethics and the three-tier review process， this study constructed a structured ethical review framework. The framework comprised three levels： basic compliance screening at the initial review， substantive risk assessment and grading at the secondary review， and escalated handling of high‑risk manuscripts at the final review， and it achieved a transformation from formal compliance verification to substantive ethical assessment led by risk grading. This could provide effective ethical risk assessment tools for journal editors and offer references for medical journals to improve pre-publication ethical governance.

Objective:To construct an early warning model for gestational diabetes mellitus (GDM) based on baseline data, vitamin D (VitD) , and thyroid function status.Methods:A prospective study was conducted to select 126 patients with GDM (GDM group) and 126 pregnant women without GDM (control group) admitted to the Obstetrics Department of Qinhuangdao First Hospital from Jan. 2022 to May. 2024. The single-factor and multi-factor LASSO Logistic regression analysis was used to analyze the influencing factors of the risk of GDM. Based on the results of the multi-factor analysis, an early warning model for GDM was constructed, evaluated, and validated.Results:Age, pre-pregnancy body mass index (BMI) , family history of diabetes, thyroid function, low density lipoprotein (LDL-C) , triglyceride (TG) , VitD, fasting plasma glucose (FPG) , glycated hemoglobin (HbA1c) and blood uric acid were compared, and the differences were statistically significant ( P < 0.05) . LASSO Logistic regression analysis showed that family history of diabetes, hypothyroidism, pre-pregnancy BMI, TG, VitD, FPG, HbA1c and blood uric acid were independently correlated with the risk of GDM ( P < 0.05) . A GDM early warning model was constructed based on the results of multiple factors, with a C-index of 0.876, indicating good predictive performance; The model evaluation and validation results show that the model has good internal and external calibration, high consistency between predicted values and actual observed values, and good predictive value and discrimination in external data sets. Conclusions:Baseline data such as hypothyroidism, VitD, and pre-pregnancy BMI are independent factors that affect the occurrence of GDM. The early warning model for GDM based on these indicators has good predictive performance and clinical applicability, and can be used as an effective model for early prediction of GDM in clinical practice, as well as guiding clinical prevention and treatment efforts.

Objective:To establish ICP-MS method for determining the Class 1 and Class 2A elemental impurities in pharmaceutical excipients polysorbates according to ICH Q3D(R2)Guidelines.Class 1 elemental impurities include As,Cd,Hg and Pb;Class 2A elemental impurities include Co,Ni and V.Methods:The analysis was performed using ICP-MS with the following parameters.Plasma mode:HMI-8,carrier gas:He,sampling depth:10.0 mm.RF power:1 600 W,the carrier gas flow,the nebulizer gas flow and the auxiliary gas flow were all 0.8 L·min-1.The plasma gas flow was 15.0 L·min-1.The speed of nebulizer pump was0.10 r·min-1.The temperature of atomizer chamber was 2.0℃.Analytical method:internal standard method.Results:The correla-tion coefficient for all elemental impurities was not less than 0.999.Spiked recoveries ranged between 85%-115.0%,with RSD is not more than 5.0%.The RSD of precision rate was not more than 10.0%.The contents of 7 elemental impurities in 15 batches of the samples were all less than PDE for injection set by ICH Q3D(R2)guidelines.Conclusion:The developed ICP-MS method demonstrates high sensitivity,good precision,and accuracy,making it suitable for controlling the Class 1 and Class 2A elemental impurities in polysorbate pharma-ceutical excipients.The results shows low risks of elemental impurities in commercial pharmaceutical excipients polysorbates.

Objective:To construct an early warning model for gestational diabetes mellitus (GDM) based on baseline data, vitamin D (VitD) , and thyroid function status.Methods:A prospective study was conducted to select 126 patients with GDM (GDM group) and 126 pregnant women without GDM (control group) admitted to the Obstetrics Department of Qinhuangdao First Hospital from Jan. 2022 to May. 2024. The single-factor and multi-factor LASSO Logistic regression analysis was used to analyze the influencing factors of the risk of GDM. Based on the results of the multi-factor analysis, an early warning model for GDM was constructed, evaluated, and validated.Results:Age, pre-pregnancy body mass index (BMI) , family history of diabetes, thyroid function, low density lipoprotein (LDL-C) , triglyceride (TG) , VitD, fasting plasma glucose (FPG) , glycated hemoglobin (HbA1c) and blood uric acid were compared, and the differences were statistically significant ( P < 0.05) . LASSO Logistic regression analysis showed that family history of diabetes, hypothyroidism, pre-pregnancy BMI, TG, VitD, FPG, HbA1c and blood uric acid were independently correlated with the risk of GDM ( P < 0.05) . A GDM early warning model was constructed based on the results of multiple factors, with a C-index of 0.876, indicating good predictive performance; The model evaluation and validation results show that the model has good internal and external calibration, high consistency between predicted values and actual observed values, and good predictive value and discrimination in external data sets. Conclusions:Baseline data such as hypothyroidism, VitD, and pre-pregnancy BMI are independent factors that affect the occurrence of GDM. The early warning model for GDM based on these indicators has good predictive performance and clinical applicability, and can be used as an effective model for early prediction of GDM in clinical practice, as well as guiding clinical prevention and treatment efforts.

Objective:To establish ICP-MS method for determining the Class 1 and Class 2A elemental impurities in pharmaceutical excipients polysorbates according to ICH Q3D(R2)Guidelines.Class 1 elemental impurities include As,Cd,Hg and Pb;Class 2A elemental impurities include Co,Ni and V.Methods:The analysis was performed using ICP-MS with the following parameters.Plasma mode:HMI-8,carrier gas:He,sampling depth:10.0 mm.RF power:1 600 W,the carrier gas flow,the nebulizer gas flow and the auxiliary gas flow were all 0.8 L·min-1.The plasma gas flow was 15.0 L·min-1.The speed of nebulizer pump was0.10 r·min-1.The temperature of atomizer chamber was 2.0℃.Analytical method:internal standard method.Results:The correla-tion coefficient for all elemental impurities was not less than 0.999.Spiked recoveries ranged between 85%-115.0%,with RSD is not more than 5.0%.The RSD of precision rate was not more than 10.0%.The contents of 7 elemental impurities in 15 batches of the samples were all less than PDE for injection set by ICH Q3D(R2)guidelines.Conclusion:The developed ICP-MS method demonstrates high sensitivity,good precision,and accuracy,making it suitable for controlling the Class 1 and Class 2A elemental impurities in polysorbate pharma-ceutical excipients.The results shows low risks of elemental impurities in commercial pharmaceutical excipients polysorbates.

OBJECTIVE To develop a rapid method for detection of activated RhoA protein using the high content imaging system(HCIS).METHODS Hek293 or CHO cells were seeded in 96-well plates and subjected to starvation treatment after attachment.Hek293 cells were incubated with nocodazole,a RhoA agonist,at concentrations of 0(vehicle control),10-11,10-10,10-9,10-8,10-7,10-6,10-5 and 10-4 mol·L-1 for 3,10 and 30 min respectively.CHO cells were incubated with nocodazole,lyso-phosphatidic acid(LPA)and calpain at the same concentrations for 3,10 and 30 min respectively.Imme-diately after incubation,the cells were fixed with 3.7%formaldehyde solution and stained using Hoechst and rhodamin phallodin at room temperature and protected from light.Images were captured using HCIS and analyzed statistically.Changes in the mean fluorescence intensity(MFI)were used to assess the activation of RhoA protein by the drugs.RESULTS Compared with the vehicle control group,the MFI of Hek293 cells treated with nocodazole for 3 min significantly increased at concentra-tions ranging from 10-10 to 10-6 mol·L-1(P<0.01).When the treatment duration was extended to 30 min,MFI elevations were observed at concentrations between 10-10 and 10-4 mol·L-1(P<0.01),indicating the activation of RhoA protein.In CHO cells,compared with the vehicle control group,MFI was increased after 10-10-10-6 mol·L-1 nocodazole treatment of 10 min and 30 min(P<0.05,P<0.01).Similarly,MFI was also increased under various conditions of LPA and calpeptin treatment.LPA 10-11-10-4 mol·L-1 treatment of 3 min and 10-11,10-8-10-4 mol·L-1 treatment of 10 min and 10-11-10-9,10-7,10-6,10-4 mol·L-1 treatment of 30 min all resulted in an elevated MFI(P<0.05,P<0.01).Calpeptin 10-11-10-6,10-4 mol·L-1 treatment of 10 min and 10-11 and 10-4 mol·L-1 treatment of 30 min also resulted in an elevated MFI(P<0.05,P<0.01).These results indicated that RhoA protein was effectively activated.CONCLUSION A method for rapid detection of RhoA protein activation has been established,which is capable high-throughput,rapid and easy detection of activated RhoA protein.

Objective:To explore the mechanism of ubiquitin-specific protease 11(USP11)affecting the proliferation and invasion of oral squamous cell carcinoma(OSCC)cells by regulating IGF2BP3 expression.Methods:USP11 expression in OSCC tissues and adja-cent tissues from OSCC patients(n=50)was detected by immunohistochemistry and western blot,and USP11 expression in normal hu-man oral keratinocyte(HOK)cell line and human OSCC cell lines SCC-25 and CAL-27 was detected by western blot.SCC-25 and CAL-27 cells were transfected with siRNA USP11(si-USP11)or siRNA negative control(si-NC).Western blot was performed to de-tect the silencing efficiency of USP11.CCK-8,wound healing assay and Transwell assay were carried out to evaluate the effects of USP11 silencing on cell proliferation,migration and invasion.Western blot was employed to detect IGF2BP3 expression after the knockdown of USP11.Nude mice were inoculated with SCC-25 cells to construct the transplanted tumor model,and the inhibitory effect of USP11 knock-down on SCC-25 cell tumorigenicity was investigated.Results:The USP11 protein level in carcinoma tissues of OSCC patients was significantly higher than in the adjacent tissues,USP11 protein expression was significantly higher in SCC-25 and CAL-27 cells than in HOK cells.The knockdown of USP11 markedly reduced the proliferation,migration and invasion of SCC-25 and CAL-27 cells,and down-regulated the expression of IGF2BP3 cells.Compared with the USP11 silencing group,the proliferation,migration and invasion of SCC-25 and CAL-27 cells were significantly increased in the simultaneous knockdown of USP11 and overexpression of IGF2BP3 cells.Compared with the USP11 overexpression group,the proliferation,migration and invasion of SCC-25 and CAL-27 cells were decreased in the simultaneous IGF2BP3 knockdown and USP11 overexpression cells.Tumorigenicity experiments in nude mice showed that the tumor volume and weight were significantly declined by USP11 knockdown.Conclusion:USP11 is highly expressed in OSCC tissues,which may promote the proliferation,migration and invasion of OSCC cells through up-regulation of IGF2BP3 expression.

Background and purpose:Thyroid dysfunction can frequently be discovered in breast cancer patients during long-term follow-up after receiving post-operative radiation therapy(PORT).This study aimed to compare serum levels of thyroid transcription factors(TTFs)TTF-1 and paired box 8(PAX-8)before and after PORT in breast cancer patients,combined with the results of serological thyroid indicators tests,and to analyze the relationship between the changes in serum levels of these two kinds of TTFs and thyroid dysfunction after breast cancer PORT.Methods:Female breast cancer patients without thyroid disease records who received PORT in Department of Radiation Oncology,Shanghai Ninth People's Hospital Huangpu Branch,Shanghai Jiao Tong University School of Medicine from Jan.2022 to Jun.2022 were prospectively selected,and were divided into two groups according to being with or without supraclavicular radiation field.All the patients had given informed consent before joining the study.The study design was approved by the ethic committee of our hospital(Ethic Approval No.2021-KY-2).Serum levels of TTF-1 and PAX-8,serological thyroid indicators[triiodothyronine(T3),tetraiodothyronine(T4),free triiodothyronine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH)and thyroid peroxidase antibody(TPO-Ab)]were recorded before PORT,at the end of PORT,6,12 and 24 months after the end of PORT,respectively.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:Eighty patients were enrolled in this study(40 in each group).A total of 19 patients who had hypothyroidism were divided in two groups,15 in supraclavicular field group(SC group)and 4 in non-supraclavicular field group(NSC group),respectively(P=0.004).Levels of TTF-1[5.70(5.11,7.13)vs 6.68(5.15,7.57),P=0.296]and PAX-8(5.26±1.01 vs 5.66±1.37,P=0.149)did not show statistically significant deference between two groups before PORT.In SC group,levels of TTF-1 and PAX-8 gradually rose in 12 months after the end of PORT.In NCS group,levels of TTF-1 and PAX-8 did not change significantly during 24 months after the end of PORT.Test results of serum TTF-1 between two groups were statistically different at 6 months[6.99(4.73,13.94)vs 5.79(5.01,6.28),P=0.049],12 months[7.65(5.02,17.85)vs 5.43(4.52,6.22),P=0.005]after the end of PORT,while test results of serum PAX-8 between two groups were statistically different at 12 months[6.79(4.86,14.30)vs 5.81(4.70,7.25),P=0.042]after the end of PORT.The median values of TTF-1 and PAX-8 test results at 12 months after the end of PORT in SC group which were both significantly higher compared with NSC group were selected as the referent thresholds.Patients in SC group whose test results were higher than referent thresholds were defined as TTF-1/PAX-8 elevating subgroups,and patients whose test results under the threshold defined as TTF-1/PAX-8 normal subgroups.The incidences of hypothyroidism were higher in elevation subgroups than in normal subgroups(65.0%vs 10.0%,60.0%vs 15.0%,respectively,P=0.001,P=0.008,respectively).Positive correlations were observed between the elevation of TTF-1/PAX-8 at 12 months after the end of PORT and hypothyroidism after breast cancer supraclavicular field radiation(OR=9.702,3.930,and P=0.020,0.046,respectively)according to multivariate analysis.Conclusion:Thyroid dysfunction after breast cancer PORT was mainly manifested with hypothyroidism;supraclavicular field radiation may significantly increase the incidence of hypothyroidism;serum levels of TTF-1 and PAX-8 elevated obviously in breast cancer PORT patients who had hypothyroidism after receiving supraclavicular field radiation.

Background and purpose:Thyroid dysfunction can frequently be discovered in breast cancer patients during long-term follow-up after receiving post-operative radiation therapy(PORT).This study aimed to compare serum levels of thyroid transcription factors(TTFs)TTF-1 and paired box 8(PAX-8)before and after PORT in breast cancer patients,combined with the results of serological thyroid indicators tests,and to analyze the relationship between the changes in serum levels of these two kinds of TTFs and thyroid dysfunction after breast cancer PORT.Methods:Female breast cancer patients without thyroid disease records who received PORT in Department of Radiation Oncology,Shanghai Ninth People's Hospital Huangpu Branch,Shanghai Jiao Tong University School of Medicine from Jan.2022 to Jun.2022 were prospectively selected,and were divided into two groups according to being with or without supraclavicular radiation field.All the patients had given informed consent before joining the study.The study design was approved by the ethic committee of our hospital(Ethic Approval No.2021-KY-2).Serum levels of TTF-1 and PAX-8,serological thyroid indicators[triiodothyronine(T3),tetraiodothyronine(T4),free triiodothyronine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH)and thyroid peroxidase antibody(TPO-Ab)]were recorded before PORT,at the end of PORT,6,12 and 24 months after the end of PORT,respectively.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:Eighty patients were enrolled in this study(40 in each group).A total of 19 patients who had hypothyroidism were divided in two groups,15 in supraclavicular field group(SC group)and 4 in non-supraclavicular field group(NSC group),respectively(P=0.004).Levels of TTF-1[5.70(5.11,7.13)vs 6.68(5.15,7.57),P=0.296]and PAX-8(5.26±1.01 vs 5.66±1.37,P=0.149)did not show statistically significant deference between two groups before PORT.In SC group,levels of TTF-1 and PAX-8 gradually rose in 12 months after the end of PORT.In NCS group,levels of TTF-1 and PAX-8 did not change significantly during 24 months after the end of PORT.Test results of serum TTF-1 between two groups were statistically different at 6 months[6.99(4.73,13.94)vs 5.79(5.01,6.28),P=0.049],12 months[7.65(5.02,17.85)vs 5.43(4.52,6.22),P=0.005]after the end of PORT,while test results of serum PAX-8 between two groups were statistically different at 12 months[6.79(4.86,14.30)vs 5.81(4.70,7.25),P=0.042]after the end of PORT.The median values of TTF-1 and PAX-8 test results at 12 months after the end of PORT in SC group which were both significantly higher compared with NSC group were selected as the referent thresholds.Patients in SC group whose test results were higher than referent thresholds were defined as TTF-1/PAX-8 elevating subgroups,and patients whose test results under the threshold defined as TTF-1/PAX-8 normal subgroups.The incidences of hypothyroidism were higher in elevation subgroups than in normal subgroups(65.0%vs 10.0%,60.0%vs 15.0%,respectively,P=0.001,P=0.008,respectively).Positive correlations were observed between the elevation of TTF-1/PAX-8 at 12 months after the end of PORT and hypothyroidism after breast cancer supraclavicular field radiation(OR=9.702,3.930,and P=0.020,0.046,respectively)according to multivariate analysis.Conclusion:Thyroid dysfunction after breast cancer PORT was mainly manifested with hypothyroidism;supraclavicular field radiation may significantly increase the incidence of hypothyroidism;serum levels of TTF-1 and PAX-8 elevated obviously in breast cancer PORT patients who had hypothyroidism after receiving supraclavicular field radiation.

Objective:To explore the common signaling pathways of Helicobacter pylori(Hp) infection and rosacea and screen Hub genes by bioinformatic analysis. Methods:Gene expression data sets related to Hp (GSE70394) and rosacea (GSE65914) were downloaded from GEO database. The common differentially expressed genes (DEGs) were screened by using the limma package of R and Venn diagram. Metascape database was used for gene ontology(GO) enrichment analysis, and clusterProfiler package of R was used for Kyoto encyclopedia of genes and genomes(KEGG) analysis on up-regulated and down-regulated genes. Subsequently, STRING and Cytoscape software were used to establish protein-protein interaction(PPI) network and its internal plug-in MCODE and Cytohubba were applied to screen key functional modules and Hub genes, then Hub genes were imported into GeneMANIA to construct Hub genes co-expression network. Finally, GO and KEGG enrichment analysis of Hub genes were performed again.Results:GSE70394 and GSE65914 data sets included three samples of AGS cells without Hp infection and three samples of AGS cells 24 hours after Hp infection, skin tissues from nineteen rosacea patients and ten healthy volunteers, respectively. Finally, 139 common DEGs were obtained including 93 up-regulated genes and 46 down-regulated genes. GO enrichment analysis mainly focused on smooth muscle cell regulation, vascular development and lipid metabolism. KEGG enrichment analysis mainly involved lipid and atherosclerosis, inflammatory response and immune-related pathways, such as PPAR signaling pathway, cytokine-cytokine receptor interaction, Th17 cell differentiation, IL-17 signaling pathway and NF-κB signaling pathway. Total of 16 Hub genes were identified by Cytohubba, including SPRR1B, GCLM, KRT16, GPX2, S100A2, SOD2, MMP1, MSMO1, HMOX1, GLRX, IL-1β, CXCL1, PPARγ, HMGCS1, SRXN1 and SPRR3.Conclusion:There is a link existing between Hp infection infection and rosacea. Hp may be involved in the occurrence and development of rosacea by mediating inflammatory immune response and regulating lipid metabolism, the selected Hub genes and related signaling pathways may provide a theoretical reference for subsequent correlation analysis.