Objective:To investigate the mediating effect of inflammatory factors in the association between low density lipoprotein-cholesterol(LDL-C) and thyroid associated ophthalmopathy(TAO).Methods:This study was a prospective study, which icluded a total of 86 patients with Graves′ disease who attended the Department of Endocrinology of the First Affiliated Hospital of Zhengzhou University from January 2021 to June 2022. Among them, there were 56 patients with Graves′ disease accompanied by TAO, including 30 cases in the inactive group and 26 in the active group. Additionally, there were 30 cases having Graves′ disease alone. The relationship between LDL-C, inflammatory factors, and the onset and activity of TAO were analyzed using binary logistic regression. Mediation analysis was used to explore the mediating effect of inflammatory factors in the association between LDL-C and TAO onset and activity.Results:Interleukin(IL) -6 was a potential mediator that linking the association between LDL-C and TAO onset: LDL-C had a direct effect on TAO(Total effect value=0.274, 95% CI 0.161-0.386), while IL-6(mediated effect=0.067, 95% CI 0.011-0.123) and IL-17(mediated effect=0.042, 95% CI 0.007-0.077) partially mediated the effect of LDL-C on TAO, accounting for 24.45% and 15.33% of the total effect, respectively. IL-6 was a potential mediator of the association between LDL-C and TAO activity: LDL-C had a direct effect on TAO activity(Total effect value=0.320, 95% CI 0.204-0.435), and IL-6(mediated effect=0.103, 95% CI 0.021-0.185) partially mediated the effect of LDL-C on TAO activity, with a mediation effect of 32.19%. Conclusion:IL-6 plays a partiall mediating role in the association of LDL-C with TAO onset and activity.

Objective:To study the correlation between adverse clinical outcomes and early postnatal weight loss(representing the results of fluid management) during hospitalization in extremely premature infants(EPIs).Methods:From January 2019 to March 2023, EPIs (gestational age (GA)<28 weeks) admitted to neonatal intensive care unit(NICU) of our hospital were retrospectively analyzed. According to weight loss (WL) within the first 3 d after birth, the infants were assigned into no-WL group, WL<6% group, WL 6%-10% group and WL>10% group. The following items were compared among the four groups: fluid intake within the first 7 d after birth, the incidences of hemodynamically significant patent ductus arteriosus (hsPDA), PDA requiring surgical ligation, duration of invasive mechanical ventilation, ≥stage II necrotizing enterocolitis(NEC), grade 3-4 intraventricular hemorrhage(IVH), moderate bronchopulmonary dysplasia (BPD), severe BPD, mortality rates and total length of hospital stay.Results:A total of 119 EPIs were enrolled, including 41 in no-WL group, 22 in WL<6% group, 31 in WL 6%-10% group and 25 in WL>10% group. Among the four groups, no significant differences existed in fluid intake on d1 and d5-d7 after birth ( P>0.05). WL 6%-10% and >10% groups had significantly lower fluid intake during d2-d4 than no-WL group ( P<0.05).On d4, WL 6%-10% and >10% groups had lower fluid intake than WL <6% and no-WL groups( P<0.05).WL 6%-10% and >10% groups showed lower incidences of hsPDA than no-WL group ( P<0.05).WL>10% group had lower incidences of ≥stage II NEC, moderate BPD, shorter duration of invasive mechanical ventilation and total hospital stay than no-WL group( P<0.05). No significant differences existed in the incidences of PDA requiring surgical ligation, grade 3-4 IVH, severe BPD and mortality rates among the four groups ( P>0.05). Conclusions:For EPIs, a certain degree of WL within the first 3 d after birth is beneficial to reduce the incidences of hsPDA, NEC, moderate BPD, duration of invasive mechanical ventilation and total hospital stay. Focusing on body weight is helpful for a more optimal fluid management strategy in the early postnatal period.

Objective To investigate the anti-inflammatory effect of 25-OH vitamin D(25-OH-VD)on neonatal infectious pneumonia(NIP)and its mechanism.Methods A total of 65 children with NIP admitted to Chengdu Women and Children's Central Hospital from January 2022 to January 2023 were selected.According to the severity of the disease,they were divided into mild group(n=34)and severe group(n=31),and 60 healthy neonates in the same period were selected as the control group.Serum 25-OH-VD,interleukin-2(IL-2),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)and IL-1β levels were measured by ELISA.The expressions of vitamin D receptor(VDR),transforming growth factor-β(TGF-β)/nuolea Yes-associated protein(n-YAP)and nuclear transcriptional coactivator PDZ-binding motif(n-TAZ)pathway related proteins in peripheral blood mononuclear cells were detected by Western blot.NIP in vitro models were established by lipopolysaccharide(LPS)stimulation of human lung epithelial cells,which were divided into control group,LPS group and LPS+VD group.Cell viability was detected by CCK-8 assay.The mRNA expressions of recombinant cytochrome P450 27B1(CYP27B1)and VDR in each group were detected by qRT-PCR.The number of YAP positive nuclei in each group was detected by immunocytochemistry.The nuclear translocation of YAP/TAZ complex in each group was detected by immunofluorescence.The expression of inflammatory factor-related proteins in each group was detected by Western blot.Results Compared with the control group,the serum levels of IL-2(1.91±0.18 μ g/L,2.63±0.27 μg/L vs 1.05±0.12 μg/L),IFN-γ(1.73±0.13 μg/L,2.18±0.19 μg/L vs 1.03±0.07 μg/L),TNF-α(1.79±0.08 μg/L,2.38±0.13 μg/L vs 0.97±0.04 μg/L),IL-1 β(2.18±0.07 μg/L,2.59±0.11μg/L vs 0.96±0.02 μg/L),TGF-β(1.67±0.21,2.43±0.42 vs 1.02±0.04),n-YAP(2.08±0.11,4.23±0.37 vs 0.99±0.02)and n-TAZ(2.47±0.42,4.21±0.58 vs 1.03±0.05)proteins of the children in the mild and severe groups were gradually increased,but the content of 25-OH-VD(12.57±2.21 μg/L,7.85±2.03 μg/L vs 16.76±1.02 μg/L)and the expression of VDR(0.73±0.09,0.51±0.06 vs 1.03±0.08)proteins were gradually decreased,and the differences were significant(F=18.983～56.782,all P＜0.001).Cell experiment results showed that cellular survival rate was lower at 12 h(76.23％±0.73％vs 116.72％±2.14％),24 h(57.23％±0.94％vs 125.76％±1.67％)and 48 h(41.23％±0.56％vs 138.56％±1.35％)in the LPS group compared with the control group(t=10.342,26.562,37.821),but the rate of cytosolic n-YAP positivity(47.35±3.47 vs 12.46±1.34),the rate of nuclear translocation of the YAP/TAZ complex(2.56％±0.32％vs 1.01％±0.06％)(t=46.362,26.921),the protein expression levels of IL-2(2.03±0.09vs 1.03±0.08),IFN-γ(2.07±0.21 vs 1.02±0.04),TNF-α(2.18±0.11 vs 0.99±0.02)and IL-1β(3.17±0.42 vs 1.03±0.05)were up-regulated(t=28.341,26.713,31.235,47.823),with significant differences(all P＜0.001),while there was no significant difference in the mRNA expression of CYP27B1 and VDR(t=0.872,0.786,all P＞0.05).Compared with the LPS group,the cell survival rate at 12h(85.23％±0.36％),24h(79.82％±0.63％)and 48h(76.28％±0.72％)and the mRNA expression of CYP27B1(4.42±0.14)and VDR(5.13±0.56)were elevated in the LPS+VD group,while the nucleus n-YAP positivity(24.41±3.23),nuclear translocation of the YAP/TAZ complex(1.47％±0.26％),IL-2(1.21±0.06),IFN-γ(1.13±0.42),TNF-α(1.03±0.37)and IL-1β(1.61±0.58)protein levels were down-regulated,and the differences were significant(t=7.263,19.892,23.145,27.872,26.982,14.762,13.623,18.273,25.314,27.873,22.134,all P＜0.0 1).Conclusion The serum 25-OH-VD level is related to the severity of NIP.Exogenous VD supplementation may play an anti-inflammatory role in reducing NIP injury by regulating the TGF-β-mediated YAP/TAZ nuclear translocation mechanism.

Objective To understand the current situation of quality management and implementation of risk-based quality management in clinical trial institutions.Methods In the form of questionnaires,Questionnaire Star was used to create the questionnaire,which was sent to clinical trial organisations in all provinces and cities to fill in through emails and institutional WeChat groups.Results The questionnaire results from 123 clinical trial institutions from 25 provinces were included for analysis.The quality management status was as follows:104(84.6%)institutions of the main quality management mode were the internal quality control by GCP department.On average,each institution had 3、4 full-time staff for quality management,with an average of 1 full-time staff to manage 16.8 projects and 10.9 specialties.In the last three years,65(52.8%)institutions conducted training for researchers 2-3 times/year.Ninety-five(77.2%)institutions had established a clinical trial funding allocation system.Forty-nine(39.2%)institutions had established GCP informatization management system and 44(35.2%)institutions had established risk-based quality management model.In the case of coordination between the clinical trial institution and the sponsor,47(41.2%)institutions did not not aware of the sponsor's/CRO's quality management plan in their collaboration with the sponsor.Conclusion The surveyed institutions have weaknesses,such as insufficient dedicated personnel for quality management,low utilization rate of GCP information systems.The collaborative capacity between clinical trial institutions and sponsors needs to be improved,and the implementation rate of risk-based quality management is also low.