BACKGROUND:Preliminary research by our group suggests that targeting fibroblast growth factor receptor 1(FGFR1)may be an effective strategy for treating RA. OBJECTIVE:To investigate the effects of an FGFR1 inhibitor(PD173074)on bone destruction in rats with collagen-induced arthritis. METHODS:Twenty-five female Sprague-Dawley rats were randomly divided into five groups:normal control group,model group,methotrexate group,low-dose PD173074 group,and high-dose PD173074 group.Except for the normal control group,rat models of type Ⅱ collagen-induced arthritis were made in each group.After successful modeling,rats were injected intraperitoneally with sterile PBS in the normal and model groups,1.04 mg/kg methotrexate in the methotrexate group,and 5 and 20 mg/kg in the low-dose group and high-dose PD173074 groups,once a week.After 4 weeks of drug administration,clinical symptoms and joint swelling in rats were observed.Micro-CT was used for three-dimensional reconstruction and analysis of the ankle joints.Pathological changes in the ankle joints were observed.Periarticular angiogenesis and the expression of receptor activator of nuclear factor-Κb ligand were detected.The expression levels of p-FGFR1,vascular endothelial growth factor A,and tartrate-resistant acid phosphatase in the synovial membrane were measured.Pathological changes in the liver,spleen,and kidney were observed and liver,spleen,and kidney indices were calculated. RESULTS AND CONCLUSION:PD173074 could alleviate clinical symptoms and joint swelling,delay bone loss,improve bone structure,reduce synovial invasion and cartilage bone erosion,reduce the number of periarticular osteoclasts,inhibit angiogenesis in synovial tissues,reduce the expression of receptor activator of nuclear factor-Κb ligand,and inhibit the expression of FGFR1 phosphorylated protein,tartrate-resistant acid phosphatase and vascular endothelial growth factor A.Pathologic observation of the liver,spleen and kidney in rats showed no obvious toxic side effects after PD173074 treatment.To conclude,the FGFR1 inhibitor can delay the progression of joint inflammation and bone destruction and inhibit angiogenesis in the rat model of type Ⅱ collagen-induced arthritis.The therapeutic effect of PD173074 has been preliminarily validated in the type Ⅱ collagen-induced arthritis model and may act by inhibiting FGFR1 phosphorylation,which provides a direction for the search of new therapeutic targets for rheumatoid arthritis.

BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

With the extensive application of nuclear technology in industry, agriculture, and medicine, the safety issues associated with neutron radiation have become increasingly prominent. Due to their high penetrability and strong ionization effect, neutrons can cause serious health risks by directly damaging DNA or inducing secondary γ radiation. Therefore, the neutron radiation protection has become a core challenge in radiation protection, especially the research and development of neutron shielding materials. To ensure the safe development of nuclear technology, neutron shielding materials are indispensable and constitute a fundamental core technology for radiation protection. This paper reviews the theory of neutron radiation protection and the research progress of neutron shielding materials, with a focus on the current application status and existing problems of neutron shielding materials. This article also discusses the future development trends. This review aims to provide theoretical support and technical references for the safe application and development of nuclear technology.

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

OBJECTIVE: Angelicae Sinensis Radix (ASR, Danggui in Chinese), Cistanches Herba (CH, Roucongrong in Chinese), Ginseng Radix et Rhizoma (PG, Renshen in Chinese), and Panacis Quinquefolii Radix (PQ, Xiyangshen in Chinese), widely used as medicine and dietary supplement around the world, are susceptible to fungal and mycotoxin contamination. In this study, we aim to analyze their fungal community by DNA metabarcoding. METHODS: A total of 12 root samples were collected from three main production areas in China. The samples were divided into four groups based on herb species, including ASR, CH, PG, and PQ groups. The fungal community on the surface of four root groups was investigated through DNA metabarcoding via targeting the internal transcribed spacer 2 region (ITS2). RESULTS: All the 12 samples were detected with fungal contamination. Rhizopus (13.04%-74.03%), Aspergillus (1.76%-23.92%), and Fusarium (0.26%-15.27%) were the predominant genera. Ten important fungi were identified at the species level, including two potential toxigenic fungi (Penicillium citrinum and P. oxalicum) and eight human pathogenic fungi (Alternaria infectoria, Candida sake, Hyphopichia burtonii, Malassezia globosa, M. restricta, Rhizopus arrhizus, Rhodotorula mucilaginosa, and Ochroconis tshawytschae). Fungal community in ASR and CH groups was significantly different from other groups, while fungal community in PG and PQ groups was relatively similar. CONCLUSION DNA metabarcoding revealed the fungal community in four important root herbs. This study provided an important reference for preventing root herbs against fungal and mycotoxin contamination.

Background Silicosis is an occupational disease mainly characterized by pulmonary progressive fibrosis induced by the accumulation of free silica (SiO₂) in the lungs due to long-term exposure to SiO₂ dust. It has been shown that neutrophil extracellular traps (NETs) are increased in the lung tissues of silicotic mice after 28 d SiO₂ exposure, but it is unclear how the levels of NETs change throughout entire progression of silicosis in mice. Objective To observe the levels of NETs and pathological changes in the lungs of silicotic mice after different duration of SiO₂ exposure, and to confirm the possible role and significance of NETsin the development of SiO₂-induced pulmonary fibrosis. Methods A total of 28 SPF male C57BL/6J mice were randomly divided into a control group, and a model group, and the model group was subdivided into, a 2 d model group, a 7 d model group, and a 28 d model group, with 7 mice in each group. The mice in the model groups were given intratracheal instillation with 10 mg SiO₂ suspension (50 μL), and the mice in the control group were received same volume of saline. Mice were sacrificed and samples were collected at designed time points. The pathological changes of lung tissues of mice were observed after hematoxylin-eosin (HE) and Van Gieson (VG) staining. Immunofluorescence was used to observe the NETs markers citrullination histone H3 (CitH3) and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF), and the percentage of NETs-positive cells was calculated. PicoGreen fluorescent dye kit was used to detect the content of extracelluar DNA (ex-DNA) in mouse BALF, and the expression levels of fibrosis-related proteins α-smooth muscle actin (α-SMA) and fibronectin (FN) and NETs marker CitH3 in lung tissues of mice were detected by Western blot (WB). Results Compared with the control group, inflammatory cells accumulation, alveolar wall thickening, and collagen deposition were obviously observed in the lungs of the silicosis model groups, and a large number of silicone nodules were recorded in the lung tissues in the 28 d group. Compared with the control group, the expressions of α-SMA and FN in the lung tissue of the 28 d group were significantly increased (P<0.05). The percentages of NETs in BALF increased significantly in the 2 d and the 7 d model group, then decreased in the 28 d model group (P<0.05). Compared with the control group (7.434±0.258) ng·mL⁻¹, the ex-DNA levels in BALF of mice in the 2 d [(35.110±6.331) ng·mL⁻¹], the 7 d [(39.491±6.948) ng·mL⁻¹], and the 28 d [(23.360±4.809) ng·mL⁻¹] model groups were increased (P<0.05), and the increase of ex-DNA in the 2 d and the 7 d model groups were statistically significant (P<0.05). In comparison with the control group, the protein level of CitH3 was significantly increased in the lung tissues of mice in the 7 d model group (P<0.05). Conclusion The content of NETs increases significantly and reaches a peak in the early inflammatory stage of silicosis, and decreases as the disease progresses to the fibrotic stage, suggesting that NETs may play a role in early stage of silicosis.

Objective:To evaluate the association between long-term exposure to ambient ozone (O 3) and sperm quality. Methods:From January 1, 2014, to December 31, 2019, healthy sperm donors were recruited through the Human Sperm Bank of Shandong University Affiliated Reproductive Hospital. A total of 37 977 sperm donation data from 2 971 healthy volunteers were analyzed. The average annual O 3 concentration (0.01°× 0.01°) was matched according to household address. A multivariate mixed-effect model was used to analyze the exposure-response relationship between the average O 3 exposure concentration and sperm quality in the previous year, with each donor as a random intercept. All results were presented as % changes with 95% confidence intervals ( CIs) for all sperm parameters associated with 10 μg/m 3 increases in O 3. The effects of individual characteristics on the association between O 3 and sperm quality were evaluated by stratified analysis. Results:The average O 3 concentration in the year before semen collection was (107.09±7.50) μg/m 3. Each 10 μg/m 3 increase in O 3 was associated with declined sperm concentration (-3.12%, 95% CI:-4.55%, -1.67%), total sperm count (-5.21%, 95% CI:-7.28%, -3.09%), total sperm motility (-1.49%, 95% CI:-2.37%, -0.61%), progressive motility (-2.53%, 95% CI:-3.78%, -1.26%), total motile sperm count (-5.82%, 95% CI:-8.17%, -3.41%), and progressively motile sperm count (-6.22%, 95% CI:-8.73%, -3.64%). Men aged 30 and above, obese, and with lower education levels might be more susceptible to the influence of O 3 on sperm quality, but the difference was not statistically significant ( P>0.05). Conclusion:Long-term exposure to O 3 in Shandong Province is associated with a decrease in sperm quality.

Objective:To assess the prevalence and type of tissue prolapse (TP) occurring after endovascular treatment (ET), investigate the association between TP types and plaque morphological characteristics before ET, and observe in-stent neointimal hyperplasia (NIH) using optical coherence tomography (OCT).Methods:Patients who underwent carotid artery stenting and received pre- and post-ET OCT assessment at Jinling Hospital between July 2018 and December 2019 were collected. Baseline plaque characteristics and TP features were evaluated using OCT. The TPs were classified into two categories: smooth TP (STP) and irregular and/or high attenuated TP (I/HTP). The association between I/HTP and plaque characteristics was analyzed, while NIH feature was also summarized.Results:A total of 29 patients were included in the study, of whom 23 patients (79.3%) presented with TP. Among these 23 patients, 9 were classified as I/HTP and 14 were classified as STP. Compared with STP, I/HTP was more commonly observed in lipid-rich plaques (7/9 vs 2/14, P=0.007), and lesions with cap rupture (7/9 vs 4/14, P=0.036). Additionally, the longitudinal length of TP appeared to be longer in cases with I/HTP compared to those with STP [3.0 (1.5, 4.6) mm vs 1.1 (0.7, 3.2) mm, Z=1.294, P=0.201]. Six patients underwent OCT follow-up for a mean duration of 6.7 months, of whom 3 patients with I/HTP showed severe heterogeneous NIH (50.1%-61.8%), while 1 patient with STP and 2 patients without TP only demonstrated mild NIH. Conclusions:The study observed that I/HTP was commonly found in plaques with larger lipid core and/or cap rupture, and suggested a potential relationship between I/HTP and NIH. These preliminary findings obtained from a limited sample should be verified by prospective large-scale studies.

Objective:To identify the risk factors and to construct a predictive model for early postnatal mortality (with the first 7 days of life) in extremely preterm infants.Methods:This retrospective study involved 244 extremely preterm infants with a gestational age of 22 to 27 weeks and 6 days, born at the Affiliated Hospital of Jining Medical College from January 2017 to December 2022. They were divided into an early survival group ( n=140) and an early mortality group ( n=84), based on survival for ≥7 days after birth. LASSO and logistic regression were used to select risk factors for early mortality. A nomogram predictive model was constructed using the R software program. The goodness-of-fit tests, area under the curve (AUC), calibration curves, and decision curves were used to evaluate its performance and clinical usefulness. Results:LASSO regression and multivariate logistic regression analyses showed that breech delivery ( OR=3.055, 95% CI: 1.125-8.296), intubation in the delivery room ( OR=4.320, 95% CI: 1.328-14.053), diagnosis of grade Ⅲ-Ⅳ neonatal respiratory distress syndrome within 6 h after birth ( OR=11.552, 95% CI: 3.056-43.677), and use of adrenaline in the delivery room ( OR=10.706, 95% CI: 1.454-78.816) were risk factors for early mortality in extremely preterm infants. Conversely, large gestation age ( OR=0.234, 95% CI: 0.125-0.436), antenatal administration of corticosteroids to promote fetal lung maturity ( OR=0.046, 95% CI: 0.014-0.145), and the use of pulmonary surfactant within 6 h after birth ( OR=0.021, 95% CI: 0.004-0.122) were protective factors against mortality. The goodness of fit test of the early death risk nomogram prediction model for extremely preterm infants indicates a good fit ( P=0.702). The AUC of the model was 0.963 (95% CI: 0.943-0.983), with a sensitivity of 0.904 (95% CI: 0.806-0.949), specificity of 0.892 (95% CI: 0.829-0.938), and accuracy of 0.880. Decision curve analysis indicated that a threshold probability>2% would yield a net benefit. Conclusions:Breech delivery, intubation in the delivery room, use of adrenaline in the delivery room, and the diagnosis of grade Ⅲ-Ⅳ neonatal respiratory distress syndrome within 6 h post-birth are independent risk factors for early mortality in extremely preterm infants. Large gestational age, antenatal administration of corticosteroids to promote fetal lung maturity and use of pulmonary surfactant within 6 h after birth are protective factors. The constructed prediction model based on the aforementioned factors can quantitatively, conveniently, and intuitively assess the risk of early mortality in extremely preterm infants.

Objective:To conduct a phased summary and analysis of the operation and quality control (QC) of the first human milk bank (HMB) in East China over a ten-year period.Methods:Data on the operation of the HMB at Women's Hospital of Nanjing Medical University, characteristics of donors and recipients, clinical application of donated milk, and operational costs from August 1, 2013, to July 31, 2023, were collected, organized, analyzed, and described. Quality and safety management of the HMB began in 2016, with QC measures implemented. Chi-square tests were used to compare data related to the operation of the HMB, donors, and recipient infants before QC (2013-2015) and after QC (2016-2023). Results:Over the ten-year period since its establishment, the HMB received donor human milk (DHM) from 1 974 donors, totaling 9 390.41 liters. The qualification rate of donors was 86.47% (1 707/1 974), with a qualification rate of DHM of 98.01% (9 203.21/9 390.41) and 21 757 donation instances, with the highest individual donation count reaching 195 times. In the past 10 years, due to the epidemic of the new coronavirus in 2020, the number of milk donors, the amount of DHM and the total number of milk donations decreased significantly, but the amount of DHM per capita and the number of milk donations per capita showed a continuous upward trend. Compared to the period before QC, the qualification rate of donors [96.75% (1 253/1 295) vs. 66.86% (454/679), χ 2=340.33, P<0.001] and the qualification rate of DHM [98.19% (8 366.76/8 521.08) vs. 96.22% (836.45/869.33), χ 2=16.33, P<0.001] both improved after QC. A total of 11 197 recipients received 6 615.38 liters of DHM, with a utilization rate of 71.88% (6 615.38/9 203.21). The current operation mode of the HMB is "voluntary donation, free use". Over ten years, the costs for consumables, testing, labor, energy, and fixed assets amounted to 9.36 million CNY, with an operational cost of 996.32 CNY per liter (9.36 million/9 390.41 L) and approximately 1.00 CNY per milliliter of DHM. Conclusions:The hospital's HMB has been operating stably for ten years, and abundant DHM benefits many newborns. QC measures have effectively increased the qualification rates of both donors and DHM, providing better nutritional support for the treatment of critically ill infants. However, the operational costs of the HMB are relatively high, necessitating the exploration of an operational model suitable for China's national conditions.