BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

The continuous development and advancement of organ transplantation technology has brought the possibility of fertility to patients with uterine infertility. However， the emergence of new technology always requires careful ethical deliberation， such as a comparative analysis of relevant benefits and risks， to prevent technology from bringing unnecessary negative impacts or even disasters to human beings and society. After a comprehensive ethical analysis of uterus transplantation technology， it was concluded that its risks were high， the costs were excessive， and the benefits were uncertain. Therefore， given the current situation， it is necessary to establish strict preconditions for the research and application of uterus transplantation technology and strengthen supervision， to avoid possible abuses of technology and ethical risks.

Background Chlorinated perfluoroalkyl ether sulfonate Cl-PFAES, trade name F-53B, a novel per- and polyfluoroalkyl substance (PFAS), has been shown to induce multi-organ toxicity in humans and cross the blood-brain barrier. However, its toxic effects and underlying mechanisms on neural stem cells (NSCs) remain unclear. Objective To investigate the impact of F-53B on NSCs proliferation and differentiation through oxidative stress and explore its potential molecular mechanisms in associations with mitochondrial function damage and the expression of autophagy-related gene (PINK1/Parkin). Methods Primary NSCs isolated from neonatal C57BL/6 mice were used as a model and exposed to F-53B at concentrations of 0, 33, or 100 μmol·L⁻¹ for 24 h. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, while proliferation was evaluated by the 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay. Immunofluorescence staining was performed to observe differentiation phenotypes. Intracellular and mitochondrial reactive oxygen species (ROS) levels were quantified using dihydroethidium (DHE) and MitoSOX probes, respectively. Mitochondrial morphology was observed using MitoTracker Green. ATP level was measured with a commercial kit. Additionally, real-time quantitative polymerase chain reaction (qPCR) was conducted to quantify the expression of PINK1 and Parkin genes. Results Exposure to 100 μmol·L⁻¹ F-53B significantly reduced cell viability to 93.6% of the control group (P<0.01), and decreased the proportion of EdU⁺ cells (P<0.01), indicating proliferation inhibition. The differentiation analysis showed a reduction in neuronal generation, axonal shortening, and an increase in astrocytes. The 100 μmol·L⁻¹ F-53B exposure elevated intracellular ROS to 122% (P<0.01) and mitochondrial ROS (MitoROS) to 135% (P<0.001) of the control levels, leading to mitochondrial fragmentation. The ATP levels after the F-53B exposure decreased to 62.4% relative to the control group (P<0.001). Furthermore, the mRNA expression levels of PINK1 and Par after the F-53B exposure were notably reduced (P<0.05). Conclusion F-53B may induce oxidative stress, thereby disrupting mitochondrial morphology and function while inhibiting the PINK1/Parkin-mediated mitophagy pathway, ultimately leading to impaired neural stem cell proliferation and abnormal differentiation. This study provides new insights into the neurotoxicity mechanisms of F-53B.

Objective To investigate the effects of Nel-like type 1 molecule(NELL-1)on the proliferation and osteogenic differenti-ation of stem cells from human exfoliated deciduous teeth(SHEDs).Methods SHEDs was isolated,cultured,and identified.The third generation SHEDs were used for subsequent experiments.SHEDs were divided into 4 groups,and NELL-1 was added to each group at concentrations of 0(control group),50,100,and 200 ng/mL.Cell activity was measured by CCK-8 assay and crystal violet staining.The changes in osteogenic ability were detected by alkaline phosphatase activity.The expression levels of osteogenesis-related genes ALP,OCN and Runx-2 by RT-qPCR were detected.Western blot was used to detect the expression of osteogenesis-related pro-teins ALP,Runx-2 and Col-Ⅰ.Results SHEDs exhibited stem cell characteristics,and 50 ng/mL of NELL-1 protein had a promo-ting effect on SHEDs proliferation(P＜0.01).Alkaline phosphatase activity assay showed that after the addition of NELL-1,the osteo-genic effect of each group was better than that of the control group and 50 ng/mL of NELL-1 was the best(P＜0.05).RT-qPCR and Western blot results showed that 50 ng/mL of NELL-1 significantly promoted the expression of osteoblast-related genes including ALP,OCN and Runx-2 and the protein expression of ALP,Runx-2 and Col-Ⅰ(P＜0.05).Conclusion NELL-1 can promote the prolifera-tion and osteogenic differentiation of SHEDs.

Objective To investigate the effects of Nel-like type 1 molecule(NELL-1)on the proliferation and osteogenic differenti-ation of stem cells from human exfoliated deciduous teeth(SHEDs).Methods SHEDs was isolated,cultured,and identified.The third generation SHEDs were used for subsequent experiments.SHEDs were divided into 4 groups,and NELL-1 was added to each group at concentrations of 0(control group),50,100,and 200 ng/mL.Cell activity was measured by CCK-8 assay and crystal violet staining.The changes in osteogenic ability were detected by alkaline phosphatase activity.The expression levels of osteogenesis-related genes ALP,OCN and Runx-2 by RT-qPCR were detected.Western blot was used to detect the expression of osteogenesis-related pro-teins ALP,Runx-2 and Col-Ⅰ.Results SHEDs exhibited stem cell characteristics,and 50 ng/mL of NELL-1 protein had a promo-ting effect on SHEDs proliferation(P＜0.01).Alkaline phosphatase activity assay showed that after the addition of NELL-1,the osteo-genic effect of each group was better than that of the control group and 50 ng/mL of NELL-1 was the best(P＜0.05).RT-qPCR and Western blot results showed that 50 ng/mL of NELL-1 significantly promoted the expression of osteoblast-related genes including ALP,OCN and Runx-2 and the protein expression of ALP,Runx-2 and Col-Ⅰ(P＜0.05).Conclusion NELL-1 can promote the prolifera-tion and osteogenic differentiation of SHEDs.

Organ transplantation has demonstrated its significant values by its excellent effectiveness in health reconstruction and life survival, where organ donation is a major component in promoting the development of organ transplantation in China. In recent years, an important progress has been made in organ transplantation in China with an annually increased organ donation rate. In spite of this, there is a serious fact confronted by us that the donated organ quantity is insufficient, which may be solved by further improvement of medical science and public health policy. According to the international experience, an incentive system may improve the organ donation rate effectively although the hidden ethic property of the incentive system itself may have an essentially conflict with the altruism contained in the organ donation. Therefore, in this article, the property of the incentive system, the interaction between organ donation and incentive system and the ethic justification of the system was reviewed, aiming to provide a reference for the further development of the organ donation and transplantation business in China.

Objective:To analyze the immunology-related risk factors for short-term prognosis in patients with demyelinating diseases of central nervous system, and to evaluate their predictive value.Methods:From January 2012 to October 2022 in Beijing Tiantan Hospital of Capital Medical University and General Hospital of Tianjin Medical University, the clinical data of 362 patients with demyelinating diseases of central nervous system were analyzed, including neuromyelitis optic spectrum disease (NMOSD) 181 cases, multiple sclerosis (MS) 129 cases, anti-myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) 38 cases, acute disseminated encephalomyelopathy (ADEM) 14 cases. According to the expanded disability status scale (EDSS) score at discharge, the patients were divided into good prognosis group (EDSS≤3 scores, 267 cases) and poor prognosis group (EDSS>3 scores, 95 cases). The clinical data, admission severity (admission EDSS score), treatment, autoantibodies and immunoglobulin level and serum inflammatory factor level were compared between two groups. Multivariate Logistic regression was used to analyze the independent risk factors of short-term prognosis in patients with demyelinating diseases of central nervous system; and the predictive efficacy was evaluated by receiver operating characteristic (ROC) curve.Results:Compared with the good prognosis group, the admission EDSS score in the poor prognosis group was significantly higher: 2.5 (1.5) scores vs. 6.5 (3.5) scores. The positive rates of autoimmune disease-related antibody, systemic autoantibody, anti-nuclear antibody, anti-extractable nuclear antigen antibody, thyroid peroxidase antibody and thyroid globulin antibody were significantly higher: 89.5% (85/95) vs. 59.6% (159/267), 75.8% (72/95) vs. 52.1% (139/267), 65.3% (62/95) vs. 38.6% (103/267), 42.1% (40/95) vs. 23.2% (62/267), 40.0% (38/95) vs. 19.1% (51/267) and 42.1% (40/95) vs. 19.9% (53/267). The serum IgM was significantly lower: 0.84 (0.78) g/L vs. 1.00 (0.75) g/L. The serum tumor necrosis factor-α, interleukin-2 receptor and cerebrospinal fluid IgG were significantly higher: 8 055 (3 118) pg/L vs. 6 830 (3 515) pg/L, 348 (175) kU/L vs. 314 (146) kU/L and 47.50 (46.50) g/L vs. 33.00 (24.00) g/L. And there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that the admission EDSS score and anti-nuclear antibody positive were the independent risk factors of short-term prognosis in patients with demyelinating diseases of central nervous system ( OR = 5.034 and 6.942, 95% CI 3.289 to 7.705 and 2.250 to 21.422, P<0.01). ROC curve analysis result showed that the area under the curve of anti-nuclear antibody positive combined with admission EDSS score predicted the short-term prognosis in patients with demyelinating diseases of central nervous system was 0.972, with a sensitivity of 90.5%, and a specificity of 92.5%. Conclusions:The admission EDSS score and anti-nuclear antibody positive are the independent risk factors for poor prognosis in patients with demyelinating diseases of central nervous system. And the combination of two indexes can better predict the short-term prognosis.

Somatic symptom disorder are common in childhood, and associated with high-risk adult psychiatric disorders and more unexplained hospitalization.They are one of the factors that seriously hinder health sound growth of children.In this article, domestic and foreign studies on somatic symptom disorders were reviewed to discuss their concept change, etiology and pathogenesis, clinical manifestation, diagnosis, evaluation and treatment, in order to facilitate early identification and treatment of somatic symptom disorders in childhood.

Non-suicidal self-injury (NSSI) refers to the behavior that intentionally and directly injures one′s own body organization without suicidal intention, which is not recognized by the society.Children have gradually become a high-risk group of NSSI behavior, which seriously affects children′s physical and mental health.This review aims to summarize the epidemiology, influencing factors, behavior characteristics, treatment and prognosis of children′s NSSI behavior, aiming to identify children′s NSSI behavior and provide interventions as early as possible to prevent the occurrence of repeated NSSI behavior.

ObjectiveSalidroside is the most abundant natural active compound in the famous Chinese herbal medicine Rhodiolae Crenulatae Radix et Rhizoma. This study aims to explore the effect of salidroside on the proliferation， migration， invasion， and apoptosis of human hepatoma （HepG2） cells. MethodThe HepG2 cells without any treatment were selected as the blank group， and the HepG2 cells in the salidroside groups were treated with salidroside at final concentrations of 20， 40， 80 μmol·L^-1， respectively. A multifunctional cell analyzer， scratch assay， and Transwell assay were employed to determine the proliferation， migration， and invasion of HepG2 cells， respectively. An inverted microscope was used to observe the morphology， and a transmission electron microscope to observe the mitochondria of HepG2 cells. Flow cytometry was employed to determine the apoptosis and cycle distribution of HepG2 cells. Real-time fluorescent quantitative polymerase chain reaction ( Real-time PCR ) and Western blot were employed to determine the expression of apoptosis-associated genes and migration-， invasion-， and apoptosis-associated proteins， respectively， in HepG2 cells. ResultCompared with the blank group， salidroside （20， 40， 80 μmol·L^-1） decreased the cell index and increased the healing area in a time- and dose-dependent manner （P<0.05）. Compared with that in the blank group， the HepG2 cells that could pass through Matrigel reduced in the salidroside （20， 80 μmol·L^-1） groups. Compared with the blank group， salidroside （20， 40， 80 μmol·L^-1） increased the total apoptosis rate in a dose dependence manner and blocked the cells in the G₂/M phase （P<0.05）. Compared with the blank group， salidroside up-regulated the expression of epithelial-cadherin （E-cadherin） in a dose-dependent manner （P<0.05） and down-regulated that of nerve-cadherin （N-cadherin） in the 20 and 80 μmol·L^-1 groups （P<0.05）. Compared with the blank group， salidroside （20， 40， 80 μmol·L^-1） up-regulated the mRNA level of cysteine-containing aspartate-specific protease -3 （Caspase-3） and the protein levels of B-cell lymphoma-2 （Bcl-2） associated X protein （Bax）， Caspase-3， and cysteine-containing aspartate-specific protease-9 （Caspase-9） in a dose-dependent manner （P<0.05）， while it down-regulated the protein levels of the actin-binding protein Girdin and Bcl-2 in a dose-dependent manner （P<0.05）. ConclusionSalidroside inhibited the proliferation， migration， and invasion and induced the apoptosis of HepG2 cells through the mitochondrial pathway. The results suggest that salidroside can be used as a potential chemotherapy candidate for liver cancer.