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.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE 02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD 01/RHD 01; RHAG genotype was RHAG 01/RHAG 01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE 02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.

ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg^-1）， and high-（10 g·kg^-1）， medium-（5 g·kg^-1）， low-dose （2.5 g·kg^-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.

Objective To evaluate the effect of a multidisciplinary collaborative quality control management (hereinafter referred to as "QC management") on improving the performance of biological safety cabinets in hospital. Methods A total of 63 ClassⅡbiological safety cabinets in active use at Peking University Third Hospital were selected as the study subjects using the before-after study mode. Conventional management was implemented on the biological safety cabinets from 2018 to 2021. QC management was used in 2022. The compliance of biological safety cabinets management norm and performance differences under the two models were compared. Results The median and the 25th and 75th percentiles [M(P₂₅, P₇₅)] of the service life among these 63 biological safety cabinets were 3 (1,6) years. The overall performance pass rate and inflow velocity pass rate of biological safety cabinets were higher in the QC management than that in the conventional management (90.5% vs 65.1%, 96.8% vs 84.1%, both P<0.05). However, there was no significant difference in downflow velocity, high-efficiency particulate air filter integrity, cleanliness, airflow smoke pattern, noise, and illumination pass rates of biosafety cabinets before and after the implementation of QC management (79.4% vs 88.9%, 90.5% vs 100.0%, 96.8% vs 100.0%, 85.7% vs 100.0%, 100.0% vs 100.0%, and 85.7% vs 96.8%, respectively; all P>0.05). Conclusion sQC management improves the standardization of biological safety cabinet management and key performance indicators in hospital.

ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg^-1）， and high-（10 g·kg^-1）， medium-（5 g·kg^-1）， low-dose （2.5 g·kg^-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.