1.Targeting fibroblast growth factor receptor 1 signaling to improve bone destruction in rheumatoid arthritis
Haihui HAN ; Lei RAN ; Xiaohui MENG ; Pengfei XIN ; Zheng XIANG ; Yanqin BIAN ; Qi SHI ; Lianbo XIAO
Chinese Journal of Tissue Engineering Research 2025;29(9):1905-1912
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.
2.Feasibility study on the clinical translation of a remote jaundice monitoring system for home-based screening of neonatal hyperbilirubinemia.
Xiao-Fan SUN ; Yi ZHENG ; Ai-Ling SU ; Shu-Ping HAN ; Xiao-Yue DONG
Chinese Journal of Contemporary Pediatrics 2025;27(9):1057-1061
OBJECTIVES:
To evaluate the clinical utility and translational potential of a remote jaundice monitoring system for home-based screening of neonatal hyperbilirubinemia.
METHODS:
A prospective self-controlled study was conducted, enrolling 538 newborns with gestational age ≥35 weeks, birth weight ≥2 000 g, and postnatal age ≤14 days at the Women's Hospital of Nanjing Medical University from March to October 2023. Four screening protocols with different predictive indicators were developed based on the Chinese Neonatal Transcutaneous Hourly Bilirubin Nomogram. The effectiveness of the system was evaluated, and the feasibility of using the remote jaundice monitoring system in actual home settings was analyzed.
RESULTS:
A total of 538 paired transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) measurements showed a strong correlation (r=0.85, P<0.001), with 95.0% (511/538) of samples within the 95% limits of agreement. Using TcB ≥ the 95th percentile as the predictive indicator, the system achieved 100% sensitivity, 46.2% specificity, and an area under the receiver operating characteristic curve of 0.731 (95%CI: 0.682-0.780). This approach could reduce unnecessary hospital visits by 41.4% (221/538).
CONCLUSIONS
The system integrates the QBH-801 transcutaneous bilirubinometer, intelligent early warning, and remote guidance services, establishing a closed-loop "hospital-to-home" management model. It demonstrates high safety and feasibility, with significant clinical translational value.
Humans
;
Infant, Newborn
;
Female
;
Male
;
Bilirubin/blood*
;
Feasibility Studies
;
Prospective Studies
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Hyperbilirubinemia, Neonatal/diagnosis*
;
Neonatal Screening/methods*
;
Jaundice, Neonatal/diagnosis*
3.Mechanism of Aerobic Exercise in Delaying Brain Aging in Aging Mice by Regulating Tryptophan Metabolism
De-Man ZHANG ; Chang-Ling WEI ; Yuan-Ting ZHANG ; Yu JIN ; Xiao-Han HUANG ; Min-Yan ZHENG ; Xue LI
Progress in Biochemistry and Biophysics 2025;52(6):1362-1372
ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.
4.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
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.
5.Transcriptomic analysis of key genes involved in sex differences in intellectual development.
Jia-Wei ZHANG ; Xiao-Li ZHENG ; Hai-Qian ZHOU ; Zhen ZHU ; Wei HAN ; Dong-Min YIN
Acta Physiologica Sinica 2025;77(2):211-221
Intelligence encompasses various abilities, including logical reasoning, comprehension, self-awareness, learning, planning, creativity, and problem-solving. Extensive research and practical experience suggest that there are sex differences in intellectual development, with females typically maturing earlier than males. However, the key genes and molecular network mechanisms underlying these sex differences in intellectual development remain unclear. To date, Genome-Wide Association Studies (GWAS) have identified 507 genes that are significantly associated with intelligence. This study first analyzed RNA sequencing data from different stages of brain development (from BrainSpan), revealing that during the late embryonic stage, the average expression levels of intelligence-related genes are higher in males than in females, while the opposite is observed during puberty. This study further constructed interaction networks of intelligence-related genes with sex-differential expression in the brain, including the prenatal male network (HELP-M: intelligence genes with higher expression levels in prenatal males) and the pubertal female network (HELP-F: intelligence genes with higher expression levels in pubertal females). The findings indicate that the key genes in both networks are Ep300 and Ctnnb1. Specifically, Ep300 regulates the transcription of 53 genes in both HELP-M and HELP-F, while Ctnnb1 regulates the transcription of 45 genes. Ctnnb1 plays a more prominent role in HELP-M, while Ep300 is more crucial in HELP-F. Finally, this study conducted sequencing validation on rats at different developmental stages, and the results indicated that in the prefrontal cortex of female rats during adolescence, the expression levels of the intelligence genes in HELP-F, as well as key genes Ep300 and Ctnnb1, were higher than those in male rats. These genes were also involved in neurodevelopment-related biological processes. The findings reveal a sex-differentiated intelligence gene network and its key genes, which exhibit varying expression levels during the neurodevelopmental process.
Female
;
Intelligence/physiology*
;
Male
;
Sex Characteristics
;
Animals
;
Brain/growth & development*
;
E1A-Associated p300 Protein/physiology*
;
beta Catenin/physiology*
;
Transcriptome
;
Rats
;
Gene Expression Profiling
;
Genome-Wide Association Study
6.Establishment of predictive model for postoperative delirium in patients undergoing gastrointestinal surgery
Yichun ZHENG ; Yang HAN ; Keshi YAN ; Jianming XIAO ; Ju GAO ; Yali GE
Chinese Journal of Anesthesiology 2025;45(9):1117-1123
Objective:To construct a predictive model for postoperative delirium (POD) in patients undergoing gastrointestinal surgery using machine learning.Methods:This retrospective study used clinical data from patients who underwent gastrointestinal surgery at Subei People′s Hospital between September 2022 and April 2024. The entire dataset was randomly divided into the training and validation sets in an 8∶2 ratio. Multivariate logistic regression analysis was conducted to identify the factors influencing POD. Eleven machine learning models were established and compared. The performance of the models was validated using metrics, including accuracy, precision, recall, Youden′s index, F1 score, Matthews′ correlation coefficient, Kappa coefficient, log loss, and Brier score. Receiver operating characteristic and calibration curves were plotted to assess the discrimination and consistency of the model. Shapley additive explanations were used in Python for interpretative analysis of the model with the best predictive performance, and the importance of the feature parameters was ranked.Results:A total of 1, 785 patients were ultimately included, of which 833 (46.67%) experienced POD. The results of multivariate logistic regression analysis revealed that advanced age, lower preoperative serum calcium ion concentration, postoperative pulmonary infection, and higher preoperative systolic blood pressure were independent risk factors for POD in patients undergoing gastrointestinal surgery, while laparoscopic surgery was a protective factor ( P<0.05). Among the 11 machine learning models, the categorical feature gradient boosting model exhibited the best performance, with an area under the receiver operating characteristic curve of 0.82 (95% confidence interval 0.77-0.87). The ranking of feature importance indicated that age had the greatest contribution in predicting POD. Conclusions:The predictive model for POD established based on the categorical boosting algorithm has higher predictive efficacy and clinical application value in patients undergoing gastrointestinal surgery.
7.Association of cadmium internal exposure levels with blood lipid in adults aged 18 to 79 years in China
Haocan SONG ; Saisai JI ; Zheng LI ; Yawei LI ; Feng ZHAO ; Yingli QU ; Yifu LU ; Yingying HAN ; Junxin LIU ; Jiayi CAI ; Tian QIU ; Wenli ZHANG ; Xiao LIN ; Junfang CAI ; Yuebin LYU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2025;59(8):1254-1263
Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.
8.Filter's retraction hook capture technique of pull-assisted method for endovascular retrieval of conical inferior vena cava filter whose hook attached to the wall
Xuan TIAN ; Jianlong LIU ; Han ZHENG ; Jinyong LI ; Xiao LIU ; Mi ZHOU ; Wei JIA ; Peng JIANG ; Zhiyuan CHENG ; Yunxin ZHANG ; Chengjia QU ; Run HUA ; Chenyang TIAN
Chinese Journal of General Surgery 2025;40(11):856-862
Objective:To investigate the clinical application value of a novel filter's retraction hook capture technique of pull-assisted method for the endovascular retrieval of conical inferior vena cava (IVC) filters whose hook attached to the wall.Methods:From January 2020 to December 2024, patients with conical filters whose hook attached to the wall admitted at Beijing Jishuitan Hospital were enrolled consecutively.Results:A total of 46 patients underwent filter retrieval using filter's retraction hook capture technique of pull-assisted method. Among these patients, 39 cases (84.8%) were successful in filter retrieval, with the penetration distance of cranial anchor vertex of 3.3(2.5, 4.4) mm, and 13 (33.3%) filters were deformed. The other 7 cases were unsuccessful, with a penetration distance of cranial anchor vertex of 5.0 (4.3, 5.0) mm, and 6 (85.7%) filters were deformed. There was a statistically significant difference between the two groups ( P<0.05). One case (2.2%) had IVC injury, one case (2.2%) experienced filter fracture, and no symptomatic pulmonary embolism occurred. Logistic regression analysis showed that filter deformation was an independent dangerous factor for filter's retraction. Conclusions:Filter's retraction hook capture technique of pull-assisted method is effective in removing conical filters whose hook attached to the wall, with no symptomatic PE occurring. This method can be considered as a new adjuvant technique for filter retrieval.
9.Mechanism of Ferroptosis in Cerebral Ischemia-reperfusion and Interventional Mechanism of Huoxue Huayu Jiedu Prescription Based on "Blood Stasis and Toxin" Pathogenesis
Jiayue HAN ; Danyi PAN ; Jiaxuan XIAO ; Yuchen LIU ; Jiyong LIU ; Yidi ZENG ; Jinxia LI ; Caixing ZHENG ; Hua LI ; Wanghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):51-60
ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury, as well as the protective role of Huoxue Huayu Jiedu prescription (HXHYJDF) against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups: sham group, model group, deferoxamine (DFO) group (100 mg·kg-1), low-dose HXHYJDF group (4.52 g·kg-1), medium-dose HXHYJDF group (9.04 g·kg-1), and high-dose HXHYJDF group (18.07 g·kg-1), with ten rats in each group. Except for the sham group, the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1st, 3rd, 5th, and 7th days post-reperfusion using the modified neurological severity scores (m-NSS). Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin (HE) staining and transmission electron microscopy. The contents of malondialdehyde (MDA), glutathione (GSH), divalent iron ions (Fe2+), and reactive oxygen species (ROS) in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and Western blot (WB) were used to detect the expression of iron death marker proteins glutathione peroxidase 4 (GPX4), ferroportin-1 (FPN1), transferrin receptor protein 1 (TfR1), and ferritin mitochondrial (FtMt) in brain tissue. ResultsCompared with the sham group, the mNSS score of the model group was significantly increased (P<0.01). HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced, and the intercellular space was widened. The nucleus was fragmented, and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded, and the mitochondrial cristae decreased. The matrix was lost and vacuolated, and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS increased significantly (P<0.01). The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased (P<0.01), and the expression of FtMt and TfR1 proteins was significantly increased (P<0.01). Compared with those of the model group, the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3rd and 5th days, respectively (P<0.05, P<0.01). The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS decreased significantly (P<0.05, P<0.01). The content of GSH in the low-dose HXHYJDF group increased significantly (P<0.01), and the contents of MDA and ROS decreased significantly (P<0.01). The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly (P<0.01), and the expression of FtMt and TfR1 decreased significantly (P<0.01). The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly (P<0.05), and the expression of TfR1 decreased significantly (P<0.01). WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose, medium-dose, and low-dose HXHYJDF groups were significantly up-regulated (P<0.01), and the expression levels of FtMt and TfR1 proteins were significantly down-regulated (P<0.01). ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury, improve the pathological morphology of the infarcted brain tissue, and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury, with increased levels of MDA, Fe2+, ROS, and TfR1 and decreased levels of FtMt, FPN1, GPX4, and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins, promoting the discharge of free iron, reducing brain iron deposition, alleviating oxidative stress, and inhibiting ferroptosis.
10.Progress on antisense oligonucleotide in the field of antibacterial therapy
Jia LI ; Xiao-lu HAN ; Shi-yu SONG ; Jin-tao LIN ; Zhi-qiang TANG ; Zeng-ming WANG ; Liang XU ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2025;60(2):337-347
With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.


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