1.THBS4 in Disease: Mechanisms, Biomarkers, and Therapeutic Opportunities
De-Ying HUANG ; Yan-Hong LI ; Xiu-Feng BAI ; Yi LIU
Progress in Biochemistry and Biophysics 2025;52(9):2217-2232
		                        		
		                        			
		                        			Thrombospondin 4 (THBS4; TSP4), a crucial component of the extracellular matrix (ECM), serves as an important regulator of tissue homeostasis and various pathophysiological processes. As a member of the evolutionarily conserved thrombospondin family, THBS4 is a multidomain adhesive glycoprotein characterized by six distinct structural domains that mediate its diverse biological functions. Through dynamic interactions with various ECM components, THBS4 plays pivotal roles in cell adhesion, proliferation, inflammation regulation, and tissue remodeling, establishing it as a key modulator of microenvironmental organization. The transcription and translation of THBS4 gene, as well as the activity of the THBS4 protein, are tightly regulated by multiple signaling pathways and extracellular cues. Positive regulators of THBS4 include transforming growth factor-β (TGF-β), interferon-γ (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), bone morphogenetic proteins (BMP12/13), and other regulatory factors (such as B4GALNT1, ITGA2/ITGB1, PDGFRβ, etc.), which upregulate THBS4 at the mRNA and/or protein level. Conversely, oxidized low-density lipoprotein (OXLDL) acts as a potent negative regulator of THBS4. This intricate regulatory network ensures precise spatial and temporal control of THBS4 expression in response to diverse physiological and pathological stimuli. Functionally, THBS4 acts as a critical signaling hub, influencing multiple downstream pathways essential for cellular behavior and tissue homeostasis. The best-characterized pathways include: (1) the PI3K/AKT/mTOR axis, which THBS4 modulates through both direct and indirect interactions with integrins and growth factor receptors; (2) Wnt/β-catenin signaling, where THBS4 functions as either an activator or inhibitor depending on the cellular context; (3) the suppression of DBET/TRIM69, contributing to its diverse regulatory roles. These signaling connections position THBS4 as a master regulator of cellular responses to microenvironmental changes. Substantial evidence links aberrant THBS4 expression to a range of pathological conditions, including neoplastic diseases, cardiovascular disorders, fibrotic conditions, neurodegenerative diseases, musculoskeletal disorders, and atopic dermatitis. In cancer biology, THBS4 exhibits context-dependent roles, functioning either as a tumor suppressor or promoter depending on the tumor type and microenvironment. In the cardiovascular system, THBS4 contributes to both adaptive remodeling and maladaptive fibrotic responses. Its involvement in fibrotic diseases arises from its ability to regulate ECM deposition and turnover. The diagnostic and therapeutic potential of THBS4 is particularly promising in oncology and cardiovascular medicine. As a biomarker, THBS4 expression patterns correlate significantly with disease progression and patient outcomes. Therapeutically, targeting THBS4-mediated pathways offers novel opportunities for precision medicine approaches, including anti-fibrotic therapies, modulation of the tumor microenvironment, and enhancement of tissue repair. This comprehensive review systematically explores three key aspects of THBS4 research(1) the fundamental biological functions of THBS4 in ECM organization; (2) its mechanistic involvement in various disease pathologies; (3) its emerging potential as both a diagnostic biomarker and therapeutic target. By integrating recent insights from molecular studies, animal models, and clinical investigations, this review provides a framework for understanding the multifaceted roles of THBS4 in health and disease. The synthesis of current knowledge highlights critical research gaps and future directions for exploring THBS4-targeted interventions across multiple disease contexts. Given its unique position at the intersection of ECM biology and cellular signaling, THBS4 represents a promising frontier for the development of novel diagnostic tools and therapeutic strategies in precision medicine. 
		                        		
		                        		
		                        		
		                        	
2.Diagnostic Techniques and Risk Prediction for Cardiovascular-kidney-metabolic (CKM) Syndrome
Song HOU ; Lin-Shan ZHANG ; Xiu-Qin HONG ; Chi ZHANG ; Ying LIU ; Cai-Li ZHANG ; Yan ZHU ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(10):2585-2601
		                        		
		                        			
		                        			Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention. 
		                        		
		                        		
		                        		
		                        	
		                				3.Systematic characterization and identification of the chemical constituents of the Schisandra chinensis  decoction based on a hybrid scanning technique of UHPLC/IM-QTOF-MS
		                			
		                			Li-li HONG ; Hong-da WANG ; Xiao-yan XU ; Wan-di HU ; Jing-yuan LIU ; Xiao-ying WANG ; Xiu-mei GAO ; Wen-zhi YANG
Acta Pharmaceutica Sinica 2024;59(3):678-692
		                        		
		                        			
		                        			 italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, 
		                        		
		                        	
4.A Retrospective Study on the Qianyang Fengsui Dan Combined with Flying Needle Therapy in the Treatment of Kidney-Yang Deficiency Type of Insomnia
Hong-Yan YANG ; Bao-Ting XU ; Ling-Ling DONG ; Xiu-Hong LIU ; Yuan-Min LI ; Qing-Bo MIAO ; Chao-Peng LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):664-670
		                        		
		                        			
		                        			Objective To analyze the clinical efficacy of the Qianyang Fengsui Dan(combined with flying needle therapy)in the treatment of kidney-yang deficiency type of insomnia.Methods A retrospective study was conducted to select 82 patients with insomnia admitted to the Department of Traditional Chinese Medicine of Dezhou Hospital of Traditional Chinese Medicine from November 2020 to November 2021,and they were divided into an observation group and a control group according to whether or not they were treated with Qianyang Fengsui Dan combined with flying needle therapy,with 41 cases in each group.The control group was treated with Estazolam,while the observation group was treated with Qianyang Fengsui Dan combined with flying needle therapy on the basis of the treatment of the control group,and the course of treatment was 1 month.The changes of Pittsburgh Sleep Quality Index(PSQI)scores and Epworth Sleepiness Scale(ESS)scores,as well as polysomnographic parameters were observed before and after treatment in the two groups.The changes of γ-aminobutyric acid(GABA),glutamate(GA),substance P(SP),and neuropeptide Y(NPY)levels were compared before and after treatment between the two groups.And followed up for 1 year to compare the incidence of relapce of the two groups of patients.Results(1)The total effective rate was 95.12%(39/41)in the observation group and 63.41%(26/41)in the control group,and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,PSQI scores and ESS scores of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving PSQI scores and ESS scores,and the differences were statistically significant(P<0.05).(3)After treatment,sleep efficiency,awakening time,sleep latency,REM,and total sleep time were significantly improved in the two groups(P<0.05),and the observation group was significantly superior to the control group in improving sleep efficiency,awakening time,sleep latency,REM,and total sleep time,and the differences were statistically significant(P<0.05).(4)After treatment,the serum GABA,GA,SP,and NPY levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the serum GABA,GA,SP,and NPY levels,and the differences were all statistically significant(P<0.05).(5)After treatment,follow-up for 1 year,the recurrence rate of the observation group was 0,and there were 7 cases of recurrence in the control group,and the recurrence rate of the control group was 17.07%(7/41),and the recurrence rate of the observation group was lower than that of the control group,and the difference was statistically significant(P<0.05).Conclusion The combination of flying needle therapy and Qianyang Fengsui Dan can effectively relieve insomnia and fatigue in patients with insomnia,reduce daytime drowsiness,regulate the release of blood monoamine neurotransmitters,and reduce the relapse rate,and its efficacy is superior to that of simple western medicine treatment.
		                        		
		                        		
		                        		
		                        	
5.Inhibition effect of kudinoside D on lipid deposition in hepatocytes and its mechanism
Cai-Cai XUE ; Yan-Xiang LI ; Xiu-Mei QIAO ; Jin-Yong PENG ; Jin-Hong WANG
Chinese Pharmacological Bulletin 2024;40(9):1688-1694
		                        		
		                        			
		                        			Aim To investigate the effect of kudinoside D(KD-D)on palmitic acid(PA)-induced lipid depo-sition in hepatocytes.Methods Mouse hepatocytes AML-12 were cultured and randomly divided into the Control group,PA group,PA+KD-D 20 μmol·L-1 group,PA+KD-D 40 μmol·L-1 group and PA+KD-D 80 μmol·L-1 group.AML-12 cells in PA and KD-D groups were treated with PA(0.4 mmol·L-1)for 24 h.AML-12 cells in KD-D groups were incubated with KD-D for 1 h before stimulation with PA.MTT as-say was used to detect cell survival rate,oil red O stai-ning and transmission electron microscopy were used to detect lipid deposition in cells,DCFH-DA fluorescence probe was used to detect intracellular reactive oxygen species(ROS)and MitoSOX mitochondrial superoxide red fluorescence probe was used to detect mitochondrial superoxide content in cells.Results KD-D at differ-ent concentrations improved PA-induced changes in cell morphology significantly.Compared with the Con-trol group,cells in PA group showed a significant in-crease in intracellular lipid droplets.Compared with PA group,the red lipid droplets in KD-D groups de-creased.The results of transmission electron microsco-py demonstrated that KD-D reduced PA-induced hepat-ic steatosis and improved ultrastructure.In addition,KD-D significantly decreased PA-induced cellular ROS level(P<0.01)and reduced mitochondrial superox-ide content(P<0.01).Conclusion KD-D inhibits PA-induced lipid deposition by regulating the cellular oxidative stress levels in AML-12 cells.
		                        		
		                        		
		                        		
		                        	
6.Compliance and Influencing Factors of Endoscopic Screening in High-Risk Population of Upper Gastroin-testinal Cancer in Chongqing
Jia DU ; Zhikai YU ; Yan ZHANG ; Qing GUO ; Shenglin ZHAO ; Xiu LIU ; Hong ZHOU ; Mei HE
China Cancer 2024;33(12):1019-1026
		                        		
		                        			
		                        			[Purpose]To analyze the compliance and influencing factors of endoscopic screening in high-risk population of upper gastrointestinal cancer(UGC)in Chongqing Municipality.[Methods]Risk assessment of UGC was conducted among residents aged 40~74 years old in the areas covered by the Chongqing Urban Cancer Early Diagnosis and Treatment Program from 2012 to 2019.The residents with high risk of UGC were advised to receive free endoscopic screening in designated hospitals.The compliance and influencing factors of endoscopic screening among high-risk sub-jects were analyzed.[Results]There were 266 611 residents who completed the questionnaires and UGC risk assessment,among whom 48 000(18.00%)were assessed as high risk.A total of 9 162 high-risk individuals received the following endoscopic screening with a compliance rate of 19.09%.Multivariate Logistic regression analysis showed that residents aged 45~64 years old,with high school or above education,divorced or widowed status,occupational exposure to haza-rdous substances,hot food preference,high fat diet,frequent consumption of pickled and dried food,exposure to kitchen fume,psychic trauma or depression,upper gastrointestinal disease his-tory and family history of UGC were likely to accept endoscopic screening;while those aged 70 years old and above,current smokers,and having regular physical exercise were likely to have low compliance.[Conclusion]Among high-risk residents of UGC in Chongqing,the compliance to endoscopic screening needs be improved,health education and management should be targeted to those likely to have low compliance.
		                        		
		                        		
		                        		
		                        	
7.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
		                        		
		                        			
		                        			Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
		                        		
		                        		
		                        		
		                        	
8.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
		                        		
		                        			
		                        			Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
		                        		
		                        		
		                        		
		                        	
9.Clinical characteristics and nutritional status of children with Crohn's disease and risk factors for malnutrition
Dong-Dan LI ; Xiao-Lin YE ; Mei-Chen WANG ; Hong-Mei HUANG ; Jie YAN ; Tian-Zhuo ZHANG ; Fei-Hong YU ; De-Xiu GUAN ; Wen-Li YANG ; Lu-Lu XIA ; Jie WU
Chinese Journal of Contemporary Pediatrics 2024;26(11):1194-1201
		                        		
		                        			
		                        			Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6%) and 50 girls (42.4%),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7%,87/118),diarrhea (37.3%,44/118),and hematochezia (32.2%,38/118),and 63.6% (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6% (75/118),and the children with moderate or severe malnutrition accounted for 67% (50/75). There were 50 children (42.4%) with emaciation,8 (6.8%) with growth retardation,and 9 (7.6%) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3%),anemia in 74 children (62.7%),and a reduction in 25 hydroxyvitamin D in 15 children (60%,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.
		                        		
		                        		
		                        		
		                        	
10.Distribution and antimicrobial resistance of pathogens from wound of burned patients in a tertiary first-class hospital from 2020 to 2022
Xiu-Cun LI ; En-Hua SUN ; Yan-Yan DONG ; Hui-Cui SHAN ; Hong-Xia ZHOU ; Xiao-Rong LUAN
Chinese Journal of Infection Control 2024;23(9):1126-1134
		                        		
		                        			
		                        			Objective To analyze the distribution and antimicrobial resistance of pathogens from wounds of burned patients,providing reference for the rational use of antimicrobial agents and healthcare-associated infection(HAI)prevention and control.Methods Clinical data of burned patients admitted to a tertiary first-class hospital from Ja-nuary 2020 to December 2022 were analyzed retrospectively,pathogens in the wound was cultured,identified,and performed antimicrobial susceptibility analysis.Results From 2020 to 2022,a total of 588 burned patients were ad-mitted,734 strains of pathogens were detected,including 415 strains(56.54%)of Gram-negative bacteria,306 strains(41.69%)of Gram-positive bacteria,and 13(1.77%)strains of fungi.The top 5 pathogens were Staphy-lococcus aureus,Escherichia coli,Pseudomonas aeruginosa,Klebsiella pneumoniae,and Enterobacter cloacae.Staphylococcus aureus had higher resistance rates(93.02%-97.37%)to penicillin G,resistance rate to oxacillin increased from 11.63%to 21.92%.Pseudomonas aeruginosa mainly exhibited resistance to ticarcillin/clavulanic acid,aztreonam,and levofloxacin,resistance rates to imipenem and meropenem were 15.00%-38.10%and 10.00%-33.33%,respectively.Susceptibility of Enterobacterales bacteria to cephalosporins enhanced with the increased of cephalosporin generations,and exhibited higher resistance to commonly used antimicrobial agents.Conclusion Over the past three years,there has been no significant change in the detection of major pathogens and antimicrobial resistance in wounds of burned patients in this hospital.Antimicrobial resistance of Staphylococcus aureus and En-terobacterales is relatively severe,and it is necessary to carry out surveillance on pathogens from burn wounds in corresponding areas.
		                        		
		                        		
		                        		
		                        	
            
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