1.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
		                        		
		                        			
		                        			With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
		                        		
		                        		
		                        		
		                        	
2.Clinical study of atorvastatin combined with indobufen in the treatment of elderly patients with diabetic kidney disease complicated with large atheromatous ischemic stroke during convalescence
Meijie LI ; Yan MA ; Wei SHI ; Lina ZHANG ; Kang BAI ; Shuqin GUO
Chinese Journal of Postgraduates of Medicine 2024;47(3):247-253
		                        		
		                        			
		                        			Objective:To investigate the efficacy and safety of atorvastatin combined with indobufen in the treatment of elderly patients with diabetic kidney disease (DKD) complicated with large atheromatous ischemic stroke (LAA-IS) during convalescence.Methods:The clinical data of 102 elderly patients with DKD complicated with LAA-IS during convalescence from September 2018 to April 2022 in Baoding Second Central Hospital were retrospectively analyzed. Among them, 51 patients were treated with atorvastatin combined with indobufen (observation group), 51 patients were treated with atorvastatin combined with aspirin (control group), and both groups were treated continuously for 6 months. The prethrombotic state indexes, neurological function and quality of daily life, carotid artery ultrasound indexes, renal fibrosis indexes before treatment and after treatment were compared between two group. The prethrombotic state indexes included arachidonic acid (AA) and adenosine diphosphate (ADP) induction platelet aggregation rate, fibrinogen (FIB), protein C; the National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function, and the modified Barthel index (MBI) was used to evaluate the quality of daily life; carotid artery ultrasound indexes included carotid artery intima-media thickness (IMT) and maximum plaque area; the renal fibrosis indexes included transforming growth factor-β 1 (TGF-β 1), matrix metalloproteinase-9 (MMP-9), hyaluronic acid and platelet derived growth factor-BB (PDGF-BB). The adverse reactions were recorded. Results:There were no statistical differences in the all indexes before treatment between two groups ( P>0.05). In two groups, compared before treatment, the AA induction platelet aggregation rate, ADP induction platelet aggregation rate, FIB, NIHSS score, IMT and maximum plaque area after treatment were significantly lower, the protein C and MBI score were significantly higher, and there were statistical differences ( P<0.01); but there were no statistical differences after treatment between two groups ( P>0.05). The TGF-β 1, MMP-9, hyaluronic acid and PDGF-BB after treatment in two groups were significantly lower than before treatment, and the indexes in observation group were significantly lower than those in control group: (39.46 ± 6.89) μg/L vs. (45.04 ± 8.20) μg/L, (278.46 ± 49.39) μg/L vs. (327.30 ± 57.28) μg/L, (102.37 ± 20.62) μg/L vs. (116.84 ± 24.97) μg/L vs. (25.26 ± 4.45) μg/L vs. (28.13 ± 5.08) μg/L, with statistically significant differences( P<0.01). The incidence of adverse reactions in observation group was significantly lower than that in control group: 7.84% (4/51) vs. 23.53% (12/51), and there was statistical difference ( P<0.05). Conclusions:Compared with atorvastatin combined with aspirin, atorvastatin combined with indobufen in elderly patients with DKD complicated with LAA-IS during convalescence has the same effect in improving the related indicators of prethrombotic state, reducing neurological function deficit, improving the ability of daily living, and reversing carotid atherosclerosis. However, atorvastatin combined with indobufen can further protect renal function with higher safety.
		                        		
		                        		
		                        		
		                        	
3.Deferoxamine mesylate improves the repair of jaw bone defects in an ovariectomized rat model of osteoporosis
Ai TIAN ; Li LI ; Tianjiao XIAO ; Jiabing KANG ; Jifan ZHAN ; Yan WEI ; Helin CHEN
Chinese Journal of Tissue Engineering Research 2024;28(20):3143-3149
		                        		
		                        			
		                        			BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering. OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats. METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat's bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels;and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages. RESULTS AND CONCLUSION:The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group.Iron levels in the liver,jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting,while the iron levels were significantly decreased after deferoxamine mesylate intervention(P<0.05).In the early stage of bone defect repair,more inflammatory cell infiltration,less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group(P<0.05);after deferoxamine mesylate treatment,inflammatory cell infiltration was reduced,a small amount of new bone matrix was produced and collagen fibers increased significantly(P<0.05).In the middle and late stages of bone defect repair,Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment(P<0.05).Compared with the sham-operated group,the osteoclast number,serum calcitonin level,and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group,while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate.To conclude,in ovariectomized rats with high iron intervention,elevated iron levels can be seen in multiple tissues,accompanied by reduced new bone production in the mandibular bone defect area.Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues,improve bone formation in iron-accumulated osteoporotic rats,and promote bone healing in the mandibular bone defect area.
		                        		
		                        		
		                        		
		                        	
4.Interleukin-4 regulates macrophage polarization and osteogenic differentiation of bone marrow mesenchymal stem cells
Jie ZHANG ; Tianjiao XIAO ; Li LI ; Jiabing KANG ; Jifan ZHAN ; Yan WEI ; Ai TIAN
Chinese Journal of Tissue Engineering Research 2024;28(25):3960-3966
		                        		
		                        			
		                        			BACKGROUND:Interleukin-4 can promote the osteogenic effect of bone substitute materials,but its molecular mechanism is not yet clear.Further elucidating the mechanism of interleukin-4 promoting osteogenic effect can help find safe,economical,and effective methods for the regeneration treatment of alveolar bone defects in patients. OBJECTIVE:To explore the effect of interleukin-4 intervention on polarization transformation of macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells and its possible mechanism. METHODS:RAW264.7 cells in the M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours.RAW264.7 cells in the interleukin-4+M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours and then interleukin-4 was added for 24 hours.RAW264.7 cells in the interleukin-4+AG+M1 group were induced with interferon gamma + lipopolysaccharide for 24 hours,and then interleukin-4 and AG-490,a JAK/STAT pathway inhibitor,were added for 24 hours.After intervention,immunofluorescence staining was used to analyze the expression of inducible nitric oxide synthase and CD206,the phenotypic marker protein of macrophages.ELISA kit was used to detect the expression of interleukin-10 and tumor necrosis factor-α in the supernatant of cell culture.The gene expressions of nodular receptor protein-3(NLRP3),interleukin-1β,and caspase-1 were detected by RT-qPCR.The expression levels of tyrosine protein kinase 1(JAK1)/phosphorylated tyrosine protein kinase 1(p-JAK1),signal transduction and transcription activator 6(STAT6)/phosphorylated signal transduction and transcription activator 6(p-STAT6),NLRP3,pro-interleukin-1β and pro-caspase-1 were detected by western blot assay.Then,RAW264.7 cells in the above four groups were indirectly co-cultured with bone marrow mesenchymal stem cells by transwell for 24 hours,followed by alkaline phosphatase staining and alizarin red staining.The mRNA expressions of alkaline phosphatase,collagen type I,and osteocalcin were detected by RT-qPCR. RESULTS AND CONCLUSION:(1)Immunofluorescence and ELISA results showed that interleukin-4 intervention could promote the expression of CD206 and interleukin-10 in M2 macrophages,and inhibit the secretion of inducible nitric oxide synthase and tumor necrosis factor-α.(2)RT-qPCR results showed that interleukin-4 could suppress the expression of NLRP3,interleukin-1β,and caspase-1 mRNAs.(3)Western blot assay showed that interleukin-4 could promote the expression of JAK1/p-JAK1,STAT6/p-STAT6 and NLRP3 proteins.(4)The alkaline phosphatase staining and alizarin red staining of bone marrow mesenchymal stem cells co-cultured with the interleukin-4+M1 group were significantly enhanced,and the mRNA expressions of alkaline phosphatase,collagen type I,and osteocalcin were significantly increased.It is concluded that interleukin-4 may inhibit the activation of NLRP3 by up-regulating JAK1/STAT6 pathway,thus promoting the transformation of macrophages from M1 polarization to M2 polarization,and finally enhancing the osteogenic differentiation ability of bone marrow mesenchymal stem cells.
		                        		
		                        		
		                        		
		                        	
5.Predictive value of fibrinogen-albumin-ratio in adult hemorrhage after extracorporeal membrane oxygenation
Fan LI ; Wei LAI ; Hua YAO ; Yan KANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(09):1319-1326
		                        		
		                        			
		                        			Objective To explore the clinical value of fibrinogen-albumin-ratio (FAR) in adult extracorporeal membrane oxygenation (ECMO) hemorrhage. Methods The clinical data of adult patients receiving ECMO in the West China Hospital from 2018 to 2020 were analyzed retrospectively. Patients were divided into a bleeding group and a non-bleeding group based on whether they experienced bleeding after ECMO. Logistic regression analysis was used to study the relationship between FAR and bleeding, as well as risk factors for death. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive ability of FAR. According to the optimal cut-off value of FAR for predicting hemorrhage, patients were divided into a high-risk group and a low-risk group, and the occurrence of bleeding was compared between the two groups. Results A total of 125 patients were enrolled in this study, including 85 males and 40 females, aged 46.00 (31.50, 55.50) years. Among them, 58 patients received veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and 67 patients received veno-venous extracorporeal membrane oxygenation (VV-ECMO). There were 49 patients having bleeding, and the lactate level was higher (P=0.026), the platelet count before ECMO initiation and 24 h after ECMO initiation was lower (P=0.031, 0.020), the fibrinogen level 24 h after ECMO initiation was lower (P=0.049), and the proportion of myocarditis patients was higher (P=0.017) in the bleeding group than those of the non-bleeding group. In the subgroup analysis of ECMO mode, the higher D-Dimer, lactate level and lower FAR before and 24 h after ECMO initiation were associated with bleeding in the VA-ECMO group (P=0.017, 0.011, 0.033, 0.005). The 24 h FAR was independently correlated with bleeding (P=0.048), and AUC was 0.714. The cut-off value was 55.73. According to this optimal cut-off value, 25 patients were divided into the high-risk group (≤55.73) and 33 into the low-risk group (>55.73). There was a higher incidence of bleeding in the high-risk group compared to the low-risk group (unadjusted P=0.002; P=0.013 for multivariable adjustment). In the VV-ECMO group, the relationship between FAR and bleeding events was not significant (P>0.05). Conclusion Low 24 h FAR is an independent risk factor for bleeding in VA-ECMO patients, and the diagnostic cut-off value is 55.73.
		                        		
		                        		
		                        		
		                        	
6.Exploring the regulatory effects of abdominal breathing training on brain function based on electroencephalogram signals
Ruoshui WANG ; Tianyi LYU ; Xirui ZHAO ; Dan LIN ; Jiaxuan LYU ; Chaoyang ZHANG ; Xinzheng ZHANG ; Kang YAN ; Yulong WEI
Journal of Beijing University of Traditional Chinese Medicine 2024;47(9):1322-1332
		                        		
		                        			
		                        			Objective To investigate the effects of qigong abdominal breathing training on human brain function.Methods Seventy-two university students were recruited and randomly divided into the control and treatment groups in a 1:1 ratio. Both the control and treatment groups underwent the same standing pile work operation. However,only the treatment group received additional abdominal breathing training. The intervention process comprised two phases:2 weeks of intensive training and 6 weeks of counseling training. Electrocardiogram and electroencephalogram (EEG) tests were performed before (baseline period) and after training respectively. Sample entropy algorithm and empirical mode decomposition were used to analyze the EEG signals. The sample entropy complexity index and the correlation between EEG changes and respiratory curves were calculated to explore the brain function regulation effect. Results The complexity of different brain regions in the treatment group was higher than that of the control group after training. A large difference was observed when comparing the brain complexity in the temporoparietal junction,posterior temporal,parietal,parietal-occipital junction,and occipital regions. The brain complexity in the posterior temporal region of the treatment group was significantly higher than that of the control group after the intervention,with a significant difference (P<0.05). In the control group,the brain complexity in the frontal pole,anterior temporal,frontal reion,frontal-temporal junction,frontal-central junction,middle temporal,central,and temporal-parietal junction regions decreased to different degrees. However,the comparison between before and after was not significant. Furthermore,brain complexity in the central-parietal junction,posterior temporal,parietal,parietal-occipital junction,and occipital regions increased to different degrees in the control group;however,the difference was not significant. The brain complexity of the treatment group in the frontotemporal junction,middle temporal,and temporoparietal junction areas decreased slightly;however,the before-and-after comparison was not significant. The brain complexity of the treatment group in the frontal pole,frontotemporal,frontal,frontal-central junction,central,central-parietal junction,posterior-temporal,parietal,parietal-occipital junction,and occipital areas increased. The posterior-temporal,parietal,parietal-occipital junction,and occipital areas had more significant increases than the other areas. However,the before-and-after comparison was not significant. In both groups,brain complexity decreased in the frontotemporal junction,middle temporal,and temporoparietal junction areas and increased in the parietal,parieto-occipital junction,and occipital areas. The comparison of complexity between the treatment and control groups in P3 and PO3 leads after training was significant. P3 and PO3 are situated in the parietal region and parieto-occipital junction areas,respectively,indicating that antebellum breathing also affects brain function in these regions. The correlation between the respiratory curve and EEG components was enhanced after training. Conclusion Abdominal breathing training can significantly increase the complexity of the corresponding brain regions (posterior temporal,parietal,and parieto-occipital junction regions),and a significant correlation was observed between the two.
		                        		
		                        		
		                        		
		                        	
7.Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia
Guochang XUE ; Huali ZHANG ; Xuexing DING ; Fu XIONG ; Yanhong LIU ; Hui PENG ; Changlin WANG ; Yi ZHAO ; Huili YAN ; Mingxing REN ; Chaoying MA ; Hanming LU ; Yanli LI ; Ruifeng MENG ; Lingjun XIE ; Na CHEN ; Xiufang CHENG ; Jiaojiao WANG ; Xiaohong XIN ; Ruifen WANG ; Qi JIANG ; Yong ZHANG ; Guijuan LIANG ; Yuanzheng LI ; Jianing KANG ; Huimin ZHANG ; Yinying ZHANG ; Yuan YUAN ; Yawen LI ; Yinglin SU ; Junping LIU ; Shengjie DUAN ; Qingsheng LIU ; Jing WEI
Chinese Journal of Pediatrics 2024;62(6):535-541
		                        		
		                        			
		                        			Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).
		                        		
		                        		
		                        		
		                        	
8.Association of adipocytokine pathway gene polymorphisms with NAFLD in obese children
Jie WANG ; Xiongfeng PAN ; Jia WEI ; Xiongwei LI ; Haixiang ZHOU ; Ning'an XU ; Rutong KANG ; Yan ZHONG ; Jiayou LUO
Journal of Central South University(Medical Sciences) 2024;49(5):775-783
		                        		
		                        			
		                        			Objective:Non-alcoholic fatty liver disease(NAFLD)has significant genetic susceptibility.Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis.However,the association between adipocytokine pathway genes and NAFLD remains unclear.This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children. Methods:A case-control study was conducted,dividing obese children into NAFLD and control groups.Peripheral venous blood(2 mL)was collected from each participant for DNA extraction.A total of 14 single nucleotide polymorphisms(SNP)in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing.Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children.Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression.Generalized multifactor dimensionality reduction(GMDR)was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children. Results:A total of 1 022 children were included,with 511 in the NAFLD group and 511 in the control group.After adjusting for age,gender,and BMI,multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models:heterozygote model(CG vs CC,OR=0.58,95%CI 0.36 to 0.95,P=0.029),dominant model(GG+CG vs CC,OR=0.62,95%CI 0.38 to 1.00,P=0.049),and overdominant model(CC+GG vs CG,OR=1.72,95%CI 1.06 to 2.80,P=0.028).PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models:heterozygous model(CT vs CC,OR=1.51,95%CI 1.10 to 2.07,P=0.011),dominant model(CT+TT vs CC,OR=1.50,95%CI 1.10 to 2.03,P=0.010),overdominant model(CC+TT vs CT,OR=0.67,95%CI 0.49 to 0.92,P=0.012),and additive model(CC vs CT vs TT,OR=1.40,95%CI 1.07 to 1.83,P=0.015).No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD.GMDR analysis,adjusted for age,gender,and BMI,revealed no statistically significant interactions among the 14 SNPs(all P>0.05). Conclusion:Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children.However,no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.
		                        		
		                        		
		                        		
		                        	
9.CP-25 inhibits GRK2 activity to treat osteoarthritis in mice
Hui-Min WANG ; Xu-Lei WANG ; Zhu-Ping CHU ; Ting-Ting GUO ; Nuo XU ; Kang WANG ; Ying LI ; Wei WEI ; Shang-Xue YAN
Chinese Pharmacological Bulletin 2024;40(5):936-944
		                        		
		                        			
		                        			Aim To investigate the protective poten-tial of paeoniflorin 6-oxy-benzenesulfonate(CP-25)in preserving knee cartilage integrity in osteoarthritis mice through inhibition of GRK2 activity.Methods The posttraumatic osteoarthritis model was established fol-lowing DMM surgery.The experiment consisted of a sham operation group,a model group,a CP-25 admin-istration group,and a paroxetine positive control group.Intragastric administration commenced after the surgery.After 12 weeks of administration,the animals were euthanized.Micro-CT imaging was used to ob-serve the knee cartilage degeneration and abnormal bone remodeling,and the joint histopathology of mice was observed by staining with ferrubens solid green.Immunohistochemistry and immunofluorescence were used to detect the expression level of related molecules in cartilage tissue.Furthermore,Western blot was em-ployed to determine GRK2 and EP4 membrane protein expression levels as well as total protein levels of GRK2 and MMP13 following CP-25 treatment.Results Compared with the sham operation group,the articular cartilage in the model group was significantly degrad-ed,with the cartilage surface calcifying and osteo-phytes forming.CP-25 could significantly reduce the number of osteophytes and the thickness of the sub-chondral plate of articular cartilage,promote the regen-eration of the cartilage matrix,reduce the expression of cartilage matrix degradation protein,and have a signifi-cant protective effect on knee cartilage.Immunohisto-chemical and immunofluorescence results showed that compared with the model group,CP-25 treatment sig-nificantly decreased the expressions of GRK2,AD-AMTS5 and MMP13 in knee tissue and increased the expressions of Col Ⅱ and Aggrecan in knee tissue.The results of in vitro experiments showed that CP-25 ad-ministration could significantly reduce the expression levels of GRK2 membrane protein and total protein,in-crease the level of EP4 membrane protein,and de-crease the level of MMP13.Conclusions The ad-ministration of CP-25 can significantly promote the re-generation of articular cartilage matrix in OA mice,re-duce the degradation of cartilage matrix,and exhibit therapeutic effects on OA.The mechanism behind this is related to the inhibition of GRK2-mediated cartilage matrix metabolism.
		                        		
		                        		
		                        		
		                        	
10.Mechanism of artemisinin inhibiting malignant biological behavior of colorectal cancer cells stimulated by glucose
Yong-Na PAN ; Yue-Feng CHANG ; Jing-Jing GUO ; Yi-Li SUN ; Lan WEI ; Chun-Yan YANG ; Jin-Wang KANG
Journal of Regional Anatomy and Operative Surgery 2024;33(5):388-393
		                        		
		                        			
		                        			Objective To investigate the effect of artemisinin(ART)on the malignant biological behavior of colorectal cancer(CRC)cells stimulated by glucose and its mechanism.Methods The concentration gradients of 0,5,10,20,40 and 60 μmol/L of ART were used to treat the human colorectal cancer cell line SW480,and then the cell viability was detected by CCK-8.Cell apoptosis was detected by flow cytometry.Transwell was used to detect the cell migration and invasion.Western blot was used to detect the apoptosis,epithelial-mesenchymal transition(EMT)and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)related proteins expression.Results Compared with the 0 μmol/L of ART,the viability of SW480 cells decreased under 5,10,20,40,60 μmol/L of ART treatment(P<0.05),and IC50 was 36.91 μmol/L.Therefore,the cells treated with 10,20 and 40 μmol/L of ART were as the low-dose,medium-dose and high-dose ART groups,the cells treated with 0 μmol/L of ART were as the control group,and the cells treated with 40 μmol/L of ART and 10 μmol/L of Coumermycin A1 were as the Coumermycin A1 group.Compared with the control group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the low-dose ART group,the medium-dose ART group,and the high-dose ART group decreased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin increased(P<0.05).Compared with the high-dose ART group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the Coumermycin A1 group increased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin decreased(P<0.05).Conclusion ART may inhibit the viability,migration,invasion and EMT of glucose-stimulated CRC cells and promote apoptosis by inhibiting the JAK2/STAT3 signaling pathway.
		                        		
		                        		
		                        		
		                        	
            
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