1.ZIP4 promotes glycolysis in cholangiocarcinoma cells by enhancing H3K4me3 modification and activating MYCN transcription
Jiwen WANG ; Cheng ZHANG ; Dexiang ZHANG ; Xiaoling NI ; Kun FAN ; Houbao LIU
Chinese Journal of Clinical Medicine 2025;32(3):410-420
		                        		
		                        			
		                        			Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P<0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P<0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P<0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P<0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.
		                        		
		                        		
		                        		
		                        	
2.Research progress of bionic intramedullary nail of proximal femur based on "lever-fulcrum balance and reconstruction" theory in the treatment of senile intertrochanteric femoral fractures
Changjun HE ; Kun ZHANG ; Congming ZHANG ; Cheng REN ; Deyin LIU ; Yibo XU ; Na YANG ; Teng MA
International Journal of Surgery 2024;51(3):207-211
		                        		
		                        			
		                        			Femoral intertrochanteric fracture is one of the common types of fractures in the elderly. With the general improvement of medical and living standards, the number of elderly people is increasing, and the problem of osteoporosis has also become relatively prominent. Therefore, low violence can usually cause fractures in this area of the elderly, which has a significant negative impact on the quality of life of elderly patients. With the further development of medical technology and internal fixation materials, the emergence of proximal femoral nail antirotation(PFNA) has greatly improved the treatment effect of femoral intertrochanteric fractures in elderly patients. However, with the increasing number of patients treated, internal fixation failures have gradually been reported. In recent years, proximal femoral biomimetic intramedullary nail(PFBN) has been reported to have good clinical efficacy. Therefore, this article mainly elaborates on the theoretical basis, design characteristics, biomechanics, and clinical efficacy research of PFBN, providing more reference for the clinical treatment of femoral intertrochanteric fractures in elderly patients in the future.
		                        		
		                        		
		                        		
		                        	
3.Effect of Shegan Mahuangtang and Its Pungent and Bitter Chinese Herbs on Airway Inflammation and Expression of TRPV1/TAS2R14 in Lung Tissue of Rat Model of Cold Asthma
Yamei YUAN ; Weidong YE ; Yue CHENG ; Qiuhui LI ; Jiaxin LIU ; Jiale QIAO ; Kun WANG ; Xiangming FANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):1-9
		                        		
		                        			
		                        			ObjectiveTo investigate the effects of Shegan Mahuangtang and its pungent and bitter Chinese herbs on the expression of transient receptor potential vanilloid-1 (TRPV1) and bitter taste receptor 14 (TAS2R14) in the lung tissue of the rat model of cold asthma. MethodSeventy SD rats were randomized into 7 groups: normal, model, Shegan Mahuangtang, pungent Chinese herbs, bitter Chinese herbs (6.43 g·kg-1), dexamethasone (0.5 g·kg-1), and Guilong Kechuanning (10 g·kg-1). The rat model of cold asthma was established by intraperitoneal injection and subcutaneous injection of 10% ovalbumin (OVA) and aluminium hydroxide in the limbs, combined with 2% OVA atomization and cold (2-4 ℃) stimulation. The rats were treated with corresponding drugs by gavage and atomization, and the normal and model groups were treated with the same amount of normal saline for 3 weeks. After the last excitation, airway inflammation and cell proliferation were observed by hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining of the lung tissue. The levels of interleukin-5 (IL-5), tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin (TSLP), and transforming growth factor-β1 (TGF-β1) in the serum were measured by enzyme-linked immunosorbent assay (ELISA). The expression of TRPV1 and TAS2R14 was detected by immunofluorescence. The expression of TRPV1, TAS2R14, phospholipase Cβ2 (PLCβ2), B-cell lymphoma-2 (Bcl-2), and α-smooth muscle actin (α-SMA) in the lung tissue was determined by Western blot. ResultCompared with the normal group, the model group showed decreased water intake, food intake, and body weight, increased airway inflammatory cell infiltration, goblet cell proliferation, tissue fibrosis and collagen deposition, elevated levels of IL-5, TNF-α, TSLP, and TGF-β1 in the serum (P<0.01), upregulated expression of TRPV1, PLCβ2, and α-SMA, and downregulated expression of TAS2R14 and Bcl-2 (P<0.05, P<0.01). Compared with model group, Shecgan Mahuangtang, pungent Chinese herbs, and bitter Chinese herbs increased the water intake, food intake, and body weight, reduced the inflammatory cell infiltration and goblet cell proliferation, alleviated tissue fibrosis and collagen deposition, lowered the levels of IL-5, TNF-α, TSLP, and TGF-β1 in the serum (P<0.01), downregulated the expression of TRPV1, PLCβ2, and α-SMA, and upregulated the expression of TAS2R14 and Bcl-2 (P<0.05, P<0.01). ConclusionShegan Mahuangtang and its pungent and bitter Chinese herbs can reduce OVA-induced airway inflammation, downregulate the expression of TRPV1, PLCβ2, and α-SMA, and upregulate the expression of TAS2R14 and Bcl-2 in asthmatic rats. Moreover, bitter Chinese herbs outperformed pungent Chinese herbs, and the combination of them enhanced the therapeutic effect. It is suggested that Shegan Mahuangtang and its pungent and bitter Chinese herbs may ameliorate the OVA-induced airway inflammation by inhibiting TRPV1 and activating TAS2R14. 
		                        		
		                        		
		                        		
		                        	
4.Early outcomes of domestic left ventricular assist device implantation with or without concomitant mitral valvuloplasty
Zhihua WANG ; Zeyuan ZHAO ; Junlong HU ; Junjie SUN ; Kun LIU ; Xiaoxia DUAN ; Sheng WANG ; Zhaoyun CHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(11):1599-1605
		                        		
		                        			
		                        			Objective  To compare the early outcomes of domestic third-generation magnetically levitated left ventricular assist device (LVAD) with or without concomitant mitral valvuloplasty (MVP). Methods  The clinical data of 17 end-stage heart failure patients who underwent LVAD implantation combined with preoperative moderate to severe mitral regurgitation in Fuwai Central China Cardiovascular Hospital from May 2018 to March 2023 were retrospectively analyzed. The patients were divided into a LVAD group and a LVAD+MVP group based on whether MVP was performed simultaneously, and early outcomes were compared between the two groups. Results  There were 4 patients in the LVAD group, all males, aged (43.5±5.9) years, and 13 patients in the LVAD+MVP group, including 10 males and 3 females, aged (46.8±16.7) years. All the patients were successful in concomitant MVP without mitral reguragitation occurrence. Compared with the LVAD group, the LVAD+MVP group had a lower pulmonary artery systolic pressure and pulmonary artery mean pressure 72 h after operation, but the difference was not statistically different (P>0.05). Pulmonary artery systolic pressure was significantly lower 1 week after operation, as well as pulmonary artery systolic blood pressure and pulmonary artery mean pressure at 1 month after operation (P<0.01). There was no statistically significant difference in blood loss, operation time, cardiopulmonary bypass time, aortic cross-clamping time, mechanical ventilation time, or ICU stay time between the two groups (P>0.05). The differences in 1-month postoperative mortality, acute kidney injury, reoperation, gastrointestinal bleeding, and thrombosis and other complications between the two groups were not statistically significant (P>0.05). Conclusion  Concomitant MVP with implantation of domestic third-generation magnetically levitated LVAD is safe and feasible, and concomitant MVP may improve postoperative hemodynamics without significantly increasing perioperative mortality and complication rates.
		                        		
		                        		
		                        		
		                        	
5.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
		                        		
		                        			 Objective:
		                        			This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. 
		                        		
		                        			Methods:
		                        			Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. 
		                        		
		                        			Results:
		                        			In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. 
		                        		
		                        			Conclusion
		                        			In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines. 
		                        		
		                        		
		                        		
		                        	
6.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
		                        		
		                        			 Objective:
		                        			This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. 
		                        		
		                        			Methods:
		                        			Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. 
		                        		
		                        			Results:
		                        			In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. 
		                        		
		                        			Conclusion
		                        			In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines. 
		                        		
		                        		
		                        		
		                        	
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.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
		                        		
		                        			 Objective:
		                        			This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. 
		                        		
		                        			Methods:
		                        			Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. 
		                        		
		                        			Results:
		                        			In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. 
		                        		
		                        			Conclusion
		                        			In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines. 
		                        		
		                        		
		                        		
		                        	
9.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
		                        		
		                        			 Objective:
		                        			This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. 
		                        		
		                        			Methods:
		                        			Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. 
		                        		
		                        			Results:
		                        			In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. 
		                        		
		                        			Conclusion
		                        			In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines. 
		                        		
		                        		
		                        		
		                        	
10.Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study
Yang ZOU ; Shuo JI ; Hui Wen YANG ; Tao MA ; Yue Kun FANG ; Zhi Cheng WANG ; Miao Miao LIU ; Ping Hui ZHOU ; Zheng Qi BAO ; Chang Chun ZHANG ; Yu Chen YE
Neurospine 2024;21(1):273-285
		                        		
		                        			 Objective:
		                        			This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. 
		                        		
		                        			Methods:
		                        			Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. 
		                        		
		                        			Results:
		                        			In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. 
		                        		
		                        			Conclusion
		                        			In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines. 
		                        		
		                        		
		                        		
		                        	
            
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