1.Expression and clinical significance of serum CXCL1 and PRDM5 in lymph node metastasis of progressive gastric cancer
Xiaoying DING ; Zhichao DONG ; Jianna MAO ; Changqing GUO ; Aimin YUE
The Journal of Practical Medicine 2025;41(20):3206-3213
Objective To investigate the relationship between serum CXC chemokine ligand 1(CXCL1)and positive regulatory zone zinc finger protein 5(PRDM5)levels and lymph node metastasis of progressive gastric cancer and to analyze their predictive value for patients'prognosis.Methods 203 patients with progressive gastric cancer diagnosed in our hospital from June 2020 to March 2023 were selected and divided into the lymph node metastasis group(n=90)and the no-lymph node metastasis group(n=113)based on the presence or absence of lymph node metastasis,and the differences in the general information of the two groups were analyzed and compared,and the diagnostic value of CXCL1 and PRDM5 in lymph node metastasis of progressive gastric cancer was analyzed by plotting the ROC curve.Logistic regression was used to analyze the risk factors of lymph node metastasis in patients with progressive gastric cancer.Follow up for 2 years,draw Kapan Meier curves to compare the prognosis of patients with advanced gastric cancer lymph node metastasis at different levels of CXCL1 and PRDM5.Results The CXCL1 level in the lymph node metastasis group was higher than that in the no-lymph node metastasis group,and its PRDM5 level was lower than that in the no-lymph node metastasis group(P<0.05).The AUCs for diagnosing lymph node metastasis of progressed gastric cancer were 0.755 and 0.844 for CXCL1 and PRDM5,respectively,and the AUC for the combination of the two was 0.898(95%CI 0.848~0.936).The sensitivity and specificity were 88.89%and 77.88%,respectively(P<0.05).Tumor size,differentation degree,serum CEA,serum CA19-9,CXCL1,and PRDM5 levels were all risk factors for lymph node metastasis in patients with progressive gastric cancer(P<0.05).The survival time of patients with CXCL1>96.13 pg/mL is(15.13±0.85)months,while the survival time of patients with CXCL1≤96.13 pg/mL is(19.06±0.66)months.The survival time of patients with CXCL1≤96.13 pg/mL is longer than that of patients with CXCL1>96.13 pg/mL(P<0.05).The survival time of patients with PRDM>100.85 pg/mL is(18.62±0.69)months,while the survival time of patients with PRDM≤100.85 pg/mL is(14.60±0.78)months.The survival time of patients with PRDM>100.85 pg/mL is longer than that of patients with PRDM≤100.85 pg/mL(P<0.05).Conclusion The abnormal expression of CXCL1 and PRDM5 is related to lymph node metastasis in patients with progressive gastric cancer,and the combined detection of the two is of high value in the assessment of lymph node metastasis and prognosis in patients with progressive gastric cancer.
2.Quantitative evaluation of left ventricular remodeling in left bundle branch block induced cardiomyopathy by multimodal imaging
Xiaoxian WANG ; Changqing MIAO ; Beibei GE ; Mingxia LI ; Fen CHEN ; Fang XU ; Ning ZHANG ; Guanjun GUO ; Wei XU ; Wenzhi SHEN ; Yingming ZHAO ; Jing YAO
Chinese Journal of Ultrasonography 2025;34(1):26-32
Objective:To quantitatively evaluate the effects of left bundle branch block(LBBB)on left ventricular structure,function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography(SPECT),and to investigate the relationship between myocardial work,myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy(LBBB-CM).Methods:Fourteen male beagle dogs were selected,and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram(ECG),transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs(normal control group)matched by age and weight. The correlation between myocardial perfusion(percentage of regional tracer uptake)and myocardial work parameters,myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline,the left ventricular end-diastolic volume of 12 months after the ablation increased[(20.78 ± 5.32)ml vs(26.71 ± 7.94)ml, P = 0.003],left ventricular ejection fraction decreased[(59.17 ± 5.67)% vs(47.69 ± 5.45)%, P<0.001];left ventricular global/segmental longitudinal strain,global/segmental constructive work and global/segmental work efficiency decreased(all P<0.05),left ventricular global/segmental wasted work increased(all P<0.001). Heterogenous perfusion defect was observed in LBBB dogs by SPECT,compared with lateral wall segments,the percentage of regional tracer uptake of septum was decreased(all P<0.05). Gross anatomical and myocardial pathological changes were manifested as cardiomegaly,flaky or focal grayish thickening of endocardium,cardiomyocyte degeneration and fibrosis. Compared with normal control group,the collagen fiber volume fraction(CVF)in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased(all P<0.05). Percentage of regional tracer uptake was positively correlated with segmental myocardial work(SMW)and segmental myocardial efficiency(SWE)( r s = 0.49,0.31;both P<0.001),and negatively correlated with CVF and segmental wasted work(SWW)( r s = -0.51,-0.49;both P<0.001). Conclusions:Isolated LBBB is not benign,which can result in left ventricular remodeling,decreased cardiac constructive function,abnormal myocardial perfusion,endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion,as non-invasive examination,can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.
3.Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults (version 2025)
Bobin MI ; Faqi CAO ; Weixian HU ; Wu ZHOU ; Chenchen YAN ; Hui LI ; Yun SUN ; Yuan XIONG ; Jinmi ZHAO ; Qikai HUA ; Xinbao WU ; Xieyuan JIANG ; Dianying ZHANG ; Zhongguo FU ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Tengbo YU ; Jinhai TAN ; Xi CHEN ; Fengfei LIN ; Zhangyuan LIN ; Dongfa LIAO ; Aiguo WANG ; Shiwu DONG ; Gaoxing LUO ; Zhao XIE ; Dong SUN ; Dehao FU ; Yunfeng CHEN ; Changqing ZHANG ; Kun LIU ; Deye SONG ; Yongjun RUI ; Fei WU ; Ximing LIU ; Junwen WANG ; Meng ZHAO ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Xiao CHEN ; Guandong DAI ; Shiyuan FANG ; Wenchao SONG ; Ming CHEN ; Guanghua GUO ; Yongqing XU ; Lei YANG ; Wenqian ZHANG ; Kun ZHANG ; Xin TANG ; Hua CHEN ; Weiguo XU ; Shuquan GUO ; Yong LIU ; Xiaodong GUO ; Zhewei YE ; Liming XIONG ; Tian XIA ; Hongbin WU ; Qisheng ZHOU ; Mengfei LIU ; Yiqiang HU ; Yanjiu HAN ; Hang XUE ; Kangkang ZHA ; Wei CHEN ; Zhiyong HOU ; Bin YU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Guohui LIU
Chinese Journal of Trauma 2025;41(5):421-432
Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.
4.Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury (version 2025)
Aijun XU ; Shuixia LI ; Bo CHEN ; Mengyuan YE ; Lejiao LANG ; Ning NING ; Lin ZHANG ; Changqing LIU ; Zhonglan CHEN ; Weihu MA ; Weishi LI ; Xiaoning WANG ; Dongmei BIAN ; Jiancheng ZENG ; Xin WANG ; Yuan GAO ; Yaping CHEN ; Jiali CHEN ; Yun HAN ; Xiuting LI ; Yang ZHOU ; Xiaojing SU ; Qiong ZHANG ; Tianwen HUANG ; Ping ZHANG ; Hua LIN ; Xingling XIAO ; Ruifeng XU ; Fanghui DONG ; Bing HAN ; Luo FAN ; Yanling PEI ; Suyun LI ; Xiaoju TAN ; Rongchen GUO ; Yefang ZOU ; Xiaoyun HAN ; Junqin DING ; Yi WANG ; Shuhua DENG ; Jinli GUO ; Yinhua LIANG ; Yuan CEN ; Xiaoqin LIU ; Junru CHEN ; Haiyang YU ; Lunlan LI ; Ying REN ; Yunxia LI ; Jianli LU ; Ying YING ; Lan WEI ; Yin WANG ; Qinhong XU ; Yanqin ZHANG ; Yang LYU ; Shijun ZHANG ; Sui WENJIE ; Sanlian HU ; Shuhong YANG ; Guoqing LI ; Jingjing AN ; Baorong HE ; Leling FENG
Chinese Journal of Trauma 2025;41(6):530-541
Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.
5.C6TSEDRVAJZ, a combination of small-molecule compounds, induces differentiation of human placental fibroblasts into epithelioid cells in vitro.
Zhenjia DAI ; Qunwei GAO ; Mengjiao YING ; Ao WANG ; Juan HONG ; Chunjing WANG ; Yu GUO ; Changqing LIU ; Gaofeng LIU
Journal of Southern Medical University 2025;45(2):322-330
OBJECTIVES:
To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds.
METHODS:
HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O2), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated.
RESULTS:
Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%.
CONCLUSIONS
The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans
;
Fibroblasts/drug effects*
;
Pregnancy
;
Female
;
Cell Differentiation/drug effects*
;
Pyrimidines/pharmacology*
;
Placenta/cytology*
;
Cells, Cultured
;
Pyridines/pharmacology*
;
Pyrazoles/pharmacology*
;
Epithelial Cells/cytology*
6.Expression and clinical significance of serum CXCL1 and PRDM5 in lymph node metastasis of progressive gastric cancer
Xiaoying DING ; Zhichao DONG ; Jianna MAO ; Changqing GUO ; Aimin YUE
The Journal of Practical Medicine 2025;41(20):3206-3213
Objective To investigate the relationship between serum CXC chemokine ligand 1(CXCL1)and positive regulatory zone zinc finger protein 5(PRDM5)levels and lymph node metastasis of progressive gastric cancer and to analyze their predictive value for patients'prognosis.Methods 203 patients with progressive gastric cancer diagnosed in our hospital from June 2020 to March 2023 were selected and divided into the lymph node metastasis group(n=90)and the no-lymph node metastasis group(n=113)based on the presence or absence of lymph node metastasis,and the differences in the general information of the two groups were analyzed and compared,and the diagnostic value of CXCL1 and PRDM5 in lymph node metastasis of progressive gastric cancer was analyzed by plotting the ROC curve.Logistic regression was used to analyze the risk factors of lymph node metastasis in patients with progressive gastric cancer.Follow up for 2 years,draw Kapan Meier curves to compare the prognosis of patients with advanced gastric cancer lymph node metastasis at different levels of CXCL1 and PRDM5.Results The CXCL1 level in the lymph node metastasis group was higher than that in the no-lymph node metastasis group,and its PRDM5 level was lower than that in the no-lymph node metastasis group(P<0.05).The AUCs for diagnosing lymph node metastasis of progressed gastric cancer were 0.755 and 0.844 for CXCL1 and PRDM5,respectively,and the AUC for the combination of the two was 0.898(95%CI 0.848~0.936).The sensitivity and specificity were 88.89%and 77.88%,respectively(P<0.05).Tumor size,differentation degree,serum CEA,serum CA19-9,CXCL1,and PRDM5 levels were all risk factors for lymph node metastasis in patients with progressive gastric cancer(P<0.05).The survival time of patients with CXCL1>96.13 pg/mL is(15.13±0.85)months,while the survival time of patients with CXCL1≤96.13 pg/mL is(19.06±0.66)months.The survival time of patients with CXCL1≤96.13 pg/mL is longer than that of patients with CXCL1>96.13 pg/mL(P<0.05).The survival time of patients with PRDM>100.85 pg/mL is(18.62±0.69)months,while the survival time of patients with PRDM≤100.85 pg/mL is(14.60±0.78)months.The survival time of patients with PRDM>100.85 pg/mL is longer than that of patients with PRDM≤100.85 pg/mL(P<0.05).Conclusion The abnormal expression of CXCL1 and PRDM5 is related to lymph node metastasis in patients with progressive gastric cancer,and the combined detection of the two is of high value in the assessment of lymph node metastasis and prognosis in patients with progressive gastric cancer.
7.Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults (version 2025)
Bobin MI ; Faqi CAO ; Weixian HU ; Wu ZHOU ; Chenchen YAN ; Hui LI ; Yun SUN ; Yuan XIONG ; Jinmi ZHAO ; Qikai HUA ; Xinbao WU ; Xieyuan JIANG ; Dianying ZHANG ; Zhongguo FU ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Tengbo YU ; Jinhai TAN ; Xi CHEN ; Fengfei LIN ; Zhangyuan LIN ; Dongfa LIAO ; Aiguo WANG ; Shiwu DONG ; Gaoxing LUO ; Zhao XIE ; Dong SUN ; Dehao FU ; Yunfeng CHEN ; Changqing ZHANG ; Kun LIU ; Deye SONG ; Yongjun RUI ; Fei WU ; Ximing LIU ; Junwen WANG ; Meng ZHAO ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Xiao CHEN ; Guandong DAI ; Shiyuan FANG ; Wenchao SONG ; Ming CHEN ; Guanghua GUO ; Yongqing XU ; Lei YANG ; Wenqian ZHANG ; Kun ZHANG ; Xin TANG ; Hua CHEN ; Weiguo XU ; Shuquan GUO ; Yong LIU ; Xiaodong GUO ; Zhewei YE ; Liming XIONG ; Tian XIA ; Hongbin WU ; Qisheng ZHOU ; Mengfei LIU ; Yiqiang HU ; Yanjiu HAN ; Hang XUE ; Kangkang ZHA ; Wei CHEN ; Zhiyong HOU ; Bin YU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Guohui LIU
Chinese Journal of Trauma 2025;41(5):421-432
Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.
8.Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury (version 2025)
Aijun XU ; Shuixia LI ; Bo CHEN ; Mengyuan YE ; Lejiao LANG ; Ning NING ; Lin ZHANG ; Changqing LIU ; Zhonglan CHEN ; Weihu MA ; Weishi LI ; Xiaoning WANG ; Dongmei BIAN ; Jiancheng ZENG ; Xin WANG ; Yuan GAO ; Yaping CHEN ; Jiali CHEN ; Yun HAN ; Xiuting LI ; Yang ZHOU ; Xiaojing SU ; Qiong ZHANG ; Tianwen HUANG ; Ping ZHANG ; Hua LIN ; Xingling XIAO ; Ruifeng XU ; Fanghui DONG ; Bing HAN ; Luo FAN ; Yanling PEI ; Suyun LI ; Xiaoju TAN ; Rongchen GUO ; Yefang ZOU ; Xiaoyun HAN ; Junqin DING ; Yi WANG ; Shuhua DENG ; Jinli GUO ; Yinhua LIANG ; Yuan CEN ; Xiaoqin LIU ; Junru CHEN ; Haiyang YU ; Lunlan LI ; Ying REN ; Yunxia LI ; Jianli LU ; Ying YING ; Lan WEI ; Yin WANG ; Qinhong XU ; Yanqin ZHANG ; Yang LYU ; Shijun ZHANG ; Sui WENJIE ; Sanlian HU ; Shuhong YANG ; Guoqing LI ; Jingjing AN ; Baorong HE ; Leling FENG
Chinese Journal of Trauma 2025;41(6):530-541
Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.
9.Quantitative evaluation of left ventricular remodeling in left bundle branch block induced cardiomyopathy by multimodal imaging
Xiaoxian WANG ; Changqing MIAO ; Beibei GE ; Mingxia LI ; Fen CHEN ; Fang XU ; Ning ZHANG ; Guanjun GUO ; Wei XU ; Wenzhi SHEN ; Yingming ZHAO ; Jing YAO
Chinese Journal of Ultrasonography 2025;34(1):26-32
Objective:To quantitatively evaluate the effects of left bundle branch block(LBBB)on left ventricular structure,function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography(SPECT),and to investigate the relationship between myocardial work,myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy(LBBB-CM).Methods:Fourteen male beagle dogs were selected,and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram(ECG),transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs(normal control group)matched by age and weight. The correlation between myocardial perfusion(percentage of regional tracer uptake)and myocardial work parameters,myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline,the left ventricular end-diastolic volume of 12 months after the ablation increased[(20.78 ± 5.32)ml vs(26.71 ± 7.94)ml, P = 0.003],left ventricular ejection fraction decreased[(59.17 ± 5.67)% vs(47.69 ± 5.45)%, P<0.001];left ventricular global/segmental longitudinal strain,global/segmental constructive work and global/segmental work efficiency decreased(all P<0.05),left ventricular global/segmental wasted work increased(all P<0.001). Heterogenous perfusion defect was observed in LBBB dogs by SPECT,compared with lateral wall segments,the percentage of regional tracer uptake of septum was decreased(all P<0.05). Gross anatomical and myocardial pathological changes were manifested as cardiomegaly,flaky or focal grayish thickening of endocardium,cardiomyocyte degeneration and fibrosis. Compared with normal control group,the collagen fiber volume fraction(CVF)in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased(all P<0.05). Percentage of regional tracer uptake was positively correlated with segmental myocardial work(SMW)and segmental myocardial efficiency(SWE)( r s = 0.49,0.31;both P<0.001),and negatively correlated with CVF and segmental wasted work(SWW)( r s = -0.51,-0.49;both P<0.001). Conclusions:Isolated LBBB is not benign,which can result in left ventricular remodeling,decreased cardiac constructive function,abnormal myocardial perfusion,endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion,as non-invasive examination,can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.
10.Rho kinase inhibitor Y27632 promotes survival of human induced pluripotent stem cells during differentiation into functional midbrain dopaminergic progenitor cells in vitro
Yangyang LI ; Jiajia XU ; Chengcheng JIANG ; Zilong CHEN ; Ying CHEN ; Mengjiao YING ; Ao WANG ; Caiyun MA ; Chunjing WANG ; Yu GUO ; Changqing LIU
Journal of Southern Medical University 2024;44(2):236-243
Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

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