1.Hypertrophic Cardiomyopathy: Mechanisms of Pathogenicity.
Bao Xi WANG ; Yue Ting ZHOU ; Yi Pin ZHAO ; Yong CHENG ; Jun REN ; Guan Chang TAN ; Xiao Hu WANG
Biomedical and Environmental Sciences 2025;38(8):988-1000
Hypertrophic cardiomyopathy (HCM) is a major contributor to cardiovascular diseases (CVD), the leading cause of death globally. HCM can precipitate heart failure (HF) by causing the cardiac tissue to weaken and stretch, thereby impairing its pumping efficiency. Moreover, HCM increases the risk of atrial fibrillation, which in turn elevates the likelihood of thrombus formation and stroke. Given these significant clinical ramifications, research into the etiology and pathogenesis of HCM is intensifying at multiple levels. In this review, we discuss and synthesize the latest findings on HCM pathogenesis, drawing on key experimental studies conducted both in vitro and in vivo. We also offer our insights and perspectives on these mechanisms, while highlighting the limitations of current research. Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.
Cardiomyopathy, Hypertrophic/physiopathology*
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Humans
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Animals
2.Development of A High-performance Rectangular Ion Trap for Multi-reflection Time-of-Flight Mass Spectrometer
Xiao-Xia CHEN ; Yi REN ; Qi HUANG ; Da-Jun XIANG ; Chang-Wei LI ; Yi HONG ; Lei LI ; Zheng-Xu HUANG ; Mei LI ; Jing-Wei XU ; Zhen ZHOU
Chinese Journal of Analytical Chemistry 2025;53(1):38-46
As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.
3.Bioequivalence study of ezetimibe tablets in Chinese healthy subjects
Pei-Yue ZHAO ; Tian-Cai ZHANG ; Yu-Ning ZHANG ; Ya-Fei LI ; Shou-Ren ZHAO ; Jian-Chang HE ; Li-Chun DONG ; Min SUN ; Yan-Jun HU ; Jing LAN ; Wen-Zhong LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2378-2382
Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90%CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90%CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.
4.Injurious effects of neutrophil extracellular trapping network on kidney of diabetic mice and its mechanisms
Wei-Hao CHEN ; Xiao-Jun REN ; Xin-Yue CHANG ; Guan-Rui LI ; Yan-Hong WANG
Chinese Pharmacological Bulletin 2024;40(12):2262-2269
Aim To investigate the promotional effects of neutrophil extracellular traps(NETs)on renal tissue damage and intestinal flora disruption induced by dia-betic kidney disease(DKD)and the potential mecha-nisms.Methods C57BL/6 mice were divided into:control group(NC),DNase Ⅰ control group(DNase Ⅰ)diabetic nephropathy group(DKD),and DNase Ⅰ treated group(DKD+DNase Ⅰ).The pathological changes of mouse kidney were observed by PAS,MAS-SON,and HE staining.The expression and distribu-tion of the relevant proteins of NETs in renal tissue of the mice in each group were observed by immunohisto-chemistry.The expression and distribution of coke-death-related proteins in the kidney tissues of mice in each group were observed by immunohistochemistry.The protein expression of NETs-related indexes,focal death-related indexes and NF-κB signaling pathway-re-lated indexes in kidney tissue of mice in each group were detected by immunoblotting.Results The ex-pression of indicators related to NETs was elevated in the DKD group,and their expression decreased after degradation of NETs by DNase Ⅰ(P<0.01).Patho-logical staining results showed that the kidneys of DKD mice were structurally abnormal,and the structure was improved after degradation of NETs by DNase Ⅰ.The results of immunohistochemical staining and immunob-lotting showed that the expression of pyroptosis-related proteins in kidney tissues of mice in the DKD group was elevated compared with that in the control group(P<0.01).NF-κB-related signaling pathway protein expression profile expression rose,and its expression decreased after degradation of NETs by DNase Ⅰ(P<0.01)Conclusions NETs are generated in diabetic nephropathy and promote the onset of renal focal death and activation of the NF-κB signaling pathway,thereby exacerbating diabetes-induced kidney injury.
5.Study on the Application of Indocyanine Green Fluorescence Guided Laparo-scopic Lymph Node Resection in Clinical Early Stage Cervical Cancer Staging Surgery
Biao TANG ; Xiaoyan REN ; Ling WU ; Jun CHANG ; Shaolan YU ; Wenjuan WU ; Qiufan LI ; Gang WANG
Journal of Practical Obstetrics and Gynecology 2024;40(9):734-738
Objective:To explore the feasibility and application value of indocyanine green(ICG)lymph node tracer in clinical early stage cervical cancer staging surgery.Methods:A retrospective analysis was performed on 31 patients with early clinical stage(ⅠA1-ⅡA1)cervical cancer who underwent laparoscopic radical hysterectomy,pelvic lymph node resection and para-aortic lymph node sampling were selected as the study subjects in Sichuan Provincial Maternal and Child Health Care Hospital from April 1,2022 to July 31,2023.They were divided into the ICG fluorescence tracer group(ICG group,17 cases)and the conventional surgery group(control group,14 ca-ses)based on whether ICG was injected or not.The resected lymph nodes were classified and submitted for ex-amination according to location and whether they presented visualization.The method of contingency coefficient was used to analyze the correlations between lymph node visualization patterns and lymph node metastasis and clinicopathological characteristics,and the perioperative data of the two groups were compared.Results:①The postoperative stage of 8 patients(25.8%)(4 in each group)were improved compared with the preoperative clini-cal stage.The number of resected lymph nodes in the ICG group was less than that in the control group(18±9 nodes/person vs.26±11 nodes/person,P<0.05).There were no statistically significant differences in operation time,intraoperative blood loss,postoperative FIGO(2018)staging,lymph node metastasis rate,and positive rate of resected lymph nodes between the two groups(P>0.05).②The visualization rate in the ICG group was 64.71%(11/17).There was no statistically significant difference in the positive rate between the visualized and non-visualized lymph nodes(P>0.05).There was a significant correlation between lymph node visualization and lymph node metastasis(C=0.707,P<0.05),and a significant correlation was found between lymph node visual-ization and lymph node metastasis in the same patient(C=0.557,P<0.05).Conclusions:The rate of lymph node metastasis in clinical early stage cervical cancer is low.ICG fluorescence visualization can trace lymph nodes and predict the risk of metastasis.By only resecting the visualized lymph nodes under the guidance of ICG tracer,the lymph node metastasis status of early-stage cervical cancer can be fully evaluated,which is worthy of further research.
6.Study on the Application of Indocyanine Green Fluorescence Guided Laparo-scopic Lymph Node Resection in Clinical Early Stage Cervical Cancer Staging Surgery
Biao TANG ; Xiaoyan REN ; Ling WU ; Jun CHANG ; Shaolan YU ; Wenjuan WU ; Qiufan LI ; Gang WANG
Journal of Practical Obstetrics and Gynecology 2024;40(9):734-738
Objective:To explore the feasibility and application value of indocyanine green(ICG)lymph node tracer in clinical early stage cervical cancer staging surgery.Methods:A retrospective analysis was performed on 31 patients with early clinical stage(ⅠA1-ⅡA1)cervical cancer who underwent laparoscopic radical hysterectomy,pelvic lymph node resection and para-aortic lymph node sampling were selected as the study subjects in Sichuan Provincial Maternal and Child Health Care Hospital from April 1,2022 to July 31,2023.They were divided into the ICG fluorescence tracer group(ICG group,17 cases)and the conventional surgery group(control group,14 ca-ses)based on whether ICG was injected or not.The resected lymph nodes were classified and submitted for ex-amination according to location and whether they presented visualization.The method of contingency coefficient was used to analyze the correlations between lymph node visualization patterns and lymph node metastasis and clinicopathological characteristics,and the perioperative data of the two groups were compared.Results:①The postoperative stage of 8 patients(25.8%)(4 in each group)were improved compared with the preoperative clini-cal stage.The number of resected lymph nodes in the ICG group was less than that in the control group(18±9 nodes/person vs.26±11 nodes/person,P<0.05).There were no statistically significant differences in operation time,intraoperative blood loss,postoperative FIGO(2018)staging,lymph node metastasis rate,and positive rate of resected lymph nodes between the two groups(P>0.05).②The visualization rate in the ICG group was 64.71%(11/17).There was no statistically significant difference in the positive rate between the visualized and non-visualized lymph nodes(P>0.05).There was a significant correlation between lymph node visualization and lymph node metastasis(C=0.707,P<0.05),and a significant correlation was found between lymph node visual-ization and lymph node metastasis in the same patient(C=0.557,P<0.05).Conclusions:The rate of lymph node metastasis in clinical early stage cervical cancer is low.ICG fluorescence visualization can trace lymph nodes and predict the risk of metastasis.By only resecting the visualized lymph nodes under the guidance of ICG tracer,the lymph node metastasis status of early-stage cervical cancer can be fully evaluated,which is worthy of further research.
7.Study on the Application of Indocyanine Green Fluorescence Guided Laparo-scopic Lymph Node Resection in Clinical Early Stage Cervical Cancer Staging Surgery
Biao TANG ; Xiaoyan REN ; Ling WU ; Jun CHANG ; Shaolan YU ; Wenjuan WU ; Qiufan LI ; Gang WANG
Journal of Practical Obstetrics and Gynecology 2024;40(9):734-738
Objective:To explore the feasibility and application value of indocyanine green(ICG)lymph node tracer in clinical early stage cervical cancer staging surgery.Methods:A retrospective analysis was performed on 31 patients with early clinical stage(ⅠA1-ⅡA1)cervical cancer who underwent laparoscopic radical hysterectomy,pelvic lymph node resection and para-aortic lymph node sampling were selected as the study subjects in Sichuan Provincial Maternal and Child Health Care Hospital from April 1,2022 to July 31,2023.They were divided into the ICG fluorescence tracer group(ICG group,17 cases)and the conventional surgery group(control group,14 ca-ses)based on whether ICG was injected or not.The resected lymph nodes were classified and submitted for ex-amination according to location and whether they presented visualization.The method of contingency coefficient was used to analyze the correlations between lymph node visualization patterns and lymph node metastasis and clinicopathological characteristics,and the perioperative data of the two groups were compared.Results:①The postoperative stage of 8 patients(25.8%)(4 in each group)were improved compared with the preoperative clini-cal stage.The number of resected lymph nodes in the ICG group was less than that in the control group(18±9 nodes/person vs.26±11 nodes/person,P<0.05).There were no statistically significant differences in operation time,intraoperative blood loss,postoperative FIGO(2018)staging,lymph node metastasis rate,and positive rate of resected lymph nodes between the two groups(P>0.05).②The visualization rate in the ICG group was 64.71%(11/17).There was no statistically significant difference in the positive rate between the visualized and non-visualized lymph nodes(P>0.05).There was a significant correlation between lymph node visualization and lymph node metastasis(C=0.707,P<0.05),and a significant correlation was found between lymph node visual-ization and lymph node metastasis in the same patient(C=0.557,P<0.05).Conclusions:The rate of lymph node metastasis in clinical early stage cervical cancer is low.ICG fluorescence visualization can trace lymph nodes and predict the risk of metastasis.By only resecting the visualized lymph nodes under the guidance of ICG tracer,the lymph node metastasis status of early-stage cervical cancer can be fully evaluated,which is worthy of further research.
8.Study on the Application of Indocyanine Green Fluorescence Guided Laparo-scopic Lymph Node Resection in Clinical Early Stage Cervical Cancer Staging Surgery
Biao TANG ; Xiaoyan REN ; Ling WU ; Jun CHANG ; Shaolan YU ; Wenjuan WU ; Qiufan LI ; Gang WANG
Journal of Practical Obstetrics and Gynecology 2024;40(9):734-738
Objective:To explore the feasibility and application value of indocyanine green(ICG)lymph node tracer in clinical early stage cervical cancer staging surgery.Methods:A retrospective analysis was performed on 31 patients with early clinical stage(ⅠA1-ⅡA1)cervical cancer who underwent laparoscopic radical hysterectomy,pelvic lymph node resection and para-aortic lymph node sampling were selected as the study subjects in Sichuan Provincial Maternal and Child Health Care Hospital from April 1,2022 to July 31,2023.They were divided into the ICG fluorescence tracer group(ICG group,17 cases)and the conventional surgery group(control group,14 ca-ses)based on whether ICG was injected or not.The resected lymph nodes were classified and submitted for ex-amination according to location and whether they presented visualization.The method of contingency coefficient was used to analyze the correlations between lymph node visualization patterns and lymph node metastasis and clinicopathological characteristics,and the perioperative data of the two groups were compared.Results:①The postoperative stage of 8 patients(25.8%)(4 in each group)were improved compared with the preoperative clini-cal stage.The number of resected lymph nodes in the ICG group was less than that in the control group(18±9 nodes/person vs.26±11 nodes/person,P<0.05).There were no statistically significant differences in operation time,intraoperative blood loss,postoperative FIGO(2018)staging,lymph node metastasis rate,and positive rate of resected lymph nodes between the two groups(P>0.05).②The visualization rate in the ICG group was 64.71%(11/17).There was no statistically significant difference in the positive rate between the visualized and non-visualized lymph nodes(P>0.05).There was a significant correlation between lymph node visualization and lymph node metastasis(C=0.707,P<0.05),and a significant correlation was found between lymph node visual-ization and lymph node metastasis in the same patient(C=0.557,P<0.05).Conclusions:The rate of lymph node metastasis in clinical early stage cervical cancer is low.ICG fluorescence visualization can trace lymph nodes and predict the risk of metastasis.By only resecting the visualized lymph nodes under the guidance of ICG tracer,the lymph node metastasis status of early-stage cervical cancer can be fully evaluated,which is worthy of further research.
9.Study on the Application of Indocyanine Green Fluorescence Guided Laparo-scopic Lymph Node Resection in Clinical Early Stage Cervical Cancer Staging Surgery
Biao TANG ; Xiaoyan REN ; Ling WU ; Jun CHANG ; Shaolan YU ; Wenjuan WU ; Qiufan LI ; Gang WANG
Journal of Practical Obstetrics and Gynecology 2024;40(9):734-738
Objective:To explore the feasibility and application value of indocyanine green(ICG)lymph node tracer in clinical early stage cervical cancer staging surgery.Methods:A retrospective analysis was performed on 31 patients with early clinical stage(ⅠA1-ⅡA1)cervical cancer who underwent laparoscopic radical hysterectomy,pelvic lymph node resection and para-aortic lymph node sampling were selected as the study subjects in Sichuan Provincial Maternal and Child Health Care Hospital from April 1,2022 to July 31,2023.They were divided into the ICG fluorescence tracer group(ICG group,17 cases)and the conventional surgery group(control group,14 ca-ses)based on whether ICG was injected or not.The resected lymph nodes were classified and submitted for ex-amination according to location and whether they presented visualization.The method of contingency coefficient was used to analyze the correlations between lymph node visualization patterns and lymph node metastasis and clinicopathological characteristics,and the perioperative data of the two groups were compared.Results:①The postoperative stage of 8 patients(25.8%)(4 in each group)were improved compared with the preoperative clini-cal stage.The number of resected lymph nodes in the ICG group was less than that in the control group(18±9 nodes/person vs.26±11 nodes/person,P<0.05).There were no statistically significant differences in operation time,intraoperative blood loss,postoperative FIGO(2018)staging,lymph node metastasis rate,and positive rate of resected lymph nodes between the two groups(P>0.05).②The visualization rate in the ICG group was 64.71%(11/17).There was no statistically significant difference in the positive rate between the visualized and non-visualized lymph nodes(P>0.05).There was a significant correlation between lymph node visualization and lymph node metastasis(C=0.707,P<0.05),and a significant correlation was found between lymph node visual-ization and lymph node metastasis in the same patient(C=0.557,P<0.05).Conclusions:The rate of lymph node metastasis in clinical early stage cervical cancer is low.ICG fluorescence visualization can trace lymph nodes and predict the risk of metastasis.By only resecting the visualized lymph nodes under the guidance of ICG tracer,the lymph node metastasis status of early-stage cervical cancer can be fully evaluated,which is worthy of further research.
10.Study on the Application of Indocyanine Green Fluorescence Guided Laparo-scopic Lymph Node Resection in Clinical Early Stage Cervical Cancer Staging Surgery
Biao TANG ; Xiaoyan REN ; Ling WU ; Jun CHANG ; Shaolan YU ; Wenjuan WU ; Qiufan LI ; Gang WANG
Journal of Practical Obstetrics and Gynecology 2024;40(9):734-738
Objective:To explore the feasibility and application value of indocyanine green(ICG)lymph node tracer in clinical early stage cervical cancer staging surgery.Methods:A retrospective analysis was performed on 31 patients with early clinical stage(ⅠA1-ⅡA1)cervical cancer who underwent laparoscopic radical hysterectomy,pelvic lymph node resection and para-aortic lymph node sampling were selected as the study subjects in Sichuan Provincial Maternal and Child Health Care Hospital from April 1,2022 to July 31,2023.They were divided into the ICG fluorescence tracer group(ICG group,17 cases)and the conventional surgery group(control group,14 ca-ses)based on whether ICG was injected or not.The resected lymph nodes were classified and submitted for ex-amination according to location and whether they presented visualization.The method of contingency coefficient was used to analyze the correlations between lymph node visualization patterns and lymph node metastasis and clinicopathological characteristics,and the perioperative data of the two groups were compared.Results:①The postoperative stage of 8 patients(25.8%)(4 in each group)were improved compared with the preoperative clini-cal stage.The number of resected lymph nodes in the ICG group was less than that in the control group(18±9 nodes/person vs.26±11 nodes/person,P<0.05).There were no statistically significant differences in operation time,intraoperative blood loss,postoperative FIGO(2018)staging,lymph node metastasis rate,and positive rate of resected lymph nodes between the two groups(P>0.05).②The visualization rate in the ICG group was 64.71%(11/17).There was no statistically significant difference in the positive rate between the visualized and non-visualized lymph nodes(P>0.05).There was a significant correlation between lymph node visualization and lymph node metastasis(C=0.707,P<0.05),and a significant correlation was found between lymph node visual-ization and lymph node metastasis in the same patient(C=0.557,P<0.05).Conclusions:The rate of lymph node metastasis in clinical early stage cervical cancer is low.ICG fluorescence visualization can trace lymph nodes and predict the risk of metastasis.By only resecting the visualized lymph nodes under the guidance of ICG tracer,the lymph node metastasis status of early-stage cervical cancer can be fully evaluated,which is worthy of further research.

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