1.Effect of Wenshen Tongluo Zhitong formula on mouse H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system
Shijie ZHOU ; Muzhe LI ; Li YUN ; Tianchi ZHANG ; Yuanyuan NIU ; Yihua ZHU ; Qinfeng ZHOU ; Yang GUO ; Yong MA ; Lining WANG
Chinese Journal of Tissue Engineering Research 2025;29(1):8-15
BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.
2.Validating Multicenter Cohort Circular RNA Model for Early Screening and Diagnosis of Gestational Diabetes Mellitus
Shuo MA ; Yaya CHEN ; Zhexi GU ; Jiwei WANG ; Fengfeng ZHAO ; Yuming YAO ; Gulinaizhaer ABUDUSHALAMU ; Shijie CAI ; Xiaobo FAN ; Miao MIAO ; Xun GAO ; Chen ZHANG ; Guoqiu WU
Diabetes & Metabolism Journal 2025;49(3):462-474
Background:
Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed.
Methods:
High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression.
Results:
Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts.
Conclusion
Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.
3.Validating Multicenter Cohort Circular RNA Model for Early Screening and Diagnosis of Gestational Diabetes Mellitus
Shuo MA ; Yaya CHEN ; Zhexi GU ; Jiwei WANG ; Fengfeng ZHAO ; Yuming YAO ; Gulinaizhaer ABUDUSHALAMU ; Shijie CAI ; Xiaobo FAN ; Miao MIAO ; Xun GAO ; Chen ZHANG ; Guoqiu WU
Diabetes & Metabolism Journal 2025;49(3):462-474
Background:
Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed.
Methods:
High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression.
Results:
Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts.
Conclusion
Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.
4.Validating Multicenter Cohort Circular RNA Model for Early Screening and Diagnosis of Gestational Diabetes Mellitus
Shuo MA ; Yaya CHEN ; Zhexi GU ; Jiwei WANG ; Fengfeng ZHAO ; Yuming YAO ; Gulinaizhaer ABUDUSHALAMU ; Shijie CAI ; Xiaobo FAN ; Miao MIAO ; Xun GAO ; Chen ZHANG ; Guoqiu WU
Diabetes & Metabolism Journal 2025;49(3):462-474
Background:
Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed.
Methods:
High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression.
Results:
Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts.
Conclusion
Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.
5.Validating Multicenter Cohort Circular RNA Model for Early Screening and Diagnosis of Gestational Diabetes Mellitus
Shuo MA ; Yaya CHEN ; Zhexi GU ; Jiwei WANG ; Fengfeng ZHAO ; Yuming YAO ; Gulinaizhaer ABUDUSHALAMU ; Shijie CAI ; Xiaobo FAN ; Miao MIAO ; Xun GAO ; Chen ZHANG ; Guoqiu WU
Diabetes & Metabolism Journal 2025;49(3):462-474
Background:
Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed.
Methods:
High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression.
Results:
Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts.
Conclusion
Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or midterm diagnosis of GDM, offering clinical tools for early GDM screening.
6.Evaluation of surgical efficacy in patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023
Xixi CHENG ; Yu FENG ; Xu WANG ; Zhiyi WANG ; Jiaxi LEI ; Mingzhe JIANG ; Guobing YANG ; Xiaojuan ZHANG ; Shijie YANG ; Liying WANG
Chinese Journal of Schistosomiasis Control 2025;37(3):247-254
Objective To evaluate the therapeutic efficacy for surgical treatments among patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023, so as to provide insights into optimization of the diagnosis and treatment strategies against hepatic cystic echinococcosis. Methods The demographic and clinical data of all echinococcosis cases included in central government fiscal transfer payment program for echinococcosis control and undergoing surgical treatments in Gansu Province from 2006 to 2023 were captured. Hepatic cystic echinococcosis patients with complete medical records and follow-up data were included in the study, and patients’ characteristics, including hospital where patients received diagnosis and treatment, methods of case identification, year of surgery, classification of lesions, number of lesions, size of lesions, course of disease, surgical methods, and post-surgical follow-up data. The cure and recurrence of hepatic cystic echinococcosis were evaluated according to the Guidelines for Management of Echinococcosis Patients in the Central Government Fiscal Transfer Payment Program, and the cure and recurrent rates were calculated. Results Data were collected from 1 686 surgical patients with hepatic cystic echinococcosis. According to the inclusion and exclusion criteria, 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments were included during the period from 2006 to 2022, including 1 166 cured patients (95.42%) and 88 patients with postsurgical recurrence (7.20%), and the cure rate of surgical treatments appeared a tendency towards a rise among patients with hepatic cystic echinococcosis from 2008 to 2022 (χ2trend = 19.39, P < 0.05). The cure rates of hepatic cystic echinococcosis were 100% (177/177), 94.81% (128/135) and 94.62% (861/910) among patients detected through regular physical examinations, screened by the central government fiscal transfer payment program for echinococcosis control, and those who passively sought healthcare services, respectively (χ2 = 9.95, P < 0.05). The cure rates of hepatic cystic echinococcosis were 95.96% (1 046/1 090) among patients with a disease course of 2 years and less and 90.90% (120/132) among patients with a disease course of over 2 years (χ2 = 6.87, P < 0.05), and there were significant differences in the cure rates among patients with hepatic cystic echinococcosis in terms of number of lesions (χ2 = 24.44, P < 0.05) and surgical methods (P < 0.05). The cure rate of hepatic cystic echinococcosis patients was significantly higher following initiation of the central government fiscal transfer payment program for echinococcosis control (96.06%, 1 096/1 141) than before the program (86.42%, 70/81) (χ2 = 16.06, P < 0.05), and the cure rate of hepatic cystic echinococcosis patients was significantly higher in designated hospitals (96.48%, 741/768) than in non-designated hospitals (93.37%, 366/392) (χ2 = 5.78, P < 0.05). The median follow-up period was 4 (interquartile range, 7) years among 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments. The recurrent rate of hepatic cystic echinococcosis appeared a tendency towards a decline from 2008 to 2022 (χ2trend = 36.86, P < 0.05), with a reduction from 23.08% (9/39) in 2008 to 1.85% (1/54) in 2021, and the post-surgical recurrence rate of hepatic cystic echinococcosis was lower following initiation of the central government fiscal transfer payment program for echinococcosis control (5.87%, 67 / 1 141) than before the program (25.93%, 21/81) (χ2 = 45.51, P < 0.05). In addition, the post-surgical recurrence rate of hepatic cystic echinococcosis was higher in non-designated hospitals (10.46%, 41/392) than in designated hospitals (5.60%, 43/768) (χ2 = 9.12, P < 0.05), and there was a significant difference in the post-surgical recurrence rate among patients with hepatic cystic echinococcosis in terms of surgical methods (P < 0.05), with the highest recurrence rate (11.54%) seen among patients undergoing percutaneous fine-needle aspiration of cyst fluids-based surgical procedures (P < 0.05). Conclusion Since the initiation of the central government fiscal transfer payment program for echinococcosis control in Gansu Province in 2006, an increase in the surgical cure rate and a reduction in the recurrence of hepatic cystic echinococcosis had been found among patients with hepatic cystic echinococcosis, indicating a high overall therapeutic efficacy.
7.The value of new coagulation markers in the diagnosis and prognosis evaluation of neonatal disseminated intravascular coagulation
Shijie ZHANG ; Xianchun MENG ; Pingping SUN ; Jingjing YANG ; Jing WU
Tianjin Medical Journal 2024;52(2):206-210
Objective To investigate the value of thrombomodulin(TM),thrombin-antithrombin complex(TAT),α2 plasmin inhibitor-plasmin complex(PIC)and tissue plasminogen activator-inhibitor complex(t-PAIC)in the diagnosis and prognosis of neonatal disseminated intravascular coagulation(DIC).Methods Eighty-seven DIC neonates(the observation group)were included and divided into the survival group(66 cases)and the death group(21 cases)based on their outcomes at discharge.And 50 healthy newborns born in the same period were selected as the control group.The clinical data of neonates were collected,and risk factors of neonatal DIC were analyzed by Logistic regression.The differences of TM,TAT,PIC and t-PAIC levels in different groups were analyzed.The receiver operating characteristic(ROC)curve was used to analyze values of TM,TAT,PIC and t-PAIC in the diagnosis and prognosis of neonatal DIC.Results The incidence of low Apgar score,birth asphyxia,IVH,sepsis and maternal pregnancy induced hypertension syndrome(PIH)were higher in the observation group than those in the control group(P<0.05).Multivariate Logistic regression analysis showed that low Apgar score,birth asphyxia,sepsis and PIH were independent risk factors for neonatal DIC.TM,TAT,PIC and t-PAIC levels were higher in the observation group than those in the control group(P<0.05).ROC curve showed that the combined diagnosis value of TM,TAT,PIC and t-PAIC was better than that of single diagnosis of neonatal DIC.TM and TAT levels were higher in the death group than those in the survival group(P<0.05),and there were no significant differences in PIC and t-PAIC levels between the two groups.Multivariate Logistic regression analysis showed that elevated TAT level was an independent risk factor for neonatal DIC prognosis.ROC curve showed that when TAT was 21.72 μg/L,the area under the curve for predicting neonatal DIC prognosis was 0.772(95%CI:0.666-0.878),and the sensitivity and specificity were 76.2%and 71.2%,respectively.Conclusion The combined application of TM,TAT,PIC and t-PAIC has important clinical value in diagnosis and prognosis evaluation of neonatal DIC.
8.Mechanism underlying the effect of Liuwei Dihuang Pill on osteolysis and osteogenesis induced by titanium particles
Zhiqi ZHU ; Sijie YUAN ; Zilin ZHANG ; Shijie JI ; Mingsong MENG ; Anming YAN ; Jing HAN
Chinese Journal of Tissue Engineering Research 2024;28(3):392-397
BACKGROUND:At present,a large number of studies have found that Liuwei Dihuang Pill can be used to treat osteoporosis,but there are few related studies on the differentiation and mineralization of osteoblasts induced by wear particles using Liuwei Dihuang Pill. OBJECTIVE:To investigate the positive effect of different concentrations of Liuwei Dihuang Pill-containing serum on titanium particle-induced mouse MC3T3-E1 osteoblast in vitro osteolysis model. METHODS:Drug-containing serum was extracted after oral administration of Liuwei Dihuang Pill.The best concentration of Liuwei Dihuang Pill-containing serum and titanium particles on the viability of MC3T3-E1 cells was screened.MC3T3-E1 cells were divided into three groups.The blank group was given osteoblastic differentiation culture.The model group was given titanium particles(5 μg/mL)ossification culture.The drug-containing serum group was given titanium particles(5 μg/mL)+ Liuwei Dihuang Pill-containing serum(10%,15%and 20%doses).Osteoblast viability was detected by CCK-8 assay.Cell alkaline phosphatase activity was detected by alkaline phosphatase staining.Cell mineralization was detected by silver nitrate(Von Kossa)and alizarin red staining.Expression levels of bone differentiation-related genes Runx-2,Osterix,Ocn,Axin,Alp,and Opn were detected by qRT-PCR.Wnt/β-catenin signaling pathways β-catenin,p-GSK-3β,GSK-3β,Runx2 and Osterix protein expression levels were detected by western blot assay. RESULTS AND CONCLUSION:(1)Liuwei Dihuang Pill-containing serum culture reversed the decrease in alkaline phosphatase activity of MC3T3E-1 cells induced by titanium particles,increased the alizarin red staining and calcification of MC3T3E-1 cells,increased the expression of osteogenesis-related genes in MC3T3E-1 cells,and increased the expression of proteins related to the Wnt/β-catenin signaling pathway.(2)These findings indicate that Liuwei Dihuang Pill-containing serum can reverse the inhibitory effect of titanium particles on the differentiation and mineralization of osteoblasts,upregulate the expression of osteogenesis-related genes,and its mechanism is related to the regulation of Wnt/β-catenin signaling pathway,suggesting that Liuwei Dihuang Pill is expected to become an effective drug for preventing aseptic loosening of artificial joints.
9.New interpretation of the theoretical connotation of the correspondence between prescription and syndrome from the longitudinal perspective of"traditional Chinese medicine state"
Shijie QIAO ; Chao FU ; Ziyao CAI ; Wen TANG ; Zhanglin WANG ; Zhibin WANG ; Kang TONG ; Mingzhu LI ; Hairui HAN ; Duoduo LIN ; Shaodong ZHANG ; Huangwei LEI ; Yang WANG ; Candong LI
Journal of Beijing University of Traditional Chinese Medicine 2024;47(6):760-764
The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.
10.Correlation between CHA 2DS 2-VASC score and recurrence of paroxysmal atrial fibrillation after radiofrequency ablation
Ruijuan DU ; Qingmin WEI ; Yanming FAN ; Shijie WANG ; Yanlong ZHANG ; Guoqing GE
Chinese Journal of General Practitioners 2024;23(1):52-56
Objective:To investigate the correlation between CHA 2DS 2-VASC score and the recurrence risk of paroxysmal atrial fibrillation after radiofrequency ablation. Methods:It was a retrospective cohort study. A total of 150 patients who underwent radiofrequency ablation for paroxysmal atrial fibrillation in Xingtai People′s Hospital from January 2017 to January 2021 were consecutively included in the study. According to the preoperative CHA 2DS 2-VASC score, patients were divided into high score group (≥3 points, n=90) and low score group (<3 points, n=60). Baseline clinical data was collected. All patients underwent circumferential pulmonary vein isolation, and those with atrial flutter before ablation also underwent tricuspid isthmus isolation. Holter and electrocardiogram examinations were performed at 3, 6 months and 1 year after ablation to evaluate whether there was recurrence of atrial fibrillation. Univariate and multivariate Cox regression was used to analyze the risk factors for recurrence of atrial fibrillation after radiofrequency ablation. Results:Among 150 patients 90 were males and 60 were females with a mean age of (64.0±3.6) years. There were no significant differences in age, sex, and proportion of hypertension, diabetes, chronic heart failure and stroke or transient ischemic attack (TIA), medication of antiarrhythmic and anticoagulant drugs between the two groups (all P>0.05). The longest duration of atrial fibrillation in the high score group was significantly longer than that in the low score group (26.0±6.1) hours vs. (10.0±2.1) hours, P<0.05). There were no patients with cardiac tamponade, atrial esophageal fistula and severe vascular puncture complications in the two groups. During the follow-up period, the recurrence rate in the high score group was significantly higher than that in the low score group (16.7% (15/90) vs. 8.3% (5/60), P<0.05). Multivariate Cox regression analysis showed that CHA 2DS 2-VASC score≥3 was an independent risk factor for atrial fibrillation recurrence in patients with paroxysmal atrial fibrillation after radiofrequency ablation ( HR=3.84, 95% CI: 1.87-7.89, P=0.02). Conclusion:CHA 2DS 2-VASC score≥3 is an independent risk factor for atrial fibrillation recurrence in patients with paroxysmal atrial fibrillation after radiofrequency ablation.

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