1.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.
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.The effect of Ba Duan Jin on the balance of community-dwelling older adults: a cluster randomized control trial
Leilei DUAN ; Yubin ZHAO ; Yuliang ER ; Pengpeng YE ; Wei WANG ; Xin GAO ; Xiao DENG ; Ye JIN ; Yuan WANG ; Cuirong JI ; Xinyan MA ; Cong GAO ; Yuhong ZHAO ; Suqiu ZHU ; Shuzhen SU ; Xin'e GUO ; Juanjuan PENG ; Yan YU ; Chen YANG ; Yaya SU ; Ming ZHAO ; Lihua GUO ; Yiping WU ; Yangnu LUO ; Ruilin MENG ; Haofeng XU ; Huazhang LIU ; Huihong RUAN ; Bo XIE ; Huimin ZHANG ; Yuhua LIAO ; Yan CHEN ; Linhong WANG
Chinese Journal of Epidemiology 2024;45(2):250-256
Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.
6.Clinical investigation of Q. Flex for improvement of PET/CT image quality and quantitative accuracy of pulmonary nodules
Dong DAI ; Jianjing LIU ; Di LU ; Guoqing SUI ; Yaya WANG ; Xueyao LIU ; Yuanfang YUE ; Zhen YANG ; Qing YANG ; Jie FU ; Wengui XU ; Ziyang WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(2):98-103
Objective:To compare the imaging quality and metabolic quantitative parameters of pulmonary nodules between Q. Flex whole information five-dimensional (5D) and conventional three-dimensional (3D) PET/CT imaging for clinical evaluation.Methods:Fifty-four patients (30 males, 24 females, age: 60(42, 75) years; 78 solid pulmonary nodules (maximum diameter≤3 cm) with abnormal uptake of 18F-FDG) from Tianjin Cancer Hospital Airport Hospital between June 2022 and August 2022 were enrolled in this retrospective study. All patients underwent 5D scanning and 3D, 5D reconstruction. Image quality scores, signal-to-noise ratio (SNR), SUV max, SUV mean and metabolic tumor volume (MTV) of pulmonary nodules of 5D group and 3D group were evaluated and compared with χ2 test and Wilcoxon signed rank test. Correlation of quantitative parameters between 2 groups were analyzed by using Spearman rank correlation analysis. Results:Thirty-five of 78(45%) pulmonary nodules with image quality score≥4 were found in 5D group, which were more than those in 3D group (22/78(28%); χ2=4.67, P=0.031). Meanwhile, SNR, SUV max, SUV mean, and MTV were significantly positively correlated between the 2 groups ( rs values: 0.86, 0.86, 0.85, and 0.95, all P<0.001). SNR, SUV max and SUV mean of pulmonary nodules in 5D group were significantly higher than those in 3D group, which were 37.46(18.42, 62.00) vs 32.72(16.97, 54.76) ( z=-4.07, P<0.001), 9.71(5.48, 13.82) vs 8.96(4.82, 12.63) ( z=-3.05, P<0.001) and 6.30(3.39, 8.94) vs 5.61(2.99, 7.63)( z=-4.07, P<0.001) respectively. MTV of pulmonary nodules in 5D group was significantly lower than that in 3D group, which was 1.72(0.66, 2.74) cm 3vs 1.98(1.06, 4.63) cm 3 ( z=-7.13, P<0.001). Quantitative parameters of lower lung field and nodules with maximum diameters of >10 mm and ≤20 mm based on 5D scanning changed most significantly compared with those based on 3D scanning ( z values: from -5.23 to -2.48, all P<0.05). Conclusion:Q. Flex 5D PET significantly improves the quantitative accuracy of SUV and MTV of pulmonary nodules, and the improvement of image quality is substantial without increasing the radiation dose, which has clinical practical value.
7.Changes of fasting plasma glucose level before and after menopause: Research based on Kailuan health checkup cohort
Yaya ZHANG ; Qiaoyun DAI ; Shouling WU ; Shuohua CHEN ; Xueying YANG ; Yuntao WU ; Xu MA ; Jianmei WANG
Chinese Journal of Endocrinology and Metabolism 2024;40(1):22-29
Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.
8.Clinical genetic analysis of a epileptic family with DEPDC5 gene variant and a patient with a de novo variant in the GABRA1 gene
Yaya YANG ; Yidan WANG ; Jian GAO
Chinese Journal of Neurology 2024;57(10):1127-1135
Objective:To report a large family of epileptic seizures caused by DEPDC5 gene variation, and to conduct a clinical genetic analysis on a proband in this family with both DEPDC5 gene mutation and a de novo GABRA1 gene mutation. Methods:The medical records of a family suffering from epilepsy due to a newly identified DEPDC5 gene variant were compiled from cases admitted to Hebei General Hospital in January 2024. The relevant genetic detection was carried out by sampling the peripheral blood of the family members. The whole exome sequencing techniques were employed for the identification of pathogenic mutation sites in the proband. The next generation sequencing technology was utilized for other family members to identify disease-causing mutation sites associated with the clinical phenotype of patients, and these findings were confirmed using first-generation Sanger sequencing technology. Results:The proband, who experienced seizures in early childhood and harbored two gene mutation sites, exhibited an early onset age along with significant delays in both intellectual and motor development. The primary clinical manifestations included focal seizures, myoclonus, and tonic-clonic symptoms. When compared with other family members who had the onset of epilepsy during adolescence, carried only one mutation site, and had generalized epileptic seizures and mostly accompanied by attention deficit hyperactivity disorder, the proband showed obvious clinical heterogeneity. The results of whole exome sequencing indicated that the proband had both GABRA1 c.640C>T(p.Arg214Cys) and DEPDC5 c.4348A>T(p.Lys1450 *) mutations inherited from the father. The mutation inherited from the father was reported here for the first time and had not been reported before, with the paternal mutation traceable to the proband's grandfather, while the proband's mother and grandmother were found to be devoid of the mutation. In this family, 5 patients with similar seizure phenotype all had pathogenic mutations at the same locus of the DEPDC5 gene(c.4348A>T, p.Lys1450 *), and the remaining 3 patients with seizure symptoms were not tested. Conclusions:The DEPDC5 gene mutation is the cause of the disease in this family, and the c.4348A>T is the newly discovered mutation site. The proband carries the mutation sites of both GABRA1 gene and DEPDC5 gene. The clinical manifestations of proband are significantly heterogeneous compared with those of his family members.
9.Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs
Xiao ZUO ; Pengfei HAN ; Ding YUAN ; Ying XIAO ; Yushi HUANG ; Rui LI ; Xia JIANG ; Li FENG ; Yijun LI ; Yaya ZHANG ; Ping ZHU ; Hongge WANG ; Ning WANG ; Y. James KANG
Tissue Engineering and Regenerative Medicine 2024;21(4):641-651
BACKGROUND:
Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys.
RESULTS:
Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome.
CONCLUSION
This cell-based vascular graft is ready to undergo clinical trials for human patients.
10.Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge
Dongmei ZHANG ; Yaya ZHOU ; Yanling MA ; Ping CHEN ; Jian TANG ; Bohan YANG ; Hui LI ; Mengyuan LIANG ; YuE XUE ; Yao LIU ; Jianchu ZHANG ; Xiaorong WANG
Journal of Korean Medical Science 2023;38(15):e120-
Background:
Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear.
Methods:
We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19.
Results:
In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing.Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group.
Conclusion
This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

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