1.CircRNA Circ_0120051 Inhibits the Fibrotic Phenotype of Myocardial Fibroblasts via Targeting miR-144-3p/IDH2 Axis
Yu LIANG ; Zhiqin HU ; Yihong WEN ; Huayan WU ; Ya WNAG ; Yupeng LIU ; Zhixin SHAN ; Xianhong FANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):196-205
ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1(SLC8A1) mRNA in the myocardium of healthy organ donors (n=24) and heart failure (HF) patients (n=21) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts (mCFs) with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay, respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation (RIP) was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 (Idh2) mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients, while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression, and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA (siRNA) could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.
2.CircSLC8A1_005 Inhibits the Fibrotic Phenotype of Cardiac Fibroblasts by Encoding Protein
Yating HU ; Yuan GAO ; Huayan WU ; Yu LIANG ; Hui LI ; Jindong XU ; Yupeng LIU ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):35-44
ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes, collagen type I alpha 1 chain (Col1a1), collagen type Ⅲ alpha 1 chain (Col3a1) and smooth muscle actin alpha 2 (Acta2), in mouse cardiac fibroblasts (mCFs) were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay, respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site (IRES) in circSLC8A1_005. CircSLC8A1_005-translated protein, SLC8A1-605aa, and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation (RIP) was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 (Sod2) mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs, and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku, which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 (Sod2) expression, but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA, and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein, and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.
3.Study on the Optimal Harvesting Period of Platycodonis Radix by Grey Correlation Method and TOPSIS Method Based on Entropy Weight Method
Yajiang JING ; Jianping HUANG ; Qilong WANG ; Jia AN ; Xiang WANG ; Yupeng WANG ; Gang ZHANG ; Liang PENG ; Jing GAO ; Changli WANG ; Yonggang YAN
Chinese Journal of Modern Applied Pharmacy 2024;41(9):1229-1237
OBJECTIVE
To improve the quality evaluation method of Platycodonis Radix, to study the differences in the quality of three-years-old Platycodonis Radix under different harvesting periods, and to determine the optimal harvesting period of Platycodonis Radix.
METHODS
The leachate, ash, moisture, refractive index and the content of six saponins were used as the quality evaluation indexes. The differences between the herbs of Platycodonis Radix at different harvesting periods were characterized with the help of mathematical and statistical methods. And link the entropy weight method, gray correlation analysis and TOPSIS method were combined to obtain the statistical analysis of the relevant indexes and the quality ranking information of the herbs in different harvesting periods.
RESULTS
There were significant differences between the quality evaluation indexes of three-years-old Platycodonis Radix at different harvesting periods. The added multi-indicator testing had improved the quality evaluation system of Platycodonis Radix and enhanced the "Drug properties-Effectiveness" linkage of the herbs. And the results of the comprehensive quality evaluation model showed that the herbs harvested around October 21 (Frost’s Descent) were ranked best in terms of comprehensive index.
CONCLUSION
In order to ensure the quality of Platycodonis Radix, the best harvesting period for three-years-old Platycodonis Radix is determined around the "Frost’s Descent" season, taking into account the characteristics of the herbs' appearance and the material basis of herbs.
4.Research progress on work-related musculoskeletal disorders in primary and secondary school teachers
Yupeng YUAN ; Bo WANG ; Yang ZHANG ; Dong LIANG
Journal of Environmental and Occupational Medicine 2024;41(11):1325-1330
Work-related musculoskeletal disorders (WMSDs) are common and serious occupational health problems faced by primary and secondary school teachers around the world. The high prevalence of WMSD brings great harm to the physical health, psychology, daily work and life of primary and secondary school teachers. This project systematically reviewed the basic situation of WMSDs in primary and secondary school teachers at home and abroad, summarized the prevalence rate, involved body parts and main hazards of WMSDs in primary and secondary school teachers, and concluded the personal factors, occupational factors and social psychological factors leading to WMSDs. Based on this, a set of basic prevention and control measures of WMSDs were proposed from five perspectives: organizational training, organizational management, ergonomic design, individual behavior and social psychology, in order to provide a scientific basis for the prevention and treatment of WMSDs.
5.Prediction of Venous Trans-Stenotic Pressure Gradient Using Shape Features Derived From Magnetic Resonance Venography in Idiopathic Intracranial Hypertension Patients
Chao MA ; Haoyu ZHU ; Shikai LIANG ; Yuzhou CHANG ; Dapeng MO ; Chuhan JIANG ; Yupeng ZHANG
Korean Journal of Radiology 2024;25(1):74-85
Objective:
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology associated with venous sinus stenosis. This study aimed to develop a magnetic resonance venography (MRV)-based radiomics model for predicting a high trans-stenotic pressure gradient (TPG) in IIH patients diagnosed with venous sinus stenosis.
Materials and Methods:
This retrospective study included 105 IIH patients (median age [interquartile range], 35 years [27– 42 years]; female:male, 82:23) who underwent MRV and catheter venography complemented by venous manometry. Contrast enhanced-MRV was conducted under 1.5 Tesla system, and the images were reconstructed using a standard algorithm. Shape features were derived from MRV images via the PyRadiomics package and selected by utilizing the least absolute shrinkage and selection operator (LASSO) method. A radiomics score for predicting high TPG (≥ 8 mmHg) in IIH patients was formulated using multivariable logistic regression; its discrimination performance was assessed using the area under the receiver operating characteristic curve (AUROC). A nomogram was constructed by incorporating the radiomics scores and clinical features.
Results:
Data from 105 patients were randomly divided into two distinct datasets for model training (n = 73; 50 and 23 with and without high TPG, respectively) and testing (n = 32; 22 and 10 with and without high TPG, respectively). Three informative shape features were identified in the training datasets: least axis length, sphericity, and maximum three-dimensional diameter.The radiomics score for predicting high TPG in IIH patients demonstrated an AUROC of 0.906 (95% confidence interval, 0.836– 0.976) in the training dataset and 0.877 (95% confidence interval, 0.755–0.999) in the test dataset. The nomogram showed good calibration.
Conclusion
Our study presents the feasibility of a novel model for predicting high TPG in IIH patients using radiomics analysis of noninvasive MRV-based shape features. This information may aid clinicians in identifying patients who may benefit from stenting.
6.Surgical intervention strategies for hiatal hernia
Kunpeng QU ; Tongying YI ; Qi ZHANG ; Tingbao CAO ; Yupeng ZHANG ; Nan LI ; Lina LIANG
Chinese Journal of Digestive Surgery 2023;22(9):1059-1065
Hiatal hernia (HH) is a prevalent medical condition characterized by the protrusion of abdominal contents into the thoracic cavity through an enlarged diaphragmatic esophageal hiatus. The most common clinical manifestations of HH include acid reflux, heartburn, belching, coughing, and chest pain. Currently, there is a lack of standardized comprehensive treatment protocols for different types of HH, presenting significant challenges in their clinical management. In light of this, individualized treatment approaches should be followed by surgical practitioners when dealing with HH, in order to formulate the most appropriate clinical treatment plan tailored to each patient′s specific circumstances.
7.Predictive value of PTH level on day 1 after surgery for papillary thyroid carcinoma in patients with permanent hypoparathyroidism.
Jinwei GAO ; Qi ZHANG ; Zesheng WANG ; Yibin GUO ; Shengchang LIANG ; Yupeng ZHANG ; Kunpeng QU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(5):365-369
Objective:To investigate the relationship between parathyroid hormone(PTH) level and permanent hypoparathyroidism(PHPP) on the first day after radical papillary thyroidectomy, and its predictive value. Methods:A total of 80 patients with papillary thyroid cancer who underwent total thyroid resection and central lymph node dissection were collected and analyzed from January 2021 to January 2022. According to whether PHPP occurred after surgery, the patients were divided into hypoparathyroidism group and normal parathyroid function group, and univariate and binary logistics regression were used to analyze the correlation between PTH and serum calcium levels and PHPP on the first day after surgery in two groups. The dynamic changes of PTH at different time points after operation were analyzed. The area under the receiver operating characteristic was used to evaluate the predictive power of PTH on the development of PHPP after surgery. Results:Among the 80 patients with papillary thyroid cancer, 10 cases developed PHPP, with an incidence rate of 12.5%. Binary logistics regression analysis showed that PTH on the first postoperative day(OR=14.534, 95%CI: 2.377-88.858, P=0.004) was an independent predictive risk factor for postoperative PHPP. Taking PTH=8.75 ng/L on the first postoperative day as the cut-off value, the AUC of the area under the curve was 0.874(95%CI: 0.790-0.958, P<0.001), the sensitivity was 71.4%, the specificity was 100%, and the Yoden index was 0.714. Conclusion:PTH level on the first day after total thyroid papillary carcinoma surgery is closely related to PHPP, and is an independent predictor of PHPP.
Humans
;
Calcium
;
Hypoparathyroidism/surgery*
;
Parathyroid Glands
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Parathyroid Hormone
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Postoperative Complications/surgery*
;
Thyroid Cancer, Papillary/surgery*
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Thyroid Neoplasms/complications*
;
Thyroidectomy
8.Mental health, health-related quality of life, and lung function after hospital discharge in healthcare workers with severe COVID-19: a cohort study from China.
Lijuan XIONG ; Qian LI ; Xiongjing CAO ; Huangguo XIONG ; Daquan MENG ; Mei ZHOU ; Yanzhao ZHANG ; Xinliang HE ; Yupeng ZHANG ; Liang TANG ; Yang JIN ; Jiahong XIA ; Yu HU
Journal of Zhejiang University. Science. B 2023;24(3):269-274
Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is highly contagious and can cause death in severe cases. As reported by the World Health Organization (WHO), as of 6:36 pm Central European Summer Time (CEST), 12 August 2022, there had been 585 950 285 confirmed cases of COVID-19, including 6 425 422 deaths (WHO, 2022).
Humans
;
COVID-19
;
SARS-CoV-2
;
Mental Health
;
Cohort Studies
;
Quality of Life
;
China/epidemiology*
;
Health Personnel
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Hospitals
;
Lung
9.Study on the consistency and correlation of different methods for measuring energy consumption in patients with severe acute pancreatitis
Jing LIU ; Yao WU ; Xin HUANG ; Huajing KE ; Yupeng LEI ; Wenhua HE ; Yin ZHU ; Nonghua LYU ; Liang XIA
Chinese Journal of Digestion 2022;42(6):378-382
Objective:To analyze the consistency and correlation of indirect calorimetry (IC) and Harris-Benedict estimation method (H-B) in measuring energy consumption in patients with severe acute pancreatitis (SAP), as well as the characteristics of energy metabolism at resting state of SAP patients with different etiologies, and so as to guide the formulation of clinical energy nutrition support program.Methods:From February 1 to December 31, 2019, 61 SAP patients admitted into the intensive care unit of the First Affiliated Hospital of Nanchang University were enrolled. Collected relevant data of patients, such as the etiology of SAP, whether mechanical ventilation was needed, as well as the metabolic status. All SAP patients accepted IC test on the first day after admission to intensive care unit. According to the energy consumption measured by IC (hereinafter referred to as IC value) and the energy consumption measured by H-B (hereinafter referred to as H-B value), SAP patients were determined to be in high, normal or low metabolic state. Bland-Altman method and Pearson linear regression were used to analyze the consistency and correlation of the two methods in measuring energy consumption, and the linear equation was fitted. Paired t test was used for statistical analysis. Results:Among the 61 SAP patients, 13 cases were biliary SAP, 30 cases were hyperlipidemic SAP, 6 cases were alcoholic SAP, and 12 cases were SAP of other causes or unknown causes. Nineteen cases needed mechanical ventilation and 42 cases did not need mechanical ventilation. There were 70.5% (43/61) of SAP patients in high metabolic state, 13.1%(8/61) of SAP patients in normal metabolic state, and 16.4% (10/61) of SAP patients in low metabolic state. The IC value in 61 SAP patients was higher than H-B value((8 604.7±367.8) kJ/d vs. (6 491.2±133.7) kJ/d), and the difference was statistically significant ( t=5.95, P<0.001). The IC value in patients with hyperlipidemic, alcoholic and biliary SAP was (8 815.2±537.9), (7 631.2±890.5), and (8 108.0±933.1) kJ/d, respectively, and the H-B value was (6 869.6±204.5), (5 916.8±153.7), and (5 974.2±200.9) kJ/d, respectively. The IC value in patients with biliary or hyperlipidemic SAP were higher than H-B value, and the differences were statistically significant( t=2.29 and 3.38, both P<0.05). The IC value and H-B value in SAP patients with mechanical ventilation and without mechanical ventilation were (10 485.0±741.1) and (6 462.6±222.8) kJ/d, (6 595.1±364.7) and (6 503.2±166.7) kJ/d, respectively. The IC value in SAP patients with mechanical ventilation was higher than H-B value and the IC value in SAP patients without mechanical ventilation, and the differences were statistically significant ( t=4.71 and 5.20, both P<0.001). The consistency analyzed by Bland-Altman method showed that the two methods had obvious biases, and the average bias value was 92.2 kJ/d. The result of Pearson linear regression analysis indicated that there was a linear relationship between two methods ( r=0.44, P<0.001). The linear equation fitted by the univariate regression was Y=1.240 6 X+ 154.42, in which X was the H-B value and Y was the IC value. Conclusions:SAP patients are mostly in a hypermetabolic state in the early stages of the disease. The IC value is higher than H-B value, and it is recommended to use IC to measure energy consumption in SAP patients.
10.Factors affecting phenotypes in the patients with MMACHC gene c. 609G>A homozygous variant cblC type methylmalonic acidemia combined with homocysteinuria
Ruxuan HE ; Ruo MO ; Yao ZHANG ; Ming SHEN ; Lulu KANG ; Zhehui CHEN ; Yi LIU ; Jinqing SONG ; Hongwu ZHANG ; Hongxin YAO ; Yupeng LIU ; Hui DONG ; Ying JIN ; Mengqiu LI ; Jiong QIN ; Hong ZHENG ; Yongxing CHEN ; Haiyan WEI ; Dongxiao LI ; Xiyuan LI ; Rongxiu ZHENG ; Huifeng ZHANG ; Min HUANG ; Chunyan ZHANG ; Yuwu JIANG ; Desheng LIANG ; Yaping TIAN ; Yanling YANG
Chinese Journal of Medical Genetics 2022;39(6):565-570
Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.


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