1.Cardiomyocyte-specific long noncoding RNA Trdn-as induces mitochondrial calcium overload by promoting the m6A modification of calsequestrin 2 in diabetic cardiomyopathy.
Xiaohan LI ; Ling LIU ; Han LOU ; Xinxin DONG ; Shengxin HAO ; Zeqi SUN ; Zijia DOU ; Huimin LI ; Wenjie ZHAO ; Xiuxiu SUN ; Xin LIU ; Yong ZHANG ; Baofeng YANG
Frontiers of Medicine 2025;19(2):329-346
Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca2+ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca2+ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m6A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca2+ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals
;
Diabetic Cardiomyopathies/pathology*
;
RNA, Long Noncoding/genetics*
;
Myocytes, Cardiac/metabolism*
;
Mice
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Calsequestrin/genetics*
;
Calcium/metabolism*
;
Male
;
Sarcoplasmic Reticulum/metabolism*
;
Methyltransferases/metabolism*
;
Mice, Inbred C57BL
;
Mitochondria, Heart/metabolism*
;
Disease Models, Animal
;
Mitochondria/metabolism*
2.Construction of Nomogram prediction model of myopia risk and lifestyle among primary school students in Tianjin City
LIU Shengxin, DU Bei, JIN Nan, TANG Chunyu, SONG Desheng, ZHANG Xin, WEI Ruihua
Chinese Journal of School Health 2024;45(1):21-24
Objective:
To explore the relationship between lifestyle and myopia and construct Nomogram model to predict myopia risk among primary school students in Tianjin, so as to provide a scientific basis for precision myopia prevention and control.
Methods:
From April to July of 2022, a census method was used to conduct vision testing and lifestyle related questionnaires among 373 180 primary school students in 15 districts of Tianjin. The relationship between lifestyle and myopia was analyzed by the multivariate Logistic regression, and a nomogram prediction model was constructed to predict myopia risk.
Results:
The detection rate of myopia among primary school students in Tianjin was 37.6%. The results of the multivariate Logistic regression showed that daily outdoor activity time of 1-2 h ( OR =0.94) and >2 h ( OR =0.84), time of using daily electronic devices of >2 h ( OR =1.03), daily paper materials reading and writing time of 1-2 h ( OR =1.02) and >2 h ( OR =1.09), weekly fresh vegetable intake of 2-6 times ( OR =0.93) and ≥7 times ( OR =0.88) were statistically correlated with myopia ( P <0.01). The Nomogram prediction model showed that the factors associated with myopia were grade, family history of myopia, gender, daily outdoor activity time, weekly frequency of fresh vegetable intake, daily paper materials reading and writing time, and time of using daily electronic devices time.
Conclusions
The lifestyle of primary school students in Tianjin is associated with myopia. The constructed nomogram model could provide a scientific basis for identifying key intervention populations for myopia prevention and taking targeted prevention and control measures.
3.Analysis of Knee Joint Stress During Drop Jump Landing in Females with Generalised Joint Hypermobility
Furong XIANG ; Shengxin TANG ; Xinxin LIU ; Yining CHEN ; Xikai LIN ; Jian CHEN
Journal of Medical Biomechanics 2023;38(2):E317-E323
Objective To analyze the differences of von Mises stress distribution in knee cartilage and meniscus in female with generalised joint hypermobility (GJH) and healthy female during drop jump landing. Methods The kinematic and ground reaction force (GRF) characteristics of knee joint in female with GJH and healthy female at the moment of peak vertical GRF (VGRF) during loading phase of drop jump landing were collected. The knee joint reaction force was calculated via inverse dynamics, and the combined force of knee joint along long axis of the femur was applied as the load. Based on three-dimensional (3D) finite element model of a female knee joint, numerical simulations were performed separately during drop jump landing of subjects in two groups, and von Mises stresses and stress distribution of knee cartilage and meniscus were calculated. Results At the moment of peak VGRF during drop jump landing, knee flexion and valgus angles in GJH group and control group showed a statistical significance (P<0. 05). Compared with control group, knee flexion angle decreased and valgus angle increased in GJH group. During drop jump landing, GJH group bore larger stress inside the knee joint, and stress distribution in weight-bearing areas of the medial and lateral tibiofemoral compartments was uneven, while the lateral femoral cartilage lateral condyle, the anterior and middle lateral of lateral tibial cartilage, the anterior angle and body lateral margin of lateral meniscus were stress concentration sites. Conclusions For females with GJH, the stability of knee joint decreases and force lines change in jumping events, due to the increased range of motion of knee joint and relaxation of joint capsule, which increases the risk of cartilage and meniscal injury in lateral knee joint. During jumping sports, females with GJH should especially prevent knee joint injury caused by altered force lines in frontal plane of knee joint.
4.Meta-analysis of repeated low-level red light therapy for retarding myopia progression in children
Hongmei ZHANG ; Yun ZHU ; Shengxin LIU ; Bingqin LI ; Ruihua WEI
Chinese Journal of Experimental Ophthalmology 2023;41(4):357-365
Objective:To systematically evaluate the effect of repeated low-level red light (RLRL) therapy on controlling the progression of myopia in children.Methods:Medline, Embase, Cochrane Library, Web of Science, ClinicalTrial.gov and the CNKI, VIP, Wanfang database, and Chinese Clinical Trial Registry (www.chictr.org.cn) were searched from their establishment to September 2022 to obtain the randomized controlled trial (RCT) about RLRL controlling myopia progression in children.Grey literature was also searched.Inclusion and exclusion criteria were developed according to the PICOS principle.Two researchers screened the literature independently, extracted data, and assessed the risk of bias in the included studies using the Cochrane collaboration tool for assessing risk of bias.The data were imported into RevMan 5.4 software for meta-analysis.Mean and standard deviation of data were used to obtain mean differences and 95% confidence intervals of included studies.Changes in spherical equivalent (SE) and axial length (AL) were compared between before and after the intervention in RLRL and single-vision spectacle (experimental group) and single-vision spectacle (control group). The GRADE system was used to grade the quality of evidence for the outcome indicators.Results:A total of 157 studies were obtained.After the screening, 7 RCT studies including 1 038 study subjects met the inclusion criteria.Meta-analysis results showed that retarded SE progression was retarded and AL elongation was reduced significantly after different follow-up durations (1, 3, 6, 12 and 24 months) in experimental group compared with control group.As the follow-up duration extended from 1 month to 24 months, the retard of SE progression increased from 0.14 to 0.93 D, and the reduction of AL increased from 0.07 to 0.48 mm.Both 635 and 650 nm red light significantly retarded SE progression and reduced AL elongation.The two outcome indicators, SE change and AL change were moderate-strength evidence by GRADE.Conclusions:The current moderate-strength evidence shows that RLRL can better retard myopia progression in children than single-vision spectacle glasses.
5.Clinical value of endoscopic biliary drainage for biliary fistula
Dexin CHEN ; Shengxin CHEN ; Lang WU ; Wenjing LIU ; Kaixuan FANG ; Yaqi ZHAI ; Mingyang LI ; Enqiang LINGHU
Chinese Journal of Digestive Endoscopy 2023;40(12):973-978
Objective:To evaluate the efficacy and safety of endoscopic biliary drainage for biliary fistula.Methods:Data of consecutive 409 biliary fistula patients who were treated and diagnosed at the First Medical Center of Chinese PLA General Hospital from November 2002 to November 2022 were reviewed, and 53 patients who received endoscopic retrograde cholangiopancreatography (ERCP) drainage were finally included. General information, procedural conditions, clinical outcomes and adverse events were analyzed. The patients were categorized into two groups: the endoscopic retrograde biliary drainage (ERBD) group ( n=46) and the endoscopic nasobiliary drainage (ENBD) group ( n=7). Procedural characteristics, operation outcomes, and operation time were compared between the two groups. Results:There were 36 males and 17 females, with the age of 52.2±12.7 years, among whom 58.5% (31/53) were secondary to cholecystectomy. Clinical success was achieved in 83.0% (44/53) patients, with the operation time of 27.0 (13.5, 33.5) minutes and the treatment session of 1 (1, 2). The time to resolution was 89 (47, 161) days. The success rate of ERCP for low-grade biliary fistula was higher compared with that of high-grade biliary fistula [96.4% (27/28) VS 68.0% (17/25), χ2=7.57, P=0.006]. Bridging drainage achieved higher success rate compared with that of non-bridging drainage [91.7% (33/36) VS 64.7% (11/17), χ2=5.95, P=0.015], while different diameters of stents (≥10 Fr VS <10 Fr) achieved similar success rate [81.8% (27/33) VS 84.6% (11/13), χ2=0.05, P=0.822]. Adverse events occurred in 10 patients (18.9%), including 6 pancreatitis, 2 bleeding, 1 cholangitis and 1 death. Except for 1 death, 9 other adverse events were mild and managed with conservative treatment without interventions. There was no significant difference in clinical success rate [6/7 VS 82.6% (38/46), χ2=0.04, P=0.838] or the median operation time [28.0 min VS 23.0 min, Z=0.38, P=0.774] between ENBD group and ERBD group. Conclusion:Endoscopic biliary drainage is safe and effective for biliary fistula. ENBD and ERBD have comparable clinical efficacy. ERCP for low-grade biliary fistula may achieve a higher success rate, and bridging drainage may facilitate fistula resolution.
6.The association between myopic refraction and near work among children and adolescents based on genetic risk score
Shengxin LIU ; Xinyue ZHI ; Wei XI ; Rui SHI ; Wenjuan XIONG ; Xin ZHANG
Chinese Journal of Preventive Medicine 2021;55(4):446-452
Objective:To explore the relationship between myopic refraction and near work in children and adolescents with different genetic risks.Methods:From September to December 2016, Nankai District and Hongqiao District of Tianjin were taken as the study sites. Using the method of stratified cluster random sampling, 533 children and adolescents aged 6-14 years from one primary school and one junior middle school in each of the two districts were included as the study subjects. Refraction measurements by an auto-kerato-refractor and questionnaire survey about near work were conducted. 11 single nucleotide polymorphisms in the selected myopia susceptibility genes were detected, and the genetic risk of each individual was scored. After grouping by genetic risk score, the relationship between myopia and near work was analyzed by the multivariate logistic regression, and the relationship between near work and refraction was analyzed by the multivariate linear regression.Results:The age of 553 subjects was (9.8±2.5) years, including 295 boys (53.3%). The overall detection rate of myopia was 62.0%. The spherical equivalent refraction (SER) was (-1.30±1.85) D. The results of the multivariate logistic regression showed that in the low risk group of GRS, compared with those with continuous near work time less than half an hour, those with continuous near work time no less than half an hour had a higher risk of myopia [ OR ( 95%CI) = 2.64 (1.07, 6.52)]. In the moderate risk group of GRS, the risk of myopia increased with the increase of daily computer use [ OR ( 95%CI) = 2.14 (1.03, 4.77)]. In the high risk group of GRS, the risk of myopia increased with the increase of the total daily reading and writing time [ OR ( 95%CI) = 1.27 (1.01, 1.59)]. The results of the multivariate linear regression showed that in the low risk group of GRS, with increase of 1 hour in the total daily reading and writing time and mobile phone time, the SER decreased by 0.18 D (95% CI:-0.30, -0.07) and 0.95 D (95% CI:-1.51, -0.39), respectively. In the moderate risk group of GRS, with increase of 1 hour in the total daily reading and writing time and computer use time, the SER decreased by 0.25 D (95% CI:-0.31, -0.18) and 0.57 D (95% CI:-0.97, -0.18), respectively. In the high risk group of GRS, with increase of 1 hour in the daily total reading and writing time, the SER decreased by 0.33 D (95% CI:-0.43, -0.22). Conclusion:Continuous near work time no less than half an hour, daily computer use time, the total daily reading and writing time, and daily mobile phone use time were associated with myopic refraction in children and adolescents.
7.Related environmental factors of refractive parameters in children and adolescents aged 6-14
Tingkai CUI ; Shengxin LIU ; Wei XI ; Lei GAO ; Sheng YE ; Xin ZHANG
Chinese Journal of Preventive Medicine 2021;55(4):453-459
Objective:To explore the relationship between environmental factors and refractive parameters of children and adolescents aged 6 to 14 years old.Methods:A total of 566 students aged 6 to 14 years old were selected by using random cluster sampling method in Nankai District and Hongqiao District of Tianjin from September to December 2016. Questionnaires were conducted and refractive parameters were measured including axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD) and lens thickness (LT). Vitreous chamber depth (VCD), corneal radius (CR), the ratio of axial length to corneal radius (AL/CR) and equivalent spherical diopter (SER) were calculated. Multivariate generalized linear model was used to analyze the related factors of refractive parameters.Results:The average age of the subjects was (9.8±2.5) years old, including 302 male students (53.4%). The overall SER, AL, CCT, ACD, LT, VCD, CR and AL/CR ratios were (-1.31±1.85) D, (23.67±1.16) mm, (23.67±1.16) mm, (546.60±31.98) μm, (3.06±0.27) mm, (3.48±0.21) mm, (17.12±1.13) mm, (7.78±0.25) mm and 3.04±0.14, respectively. Multivariate generalized linear model analysis showed that after adjusting for age, gender, height, weight, education level of parents, occupation of parents and family income, compared with those whose daily reading and writing time>6 hours, the AL and VCD of students with daily reading and writing time ≤ 2 hours, 3-4 hours or 5-6 hours were smaller, and the AL/CR ratio of students with daily reading and writing time ≤ 2 hours or 3-4 hours were also smaller (all P<0.05). Compared with those having daily sleep time>9 hours, the students with daily sleep time of 8 hours or 9 hours had higher AL, while the students with daily sleep time of 8 hours had higher CCT, and the students with daily sleep time ≤ 7 hours had higher CR (all P<0.05). Compared with those whose daily electronic screen usage time>1.5 hours, the AL, VCD and CR of students who used electronic screen ≤1.5 hours per day were lower (all P<0.05). Conclusions:Daily reading and writing time, daily electronic screen use time and daily sleep time are the main environmental factors related to eye refractive parameters.
8.Protective effect of resolvin D2 on inflammatory response and endoplasmic reticulum stress injury of CVB3-induced viral myocarditis mice and its mechanism
Zhewei SHI ; Caizhen QIAN ; Shengxin LIU ; Lisha GE ; Chengfan QIN ; Yuechun LI
Chinese Journal of Microbiology and Immunology 2021;41(7):531-537
Objective:To clarify the anti-inflammatory effects and anti-endoplasmic reticulum stress effects of resolvin D2 (RvD2) in viral myocarditis mice and to explore its possible mechanism.Methods:Fifty male BALB/c mice were collected and assigned corresponding numbers. Then 40 male BALB/c mice were selected randomly with 10 mice in each group. They were set as normal control group, RvD2 control group, viral myocarditis group and RvD2 treatment group. Afterwards, mice in the RvD2 control group received continuous intraperitoneal injection of RvD2 for 7 days, while mice in the viral myocarditis group received intraperitoneal injection of Coxsackievirus B3 virus (CVB3) in the purpose of constructing an animal model of viral myocarditis. Then, mice in the RvD2 treatment group were given continuous intraperitoneal injection of RvD2 for 7 days. After these 7 days, the mice of each group were sacrificed and their cardiac tissue and serum samples were taken. The expression levels of serum inflammatory factors including IL-1β and TNF-α were detected by ELISA in each group of mice, and HE staining were used to detect the inflammatory cell infiltration in myocardial tissue of each group. Meanwhile, the expression levels of inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue in each group of mice were detected by Western blot experiment. The remaining 10 BALB/c mice were treated with intraperitoneal injection of RvD2 as well as GPR18 protein inhibitors after constructing the animal model of viral myocarditis mentioned above. In the end, the expression levels of GPR18 protein, inflammation-related proteins including IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue of each group were detected by Western blot experiments.Results:Compared with the normal control group, the expression levels of inflammatory factors IL-1β and TNF-α in the serum of mice with viral myocarditis were significantly increased, and the degree of infiltration of inflammatory cells in myocardial tissue was also significantly increased. Besides, the expression levels of the inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins including GRP78 and Chop increased largely. While compared with the viral myocarditis group, the expression levels of serum inflammatory factors IL-1β and TNF-α in the mice of the RvD2 treatment group were significantly reduced and the degree of infiltration of inflammatory cells in the cardiac tissue was significantly reduced. Also, the expression levels of inflammation-related proteins IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins GRP78 and Chop were significantly reduced. After intraperitoneal injection of RvD2 and GPR18 inhibitor, in the mice treated with viral myocarditis, the expression levels of IL-1β, TNF-α and endoplasmic reticulum stress-related proteins like GRP78 and Chop in myocardial tissue of these mice significantly increased when it came to compare with the RvD2 treatment group, while the expression levels of GPR18 protein were significantly reduced.Conclusions:RvD2 can inhibit the inflammatory response and endoplasmic reticulum stress injury in mice with viral myocarditis by binding to the membrane protein receptor GPR18, thus exerting a protective effect on heart.
9.The association between myopic refraction and near work among children and adolescents based on genetic risk score
Shengxin LIU ; Xinyue ZHI ; Wei XI ; Rui SHI ; Wenjuan XIONG ; Xin ZHANG
Chinese Journal of Preventive Medicine 2021;55(4):446-452
Objective:To explore the relationship between myopic refraction and near work in children and adolescents with different genetic risks.Methods:From September to December 2016, Nankai District and Hongqiao District of Tianjin were taken as the study sites. Using the method of stratified cluster random sampling, 533 children and adolescents aged 6-14 years from one primary school and one junior middle school in each of the two districts were included as the study subjects. Refraction measurements by an auto-kerato-refractor and questionnaire survey about near work were conducted. 11 single nucleotide polymorphisms in the selected myopia susceptibility genes were detected, and the genetic risk of each individual was scored. After grouping by genetic risk score, the relationship between myopia and near work was analyzed by the multivariate logistic regression, and the relationship between near work and refraction was analyzed by the multivariate linear regression.Results:The age of 553 subjects was (9.8±2.5) years, including 295 boys (53.3%). The overall detection rate of myopia was 62.0%. The spherical equivalent refraction (SER) was (-1.30±1.85) D. The results of the multivariate logistic regression showed that in the low risk group of GRS, compared with those with continuous near work time less than half an hour, those with continuous near work time no less than half an hour had a higher risk of myopia [ OR ( 95%CI) = 2.64 (1.07, 6.52)]. In the moderate risk group of GRS, the risk of myopia increased with the increase of daily computer use [ OR ( 95%CI) = 2.14 (1.03, 4.77)]. In the high risk group of GRS, the risk of myopia increased with the increase of the total daily reading and writing time [ OR ( 95%CI) = 1.27 (1.01, 1.59)]. The results of the multivariate linear regression showed that in the low risk group of GRS, with increase of 1 hour in the total daily reading and writing time and mobile phone time, the SER decreased by 0.18 D (95% CI:-0.30, -0.07) and 0.95 D (95% CI:-1.51, -0.39), respectively. In the moderate risk group of GRS, with increase of 1 hour in the total daily reading and writing time and computer use time, the SER decreased by 0.25 D (95% CI:-0.31, -0.18) and 0.57 D (95% CI:-0.97, -0.18), respectively. In the high risk group of GRS, with increase of 1 hour in the daily total reading and writing time, the SER decreased by 0.33 D (95% CI:-0.43, -0.22). Conclusion:Continuous near work time no less than half an hour, daily computer use time, the total daily reading and writing time, and daily mobile phone use time were associated with myopic refraction in children and adolescents.
10.Related environmental factors of refractive parameters in children and adolescents aged 6-14
Tingkai CUI ; Shengxin LIU ; Wei XI ; Lei GAO ; Sheng YE ; Xin ZHANG
Chinese Journal of Preventive Medicine 2021;55(4):453-459
Objective:To explore the relationship between environmental factors and refractive parameters of children and adolescents aged 6 to 14 years old.Methods:A total of 566 students aged 6 to 14 years old were selected by using random cluster sampling method in Nankai District and Hongqiao District of Tianjin from September to December 2016. Questionnaires were conducted and refractive parameters were measured including axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD) and lens thickness (LT). Vitreous chamber depth (VCD), corneal radius (CR), the ratio of axial length to corneal radius (AL/CR) and equivalent spherical diopter (SER) were calculated. Multivariate generalized linear model was used to analyze the related factors of refractive parameters.Results:The average age of the subjects was (9.8±2.5) years old, including 302 male students (53.4%). The overall SER, AL, CCT, ACD, LT, VCD, CR and AL/CR ratios were (-1.31±1.85) D, (23.67±1.16) mm, (23.67±1.16) mm, (546.60±31.98) μm, (3.06±0.27) mm, (3.48±0.21) mm, (17.12±1.13) mm, (7.78±0.25) mm and 3.04±0.14, respectively. Multivariate generalized linear model analysis showed that after adjusting for age, gender, height, weight, education level of parents, occupation of parents and family income, compared with those whose daily reading and writing time>6 hours, the AL and VCD of students with daily reading and writing time ≤ 2 hours, 3-4 hours or 5-6 hours were smaller, and the AL/CR ratio of students with daily reading and writing time ≤ 2 hours or 3-4 hours were also smaller (all P<0.05). Compared with those having daily sleep time>9 hours, the students with daily sleep time of 8 hours or 9 hours had higher AL, while the students with daily sleep time of 8 hours had higher CCT, and the students with daily sleep time ≤ 7 hours had higher CR (all P<0.05). Compared with those whose daily electronic screen usage time>1.5 hours, the AL, VCD and CR of students who used electronic screen ≤1.5 hours per day were lower (all P<0.05). Conclusions:Daily reading and writing time, daily electronic screen use time and daily sleep time are the main environmental factors related to eye refractive parameters.


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