1.Effect of transcutaneous phrenic nerve stimulation in preventing ventilator-induced diaphragmatic dysfunction in invasive mechanically ventilated patients.
Yuhua SHEN ; Hongyan ZHANG ; Lingyan WANG ; Xianbin SONG ; Xianjiang WANG ; Aili CAO
Chinese Critical Care Medicine 2025;37(4):343-347
OBJECTIVE:
To explore the preventive effect of transcutaneous phrenic nerve stimulation on ventilator-induced diaphragmatic dysfunction (VIDD) in patients requiring invasive mechanical ventilation.
METHODS:
A randomized controlled trial was conducted. The patients requiring invasive mechanical ventilation admitted to the intensive care unit (ICU) of Jiaxing First Hospital from November 2022 to December 2023 were enrolled. Participants were randomized into the control group and the observation group using a random number table. The control group was given ICU standardized nursing intervention, including turning over and slapping the back, raising the head of the bed, sputum aspiration on demand, aerosol inhalation, oral care, and monitoring of airbag pressure and gastric retention, the observation group was given additional transcutaneous phrenic nerve stimulation intervention on the basis of ICU standardized nursing intervention. The stimulation intensity was set to 10 U, the pulse frequency was set to 40 Hz, and the stimulation frequency was set to 12 times/min. Transcutaneous phrenic nerve stimulation was administered once a day for 30 minutes each time, for a total of 5 days. Diaphragm thickening fraction (DTF) and arterial blood gas parameters on days 1, 3, and 5 of intervention were compared between the two groups. After 5 days of intervention, other parameters including the incidence of VIDD, duration of mechanical ventilation, and length of ICU stay were compared.
RESULTS:
A total of 120 patients requiring invasive mechanical ventilation were enrolled, with 16 dropouts (dropout rate was 13.33%). Ultimately, 51 patients in the control group and 53 patients in the observation group were analyzed. Baseline characteristics, including gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, albumin (Alb), hemoglobin (Hb), and disease type, showed no significant differences between the two groups. DTF in both groups gradually increased over duration of intervention [DTF on days 1, 3, and 5 in the control group was (20.83±2.33)%, (21.92±1.27)%, and (23.93±2.33)%, respectively, and that in the observation group was (20.89±1.96)%, (22.56±1.64)%, and (25.34±2.38)%, respectively], with more significant changes in DTF in the observation group, showing time effects (Ftime = 105.975, P < 0.001), intervention effects (Fintervention = 7.378, P = 0.008), and interaction effects (Finteraction = 3.322, P = 0.038). Arterial blood gas parameters did not differ significantly before intervention between the groups, but after 5 days of intervention, arterial partial pressure of oxygen (PaO2) in the observation group was significantly higher than that in the control group [mmHg (1 mmHg≈0.133 kPa): 100.72±15.75 vs. 93.62±15.54, P < 0.05], and arterial partial pressure of carbon dioxide (PaCO2) was significantly lower than that in the control group (mmHg: 36.53±3.10 vs. 37.69±2.02, P < 0.05). At 5 days of intervention, the incidence of VIDD in the observation group was significantly lower than that in the control group [15.09% (8/53) vs. 37.25% (19/51), P < 0.05], and both duration of mechanical ventilation and length of ICU stay were significantly shorter than those in the control group [duration of mechanical ventilation (days): 7.93±2.06 vs. 8.77±1.76, length of ICU stay (days): 9.64±2.35 vs. 11.01±2.01, both P < 0.05].
CONCLUSIONS
Transcutaneous phrenic nerve stimulation can improve diaphragmatic and respiratory function in patients receiving invasive mechanical ventilation, reduce the incidence of VIDD, and shorten the duration of mechanical ventilation and length of ICU stay.
Humans
;
Transcutaneous Electric Nerve Stimulation
;
Respiration, Artificial/adverse effects*
;
Diaphragm/physiopathology*
;
Phrenic Nerve
;
Intensive Care Units
;
Male
;
Female
;
Middle Aged
2.Expert consensus: reducing free-sugar for caries prevention
Xiaojuan ZENG ; Xuenan LIU ; Min LIU ; Yan SI ; Ying ZHANG ; Jianqiang LAI ; Xianbin DING ; Chang SU ; Xiang SI ; Youguang LU ; Huancai LIN ; Shuguo ZHENG ; Wensheng RONG ; Minquan DU ; Xiaoyan OU ; Rongmin QIU ; Maigeng ZHOU ; Chunxiao WANG
Chinese Journal of Stomatology 2025;60(4):311-319
In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.
3.Current status of water management for terminal rinsing of digestive endoscope in 104 medical institutions in Fujian Province
Lijun QIU ; Xianbin GUO ; Yanyi GUO ; Xuan LIN ; Yanqing ZHANG ; Yufang CHEN ; Qiaomei WANG ; Yudai CHEN
Chinese Journal of Nosocomiology 2025;35(20):3162-3167
OBJECTIVE To investigate the current status of water management for terminal rinsing of digestive en-doscope in medical institutions in Fujian Province,and to provide reference for improving regional quality control standards.METHODS An electronic questionnaire survey was conducted from Jul.2024 to Aug.2024 through convenient sampling in secondary and above hospitals of 9 prefecture-level cities in Fujian Province.The survey covered topics such as water treatment system configuration,maintenance and water quality monitoring.RESULTS A total of 108 questionnaires were distributed and 104 valid questionnaires were collected,with an effec-tive response rate of 96.30%.The survey revealed that 78.85%(82/104)of the hospitals adopted separate water supply for each department,and 82.69%used purified water for terminal rinsing.Only 19.23%installed the final filter membrane at the water outlet.In addition,66.35%of the hospitals did not specify the service life of the wa-ter supply pipeline,and the pipeline disinfection implementation rate was 60.58%,but 31.75%of them had ir-regular disinfection frequencies,with chlorine-based disinfectants(50.79%)and peracetic acid(34.92%)being the main disinfectants.The regular conductivity monitoring rate was 47.12%,and the microbial monitoring cov-erage rate reached 90.38%,with the monitoring frequency mainly being once every quarter(60.64%),but only 20.21%used R2A medium,and 12.77%adopted the membrane filtration method for inoculation.Tertiary hospi-tals were superior to secondary hospitals in terms of film membrane pore size pass rate(87.50%vs.56.86%),pipeline disinfection implementation rate(71.43%vs.50.91%)and advanced detection method application(P<0.05).CONCLUSIONS There are issues in the management of water used for terminal rinsing of digestive endo-scopes in Fujian Province,including non-standard equipment maintenance,inconsistent monitoring methods and insufficient awareness among management personnel.It is recommended to enhance management quality by optimizing the water treatment system setup,establishing standardized monitoring procedures and strengthening professional training for personnel.
4.Expert consensus: reducing free-sugar for caries prevention
Xiaojuan ZENG ; Xuenan LIU ; Min LIU ; Yan SI ; Ying ZHANG ; Jianqiang LAI ; Xianbin DING ; Chang SU ; Xiang SI ; Youguang LU ; Huancai LIN ; Shuguo ZHENG ; Wensheng RONG ; Minquan DU ; Xiaoyan OU ; Rongmin QIU ; Maigeng ZHOU ; Chunxiao WANG
Chinese Journal of Stomatology 2025;60(4):311-319
In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.
5.Current status of water management for terminal rinsing of digestive endoscope in 104 medical institutions in Fujian Province
Lijun QIU ; Xianbin GUO ; Yanyi GUO ; Xuan LIN ; Yanqing ZHANG ; Yufang CHEN ; Qiaomei WANG ; Yudai CHEN
Chinese Journal of Nosocomiology 2025;35(20):3162-3167
OBJECTIVE To investigate the current status of water management for terminal rinsing of digestive en-doscope in medical institutions in Fujian Province,and to provide reference for improving regional quality control standards.METHODS An electronic questionnaire survey was conducted from Jul.2024 to Aug.2024 through convenient sampling in secondary and above hospitals of 9 prefecture-level cities in Fujian Province.The survey covered topics such as water treatment system configuration,maintenance and water quality monitoring.RESULTS A total of 108 questionnaires were distributed and 104 valid questionnaires were collected,with an effec-tive response rate of 96.30%.The survey revealed that 78.85%(82/104)of the hospitals adopted separate water supply for each department,and 82.69%used purified water for terminal rinsing.Only 19.23%installed the final filter membrane at the water outlet.In addition,66.35%of the hospitals did not specify the service life of the wa-ter supply pipeline,and the pipeline disinfection implementation rate was 60.58%,but 31.75%of them had ir-regular disinfection frequencies,with chlorine-based disinfectants(50.79%)and peracetic acid(34.92%)being the main disinfectants.The regular conductivity monitoring rate was 47.12%,and the microbial monitoring cov-erage rate reached 90.38%,with the monitoring frequency mainly being once every quarter(60.64%),but only 20.21%used R2A medium,and 12.77%adopted the membrane filtration method for inoculation.Tertiary hospi-tals were superior to secondary hospitals in terms of film membrane pore size pass rate(87.50%vs.56.86%),pipeline disinfection implementation rate(71.43%vs.50.91%)and advanced detection method application(P<0.05).CONCLUSIONS There are issues in the management of water used for terminal rinsing of digestive endo-scopes in Fujian Province,including non-standard equipment maintenance,inconsistent monitoring methods and insufficient awareness among management personnel.It is recommended to enhance management quality by optimizing the water treatment system setup,establishing standardized monitoring procedures and strengthening professional training for personnel.
6.The relationship between three serum indicators and cardiac function and myocardial injury indicators in patients with CHD and angina pectoris
Chunru ZHANG ; Jian LÜ ; Daliang ZHOU ; Xianbin SUN ; Dan HAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(1):33-37
Objective To analyze the correlation of serum levels of GAT A-binding protein 3(GATA-3),T cell immunoglobulin domain and mucin domain protein-3(Tim-3)and retinoid-related orphan nuclear receptor gamma t(RORγt)with cardiac function and myocardial injury in-dicators in patients with coronary heart disease(CHD)and angina pectoris.Methods A retrospec-tive analysis was performed on 120 CHD patients with angina pectoris(observation group)in our hospital from December 2020 to December 2023.They were divided into stable angina subgroup(53 cases)and unstable angina subgroup(67 cases)according to the results of electrocardiography and coronary angiography.Another 120 healthy individuals taking physical examination in our hospital during the same period were subjected and served as the control group.ELISA was used to detect the serum levels of GATA-3,Tim-3 and RORγt.Left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular short-axis shortening rate(FS)were measured by echocardio-graphy.Creatine kinase(CK)and creatine kinase isoenzyme(CK-MB)were detected by biochemi-cal analyzer,and troponin Ⅰ(cTnⅠ)and heart fatty acid binding protein(H-FABP)were detected by electrochemiluminescence immunoassay.Pearson analysis was applied to analyze the correlation the correlation of serum levels of GATA-3,Tim-3 and RORγt with cardiac function and myocar-dial injury indicators.ROC curve was plotted to analyze the predictive value of the above three in-dicators for unstable angina.Results The serum levels of Tim-3 and ROR y t were significantly higher,and that of GATA-3 was obviously lower in the observation group than the control group(397.14±78.42 ng/L vs 246.45±56.81 ng/L,P<0.01;93.18±19.94 ng/L vs 35.72±7.79 ng/L,P<0.01;38.21±9.45 ng/L vs 71.62±14.98 ng/L,P<0.01).The LVEDD and LVESD values were notably higher,while the LVEF and LVFS values were remarkably lower in the observation group than the control group(P<0.01).The observation group has statistically higher cTnⅠ,CK,CK-MB,and H-FABP levels than the control group(P<0.01).In the CHD patients with angina pectoris,serum GATA-3 level was positively correlated with LVEF and LVFS,and negatively with LVEDD,LVESD,cTnⅠ,CK,CK-MB,and H-FABP;Tim-3 and RORγt were negatively corre-lated with LVEF and LVFS,and positively with LVEDD,LVESD,cTnⅠ,CK,CK-MB,and H-FABP(P<0.01).The AUC value of GATA-3,Tim-3,and RORγt alone and in combination in predicting unstable angina was 0.859,0.827,0.780,and 0.921,respectively,with that of combina-tion significantly higher than that of above indicators alone(Z=1.993,3.021,4.532,P=0.036,0.007,0.001).Conclusion As the disease progresses in CHD patients with angina pectoris,serum levels of Tim-3 and RORγt are increasing,while that of GATA-3 is decreasing,and all of them are closely associated with heart function and myocardial injury indicators.
7.The relationship between three serum indicators and cardiac function and myocardial injury indicators in patients with CHD and angina pectoris
Chunru ZHANG ; Jian LÜ ; Daliang ZHOU ; Xianbin SUN ; Dan HAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(1):33-37
Objective To analyze the correlation of serum levels of GAT A-binding protein 3(GATA-3),T cell immunoglobulin domain and mucin domain protein-3(Tim-3)and retinoid-related orphan nuclear receptor gamma t(RORγt)with cardiac function and myocardial injury in-dicators in patients with coronary heart disease(CHD)and angina pectoris.Methods A retrospec-tive analysis was performed on 120 CHD patients with angina pectoris(observation group)in our hospital from December 2020 to December 2023.They were divided into stable angina subgroup(53 cases)and unstable angina subgroup(67 cases)according to the results of electrocardiography and coronary angiography.Another 120 healthy individuals taking physical examination in our hospital during the same period were subjected and served as the control group.ELISA was used to detect the serum levels of GATA-3,Tim-3 and RORγt.Left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular short-axis shortening rate(FS)were measured by echocardio-graphy.Creatine kinase(CK)and creatine kinase isoenzyme(CK-MB)were detected by biochemi-cal analyzer,and troponin Ⅰ(cTnⅠ)and heart fatty acid binding protein(H-FABP)were detected by electrochemiluminescence immunoassay.Pearson analysis was applied to analyze the correlation the correlation of serum levels of GATA-3,Tim-3 and RORγt with cardiac function and myocar-dial injury indicators.ROC curve was plotted to analyze the predictive value of the above three in-dicators for unstable angina.Results The serum levels of Tim-3 and ROR y t were significantly higher,and that of GATA-3 was obviously lower in the observation group than the control group(397.14±78.42 ng/L vs 246.45±56.81 ng/L,P<0.01;93.18±19.94 ng/L vs 35.72±7.79 ng/L,P<0.01;38.21±9.45 ng/L vs 71.62±14.98 ng/L,P<0.01).The LVEDD and LVESD values were notably higher,while the LVEF and LVFS values were remarkably lower in the observation group than the control group(P<0.01).The observation group has statistically higher cTnⅠ,CK,CK-MB,and H-FABP levels than the control group(P<0.01).In the CHD patients with angina pectoris,serum GATA-3 level was positively correlated with LVEF and LVFS,and negatively with LVEDD,LVESD,cTnⅠ,CK,CK-MB,and H-FABP;Tim-3 and RORγt were negatively corre-lated with LVEF and LVFS,and positively with LVEDD,LVESD,cTnⅠ,CK,CK-MB,and H-FABP(P<0.01).The AUC value of GATA-3,Tim-3,and RORγt alone and in combination in predicting unstable angina was 0.859,0.827,0.780,and 0.921,respectively,with that of combina-tion significantly higher than that of above indicators alone(Z=1.993,3.021,4.532,P=0.036,0.007,0.001).Conclusion As the disease progresses in CHD patients with angina pectoris,serum levels of Tim-3 and RORγt are increasing,while that of GATA-3 is decreasing,and all of them are closely associated with heart function and myocardial injury indicators.
8.Effectiveness of modified temporomandibular joint disc reduction and suture with tragus incision assisted by arthroscopy.
Sen LIU ; Lin ZHANG ; Liangying GUO ; Xianbin MENG ; Zhigang WU
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(11):1352-1358
OBJECTIVE:
To investigate the effectiveness of modified temporomandibular joint disc reduction and suture with tragus incision assisted by arthroscopy for temporomandibular joint anterior disc displacement (ADD).
METHODS:
A clinical data of 30 patients (45 sides) with temporomandibular joint ADD, who met selective criteria and were admitted between September 2022 and February 2024, was retrospectively analyzed. Among them, 15 patients (23 sides) were treated with temporomandibular joint disc reduction and suture via small incision (open operation group), and 15 patients (22 sides) with modified temporomandibular joint disc reduction and suture with tragus incision assisted by arthroscopy (arthroscopy group). There was no significant difference in gender, age, disease duration, affected side, Wilkes-Bronstein stage, preoperative visual analogue scale (VAS) score, maximal interincisal opening (MIO), and temporomandibular joint dysfunction index (DI), craniomandibular index (CMI), palpation index (PI), and other baseline data between groups ( P>0.05). VAS score, MIO, and temporomandibular joint function indicators (PI, DI, CMI) of patients were recorded at 3 months after operation, and the difference (change value) of the above indicators between pre- and post-operation was calculated. At 1 week after operation, MRI was performed to evaluate the reduction of the articular disc compared to the preoperative image. The results were classified as excellent, good, and poor, with excellent and good being considered effective reduction. The condition of condyle process repair was observed by cone beam CT (CBCT) at 3 months after operation.
RESULTS:
All incisions healed by first intention in the two groups. All patients were followed up 3-18 months (mean, 8.2 months). Facial nerve injury occurred in 3 cases in the open operation group and 1 case in the arthroscopy group, all of which returned to normal after physiotherapy and drug treatment. At 3 months after operation, MIO and VAS scores of both groups significantly improved when compared with those before operation ( P<0.05), and temporomandibular joint function indicators (PI, DI, CMI) significantly decreased ( P<0.05). The change values of MIO and temporomandibular joint function indicators in arthroscopy group were significantly higher than those in open operation group ( P<0.05). There was no significant difference in the change value of VAS score between groups ( P>0.05). There was no recurrence during follow-up. Postoperative MRI review showed that the effective reduction rate of joint disc was 95.65% (22/23) in the open operation group and 95.45% (21/22) in the arthroscopy group, with no significant difference between groups ( P>0.05). Postoperative CBCT found that early and timely effective reduction of joint disc was conducive to condyle process repair and reconstruction.
CONCLUSION
Modified temporomandibular joint disc reduction and suture with tragus incision assisted by arthroscopy has a clear effect in the treatment of ADD, with less trauma, fewer postoperative complications, and good early effectiveness.
Humans
;
Arthroscopy/methods*
;
Retrospective Studies
;
Temporomandibular Joint Disorders/surgery*
;
Temporomandibular Joint Disc/surgery*
;
Male
;
Treatment Outcome
;
Female
;
Suture Techniques
;
Adult
;
Joint Dislocations/surgery*
;
Range of Motion, Articular
;
Middle Aged
;
Pain Measurement
;
Young Adult
;
Sutures
9.Analysis on effect of high-frequency electric snare device under electronic laryngoscope in treating epiglottic cyst
Xianbin LAN ; Shaoping PENG ; Guiqing WU ; Taihai DENG ; Yue LI ; Jiali ZHANG
Chongqing Medicine 2024;53(8):1214-1217,1225
Objective To explore the clinical efficacy of high-frequency electric snare device under elec-tronic laryngoscope in the treatment of epiglottic cyst.Methods A total of 100 patients with definitely diag-nosed epiglottic cyst receiving outpatient operation treatment in the First Affiliated Hospital of Gannan Medi-cal University from April 2021 to March 2023 were selected as the research subjects and included into the ob-servation group and control group according to the visiting order,50 cases in each group.The observation group was treated with high-frequency electric snare for epiglottic cyst resection under electronic laryngo-scope,and the control group was treated with laryngeal tissue forceps under electronic laryngoscope for uncov-ering operation of epiglottic cyst.The operation time,intraoperative blood loss volume,pain degree within postoperative 24 h,pain duration,complete resection rate and recurrence rate in postoperative 3 months were compared between the two operation methods.Results The operation time,intraoperative blood loss volume,VAS score within postoperative 24 h and pain duration in the observation group were significantly less than those in the control group,the complete resection rate was significantly higher than that in the control group,and the differences were statistically significant (P<0.05).The two groups were followed up for 3 months. Only 2 cases in the control group relapsed,which were epiglottic multiple cyst,and the recurrence rate had no statistical difference between the two groups (P>0.05).No dyspnea,massive bleeding and epiglottic adhesion appeared.Conclusion The high-frequency electric snare device under electronic laryngoscope for treating epi-glottic cyst has the advantages of short operation time,less blood loss,postoperative light pain and high com-plete resection rate.
10.METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity.
Xiaoyang DOU ; Lulu HUANG ; Yu XIAO ; Chang LIU ; Yini LI ; Xinning ZHANG ; Lishan YU ; Ran ZHAO ; Lei YANG ; Chuan CHEN ; Xianbin YU ; Boyang GAO ; Meijie QI ; Yawei GAO ; Bin SHEN ; Shuying SUN ; Chuan HE ; Jun LIU
Protein & Cell 2023;14(9):683-697
METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals
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Mice
;
Methylation
;
Chromatin
;
Histones/metabolism*
;
RNA, Messenger/genetics*
;
Methyltransferases/metabolism*
;
RNA/metabolism*

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