DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Objective:To explore the effect of the Nurse-Mini-CEX assessment method combined with PBL teaching mode in the cultivation of core competencies of undergraduate nursing students during ICU internships.Methods:A total of 64 nursing students interning in the ICU of a Third-grade Class-A hospital in Wuhu City from Sep 2022 to Aug 2023 were selected and randomly divided into 8 groups(8 students in each group).Using cluster sampling,4 groups(32 students)were assigned to the experimental group,receiving training via Nursing-Mini-CEX combined with PBL,while the remaining 4 groups(32 students)served as the control group,undergoing traditional clinical teaching.All students completed a 2-month pre-ICU clinical internship,followed by a 4-week ICU internship.Results:Compared to the control group,the experimental group showed significantly higher scores in five dimensions of nursing competency:nursing consultation,nursing physical examination,nursing diagnosis,nursing interventions,and holistic evaluation(P＜0.05).Additionally,the experimental group outperformed the control group in core competencies,including clinical nursing skills,leadership,interpersonal communication,professional development,critical thinking and research ability(P＜0.05).Self-efficacy in learning ability and behavior,as well as scores in personal accomplishment,depersonalization,and emotional exhaustion,were also higher in the experimental group(P＜0.05).Furthermore,the experimental group reported greater satisfaction with training content,teaching effectiveness,clinical skill development,teamwork cultivation,and overall satisfaction(P＜0.05).Conclusions:Nursing-Mini-CEX assessment combined with PBL teaching mode effectively enhances core competencies and self-efficacy,reduces burnout among ICU nursing interns,and achieve good clinical results,providing a theoretical and practical basis for the teaching and training of nursing students in ICU.However,as a single-center study,further validation and broader studies are warranted.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Objective:To explore the effect of the Nurse-Mini-CEX assessment method combined with PBL teaching mode in the cultivation of core competencies of undergraduate nursing students during ICU internships.Methods:A total of 64 nursing students interning in the ICU of a Third-grade Class-A hospital in Wuhu City from Sep 2022 to Aug 2023 were selected and randomly divided into 8 groups(8 students in each group).Using cluster sampling,4 groups(32 students)were assigned to the experimental group,receiving training via Nursing-Mini-CEX combined with PBL,while the remaining 4 groups(32 students)served as the control group,undergoing traditional clinical teaching.All students completed a 2-month pre-ICU clinical internship,followed by a 4-week ICU internship.Results:Compared to the control group,the experimental group showed significantly higher scores in five dimensions of nursing competency:nursing consultation,nursing physical examination,nursing diagnosis,nursing interventions,and holistic evaluation(P＜0.05).Additionally,the experimental group outperformed the control group in core competencies,including clinical nursing skills,leadership,interpersonal communication,professional development,critical thinking and research ability(P＜0.05).Self-efficacy in learning ability and behavior,as well as scores in personal accomplishment,depersonalization,and emotional exhaustion,were also higher in the experimental group(P＜0.05).Furthermore,the experimental group reported greater satisfaction with training content,teaching effectiveness,clinical skill development,teamwork cultivation,and overall satisfaction(P＜0.05).Conclusions:Nursing-Mini-CEX assessment combined with PBL teaching mode effectively enhances core competencies and self-efficacy,reduces burnout among ICU nursing interns,and achieve good clinical results,providing a theoretical and practical basis for the teaching and training of nursing students in ICU.However,as a single-center study,further validation and broader studies are warranted.

Objective:To explore the application effect of ICU nursing sub-specialty management model in the clinical treatment of ICU patients.Methods:Based on the actual needs of ICU patients,a precise and systematic management plan including organizational structure,workflow,linkage mechanism,quality control system,dynamic follow-up,and scientific research transformation was formulated,to construct a working model of multi-linkage,multi-direction supplement and coordinated development of two-way feedback mechanism in sub-specialty nursing.The control group was set before the implementation of ICU nursing sub-specialty management mode(Jan 1 to Dec 31,2021),and the intervention group was set after the implementation of ICU nursing sub-specialty management model(Jan 1 to Dec 31,2022).The core competence,specialty,sensitive indicators,satisfaction,and impact on patients were compared before and after implementation.Results:After the implementation of the ICU nursing sub-specialty management model,the core competence of nurses was improved,and the hospitalization time and mechanical ventilation time of patients were reduced,the incidence of re-entry ICU,acquired weakness,acquired dysphagia and incontinence dermatitis was decreased,the proportion of unplanned extubation was decreased,and the satisfaction of patients,nurses,doctors and students was improved(P＜0.05).Conclusion:The construction of ICU nursing sub-specialty management model can effectively promote the construction of ICU nursing sub-specialty,improve the core competence of nurses,reshape the connotation of nursing,improve the prognosis of patients,and ultimately promote the benign and sustainable development of hospital nursing.

Objective:To integrate the best evidence for early rehabilitation of mechanically ventilated ICU-acquired weakness (ICU-AW) patients using evidence-based methods, providing evidence-based basis for standardized evaluation and intervention of early exercise therapy for mechanically ventilated ICU-AW patients.Methods:A systematic search was conducted on the American Thoracic Society (ATS) Clinical Practice Guidelines, Registered Nurses' Association of Ontario (RNAO), Guidelines International Network (GIN), Canadian Medical Association Clinical Practice Guideline Library (CMACPGL), BMJ Clinical Evidence, UpToDate, Scottish Intercollegiate Guidelines Network (SIGN), PubMed, Cochrane Library, National Guideline Clearinghouse (NGC), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), UM-library, Physiotherapy Evidence Database (PEDro), National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Chinese Medical Pulse Guidelines Website, CNKI and Wanfang data and other Chinese and English databases, professional team websites, and guideline websites for expert consensus, guidelines, randomized collected trial (RCT), systematic reviews and other evidence on early exercise rehabilitation for mechanically ventilated ICU-AW patients. The search time limit was from the establishment of the database to December 31, 2023. Literature search, screening, evaluation, information extraction was independently conducted by two evaluators with cross checking, and quality evaluation of the included literature was conducted.Results:A total of 21 literatures were enrolled, including 5 guidelines, 5 systematic reviews, 4 expert consensuses, and 7 RCT, all of which with high evidence level and all were enrolled. They were summarized into seven aspects with assessment screening, exercise safety standards, precautions, setting of exercise time, exercise intensity, exercise sequence, and recommended exercise content as the core, and 32 best evidences.Conclusions:The evidence summarized can provide evidence-based basis for standardized assessment and intervention of early exercise rehabilitation in mechanically ventilated ICU-AW patients. ICU medical practitioners need to combine the actual clinical environment, individual differences and rehabilitation goals of patients, to provide targeted health guidance and intervention for the prevention of ICU-AW in mechanically ventilated patients.

Objective:To investigate whether there are differences in clinical outcomes and perinatal outcomes associated with different initial dosages of gonadotropin (Gn) in expected poor prognosis young patients, diagnosed according to the POSEIDON criteria, undergoing the early-follicular phase long-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol.Methods:This retrospective cohort study analyzed clinical data from patients who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)-fresh embryo transfer (ET) cycle at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University between January 1, 2016, and June 30, 2022. Patients included in the study were those who underwent ovarian stimulation with the early-follicular phase long-acting GnRH-a long protocol and young expected poor prognosis. Patients were divided into three groups based on the starting Gn dosage: low-dose group (Gn<225 U), medium-dose group (225 U≤Gn<300 U), and high-dose group (Gn=300 U). Clinical and perinatal outcomes were compared among the three groups. Results:A total of 1 659 cycles were included in the study, with 316 cycles in the low-dose group, 536 cycles in the medium-dose group, and 807 cycles in the high-dose group. The number of oocytes retrieved in the high-dose group [6.00 (4.00,9.00)] was less than that in the medium-dose group [8.00 (6.00,11.00)] and the low-dose group [11.00 (7.00,13.00)], which in the medium-dose group was less than that in the low-dose group, and the differences were statistically significant (all P<0.017). There were no significant statistical differences in oocyte maturation rate, normal fertilization rate of IVF/ICSI, or high-quality embryo rate among the three groups (all P>0.05). The blastocyst formation rates decreased sequentially in the low-dose group [20.33% (425/2 090)], medium-dose group [17.28% (510/2 951)], and high-dose group [14.62% (518/3 542)], with significant differences between each pair of groups (all P<0.017). There were no significant differences in clinical pregnancy rate, biochemical pregnancy rate, ectopic pregnancy rate, miscarriage rate, chromosomal abnormalities in miscarriage tissues, or preterm birth rate among the three groups (all P>0.05). However, the live birth rate was significantly lower in the high-dose group [47.83% (386/807)] than in the low-dose group [57.28% (181/316), P=0.004]. After adjusting for confounding factors using multivariate logistic regression, the high starting Gn dosage was found to be an independent risk factor for decreased live birth rate (a OR=0.659, 95% CI: 0.462-0.941, P=0.022). There were no significant differences in perinatal outcomes among the groups, regardless of whether confounding factors were adjusted for (all P>0.05). Conclusion:In young patients with expected poor prognosis undergoing their first ovarian stimulation with the long-acting follicular phase protocol, increasing the starting Gn dosage does not increase the number of oocytes retrieved and is associated with a lower blastocyst formation rate and a reduced live birth rate, but does not increase the risk of adverse perinatal outcomes.

Objective:To investigate whether there are differences in clinical outcomes and perinatal outcomes associated with different initial dosages of gonadotropin (Gn) in expected poor prognosis young patients, diagnosed according to the POSEIDON criteria, undergoing the early-follicular phase long-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol.Methods:This retrospective cohort study analyzed clinical data from patients who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)-fresh embryo transfer (ET) cycle at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University between January 1, 2016, and June 30, 2022. Patients included in the study were those who underwent ovarian stimulation with the early-follicular phase long-acting GnRH-a long protocol and young expected poor prognosis. Patients were divided into three groups based on the starting Gn dosage: low-dose group (Gn<225 U), medium-dose group (225 U≤Gn<300 U), and high-dose group (Gn=300 U). Clinical and perinatal outcomes were compared among the three groups. Results:A total of 1 659 cycles were included in the study, with 316 cycles in the low-dose group, 536 cycles in the medium-dose group, and 807 cycles in the high-dose group. The number of oocytes retrieved in the high-dose group [6.00 (4.00,9.00)] was less than that in the medium-dose group [8.00 (6.00,11.00)] and the low-dose group [11.00 (7.00,13.00)], which in the medium-dose group was less than that in the low-dose group, and the differences were statistically significant (all P<0.017). There were no significant statistical differences in oocyte maturation rate, normal fertilization rate of IVF/ICSI, or high-quality embryo rate among the three groups (all P>0.05). The blastocyst formation rates decreased sequentially in the low-dose group [20.33% (425/2 090)], medium-dose group [17.28% (510/2 951)], and high-dose group [14.62% (518/3 542)], with significant differences between each pair of groups (all P<0.017). There were no significant differences in clinical pregnancy rate, biochemical pregnancy rate, ectopic pregnancy rate, miscarriage rate, chromosomal abnormalities in miscarriage tissues, or preterm birth rate among the three groups (all P>0.05). However, the live birth rate was significantly lower in the high-dose group [47.83% (386/807)] than in the low-dose group [57.28% (181/316), P=0.004]. After adjusting for confounding factors using multivariate logistic regression, the high starting Gn dosage was found to be an independent risk factor for decreased live birth rate (a OR=0.659, 95% CI: 0.462-0.941, P=0.022). There were no significant differences in perinatal outcomes among the groups, regardless of whether confounding factors were adjusted for (all P>0.05). Conclusion:In young patients with expected poor prognosis undergoing their first ovarian stimulation with the long-acting follicular phase protocol, increasing the starting Gn dosage does not increase the number of oocytes retrieved and is associated with a lower blastocyst formation rate and a reduced live birth rate, but does not increase the risk of adverse perinatal outcomes.

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

OBJECTIVE: To explore the predictive value of diaphragmatic thickening fraction (DTF) combined with Medical Research Council-score (MRC score) on the outcome of weaning from mechanical ventilation in ICU-acquired weakness (ICU-AW) patients. METHODS: A retrospective case-control study was conducted. The clinical data of mechanically ventilated patients with an MRC score of less than 48 admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from January 2022 to March 2023 were collected, including general information, ultrasound indicators, MRC scores, main clinical outcomes, and weaning outcomes. Patients were divided into successful weaning group and failed weaning group according to whether the patient could maintain effective autonomous breathing for at least 48 hours without using an invasive or non-invasive ventilator. The clinical data of the two groups were compared. Receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of DTF and MRC score alone or in combination for successful weaning of patients. RESULTS: A total of 87 patients were enrolled, of which 58 were successful weaning and 29 were failed weaning. There were no statistically significant differences in general data such as gender, age, underlying disease, heart rate (HR), mean arterial pressure (MAP), pH value, blood lactic acid (Lac), oxygenation index (PaO₂/FiO₂), and severity scores between the two groups. Compared with the failed weaning group, the DTF and MRC scores of patients in the successful weaning group were significantly increased [DTF: (26.02±2.68)% vs. (22.79±5.40)%, MRC score: 38.90±2.78 vs. 33.24±3.78, both P < 0.05]. The duration of mechanical ventilation and the length of ICU stay of patients in the successful weaning group were significantly shorter than those in the failed weaning group [duration of mechanical ventilation (hours): 102.21±32.60 vs. 113.14±41.34, length of ICU stay (days): 6.48±2.18 vs. 10.11±4.01, both P < 0.05], and the re-intubation rate and ICU hospitalization cost were significantly lowered [re-intubation rate: 6.90% (4/58) vs. 27.59% (8/29), ICU hospitalization cost (10 000 RMB): 4.99±0.87 vs. 7.85±2.45, both P < 0.05]. ROC curve analysis showed that the area under the ROC curve (AUC) of DTF and MRC score for predicting successful weaning in ICU-AW mechanical ventilation patients was 0.839 [95% confidence interval (95%CI) was 0.746-0.931] and 0.799 (95%CI was 0.701-0.899), respectively. Using DTF ≥ 25.01% as the optimal cut-off value to predict successful weaning, the sensitivity was 82.76%, and the specificity was 72.41%. Predicting successful weaning based on an optimal cut-off value of MRC score of ≥ 35.50 had a sensitivity of 79.31% and a specificity of 70.69%. Based on the DTF ≥ 25.01% combined with MRC score ≥ 35.50, it was predicted that the weaning would be successful, with an AUC of 0.887 (95%CI was 0.812-0.962), sensitivity increased to 89.70%, and specificity increased to 79.30%. CONCLUSIONS The DTF and MRC score have good guiding value for the selection of weaning timing and predicting the weaning outcomes in ICU-AW patients. Compared with independent DTF and MRC score, the combination of DTF and MRC score improves the predictive value of successful weaning in ICU-AW patients.
Humans ; Respiration, Artificial ; Ventilator Weaning ; Case-Control Studies ; Retrospective Studies ; Intensive Care Units