Background: Malignant vasovagal syncope (VVS) is characterized by cardiac arrest lasting more than 3 seconds during a syncope episode or head-up tilt test (HUTT). We aim to conduct a risk assessment for potential malignant VVS before the HUTT by using economic, simple and convenient demographic data, in order to prevent adverse outcomes for pediatric VVS.Purpose: To explore the correlation between demographic factors and pediatric malignant VVS, and verify the value of these factors in early risk assessment for malignant VVS before HUTT, so as to optimize test safety and reduce adverse events. Methods: We conducted a retrospective analysis of the clinical data of 3,734 children who were initially diagnosed with VVS due to unexplained syncope and presyncope. Finally, 122 children who met the diagnostic criteria for malignant VVS were included in the malignant VVS group, and 661 children who did not meet the criteria during the same period were matched as the control group. By analyzing demographic data and other factors, we attempted to clarify the association between these factors and malignant VVS. Results: Linear relationship: age and body mass index (BMI) have independent protective effects on malignant VVS. For every 1-year increase in age and every 1 kg/m2 increase in BMI, the risk of malignant VVS decreases by 12% and 9%, respectively. Nonlinear relationship: When the age is <12.9 years old, for every additional year of age, the risk of malignant VVS decreases by 20%. For ages 12.9 years and above, the efficacy is not significant. There is no significant nonlinear relationship between BMI and malignant VVS. Conclusion Age and BMI are independent protective factors for pediatric malignant VVS. Before the age of 12.9 years, the incidence of malignant VVS gradually decreases with the increase in age, and thereafter there is no significant impact.

Repeat expansion diseases(REDs) are a group of genetic disorders caused by the pathological expansion of specific short tandem repeats(STRs) in genomic DNA. They are characterized by significant clinical and genetic heterogeneity. Owing to the complexity of their pathogenesis, effective treatments remain elusive. With the in-depth analysis of the pathogenesis of these diseases, along with the development and innovation of targeting tools in recent years, targeted therapy strategies have become a research hotspot, and some antisense oligonucleotide drugs have entered the clinical trial stage. This article aims to review the latest advances in basic research and clinical trial outcomes of targeted therapy at the DNA, RNA and protein levels. Currently, this field still faces key bottlenecks including a high risk of off-target effects, low delivery efficiency, and challenges in clinical translation. Future efforts should focus on the optimization and refinement of targeting tools and delivery vectors, as well as multilevel collaborative combination therapeutic strategies.Combined with precise clinical classification and staging, this will promote the fundamental transformation of REDs treatment from symptomatic supportive care to etiological intervention.

Objective: Pembrolizumab and dostarlimab are immune checkpoint inhibitors that target programmed death receptor 1 (PD-1). Combination anti-PD-1 regimens have been shown to exhibit favorable survival benefits when treating advanced endometrial cancer (EC). Which treatment was preferable will need to be confirmed by a cost-effectiveness comparison between them. Methods: Based on patient and clinical parameters from RUBY and NRG-GY018 phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost-effectiveness of dostarlimab plus chemotherapy (DC), pembrolizumab plus chemotherapy (PC), and chemotherapy alone (C) treatment for patients with mismatch repair-proficient microsatellite-stable (pMMR-MSS) and mismatch repair-deficient microsatellite instability-high (dMMR-MSI-H) advanced EC from the American payers’ perspective. The main results include total cost, life-years (LYs), quality-adjusted lifeyears (QALYs), and the incremental cost-effectiveness ratio (ICER) at a $150,000/QALY of willingness-to-pay. Results: In the pMMR-MSS population, DC, PC, and C produced costs (QALYs) of $99,205 (3.02), $322,530 (3.25), and $421,923 (4.40), resulting in corresponding ICERs of $974,177/ QALY (PC vs. C), $234,527/QALY (DC vs. C), $86,671/QALY (DC vs. PC), respectively; In the dMMR-MSI-H population, DC, PC, and C obtained costs (QALYs) of $120,177 (5.73), $691,399 (8.43), and $708,787 (11.26), yielding ICERs of $266,423/QALY (PC vs. C), $135,165/QALY (DC vs. C), $7,866/QALY (DC vs. PC), respectively. Conclusion In the US, DC was a more cost-effective treatment than PC for patients with advanced EC irrespective of MMR status. However, compared to C, DC was associated with more cost-effectiveness in the dMMR-MSI-H population.

ObjectiveTo explore the potential mechanisms of kidney-tonifying and blood-activating acupuncture for Alzheimer's disease. MethodsMale SAMP8 mice were randomly divided into a model group， acupuncture group， non-acupoint group， and donepezi group， with 10 mice in each group， and 10 SAMR1 mice as normal group. The acupuncture group received acupuncture at Baihui （GV 20）， Xuehai （SP 10）， Shenshu （BL 23）， and Geshu （BL 17）. Xuehai （SP 10）， Shenshu （BL 23）， and Geshu （BL 17） were stimulated on the left side first and then on the right side alternately， once a day. The non-acupoint group received acupuncture at fixed bilateral non-meridian， non-acupoint points under the ribs， once a day. The model and normal groups underwent equivalent handling and restraint stress without acupuncture. The donepezi group received 1 mg/kg donepezil via gastric gavage daily. All groups were treated for 4 weeks. After treatment， Morris water maze tests （to record orientation sailing latency， number of traverses through the platform quadrant） and open field （to record distance travelled） were used to evaluate learning and memory abilities； hippocampal neuronal damage was analyzed via HE and Nissl staining； mitochondrial membrane potential and reactive oxygen species （ROS） were measured using assay kits； Western blot and qRT-PCR were performed to detect silencing information regulator 1 （SIRT1）， peroxisome proliferator-activated receptor gamma coactivator 1-alpha （PGC-1α）， and mRNA expression levels. ResultsCompared with the normal group， mice in the model group and non-acupoint group showed elevated orientation sailing latency and relative multiplicity of ROS in hippocampal tissues， and reduced number of traverses through the platform quadrant， distance of movement in the open-field experiment， number of Nissl-staining-positive cells in the hippocampal tissues， mitochondrial membrane potential， and protein levels and mRNA expression of SIRT1， PGC-1α （P＜0.01）； HE staining showed that the hippocampal tissues of the mice was loosely arranged， with reduced number of neurons and vacuolar degeneration； Nissl staining showed that pyramidal neurons in the hippocampal region were not neatly arranged， and the number of Nissl bodies in the cytoplasm was less and the staining was lighter. Compared with the model group， mice in the acupuncture group and donepezil group had lower orientation sailing latency and relative multiplicity of ROS in the hippocampal tissue， higher number of traverses through the platform quadrant， distance of movement in the open-field experiment， number of Nissl-stained positive cells in the hippocampal tissue， mitochondrial membrane potential， and protein levels and mRNA expression of SIRT1 and PGC-1α （P＜0.01）， and HE staining and Nissl staining showed significant improvement in hippocampal histopathological damage. Compared with the donepezil group， the orientation sailing latency shortened in the acupuncture group of mice （P＜0.01）. ConclusionKidney-tonifying and blood-activating acupuncture method can alleviate the SIRT1/PGC-1α signalling pathway in the hippocampal tissue and improve the mitochondrial function， thus alleviating the neuronal damage， which is one of the possible mechanisms for its treatment of Alzheimer's disease.

Objective: Pembrolizumab and dostarlimab are immune checkpoint inhibitors that target programmed death receptor 1 (PD-1). Combination anti-PD-1 regimens have been shown to exhibit favorable survival benefits when treating advanced endometrial cancer (EC). Which treatment was preferable will need to be confirmed by a cost-effectiveness comparison between them. Methods: Based on patient and clinical parameters from RUBY and NRG-GY018 phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost-effectiveness of dostarlimab plus chemotherapy (DC), pembrolizumab plus chemotherapy (PC), and chemotherapy alone (C) treatment for patients with mismatch repair-proficient microsatellite-stable (pMMR-MSS) and mismatch repair-deficient microsatellite instability-high (dMMR-MSI-H) advanced EC from the American payers’ perspective. The main results include total cost, life-years (LYs), quality-adjusted lifeyears (QALYs), and the incremental cost-effectiveness ratio (ICER) at a $150,000/QALY of willingness-to-pay. Results: In the pMMR-MSS population, DC, PC, and C produced costs (QALYs) of $99,205 (3.02), $322,530 (3.25), and $421,923 (4.40), resulting in corresponding ICERs of $974,177/ QALY (PC vs. C), $234,527/QALY (DC vs. C), $86,671/QALY (DC vs. PC), respectively; In the dMMR-MSI-H population, DC, PC, and C obtained costs (QALYs) of $120,177 (5.73), $691,399 (8.43), and $708,787 (11.26), yielding ICERs of $266,423/QALY (PC vs. C), $135,165/QALY (DC vs. C), $7,866/QALY (DC vs. PC), respectively. Conclusion In the US, DC was a more cost-effective treatment than PC for patients with advanced EC irrespective of MMR status. However, compared to C, DC was associated with more cost-effectiveness in the dMMR-MSI-H population.

OBJECTIVES: To explore the risk factors of feeding intolerance (FI) in critically ill children receiving enteral nutrition (EN) and to construct a prediction nomogram model for FI. METHODS: A retrospective study was conducted to collect data from critically ill children admitted to the Pediatric Intensive Care Unit of Xiangya Hospital, Central South University, between January 2015 and October 2020. The children were randomly divided into a training set (346 cases) and a validation set (147 cases). The training set was further divided into a tolerance group (216 cases) and an intolerance group (130 cases). Multivariate logistic regression analysis was used to screen for risk factors for FI in critically ill children receiving EN. A nomogram was constructed using R language, which was then validated on the validation set. The model's discrimination, calibration, and clinical net benefit were evaluated using receiver operating characteristic curves, calibration curves, and decision curves. RESULTS: Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition were identified as independent risk factors for FI in critically ill children receiving EN (P<0.05). Based on these factors, a nomogram prediction model for FI in critically ill children receiving EN was developed. The area under the receiver operating characteristic curve for the training set and validation set was 0.934 (95%CI: 0.906-0.963) and 0.852 (95%CI: 0.787-0.917), respectively, indicating good discrimination of the model. The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit (χ 2=12.559, P=0.128). Calibration curve and decision curve analyses suggested that the model has high predictive efficacy and clinical application value. CONCLUSIONS Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition are independent risk factors for FI in critically ill children receiving EN. The nomogram model developed based on these factors exhibits high predictive efficacy and clinical application value.
Humans ; Critical Illness ; Enteral Nutrition/adverse effects* ; Male ; Risk Factors ; Female ; Child, Preschool ; Infant ; Nomograms ; Retrospective Studies ; Child ; Logistic Models

OBJECTIVES: To study the effects of early respiratory training combined with swallowing function training on physical development and neurodevelopment at a corrected gestational age of 6 months in infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 69 BPD infants who could not be fed completely orally were prospectively selected from the Department of Neonatology of Hunan Children's Hospital between January 2018 and January 2021. Based on a random number table, the infants were divided into a conventional group (35 cases) and a training group (34 cases) (with 8 cases lost to follow-up; the final follow-up included 31 cases in the training group and 30 cases in the conventional group). Both groups received routine clinical treatment and care, while the training group additionally received respiratory and swallowing function training until the infants could independently feed orally. The weight, length, Gesell Developmental Schedule (GDS) results, readmission rate, and multiple readmission rate (two or more admissions) were compared between the two groups at a corrected age of 6 months. RESULTS: At corrected gestational age of 6 months, the training group had higher weight, length, and GDS scores in personal-social, language, gross motor, fine motor, and adaptive development compared to the conventional group (P<0.05). The readmission rate and multiple readmission rate were lower in the training group compared to the conventional group (P<0.05). CONCLUSIONS Early respiratory training combined with swallowing function training for BPD infants in a neonatal intensive care unit setting helps improve physical and neurological development and reduces the readmission rate.
Humans ; Bronchopulmonary Dysplasia/physiopathology* ; Prospective Studies ; Male ; Female ; Infant ; Deglutition/physiology* ; Gestational Age ; Infant, Newborn ; Breathing Exercises ; Child Development