OBJECTIVES: Nerve growth factor (NGF) induces neuron transdifferentiation of adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the secretion of epinephrine (EPI), which may be involved in the pathogenesis of bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator of neurogenesis in the nervous system, has been proved to be elevated in AMCCs with neuron transdifferentiation in vivo. This study aims to explore the role of MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms. METHODS: Rat AMCCs were isolated and cultured. AMCCs were transfected with siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological changes were observed using light and electron microscope. Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal markers), extracellular regulated protein kinases (ERK), phosphorylated extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular supernatant were measured using ELISA. RESULTS: Cells with both tyrosine hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference reversed the effect of NGF, causing increases in the levels of PNMT and EPI, conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 overexpression significantly increased the number of cell processes and peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs in the NGF+PD98059 group were decreased (all P<0.05). After treatment with PD98059 and dexamethasone, the effect of NGF on promoting the transdifferentiation of AMCCs was inhibited, and the number of cell processes and EPI levels were decreased (both P<0.05). In addition, the activity of the pERK/MASH1 pathway activated by NGF was also inhibited. CONCLUSIONS MASH1 is the key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron transdifferentiation is probably mediated via pERK/MASH1 signaling.
Animals ; Rats ; Adrenal Medulla ; Cell Transdifferentiation ; Chromaffin Cells ; Dexamethasone ; Epinephrine/pharmacology* ; Mammals ; Nerve Growth Factor ; Neurons ; Peripherins ; Protein Kinases ; Tyrosine 3-Monooxygenase

Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.
Humans ; Choline/metabolism* ; Phosphatidylcholines/metabolism* ; Central Nervous System/metabolism*

OBJECTIVE: To investigate the survival of patients with cardiac arrest and cardiopulmonary resuscitation (CA-CPR), and to analyze the factors influencing survival at 30 days after restoration of spontaneous circulation (ROSC). METHODS: A retrospective cohort study was conducted. Clinical data of 538 patients with CA-CPR admitted to the People's Hospital of Ningxia Hui Autonomous Region from January 2013 to September 2020 were enrolled. The gender, age, underlying disease, cause of CA, type of CA, initial rhythm, presence or absence of endotracheal intubation, defibrillation, use of epinephrine, and 30-day survival rate of patients were collected. The etiology of CA and 30-day survival rate among patients with different ages were compared, as well as the clinical data between patients who survived and died at 30 days after ROSC were also compared. Multivariate Logistic regression was used to analyze the relevant factors affecting the 30-day survival rate of patients. RESULTS: Among 538 patients with CA-CPR, 67 patients with incomplete information were excluded, and 471 patients were enrolled. Among 471 patients, 299 were males and 172 were females. Aged from 0 to 96 years old, 23 patients (4.9%) were < 18 years old, 205 patients (43.5%) were 18 to 64 years old, and 243 patients (51.6%) were ≥ 65 years old. 302 cases (64.1%) achieved ROSC, and 46 patients (9.8%) survived for more than 30 days. The 30-day survival rate of patients aged < 18 years old, 18-64 years old and ≥ 65 years old was 8.7% (2/23), 12.7% (26/205) and 7.4% (18/243), respectively. The main causes of CA in patients younger than 18 years were severe pneumonia (13.1%, 3/23), respiratory failure (13.1%, 3/23), and trauma (13.1%, 3/23). The main causes were acute myocardial infarction (AMI; 24.9%, 51/205), respiratory failure (9.8%, 20/205), and hypoxic brain injury (9.8%, 20/205) in patients aged 18-64 years old, and AMI (24.3%, 59/243) and respiratory failure (13.6%, 33/243) in patients aged ≥ 65 years old. Univariate analysis results revealed that the 30-day survival rate of patients with CA-CPR may be related to the the cause of CA was AMI, initial rhythm was ventricular tachycardia/ventricular fibrillation, endotracheal intubation and epinephrine. Multivariate Logistic regression analysis results showed that CA was caused by AMI [odds ratio (OR) = 0.395, 95% confidence interval (95%CI) was 0.194-0.808, P = 0.011] and endotracheal intubation (OR = 0.423, 95%CI was 0.204-0.877, P = 0.021) was a protective factor for 30 days of survival after ROSC in patients with CA-CPR. CONCLUSIONS The 30-day survival rate of CA-CPR patients was 9.8%. The 30-day survival rate of CA-CPR patients with AMI after ROSC is higher than that of patients with other CA causes, and early endotracheal intubation can improve the prognosis of patients.
Female ; Male ; Humans ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Survival Rate ; Heart Arrest ; Hospitals ; Epinephrine ; Ventricular Fibrillation

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.
Rats ; Animals ; Periploca ; Cysteine ; Cytidine Diphosphate Choline ; Network Pharmacology ; Phosphorylcholine ; Metabolomics ; Arthritis, Rheumatoid/drug therapy* ; Biomarkers ; Glycerophospholipids ; Methionine ; Purines ; Chromatography, High Pressure Liquid

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.
Adult ; Female ; Humans ; Infant, Newborn ; Pregnancy/metabolism* ; Betaine/metabolism* ; Birth Weight/physiology* ; Choline/metabolism* ; Cohort Studies ; Fetal Development/physiology* ; Fetal Weight/physiology* ; Homocysteine/metabolism* ; Methionine/metabolism* ; Pregnancy, Twin/physiology* ; Biomarkers/metabolism* ; Pregnancy Trimesters/physiology* ; Pregnancy Outcome

OBJECTIVE: To establish a snail control approach for spraying chemicals with drones against Oncomelania hupensis in complex snail habitats in hilly regions, and to evaluate its molluscicidal effect. METHODS: The protocol for evaluating the activity of spraying chemical molluscicides with drones against O. hupensis snails was formulated based on expert consultation and literature review. In August 2022, a pretest was conducted in a hillside field environment (12 000 m²) north of Dafengji Village, Dacang Township, Weishan County, Yunnan Province, which was assigned into four groups, of no less than 3 000 m² in each group. In Group A, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with drones at a dose of 40 g/m², and in Group B, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with drones at a dose of 40 g/m², while in Group C, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with knapsack sprayers at a dose of 40 g/m², and in Group D, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with knapsack sprayers at a dose of 40 g/m². Then, each group was equally divided into six sections according to land area, with Section 1 for baseline surveys and sections 2 to 6 for snail surveys after chemical treatment. Snail surveys were conducted prior to chemical treatment and 1, 3, 5, 7 days post-treatment, and the mortality and corrected mortality of snails, density of living snails and costs of molluscicidal treatment were calculated in each group. RESULTS: The mortality and corrected mortality of snails were 69.49%, 69.09%, 53.57% and 83.48%, and 68.58%, 68.17%, 52.19% and 82.99% in groups A, B, C and D 14 days post-treatment, and the density of living snails reduced by 58.40%, 63.94%, 68.91% and 83.25% 14 days post-treatment relative to pre-treatment in four groups, respectively. The median concentrations of chemical molluscicides were 37.08, 35.42, 42.50 g/m² and 56.25 g/m² in groups A, B, C and D, and the gross costs of chemical treatment were 0.93, 1.50, 0.46 Yuan per m² and 1.03 Yuan per m² in groups A, B, C and D, respectively. CONCLUSIONS The molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against O. hupensis snails is superior to manual chemical treatment without environmental cleaning, and chemical treatment with drones and manual chemical treatment show comparable molluscicidal effects following environmental cleaning in hilly regions. The cost of chemical treatment with drones is slightly higher than manual chemical treatment regardless of environmental cleaning. Spraying 5% niclosamide ethanolamine salt granules with drones is recommended in complex settings with difficulty in environmental cleaning to improve the molluscicidal activity and efficiency against O. hupensis snails.
Niclosamide/pharmacology* ; Ethanolamine/pharmacology* ; Unmanned Aerial Devices ; China ; Molluscacides/pharmacology* ; Ethanolamines

BACKGROUND: Nasal insertion is the preferred method for non-intubated patients in flexible bronchoscopy; however, the relatively narrow nasal cavity results in difficulties related to bronchoscope insertion. This study aimed to investigate whether pre-operative nasal probe tests could reduce the time to pass the glottis, improve the first-pass success rate and patients' tolerance, and reduce postoperative bleeding. METHODS: This three-arm prospective randomized controlled trial was conducted in a tertiary hospital between May and October 2020. Three hundred patients requiring diagnosis and treatment using flexible bronchoscopy were randomly allocated to three groups: control group, simple cotton bud detection group (CD group), and adrenaline + lidocaine detection group (AD group). The primary outcome was the time to pass the glottis. Secondary outcomes included the first-pass success rate, the patients' tolerance scores, and post-operative bleeding. One-way analysis of variance, Kruskal-Wallis H test, Chi-squared test, Fisher's exact test, and Bonferroni's multiple comparison tests were used in this study. RESULTS: In total, 189 men and 111 women were enrolled in this study, with a mean age of 55.72 ± 12.86 years. The insertion time was significantly shorter in the AD group than in the control group (18.00 s [12.00-26.50 s] vs . 24.00 s [14.50-45.50 s], P = 0.005). Both the AD (99% vs . 83%, χ2 = 15.62, P < 0.001) and CD groups (94% vs . 83%, χ2 = 5.94, P = 0.015) had a significantly higher first-pass success rate than the control group. Compared with the control group, post-operative bleeding (1% vs . 13%, χ2 = 11.06, P < 0.001) was significantly lower in the AD group. However, no significant difference was found in the patients' tolerance scores. CONCLUSIONS: Pre-operative nasal cavity probe tests especially with adrenaline and lidocaine during flexible bronchoscopy can significantly reduce the time to pass the glottis, improve the first-pass success rate, and reduce post-operative nasal bleeding. Pre-operative nasal probe tests are recommended as a time-saving procedure for patients undergoing flexible bronchoscopy. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000032668; http://www.chictr.org.cn/showprojen.aspx?proj=53321 .
Adult ; Aged ; Bronchoscopes ; Bronchoscopy/methods* ; Epinephrine/therapeutic use* ; Female ; Humans ; Lidocaine/therapeutic use* ; Male ; Middle Aged ; Postoperative Hemorrhage/prevention & control* ; Prospective Studies

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) in children with cardiac arrest (CA) and the influencing factors for prognosis. METHODS: A retrospective analysis was performed on the medical records of the children who developed CA in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from June 2016 to June 2021. According to the presence or absence of AKI within 48 hours after return of spontaneous circulation (ROSC) for CA, the children were divided into two groups: AKI (n=50) and non-AKI (n=113). According to their prognosis on day 7 after ROSC, the AKI group was further divided into a survival group (n=21) and a death group (n=29). The multivariate logistic regression analysis was used to investigate the risk factors for early AKI in the children with CA and the influencing factors for prognosis. RESULTS: The incidence rate of AKI after CA was 30.7% (50/163). The AKI group had a 7-day mortality rate of 58.0% (29/50) and a 28-day mortality rate of 78.0% (39/50), and the non-AKI group had a 7-day mortality rate of 31.9% (36/113) and a 28-day mortality rate of 58.4% (66/113). The multivariate logistic regression analysis showed that long duration of cardiopulmonary resuscitation (OR=1.164, 95%CI: 1.088-1.246, P<0.001), low baseline albumin (OR=0.879, 95%CI: 0.806-0.958, P=0.003), and adrenaline administration before CA (OR=2.791, 95%CI: 1.119-6.961, P=0.028) were closely associated with the development of AKI after CA, and that low baseline pediatric critical illness score (OR=0.761, 95%CI: 0.612-0.945, P=0.014), adrenaline administration before CA (OR=7.018, 95%CI: 1.196-41.188, P=0.031), and mechanical ventilation before CA (OR=7.875, 95%CI: 1.358-45.672, P=0.021) were closely associated with the death of the children with AKI after CA. CONCLUSIONS Albumin should be closely monitored for children with ROSC after CA, especially for those with long duration of cardiopulmonary resuscitation, low baseline pediatric critical illness score, adrenaline administration before CA, and mechanical ventilation before CA, and such children should be identified and intervened as early as possible to reduce the incidence of AKI and the mortality rate.
Child ; Humans ; Prognosis ; Retrospective Studies ; Critical Illness ; Heart Arrest/complications* ; Acute Kidney Injury/epidemiology* ; Intensive Care Units, Pediatric ; Risk Factors ; Epinephrine ; Albumins

Objective: To determine the characteristics and progress of the visual acuity and refractive state of schoolchildren in Huangzhong District, Xining City, Qinghai Province in China. Methods: Cohort study. Department of Ophthalmology, Beijing Children's Hospital carried out a cohort study by collecting the visual acuity and refractive state of Grade 1-5 schoolchildren among 16 primary schools in Huangzhong District, Xining City, Qinghai Province in September 2020 and July 2021. Cycloplegic retinoscopy with eye drop which contained tropicamide (0.5%) and phenylephrine hydrochloride (0.5%) was performed in children with low vision(<1.0). Myopia was defined as the spherical equivalent (SE) ≤-0.5 D after cycloplegic retinoscopy. Measurement data was analyzed by t-test and enumeration data was analyzed by χ² test. Multiple linear regression was used to analyze the influencing factors. Results: The 2 489 individuals with repeated tests in two years were included in the follow-up study, among whom the prevalence of myopia was 26.24%(653/2 489) in 2020, while 32.94% (820/2 489)respectively in 2021. The incidence of myopia in one school year from grades 1 to 5 was 11.19%(47/420), 5.44%(21/386), 6.39%(25/391), 11.52%(44/382) and 11.67%(30/257). The average SE of children in all grades in 2021 increased negatively from the previous year (Grade 1 to Grade 5 increased respectively: 0.40 D, 0.69 D, 0.62 D, 0.52 D and 0.37 D). Conclusions: The prevalence of myopia among schoolchildren in Huangzhong District, Xining City, Qinghai Province was relatively high. There were two peaks of myopia incidence in the first, fourth and fifth grades. Female, age, and the baseline of SE were the related influencing factors for myopia progression.
Child ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Mydriatics ; Myopia/epidemiology* ; Ophthalmic Solutions ; Phenylephrine ; Prevalence ; Prospective Studies ; Tropicamide