Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.

OBJECTIVES: To study the clinical and genetic characteristics of children with congenital adrenal hyperplasia (CAH). METHODS: Clinical data, laboratory findings, and genetic test results of 63 children diagnosed with CAH at Henan Children's Hospital from January 2017 to December 2024 were retrospectively reviewed. RESULTS: Of the 63 patients, the mean age at the first visit was (21 ± 14) days; 29 (46%) were of male sex and 34 (54%) were of female sex. The predominant clinical manifestations were poor weight gain or weight loss (92%, 58/63), poor feeding (84%, 53/63), skin hyperpigmentation (83%, 52/63), and female external genital anomalies (100%, 34/34). Laboratory abnormalities included hyponatremia (87%, 55/63), hyperkalemia (68%, 43/63), metabolic acidosis (68%, 43/63), and markedly elevated 17-hydroxyprogesterone (92%, 58/63), testosterone (89%, 56/63), and adrenocorticotropic hormone (81%, 51/63). Among 49 patients who underwent genetic testing, CYP21A2 variants were identified in 90% (44/49), with c.293-13A/C>G (33%, 30/91) and large deletions/gene conversions (29%, 26/91) being the most frequent; STAR (8%, 4/49) and HSD3B2 (2%, 1/49) variants were also detected. Following hormone replacement therapy, electrolyte disturbances were corrected in 57 cases, with significant reductions in 17-hydroxyprogesterone, adrenocorticotropic hormone, and testosterone levels (P<0.001). CONCLUSIONS CAH presenting in neonates or young infants is characterized by electrolyte imbalance, external genital anomalies, and abnormal hormone levels. Genetic testing enables definitive subtype classification; in CYP21A2-related CAH, c.293-13A/C>G is a hotspot variant. These findings underscore the clinical value of genetic testing for early diagnosis and genetic counseling in CAH. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(11): 1367-1372.
Humans ; Adrenal Hyperplasia, Congenital/diagnosis* ; Male ; Female ; Retrospective Studies ; Infant ; Infant, Newborn

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:This study analyzed the provincial policy on the"dual channel"management of drugs,provided suggestions for improving the"dual channel"management models.Methods:From May 10,2021 to April 10,2024,the official websites of the Healthcare Security Administration and the Health Commission of various provinces were searched for policy documents related to the"dual channel"management,and the text data were statistically analyzed.Results:The"dual-channel"management policies of various provinces coexisted with commonalities and differences.Conclusions:It is recommended to refine the access standards of the drug catalog,standardize the setting of the entry threshold of pharmaceutical institutions,scientifically determine the level of medical insurance treatment,and formulate differentiated drug identification and management methods,so as to further weaken the policy restrictive factors.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To compare the clinical characteristics of diabetes mellitus(DM)patients complicated with pyogenic liver abscess(PLA)and non-DM(NDM)patients complicated with PLA,and provide evidence for clinical diagnosis and treatment.Methods PLA patients who admitted to an affiliated hospital of Anhui Medical University from July 2002 to February 2022 were selected and divided into DM+PLA group and NDM+PLA group according to whether they had DM.General condition,clinical manifestations and signs.complications,biochemical and patho-genic examination results,imaging findings,as well as clinical efficacy and influencing factors of the two groups of patients were analyzed retrospectively.Results 695 PLA patients were included in the analysis,191(27.5％)in the DM+PLA group and 504(72.5％)in the NDM+PLA group.The proportions of males and complication of hypertension in the DM+PLA group were higher than those in the NDM+PLA group,while the proportion of bi-liary diseases and malignant tumors was lower(all P＜0.05).The proportions of patients developing fever,fa-tigue,as well as concurrent anemia and hypoalbuminemia in the DM+PLA group were higher than those in the NDM+PLA group(all P＜0.05).Compared with the NDM+PLA group,the neutrophil count and percentage in the DM+PLA group increased,while total protein,albumin content,and albumin/globulin ratio all decreased(all P＜0.05).The proportions of the detection of Klebsiella pneumoniae and the occurrence of liver right lobe abscess in DM+PLA patients were higher than those of the NDM+PLA group(both P＜0.05).Multivariate logistic re-gression analysis revealed that malignant tumor was a risk factor for affecting the clinical efficacy of PLA patients,invasive treatment was a protect factor for affecting the clinical efficacy of PLA patients,while blood sugar was a risk factor for affecting the clinical efficacy of NDM+PLA patients.Conclusion DM+PLA patients have more se-vere infection symptoms than NDM+PLA patients,and are accompanied by higher proportions of Klebsiella pneu-moniae infection and liver right lobe abscess.It is necessary to strengthen attention to patients with malignant tumor and control blood sugar level,and timely supplement with invasive treatment if necessary.

Objective To establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for simultaneous determination of meropenem,linezolid,voriconazole and posaconazole in children with small volume of plasma,and to use the method in children therapeutic drug monitoring(TDM).Methods The plasma samples were precipitated protein by methanol.And then,the analytes were gradient eluted on an EVO-C18 column by HPLC-MS/MS with mobile phase consisted of water(0.1％formic acid)-acetonitrile(0.1％formic acid)at the flow rate of 0.5 mL·min 1.Ions were monitored in the multiple reaction monitoring(MRM)mode,using positive ion electrospray ionization(ESI).Results Meropenem had a good liner relationship in 0.5-64.0 μg·mL-1(r=0.999 2),0.2-25.6 μg·mL-1 for linezolid and voriconazole(r=0.999 2,r=0.999 9),and 0.1-12.8 μg·mL-1 for posaconazole(r=0.998 9).Accuracy,precision,matrix effect and stability studies all met the requirements.This method was fully verified,and applied to determine the plasma antimicrobial concentrations of 49 pediatric patients.Conclusion The method is simple,rapid,sensitive and suitable for children's plasma concentration monitoring of four antimicrobials.