Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective To analyze the status and trend for the mortality and DALY rates of child growth failure (CGF) in children aged < 5 years in China from 1990 to 2019, so as to provide a scientific basis for CGF prevention and control. Methods The mortality and DALY rates of CGF in children aged < 5 years from 1990 to 2019 were obtained from GBD 2019. The changes of these indicators with the years in China , the United States, Japan, Russia, India and the global were compared and analyzed. Results In 2019, the mortality of child wasting, child stunting and child underweight in children aged < 5 years in China were 9.62/100 000, 1.23/100 000, and 1.29/100 000 respectively, the mortality rates were 867.50/100 000 , 129.23/100 000 , and 112.87/100 000 rescpectively, higher than those of the United States, Japan, and Russia, and far lower than those of India and the global. The disease burden of three types of CGF were all higher in males than females, and higher in children aged < 1 years than children aged 1-4 years. From 1990 to 2019, the mortality and DALY rates of CGF in children aged < 5 years in China decreased from 300.41/100 000 and 26 445.38/100 000 to 10.49/100 000 and 943.57/100 000, respectively. China had the largest drop rate compared with all analyzed countries. As for children aged < 5 years in China, the DALY rate of lower respiratory infection ranked first in all the diseases caused by CGF. Conclusion From 1990 to 2019, the disease burden of CGF in children aged < 5 years has shown a significant decrease in China , but it is still far behind the developed countries. In the future, more attention should be paid to the problems of child growth in hope of reducing the mortality and DALY rates of CGF.

Based on GC-MS and network pharmacology, the active constituents, potential targets, and mechanism of essential oil from Gleditsiae Fructus Abnormalis(EOGFA) against cerebral ischemia/reperfusion(I/R) injury were explored, and the effective constituents were verified by experiment. To be specific, GC-MS was used identify the constituents of the volatile oil. Secondly, the targets of the constituents and disease were predicted by network pharmacology, and the drug-constituent-target network was constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets. Molecular docking was performed to investigate the binding affinity between the active constituents and the targets. Finally, SD rats were used for experimental verification. The I/R injury model was established, and the neurological behavior score, infarct volume, and pathological morphology of brain tissue were measured in each group. The content of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression of vascular endothelial growth factor(VEGF) by Western blot. A total of 22 active constituents and 17 core targets were screened out. The core targets were involved in 56 GO terms and the major KEGG pathways of TNF signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. Molecular docking showed that the active constituents had high affinity to the targets. The results of animal experiment suggested that EOGFA can alleviate the neurological impairment, decrease the cerebral infarct volume and the content of IL-1β, IL-6 and TNF-α, and down-regulate the expression of VEGF. The experiment verified the part results of network pharmacology. This study reflects the multi-component, multi-target, and multi-pathway characteristics of EOGFA. The mechanism of its active constituents is related to TNF and VEGF pathways, which provides a new direction for in-depth research on and secondary development of Gleditsiae Fructus Abnormalis.
Animals ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Oils, Volatile ; Gas Chromatography-Mass Spectrometry ; Interleukin-6 ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A ; Reperfusion Injury ; Cerebral Infarction

Humans ; Consensus ; Liver Neoplasms/therapy* ; China

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ² test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cohort Studies ; Colorectal Neoplasms/pathology* ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms/secondary* ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies

Objective:To explore the expression of microRNA-4695-5p in the serum of colorectal cancer patients and its effect on the proliferation and invasion of colorectal cancer CACO-2 cells.Methods:A total of 43 serum samples of colorectal cancer patients who were admitted to the Department of Gastrointestinal Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University from March 2018 to November 2021 were selected, and serum samples of 43 healthy people who underwent outpatient physical examination were used as controls. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels in the serum of colorectal cancer patients and those of healthy individuals. The miR-4695-5p overexpression plasmid or the negative control plasmid were transfected into CACO-2 cells, namely the miR-4695-5p group and the control group, and the transfection efficiency was verified by qRT-PCR. CCK8 method and Transwell experiment were used to detect the effect of overexpression of miR-4695-5p on the proliferation and invasion of CACO-2 cells. The dual luciferase reporter gene experiment was used to verify the targeted binding relationship between miR-4695-5p and Ras-related C3 botulinum toxin substrate 1 (RAC1). qRT-PCR and Western blot were used to detect the effect of overexpression of miR-4695-5p on the expression of RAC1 gene and Wnt/β-Catenin signaling pathway protein.The software of SPSS28.0 was used to conduct data analysis. The measurement data of normal distribution were espressed by Mean±SD. The t-test was used to compare the means between two groups, and the one-way analysis of variance was used to compare the means of multiple groups. Results:The expression level of miR-4695-5p in the serum of patients with colorectal cancer was significantly lower than that of healthy individuals ( P<0.01). The relative expression levels of miR-4695-5p in the control group and miR-4695-5p group were 1.09 ± 0.65 and 8.83±2.03, respectively. The expression level of miR-4695-5p in CACO-2 cells in the miR-4695-5p group was 8.10 times that of the control group, and CACO-2 cells overexpressing miR-4695-5p were successfully constructed ( P<0.01). Compared with the control group, the proliferation ability of CACO-2 cells in the miR-4695-5p group was significantly reduced ( P<0.05), and the invasion ability of CACO-2 cells was significantly reduced ( P<0.01). Bioinformatics tools and dual luciferase reporter gene experiments confirmed that miR-4695-5p can target and bind RAC1 ( P<0.01). Compared with the control group, the expression of RAC1 gene in the miR-4695-5p group was significantly decreased ( P<0.01), and the expression of Wnt/β-Catenin signaling pathway proteins Wnt3a, β-catenin, and c-MYC decreased significantly. Conclusions:miR-4695-5p is lowly expressed in the serum of colorectal cancer patients. miR-4695-5p inhibits the proliferation and invasion of colorectal cancer CACO-2 cells by targeting the inhibition of RAC1 gene expression and down-regulating the activity of the Wnt/β-Catenin signaling pathway.