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.

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

[This corrects the article DOI: 10.1016/j.apsb.2021.07.027.].

During the development of therapeutic microRNAs (miRNAs or miRs), it is essential to define their pharmacological actions. Rather, miRNA research and therapy mainly use miRNA mimics synthesized in vitro. After experimental screening of unique recombinant miRNAs produced in vivo, three lead antiproliferative miRNAs against human NSCLC cells, miR-22-3p, miR-9-5p, and miR-218-5p, were revealed to target folate metabolism by bioinformatic analyses. Recombinant miR-22-3p, miR-9-5p, and miR-218-5p were shown to regulate key folate metabolic enzymes to inhibit folate metabolism and subsequently alter amino acid metabolome in NSCLC A549 and H1975 cells. Isotope tracing studies further confirmed the disruption of one-carbon transfer from serine to folate metabolites by all three miRNAs, inhibition of glucose uptake by miR-22-3p, and reduction of serine biosynthesis from glucose by miR-9-5p and -218-5p in NSCLC cells. With greater activities to interrupt NSCLC cell respiration, glycolysis, and colony formation than miR-9-5p and -218-5p, recombinant miR-22-3p was effective to reduce tumor growth in two NSCLC patient-derived xenograft mouse models without causing any toxicity. These results establish a common antifolate mechanism and differential actions on glucose uptake and metabolism for three lead anticancer miRNAs as well as antitumor efficacy for miR-22-3p nanomedicine, which shall provide insight into developing antimetabolite RNA therapies.

ObjectiveTo explore the effect of Chaishao Liujuntang on Hedgehog signaling pathway in rats with chronic atrophic gastritis （CAG） of liver depression and spleen deficiency. MethodWistar rats were randomized into normal group and modeling group. CAG with the liver depression and spleen deficiency syndrome was induced in rats in the modeling group with a compound method. After modeling， they were classified into the model group， vitacoenzyme group， Chaishao Liujuntang group， GDC-0449 （blocker） group， and Chaishao Liujuntang + GDC-0449 group. Normal group and model group were given （ig） normal saline. Vitacoenzyme and Chaishao Liujuntang group received （ig） corresponding drugs at 240 mg·kg^-1·d^-1 and 5.1 g·kg^-1·d^-1， respectively， and GDC-0449 group was treated （ip） with GDC-0449 at 50 mg·kg^-1·d^-1. For the Chaishao Liujuntang + GDC-0449 group， rats received GDC-0449 （ip） at 50 mg·kg^-1·d^-1 and Chaishao Liujuntang （ig） at 5.1 g·kg^-1·d^-1. The administration lasted 4 weeks. The pathological morphology of rat gastric mucosa was observed based on hematoxylin-eosin （HE） staining. mRNA and protein expression of sonic hedgehog （Shh）， 12th transmembrane receptor Patched1 （Ptch1）， and glioma-associated oncogene homolog 1 （Gli1） in gastric mucosa tissues was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot. Content of serum interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with normal group， the model group demonstrated decrease in gland cells， glandular atrophy， large lumen volume， plasma cell infiltration， intestinal metaplasia， decrease in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa （P<0.01）， and rise of serum IL-1β and TNF-α content （P<0.01）. Compared with model group， vitacoenzyme group and Chaishao Liujuntang group showed ordered cells， alleviation of gland atrophy， and no obvious inflammatory infiltration， and GDC-0499 group and Chaishao Liujuntang + GDC-0449 showed no significant improvement. Significant rise in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa tissues of vitacoenzyme group and Chaishao Liujuntang group （P<0.01）， no significant difference in serum IL-1β content and significant decrease in TNF-α content in vitacoenzyme group （P<0.01）， significant reduction in content of serum IL-1β and TNF-α in Chaishao Liujuntang group （P<0.05， P<0.01） were observed compared with those in the model group. The mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa and the content of serum IL-1β and TNF-α were insignificantly different between the GDC-0449 group and Chaishao Liujuntang + GDC-0449 group. ConclusionChaishao Liujuntang can effectively improve the pathological state of gastric mucosa in CAG rats with liver depression and spleen deficiency， which may be related to the activation of Hedgehog signaling pathway and the decrease of IL-1β and TNF-α content.

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation ( RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid ( CONCLUSIONS For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.
Birth Weight ; Cesarean Section ; China ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Pregnancy ; Retrospective Studies

With the understanding of microRNA (miRNA or miR) functions in tumor initiation, progression, and metastasis, efforts are underway to develop new miRNA-based therapies. Very recently, we demonstrated effectiveness of a novel humanized bioengineered miR-124-3p prodrug in controlling spontaneous lung metastasis in mouse models. This study was to investigate the molecular and cellular mechanisms by which miR-124-3p controls tumor metastasis. Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3p in A549 cells, which were assembled into multiple cellular components critical for metastatic potential. Among them, plectin (PLEC) was verified as a new direct target for miR-124-3p that links cytoskeleton components and junctions. In miR-124-3p-treated lung cancer and osteosarcoma cells, protein levels of vimentin, talin 1 (TLN1), integrin beta-1 (ITGB1), IQ motif containing GTPase activating protein 1 (IQGAP1), cadherin 2 or N-cadherin (CDH2), and junctional adhesion molecule A (F11R or JAMA or JAM1) decreased, causing remodeling of cytoskeletons and disruption of cell-cell junctions. Furthermore, miR-124-3p sharply suppressed the formation of focal adhesion plaques, leading to reduced cell adhesion capacity. Additionally, efficacy and safety of biologic miR-124-3p therapy was established in an aggressive experimental metastasis mouse model

MicroRNAs (miRNAs or miRs) are small noncoding RNAs derived from genome to control target gene expression. Recently we have developed a novel platform permitting high-yield production of bioengineered miRNA agents (BERA). This study is to produce and utilize novel fully-humanized BERA/miR-328-3p molecule (hBERA/miR-328) to delineate the role of miR-328-3p in controlling nutrient uptake essential for cell metabolism. We first demonstrated successful high-level expression of hBERA/miR-328 in bacteria and purification to high degree of homogeneity (>98%). Biologic miR-328-3p prodrug was selectively processed to miR-328-3p to suppress the growth of highly-proliferative human osteosarcoma (OS) cells. Besides glucose transporter protein type 1, gene symbol solute carrier family 2 member 1 (GLUT1/), we identified and verified large neutral amino acid transporter 1, gene symbol solute carrier family 7 member 5 (LAT1/) as a direct target for miR-328-3p. While reduction of LAT1 protein levels by miR-328-3p did not alter homeostasis of amino acids within OS cells, suppression of GLUT1 led to a significantly lower glucose uptake and decline in intracellular levels of glucose and glycolytic metabolite lactate. Moreover, combination treatment with hBERA/miR-328 and cisplatin or doxorubicin exerted a strong synergism in the inhibition of OS cell proliferation. These findings support the utility of novel bioengineered RNA molecules and establish an important role of miR-328-3p in the control of nutrient transport and homeostasis behind cancer metabolism.

Drug-metabolizing enzymes, transporters, and nuclear receptors are essential for the absorption, distribution, metabolism, and excretion (ADME) of drugs and xenobiotics. MicroRNAs participate in the regulation of ADME gene expression imperfect complementary Watson-Crick base pairings with target transcripts. We have previously reported that Cytochrome P450 3A4 (CYP3A4) and ATP-binding cassette sub-family G member 2 (ABCG2) are regulated by miR-27b-3p and miR-328-3p, respectively. Here we employed our newly established RNA bioengineering technology to produce bioengineered RNA agents (BERA), namely BERA/miR-27b-3p and BERA/miR-328-3p, fermentation. When introduced into human cells, BERA/miR-27b-3p and BERA/miR-328-3p were selectively processed to target miRNAs and thus knock down and mRNA and their protein levels, respectively, as compared to cells treated with vehicle or control RNA. Consequently, BERA/miR-27b-3p led to a lower midazolam 1'-hydroxylase activity, indicating the reduction of CYP3A4 activity. Likewise, BERA/miR-328-3p treatment elevated the intracellular accumulation of anticancer drug mitoxantrone, a classic substrate of ABCG2, hence sensitized the cells to chemotherapy. The results indicate that biologic miRNA agents made by RNA biotechnology may be applied to research on miRNA functions in the regulation of drug metabolism and disposition that could provide insights into the development of more effective therapies.

Objective To evaluate the effect of curcumin pretreatment on brain injury induced by intestinal ischemia-reperfusion (I/R) in mice.Methods Forty-eight male C57BL/6 mice,aged 8 weeks,weighing 20-24 g,were divided into 3 groups (n =16 each) using a random number table:sham operation group (Sham group),intestinal I/R group (I/R group) and curcumin pretreatment group (CUR group).Mice were subjected to 75 min superior mesenteric artery occlusion followed by 24 h reperfusion to establish the model of brain injury induced by intestinal I/R in mice.Curcumin 200 mg/kg (in 30 ml of 10％ dimethyl sulfoxide) was intraperitoneally injected at 30 min before ischemia in CUR group,while 10％ dinethyl sulfoxide 30 ml was given instead of curcumin in Sham group and I/R group.Two percent Evans blue (EB) in 4 ml/kg of normal saline was injected via the caudal vein at 23 h of reperfusion,1 h later mice were sacrificed,and hippocampi were removed for determination of EB content.Mice were sacrificed at 24 h of reperfusion,hippocampal tissues were isolated for determination of wet to dry weight ratio (W/D ratio) and cell apoptosis (by TUNEL) and for examination of the pathological changes (with a light microscope),and brain tissues were isolated for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents (by enzyme-linked immunosorbent assay),malondialdehyde (MDA) content (by thiobarbituric acid method),superoxide dismutase (SOD) activity (by xanthine oxidase method) and expression of caspase-3 (by Western blot).Apoptosis rate was calculated.Results Compared with Sham group,the W/D ratio of hippocampal tissues,EB content and apoptosis rate were significant increased,the contents of MDA,TNF-α and IL-6 in brain tissues were increased,SOD activity was decreased,and the expression of caspase-3 was up-regulated in I/R and CUR groups (P＜0.05).Compared with I/R group,the W/D ratio of hippocampal tissues,EB content and apoptosis rate were significant decreased,the contents of MDA,TNF-α and IL-6 in brain tissues were decreased,SOD activity was increased,and the expression of caspase-3 was down-regulated (P＜0.05),and the pathological changes of hippocampal tissues were significantly reduced in CUR group.Conclusion Curcumin pretreatment can reduce brain injury induced by intestinal I/R in mice,and the mechanism may be related to inhibiting inflammatory responses,lipid peroxidation and cell apoptosis.