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Chinese Medical Journal ; (24): 2665-2673, 2020.
Article in English | WPRIM | ID: wpr-877883


BACKGROUND@#Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.@*METHODS@#This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12.@*RESULTS@#A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.@*CONCLUSION@#Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.@*TRIAL, NCT03066609;

Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , China , Double-Blind Method , Humans , Psoriasis/drug therapy , Severity of Illness Index , Treatment Outcome
Article in Chinese | WPRIM | ID: wpr-297192


<p><b>OBJECTIVE</b>To investigate the value of combined determination of neutrophil CD64 and procalcitonin (PCT) in the early diagnosis of neonatal bacterial infection.</p><p><b>METHODS</b>According to discharge diagnosis, 37 neonates with bacterial infection were divided into sepsis (n=15) and ordinary infection (non-sepsis) groups (n=22). Twenty-one neonates without infection who were hospitalized during the same period of time were enrolled as the control group. Venous blood samples were collected immediately after admission. Flow cytometry was used to measure the serum level of neutrophil CD64. Chemiluminescence and immune transmission turbidimetry were used to measure the serum levels of PCT and CRP respectively.</p><p><b>RESULTS</b>The sepsis group had higher serum levels of neutrophil CD64, PCT, and CRP than the control group (P<0.01), the ordinary infection group had a higher serum level of neutrophil CD64 than the control group (P<0.01), and the sepsis group had higher serum levels of PCT and CRP than the ordinary infection group (P<0.01). The areas under the ROC curve (AUC) of neutrophil CD64, PCT, and CRP in diagnosing bacterial infection were 0.818, 0.818, and 0.704 respectively, and the AUC of combined neutrophil CD64 and PCT was 0.926. A combination of neutrophil CD64 and PCT had a sensitivity of 97.29% and an accuracy of 89.65% in the early diagnosis of neonatal bacterial infection.The sensitivity and accuracy were higher than those of a combination of CRP and neutrophil CD64 or PCT as well as neutrophil CD64, PCT, or CRP alone for the early diagnosis of neonatal bacterial infection.</p><p><b>CONCLUSIONS</b>The combined determination of neutrophil CD64 and PCT can improve the sensitivity and accuracy in the diagnosis of neonatal bacterial infection, which helps with early identification of bacterial infection.</p>

Bacterial Infections , Blood , Diagnosis , C-Reactive Protein , Calcitonin , Blood , Early Diagnosis , Female , Humans , Infant, Newborn , Male , Neutrophils , Chemistry , ROC Curve , Receptors, IgG , Blood
Article in Chinese | WPRIM | ID: wpr-340571


<p><b>OBJECTIVE</b>To investigate the effect of Nogo-66 receptor (NgR) silencing with specific small interfering RNA (siRNA) on brain injury repair in preterm rats with brain injury caused by intrauterine infection and related mechanism of action.</p><p><b>METHODS</b>The pregnant Sprague-Dawley rats (with a gestational age of 15 days) were selected, and premature delivery was induced by RU486 or lipopolysaccharide (LPS). The preterm rats delivered by those treated with RU486 were selected as the control group. The preterm rats with brain injury caused by intrauterine infection induced by LPS were divided into model, empty vector, and NgR-siRNA groups, with 36 rats in each group. The rats in the control and model groups were given routine feeding only, and those in the empty vector and NgR-siRNA groups were given an injection of lentiviral empty vector or NgR-siRNA lentivirus via the lateral ventricle on postnatal day 1 (P1) and then fed routinely. On P3, P7, and P14, 8 rats in each group were randomly selected and sacrificed to harvest the brain tissue. RT-PCR was used to measure the mRNA expression of NgR. Western blot was used to to measure the protein expression of active RhoA. The immunofluorescence histochemistry was used to determine the degree of activation of microglial cells and the morphology of oligodendrocyte precursor cells (OPCs). Hematoxylin and eosin staining was used to observe the pathological changes in brain tissue. The behavioral score was evaluated on P30.</p><p><b>RESULTS</b>On P3, the NgR-siRNA group had significantly lower mRNA expression of NgR and protein expression of active RhoA in brain tissue than the model and empty vector groups (P<0.05). In each group, the mRNA expression of NgR was positively correlated with the protein expression of active RhoA (P<0.05). The results of immunofluorescence histochemistry showed that on P3, the NgR-siRNA group had a significantly reduced fluorescence intensity of the microglial cells labeled with CD11b compared with the model and empty vector groups (P<0.05). The OPCs labeled with O4 antibody in the four groups were mainly presented with tripolar cell morphology. The results of pathological examination showed a normal structure of white matter with clear staining in the periventriclar area in the control group, a loose structure of white matter with disorganized fibers and softening lesions in the model and empty vector groups, and a loose structure of white matter with slightly disorganized fibers, slight gliocyte proliferation, and no significant necrotic lesions in the NgR-siRNA group. As for the behavioral score, compared with the model and empty vector groups, the NgR-siRNA group had a higher score in the suspension test, a longer total activity distance, and greater mean velocity and number of squares crossed, as well as a shorter time of slope test and a shorter time and distance of activity in the central area (P<0.05), while there were no significant differences in these parameters between the NgR-siRNA and control groups (P>0.05).</p><p><b>CONCLUSIONS</b>NgR silencing with specific siRNA can effectively silence the expression of NgR in pertem rats with brain injury caused by interauterine infection and has a significant neuroprotective effect in brain injury repair.</p>

Animals , Animals, Newborn , Brain Injuries , Therapeutics , Female , Gene Silencing , Infections , Lentivirus , Genetics , Male , Nogo Receptor 1 , Genetics , Pregnancy , RNA, Small Interfering , Genetics , Rats , Rats, Sprague-Dawley
Article in Chinese | WPRIM | ID: wpr-640029


Objective To explore the changes of genes associated with the nuclear factor of kappa B(NF-?B) signaling pathway in neonatal rats with early hypoxic-ischemic reperfusion brain damage(HIRBD).Methods Twenty-four SD rats at age of 7 days,with male to female of 1212,were randomized into normal control group(group A,n=8),hypoxic-ischemia reperfusion for 2 h(group B,n=8) and hypoxic-ischemia reperfusion for 4 h(group C,n=8).The tissues of hippocampus were taken for complete RNA extraction.Gene chip inspection and biological signal analysis technique were used to detect the expression of 113 involved signal molecules of NF-?B pathway.Results Compared with group A,the up-regulated expression was found in Chemokine(C-C motif) ligand 2,Dual specificity phosphatase 1,FBJ osteosarcoma oncogene(Fos) and Toll-like receptor 9.Whereas the expressions of Caspase-1,8,Mitogen-activated protein kinase kinase 6,Mitogen activated protein kinase 3 and Ras homolog gene family member a from Ras-gene famimly was found down-regulated in group B.The up-regulated expression was in Fos,IL-1? and Toll-like receptor 6,but that of down-regulation was found in Caspase-1,Extracellular matrix protein 1,Lysophosphatidic Acid G-protein-coupled receptor 2,Mucosa associated lymphoid tissue lymphoma translocation gene 1,Inhibitor of kappa B kinase epsilon and Ras homolog gene family member c.Conclusions At the early stage of HIRBD,the Toll-like receptors may induce NF-?B activation,leading to the coordinated induction of multiple genes,which is involved in inflammatory,apoptosis and cell proliferation.Genes induced by NF-?B are responsible for the physiopathological process of early brain damage in neonatal rats with HIRBD.

Article in Chinese | WPRIM | ID: wpr-639501


Objective To explore the relationship of the ratio of plasma adrenomedullin(AM)and endothelin-1(ET-1)with serum concentration of neuron-specific enolase(NSE)in full-term neonates with hypoxic-ischemic encephalopathy(HIE).Methods Plasma concentrations of AM,ET-1 and serum NSE from 32 full-term neonates with HIE were detected by radioimmunoassay(RIA)on the 1,3 and 7 d after parturition,30 neonates in the corresponding periods in our hospital were employed as controls.The infants with HIE were divided into mild,moderate or severe group in terms of diagnostic standard of HIE.Results 1.Plasma concentrations of AM and ET-1 in newborns with mild,moderate or severe HIE were significantly higher than that of control group at 1 d after life with a decline from 3-7 d(Pa