Objective To investigate the effect of Kangaroo care in improving milk intake and immune status for premature children.Methods 80 cases of premature children from June 2009 to June 2011 were chosen as the research object.They were randomly divided into the control group and the observation group with 40 patients in each group.The control group was taken with conventional care model for care,and the observation group used Kangaroo care model for mursing.The milk intake of differerent tines and immune status of the two grmps were taken for testing and comparoson.Results The milk intake vohnnes 7d,14d and 28d after care of the observation group were greater than the control group.The levds of CD3+ 、CD4+and CD4/CD8 were higher,while the CD8+ level was lower than the control group.Conclusions Kangaroo care can significantly improve milk intake and immune status of preterm children.

Objective To discuss the significance of near infrared spectroscopy (NIRS) in evaluation of intrapartum hypoxic-ischemic cerebral injury, and to provide a method to evaluate neonatal brain damage objectively and quantitatively. Methods A total of 63 neonates with fetal distress were divided into hypoxic-ischemic encephalopathy(HIE) group and non-HIE group. Thirtyfive newborns with no fetal distress were chosen as controls. Using NIRS, the brain regional oxygen saturation(rSO2) in these neonates were measured. Evaluation of brain rSO2 in the diagnosis of HIE was analyzed with receiver operating characteristic (ROC) curve. Results At the time of fetal head visible on vulval gapping and 5 min after birth, the HIE group showed decreased brain rSO2[(36. 6±5.0)% and (52. 0±4. 2)%], comparing with control group[(45. 9±4. 6)% and (59. 6±4. 4)%]and non-HIE group[(44.1±3.1) % and (57. 6±3. 5) %](P<0. 01) . The brain rSO2 was positively correlated with the pH and oxygen saturation of umbilical artery blood in all groups (P<0. 01). When the cut-off value of brain rSO2 was <39. 5% at fetal head visible on vulval gapping, the sensitivity and specificity of assessing HIE were 67% and 93%, respectively, while 70% and 86% when the cut-off value was <53. 5% at 5 min after birth. Conclusions The brain rSO2 obtained by NIRS could be used to evaluate brain oxygenation, and may be useful in predicting HIE in neonates with fetal distress.

Objective To investigate the effects of hypoxia-inducible factor-1α (HIF-1α)expression on pathogenesis of retinopathy of prematurity (ROP) and to find new target for gene therapy.Methods After liposome-mediated small interference RNA (siRNA) transfection into rat retinal endothelial cells,the cells were cultured in medium with CoCl2-induced hypoxic condition.Expression of HIF-1α mRNA was determined by fluorenscence quantitative reverse transcription-polymerase chain reaction(RT-PCR),HIF-1α protein expression was detected by Western Blot after cocultured for 8 hours.Cell proliferation was measured with 3-(4,5)-dimethylthiazol (-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay after cocultured for 24 hours.Difference between groups was compared with independent samples t test.Results Rat retinal vascular endothelial cells were successfully transfected with siRNA.Fluorescence quantitative RT-PCR results showed that at 48 hours of transfection,the expression of HIF-1α mRNA in the interference group of siRNA1,siRNA2 and siRNA4 were 0.1620 ± 0.0147,0.2034 ± 0.0251 and 0.3049 ± 0.0165,which were 16.20％,20.34 ％ and 30.49％ of blank control group (1.0000±0.0344),and were lower than that of negative control group (0.8334±0.0242) (t=16.786,8.953 and 4.087,P＜0.05 respectively).Western Blot results showed that HIF-1α protein expression was significantly inhibited by siRNA1(0.4956 ± 0.0421 ) and siRNA2 (0.6544 ± 1.0032) comparing with blank control group (3.5105 ±0.4084) and negative control group (3.4019 ± 1.0677) (t =6.861,2.893,4.567 and 5.072,P＜0.05 respectively).As for cellular proliferation activity,(49.5±2.9) ％ and (67.4±1.2) ％ of cells growth inhibition were observed after transfection with siRNA1 and siRNA2,which were higher than those of negative control group [(15.7±1.5) ％ ] (t=2.786 and 6.904,P＜0.05).Conclusions The synthetic HIF-1α siRNA could effectively inhibit the expression of HIF-1α gene and reduce cell proliferation in rat retinal endothelial cells under hypoxic condition.RNA interference technology targeting HIF-1α might become a new strategy for gene therapy of ROP.

Objective To investigate the effect of rhubarb on hyperoxia-induced new bronchopulmo-nary dysplasia ( BPD) in rats. Methods Full-term Sprague-Dawley rats were exposed or not ( control group) in 600 ml/ L oxygen 4 days after birth and injected with normal saline (BPD group),rhubarb (BPD+ rhubarb group) or a combination of rhubarb with quercetin (BPD + rhubarb + quercetin group). Immuno-histochemical staining was used to detect the pathological changes of the rat lungs. HSP70 expression level was quantified by western blot. Results Compared with control group,BPD group showed decreased radial alveolar 14 and 21 days after the drug treatment,which was rescued by the coexistence of rhubarb. Quercetin, as an inhibitor of HSP70,counteracted the effect of rhubarb. The lung of the BPD + rhubarb + quercetin group showed a similar phenotypic change with that of the BPD group. In addition,the expressions of HSP70 in lung tissues of rhubarb group at 14 days and 21 days after the treatment were higher than those of other groups, there were significant differences between rhubarb group and other groups(F = 62. 46,P < 0. 01;F = 95. 90, P < 0. 01). Conclusion Rhubarb may attenuate the hyperoxia-induced new bronchopulmonary dysplasia in rats by activating HSP70 expression.

Objective To establish SD rat model of bronchopulmonary dysplasia(BPD) and investigate the influence and mechanism of heat shock protein 70 (HSP70) on the lung tissue with BPD.Methods One hundred and twenty new born SD rats were randomly equally divided into three groups,including blank-control group,bronchopulmonary dysplasia group,rhubarb intervention group (bronchopulmonary dysplasia rats treated with rhubarb).On the 7th,14th and 21th day,10 rats were euthanasiaed after weighted of each group.Histopathology of pulmonary,hematoxylin and eosin(HE)and the expression of HSP70 in the right lung were observed respectively.Results Compared with the rat of blank-control group,the rat weight of BPD group was significantly decreased at the same time point(P ＜0.01).On the 7th day,the alveolar cavity increased,alveolar wall became thin,and pulmonary interstitial cells increased in the rat of BPD group given oxygen.By 21 days,the normal structure of the alveoli disappeared,the diameter of the alveolar cavity enlarged,the number of alveoli significantly reduced,the alveolar fusion was large,and the alveolar space became thickness,and massive of interstitial cells hyperplasia.While,in the rhubarb intervention group,the lung tissue structure kept integrity,the size of the alveoli uniform.During 14 to 21 days,the integrity of lung structure and the uniform size alveoli still existed,and alveolar septa was thin.In immunohistochemical staining and western blotting experiments,the expression of HSP70 in rhubarb intervention group increased gradually with the increase of age,which was significantly different from control group(P ＜0.01).However,the expression of HSP70 in BPD group had not significant change on the 7th,14th and 21th days(P ＞0.05).Compared with rhubarb intervention group,the expression of HSP70 in the BPD group significantly decreased on the 14th and 21th day(P ＜0.01) respectively.Conclusion Rhubarb could protect the injured lung tissue by increasing the expression of HSP70.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment