This study was designed to investigate the effect of silencing microtubule-affinity regulating kinase 4(MARK4)on the apoptosis,inflammatory cytokine release and intestinal barrier protein expression of FHC cells in a lipopolysaccharide(LPS)-induced ulcerative colitis(UC)model,and the underlying molecular mechanisms.Western blot analysis was used to measure the expression levels of MARK4 and apoptosis-related factors including Caspase-1,NLRP3,and GSDMD in colon tissues from both UC patients and healthy individuals,as well as in LPS-induced FHC cell inflammation model.FHC cells was transfected with shRNA to silence MARK4.In control(normal FHC cells),LPS(LPS-stimulated FHC cells),and MARK4-silenced+LPS(shRNA-and LPS-treated FHC cells)groups,the expression levels of Caspase-1,NLRP3,GSDMD,intestinal barrier proteins,and NF-κB pathway-related proteins were assessed by Western blotting.ELISA and RT-qPCR were used to measure the expression levels of inflammatory cytokines IL-1β,IL-6,and TNF-α;flow cytometry was utilized to assess apoptosis.Data showed that both in UC patient colon tissues and the in vitro LPS-induced FHC cell UC inflammation model,there was a significant increase in the expression of MARK4 and apoptosis-related proteins including NLRP3,Caspase-1,and GSDMD.Silencing MARK4 inhibited the expression of these apoptosis-related proteins and downregulated the inflammatory cytokines IL-1β,IL-6,and TNF-α in LPS-induced FHC cells.Silencing MARK4 also reduced apoptosis,increased the expression of intestinal barrier proteins ZO-1,Occludin,and upregulated Claudin2.Gene Set Enrichment Analysis(GSEA)indicated a positive correlation between MARK4 and the NF-κB signaling pathway.Furthermore,silencing of MARK4 inhibited the expression levels of p-P65 and p-IKKα in the NF-κB pathway.In conclusion,MARK4 is significantly upregulated in UC tissues and cells.Silencing MARK4 inhibits the activation of the NF-κB signaling pathway,thereby inhibiting the apoptosis and inflammatory factor expression of UC cells.Thus,MARK4 could be a potential therapeutic target for UC patients.

ObjectiveSerum metabolomics of acute lung injury（ALI） in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） to explore the similarities and differences in the mechanism of Qingqiao（harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color） and Laoqiao（harvested when the fruits of Forsythiae Fructus were ripe） in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week， 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide（LPS）. After successfully constructing the ALI model， these rats was randomly divided into model group， Qingqiao group and Laoqiao group， with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg^-1， while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin（HE） staining， wet-to-dry mass ratio（W/D） of lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. The levels of interleukin（IL）-6， IL-1β and tumor necrosis factor（TNF）-α in BALF were quantified using enzyme-linked immunosorbent assay（ELISA）. UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao， and serum metabolomics of rats in each group was analyzed， combined with multivariate statistical analysis with variable importance in the projection（VIP） value>1， P<0.05 from t-test， and fold change（FC）≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group， rats in the model group exhibited enlarged alveolar lumen， ruptured alveoli， interstitial hemorrhage， bronchial exudation of a large number of neutrophils and erythrocytes， and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues（P<0.01）. In contrast， compared with the model group， rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs， and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased（P<0.01）， the lung injury was significantly alleviated， but more obvious in the Qingqiao group. Compared with the blank group， the expression levels of IL-6， IL-1β and TNF-α in the BALF of the model group were significantly higher（P<0.01）. Additionally， compared with the model group， the expression levels of IL-6， IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower（P<0.01）. The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao， with 47 common components， 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats， 19 and 12 metabolites were called back by Qingqiao and Laoqiao， respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， phenylalanine metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， glycerophospholipid metabolism， α-linolenic acid metabolism， and arachidonic acid metabolism， and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， arachidonic acid metabolism， sphingolipid metabolism， phenylalanine metabolism， ascorbate and aldarate metabolism， and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI， and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism， but the metabolic pathways affected by them are different.

Objective:To summarize and evaluate the domestic and foreign evidence on the intervention and management of neuropathic pain in patients with spinal cord injury, so as to provide evidence-based basis for clinical nursing staff.Methods:According to "6S" evidence model of evidence pyramid, computer evidence retrieval was carried out. Expert consensus and evidence summary quality assessment used the corresponding evaluation criteria of JBI evidence-based Health Care Centers (2016), while evidence-based guidelines quality used AGREE Ⅱinstrument, and high quality evidence was extracted.Results:A total of 6 articles, including 5 guidelines and 1 expert consensus, were included in this study. A total of 22 pieces of evidence were extracted, including the assessment, intervention measures, feedback, education and nursing model of neuropathic pain in patients with spinal cord injury.Conclusion:This study summarizes the evidence for the intervention and management of pathologic pain in spinal cord injury, which can provide scientific basis for clinical nursing staff. As the evidence summarized in this study comes from many countries, sufficient evaluation of clinical environment and other related factors should be conducted before application to promote the quality of nursing.

OBJECTIVE: To analyze the phenotype and genetic variant of a fetus with dysplasia of cerebellar vermis. METHODS: Gestational status and family history of the gravida was taken in combination with the imaging results of the fetus. Following elected abortion, fetal tissue and peripheral blood samples of the couple were collected for the extraction of genome DNA. Whole exome sequencing was carried out to screen potential variant associated with the phenotype of the proband. Specific PCR primers were designed to verify the results by Sanger sequencing. RESULTS: Prenatal ultrasound revealed that the fetal vermis cerebellum was poorly developed, which was similar to the previous pregnancy. Whole exome sequencing revealed that the fetus has carried compound heterozygous variants of the CPLANE1 gene, namely c.7978C>T and c.7169delT, which were respectively inherited from the husband and wife. CONCLUSION The c.7978C>T and c.7169delT compound heterozygous variants of the CPLANE1 gene probably underlay the dysplasia of cerebellar vermis in the fetus, which has provided a basis for genetic counseling and prenatal diagnosis.
Abnormalities, Multiple/genetics* ; Cerebellum/diagnostic imaging* ; Eye Abnormalities/genetics* ; Female ; Fetus ; Humans ; Kidney Diseases, Cystic ; Mutation ; Phenotype ; Pregnancy ; Retina/abnormalities*

Objective:To investigate the immunogenicity and safety of a boost dose of measles, mumps, and rubella combined vaccine (MMR) for children 4 to 6 years old.Methods:Children, aged 4 to 6 years old, had vaccinated with 1 dose of measles and rubella combined vaccine(MR) at the age of 8 months and 1 dose of MMR vaccine at 18-months, were recruited in Shanxi, Inner Mongolia, and Beijing, respectively. All children were assigned into 4, 5 and 6-year-old group. The children who met inclusion and exclusion criteria were vaccinated with 1 dose MMR vaccine, and were collected blood samples before vaccination and 35 to 42 d after the vaccination. During the study period, adverse events were collected at 30 min, 1 d, 2 d, 3 d, 4-12 d, and 13 to 42 days after vaccination. Serum was tested for IgG antibodies against measles, mumps and rubella. Geometric mean concentrations (GMC) of measles, mumps, and rubella antibodies were compared among groups by analysis of variance or non-parametric test. Seropositive rates and adverse event rates were compared among groups by Chi-square test or Fisher exact test.Results:A total of 500 children were included in immunogenicity analysis and 535 children were included in safety analysis. The overall adverse event rate was 20.37%, the most of severity for adverse events was mild. The rates of local and systemic adverse events were 0.37% and 20.00%, respectively. Symptoms of local adverse events were redness. The main systemic adverse events were fever, followed by cough, rash and runny nose. Received a dose of MMR vaccine for booster immunization, the seropositive rates of measles antibody, mumps antibody and rubella antibody were above 99% for all 3 age groups, and there was no significant difference between groups. There were significant differences in mumps antibody GMC among groups ( P=0.042), but no significant differences in measles and rubella antibodies GMC. Conclusion:The immunogenicity and safety of a boosted MMR vaccintion in children aged 4, 5 and 6 years were all similar good.

Objective: To evaluate the safety of enterovirus 71（EV71）inactivated vaccines produced by Wuhan Institute of Bio Products through learning the incidence of adverse events following immunization（AEFI）in children aged 6 months to 3 years old after vaccination. Methods: According to the national requirement for vaccine safety monitoring program，data of AEFI cases after inoculated EV71 vaccines from September 2017 to October 2018 in Zhejiang Province was collected by combining active and passive monitoring. Demographic characteristics，space distribution，dose and incidence of AEFI were analyzed. Results: A total of 107 503 children were included in this study，of which 27 173 were actively monitored and 80 330 were passively monitored. The monitoring results showed that 288 cases of AEFI occurred after inoculated EV71 vaccines，the reported incidence rate was 267.90/100 000. Of 288 cases，266 cases had common reactions（247.43/100 000），14 cases had abnormal reactions（13.02/100 000）and 8 cases had complications（7.44/100 000）；145 cases were passively monitored（180.51/100 000）and 143 cases were actively monitored（526.26/100 000）；150 cases were males and 138 cases were females，with the males to females ratio of 1.09∶1. The AEFI of EV71 vaccines were reported in all the cities of Zhejiang Province，with Jinhua，Taizhou and Hangzhou ranking the top three and accounting for 50.69% of all the reported cases. About 202 cases of AEFI（70.14%）occurred after the first dose of EV71 vaccines，and 163 cases（56.60%）occurred on the day of inoculation.Most of common reactions were fever，swelling and sclerosis. The harm of the reported abnormal reactions was mild，with 8 cases of anaphylactic rash and no other serious abnormal reactions were found. Conclusion The reported incidence rate of AEFI of the domestic EV71 vaccine in children aged from 6 months to 3 years is 267.90/100 000，without serious abnormal reactions，suggesting that the EV71 vaccine is safe.

Objective: To study the correlation of lifestyle characteristics with thyroid nodules in a population-based sample of centenarians in Hainan. Methods: The study was based on China Hainan Centenarian Cohort Study (CHCCS) conducted in 18 cities and counties in Hainan province from 2014 to 2016. A group of multidisciplinary team interviewed and examined local centenarians with structured questionnaires and ultrasonography procedures. A total of 918 centenarians were analyzed after excluding those who refused ultrasonographic examinations or had relevant missing data. Thyroids of centenarians were examined by 3-year experienced sonographer, details on lifestyle characteristics and dietary habits were collected by standard procedure. Results: Of the 918 centenarians, 683 (74.4%) had thyroid nodules under the ultrasonography procedures. The prevalence of thyroid nodules in different group of areca nut consumption varied significantly (P<0.05). In multivariate logistic regression model, the results showed female and areca nut intake were independently associated with thyroid nodules in centenarians (P<0.05). Conclusions The modifiable variables including areca nut intake as well as non-modifiable such as gender are independent determinants of thyroid nodules in centenarians. Further studies are warranted to explore and verify these associations in populations with different ranges of age.

Objective To investigate the risk factors of progressive motor deficit (PMD) in patients with acute middle cerebral artery occlusion (MCAO) beyond thrombolysis time.Methods The clinical data of 123 patients with acute MCAO beyond thrombolysis time,admitted to our hospital from March 2015 to March 2017,were analyzed retrospectively.According to whether patients having National Institute of Health Stroke Scale (NIHSS) scores increased＞2 within 5 d of admission and continued for 24 h,these patients were divided into two groups:PMD group and non-PMD group.Single factor analysis was performed on all clinical parameters that might influence PMD;in addition,the influencing factors of PMD were analyzed by multiple factor Logistic regression analysis.Results Fifty-one patients (41.5％) had PMD and 72 patients (58.5％) did not have PMD.Single factor analysis showed that the differences of randomized blood glucose level,ratio of patients with PH2 type hemorrhagic transformation,intracurricular infarct pattern,radiation crown infarct and collateral circulation pathway between the PMD group and the non-PMD group were statistically significant (P＜0.05).Multiple factor Logistic regression analysis showed that ratio of patients with PH2 type hemorrhagic transformation,radiation infarct site,internal watershed infarct model and collateral circulation pathway were significantly correlated to PMD (OR=2.857,95％CI:1.037-7.869,P=0.042;OR=2.585,95％CI:1.219-5.481,P=0.013;OR=2.876,95％CI:1.327-6.232,P=0.007;OR=2.332,95％CI:1.120-4.867,P=).024).Conclusion PH2 type hemorrhagic transformation,corona radiate infarct,intemal watershed infarct model and insufficient collateral circulation pathway are the important risk factors of PMD in patients with acute MCAO beyond thrombolysis time.

Objective To explore the effects of two kinds preoperative fasting and liquid-fasting time before caesarean section on blood glucose of puerperae with GDM before and after the operation,intra-operative complications and on blood glucose of neonates.Methods With prospective study method,162 puerperae with GDM admitted to obstetrical department of Peking University First Hospital and received cesarean section under combined spinal-epidural anesthesia between April 1st and Sep. 30th in 2015,were selected as the research object,and were divided into the control group (admitted on odd-numbered days) and the observation group (admitted on even-numbered days). Puerperae in the control group were forbidden to eat solid food for 8 h and drink transparent liquid for 6 h before the operation,while those in the observation group were forbidden to eat solid food for 6 h and drink transparent liquid for 2 h before the operation. Puererae in two groups were compared about their preoperative blood glucose,incidence of intraoperative nausea and vomiting or aspiration,intra-operative quality of bleeding,postoperative exsufflation time and blood glucose half an hour after the operation, meanwhile,neonates in two groups were compared about their Apgar scores 1 min and 5 min after birth,and their blood glucose half an hour after birth. Statistical analysis was done by independent-samplest test,Mann-WhitneyU test and χ2 test.Results Difference of preoperative blood glucose of puererae in two groups was statistically significant (P<0.01). Differences of intraoperative bleeding of puererae in two groups and blood glucose of neonates half an hour after birth in two groups were statistically significant (P<0.05). There was no statistic difference in the incidence of intraoperative nausea and vomiting or aspiration,postoperative exsufflation time of puererae,or Apgar scores 1 min and 5 min after birth of neonates in two groups(P>0.05).Conclusions The scheme of forbidding puererae from eating solid food for 6 h and drinking transparent liquid for 2 h before cesarean section can reduce the incidence of preoperative hypoglycemia,maintain a smooth post-operative blood glucose, reduce intraoperative bleeding without increasing the incidence of intraoperative complications like nausea,vomiting or aspiration,or hypoglycemia of the neonates. The new fasting and liquid-fasting scheme is safe and feasible,which makes it worth promoting in clinic.

Objective To observe the effects of different levels of sodium arsenite ( NaAsO2) on mRNA expression of pigment epithelium-derived factor (PEDF) and apoptosis-related factors in PC12 cells ( rat neuron properties pheochromocytoma). Methods PC12 cells were treated with different levels of NaAsO2 [0 (control group), 2, 5, 10 μmol/L] for 24 hours. The mRNA expression of PEDF and apoptosis-related factors (Bax, Bcl-2) were detected by real-time quantitative PCR. Results There were significant differences in the mRNA expressions of PEDF between the 4 groups (F=102.28, P<0.05), the mRNA expressions of PEDF in the group of 2, 5, 10μmol/L (0.70 ± 0.07, 0.33 ± 0.04, 0.23 ± 0.10) was lower than that of control group (1.15 ± 0.11, P< 0.05); there were no significant differences in the mRNA expressions of Bax between the 4 groups (0, 2, 5, 10 μmol/L groups: 0.95 ± 0.12, 0.80 ± 0.11, 0.88 ± 0.11, 1.01 ± 0.11, F= 2.01, P> 0.05); there were significant differences in the mRNA expressions of Bcl-2 between the 4 groups (F=19.87, P<0.05), the mRNA expressions of Bcl-2 in the group of 2, 5, 10 μmol/L (0.65 ± 0.03, 0.49 ± 0.04, 0.57 ± 0.09) were lower than that of control group (0.95 ± 0.11, all P<0.05);there were significant differences in the mRNA expressions of Bax/Bcl-2 between the 4 groups (F=8.352, P<0.05), the mRNA expressions of in the group of 5, 10μmol/L (1.80 ± 0.72, 1.82 ± 0.36) were higher than that of control group (1.02 ± 0.24, all P<0.05). Conclusion NaAsO2 may increase the expression of apoptosis-related factorsBax/Bcl-2 mRNA by decreasing the expression of PEDF mRNA in PC12 cells, leading to apoptosis in PC12 cells.