Objective To explore the incidence risk of postoperative delirium in different underlying diseases and the effective measures of postoperative recovery.Methods 978 cases of emergency surgery,included acute abdomen 324 cases,358 cases of cardiovascular disease,296 cases of cranial trauma.To analyze preoperative underlying diseases,we observed the incidence rate of postoperative delirium,and the efficacy of different care on delirium recovery was compared.Results There was a higher incidence rate of postoperative delirium in patients with coronary heart disease,high blood pressure and emphysema (P ＜ 0.05),especially in patients with multiple disease (P ＜0.01).And effective psychological intervention could increase the recovery rate of delirium.Conclusion The preoperative underlying diseases has a significant impact on the occurrence of postoperative delirium,and the psychological intervention has good effect on the recovery of delirium.

Objective:To establish a lung cancer model of patient-derived tumor xenografts (PDTX) and to explore the relation-ship between primary cisplatin resistance and ERCC1 and IGFBP5 expression levels. Methods:Lung cancer tissues from 84 patients who underwent surgery were collected and implanted into nude mice. Patient characteristics for the first generation xenografts that were and were not engrafted were compared. Passage 3 xenografts were treated with cisplatin. The expression levels of ERCC1 and IGFBP5 in cisplatin-resistant and cisplatin-sensitive groups were detected using immunohistochemistry assay. Results:The model success rates were 32.14%(27/84) in first-generation xenografts, 88.89%(24/27) in second-generation xenografts, and 95.83%(23/24) in third-gener-ation xenografts. The tumorigenicity of first-generation xenografts was correlated with size, differentiation, clinical stage, and histologi-cal type. PDTX tumors maintain the histological type of parental tumors through serial passage in nude mice. ERCC1 expression level was significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group, whereas the IGFBP5 expression level was lower in the cisplatin-resistant group than in the cisplatin-sensitive group. Conclusion:Lung cancer PDTX models were successfully es-tablished, and histological characteristics of the primary cancers were retained. Therefore, the models may serve a function in preclini-cal research of lung tumor biology and for exploring the drug resistance mechanism of tumors. The cisplatin resistance of primary lung cancer may be correlated with the expression level of ERCC1 and IGFBP5 in lung carcinoma.

BACKGROUND:Fractures can induce bone cel hypoxia, and remarkably reduce the oxygen tension in cels. Hypoxia-inducible factor-2α is a key oxygen-dependent transcriptional activator to regulate the body function under hypoxia and mediate the release of various inflammatory factors after fractures.
OBJECTIVE:To explore the role of Laquinimod in expression and function of hypoxia-inducible factor-2αin osteoblasts.
METHODS: Mouse osteoblasts MC3T3-E1 (clone 14) were pretreated with Laquinimod at various concentrations(10-100μmol/L) before hypoxia in the presence or absence of specific proteasome inhibitors MG132 or N-acetyl-leucyl-leucyl-norleucine. Then, the media were pre-conditioned in 1% or 21% oxygen tension for 1 to 24 hours.
RESULTS AND CONCLUSION: Under hypoxia, the expression of hypoxia-inducible factor-2α in osteoblasts was increased remarkably, and Laquinimod could inhibit the expression of hypoxia-inducible factor-2α and its target genes in mouse MC3T3-E1 cels. Mechanisticaly, Laquinimod promoted hypoxia-inducible factor-2α degradation in a proteasome-dependent but von Hippel-Lindau protein-independent manner. Importantly, we found that Laquinimod disrupted the interaction between hypoxia-inducible factor-2α and its chaperone heat shock protein 90, but promoted the interaction between hypoxia-inducible factor-2α and the receptor of activated protein kinase C. These findings suggest that Laquinimod may promote the degradation of hypoxia-inducible factor-2α by affecting its folding and maturation. Laquinimod is a novel inhibitor of hypoxia-inducible factor-2α by changing its functional interaction with chaperone proteins heat shock protein 90 and receptor of activated protein kinase C.

Objective To investigate the clinical characteristics and associated risk factors for patients with mixed Candida/bacterial bloodstream infections (BSIs).Methods A retrospective study was conducted in the Second Affiliated hHospital of Zhejiang University School of Medicine from February 2012 to June 2015.The clinical data of cases was collected,and the clinical characteristics,the microbiology data and outcomes in patients with mixed Candida/bacterial BSIs confirmed by blood culture were compared with those with candidaemia.A Logistic regression analysis was performed to investigate the independent risk factors.Results A total of 136 candidaemia cases were analyzed including 40 cases (29.4％) of mixed Candida/boacterial BSIs and 96 cases of candidaemia.Among the 136 candidas strains,the proportion of non-albicans exceeded the albicans (50.7％ vs 49.3％),although the later was still the predominant one.There was no significant difference in the distribution of candidas strains between patients with mixed Candida/bacterial BSIs and patients with candidaemia.In patients with mixed Candida/bacterial BSIs,25 strains (61.0％) of gram-positive cocci and 16 strains (39.0％) of gram-negative bacilli were isolated.Compared with patients with candidaemia,patients with mixed Candida/bacterial BSIs needed longer period of antifungal therapy [12.0 (4.0-25.0)days vs 7.0 (3.0-13.5) days,P=0.027],but the crude 30-day and 90-day mortality did not differ between the two groups (40.0％ vs 32.3％;45.0％ vs 36.5％;both P＞0.05).Univariate analysis revealed that the prior hospital stay,ICU admission at the onset of candidaemia,blood transfusion,human albumin infusion,mechanical ventilation,linezolid use and high SOFA score were related with the occurrence of mixed Candida/bacterial BSIs (all P＜0.05).Multivariate analysis showed that only high SOFA score was the independent risk factor (P=0.003).Conclusions Gram-positive cocci were the predominant species in mixed Candida/bacterial BSIs.Compared with candidaemia,mixed Candida/bacterial BSIs needs a longer ICU stay,a longer hospital stay,and a prolonged antifungal therapy.High SOFA score is the independent risk factor for mixed Candida/ bacterial BSIs.

Objective:To investigate whether endoplasmic reticulum aminopeptidase 1 ( ERAP1) is a susceptible gene for pre-eclampsia (PE) and the possible mechanism in the pathogenesis. Methods:This retrospective study included 990 PE patients (case group) and 1 240 healthy pregnant women (control group) in six prefecture-level tertiary hospitals in Shandong Province, including the Affiliated Hospital of Qingdao University and Zaozhuang Maternal and Child Health Hospital, from September 2018 to April 2021. Peripheral blood were collected for DNA extraction. Single-nucleotide polymorphisms in the ERAP1 gene (rs30187, rs27044, and rs469783 loci) were analyzed by Taqman probe polymerase chain reaction (PCR). Two missense mutant plasmids, rs30187(c.1583A>G) and rs27044(c.2188C>G), were constructed by point mutation induction based on wild-type plasmids. Six groups (knock-down control, knock-down, over-expression control, over-expression, variant 1 and 2 groups) were set up in this study. After transfecting Htr8 cells with different transfection molecules, the expression of ERAP1 at mRNA and protein levels were detected. Besides, the effects of different transfections on cell function were detected using Transwell migration assay, Transwell invasion assay, cell scratch assay, and CCK-8 assay. Statistical analysis was performed using two independent samples t-test, rank sum test, and Chi-square test. Results:(1) There were significant differences in the genetic distribution of rs30187 (Genotype: χ2=29.25, Allele: χ2=4.68) and rs469783 (Genotype: χ2=7.01, Allele: χ2=6.45) as well as the genotype distribution of rs27044 ( χ2=28.95) between the case group and the control group (all P<0.05). Statistical analysis of the genetic model revealed that rs30187 and rs27044, both recessive models, were statistically different between the two groups with a higher frequency of CC genotypes in the case group ( χ2=20.82 and 19.97, both P<0.05), but a lower frequency in CC dominant gene pattern for rs469783 ( χ2=5.82, P=0.016). (2) Compared with the knock-down control group, the knock-down group showed significantly inhibited expression of ERAP1 (mRNA: 0.5±0.1 vs 1.0±0.0, t=7.49; protein: 0.4±0.1 vs 0.7±0.1, t=2.81; both P<0.05), reduced cell migration rate after 48 h of scratching [(16.5%±1.8%) vs (23.8%±2.4%), t=3.33, P=0.031] and decreased number of cells crossing Transwell chambers after 24 h of culture (423.7±21.3 vs 499.0±24.6, t=3.29, P=0.031). Compared with the over-expression group, variant 1 group and variant 2 group showed significantly inhibited expression of ERAP1 at mRNA (both P<0.001) and protein ( P=0.003 and 0.006) levels after transfection, decreased number of cells crossing Transwell chambers ( P=0.001 and 0.032) and down-regulated cell migration rate after 48 h of scratching [variant 1: P=0.004; variant 2: (21.1±4.6)% vs (28.3±1.1)%, t=2.10, P=0.099]. ERAP1 expression at both mRNA ( P<0.001) and protein ( P=0.008) levels, as well as cell proliferation ( P<0.001) and invasion ability ( P<0.001), were all enhanced in the over-expression group than those in the over-expression control group. Moreover, the migration rate of cells after 48 h of scratching ( P=0.002) and the number of cells crossing Transwell chambers after 24 h of culture ( P=0.001) were also increased. Conclusions:The rs30187, rs27044, and rs46978 on ERAP1 gene were all associated with PE susceptibility, with more carriers of the CC genotype in PE patients at rs30187 and rs27044 loci and more carriers of the CC genotype in healthy gravida at rs469783 locus. ERAP1 may be involved in the pathogenesis of PE by affecting the migratory and invasive ability of trophoblast cells.