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.

Objective To investigate the relationship between the changes of serum human surfactant pro-tein D(SP-D)and vascular cell adhesion molecule-1(sVCAM-1)levels and postoperative fracture healing and short-term prognosis in patients with traumatic rib fractures.Methods A total of 102 patients with traumatic rib fractures who were treated in Banan Hospital Affiliated to Chongqing Medical University from January 2020 to December 2021 were selected as the research objects.After 8 months of treatment,the healing status of the patients was analyzed and divided into non-healing group(21 cases)and healing group(81 cases).Ac-cording to the pulmonary contusion,the patients were divided into pulmonary contusion group(19 cases)and non-pulmonary contusion group(83 cases).The serum levels of SP-D and sVCAM-1 were compared between the healing group and the non-healing group,and between the pulmonary contusion group and the non-pulmo-nary contusion group.The relationship between the changes of serum SP-D and sVCAM-1 levels and postop-erative fracture healing and short-term prognosis in patients with traumatic rib fractures were studied.Results The levels of SP-D and sVCAM-1 in the healing group were lower than those in the non-healing group(P＜0.05).The levels of SP-D and sVCAM-1 in the non-pulmonary contusion group were lower than those in the pulmonary contusion group(P＜0.05).Serum SP-D and sVCAM-1 levels were independent risk factors for postoperative fracture healing and short-term prognosis.Conclusion The changes of serum SP-D and sVCAM-1 levels in patients with traumatic rib fractures are related to fracture healing and short-term prognosis,which can be used as an important reference for prognosis evaluation.

Objective:To investigate the effects of three-dimensional computed tomography angiography (3D-CTA)-assisted free medial sural artery perforator flap in repairing foot wounds.Methods:A retrospective observational study was conducted. From May 2018 to August 2021, 18 patients with foot soft tissue defects who met the inclusion criteria were admitted to the Department of Spine and Trauma Orthopedics of the Yidu Central Hospital of Weifang, including 13 males and 5 females, aged 19 to 55 years, with a wound area of 4.0 cm×3.0 cm-9.0 cm×8.0 cm at admission. Before the operation, CT scanner was used to scan the area from the supracondylar femur to the middle segment of the fibula of patients, and the obtained data were extracted into the Mimics16.0 software and analyzed to determine the pre-selected perforator, and then the image data of the pre-selected perforator side were analyzed further, and the body surface projection position of the perforating point of the medial sural artery in the calf region was marked. Based on the above examination, the flap was designed and cut according to the shape and area of the patient's foot tissue defect, and the area of flaps ranged from 5.0 cm×4.0 cm to 10.0 cm×9.0 cm. The donor sites were sutured directly or covered by skin grafting. The type of perforator, the diameters of perforator at the beginning and outlet point, and the location of the outlet point of perforator of the medial sural artery were observed under 3D-CTA examination before operation and compared to see if they were consistent with the observation under intraoperative condition. The survival of the flaps after operation was recorded. During follow-up, the satisfaction of patients with the wound repair effects, the sensory recovery of the recipient flaps, the healing of the donor wound, and whether there were complications affecting limb functions were recorded. Data were statistically analyzed with Kappa consistency test and equivalence test, and the 95% confidence intervals of measurement difference of perforator diameter and outlet point position of perforator were -0.50-0.50 mm and -2.0-2.0 cm, respectively.Results:The types of medial sural artery perforators observed during operation were type Ⅰ in 3 cases, type ⅡA in 6 cases, type ⅡB in 8 cases, and type Ⅲ in 1 case, which was consistent with the results of 3D-CTA before operation (Kappa=1.00, P<0.05). The blood vessel diameter detected by 3D-CTA before operation at the beginning of perforator of medial sural artery was (1.81±0.39) mm, and the blood vessel diameter at the outlet point of the perforator was (0.83±0.21) mm, which were close to the actual intraoperative measurement of (1.83±0.43) and (0.86±0.22) mm, respectively; equivalence test showed that the 95% confidence intervals of the measurement differences of diameter of medial sural artery perforator at beginning and outlet point were -0.18-0.22 and -0.08-0.14 mm, respectively, with both P values <0.05. The preoperative 3D-CTA detected that the perforating position at the deep fascia of the perforator of the medial sural artery, namely the vertical distance with the popliteal fold was (12.2±1.4) cm, and the horizontal distance with the posterior midline was (2.6±0.7) cm, which were respectively close to the actual intraoperative measurement of (12.4±1.4) and (2.6±0.7) cm; equivalence test showed that the 95% confidence intervals of the measurement differences in the vertical distance with the popliteal fold and the horizontal distance with the posterior midline of the outlet point of medial sural artery perforator were -1.06-1.26 and -0.46-0.66 cm, respectively, with both P values <0.05. After surgery, all flaps of 18 patients survived without vascular crisis. After 1 year of follow-up, the satisfaction degree of 16 patients was excellent and 2 patients was good with the wound repair effects, with a satisfaction ratio of 16/18; the sensory recovery of flap was evaluated as S 3 in 11 cases and S 2 in 7 cases; the donor wounds healed well without obvious scar or contracture, with no effect on limb joint functions. Conclusions:The medial sural artery perforator flap achieved good results in repairing foot wound with high degree of patient satisfaction. Preoperative application of 3D-CTA can realize the standardization, systematization, and visualization of artery perforator flap.

Objective:To investigate the causal association between immune cell and different types of sepsis by using Mendelian randomization (MR) method, and to find the immune cell phenotypes causally associated with sepsis.Methods:Summary data for various circulating immune cell phenotypes were obtained from the GWAS catalog (GCST90001391-GCST90002121). Sepsis data were sourced from the UK Biobank database. Single nucleotide polymorphisms (SNP) were used as instrumental variables. The correlation threshold of P < 5×10 -6 was used to identify the strongly correlated instrumental variables, and the code was used to remove the linkage disequilibrium and the instrumental variables with F-value < 10. Inverse variance weighting (IVW) was used as the main research method to evaluate the stability and reliability of the results, including Cochran's Q test, MR-Egger regression and Leave one out. Reverse MR analysis was performed based on the immunophenotypic results of the removal of horizontal pleiotropy, and the immune cell phenotype with one-way causal association was obtained. Odds ratio ( OR) and 95% confidence interval (95% CI) were used to represent the effect value of the results. Results:CD16 on CD14 -CD16 + monocyte had horizontal pleiotropy in sepsis ( OR = 0.965?4, 95% CI was 0.933?5-0.998?3, P = 0.039?6). There were five immunophenotypes that had reverse causal associations with the types associated with sepsis. After excluding immune cell phenotypes with horizontal pleiotropy and reverse causation, a total of 42 immune cell phenotypes with sepsis, 36 immune cell phenotypes with sepsis (28-day death in critical care), 32 immune cell phenotypes with sepsis (critical care), 44 immune cell phenotypes with sepsis (28-day death), and 30 immune cell phenotypes had potential causal associations with sepsis (under 75 years old). After false discovery rate (FDR) correction, the correlations between BAFF-R on IgD - CD38br and sepsis (28-day death) were negative and strong ( OR = 0.737?8, 95% CI was 0.635?9-0.856?0, P = 6.05×10 -5, PFDR = 0.044?2). Conclusion:A variety of immune cell phenotypes may have a protective effect on sepsis, especially BAFF-R on IgD - CD38br expression is negatively correlated with sepsis (28-day death), which provides a new idea for immune modulation therapy in sepsis.