AIM:To investigate the effect of a disintegrin and metalloproteinase(ADAM)domain-like decy-sin 1(ADAMDEC1)knockdown on the proliferation,migration and invasion of pancreatic carcinoma cells.METHODS:Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online da-tabases.Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcino-ma cell lines(MIA PaCa-2 and PANC-1)and pancreatic ductal cell line(hTERT-HPNE).The effects of ADAMDEC1 knockdown on cell proliferation,migration and invasion were evaluated using CCK-8,colony formation,wound-healing and Transwell assays.Additionally,Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers,as well as Wnt/β-catenin signaling pathway-related proteins in pancre-atic carcinoma cells.Furthermore,a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling path-way agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migra-tion.RESULTS:(1)ADAMDEC1 was highly expressed in pancreatic carcinoma cells.(2)Knockdown of ADAMDEC1 led to a significant reduction in the proliferation,migration and invasion of pancreatic carcinoma cells.(3)Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9,N-cadherin and vimentin proteins,alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related pro-teins.(4)Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation,migration,and invasion.CONCLUSION:ADAMDEC1 is highly expressed in pancreatic carcinoma.Targeted silencing of ADAMDEC1 has the potential to inhibit the prolifera-tion,migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway.

Objective To investigate the predictive value of combined plasma gluconic acid(GA),fumaric acid(FA),and pseudouridine levels at admission for acute kidney injury(AKI)in elderly patients with acute myocardial infarction(AMI).Methods A total of 78 elderly AMI patients transferred from Emergency Department to Coronary Care Unit in Fuwai Hospital during Decem-ber 2021 and July 2022 were enrolled in this prospective study.They were divided into AKI group(40 cases)and non-AKI group(38 cases)according to whether they developed AKI during hospi-talization.Plasma levels of GA,FA and pseudouridine were quantitatively detected with liquid chromatography-tandem mass spectrometry.ROC curve was plotted to assess the predictive value of these three plasma metabolites for AKI in AMI patients.Multivariate logistic regression analy-sis was applied to analyze the clinical risk factors for AKI.Results There were no statistical differences in the plasma levels of GA,FA and pseudouridine between the AKI group and the non-AKI group(P＞0.05).ROC curve analysis revealed that the plasma levels of the three indicators had no predictive value for the development of AKI in elderly AMI patients(AUC=0.576,95％CI:0.449-0.704,P=0.246;AUC=0.595,95％CI:0.467--0.721,P=0.154;AUC=0.563,95％CI:0.435-0.692,P=0.337).Multivariate logistic regression analysis revealed that left ventricu-lar ejection fraction(LVEF)was an independent predictor for AKI development in elderly AMI patients(OR=0.923,95％CI:0.870-0.978,P=0.007).Conclusion Plasma GA,FA and pseud-ouridine cannot predict the development of AKI in elderly AMI patients,while,LVEF is an inde-pendent predictor for the development.

Microglia are the main immune cells of the central nervous system and an important part of neurovascular unit (NVU). Together with endothelial cells, pericytes, vascular smooth muscle cells, astrocytes and neurons, microglia form NVU. They play an important role in maintaining the integrity of blood-brain barrier (BBB), regulating cerebral blood flow (CBF) and maintaining basic brain function. Neuroinflammation mediated by microglia can lead to cerebral circulation disorder, which is related to the occurrence and development of a variety of nervous system diseases. This paper reviews the characteristics and subtypes of microglia, the relations of microglia with brain microinflammation and cerebral microcirculation, and the correlation of microglia with central nervous system diseases.

Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles (d-SN38@NPs/iRGD). Upon intravenous injection, d-SN38@NPs with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor.

Objective To investigate the effect of endoplasmic reticulum stress on sensitivity of glioma cell line U87 to temozolomide (TMZ) and underlying mechanism.Methods (1) Glioma U87 cells were routinely cultured for 24 h in vitro;different concentrations of TMZ (0,12.5,25,50,100 μmol/L) were added to intervene the cell proliferation of U87 cells for 24 h;MTT method was used to detect the cellular proliferation inhibition rate,and half maximal inhibitory concentration (IC50) of TMZ was calculated;tunicamycin (TM) treatment (0,2,4,8 μmol/L) was given to the cells for 6 h,and then,50 μmol/L TMZ was given for 24 h,and cellular proliferation inhibition rate of U87 was detect by MTT method.(2) U87 cells were randomly divided into control group,TM group,TMZ group and TM+TMZ group;pretreatment of TM for 6 h was given to cells from TM group and TM+TMZ group;and 50 μmol/L TMZ was given to cells from TMZ group and TM+TMZ group;same amount of medium was given to cells from control group;24 h after treatment,the apoptotic rate was examined by flow cytometry;Westem blotting was used to detect the protein expressions of caspase-3,B-cell lymphoma 2 associated X protein (Bax),O-6-methlguanine-DNA methyltransferase (MGMT),glucose-regulated protein 78 (GRP78),and inositol-requiring enzyme 1 (IRE-l).Results (1) MTT showed that IC50 of TMZ was 50 μmol/L.As compared with that of 0 μmol/L TM+50 μmol/L TMZ group or 2 μmol/L TM+50 μmol/L TMZ group,the cellular proliferation inhibition rate of 4 μmol/L TM+50 μmol/L TMZ group and 8 μmol/L TM+50 μmol/L TMZ group was significantly decreased (P＜0.05).(2) As compared with TMZ group,TM+TMZ group had significantly decreased apoptotic rate (46.98％±4.79％ vs.35.74％ ±4.09％),significantly decreased caspase-3 and Bax protein expressions,and significantly increased MGMT,GRP78 and IRE-1 protein expressions (P＜0.05).Conclusion Endoplasmic reticulum stress can increase the resistance gene MGMT expression,decrease the chemotherapy sensitivity to TMZ,and induce chemoresistance ofglioma cell line U87.

Objective To investigate the risk factors of delirium in elderly patients with intertrochanteric fracture after internal fixation.Methods The data of 160 patients with intertrochanteric fractures who received internal fixation in our hospital from January 2012 to July 2014 were analyzed retrospectively.The risk factors such as age,sex,preoperative complications,preoperative cognitive function,fracture location,operation mode,operation time,anesthesia method,hospital-to-operation time and intraoperative blood loss were summarized.Results The incidence of postoperative delirium was 28.15％ in postoperative elderly patients with intertrochanteric fractures.Univariate analysis showed that delirium had correlated with preoperative cognitive impairment,preoperative preparation time,serum sodium,fentanyl,atrial fibrillation,anesthesia method,operation time and perioperative blood loss (P ＜ 0.05).The multivariate Logistic regression analysis showed that the independent risk factors of postoperative delirium were preoperative cognitive dysfunction,operative time more than 2 hours and preoperative preparation time more than 4 days.Conclusion The occurrence of postoperative delirium was associated with anesthesia method,cognitive deficits,preoperative preparation time and perioperative blood loss.The anesthesia method which had less effect on the whole body condition and less time of operation preparation can decrease the occurrence of postoperative delirium in a certain extent,which is conducive to improving the prognosis.

Objective To investigate the effects and mechanisms of valproic acid on brain edema,neurobehavioral outcome and inflammatory response after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Fifty-four SD male rats,weighting 220-250 g,were randomly divided into 3 groups (n =18):sham operation group (group sham),traumatic brain injury group (group TBI) and valproic acid treatment group (group TBI + VPA).Experimental rats were treated with valproic acid (300 mg/kg,twice daily) by intraperitoneal injection.Rat behavioral outcomes were measured by modified neurologic severity score (mNSS) tests at day 1,3,and 7 after TBI.Brain water content was measured with wet-dry weight method.The blood cells infiltration into cerebral cortex were tested with immunohistochemistry staining against ED-1 for macrophage.Inflammatory cytokines (INF-γ,tumor necrosis factor-α,interleukin-6) were measured by Western blotting.The statistical analysis were performed by ANOVA and chi-square tests using the statistical software program SPSS 13.0.Results Compared with the Sham group,the levels of brain edema,mNSS and macrophage cell infiltration were significantly increased after TBI (all P =0.00).The expressions of inflammatory cytokines were also increased significantly (all P =0.00).Compared with the TBI group,TBI + VAP group had significantly lower brain water content[3day:(80.12 ±0.59)％ vs.(82.14 ±0.67)％,P=0.04;7day:(74.74 ±0.72)％ vs.(77.93 ±0.48)％,P=0.01],and mNSS scores [3 day:(10.53 ±0.32) vs.(11.74 ±0.48),P =0.02;7 day:(7.97 ± 0.32) vs.(10.73 ± 0.42),P =0.01].VPA suppressed macrophage cell infiltration into cerebral cortex [(36.44 ± 0.72) ％ vs.(25.93 ± 0.48) ％ P =0.00].Meanwhile,VPA inhibited the expressions of inflammatory cytokines (INF-γ,TNF-α,IL-6) (P ＜ 0.05).Conclusions Treatment with VPA markedly reduced brain edema and improved neurological outcomes after TBI,possibly mediated by inhibited TBI-induced cerebral inflammatory responses and macrophage cell infiltrating into cerebral cortex.

Objective:To explore the effect of oxycontin combined with gabapentin on the clinical cure and immunity for patients with neuropathic cancer pain.Methods:80 patients with neuropathic cancer pain were enrolled in our hospital from June to 2016 July,of which patients divided into two groups randomly,Group A(n=40) accepted oxycontin treatment,and Group B (n=40) adopted gabapentin based on the patients in Group A.The VAS score and curative effect of the patients were compared between two groups;The quality of life of all patients were evaluated post-treatment,and the change of immunity indexes were compared and analyzed.Results:The VAS score of all patients was decreased significantly compared with pre-treatment (P＜0.05),and the score of Group B was lower than those patients in Group A (P＜0.05);The total remission rate of Group B was significantly higher than those of Group A (P＜0.05);after treatment,the score of appetite,emotion,sleep,daily activities,social communications of all patients decreased significantly compared with pre-treatment (P＜0.05),and the change of Group B was decrease significantly higher than those patients in Group A (P＜0.05);the immune index of two groups was significantly increased (P＜0.05),and the level of the indexes including IgG,IgA,IgM,CD4+,CD4+/CD8+ and circulating immune complex (CIC) increased compared with pre-treatment remarkably (P＜0.05),and which change in Group B was significantly higher than Group A (P＜0.05).Conclusions:Oxycontin combined with gabapentin for patients with neuropathic cancer pain deserved popularization in clinical,and which not only possessed well clinical effect,but also increased the quality of life.

OBJECTIVETo study the clinical characteristics, antibiotics sensitivity, outcome and risk factors of neonatal septicemia caused by Candida haemulonii.

METHODA retrospective analysis was performed on clinical characteristics and antibiotics sensitivity after 8 cases of neonatal septicemia caused by Candida haemulonii were identified; each of these patients had at least one positive result of bacterial culture for Candida haemulonii.

RESULTThe 8 cases born at gestational age of 178-260 d, weighing 835-2 055 g, developed the infection from May to July at 10-34 d after hospitalization. Among the 8 patients, 7 were cured, 1 died during hospitalization after the treatments were given up because of serious complications. The 8 patients with septicemia caused by Candida haemulonii had similar clinical chariacteristics to those of other neonatal candidemia, such as apnea, fever, abdominal distension, jaundice etc. They had abnormal auxiliary examination with increased C-reactive protein (CRP), declined platelet (PLT) count to different degrees. All of the 8 patients had peripherally inserted central catheter (PICC) and broad-spectrum antibiotics were applied. C. haemulonii as an emergent fungal pathogen had varying degrees of resistance to fluconazole, amphotericin B, itraconazole, or ketone, but was susceptible to voriconazole.

CONCLUSIONThe characteristics of neonatal septicemia caused by Candida haemulonii were similar to those caused by other candida, and the main risk factors are the low birth weight, PICC, and usage of broad-spectrum antibiotics. It mainly occurred in May to July which is hot and humid season.

Amphotericin B ; Anti-Bacterial Agents ; Antifungal Agents ; C-Reactive Protein ; Candida ; Candidiasis ; Fluconazole ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; Intensive Care Units, Neonatal ; Microbial Sensitivity Tests ; Retrospective Studies ; Sepsis

Objective To study the change of audiological characteristics of neonate with severe hyperbilirubi‐nemia need to be exchanged transfusion ,and to explore the correlation between the peak concentrations of serum to‐tal bilirubin and hearing loss .Methods A total of 130 cases of neonate diagnosed with severe hyperbilirubinemia need to be exchanged transfusion were included in this study .Hearing tests of auditory brainstem response (ABR) , distortion product otoacoustic emission (DPOAE) and acoustic immittance were administered to these neonates and they were followed up three months old .They were divided into the normal group ,the mild - moderate group and the severe - extreme group according to the hearing tests results of three months .The peak concentrations of ser‐um total bilirubin and hearing condition among the three groups were analyzed .Results There were 85 neonates with normal hearing (65 .38% ,85/130) ,45 with hearing loss (33 .85% ,45/130 .For 88 ears ,there were 2 cases of single ear and 43 cases of both ears) ,including 11 cases of mild - moderate group (22 ears ,24 .44% ,11/45) and 34 cases with severe - extreme group (66 ears ,75 .56% ,34/45) .There were 16 neonates (32 ears) met the crite‐rion of auditory neuropathy (12 .31% ,16/130) .The difference of the peak concentrations of serum total bilirubin a‐mong the three groups was statistically significant (F=16 .525 ,P=16 .525) .And positive correlation was observed between ABR threshold and peak serum total bilirubin concentration (r=0 .584 ,P<0 .001) .Conclusion The ma‐jor feature of the neonate with severe hyperbilirubinemia need to be exchanged transfusion was extremely severe sen‐sorineural hearing loss in both ears ;and the higher probability of serious hearing loss with the higher peak concen‐trations of serum total bilirubin .