Immunotherapy, particularly lung cancer vaccine therapy, has advantages of less side effects and low costs over classi-cal therapies of lung cancer, such as surgery, radiotherapy, and chemotherapy, as well as the relatively new molecular targeting therapy. PhaseⅢclinical trial for many kinds of non-small cell lung cancer (NSCLC) vaccines is ongoing based on deeper understanding of im-mune system and the expression of tumor antigens. This review summarizes the development of NSCLC vaccines.

Objective To investigate the effect of valproic acid (VPA) on NKG2D-ligand expression in ARK,OPM2 human myeloma cell lines and their sensitization to natural killer (NK) cell-mediated Killing.Methods Different concentrations of VPA from 0-5.0 mmol/L were used to treat ARK,OPM2 cells respectively,then the cell viabilities were tested by flow cytometry (FCM).Real-time quantitative-PCR and FCM were used to detect the changes in mRNA,protein levels of NKG2D-ligand respectively in the two cell lines treated with 1 mmol/L VPA for 48 hours.The calcein-release-assay (CARE-LASS) was carried out to detect cytotoxic changes of NK cells against mydoma cells after VPA treatment.Results VPA induced the expression of MICA/B,ULBP2 (P ＜ 0.05) and in turn enhanced the NK cytotoxicity on myeloma cells.The enhancing effect of VPA was blocked by NK cells pretreated with anti-NKG2D mAb (P ＜ 0.05).The primary mechanism of NK cell killing of myeloma cells was perforin/granzyme-mediated.Conclusion VPA can induce the expression of MICA/B,ULBP2 in ARK,OPM2 cells,thereby enhancing the cytotoxicity against myeloma cells,which implies a new mechanism of anticancer approach and may be a new approach in myeloma immunotherapy.

Objective To investigate the association of the polymorphism of rs3750344 and rs1435252 of G-protein family GABABR2 gene with obesity in population of Uygur and Han. Methods 785 Uygur subjects from Xinjiang and 425 Han subjects from Jinan Maternity and Child Care Hospital were recruited by epidemiology survey. Exposure indicators such as body mass index (BMI), total cholesterol (Tch), triglyceride (TG), fasting glucose (Glu) concentration were measured. Two single nucleotide polymorphisms (SNPs) of rs3750344 and rs1435252 of GABABR2 gene were typed with Taqman. Linkage disequilibrium and haplotype were analysed with Haploview software. Results The frequency of rs1435252 was significantly different in AA carries of Uygur subjects between overweight group (12.5%) and normal weight group (6.6%), the subject with AA genotype significantly increased risk of overweight (OR=1.43, 95% CI: 1.06~1.91). The frequency of rs1435252 was significantly different in A alleles carries of Han subjects between obesity group (80.0%) and normal weight group (65.2%), the subject with A alleles significantly increased risk of obesity (OR=2.13, 95%CI: 1.18~3.86). The C alleles of rs3750344 significantly decreased risk of obesity (OR=0.69, 95%CI: 0.49~0.97) in Uygur, but the significance disappeared after controlling for covariates of age and gender. Conclusion The rs1435252 A allele of GABABR2 gene is a risk factor for overweight or obesity in population of Uygur and Han.

Objective To compare the effects of propofol combined with fentanyl or dezocine on painless abortion and the influence on body movement.Methods From July 2016 to May 2017,240 patients with voluntary painless abortion who aged 19-45 years old in the Second People's Hospital of Linhai,were randomly divided into 3 groups according to the digital table ,with 80 cases in each group.D group was given propofol and dezocine ;F group was given propofol combined with fentanyl ;C group was the control group and was treated with propofol intravenous anesthesia,the three groups were given propofol added according to the specific situation.The operative time,recovery time and the total amount of propofol were compared among the three groups ;and the pain visual analogue scale (VAS) at 0min,15min,30min,1h,3h were comparedamong the three groups ;The incidence of respiratory depression and other adverse reactions were statistically analyzed in three groups.Results The operation time,recovery time,the total dosage of propofol in D group were (4.5 ±0.7)min,(1.2 ±0.3)min and (136.8 ±14.5)mg,respectively, which in F group were (4.6 ±0.8)min,(1.3 ±0.2)min and (139.6 ±12.1)mg,respectively,there were no statisti-cally significant differences between the two groups (all P＞0.05).The recovery time and total dosage of propofol in D group and F group were lower than those of C group [(2.4 ±0.6) min,(168.7 ±18.9) mg](t＝25.298,27.287, 11.977,27.287,all P＜0.05).The VAS scores at postoperative 0min,15min,30min,1h,3h in D group were lower than those in F group and group (t＝34.785,25.044,25.043,22.349,28.622,48.809,42.278,40.000,42.278, 40.000,all P＜0.05).The VAS scores at postoperative 0min,15min,30min,1h in F group were lower than those of C group(t＝36.978,24.406,19.846,24.406,all P ＜0.05).The incidence rates of nausea,sedentary,respiratory depression,hypotension in D group were 1.3%(1case),2.5%(2cases),1.3%(1case),0.0%(0cases), resperctively,which in F group were 0.0%(0cases),3.8%(3cases),3.8%(3cases),2.5%(2cases),which in D group,F group were lower than those in C group [6.3%(5cases),16.3%(13cases),11.3%(9cases),15.0%(12cases)](χ2＝3.925,3.657,3.925,3.657,5.889,3.152,3.152,3.657,all P＜0.05).Conclusion Propofol combined with dezocine and fentanyl used in painless abortion have good effect ,and the body movement is less ,but propofol combined with dezocine has less postoperative pain degree.

Objective:To assess the validity and reliability of the depression and somatic symptoms scale among patients with coronary heart disease.Methods:Totally 246 patients with coronary heart disease were assessed with depression and somatic symptoms scale (DSSS), Hamilton depression rating scale for depression (HAMD) and patients’ health questionnaire depression scale-9 item (PHQ-9). The structural validity was evaluated with exploratory factor analysis and confirmatory factor analysis. The validity as a screening tool was evaluated with the gold standard diagnosed by psychiatrists who were trained with the mini international neuropsychological interview (MINI) according to ICD-10. Receiver operating characteristic (ROC) curve was used to identify cutoff scores for depression. Cronbach α coefficient was used to evaluate the internal consistency.Results:Exploratory factor analysis yielded two factors: depression factor and somatic factor, and the cumulative variance was 51.8%. The fitting indexes of confirmatory factor analysis were as follows: χ2/ df=3.636, RMR=0.077, RMSEA=0.104, IFI=0.804, TLI=0.781, CFI=0.802. The intraclass correlation coefficient of DSSS and HAMD was 0.54. The area under ROC curve (AUC) was 0.828, and the best boundary value was 17 points (sensitivity and specificity: 81% and 75%, respectively). The total scores and subscale scores for internal consistency of DSSS were higher in the depression group than those in the non-depression group ( P<0.01). Cronbach α coefficient for internal consistency of DSSS was 0.917. Conclusion:The DSSS has good validity and reliability among patients with coronary heart disease for screening depression, and can be used to screen depression among patients with coronary heart disease in general hospital.

Porcine interferon-alpha (pIFN-alpha) fermentative production by recombinant Pichia pastoris was carried out in a 10-L bioreactor to study its metabolism changes and effects on fermentation under different inducing strategies, by analyzing the change patterns of the corresponding metabolism and energy regeneration. The results show that the specific activities of alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD) and formate dehydrogenase (FDH) largely increased when reducing temperature from 30 degrees C to 20 degrees C under pure methanol induction, leading significant enhancements in methanol metabolism, formaldehyde dissimilatory energy metabolism and pIFN-alpha antiviral activity. The highest pIFN-alpha antiviral activity reached 1.4 x 10(6) IU/mL, which was about 10-folds of that obtained under 30 degrees C induction. Using methanol/sorbitol co-feeding strategy at 30 degrees C, the major energy metabolism energizing pIFN-alpha synthesis shifted from formaldehyde dissimilatory energy metabolism pathway to TCA cycle, formaldehyde dissimilatory pathway was weakened and accumulation of toxic intermediate metabolite-formaldehyde was relieved, and methanol flux distribution towards to pIFN-alpha synthesis was enhanced. Under this condition, the highest pIFN-alpha antiviral activity reached 1.8 x 10(7) IU/mL which was about 100-folds of that obtained under pure methanol induction at 30 degrees C. More important, enhanced pIFN-alpha production with methanol/sorbitol co-feeding strategy could be implemented under mild conditions, which greatly reduced the fermentation costs and improved the entire fermentation performance.
Animals ; Energy Metabolism ; Fermentation ; Interferon-alpha ; biosynthesis ; genetics ; Methanol ; pharmacology ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Sorbitol ; pharmacology ; Swine

Objective:To observe the feasibility of evaluating right ventricular (RV) function by the method based on left ventricle (LV) pressure-strain ring (PSL) technique in patients with systemic lupus erythematosus (SLE), and to evaluate the efficacy of non-invasive PSL in the diagnosis of dysfunction of both LV and RV.Methods:Thirty-nine patients were enrolled with SLE who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from March 2020 to September 2021 and 57 sex- and age-matched healthy controls underwent assessment by conventional echocardiography, two-dimensional speckle tracking imaging (2D-STI) and myocardial work (MW). The echocardiographic parameters were compared between the groups. The correlations between RVMW parameters and conventional echocardiographic parameters, and between MW parameters and SLEDAI-2K score were analyzed by Spearman correlation analysis.Results:①The two groups did not show any difference at the conventional echocardiographic parameters of the LV systolic function ( P>0.05). In the SLE group, tricuspid regurgitation maximal velocity (TR V max) and right ventricular index of myocardial performance (RIMP) increased, tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular S′ (S′ tv) decreased (all P<0.05), and others did not show statistical difference (all P>0.05). ②The 2D-STI parameters: There were no significant differences in left ventricular global longitudinal strain (LV GLS) ( P>0.05), however RVGLS decreased ( P<0.05). ③The MW parameters of LV and RV: including global constructive work (GCW), global work index (GWI), global wasted work (GWW), and global work efficiency (GWE). In SLE group, LV GWE, RV GWE decreased and LV GWW, RV GWW increased ( P<0.05), others were no significant differences ( P>0.05). ④The correlation analysis: RV GWI positively correlated with TR V max ( rs=0.481). RV GCW positively correlated with TR V max ( rs=0.587). RV GWW positively correlated with right atrial area (RAA) and TR V max ( rs=0.429, 0.610), negatively correlated with S′ tv ( rs=-0.342). RV GWE positively correlated with S′ tv ( rs=0.326) and negatively correlated with RAA ( rs=-0.462) (all P<0.05). SLEDAI-2K score was negatively correlated with LV GLS ( rs=-0.333) and LV GWI ( rs=-0.326) ( P<0.05). Conclusions:The study has shown the impaired systolic function of both LV and RV in patients with SLE. PSL technique, especially RVMV based on LV PSL technique might emerged as a novel measure to evaluate systolic dysfunction in SLE patients.

Objective To explore the clinical feature,treatment and prognosis of incidental prostate cancer(IPC) after transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH).Methods From January 2009 to April 2017,24 cases undergoing TURP for benign prostatic hyperplasia and being diagnosed with prostate cancer(T1a-T1b) was retrospectivey analysed,who aged from 62 to 84 years (mean 71.8 years).Digital rectal examination (DRE) showed prostate medium texture,smooth surface,and no nodules.Ultrasound presented no low echo nodules in the prostate.Prostate volumes were 19.2-93.4 ml,with median of 40.1 ml.PSA were 1.81-9.11 ng/ml,with median of 4.12 ng/ml.The patients with PSA between 6-10 ng/ml accepted prostate biopsy,and pathological results were negative.Results The The pathology of TURP specimens in 24 cases were diagnosed prostate cancer (21 cases of T1a,3 cases of T1b).According to the new WHO/ISUP classification group,there were 18 cases of hierarchical group 1,3 cases of hierarchical group 2,1 case of hierarchical group 3,2 cases in hierarchical group 4.All patients were treated with hormonal therapy,and 7 cases (5 cases of hierarchical group 1,and 2 cases of hierarchical group 2) underwent laparoscopic radical prostatectomy (LRP) after 3 months of hormonal therapy.The specimens of prostatectomy were examined by whole-mount serial,showing 3 cases of prostate cancer (T1a) with negative margin,and 4 cases of benign prostate cells.They were followed up for 5-82 months with median of 43.5 months.No biological progression or tumor progression was found,and,1 case died of colon cancer after 26 months of follow-up.The patients' age and Gleason score of stage T1b were higher than that of stage T1a.Prostate volume and preoperative PSA had no statistically significant difference between the two stages.Conclusions The patients' age and Gleason score of stage T1b were higher than that of stage T1b.The proportion of residual tumor following TURP was high.The prognosis of incidental prostate cancer was good by hormonal therapy or radical prostatectomy.

Objective To establish the chronic low flow myocardial hibernation animal model in pigs, and to assess the diagnostic value for myocardial hibernation by using various imaging methods. Methods A total of 13 miniswine (30-40 kg) were used. All animals underwent general anesthesia and orotracheal intubation while the animals were mechanically ventilated. Under sterile conditions, left ventriculography and coronary angiography were performed by introduction of catheter into the right femoral artery. Further, a left anterolateral thoracotomy was performed in the third intercostal space. The proximal LCX was dissected free to allow placement of an ameroid constrictor. More than 1 month later, left ventriculography and coronary angiography were performed again, followed by cine MRI at rest and during stress with low dose of dobutamine (5 ?g?kg -1 ?min -1 ), respectively. Traditional and/or breath hold cine MRI were used to evaluate regional left ventricular wall motion, corresponding to basal, midventricular and apical short axis tomograms. Regional wall motion score index (WMSI) was calculated. At the same time 99m Tc MIBI myocardial SPECT was performed at rest and during nitroglycerin administration, respectively. All animals were finally sacrificed for pathological examination. Triphenyl tetrazolium chloride (TTC) staining was used to assess the myocardial infarction. Electron microscopy was used to identify myocardial cellular changes characteristic of hibernating myocardium. Results Three pigs died during surgery or within two weeks after surgery. One pig died of anesthesia during SPECT examination, 1 pig suffered from aneurysm, and another one pig showed negative findings. The other 7 pigs were found with hypokinetic ( n =4) or akinetic ( n =3) myocardial regions related to stenosed LCX (70%-99%). Resting cine MRI demonstrated decreased regional motion of the lateral and posteroinferior walls (ischemic regions) of the left ventricle ( n =7), compared with the nonischemic anteroseptal regions; but the low dose dobutamine (5 ?g?kg -1 ?min -1 ) could recover those hypokinetic or akinetic myocardial regions, characteristic of hibernating myocardium. Resting 99m Tc MIBI myocardial SPECT ( n =6) showed a fixed perfusion defect on the corresponding ischemic areas, which became reversible on the nitrate augmented myocardial perfusion imaging. It also indicated myocardial viability presented at the ischemic areas. TTC staining revealed patchy infarction of the area at risk localized to the endocardial surface ( n =3), and no myocardial infarction ( n =4). Electron microscopy of sections from the hibernating regions revealed loss of contractile materials, increased numbers of small mitochondria, and glycogen accumulation within viable cardiomyocytes, which had been described as hallmarks of hibernating myocardium. Conclusion Chronic low flow myocardial hibernation can be reproduced in an animal model during progressive coronary stenosis caused by ameroid constrictor.

Nowadays,the application of ultrasound is not only used in clinical imaging,but also extended in the study of drug delivery.Diagnostic ultrasound combined with microbubbles can effectively open the biological barriers,which can enhance the targeted delivery of drugs and be beneficial to the combination of ultrasound and disease treatment.This review summarizes the biological effects of ultrasound,the characteristics of ultrasound microbubbles and the potential ability that solving the biological barrier problems in cancer therapy by using ultrasound targeted microbubble destruction,hoping to provide some reference for the further development of therapeutic ultrasound as a safe and effective drug targeted delivery strategy.