Personalized neoantigen vaccines,a cutting-edge technology in cancer immunotherapy,have garnered significant attention in recent years.Neoantigens are unique antigens produced by tumor-specific mutations,capable of being recognized by the immune system and eliciting a specific anti-tumor immune response.This review summarizes the current state of research on neoantigen vaccines,including the mechanisms of neoantigen generation and relatively screening methods,vaccine design and production,preclinical and clinical research progress,as well as the current challenges and future development trends.We present the potential of neoantigen vaccines in personalized treatment and their significant role in improving the survival rates and quality of life of cancer patients.Additionally,this review highlights the key issues in current research and proposes potential solutions,providing a reference for future studies.

Objective:To examine the effects of liraglutide on the transforming growth factor-β1(TGF-β1)/Smads signaling pathway in renal tissues of elderly rats with type 2 diabetes mellitus(T2DM)and to explore the underlying mechanisms.Methods:A total of 75 healthy elderly male Sprague-Dawley rats aged 20 months and weighing(500±100)g were divided into the normal control group(Group N, n=25)and the model group( n=50)by using a random number table.Rats in the model group were given high-glucose and high-fat diets for 8 weeks and then were injected with a single dose(30 mg/kg)of 1% streptozotocin into the abdominal cavity.Forty-eight rats in the model group were successfully molded and were divided into the T2DM group(Group D, n=24)and the intervention group(Group LD, n=24). Rats in Group LD were abdominally injected with liraglutide in a dose of 200 μg·kg -1·d -1, and the other two groups were given an equal volume of saline.At the end of 4, 8 and 12 weeks, eight rats in each group were randomly selected and 24-hour urine collections were made to measure 24-hour urinary protein.Then the rats were anesthetized, blood samples were collected for biochemical tests, and renal tissues were removed for microscopic examination of pathological changes after HE staining.The expression of type Ⅳ collagen(Col-Ⅳ)was detected by using an immunohistochemical method, and the mRNA expression of TGF-β1, Smad3 and Smad7 was detected by using real-time fluorescence quantitative polymerase chain reaction.One-way analysis of variance was used for comparisons between the groups, and the LSD-t test was used for pairwise comparisons. Results:Compared with Group N, Group D showed thickening of the glomerular basement membrane, mesangial proliferation and interstitial fibrosis at each time-point, which grew worse with time, and the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ also increased significantly(12-week: 0.69±0.01 vs.0.15±0.01, 0.51±0.02 vs.0.02±0.01, 183.33±2.08 vs.221.67±2.08, t=89.22, 60.87 and 24.52, P<0.05), while Smad7 mRNA levels decreased( t=13.42, P<0.05). Compared with Group D, the degree of renal fibrosis was reduced, and the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ at 12-week significantly decreased( t=71.703, 37.58 and 20.04, P<0.05), while Smad7 mRNA increased( t=9.96, P<0.05)in Group LD.With prolonged intervention of liraglutide, the lesions were mitigated, the expression of TGF-β1 mRNA, Smad3 mRNA and Col-Ⅳ decreased, and Smad7 mRNA increased gradually( P<0.05)in Group LD. Conclusions:Liraglutide has anti-renal fibrosis effects via inhibiting the TGF-β1/Smads pathway, thereby reducing the production of Col-Ⅳ, and can delay the progression of renal lesions in elderly T2DM rats.

Objective:To culture and identify dermal mesenchymal stem cells (DMSCs) in skin lesions of patients with psoriasis, and to determine the expression of hairy and enhancer of split-1 (HES1) and chemokine ligand 6 (CXCL6) in DMSCs.Methods:DMSCs were isolated from skin lesions of 15 patients with psoriasis and normal skin tissues of 18 healthy controls, and then subjected to culture. Cell phenotypes were identified by flow cytometry, and mRNA and protein expression of HES1 and CXCL6 was determined by real-time fluorescence-based quantitative PCR (RT-PCR) and Western blot analysis respectively. Comparisons were performed between 2 groups by using t test. Results:There was no difference in the morphology of DMSCs between the psoriasis group and control group. The mRNA expression of HES1 and CXCL6 in the psoriasis group was 3.56 and 3.44 times that in the control group respectively, and there was a significant difference between the two groups (both P < 0.05) . The protein expression of HES1 and CXCL6 in DMSCs was significantly higher in the psoriasis group than in the control group (both P < 0.05) . Conclusion:The high expression of HES1 and CXCL6 in DMSCs from lesions may be involved in the occurrence of psoriasis.

Objective To investigate the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in Chinese patients with ischemic stroke . Methods In this multi‐center study ,2 310 continuously inpatients with ischemic stroke diagnosed in 20 stroke screening and prevention project base hospitals from June 2015 to M ay 2016 were enrolled . Carotid ultrasonography and transcranial color‐coded sonography or transcranial Doppler were performed in all patients to confirm the presence of cerebral artery stenosis or occlusion . According to the distribution of lesions ,the subjects were divided into 2 groups :the simple intracranial artery stenosis group and the simple extracranial artery stenosis group . T he difference of risk factors between the two groups was compared . Results Of the 2 310 patients with ischemic stroke ,1 516 ( 65 .6% ) had simple intracranial artery stenosis and 794 ( 34 .4% ) had simple extracranial artery stenosis . T he incidence of anterior circulation artery stenosis was higher in the group of intracranial artery stenosis than that in the extracranial artery stenosis group ( 68 .1% vs 48 .7% , P ＜0 .001) . Posterior circulation artery stenosis and combined anterior with posterior circulation artery stenosis were more common in patients with extracranial artery stenosis group than those in intracranial artery stenosis group ( 36 .4% vs 22 .1% ,14 .9% vs 9 .8% ;all P ＜0 .001) . Univariate analysis of risk factors for stroke showed that patients with intracranial arterial stenosis had a higher prevelence of hypertension , diabetes ,obesity ,and family history of stroke ,and their systolic blood pressure ,diastolic blood pressure , body mass index ( BM I) ,fasting blood‐glucose ,glycosylated hemoglobin ,triacylglycerol ,total cholesterol , and low‐density lipoprotein cholesterol were significantly higher than those in the extracranial arterial stenosis group ( all P ＜ 0 .05 ) . T he proportion of elderly ( ≥ 65 years old ) ,male and smokers in the extracranial arterial stenosis group was significantly higher than that in the intracranial arterial stenosis group ( all P ＜0 .05) . Multivariate logistic regression analysis showed that elderly ( ≥65 years old) ,male , and smoking history were independent risk factors for extracranial arterial stenosis ( OR＝ 2 .012 ,1 .637 , 1 .325 ,respectively ;all P ＜0 .05) . While hypertension ,diabetes ,less physical activity ,and high BM I levels were independent risk factors for simple intracranial arterial disease ( OR ＝ 1 .301 ,1 .252 ,1 .248 ,1 .030 , respectively ;all P ＜0 .05) . Conclusions There are significant differences in the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in patients with ischemic stroke in China .

Objective To evaluate the effect of luteolin on the growth,migration and vasculogenic mimicry formation of a melanoma cell line B16.Methods In vitro cultured B16 melanoma cells were divided into 4 groups:low-,middle-and high-dose luteolin groups treated with 2.5,5,10 μmol/L luteolin respectively,and control group treated with 0.1％ dimethyl sulfoxide (DMSO).Scratch assay,Transwell invasion assay and vascular channel formation assay were performed to assess the migration,invasion of and vascular channel formation by melanoma cells.A model of subcutaneous transplanted B 16 melanoma was established in 12 C57 mice,which were randomly and equally divided into 4 groups:control group gavaged with ultrapure water,low-,middle-and high-dose luteolin groups gavaged with 10,20,40 mg/kg luteolin respectively every day.The above treatment for the tumor-bearing mice lasted till day 28,and then these mice were sacrificed.Meanwhile,the lung and tumor tissues of the mice were excised,and the growth,metastasis and vasculogenic mimicry of transplanted melanoma were observed.Immunofluorescence and immunohistochemical studies were performed to evaluate the effects of luteolin on the expression of vascular endothelial cadherin (VE-cadherin),vascular endothelial growth factor receptor 1 (VEGFR1),VEGFR2,matrix metalloproteinase-2 (MMP-2) and MMP-9 in the transplanted melanoma.Means were compared among several groups by using one-way analysis of variation or rank sum test.Results In vitro study showed that the relative scratch width at 48 hours significantly differed among the control group,low-,middle-and high-dose luteolin groups (0.47 ± 0.04,0.64 ± 0.04,0.73 ± 0.03,0.84 ± 0.04 respectively;F =34.51,P ＜ 0.001),and the migration ability of B16 cells was significantly lower in the low-,middle-and high-dose luteolin groups than in the control group (all P ＜ 0.05).At 24 hours,there were significant differences in the number of cells crossing the Transwell membrane among the control group,low-,middle-and high-dose luteolin groups (281.00 ± 8.79,169.00 ± 15.35,92.00 ± 14.79 and 57.00 ± 13.72 respectively;F =275.30,P ＜ 0.001),and the invasive ability was significantly lower in the low-,middle-and high-dose luteolin groups than in the control group (P ＜ 0.01).Meanwhile,the number of formed vascular channels also differed among the above 4 groups (20.00 ± 2.77,11.00 ± 1.28,7.00 ± 1.86 and 2.00 ± 1.32 respectively;F =48.61,P ＜ 0.001),and the number of vascular channels was significantly lower in the low-,middle-and high-dose luteolin groups than in the control group (all P ＜ 0.01).In vivo study showed that the tumor size significantly differed among the control group,low-,middle-and high-dose luteolin groups (5.10 ± 1.72,4.02 ± 2.13,2.98 ± 0.92,1.49 ± 1.13 cm3 respectively;F =28.76,P ＜ 0.001),and was significantly lower in the low-,middle-and high-dose luteolin groups than in the control group (t =3.86,7.11 and 13.06 respectively,all P ＜ 0.01).CD31-PAS double staining showed that the number of vasculogenic mimicry was significantly higher in the control group than in the low-,middle-and high-dose luteolin groups (all P ＜ 0.01).In vivo and in vitro studies both showed that the expression of vasculogenic mimicry-related markers in the cells or mouse tumor tissues was significantly lower in the high-dose luteolin group than in the control group (P ＜ 0.05).Conclusion Luteolin can effectively inhibit the growth,metastasis and vasculogenic mimicry formation of melanoma.

Objective To evaluate the efficacy and safety of preoperative intra-aortic balloon pump(IABP) insertion in acute myocardial infarction(AMI) without cardiogenic shock(CS) patients receiving off-pump coronary artery bypass grafting ( OPCABG).Methods 444 consecutive AMI patients who underwent isolated OPCABG from January 2009 to December 2016 were enrolled.158 patients who underwent preoperative IABP placement(IABP group) and the other of 286 patients who did not have IABP placement(control group).The in-hospital mortality rate, postoperative complications, mechanical ventilation time, ICU stay and hospital length were compared between the two groups.Results The overall mortality was 5.0%.135 pairs of patients were matched.The preoperative IABP insertion showed benefits in postoperative survival rate compared with the control group(0 vs.5.9%, P＝0.004).However, patients with preoperative IABP were more likely to prolong duration of mechanical ventilation and ICU stay.The postoperative length of stay in hospital didn't show significant difference between the two groups.Conclusion Survival advantage was observed from preoperative IABP insertion in AMI patients without CS under-going OPCABG.

Chemerin is a cytokine that attracts much attention in the reproductive process. This study aimed to explore the effects of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) on the maintenance of early pregnancy. The expression levels of chemerin and CMKLR1 in the decidua tissues of 20 early normal pregnant women and 20 early spontaneous abortion women were examined by Western blot and real-time polymerase chain reaction analyses. CMKLR1 receptor antagonist (α-NETA) was then intrauterinely injected into normal pregnant mice model to assess its effect on the outcome of pregnancy and the phosphorylation rate of ERK1/2 in decidua tissues.We found that the expression level of chemerin in women who had experienced early spontaneous abortion was lower than in those who had experienced normal early pregnancy (P < 0.01); conversely, CMKLR1 expression was higher in the former than in the latter (P < 0.01). In a pregnant-mouse model, the embryo resorption rate of α-NETA group was higher than that in the negative control group (61.5% vs. 10.8%) (P < 0.001). Compared with the control group, ERK1/2 phosphorylation in decidua tissues decreased in the α-NETA-treated group (P < 0.01). These results suggested that the inhibition of the chemerin/CMKLR1 signaling pathway can lead to the abortion of mouse embryos, and that chemerin/CMKLR1 may play an important role in the maintenance of early pregnancy possibly by regulating ERK1/2 phosphorylation.
Adult ; Animals ; Chemokines ; analysis ; metabolism ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; metabolism ; Mice ; Pregnancy ; metabolism ; Pregnancy Rate ; Pregnancy, Animal ; Receptors, Chemokine ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Signal Transduction ; Young Adult

Objective To explore the CT features and differential diagnosis of ovarian fibrothecoma,and to compare with postoperative pathological findings.Methods The clinical data,CT appearances and pathological signs of 15 patients with ovarian fibrothecoma and 7 patients with granulosa cell tumor were analyzed retrospectively.The plain CT values and enhanced CT values(ΔCT)of fibrothecomas and granulosa cell tumors were compared with each other.Results The ovarian fibrothecomas showed solid or cystic-solid masses with well-defined margin,mild delayed enhancement or no obvious enhancement on CT.The CT features were correspond to the pathological signs. The plain CT values of fibrothecoma and granulosa cell tumor had no significant difference(t=0.745,P=0.467).The mean ΔCT values of fibrothecoma was significantly lower than that of granulosa cell tumor(t=2.537,P=0.041).Conclusion Ovarian fibrothecoma has characteristic CT features,combined with the clinical data,which may help to improve the diagnosis.

Objective To evaluate the effectiveness of maternal prenatal education on promoting breastfeeding rate for preterm infants in neonatal intensive care unit (NICU).Methods Gravidas who were admitted to Peking University First Hospital for any risk of preterm delivery from November 2013 to December 2014 and preterm infants admitted to the NICU (length of stay ≥ 5 d) of the same hospital during the same period were involved.All the gravidas received prenatal education and completed questionnaires.Two hundred and ninety-five preterm infants who met the inclusion criteria were divided into two groups including education group (n=125) and non-education group (n=170) according to whether their mothers received prenatal education or not.Conditions of the preterm infants during hospitalization and after discharge and breastfeeding rates were comparatively analyzed between the two groups.T test,Chi-test and Wilcoxon rank-sum test were used for statistical analysis.Results (1) There were 380 gravidas received questionnaires.Among them,346 (91.1％)completed the questionnaires and were recruited in this study.Only 31.8％ (110/346) of these gravidas were active in learning more about breastfeeding and 46.2％ (160/346) of them lacked confidence in breastfeeding after the appearance of preterm delivery signs.There were significant improvements in their attitudes towards considering breastfeeding seriously and discussing with their family,confidence in breastfeeding,the importance of colostrum and how to breastfeed a preterm infant in hospital after maternal prenatal education (all P＜0.001).Prenatal education was thought to be helpful in 77.5％ (268/346) of the gravidas.(2) The two groups of preterm infants showed good homogeneities in gestational age,gender,birth weight and other basal conditions as well as in incidences of in-hospital complications and conditions after discharge (all P＞0.05).Proportions of breast milk intake (breast milk intake over total dairy intake) in preterm infants were higher in education group than those in non-education group within 5 d after birth [0.0 (0.0-16.5)％ vs 0.0 (0.0-2.5)％,Z=-3.422],＞5-≤ 7 d [33.7 (0.0-82.8)％ vs 0.0 (0.0-50.3)％,Z=-3.070],＞7-≤ 14 d [75.2(23.5-96.4)％ vs 47.6(0.0-92.2)％,Z=-2.345] and during hospitalization [58.4 (21.0-78.8)％ vs 31.9 (0.0-71.7)％,Z=-3.902] (all P＜0.05).Breastfeeding rates were higher in education group than those in non-education group at the age of 5 d [47.2％(59/125) vs 27.1％ (46/170),x2=12.747],7 d [70.4％ (88/125) vs 51.2％ (87/170),x2=11.031],three months [83.3％(65/78) vs 56.1％ (60/107),x2=15.297] and six months [64.5％ (49/76) vs 49.1％ (53/108),x2=4.282] (all P＜0.05).Exclusive breastfeeding rates in the first,third and sixth months after birth were higher in education group [45.7％(53/116),42.3％ (33/78) and 36.9％ (28/76)] than those in non-education group [21.3％ (32/150),28.0％ (30/107)and 22.2％ (24/108)] (22=17.847,4.091 and 4.703,all P＜0.05),respectively.Conclusions Most gravidas with risk factors of preterm delivery have no confidence on breastfeeding.Prenatal maternal education is an effective and feasible intervention to improve breastfeeding rate for preterm infants in NICU from early hospitalization till six months after birth.

Objective To analyze the correlation between smoking and occurrence of intracranial artery stenosis.Methods From June 2015 to May 2016,a total of 10 711 inpatients with transient ischemic attack (TIA) or ischemic stroke from 20 basel hospitals of nationwide were enrolled using a cross-sectional study,76 patients with unknown smoking and smoking cessation years were excluded.Finally,a total of 10 635 patients were enrolled.Transcranial color coded sonography and/or transcranial Doppler were used evaluate the intracranial artery stenosis lesions.The basic risk factors for cerebrovascular disease (age,sex,smoking and smoking years,whether smoking cessation and years,hypertension,diabetes,hyperlipidemia,atrial fibrillation,and family history of stroke) were recorded.According to the different smoking years,the smoking years were divided into five groups:non-smoking,smoking time ≤10-year,11 to 20-year,21 to 30-year,and >30-year groups for trend chi square test.According to the different smoking cessation years in the smokers,the smoking cessation years were divided into four groups:non-cessation,cessation time 1 to 10-year,11 to 20-year,and >20-year groups for trend chi square test.The effects of different smoking years and different smoking cessation years on the occurrence of intracranial arterial stenosis were analyzed.Results The incidence of intracranial artery stenosis in the smokers (40.4%[1 433/3 547]) was significantly higher than that in the non-smoking patients (29.4%[2 085/7 088]).There was significant difference (χ2=128.850,P<0.01),and the incidence of cerebral infarction in the smokers (91.6%[3 250/3 547]) was significantly higher than the non-smokers (85.0%[6 027/7 088]).There was significant difference (χ2=92.328,P<0.01).Smoking was an independent risk factor for intracranial artery stenosis (OR,1.603;95%CI 1.456-1.765;P<0.01).With the increase of smoking years,the detection rate of intracranial arterial stenosis increased gradually (trend χ2=115.437,P<0.01).Whether giving up smoking had no significant effect on the incidence of intracranial artery stenosis in patients with ≥20 years of smoking (trend χ2=1.043,P=0.307).Conclusions Smoking is an independent risk factor for affecting intracranial artery stenosis;the risk of disease increases with the number of smoking years.Long-term smokers (≥20 years) cannot reduce the effect on intracranial artery stenosis,even if they give up smoking.