Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

Objective:To investigate the short-term clinical outcomes of posterior percutaneous pedicle screw fixation combined with percutaneous vertebroplasty (PVP) for treating Kümmell's disease with intravertebral instability.Methods:A retrospective case series study was made on 18 patients with Kümmell's disease with intravertebral instability treated at Lishui Hospital of Zhejiang University from January 2012 to February 2016. There were 4 males and 14 females, aged 65-86 years [(76.0±5.5)years]. Segment of injury was T 7 in 1 patient, T 10 in 2, T 11 in 3, T 12 in 4, L 1 in 6, and L 2 in 2. All patients underwent posterior percutaneous pedicle screw fixation combined with PVP. The operation time, intraoperative blood loss, amount of cement injected into the vertebra, and length of postoperative hospital stay were recorded. The visual analogue scale (VAS), Oswestry disability index (ODI), Cobb angle, and wedge angle of the operative segment were recorded and compared preoperatively, postoperatively, and at the latest follow-up. Meanwhile, the complications were recorded. Results:All patients were followed up for 12-28 months [(17.7±4.4)months]. The operation time was 110-175 minutes [(137.9±21.9)minutes] and the blood loss was 50-165 ml [(110.7±35.6)ml]. The amount of cement injected into the vertebra was 2.5-6.0 ml [(4.7±0.9)ml]. The length of hospital stay was 7-14 days [(9.4±2.3)days]. The VAS was (7.8±1.2) points preoperatively, (3.3±0.7) points at 1 week postoperatively and (2.4±0.7)points at the latest follow-up. The ODI was (67.3±7.3)% preoperatively, (30.5±7.5)% at 1 week postoperatively and (21.8±8.3)% at the latest follow-up. The Cobb angle was (26.2±9.5)° preoperatively, (12.6±7.2)° at 1 week postoperatively and (16.7±6.2)°at the latest follow-up. The wedge angle was (21.1±6.1)° preoperatively, (8.4±4.6)° at 1 week postoperatively, and (13.2±4.1)° at the latest follow-up. The above clinical and radiological parameters were significantly improved after operation ( P<0.05), and showed no significant differences at the latest follow-up when compared to that at 1 week postoperatively ( P>0.05). Five patients showed slight screw loosening, but there was no obvious dislocation of internal fixation. One case developed distal vertebral compression fracture at 6 months postoperatively and cured after a second PVP. Conclusion:For Kümmell's disease with intravertebral instability, posterior percutaneous pedicle screw fixation combined with PVP can effectively restore and maintain the spinal sequence, rapidly relieve the pain and improve clinical function. However, the long-term efficacy needs further study.

Objective To evaluate the effect of precision anesthesia strategy on postoperative cognitive function in elderly patients undergoing hip replacement.Methods Seventy elderly patients of both sexes,aged 65-85 yr,weighing 50-75 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective unilateral hip replacement under general anesthesia,with years of education＞6 yr,were divided into 2 groups (n =35 each) using a random number table:precision anesthesia group (group P) and routine anesthesia group (group R).Anesthetic protocol and perioperative management were optimized using precision anesthesia strategy in group P.Routine anesthetic protocol and perioperative management were performed in group R.Peripheral venous blood samples were collected at 1 day before operation (T0) and 1,6,12 and 24 h after operation (T1-4) for determination of serum S100β protein,neuronspecific enolase (NSE),interleukin-1beta (IL-1β),IL-6,tumor necrosis factor-alpha (TNF-α) and Creactive protein (CRP) concentrations by enzyme-linked immunosorbent assay.The patient's cognitive function was assessed using Mini-Mental State Examination (MMSE) at T0 and 3 and 7 days after operation (T5,6).Results Compared with the baseline at T0,the serum S100β protein and NSE concentrations were significantly increased at T1-3,the serum IL-1β,IL-6 and TNF-α concentrations were increased at T1-4,the CRP concentrations were increased at T2,3,MMSE scores were decreased at T5 in group R,and the serum S100β protein,IL-1β and IL-6 concentrations were significantly increased at T1-3,the serum NSE and CRP concentrations were increased at T2,the serum TNF-α concentrations were increased at T1-4,and MMSE cores were decreased at T5 in group P (P＜0.05).Compared with group R,the serum S100β protein and IL-1β concentrations were significantly decreased at T1,2,the serum NSE and TNF-α concentrations were decreased at T1-3,the serum IL-6 concentrations were decreased at T2,3,and MMSE scores were increased at T5 in group P (P＜ 0.05).Conclusion Precision anesthesia strategy can improve postoperative cognitive function in elderly patients undergoing hip replacement,which is related to inhibiting inflammatory responses.

Objective To observe the effects of alprostadil injection on intestinal mucosal barrier function in patients with acute pancreatitis(AP). Methods Seventy-eight AP patients admitted in Department of Medicine in Yuhang District Second People's Hospital of Hangzhou City from May 2016 to March 2017 were divided into 2 groups using random number method,including 38 cases in the control group and 40 cases in the treatment group. Patients in the control group received routine treatment. Patients in the treatment group were given intravenous 10 μg/d alprostadil injection in addition to routine treatment continuously for 14 days. Another 40 healthy volunteers who underwent routine examination in the same period were enrolled as healthy control group. The scores of MCTSI and APACHEⅡwere recorded at admission and 2 days after the treatment. The levels of serum DAO, endotoxin (ET) and IFABP were detected by ELISA. Results There were no significant difference on the scores of MCTSI and APACHEⅡ, the levels of serum DAO, ET, IFABP before treatment between control and treatment group(P>0.05), but were increased significantly than those in the healthy control group(P<0.01). After treatment,the scores of MCTSI and APACHEⅡ,the levels of serum DAO, ET, IFABP were decreased significantly than those before treatment in two groups(P<0.05 or P<0.01), but the scores of MCTSI and APACHEⅡ, the levels of serum DAO, ET and IFABP were decreased significantly than those in the control group(3.78 ± 0.43)vs (5.89 ± 0.13),(5.65 ± 1.77)vs (9.05 ± 1.61),(2.18 ± 0.16)U/ml vs (3.22 ± 0.15)U/ml,(0.15 ± 0.06)EU/ml vs (0.25 ± 0.09)EU/ml,(62.01 ± 12.82)ng/L vs (85.43 ± 16.79)ng/L; all P<0.05). There was a significant positive correlation between serum DAO, ET, IFABP and the scores of MCTSI (P<0.01). There was a significant positive correlation between serum DAO, ET, IFABP and the scores of APACHEⅡ, too (P<0.01). Conclusions Patient with acute pancreatitis have obvious intestinal mucosal barrier injury. Alprostadil injection can improve clinical symptoms and the scores of MCTSI to a certain extent by protecting intestinal mucosal barrier function.

Objective To investigate the dynamical changes of serum SOCS-3 in patients with acute pancreatitis (AP) and discuss the potential clinical significance.Methods Seventy-five patients with AP admitted in Yuhang District Second People's Hospital of Hangzhou City from February 2015 to December 2016 were selected,who were divided into 2 groups according to disease severity:40 cases in mild AP (MAP) group and 35 cases in moderate and severe AP (MSAP + SAP) group.The levels of serum SOCS-3,IL-6 and TNF-α were determined by enzyme linked immunosorbent assay (ELISA) on the 1,3,5 and 7 day after admission.Thirty healthy people who were age and gender matched were included in the normal control group.Results The levels of serum SOCS-3,IL-6 and TNF-α in AP patients on the 1 day after admission were significantly increased than that in the control group (P ＜ 0.01 or P ＜ 0.05),which were gradually increased with the time,peaked on the 5 day and then started to decrease on 7 day after admission which was still higher than that on the 1 day after admission.The levels of serum SOCS-3,IL-6 and TNF-α in MSAP + SAP group were significantly higher than that in MAP group (P ＜0.01),and there were significant differences (F =112.80,P =0.001;F =170.21,P =0.000;F =112.82,P =0.000).Significant differences were also found among different time points between two groups (F =258.38,P =0.000;F =4.82,P =0.000;F =5.52,P =0.001).Additionally,the significantly positive correlations of SOCS-3 with IL-6 and TNF-α were found (r=0.785,r=0.828,both P＜0.01).Conclusions SOCS-3 may participate in early excessive inflammatory reactions in AP.Dynamic detection of SOCS-3 may be helpful for AP clinical classification and prognosis evaluation.

Objective To discuss the effects and related mechanisms of rapamycin preconditioning on lung injury induced by limb ischemia-reperfusion (IR) in rats.Methods Sixty healthy male SD rats, aged 4-5 months, weighing 250-300 g, were randomly divided into 5 groups (n=12 each) using a random number table: sham operation group (group S);limb ischemia-reperfusion group (group IR);rapamycin 1, 5, 10 mg/kg pretreatment groups (groups R1, R5 and R10).Ischemia-reperfusion of limb was produced by occlusion of bilateral femoral arteries for 2 h followed by 3 h reperfusion.Blood samples were collected to determine serum superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations,1ungs were removed for microscopic examination and for determination of wet/dry lung weight ratio.Results The activity of SOD in groups IR, R1 and R5 was significantly lower than that in group S (P＜0.05).The activity of SOD in groups R1, R5 and R10 was significantly higher than that in group IR, that in groups R5 and R10 was significantly higher than that in group R1, that in group R10 was significantly higher than that in the group R5 (P＜0.05).Serum MDA, IL-1β, IL-6, TNF-α concentrations and wet/dry lung weight ratio were significantly increased in groups IR, R1 and R5 (P＜0.05).Serum MDA, IL-1β, IL-6,TNF-α concentrations and wet/dry lung weight ratio were lower in groups R1, R5 and R10, those in groups R5 and R10 were significantly lower than those in group R1, those in group R10 was significantly lower than those in group R5 (P＜0.05).Compared with group S, the lung tissue injured more significantly in group IR.Compared with group IR, the lung tissue injury gradually reduced in groups R1,R5 and R10.Conclusion Rapamycin pretreatment can reduce lung injury caused by limb ischemia-reperfusion injury in rats in a dose-dependent manner, the greater the dose, the stronger the effect of reducing lung injury caused by limb ischemia-reperfusion injury.The mechanisms may involve attenuating oxidative stress and inhibiting inflammatory response.

Objective To observe the effects of human EP cells (hEPCs)transplantation on the function recovery of rats with spinal cord injury.Methods 24 SD rats (5 ones died in the process of operation)were firstly completed transection of T10 segment of spinal cord by using quick knife slices to complete animal model.19 rats after spinal cord transection were randomly divided into:the experimental group (10 cases)and the control group (9 cases). The experimental group with spinal cord injury was injected 7.5μL suspension of hEPCs (human Endothelial Progeni-tor Cells).Adjacent area of spinal cord injury in control group was injected equal amount DMEM(Dulbecco minimum essential medium.Postoperative intraperitoneal injection of cyclosporine A,an immunosuppressant,was administrated daily.At postoperative 1,2,4,6,8 weeks Basso Beatlie Bresnahan (BBB)score were administrated to record the neural function recovery of lower limbs in SCI rats.The transection spinal cord were removed from rats 8 weeks after operation to detect transplanted survival hEPCs in transection spinal cord of ratsby immunohistochemical and hybridization technique. Results 2 weeks after SCI model established,the BBB scores in the experimental group and the control group showed no statistically significant difference(t =0.61,0.69,all P >0.05).4 weeks postoperatively,the BBB score of the experimental group (1.67 -0.71)points was more than that in the control group (1.11 -0.60),the difference was statistically significant(t =3.16,P <0.05).Untill 8 weeks scores were respectively the (4.00 -1.41)of the experimental group and the (1.44 -0.89)of the control group,the difference was statistically significant(t =5.384,P <0.05). Finally it was concluded that 4,6,8 weeks after SCI,hind limbs function of the experimental group was significantly better than that of the control group,the difference had statistical significance (P <0.05).Hybridization and immuno-histochemical detection showed that the transplanted hEPCs not only live in the host but in partial hEPCs chimeric to SCI in rats of spinal cord and its vascular system.Conclusion After transplantation,hEPCs can survive,differentiate into vascular endothelial cell,and improvement spinal cord function recovery as compared with control group.

This study was aimed to investigate the induction effect ofRe-Du-Ning (RDN) Injection on rat liver microsome CYP450 enzymes. SD rats were randomly divided into the solvent control group, positive control group as well as the low, middle and high dose group of RDN (1, 2, 4 mL·kg-1·d-1). After drugs were administrated continuously for 7 days, the rats were sacrificed. The liver was weighed and prepared to microsomes. Meanwhile, the liver coefficients of rats were calculated. And the protein content was detected by BCA method. Finally, activities of five important subtypes of CYP450 enzymes such as CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A1/2 were measured by the“cocktail” method. The results showed that the levels of liver coefficients, microsome yield rate and activities of CYP450 subtypes increased significantly in the positive control group compared with the solvent control group (P < 0.01). There was no significant difference on the levels of liver coefficients, microsome yield and protein content between the low and middle dose group of RDN. However, there was significant difference on the levels of liver coefficients and microsome yield in the high dose group (P < 0.05). In terms of the influence on enzyme activity, RDN Injection can significantly induce the activities of CYP1A2 with dose dependence. It can induce the activities of CYP2C9 and CYP2C19 at the middle and high dose. However, there was no obvious influence on the activities of CYP3A1/2 and CYP2D6. It was concluded that the positive control group can obviously induce activities of CYP450, which can be used in the evaluation of induction experiments. RDN Injection had induction effect on CYP1A2, CYP2C9 and CYP2C19. But it had no influence on the activities of CYP3A1/2 and CYP2D6.

Objective To discuss the surgery methods and clinical curative effect of application of nickel titanium memory alloy embracing device fixed femoral fractures inside wall of bone block.Methods The clinical data of 27 patients on the application of nickel titanium memory alloy embracing device fixed femoral fractures inside wall with bone block were retrospectively analyzed.There were 9 cases of male and 18 cases offemale.They were 69 ~89 years old,average 76.2 years.And there were 19 cases on the left side of inside wall and 8 cases on the right side. Curative effect evaluation was conducted according to the Evans-Jensen norm and the improved Harris standard. Results Postoperative follow-up loss in 2 cases,and 24 cases received follow-up for 6 ~20 months,which had an average of 14.15 months and follow-up rate was 92.3%.Three cases died respectively because of acute heart failure, cerebral hemorrhage and cor pulmonale.Patients at the time of the last follow-up had Harris mean score(80 ~97), including the optimal 19 cases,fine 4 cases and poor in 1 case,and the excellent rate was 95.8%.Conclusion Sur-gery method of nickel titanium memory alloy embracing device fixed femoral fractures inside wall of bone has reliable fixation,and can restore the biomechanical balance and decrease complications,etc.It allows early functional exercise of hip part in load conditions to obtain ideal therapeutic effect.