Objective:To construct 68Ga-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid (HA), and evaluate its biological property and molecular imaging features. Methods:Low molecular weight (LMW) recombinant human CD44 protein was selected, and the C-terminal of the protein was modified by sulfonation and coupled to the bifunctional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA. The biological properties of the probe, such as labeling rate and in vitro stability, were studied. Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT imaging and pathological examination. Results:68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99%, and the specific activity was up to 62.22 MBq/nmol. lts stability was good in PBS, and the radiochemical purity was over 90% after incubation for 3 h. After intravenous injection, the probe was metabolized mainly by the kidneys, and its metabolic level decreased successively in the liver, lungs and blood. MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection, with SUV max and target/background ratio (TBR) max of 1.14±0.02 and 4.95±0.93, and the probe had certain atherosclerotic plaque eroded targeting, which was consistent with the pathological result. Conclusions:As a novel probe, 68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate. It has good physicochemical properties and in vivo biological properties, and can display atherosclerotic eroded plaques sensitively. 68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.

Objective:To automatically synthesize Al 18F-fibroblast activation protein inhibitor (FAPI)-74, and explore its value of clinical application. Methods:Al 18F-FAPI-74 was synthesized automatically by the commercial synthesis module CFN-MPS-100, and its yield, radiochemical purity and stability were determined. Sixteen normal Kunming (KM) mice were randomly divided into 4 groups and euthanized at 10, 30, 60 and 90 min after Al 18F-FAPI-74 injection, and the biodistribution was measured. MicroPET/CT dynamic scanning (60 min) was performed in 5 rat pancreatic tumor-bearing BALB/c nude mice to observe the tumor uptake. Al 18F-FAPI-74 PET/CT imaging was performed on 3 volunteers (1 male, 2 females; age: 37, 41, 43 years) to evaluate the clinical application value of Al 18F-FAPI-74. Results:The automated synthesis time of Al 18F-FAPI-74 was about 35 min, with the synthesis yield of (21.34±3.86)% (without attenuation correction, n=5) and the radiochemical purity more than 99%. The radiochemical purity was still more than 96% after placement at 37 ℃ for 6 h. Biodistribution in normal mice and microPET/CT dynamic scanning in tumor-bearing nude mice showed that consistently high uptake in the kidneys and bladder, and the tumor uptake was the highest at 20 min, and the maximum tumor-to-muscle ratio was 3.16±0.01 at 60 min. PET/CT imaging on volunteers showed that there was a small amount of uptake in myocardium, most organs such as the liver and lung had background uptake, and the maximum SUV max of persistent high uptake of tumor was 17.08. Conclusions:Al 18F-FAPI-74 has the advantages of simple synthesis, high yield, stable quality and good imaging performance in mice and volunteers. It is a kind of imaging agent that meets the requirements of clinical diagnosis.

Objective: To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C. Methods: Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded. Results: 108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin. Conclusion Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.

Objective To investigate the diagnostic value and biological features of protein induced by vitamin K absence or antagonist Ⅱ (PIVKA-Ⅱ) and alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC).Methods Serum samples of 72 patients with HCC (HCC group), 54 patients with hepatitis B cirrhosis (cirrhosis group) and 30 patients with chronic hepatitis B (CHB) without cirrhosis (CHB group) were tested with the PIVKA-Ⅱ and AFP detection kits.Diagnostic efficacies of PIVKA-Ⅱ and AFP were evaluated by receiver-operating characteristic curve (ROC).The cut-off value of PIVKA-Ⅱ for diagnose HCC was also determined.Sensitivities and specificities of PIVKA-Ⅱ and AFP were compared.Results The medians of PIVKA-Ⅱ levels in HCC group, cirrhosis group and CHB group were 14.36, 11.21, and 329.88 mAU/mL, respectively.The serum PIVKA-Ⅱ level in the HCC group was significantly higher than that in cirrhosis group (U=342.50, P<0.01).And serum PIVKA-Ⅱ level in cirrhosis group was also higher than that in CHB group (U=481.50,P>0.05).The serum PIVKA-Ⅱ levels in patients with BCLC stage A, B, C in HCC group were 22.13, 345.46, and 13 057.72 mAU/mL, respectively.After comparison of stage A and C with stage B, the differences were both statistically significant (stage A to B: U=119.0, P<0.01;stage B to C: U=158.0, P<0.01).The sensitivity and specificity of PIVKA-Ⅱ with a cut-off value of 30.01 mAU/mL by means of Youden index were 0.750 and 1.000, respectively.When combined PIVKA-Ⅱ with AFP, the sensitivity and specificity were 0.800 and 0.964, respectively.The area under the curve (AUC) was highest (AUC=0.930, 95%CI: 0.852-0.974), and significantly higher than that using PIVKA-Ⅱ alone (AUC=0.892, 95%CI: 0.834-0.950,x2=21.43,P<0.01).Conclusions The diagnostic value of serum PIVKA-Ⅱ is superior to AFP.Combined with AFP, serum PIVKA-Ⅱ can improve the detection rate of HCC, and has advantages during the development of HCC and can be used to monitor the condition of HCC patients.

Objective: To investigate the influence of hepatitis B virus X gene (HBx) on apoptosis of hepatic cells mediated by Fas in HePG2 cells. Methods: HBx eukaryotic vector pcDNA3.1(+)-X was transfected into HEPG2 cells with lipofectamine, and the null vector pcDNA3.1(+) and untransfected HEPG2 were used as normal controls. The cells were collected 72 h after transfection, and the expression of HBx mRNA and protein was determined using RT-PCR and Western blot, respectively. The mRNA expression of apoptosis-related genes Bcl-2 and Bax mRNA was also determined using RT-PCR. Cytotoxicity and apoptosis were evaluated using CCK-8 and flow cytometry, respectively, after HepG2-HBx and HepG2-3.1 cells were treated with stimulatory monoclonal antibody anti-Fas CH11. The t test was used for pairwise comparison. Results: The cell line HepG2-HBx was successfully established, as confirmed by RT-PCR and Western blot, and RT-PCR results showed that HepG2-HBx cells had significantly higher expression of Bcl-2 mRNA than HepG2-3.1 and HepG2 cells (P < 0.05), but had significantly lower expression of Bax mRNA than HepG2-3.1 and HepG2 cells (P < 0.05); CCK-8 and flow cytometry showed that anti-Fas CH11 had a lower cytotoxicity to HepG2-HBx cells and allowed for a lower apoptosis rate of HepG2-HBx cells compared with HepG2-3.1 and HepG2 cells. Conclusions HBx can inhibit apoptosis of hepatic cells mediated by the Fas pathway.

Objective To study the efficacy of double inverted Y-shaped airway covered stent for patients with thoracostomach-right main bronchus fistula.Methods Fifteen cases with thoracostomach-right main bronchus fistula were investigated retrospectively.All patients had accepted esophageal resection and thoracostomach esophagus anastomosis,as well as radiation therapy after surgery due to esophageal cancer. All fistulas located close to the opening of right upper lobe bronchus.According to the normal tracheobronchial diameter and length of patients,two inverted Y-shaped airway covered stents were designed individually.Stenting was performed under X-ray,and the situation of fistula and clinical symptoms improvement were investigated.Results The double inverted Y-shaped airway covered stents were implanted and fistulas were closed successfully.All patients could take normal diet,and the supine cough symptoms disappeared, without complications such as airway bleeding and pneumothorax after stenting.Conclusion The stenting of double inverted Y-shaped airway covered stent may be an effective,feasible and safe treatment for thoracostomach-right main bronchus fistula.

Intracranial aneurysms are rare in children,accounting for only 0.8％-5％ of intracranial aneurysms.Clinical features and treatment requirements of intracranial aneurysms in children are different with those in adults.Intracranial aneurysrns in children occur more commonly in male patients,complex aneurysms (posterior circulation,fusiform,dissection,infection,trauma),and postoperative recurrence or neonatal intracranial aneurysms.Usually,they have lower rate of bleeding than adult patients.In recent 10 years,treatment of intracranial aneurysms in children has gradually transformed from traditional microsurgical treatment to endovascular treatment.However,the treatment methods should be considerate comprehensively based on whether there are serious complications and locations,sizes of aneurysms,in order to achieve the treatment safety,effectiveness and persistence.

Objective To investigate the correlation of rupture risk of intracranial aneurysms with aneurysm diameter,blood pressure,neck width,gender,age,and smoking and alcohol histories of the patients.Methods Retrospective analysis of the clinical and radiological data of 928 patients with intracranial aneurysm,admitted to our hospital from January 2011 to December 2012,was performed; according to rupture situation,these patients were divide into ruptured group (n=411) and unruptured group (n=517); univariate analysis and multivaviable Logistic regression analysis were used to analyze the rupture risk of intracranial aneurysms,including aneurysm diameter,blood pressure,neck width,gender,age,and smoking and alcohol histories.Results Univariate analysis showed that there were statistical significances between the two groups on aneurysm diameter,blood pressure,aneurysm neck width,gender,smoking history (P＜0.05); multivariate Logistic regression analysis showed that aneurysm diameter was the independent risk factor of rupture of aneurysms (P=0.001).Conclusion Aneurysm diameter is a key risk of rupture for intracranial aneurysms,while rupture of intracranial aneurysms is not correlated to the blood pressure,aneurysm neck width,gender,age,and smoking and alcohol histories.

Objective To estimate the influence of palmitic acid (PA) on the proliferation of and production of inflammatory mediators by a human keratinocyte line HaCaT.Methods Cultured HaCaT cells were treated with PA of eight concentrations (0-200 μmol/L) for 3-24 hours followed by the evaluation of cell proliferation by using the cell counting kit-8.According to the proliferation assay,four concentrations (75,100,125,150 μmol/L) of PA were selected and used to treat HaCaT cells for 24 hours,then,fluorescence-based immunohistochemical staining was performed to observe the nuclear translocation of nuclear factor (NF)-κB p65,enzyme linked immunosorbent assay (ELISA) to determine the level of interleukin (IL)-6 in the supernatant of culture medium,real-time PCR to detect the mRNA expressions of peroxisome proliferator-activated receptor oα (PPARα) and IL-6,and Western blot to quantify the protein expressions of PPARα as well as total and nuclear NF-κB p65.Those HaCaT cells receiving no treatment served as the control group.Statistical analysis was carried out by one-factor analysis of variance using the GraphPad Prism 5.0 software.Results The HaCaT cells treated with PA of 50-175 μ mol/L showed accelerated proliferation compared with the control HaCaT cells (all P ＜ 0.05).PA from 75 to 150 μmol/L enhanced the nuclear translocation of NF-κB p65,mRNA and protein expressions of PPARα,as well as the mRNA expression and supernatant level of IL-6 in a dose-dependent manner.The relative expression level of nuclear NF-κB p65 protein was 0.4536 ± 0.0173,0.5184 ± 0.0206,0.5333 ± 0.0231,0.6160 ± 0.0297,and the supernatant level of IL-6 was (31.5677 ± 0.2268),(32.3773 ± 0.4156),(32.9837 ± 0.0029) and (33.6890 ± 0.0936) ng/L,in HaCaT cells treated with PA of 75,100,125 and 150 μmol/L,respectively,compared to 0.3237 ± 0.0114 (all P ＜ 0.01) and (30.4577 ± 0.5131) ng/L (all P ＜ 0.01) in the control HaCaT cells,respectively.Conclusions PA can accelerate the proliferation of HaCaT cells,enhance NF-κB nuclear transfer,PPARα expression and IL-6 secretion in a dose-dependent manner within a certain concentration range,and may exert a promoting role in the activation and expression of some inflammatory factors.

Objective To investigate the clinical significance of the 3D-CTA (three-dimensional computed tomography angiography)assisted design of finger reconstruction the second toe.Methods Between June 2010 and January 2013,five patients with finger defect received 3D-CTA assisted finger reconstruction surgeries using the second toe.Preoperative ipsilateral foot and hand 3D-CTAs were conducted and the 3D digital models were analyzed.The accurate positions and adjacent relations of vessels in both donor and recipient site were precisely marked and then the calibers of the vessels were measured.Four cases received thumb reconstructions and 1 case received little finger reconstruction.All of these surgeries were second-stage.According to Gu Yudong's classification of finger defect:second degree 2 cases,third degree 2 cases,five degree 1 case(little finger).Results With the help of 3D-CTA,five patients in this group had no vascular crisis,and all fingers survived successfully.With 4-12 months' follow-up,the algesthesia and thalposis of the reconstructed fingers gained good recoveries.The two-point discrimination was 5-10 mm.Tthe range of flexion of interphalangeal joint was 10 °-30 °.The range of flexion of the metacarpophalangeal joints was 35 °-80 °.And all patients restored walking and bearing functions with 3 months after surgeries.Conclusion The 3D-CTA reconstruction based digital model of ipsilateral foot and hand can objectively reflect the real situation of the vessels in both donor sites and recipient sites (exist of variations,routes and the calibers of the vessels),thus improve the success rate of surgery.