Abstract: Objective　To prepare a microparticle delivery system that regulates the release rate of extracellular vesicles (EVs), and to exert long-term enhancement of liver cell proliferation after only one intervention. Methods EVs was extracted by differential centrifugation. The structure of the EVs was observed by transmission electron microscopy and the membrane marker protein of EVs was detected by Western blotting. EVs-PLA microspheres with "core-shell" structure were prepared by emulsion-solvent evaporation method. Scanning and transmission electron microscopy were used to detect the morphology of EVs-PLA microspheres and EVs. The release test detected the release behavior of EVs in EVs-PLA microspheres. Scanning electron microscopy was used to detect the morphological changes of EVs-PLA microspheres at 8 weeks of release. EVs-PLA microspheres were co-cultured with hepatocytes, and Phalloidin/DAPI staining was used to observe the cell morphology and evaluate the cytotoxicity of the microspheres. CCK8-test was used to evaluate the cell proliferation activity. Western blot analysis was used to detect extracellular vesicles membrane marker protein expression. Results Comparing the ability of hepatocyte proliferation in the group treated with EVs-PLA microspheres and the control group, it was found that EVs-PLA microspheres did not cause cell apoptosis and mutation in cell structure, had biocompatibility and no cytotoxicity. The EVs-PLA microspheres with "core-shell" structure regulated the release behavior of EVs, which can continuously release EVs, exerting a continuous biological role in promoting hepatocyte proliferation after a single intervention. Conclusions The EVs-PLA microspheres can control-release EVs and promote hepatocyte proliferation continuously after a single intervention, providing a reference for further exploration of EVs-loaded delivery systems in promoting liver regeneration.

Objective To evaluate the diagnostic value of MRI in brachial plexus injury.Methods Total 98 patients with brachial plexus injury were examined by MRI before operation.Fifty-four of 98 patients MR imaging were obtained by 0.5 Tesla scanner and other 44 patients were obtained by 1.5 Tesla scanner.The scanning sequences include: SE T_1WI,T_2WI,FFE T_2WI and T_2WI SPIR. Exploration of the supraclavicular plexus was carried out and the MR imaging were compared with the operative finding in 63 patients.Thirty-five patients who had not surgery were followed-up.Results MR imaging found pre-ganglionic injuries in 45 patients and post-ganglionic injuries in 56 patients.Pre-and post-ganglionic injuries simultaneously in 16 patients among them.MR imaging can not find injury sings in 13 patients.The positive rate was 86.73%.MR imaging finding of pre-ganglionic injuries include:(1) Spinal cord edema and hemorrhage,2 patients (4.44% ).(2)Displacement of spinal cord,17 patients (37.78%).(3)Traumatic meningoceles,37 patients (82.22%).(4)Absence of roots in spinal canal, 25 patients(55.56% ).(5)Scarring in the spinal cnanl,24 patients (53.33%).(6)Denervation of erector spine,13 patients (28.89%).MR imaging finding of post-ganglionic injuries include:(1)Trunk thickening with hypointensities in T_2WI,23 patients (41.07%).(2)Nerve trunk complete loss of continuity with disappeared of nerve structure,16 patients (28.57%).(3)Continuity of nerve trunk was well with disappearance of nerve structure,14 patients(25.00%).(4)Traumatic neurofibroma,3 patients (5.36%).Conclusion MR imaging can reveal Pre-and post-ganglionic injuries of brachial plexus simultaneously.MR imaging is able to determine the location (pre-or post-ganglionic)and extent of brachial plexus injury,provided important information for treatment method selection.

OBJECTIVETo explore the follow-up visit, outcome and auxiliary diagnosis method on the cases with indeterminate antibody level measured by Western blotting as well as the related biological factors.

METHODSThe cases with indeterminate result were followed up according to the National Guideline for Detection of HIV/AIDS (2009) and samples were collected for HIV antibody detection, p24 antigen and nucleic acid were detected as a supplementary diagnosis at the same time. The samples were also be detected for HBV, HCV, TP, HTLV-I/II, ANA, and AFP, and the results were compared to that of screened positive and confirmed negative cases.

RESULTSA total of 73 were followed up successfully and taken a second HIV test, 25 cases were tested positive and 48 were tested negative for HIV during the follow-up period. For the 25 HIV positive cases, the HIV seroconversion rate was 100.00% at any time point when the interval between the first and returning detection was longer than 1 week. The major Western blotting bands for the cases with indeterminate result were p24 and gp160 and it was different between HIV positive and negative cases in Western blotting band profiles. The consistency and sensitivity of nucleic acid detection were higher than 90.00%, and were higher than that of p24 antigen (69.09% (38/55) and 27.27% (6/22)) (χ(2)(consistency) = 6.875, χ(2)(sensitivity) = 18.893, P < 0.05). The positive rates of ANA and AFP of indeterminate cases excluded from HIV infection were 20.83% (10/28) and 6.25% (3/48) and higher than that of screened positive and confirmed negative cases (0.00%), the difference had statistic significance (χ(2)(ANA) = 19.430, χ(2)(AFP) = 5.520, P < 0.05).

CONCLUSIONIt is critical to get timely diagnosis for the indeterminate cases according to the new national guideline for detection of HIV/AIDS. Nucleic acid detection has higher application value as auxiliary diagnosis for HIV infection than p24 antigen. The increased levels of ANA and AFP may be the factors resulting in the nonspecific indeterminate results.

Antibodies, Antinuclear ; blood ; Female ; Follow-Up Studies ; HIV Antibodies ; blood ; HIV Infections ; diagnosis ; immunology ; Humans ; Male ; alpha-Fetoproteins ; analysis

OBJECTIVETo evaluate the feasibility and efficacy of a new MRI imaging method--diffusion weighted imaging (DWI) with short TI version recovery-echo planar imaging (STIR-EPI) sequence in differentiating benign cervical lymph nodes from malignant ones. METHODS Twenty nasopharyngeal carcinoma patients and fourteen volunteers received both conventional MRI and DWI with STIR-EPI. Ability of detecting lymph nodes between conventional MRI and STIR-EPI-DWI was compared, and the difference of apparent diffusion coefficient (ADC) value between metastatic lymph node and normal lymph node was analyzed.

RESULTSDWI was more sensitive in detecting lymph node than conventional MRI. ADC value of metastatic lymph node (0. 766 +/- 0. 119) x 10 (-3) mm(2)/s was significantly lower than that of normal lymph node (0. 975 +/- 0. 179) x 10 - mm2/s (P < 0. 01).

CONCLUSIONAs a new MRI imaging technique in detecting cervical lymph nodes, diffusion weighted imaging ( DWI) with short TI version recovery-echo planar imaging ( STIR-EPI) sequence is more reliable and sensitive than conventional MRI imaging, providing an alternative way to differentiate benign lymph nodes from malignant ones.

Adult ; Aged ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging ; methods ; Echo-Planar Imaging ; methods ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; Neck ; Reproducibility of Results ; Sensitivity and Specificity

Objective:To explore the incidence and risk factors of peripherally inserted central catheter (PICC) related upper extremity venous thrombosis (UEVT) in patients with head and neck neoplasm so as to provide a basis for preventing thrombosis.Methods:This study used the design of prospective cohort study. From January 2016 to March 2018, UEVT follow-up examination by B ultrasound was carried out for 1 137 head and neck neoplasm patients with PICC selected by convenience sampling. Single factor and multivariate Cox regression were used to determine the risk factors of PICC related UEVT.Results:There were 3.6% (41/1 137) of patients with PICC related UEVT. Multivariate Cox regression showed that the independent risk factors of PICC related UEVT included the older patients ( RR=1.04, 95% CI: 1.01-1.07, P=0.013) , being with a history of PICC catheterization ( RR=3.22, 95% CI: 1.53-6.77, P=0.002) and high frequency of catheter delivery ( RR=1.98, 95% CI: 1.30-3.00, P=0.001) . Conclusions:Patients with head and neck neoplasm have the low incidence of PICC related UEVT. The independent risk factors of PICC related UEVT in patients with head and neck neoplasm include the older ages, history of PICC catheterization and high frequency of catheter delivery. Positive intervention should be carried out for those patients which may reduce the incidence of PICC related thrombosis.

Objective To evaluate the relationship between the changes of diffusion tensor imaging(DTI)and the clinical stages in patients with cerebral infarction. Methods One hundred and seven patients with cerebral infarction were chosen to perform conventional MRI and DTI,respectively.With double-blind method,the signal intensity of fractional anisotropy(FA)and isotropic apparent diffusion coefficient(ADCiso)in responsible to infraction regions was observed and based on their results,the relationships between the changes of DTI and the clinical stages were analyzed. Results In 29 cases of cerebral infarction in acute stage,10 were manifested as type I(hypointensity on ADCiso map,hyperintensity on FA map)and type Ⅱ(hypointensity on ADCiso map and FA map with hyper intensive circumference)on DTI;3 were manifested as type Ⅲ on DTI(iso-/Paypo-intensity on ADCiso map and FA map with normal circumference);6 were manifested as type Ⅳ on DTI(hyperintensity on ADCiso map,hypointensity on FA map).In 34 cases of cerebral infarction in sub-acute stage,2 were manifested astype Ⅰ on DTI;20 were manifested astype Ⅱ;8 were manifested as type Ⅲ and 4 were manifested as type IV.In 44 cases of cerebral infarction chronic stage.1 Was manifested as type Ⅱ on DTI;2 were manifested as type Ⅲ and 41 were manifested as type IV.Positive correlation was found between changes of DTI and clinical stages(r=0.693,P=0.000). Conclusion The intensity of infraction on DTI can directly demonstrate the clinical stages,providing precise evidence for classifying the stages of cerebral infarction.

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accu-mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi-esis and ultimately resulting in bone marrow failure. Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years (5.3%)and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML. Saponins are amphipathic glycosides found in traditional Chinese medicines. In the present study, we isolated a panel of saponins from Paris forrestii (Takht.) H. Li, a unique plant found in Tibet and Yunnan provinces, China. By examining their activities in suppressing acute myeloid leukemia cell proliferation, total saponins from Paris forrestii (TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines. TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg-ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa-tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con-firmed by the inactivation of 4EBP-1 and p70S6K,two typical downstream signal molecules in the AKT/mTOR pathway. More specifically, TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6, a recently identified oncogene in AML. RNF6 activated AKT/mTOR, and consistently, knockdown of RNF6 led to inactivation of the AKT/mTOR pathway. Furthermore, TSPf suppressed the growth of AML xenografts in nude mice models. Oral administration of 100 mg·kg-1 body weight almost fully suppressed tumor growth within 14 d, without gross toxicity. This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway. Given its low toxicity,TSPf could be developed for the treatment of AML.

Objective:To investigate the contamination status of SARS-CoV-2 in imported frozen seafood from a Russia cargo ship in Qingdao and to analyze the risk factors for infection in local stevedores.Methods:The method of "two-stage, full coverage and mixed sampling" was used to collect the seafood packaging samples for the nucleic acid detection of SARS-CoV-2 by real-time fluorescent quantitative RT-PCR. A unified questionnaire was designed to investigate 71 stevedores in two shifts through telephone interview. The stevedores were divided into two groups, with 23 in the shit with two infections was group A and 48 in the shift without infection was group B. Software Epi Info7.2 was used to identify the risk factors for SARS-CoV-2 infections in the stevedores.Results:In the frozen seafood from a Russia cargo ship, the total positive rate of SARS-CoV-2 nucleic acid in the frozen seafood was 11.53% (106/919). The positive rate of SARS-CoV-2 nucleic acid in the frozen seafood unloaded by group A (14.29%,70/490) was significantly higher than that in the frozen seafood unloaded by group B (8.39%,36/429)( χ2=7.79, P=0.01) and the viral loads detected in the frozen seafood unloaded by group A were higher than those detected in the frozen seafood unloaded by group B. The scores of personal protection and behaviors in the stevedores in group A were significantly lower than those in group B ( P<0.05), and toilet use, smoking and improper hand washing before meals were the risk factors for the infection. Conclusions:The imported frozen seafood was contaminated by SARS-CoV-2 and the contamination distribution was uneven. Supervision and management of personal occupational protection and behaviors of workers engaged in imported frozen food transportation should be strengthened. It is suggested that a closed-loop monitoring and management system for the whole process of "fishing-transport- loading/unloading" should be established by marine fishery authority.

Objective:To investigate the value of nomogram predictive model established by the risk factors of upper extremity venous thrombosis risk associated with peripherally venous inserted central catheter (PICC) in cancer patients.Methods:A total of 1 032 patients who underwent PICC insertion between January 2016 and March 2017 in Zhejiang Cancer Hospital were selected by using prospective cohort study and convenience sampling. Risk factors of upper extremity venous thrombosis risk associated with PICC in cancer patients were evaluated by using Cox regression model. The nomogram predictive model of upper extremity venous thrombosis risk associated with PICC insertion was constructed. Bootstrap method was used to complete the inside check, and figure calibration was used to verify the nomogram.Results:A multivariate Cox regression analysis showed that trombosis history ( HR = 27.82, 95% CI 8.17-94.88, P < 0.01) and hyperlipidemia ( HR = 3.01, 95% CI 1.31-6.93, P = 0.009) were independent risk factors for upper extremity venous thrombosis associated with PICC. The nomogram model C-index was 0.71 (95% CI 0.63-0.80) based on the above risk factors, which indicated that the nomogram had a good differentiation. The calibration curve for predicting the probability of upper extremity venous thrombosis risk associated with PICC within one week, two weeks and one month deviated slightly from the standard curve, suggesting that the model might overestimate the risk of upper extremity venous thrombosis associated with PICC in cancer patients. Conclusions:The nomogram model has a good predictive value and strong operability, which can be used to predict the probability of upper extremity venous thrombosis associated with PICC in cancer patients after PICC insertion. It can provide a reference for identifying the high-risk cancer patients and formulating proper therapeutic strategies.