Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

Antibiotics prescription for targeted therapy of pediatric invasive pneumococcal diseases in China: a multicenter retrospective study.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

[Reversal Effect of NVP-BEZ235 on Doxorubicin-Resistance in Burkitt Lymphoma RAJI Cell Line].

OBJECTIVE: To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line. METHODS: The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin. The levels of Pgp, p-AKT, and p-mTOR in cells were detected by Western blot. Cell viability was detected by MTT assay. IC50 was computed by SPSS. RESULTS: The doxorubicin-resistant Burkitt lymphoma cell line, RAJI/DOX, was established successfully. The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line. NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line. NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line, and the effect was obvious when it was cooperated with doxorubicin. CONCLUSION: The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line. NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.

Heterogeneous Information Network-Based Patient Similarity Search.

Patient similarity search is a fundamental and important task in artificial intelligence-assisted medicine service, which is beneficial to medical diagnosis, such as making accurate predictions for similar diseases and recommending personalized treatment plans. Existing patient similarity search methods retrieve medical events associated with patients from Electronic Health Record (EHR) data and map them to vectors. The similarity between patients is expressed by calculating the similarity or dissimilarity between the corresponding vectors of medical events, thereby completing the patient similarity measurement. However, the obtained vectors tend to be high dimensional and sparse, which makes it hard to calculate patient similarity accurately. In addition, most of existing methods cannot capture the time information in the EHR, which is not conducive to analyzing the influence of time factors on patient similarity search. To solve these problems, we propose a patient similarity search method based on a heterogeneous information network. On the one hand, the proposed method uses a heterogeneous information network to connect patients, diseases, and drugs, which solves the problem of vector representation of mixed information related to patients, diseases, and drugs. Meanwhile, our method measures the similarity between patients by calculating the similarity between nodes in the heterogeneous information network. In this way, the challenges caused by high-dimensional and sparse vectors can be addressed. On the other hand, the proposed method solves the problem of inaccurate patient similarity search caused by the lack of use of time information in the patient similarity measurement process by encoding time information into an annotated heterogeneous information network. Experiments show that our method is better than the compared baseline methods.

[Lossless ECG hybrid compression method based on JPEG 2000].

After a study on the characteristic of ECG data, we propose here in this paper a lossless compression method of ECG data, which is based on JPEG2000. It integrates both 1D and 2D compression. The method has been verified through all forty-eight records in MIT-BIH Arrhythmia database. And the result shows that the method has a better compression rate and a good computational efficiency.

[Structuralization of digestive endoscopy report based on NLP].

This paper presents a method based on NLP to realize structuralization of digestive endoscopy reports. The method is taking advantage of existing NLP's processing technologies and introducing minimal standard terminology (MST) to transform a narrative gastroscopy report into the structuralization report based on MST, whose accuracy rate is 92.3%.

[A positioning error measurement method in radiotherapy based on 3D visualization].

The positioning error in radiotherapy is one of the most important factors that influence the location precision of the tumor. Based on the CT-on-rails technology, this paper describes the research on measuring the positioning error in radiotherapy by comparing the planning CT images with the treatment CT images using 3-dimension (3D) methods. It can help doctors to measure positioning errors more accurately than 2D methods. It also supports the powerful 3D interaction such as drag-dropping, rotating and picking-up the object, so that doctors can visualize and measure the positioning errors intuitively.

[Design and practice of the Clinical Information System for ICU].

This paper presents a typical Clinical Information System for ICU and its design and implementation. This system is able to capture and archive vital data from the monitor network, providing a whole digital solution in ICU. These vital data can be used in quantitative analysis in the computer-assisted decision support.

[Consistent presentation of medical images based on CPI integration profile].

Because of different display parameters and other factors, digital medical images present different display states in different section offices of a hospital. Based on CPI integration profile of IHE, this paper implements the consistent presentation of medical images, and it is helpful for doctors to carry out medical treatments of teamwork.

[Designing and implementation of a PACS].

PACS (Picture Archiving and Communication System) is successfully applied in Huzhou Central Hospital, and is well integrated with its HIS system by WEBSERVICE middleware. The system supports DICOM 3.0 Standard, and DICOM gateways are installed for modalities that do not support DICOM so as to have implemented the digitalization of all the image departments in the hospital.

[Changes in polyamine levels in Citrus sinensis Osb. cv. Valencia callus during somatic embryogenesis].

Somatic embryogenetic capability and changes in polyamine level and their relationship were analyzed using the long-term (8 years) subcultured calli of Citrus sinensis Osb. cv. Valencia as materials. The results showed that endogenous polyamine contents in embryogenic calli were higher than those in non-embryogenic calli, and the embryogenetic capability was positively correlated to the levels of endogenous polyamines. When the calli were transferred to a differentiation medium, the putrescine content rapidly increased and reached a peak, then fell gradually. Applying exogenous putrescine raised the embryogenesis frequency and endogenous putrescine level. It indicated that increase in putrescine content at early stage of differentiation promoted embryogenesis. With the development of somatic embryo, spermidine content reached its the highest level at globular embryo stage, spermine content rose and reached a peak at a later stage of globular embryo development. Furthermore, changes of the putrescine, spermidine and spermine contents during somatic embryogenesis were similar in Valencia calli which had different ploidy levels, but their contents decreased following the increasing of ploidy level. Changes in arginine decarboxylase activity were positively correlated to the polyamine levels, which suggest that the later is a key factor in regulating the polyamine levels during somatic embryogenesis in citrus plants.

[IHE technical framework and its application].

Firstly, IHE technical framework is introduced in this paper, and the sub-framework of Schedule Workflow is also described. Secondly, the development of IHE in Japan and the formation of IHE-J are presented, and in combination with IDS system's practice in IHE-J, some ideas about developing IHE in China and the relative methods of implementation are discussed.

Inhibition of lung cancer cell proliferation by CD40 signaling through tumor necrosis factor I.

BACKGROUND AND OBJECTIVE: CD40 signaling induces growth inhibition in some tumor cells in vitro, but the precise molecular mechanism remains unclear. This study was to investigate the biological effects and mechanisms of CD40 stimulation on proliferation of lung cancer cell lines NCI-H460 and A549, changes in tumor necrosis factor receptors (TNFRs) and membrane tumor necrosis factor alpha (mTNF-alpha). METHODS: The expression of CD40 on the cell surface, and changes in TNFR and mTNF-alpha expression after CD40 stimulation were detected by the immunofluorescence technique and flow cytometry. Changes in protein contents of TNFR as well as mTNF-alpha expression after CD40 stimulation were measured by western blot. The cell proliferation rate was determined by MTT assay. The content of soluble TNF-alpha(sTNF-alpha) in the supernatant of lung cancer cells was measured by ELISA assay. RESULTS: The expression rates of CD40 in NCI-H460 and A549 were (89.0 +/- 3.2)% and (62.2 +/- 4.5)%, respectively. After 48 h of CD40 stimulation, the expression rates of TNFRI in NCI-H460 and A549 became significantly higher [(36.2 +/- 4.6)% and (38.5 +/- 5.9)%] than those in the corresponding control cells [(15.2 +/- 3.1)% and (7.2 +/- 1.9)%] (p < 0.05); while the expression rates of TNFRII were significantly lower than those in the control cells [(18.0 +/- 1.6)% and (5.8 +/- 1.2)% vs. (58.1 +/- 3.6)% and (38.8 +/- 4.3)%] (p < 0.05); the expression rates of mTNF-alpha were decreased in the two cell lines [(8.7 +/- 1.1)% and (7.0 +/- 0.9)%] as compared to those in control cells [(15.0 +/- 2.1)% and (26.5 +/- 3.2)%] (p < 0.05). The level of TNFRI protein was elevated with the downregulation of TNFRII protein in NCI-H460 and A549. The level of mTNF-alpha protein remained unchanged in the two cell lines. TNF-alpha was not detectable in the supernatant of lung cancer cells. Moreover, cell proliferation of NCI-H460 and A549 were inhibited after CD40 stimulation (p < 0.05), but the inhibition effect disappeared after blocking TNFRI. Blocking of TNF-alpha inhibited cell proliferation of the two cell lines (p < 0.05), but a synergistic effect was not observed after simultaneous stimulation with CD40. CONCLUSION: CD40 signaling inhibits the proliferation of CD40-positive lung cancer cells through mTNF-alpha/TNFRI in vitro.