AIM: To explore the effect of dihydroquercetin on visual function in mice with form deprivation myopia based on the NOD-like receptor thermoprotein domain-related protein 3(NLRP3)inflammasome pathway.METHODS: The C57BL/6 mice were randomly divided into control group and form deprivation myopia model group, and the form deprivation myopia model group was constructed by covering the right eye with a translucent eye patch. After successful modeling, the mice in the model group of form deprivation myopia were randomly divided into model group, low-, medium- and high-dose dihydroquercetin groups, and high-dose dihydroquercetin + NLRP3 agonist group. The diopter and axial length of mice in each group were detected. The kit was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in retinal tissue. RT-qPCR was used to detect the mRNA expressions of NLRP3, apoptosis-associated spot-like protein(ASC), Caspase-1, IL-1β and IL-18 in retinal tissues. Western blot was used to detect the expression of NLRP3, ASC, cleaved Caspase-1, IL-1β and IL-18 proteins in retinal tissues. TUNEL staining was used to detect apoptosis in retinal tissue.RESULTS: Compared with the control group, the diopter of the mice in the model group decreased, and axial length increased, and the SOD decreased whereas MDA, NLRP3, ASC, Caspase-1, IL-1β, IL-18 increased, and the rate of apoptosis in retinal tissue increased(all P<0.05). Compared with the model group, the diopter of mice in the low-, medium- and high-dose dihydroquercetin groups increased, axial length shortened, the SOD increased, whereas MDA, NLRP3, ASC, Caspase-1, IL-1β, IL-18 decreased, and the rate of apoptosis in retinal tissue decreased(all P<0.05). Compared with the high-dose dihydroquercetin group, the high-dose dihydroquercetin+NLRP3 agonist group had reduced diopter, increased axial length, decreased SOD levels, elevated MDA, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 levels, as well as increased apoptosis rate in retinal tissue(all P<0.05).CONCLUSION: Dihydroquercetin can improve visual function in mice with form deprivation myopia by inhibiting pyroptosis and oxidative stress responses, which may be related to the suppression of NLRP3 inflammasome. NLRP3 agonists can partially mitigate the effects of high-dose dihydroquercetin on form deprivation myopia in mice.

Macrophage extracellular traps(METs)are extracellular fibrous web-like structures produced by macro-phages.Under physiological conditions,METs capture and kill microorganisms by releasing high concentrations of granular proteins,serving as an innate immune defense mechanism and playing a vital protective role in resisting the progression of inflammatory diseases.Excessive release of METs can also exacerbate the inflammatory response and cause further tissue damage.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Objective To evaluate the relationship between atrial synchrony and paroxysmal atrial fibrillation (PAF) in patients with sick sinus syndrome (SSS) by two-dimensional speckle tracking imaging. Methods Forty-four SSS patients who underwent echocardiographic examination at Department of Ultrasound, No. 2 Hospital of Yinzhou in Ningbo City of Zhejiang Province from January 2015 to August 2016 were enrolled, including 25 without PAF and 19 with PAF. Twenty-eight normal adults who underwent echocardiographic examination at this department at the same time were included as a normal control group. The structural and functional parameters of the left ventricle of all enrolled subjects were evaluated by echocardiographic examination. After two-dimensional speckle tracking images of the right atrium free wall, atrial septum, and left atrium free wall were obtained, the time interval from the initial point of P wave on electrocardiograph to the second negative wave of the diastolic phase in two-dimensional speckle tracking images were measured to calculate the electrical-mechanical time of the right atrium free wall (P-RA), the electrical-mechanical time of the atrial septum (P-IAS), and the electrical-mechanical time (P-LA) of the left atrium free wall. Subsequently, the parameters of atrial synchrony were calculated. Conventional echocardiographic parameters, P-RA, P-IAS, P-LA, and the parameters of atrial synchrony were compared among the three groups by one-way ANOVA, and further comparisons between any two groups were performed by the SNK-q test. The relationship between the parameters of electrical-mechanical time, parameters of atrial synchrony, and PAF were analyzed by Spearman correlation analysis. Receiver operating characteristic curve (ROC) analysis was then performed to evaluate the value of the parameters of electrical-mechanical time and parameters of atrial synchrony in predicting PAF. Results The left atrial size was significantly larger in the SSS without PAF group and SSS with PAF group than in the normal control group (q=4.18, 5.37, both P＜0.05), although there was no significant difference between the SSS without PAF group and SSS with PAF group. The P-RA and P-IAS were significantly larger in the SSS without PAF group and SSS with PAF group than in the normal control group (q=4.03, 4.10; q=4.16, 4.31, all P＜0.05), but there was no significant difference between the SSS without PAF group and SSS with PAF group. The P-LA, right atrial intra-atrial synchrony, left atrial intra-atrial synchrony, and inter-atrial synchrony showed a gradually rising trend from the normal control group to the SSS without PAF group and SSS with PAF group, and the difference between any two groups was statistically significant (q=5.18, 11.23, 4.43; q=5.25, 11.74, 4.63; q=7.38, 14.67, 4.73; q=8.01, 16.37, 6.39, all P＜0.05). Spearman correlation analysis showed that P-LA, right atrial intra-atrial synchrony, left atrial intra-atrial synchrony, and inter-atrial synchrony were significantly positively correlated with PAF in patients with SSS (r=0.61, 0.55, 0.75, 0.78, all P ＜ 0.01), and the correlation between inter-atrial synchrony and PAF was the highest. ROC analysis demonstrated the optimal threshold of P-LA for prediction of PAF was 94 ms [sensitivity: 68.42%; specificity: 76.00%; the area under the ROC curve (AUC): 0.764 (95% CI: 0.612-0.879)]; the optimal threshold of right atrial intra-atrial synchrony was 19 ms [sensitivity: 57.89%; specificity: 76.00%; AUC: 0.714 (95% CI: 0.558-0.840)];the optimal threshold of left atrial intra-atrial synchrony was 42 ms [sensitivity: 78.95%; specificity: 76.00%;AUC: 0.860 (95% CI : 0.722-0.946)]; and the optimal threshold of inter-atrial synchrony was 68 ms [sensitivity:84.21%; specificity: 84.00%; AUC: 0.859 (95% CI: 0.721-0.945)]. These results suggest that left atrial intra-atrial synchrony and inter-atrial synchronization are superior to right atrial intra-atrial synchrony in predicting PAF in patients with SSS. Conclusion Atrial electro-mechanical motion time parameters and synchrony parameters are closely related to PAF in patients with SSS, and left atrial intra-atrial synchrony and inter-atrial synchronization are the most effective parameters in predicting PAF in patients with SSS.

The Internet Public Opinion Monitoring and Early Warning System for medical and health industry was designed and implemented due to the frequent occurrence of Internet public opinion, which has all-directional data collecting and analyzing functions, including big data collection, near duplicate detection, spam filtration, key public opinion early warning, region identification and tendency analysis, and can thus provide evidence for relevant departments to take effective measures for the control of Internet public opinion.

Objective To investigate the correlation between Young′s elastic modulus (EI) using shear wave elastography (SWE) and liver pathology .Methods Liver biopsy was performed on 231 patients with chronic hepatitis B (CHB) under supersonic guidance ,and SWE with EI of liver was obtained concurrently .The correlation between measured liver stiffness and pathology was analyzed by using the liver pathology as golden standards .One‐way analysis of variance and Spearman rank correlation analysis were performed for the comparison between groups and correlation between two variables , respectively .Receiver operating characteristic (ROC) curve was used to explore the predictive value of shear modulus for the liver inflammation grades and fibrosis stages .Results The EI medians of different liver inflammation grades were 6 .78 kPa (G1) ,7 .30 kPa (G2) ,9 .93 kPa (G3) and 14 .93 kPa (G4) , respectively ,which were statistically different (H=55 .19 ,P<0 .01) .And EI medians of various fibrosis stages were 6 .62 kPa (S0 -S1) ,7 .15 kPa (S2) ,9 .78 kPa (S3) and 14 .62 kPa (S4) ,respectively , which were also significantly different (H=62 .14 ,P<0 .01) .EI was positively correlated with both liver inflammation grades (r=0 .454 6 ,P<0 .01) and liver fibrosis stages (r=0 .505 6 ,P<0 .01) .The areas under the ROC for G≥2 ,G≥3 and G=4 were 0 .68 (95% CI:0 .61 -0 .75) ,0 .77 (95% CI:0 .70 -0 .84) and 0 .85 (95% CI:0 .77-0 .92) ,respectively .The areas under the ROC for S≥2 ,S≥3 and S=4 w ere 0 .73 (95% C I:0 .66 -0 .79 ) ,0 .78 (95% C I:0 .72 -0 .85 ) and 0 .83 (95% C I:0 .75 -0 .91 ) , respectively .Conclusion The EI measured by SWE is correlated with liver pathology of CHB patients , which may be used to dynamically monitor the progress of liver fibrosis .

Objective To investigate whether prophylactic antifungal treatment will reduce the incidence of fungal infection(FI)and the mortality in severe acute pancreatitis(SAP).Methods Forty consecutive patients with SAP admitted from January 2008 to December 2009 were divided into prevention group and control group with 20 cases each by random digits table.The patients in prevention group underwent routine therapy plus intravenous fluconazol as prophylactic antifungal treatment,while routine therapy only in control group.The length of hospital stay,the time when FI occurred,the incidence of FI and mortality were compared with each other.Results Compared with control group,the length of hospital stay wag shorter[(40.3±15.4)d vs.(46.5±18.5)d],the time when FI occurred was slewer[(24.5±14.3)d vs. (14.5±12.7)d],the incidence of FI[15.0%(3/20)vs.35.0%(7/20)]and the mortality [10.0%(2/20)vs. 25.0%(5/20)]were lower in prevention group,there were significant differences between the two groups(P<0.05).Conclusion Prophylactic antifungal treatment can shorten the hospital stay,delay the FI occurrence,reduce the incidence of FI and the mortality in patients with SAP.

BACKGROUND AND OBJECTIVETranscatheter arterial chemotherapy and embolization is the main method in the treatment of lung cancer, but most of the reports do not study individually to small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), hypovascular and hypervascular lung cancer. The pre-embolization perfusion of hemotherapeutics is still being used routinely and seldom report to iodized oil embolization. The article summarized the quality of life after the treatment, clinical efficiency, survival time and complications to evaluate the clinical effect of primary hypervascular NSCLC treated with embolization of emulsion of chemotherapeutics and iodized oil.

METHODSThe study totally analyzed 41 cases which confirmed by pathology and follow up study from January, 2008 to January 2009. The CT scan with IV contrast demonstrates over moderate enhanced lesion which indicate hypervascular. Within the 41 cases, 23 cases of central, 18 cases of peripheral. Suqamous carcinoma 21 cases, adenocarcinoma 15 cases and squamoadenocarcinoma 5 cases. Stage IIIb 34 cases, stage IV 7 cases. Superselective incubation with microcatheter under DSA, to embolize the capillary bed with liquefied iodized oil and the emulsion of pharmorubicin, to embolize the supply artery of the tumor with gelatin foam microparticle. The liquefied iodized oil 5 mL-10 mL, pharmorubicin 10 mg-30 mg. The longest follow up is 12 months and to compare with the references of 2007-2009.

RESULTSThe KPS is widely acclaimed after the treatment (P < 0.05), no complete response (CR), 31 cases of partial response (PR), 7 cases of no change (NC) and 3 cases of progressive disease (PD), the total efficiency (CR+PR) is 75.6%. The clinical efficiency (CR+PR+NC) is 92.68%. 33 cases of total survival tome over 12 months (80.48%), IIIb stage 29/34 (85.29%), IV stage 4/7 (57.14%). 1 case with severe complication-spinal injury.

CONCLUSIONTo treat primary hypervascular NSCLC with simple embolization of emulsion of chemotherapeutics and iodized oil is very useful and can avoid the side effect of chemotherapeutics. The key point to avoid spinal injury and other severe complications is to distinguish the spinal aretery and intratumor AV fistula by using superselective incubation with microcatheter under DSA.

Carcinoma, Non-Small-Cell Lung ; blood supply ; mortality ; therapy ; Chemoembolization, Therapeutic ; Emulsions ; Female ; Humans ; Iodized Oil ; administration & dosage ; Lung Neoplasms ; blood supply ; mortality ; therapy ; Male ; Middle Aged

Objective To investigate the synergistic therapy effects of B and T lymphocyte attenuator(BTLA) extracellular domain in combination with heat shock protein 70 (HSP70)-TC-1 antigen peptide complex on the mouse model of cervical cancer and the related immunological mechanisms. Methods(1)Detecting the BTLA and herpesvirus entry mediator (HVEM) gene expression in the tumor microenvironment after C57BL/6 mice were inoculated with TC-1 tumor cells by realtime PCR; BTLA,HVEM expression on tumor infiltrating lymphocytes cell surface were detected by flow cytometry (fluorescence intensity). (2) According to different treatments, tumor-bearing mice were divided into 5 groups, which was injected with pcDNA3. 1 (empty vector plasmid as control), psBTLA (vector plasmid which expresses BTLA extracellular domain), HSP70 (HSP70-TC-1 cell peptide complex), HSP70 +pcDNA3.1 or HSP70 + psBTLA, respectively. The weight of tumor was recorded. The expression of immunoregulatory genes in tumor microenvironment were detected. The change of lymphocyte amount and cytotoxicity were detected too; lymphocyte proliferation activity was measured by tritium thymidine incorporation assay; the concentration of interleukin (IL) 2 and interferon-γ(IFN-γ) in supernatants of spleen lymphocyte were measured by enzyme-linked immunosorbent assay (ELISA). Results (1) BTLA gene expression was gradually increased after tumor cells inoculation. The highest expression level was 2. 83 + 0. 35 at 14th day, which had statistical significance difference with the 7th day expression of 1.66±0. 25 (P < 0. 05). While HVEM mRNA expression did not change significantly (P > 0. 05). The 7th and 14th day after TC-1 cells inoculation, the average fluorescence intensity of BTLA expression on the surface of tumor infiltrating lymphocytes was 33.5 and 51.8, respectively, in which there was statistically significant difference (P <0. 05); while the difference of HVEM expression was not statistically significant (57. 2 vs 49. 3 ,P >0. 05). (2)The 28th day after inoculation, tumor inhibition rate of HSP70 + psBTLA group was 88%, which was significantly higher than other treatment groups (P <0. 05). The 28th day after TC-1 cells inoculation, combination therapy not only promoted IFN-γ and IL-2 gene (3. 12 + 0.71,3.20 + 0. 62)expression but also reduced transforming growth factor-β (TGF-β), Foxp3 and IL-10 expression (0. 25±0. 03,0. 19 +0. 03,0. 31 +0. 04;P <0. 05). It also promoted CD8+ T lymphocyte infiltration(52 +6)/high power field, cytotoxicity (65.5±2.4) %, proliferation (15.0 × 103 cpm) and cytokine IL-2 , IFN-γsecretion(824±51), (1096±112) pg/ml, which were all significantly higher than other groups (P <0. 05). Conclusion The effect of immunotherapy on tumor can be augmented by the combination of psBTLA which expresses extracellular domain of BTLA and HSP70-TC-1 tumor antigen peptide complex,which could improve the expression of the related immunoregulatory genes to establish a much better microenvironment in favor of anti-tumor immune response against the mice model of the cervix carcinoma.

Objective To explore the effect of blocking BTLA-HVEM (herpesvirus entry mediator-B and T lymphocyte attenuator) pathway on dendritic cell function and the related immunological mechanisms. Methods Murine BTLA extracellular domain eukaryotic expression vector psBTLA was constructed by gene recombination and transfected CHO by Lipofection method. Mouse bone marrow cells were induced to differentiate into DCs by GM-CSF plus IL-4. Expression of BTLA and HVEM on DCs was detected after HSPT0-TC-1 peptide complex stimulation by FACS. Expression of BT-1 and secretion of IL-12 were detected after HSP70-TC-1 peptide complex plus psBTLA transfected CHO culture supernatant stimulation on DCs. Pretreated DCs co-cultured with the same genetic background mouse splenocytes and lymphocytes proliferation and cytokine secretion were detected. Effect of psBTLA gene transfer in vivo on BT-1 expression of DCs and tumor growth on tumor-bearing mice was detected. Results Extracellular domain of murine BTLA was successfully constructed, psBTLA stable transfection CHO cells were obtained and expression of BTLA extracellular domain(sBTLA) was detected the in its culture supernatant. BTLA and HVEM expression of DCs were increased after stimulation by the antigen peptide complex. When DCs were treated with antigen peptide complex plus culture supernatant containing sBTLA, B7-1 expression and IL-12 secretion were increased. Co-cultured with splenocytes, lymphocytes proliferation and cytokine secretion, such as IL-2 and IFN-γ,, were also increased. Gene transfection with psBTLA in vivo promoted B7-1 expression on DCs and inhibited cervical cancer cells growth. Conclusion Blockade of BTLA-HVEM inhibitory pathway with sBTLA can further improve DCs function, activation of lymphocytes and promote antitumor immune response.