The mechanism of whey protein and blueberry juice mixed system fermented with Lactobacillus inhibiting Escherichia coli during storage.

The aim of this study was to identify the antimicrobial effect and mechanism of whey protein and blueberry juice mixed systems fermented with Lactobacillus against Escherichia coli during storage. The whey protein and blueberry juice mixed systems were fermented with L. casei M54, L. plantarum 67, S. thermophiles 99 and L. bulgaricus 134 and had different antibacterial activities against E. coli during storage. The antimicrobial activity of the mixed whey protein and blueberry juice mixture systems was the highest, with an inhibition zone diameter of approximately 230 mm, compared with the whey protein or blueberry juice systems alone. There were no viable E. coli cells 7 h after treatment with of the whey protein and blueberry juice mixed systems as determined by survival curve analysis. Analysis of the inhibitory mechanism showed that the release of alkaline phosphatase, electrical conductivity, protein and pyruvic acid contents, and aspartic acid transaminase and alanine aminotransferase activity in E. coli increased. These results demonstrated that these mixed systems fermented with Lactobacillus, especially those containing blueberries, could inhibit the growth of E. coli and even cause cell death by destroying the cell membrane and cell wall.

Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants of concern (VOC), such as Delta (B.1.617.2) and Omicron (B.1.1.529), has continued to drive the worldwide pandemic. Therefore, there is a high demand for vaccines with enhanced efficacy, high thermostability, superior design flexibility, and fast manufacturing speed. Here, we report a circular RNA (circRNA) vaccine that encodes the trimeric RBD of SARS-CoV-2 Spike protein. Without the need of nucleotide modification, 5-capping or 3-polyadenylation, circRNA could be rapidly produced via in vitro transcription and is highly thermostable whether stored in naked or lipid-nanoparticle (LNP)-encapsulated format. LNP-encapsulated circRNARBD elicited potent neutralizing antibodies and T cell responses, providing robust protection against Beta (B.1.351) and native viruses in mice and rhesus macaques, respectively. Notably, circRNA vaccine enabled higher and more durable antigen production than 1m{Psi}-modified mRNA vaccine, eliciting a higher proportion of neutralizing antibodies and stronger Th1-biased immune responses. Importantly, we found that circRNARBD-Omicron vaccine induced effective neutralizing antibodies against only Omicron but not Delta variant. By contrast, circRNARBD-Delta could elicit high level of neutralizing antibodies against both Delta and Omicron. Following two doses of either native- or Delta-specific vaccination, circRNARBD-Delta, but not Omicron or Beta vaccines, could effectively boost the neutralizing antibodies against both Delta and Omicron variants. These results suggest that circRNARBD-Delta is a favorable choice for vaccination to provide a broad-spectrum protection against the current variants of concern of SARS-CoV-2.

Clinical efficacy of montelukast on bronchial asthma and influence on the immune state of patients / 中国生化药物杂志

Objective To observe the effect of montelukast on bronchial asthma and influence on the immune state , in order to provide support for the treatment of montelukast.Methods 92 patients with bronchial asthma in our hospital from December 2014 to January 2016 were selected in the study and randomLy divided into two group.The control group was treated with the conventional therapy of bronchial dilation and glucocorticoid inhalation , and on this basis, the treatment group was loaded with montelukast, 10 mg/times, one times of one day, and the course of treatment was one months.Then the frequency of acute attack of asthma and the number of beta receptor agonist were before and after treatment were recorded , and the lung function the level of T lymphocyte subsets and the levels of inflammatory cytokines before treatment and after treatment were detected , and the difference between the two groups was compared.Results After treatment, t the frequency of acute attack of asthma of day and night and the number of beta receptor agonist of the treatment group were significantly lower than the control group, the FEV1%, FVC% and PEF% of the treatment group were significantly higher than the control group, the level of CD8 + was significantly lower than the control group, the ratio of CD4 +/CD8 + was higher than the control group; the levels of IL-2, INF-γwere higher than the control group, while the levels of IL-4, IL-8 were lower than the control group (P<0.05).Conclusion The montelukast has certain regulation effect on imbalance of CD4 +/CD8 +and Th1/Th2 in children with bronchial asthma, and have a good effect on the prevention of asthma.

Expression and clinical significance of PAK1 and BRAF V600E mutation in papillary thyroid carcinoma / 中华普通外科杂志

Objective To investigate the expression of P-21 activated kinase 1 (PAK1) and v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation in papillary thyroid carcinoma (PTC)and their relationship with clinicopathological characteristics.Methods Immunohistochemistry was used to detect the expression of BRAF V600E mutation and P-21 activated kinase 1 (PAK1) in 55 PTC tissues and 25 benign thyroid tissues.The correlation between their expression and clinicopathological characteristics were analyzed.Results BRAF V600E mutation and PAK1 expressed differently between PTC and benign thyroid (respectively,x2 =12.121,9.950,all P ＜ 0.01).The expression of PAK1 and BRAF V600E mutation was positively and significantly correlated with tumor invasion,grades and lymph node metastasis(P ＜ 0.05),but it had no correlation with age,gender,tumor size,multiple tumor foci and bilateral tumor foci in PTC (P ＞ 0.05).Expression of PAK1 in BRAF V600E negative PTC was higher than that in BRAF V600E positive PTC,and expression of PAK1 and BRAF V600E mutation in PTC were negatively correlated(r =-0.284,P ＜ 0.05).Conclusion Overexpression of either BRAF V600E mutation or PAK1 predicts poor prognosis of PTC patients.

Helix hydro-jet compared with the holmium laser lithotripsy in the treatment of intrahepatic bile duct stones / 中华普通外科杂志

Objective To evaluate the curative effect,safety,advantages and disadvantages of helix hydro-jet and holmium laser lithotripsy in the treatment of intrahepatic bile duct stones.Methods 158 patients of intrahepatic bile duct stones were divided into helix hydro-jet group (n =82) and helix hydro-jet group (n =76).Time of lithotripsy,frequencies of lithotripsy,residual stone,intraoperative hemorrhage,postoperative hemorrhage,stone recurrence rate,postoperative fever,and therapeutic efficacy were compared between the two groups.Results There was no significant difference between the two groups on frequency of lithotripsy,residual stone rate and stone recurrence rate (P ＞ 0.05) ; whereas intraoperative washing normal saline (2 300 ± 275) ml vs (2 850 ± 331) ml,(P =0.002),the time of lithotripsy (54.2 ± 15.3) min vs (38.1 ± 12.7) min,P =0.041,intraoperative hemorrhage (19 cases vs 29 cases,P =0.041),Intraoperative analgesia (2 cases vs 9 cases,P =0.032),postoperative hemorrhage (11 cases vs 21 cases,P =0.037),and postoperative fever (30 cases vs 62 cases,P =0.027) had significant differences(P ＜ 0.05).Conclusions Both helix hydro-jet and the holmium laser lithotripsy is safe and effective for the treatment of intrahepatic bile duct stones.Holmium laser is more efficient than Helix Hydro-jet,while helix hydro-jet is safer than holmium laser in lithotripsy.

Total trans-oral endoscopic thyroidectomy and cervical lymphadenectomy: a human cadavers surgery study / 中华外科杂志

<p><b>OBJECTIVE</b>To find an approach for trans-oral endoscopic thyroidectomy (TOET) and cervical lymphadenectomy using conventional endoscopic surgical instruments on frozen fresh cadavers.</p><p><b>METHODS</b>Six frozen fresh cadavers were used in three groups of trans-oral trocar installation experiments: oral vestibule installation, sublingual region installation, and combined bi-vestibular and sublingual installation. TOET (with pretrachealis method to thyroid fixation removal) and cervical lymphadenectomy were performed experiments on another 6 frozen fresh cadavers using the best access approach found in the aforementioned experiments.</p><p><b>RESULTS</b>In oral vestibule trocar installations, the trocars caused large lacerated wound and damaged air tightness. In sublingual installations, only one trocar could be installed in the sublingual area because the space in sublingual area was limited. In combined bi-vestibular and sublingual installations, no gland, vessel or nerve was damaged. Combined bi-vestibular and sublingual access were selected as the surgical approach on the basic of analysis the merits of each approach. TOET and cervical lymphadenectomy in area III, IV, VI, VII were performed without making any accessory damage through combined bi-vestibular and sublingual access approach.</p><p><b>CONCLUSIONS</b>TOET is feasible. Combined bi-vestibular and sublingual approach is available for TOET. Part of the cervical lymph nodes could be resected. Pretrachealis approach to thyroid fixation removal can still be used.</p>

Ursolic acid down-regulates COX-2 expression by suppressing the activation of ERK in A549 cells / 中国药科大学学报

The antitumor effect and the mechanism of action of ursolic acid in A549 cells(human non-small-cell lung cancer cells) was investigated in this paper. Firstly, MTT assay was performed to test whether ursolic acid could inhibit the growth of A549 cells. Secondly, Western blot was utilized to measure the expression level of COX-2 and the activation of MAPKs. The MTI assay revealed that ursolic acid inhibited the growth of A549 cells. The result of Western blot suggested that ursolic acid inhibited the expression of COX-2 and activation of ERK and ERK specific inhibitor PD98059 suppressed the expression of COX-2 synergistically with ursolic acid. Taken together, our data suggest that ursolic acid can suppress LPS-induced COX-2 expression in A549 cells, which could be due to the inhibition of the activation of ERK.

Study of immunological effect of dendritic cell transfected with survivin gene on the specific anti-alimentary tract tumor / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of dendritic cells (DCs) transfected with survivin gene, and to observe the effective and specific anti-tumor immunological effect induced by modified DC in vitro.</p><p><b>METHODS</b>Survivin gene was transfected to DCs with liposomes. Survivin expression could be detected both in DCs cells and in cell culture with method of Western blot. Cytokines as well as cellular surface molecule such as IL-12, TNF-alpha, CD1 alpha, CD83, MHCII, CD80 and CD86 were detected. The competence of inducing human specific cytotoxic T lymphocyte (CTLs) was also detected with MTT.</p><p><b>RESULTS</b>Survivin expression could be detected both in DCs which were transfected with survivin cDNA and in cell culture superior. The IL-12 and TNF-alpha level was (265.2 +/- 32.7), (437.1 +/- 83.5) pg/ml, and much higher in transgened DC cells than blank DC cells (P < 0.05). CD1 alpha, CD83, MHCII, CD80 and CD86 was high expressed in survivin-DC cells, however, it was low expressed in blank DC cells. The lyse rate to gastric cancer cell, colon cancer cell and bile duct cancer cell was 65%, 77%, and 85% respectively, and these were much higher than those of blank DC cells.</p><p><b>CONCLUSIONS</b>DCs transfected with survivin gene could induce specific cytotoxic T lymphocytes and strikingly raised DC cell's antigen present function, and have specific CTL killing activity.</p>

Effects of dendritic cells transfected with full length wild type P53 and modified by gastric cancer lysate on immune response / 华中科技大学学报（医学）（英德文版）

To investigate the effects of dendritic cells (DCs) transfected with full length wild type p53 and modified by gastric cancer lysates on immune response, the wild type P53 was transducted to DCs with adenovirus, and the DCs were modified by gastric cancer lysates (Lywt-P53DC). The concentration of the surface molecules (B7-1, B7-2, MHC-I , MHC-II) of all DCs was determined by FACS, and the ability of the DCs to induce efficient and specific immunological response in anti-51Cr-labeled target cells studied. BALB/c mice model infected with DCs and Mk28 was established. CTL response in mice immunized with Lywt-p53DC and the effectiveness of Lywt-p53DC in the treatment of tumor-bearing mice was assayed. FACS revealed that the surface molecules of Ly-wt-P53 DC had a high expression: for B7-1 86.70% +/- 0.07%, B7-2 18.77% +/- 0.08%, MHC-I 87.20% +/- 0.05%, MHC-II 56.70%+/-0.07%; The T lymphocytes had a specific CTL lysing ability induced by Lywt-P53DC with the CTL lysis rate being 81%. The immune protective effect of Lywt-p53DC group was more obvious than any other groups (P<0.05). The tumor diameter in Lywt-p53DC group was 3.10+/-0.31 mm, 2.73+/-0.23 mm, 3.70+/-0.07 mm on the day 13, 16 and 19, smaller than DC, wtp53DC and LyDC groups (P<0.05). On the other hand, the growth rate of tumor in Lywt-p53DC group was slower than any other groups (P<0.05). It was suggested that DCs transfected with wild type P53 and modified by gastric cancer lysates had specific CTL killing capability.

Regulative effect of IFN-gamma on the Fas/Fas L system of cholangiocarcinoma cells / 中华预防医学杂志

<p><b>OBJECTIVE</b>To detect the regulative effects of IFN-gamma on the expression of Fas and FasL of cholangiocarcinoma cells.</p><p><b>METHODS</b>We studied that the expression of Fas and FasL gene by the human cholangiocarcinoma cell line QBC939 by RT-PCR, Western blot, immunohistochemistry. At the same time, we investigated the regulative effect of IFN-gamma on them.</p><p><b>RESULTS</b>Fas and FasL mRNA and protein were expressed by cholangiocarcinoma cells. We also found IFN-gamma could upregulate the expression of the two genes (P < 0.01). However, IFN-gamma could also downregulate the ability of them to make Jurkat cells apoptotic. With the increasing of dosage and time, the effect was enhanced.</p><p><b>CONCLUSIONS</b>IFN-gamma could regulate the expression of Fas and FasL by cholangiocarcinoma cells, therefore it could reduce the ability of cholangiocarcinoma to occur immune escape. This provides new theoretical basis for immunological therapy of cholangiocarcinoma.</p>