Evaluation of the immunization effectiveness of bOPV booster immunization and IPV revaccination.

To provide a basis for further optimization of the polio sequential immunization schedule, this study evaluated the effectiveness of booster immunization with one dose of bivalent oral poliovirus vaccine (bOPV) at 48 months of age after different primary polio immunization schedules. At 48 months of age, one dose of bOPV was administered, and their poliovirus types 1-3 (PV1, PV2, and PV3, respectively)-specific neutralizing antibody levels were determined. Participants found to be negative for any type of PV-specific neutralizing antibody at 24, 36, or 48 months of age were re-vaccinated with inactivated polio vaccine (IPV). The 439 subjects who received a bOPV booster immunization at the age of 48 months had lower PV2-specific antibody levels compared with those who received IPV. One dose of IPV during basic polio immunization induced the lowest PV2-specific antibody levels. On the basis of our findings, to ensure that no less than 70% of the vaccinated have protection efficiency, we recommend the following: if basic immunization was conducted with 1IPV + 2bOPV (especially Sabin strain-based IPV), a booster immunization with IPV is recommended at 36 months of age, whereas if basic immunization was conducted with 2IPV + 1bOPV, a booster immunization with IPV is recommended at 48 months of age. A sequential immunization schedule of 2IPV + 1bOPV + 1IPV can not only maintain high levels of antibody against PV1 and PV3 but also increases immunity to PV2 and induces early intestinal mucosal immunity, with relatively good safety. Thus, this may be the best sequential immunization schedule for polio in countries or regions at high risk for polio.

Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice / 中国实验方剂学杂志

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.

Relationship between CXCL16 and natural killer T cells during renal fibrosis in mice with acute kidney injury / 中华麻醉学杂志

Objective:To evaluate the relationship between chemokine CXC-ligand 16 (CXCL16) and natural killer T cells during renal fibrosis in mice with acute kidney injury (AKI).Methods:Twenty-four healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-30 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), AKI group, control+ rCXCL16 group (group C-rCXCL16) and AKI+ rCXCL16 group.In AKI-rCXCL16 and AKI groups, folic acid 250 mg/kg was intraperitoneally injected to induce AKI in anesthetized mice, and rCXCL16 0.1 mg/kg and the equal volume of solution were intraperitoneally injected, respectively, at 3, 6, 9 and 12 days after injection of folic acid.The equal volume of solution and rCXCL16 were intraperitoneally injected at the corresponding time points in group C and group C-rCXCL16, respectively.The orbital blood samples were taken on day 14 after injection of folic acid for determination of the serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The renal tissues were obtained for measurement of the renal fibrosis size (using Sirius red staining and Masson staining), for determination of the expression of fibronectin (FN), collagen-Ⅲ (Col-Ⅲ) and α-smooth muscle actin (α-SMA) (by immunofluorescence) and expression of interleukin-4 (IL-4), mannose receptor (CD206) and arginase 1 (Arg-1) mRNA (by real-time polymerase chain reaction), and for evaluation of the ratio of CD1d Tetramer + -IL-4 + cells (by flow cytometry). Results:Compared with group C, the serum BUN and Cr concentrations were significantly increased, the renal fibrosis size was increased, the expression of IL-4, CD206, Arg-1 mRNA, FN, Col-Ⅲ and α-SMA was up-regulated, and the ratio of CD1d Tetramer + -IL-4 + cells was increased in AKI and AKI-rCXCL16 groups ( P<0.05), and no significant change was found in the parameters mentioned above in group C-rCXCL16 ( P>0.05). Compared with group AKI, the serum BUN and Cr concentrations were significantly increased, the renal fibrosis size was increased, the expression of IL-4, CD206, Arg-1 mRNA, FN, Col-Ⅲ and α-SMA was up-regulated, and the ratio of CD1d Tetramer + -IL-4 + cells was increased in group AKI-rCXCL16 ( P<0.05). Conclusion:The mechanism by which CXCL16 is involved in the process of renal fibrosis is related to the recruitment of natural killer T cells secreting IL-4 which regulates macrophage M2 polarization in mice with AKI.

Steroidogenic acute regulatory protein-related lipid transfer 4 (StarD4) promotes breast cancer cell proliferation and its mechanism / 生物医学工程学杂志

Oncogene StarD4 had the function of promoting proliferation and metastasis of triple-negative breast cancer (TNBC), but its clinical value and molecular mechanism are unknown. This paper found that StarD4 was highly expressed in cancer tissues of TNBC patients, and higher expression level of StarD4 in TNBC patient resulted in poorer prognosis. Based on transcriptomics of MDA-MB-231 cell model, the results of bioinformatics analysis showed that down-regulated expression level of StarD4 led to overall downregulation of cholesterol-relative genes and significant enrichment of cancer mechanism and pathway. Further analysis and investigation verified that StarD4 might cross-promote the protein stability of receptor ITGA5 through the cholesterol pathway to enhance TNBC progression, which provides guidance for clinical application of TNBC diagnosis and treatment.

Recombinant subgroup B avian leukosis virus combined with the subgroup J env gene significantly increases its pathogenicity.

The differences among different sub-groups of the avian leukosis virus (ALV) genome are mainly concentrated in the env gene, which binds to cell-specific receptors and determines the characteristics of viral tropism and pathogenicity. In this study, two rescued viruses rGX15MM6-2 (ALV of subgroup J, ALV-J) and rGX14FF03 (ALV of subgroup B, ALV-B) and a recombinant virus rALV-B-Jenv (ALV-B's backbone with ALV-J's env) were generated and tested utilizing both in vitro and in vivo experiments. The results showed that the replication ability of the viruses released in DF-1 cell cultures was listed in order as rGX15MM6-2 > rALV-B-Jenv > rGX14FF03. rGX15MM6-2 caused the most serious suppression of body weight gain, exhibited a significant negative effect on the development of immune organs (P < 0.05) and lower antibody responses to vaccinations with the commercial oil-emulsion vaccines (OEVs) (P<0.05) in the challenged chickens. The viral detection showed that the positive rate in blood from the birds infected with rALV-B-Jenv were respectively higher than those from the birds infected with rGX14FF03 (P < 0.05). At 25 wpi, similar tumors were found in the abdominal cavity of the birds in rGX15MM6-2 and rALV-B-Jenv groups. The results demonstrated that the ALV-J env gene significantly increases the pathogenicity of the recombinant ALV-B. With the increasing incidence of co-infections of different subgroups of ALV in the field, the possibility of viral recombination is increasing and demands further study.

Vertical transmission of ALV from ALV-J positive parents caused severe immunosuppression and significantly reduced marek's disease vaccine efficacy in three-yellow chickens.

In order to evaluate the influence of the vertical transmission of avian leukosis virus (ALV) from J subgroup (ALV-J) positive parents on the vaccine efficacy of Marek's disease virus (MDV), ALV-J positive male breeders × female breeders of Three-yellow chickens and the ALV negative male breeder × the negative female breeders were used respectively for crossbreeding to produce eggs and the hatching offspring. The commercial CVI988/Rispens vaccine was used to vaccinate the crossbred offspring at 1-day-old. At 7-days-old, the birds were inoculated with the inactivated oil-emulsion vaccines (OEVs) AIV-H5 monovalent and NDV + AIV-H9 bivalent, respectively. Then the birds were challenged with a Chinese very virulent (vv) MDV field strain GXY2 at 14-day-old. The results showed that the viral load of the challenged GXY2 in the offspring from the ALV-J positive breeders was significantly higher than that from the ALV-negative breeders' (P < 0.05), and the mortality and tumor incidence of offspring from the ALV-J positive breeders were higher than those of the ALV-negative breeders. Also the offspring of the ALV-J positive breeders exhibited a significant negative effect on the development of the immune organs (P < 0.05) and lower antibody responses to the vaccinations with the commercial OEVs (P<0.05). The MD vaccine protective index in the offspring from the ALV-J positive breeders was lower than that from the ALV-negative breeders. The results of the study demonstrated that the vertical transmission of ALV from the ALV-J positive parents caused severe immunosuppression and significantly reduced the Marek's disease vaccine efficacy in Three-yellow chickens.

Adoption of Regulations for Cell Therapy Development: Linkage Between Taiwan and Japan.

Although cell-based therapy has become a promising treatment, its practice and evaluation process remain unstandardized. Therefore, Japan initiated a dual-track regulatory framework for cell-based therapy aiming to promote and regulate the therapies to ensure that patients can access safe and effective treatments. Influenced by such pathway, Taiwan adopted the framework and initiated its own cell-based therapy regulation in 2018. This paper discusses how Japan has influenced Taiwan in developing regulations for cell-based therapy.

Role of SIRT1 in hematologic malignancies / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Sirtuin 1 (SIRT1) is a protein deacetylase, which regulates various physiological activities by deacetylating different protein substrates. An increasing number of studies have revealed critical roles of SIRT1 in different aspects of cancers including metabolism, proliferation, genomic instability, and chemotherapy resistance. Depending on the protein targets in a certain oncogenic context, SIRT1 may play a unique role in each individual blood cancer subtype. Our previous work showed that activation of SIRT1 in primitive leukemia cells of acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) promotes disease maintenance. On the other hand, an SIRT1 agonist was shown to disrupt maintenance of myelodysplastic syndrome (MDS) stem cells and holds promise as a potential therapeutic approach. Herein, we present a concise summary of the different functions of SIRT1 in hematologic malignancies.

Role of SIRT1 in hematologic malignancies / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Sirtuin 1 (SIRT1) is a protein deacetylase, which regulates various physiological activities by deacetylating different protein substrates. An increasing number of studies have revealed critical roles of SIRT1 in different aspects of cancers including metabolism, proliferation, genomic instability, and chemotherapy resistance. Depending on the protein targets in a certain oncogenic context, SIRT1 may play a unique role in each individual blood cancer subtype. Our previous work showed that activation of SIRT1 in primitive leukemia cells of acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) promotes disease maintenance. On the other hand, an SIRT1 agonist was shown to disrupt maintenance of myelodysplastic syndrome (MDS) stem cells and holds promise as a potential therapeutic approach. Herein, we present a concise summary of the different functions of SIRT1 in hematologic malignancies.

Comparing the antibody titers of sequential program of Sabin strain-based inactivated poliovirus vaccine followed by bivalent types 1 and 3 oral poliovirus vaccine in different dosage forms / 中华疾病控制杂志

Objective To evaluate the antibody titer distributions after primary vaccination by different sequential schedules of Sabin strain-based inactivated poliovirus vaccine(sIPV) and bivalent oral attenuated live poliomyelitis vaccine against types 1 and 3 (bOPV) in Drug Candy(DC) form or liquid dosage form. Methods Eligible infants of 2 months old selected in Liuzhou were assigned randomly in a ratio of 1:1:1:1 to 4 groups as following: sIPV+2bOPV(DC), sIPV+2bOPV(liquid), 2sIPV+bOPV(DC), 2sIPV+bOPV(liquid), and were vaccinated at 0, 28, 56 days. Polio neutralizing antibody titers against poliovirus types 1, 2 and 3 were tested prior to Dose 1 and at 28 days after Dose 3. Results The antibody titer distribution for type 1 was statistically different between sIPV+2bOPV(DC) and sIPV+2bOPV(liquid) (Z=-2.589, P=0.010) while no significant differences were detected between the two groups for type 2(Z=-0.331, P=0.741) and type 3(Z=-1.556, P=0.120). There were no significant differences between 2sIPV +bOPV(DC) and 2sIPV+bOPV(liquid) for the distributions(All P>0.05) (type 1: Z=-1.249, P=0.212; type 2: Z=-1.658, P=0.097; type 3: Z=-1.436, P=0.151). In the same dosage forms with different sequential schedules, the antibody titer distributions were significantly different between 2 doses sIPV and 1 dose sIPV groups(All P<0.05)(sIPV+2bOPV(liquid) vs 2sIPV+bOPV(liquid): type 1: Z=-2.766, P=0.006; type 2: Z=-9.137, P<0.001; type 3: Z=-5.529, P<0.001. sIPV+2bOPV(DC) vs 2sIPV+bOPV(DC): type 1: Z=-3.748, P<0.001; type 2: Z=-7.660, P<0.001; type 3: Z=-6.030, P<0.001). Conclusions Different dosage forms have similar immune effects, so appropriate dosage forms should be selected for vaccination according to the effectiveness, characteristics of subjects and the population density. In the case of sufficient supply of sIPV, 2 doses sIPV sequential program should be the first choice to complete the primary immunization.

Chemical constituents from root of Lasianthus acuminatissimus (II) / 中草药

Objective To study the chemical constituents from the root of Lasianthus acuminatissimus. Methods The compounds were isolated and purified by silica gel column chromatography, Sephadex LH-20, ODS column chromatography, preparative HPLC and so on. Their structures were determined on the basis of physicochemical properties and their spectroscopic data, as well as literature. Results A total of 16 compounds were separated and identified as 4-methoxyphenol (1), 3-acetylbetulinic acid (2), palmitic acid (3), 3,8-dihydroxy-2-ethoxymethyl-1-methoxy-9,10-anthraquinone (4), 1,3-dihydroxy-2-ethoxymethyl-9,10-anthraquinone (5), 1,3-dihydroxy-2-methyl-9,10-anthraquinone (6), 3,8-dihydroxy-1-methoxy-9,10-anthraquinone (7), 3-hydroxy-1-methoxy-9,10- anthraquinone (8), 1,3-dihydroxy-2-methoxymethyl-9,10-anthraquinone (9), 4-hydroxymethyl-2-furaldehyde (10), butyl benzyl phthalate (11), lasianthurin A (12), isoscopletin (13), damnacanthol (14), uncargenin A (15), and lasianthuoside A (16). Conclusion Compounds 1-11 are isolated from the genus of Lasianthus for the first time.

Comparing the immunogenicity and safety of sequential inoculation of sIPV followed by bOPV (Ⅰ+Ⅲ) in different dosage forms / 中华预防医学杂志

Objective@#To compare the safety and immunogenicity of two different sequential schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV) followed by typeⅠ+Ⅲ bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC) form or liquid dosage form).@*Methods@#This randomized, blinded, single center, parallel-group controlled trial was done from September 2015 to June 2016 in Liuzhou, Guangxi province. Healthy infants aged ≥2 months were eligible for enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules. According to the bOPV dosage form each sequential schedules, the subjects again were divided into drug candy(DC) form or liquid dosage form group, being 1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid). According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We recorded adverse events during the clinical trial (399 participants who receive at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples (excluding the quitters or subjects against trial plan), using cell culture trace against polio virus neutralization test Ⅰ, Ⅱ, Ⅲ neutralizing antibody (GMT), calculating the antibody positive rate.PolioⅠ,Ⅱand Ⅲ antibody titers were assessed by virus-neutralizing antibody assay and the seroconversion (4-fold increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total 350 samples) .@*Results@#During the vaccination, the incidence of AEs in 1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid) group were 79%, 76%, 80% and 74% (χ2=1.23, P=0.747) , respectively. The severe AEs in groups were 6%, 5%, 6% and 4% (χ2=0.57, P=0.903) , respectively, and none was considered to be vaccination related. 28 days after 3rd vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and 99% (χ2=0.94, P=0.815) , respectively, for type Ⅰ poliovirus; and 47%, 57%, 80%, 79% (χ2=31.56, P<0.001) , respectively, for type Ⅱ; and were 100%, 99%, 100%, 99% (χ2=2.02, P=0.568) , respectively, for type Ⅲ. In each group, the GMT of antibody against poliovirus typeⅠ were 4 539.68, 6 243.43, 6 819.53 and 7 916.29 (F=25.87, P<0.001) , respectively; Type Ⅱ were 12.98, 10.54, 63.75 and 84.21 (F=8.68, P=0.034) , respectively; Type Ⅲ were 1 172.55, 1 416.03, 2 648.89 and 3 250.75 (F=14.50, P=0.002) , respectively.@*Conclusion@#On the same sequential schedules, there was no significant difference between the dosage forms, all of them showed good safety and immunogenicity. In the same dosage forms with different sequential schedules, the seroconversion rate was higher in 2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing antibody GMT level against polio type Ⅱ and Ⅲ after vaccination.

Intrathecal infection of TRESK overexpression adenovirus to relieve neuropathic pain via inhibiting JNK activation and neuronal apoptosis / 实用医学杂志

Objective To observe the effect of intrathecal injection of TRESK overexpression adenoviruson phosphorylation of JNK and apoptosis of neurons in neuropathic pain rats.Methods Seventy-two male SD rats were randomly divided into six groups:groups C,S,NP,T,V,and NS,12 for each group.SNI was administrated to rats in groups NP,T,V and NS.TRESK adenovirus and negative virus were intrathecally injected after use of SNI in groups T and V,while equal volume of NS was injected to rats in group NS.MWT and TWL were measured at 1 day before operation(baseline,BL)and at 1,3,7 and 14 days after operation (days 1,3,7,and 14).Six rats in each group were sacrificed at D7 to determinate the expression of TRESK protein of DRG.The other rats were sacrificed at D14 to determinate neural apoptosis and the expressions of caspase3 and p-JNK of DRG.Results As compared with groups C,S and T,the expression of TRESK protein was significantly decreased at D7 in groups NP,NS and V (P＜0.05).Compared with groups C and S,MWT was significantly decreased at days 1,3,7 and 14 (P＜0.05),phosphorylation of JNK in DRG was significantly increased at D14 (P＜0.05),neuronal apoptosis rate and expressions of Caspase3 of DRG were significantly increased at D14 (P＜0.05) in groups NP,T,NS and V.Compared with groups NP,V and NS,MWT was significantly increased at time points of days 1,3,7 and 14 in group T (P＜0.05),phosphorylation of JNK of in DRG was significantly decreased at D14 in group T (P＜0.05),neuronal apoptosis rate and expression of Caspase3 of DRG were significantly decreased at D14 in group T (P＜0.05).Intrathecal injection ofpAd/CMV/VS-DEST-TRESK obviously reduced mechanical hyperalgesia,upregulated TRESK expression,and lowered JNK phosphorylation and NP in SNI rat.Conclusions Intrathecal injection of TRESK over expression adenovirus relieves NP via inhibiting JNK activation and neuronal apoptosis.

Development of pH-Sensitive Cationic PEGylated Solid Lipid Nanoparticles for Selective Cancer-Targeted Therapy.

Solid lipid nanoparticles (SLNs) are suitable candidates for the delivery of various anti-cancer drugs. However, currently insufficient tumor-permeability and non-specific uptake by the reticuloendothelial system limits the application of SLNs. Here, we developed novel pH-sensitive cationic polyoxyethylene (PEGylated) SLNs (PEG-SLNs+) that could accumulate long-term at various tumor sites to enhance the therapeutic efficiency of camptothecin (CPT). These CPT-loaded PEG-SLNs+ (CPT-PEG-SLNs+) were spherical nanoparticles, with small size (∼52.3±1.7 nm), positive charge (∼34.3±3.5 mV) and high entrapment efficiency (∼99.4±1.7%). Drug release profile indicated the overall released amount of CPT from CPT-PEG-SLNs+ at pH 5.5 was 20.2% more than at pH 7.4, suggesting CPT-PEG-SLNs+ were a pH-sensitive SLNs. This PEG-SLNs+ could be efficiently uptaken into cells to inhibit the proliferation of CL1-5 cells (IC50 = 0.37 ±0.21 ug/ml) or HCC36 cells (IC50 = 0.16±0.43 ug/ml). In living animal, our PEG-SLNs+ could accumulate long-term (for more than 120 hours) in various types of tumor, including human lung carcinoma (NCI-H358, CRL5802, CL1-5), human colon carcinoma (HCT-116) and human hepatocellular carcinoma (HCC36), and CPT-PEG-SLNs+ could efficiently enhance the therapeutic efficiency of CPT to suppress the growth of the HCC36 or CL1-5 tumors. Therefore, Successful development of these pH-sensitive PEGylated cationic SLNs may provide a selective and efficient drug delivery system for cancer therapy.

Study on the immunogenicity and safety of recombinant B-subunit/whole cell cholera vaccine infused with antacids in healthy population at ages of 2-6 years / 中华预防医学杂志

Objective@#To assess the immunogenicity and safety of recombinant B-subunit/whole cell cholera vaccine (rBS/WC) oral cholera vaccine (Ora Vacs) infused with antacids in healthy population at ages of 2-6 years.@*Methods@#Between December 2009 and January 2010, we recruited 900 volunteers aged 2-6 years od through giving out recruitment notice for the eligible children's parents from different vaccination clinics of Chongzuo city in Guangxi Zhuang Autonomous Region. This study was a randomized, double-blind, placebo-controlled trial, and subjects were randomly (2∶1) assigned to receive Cholera vaccine infused with antacids or placebo, and observed for safety. Serum samples of 300 subjects in immunogenicity subgroups (200 for vaccine groups, 100 for control groups) before the 1st dose and 49 d (±3 d) after immunization were collected, and determined for antibody levels against the cholera toxin (anti-CT) and cholera vibriocidal (anti-Vab) with Enzyme-linked immunosorbent assays (ELISA), based on which the GMT was calculated. There were 266 cases paired with the serum samples before and after immunization (177 for vaccine groups, 89 for control groups). The comparison of subjects' age at enrollment and the level of GMT before and after immunization between groups were analyzed by t test. The superiority test for the difference between seroconversion rates of vaccine groups and control groups were analyzed by χ2 test.@*Results@#Of 900 subjects enrolled, the number of males and females were 503 and 397 respectively (vaccine groups 335 vs. 265, control groups 168 vs. 132), the average ages of vaccine groups and control groups at enrollment were (4.8±1.2) years and (4.9±1.2) years respectively. There were no significant differences between groups in terms of gender and age (χ2=0.00, P=1.000; t=0.55, P=0.585). The 2 times increase rates of anti-CT and anti-Vab in vaccine groups after inoculation were 90.96% and 57.63% respectively, which were superiority to those of control groups (15.73% and 29.21%), and significant differences were observed between groups (χ2=15.89, χ2=3.85, P<0.001). There were significant differences between vaccine groups and control groups after inoculation in terms of GMTs of anti-CT (1∶647.56 vs. 1∶99.49) and anti-Vab antibodies (1∶16.19 vs. 1∶11.27) (t values were 15.82 and 3.43, respetively; both P values were<0.05), significant differences were observed in the growth rates when compared the GMTs of anti-CT (6.63 vs. 1.11) and anti-Vab antibodies (1.64 vs. 1.16) before inoculation between vaccine groups and control groups (t'=17.85 and 4.96, P<0.001). In terms of safety, the adverse reaction rates in vaccine groups and control groups were 37.67% (226/600) and 36.67% (110/300), respectively,the common adverse reaction including fever, nausea, vomiting, abdominal pain, diarrhea, headache, fatigue, allergies, rash, etc; and the severity degree were mainly for level 1.@*Conclusion@#Ora Vacs infused with antacids could produce an positive effect on immune response and safety.

The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.

Therapeutic effect of Artemisia argyi on oral ulcer in rats / 中南大学学报(医学版)

Objective:To determine bacteriostatic abilities ofArtemisia argyi extracts,and to explore the effect ofArtemisia argyi extracts on oral ulcer in rats.Methods:We extracted the mixture ofArtemisia argyi volatile oils and water-extraction by leaching method and evaluated the anti-microbial effect ofArtemisia argyi extracts on common oral floras in vitro.The rat cheeks were burnt by NaOH to establish the models of oral ulcer.The curative effects of crude drug of Artemisia argyi extracts at 2.0,1.0,0.5 g/mL on oral ulcer in rats were evaluated by measuring the oral ulcer healing time.Serum TNF-α level and expression of proliferating cell nuclear antigen (PCNA) were analyzed by ELASA and immunohistochemical staining.Results:Artemisia argyi extracts obviously inhibited the Staphylococcus aureus and Streptococcus.NaOH-made oral ulcer in rats were successfully established.The crude drug at 2.0 and 1.0 g/mL obviously reduced healing time,significantly inhibited the release of TNF-α,and improved the PCNA level in the ulcer tissues (All P＜0.01).The extracts obviously reduced the local inflammatory reaction and promoted tissue repair of oral ulcer.Conclusion:Artemisia argyi extracts promote tissue repair of oral ulcer via inhibiting bacterial growth,reducing the release of TNF-α and improving the PCNA level.

Design of the three-dimensional-printed individualized pedicle guide plate and its accuracy of placement / 中国组织工程研究

BACKGROUND:Surgical accuracy is a key to surgical success.The traditional positioning method mainly depends on surgeons' experience,which is too subjective to cause screw misplacement.Three-dimensional (3D) printing technology-assisted pedicle screw placement can make individualized surgical scheme,most importantly,it is accurate and simple showing promising application prospect.OBJECTIVE:To design an individualized pedicle guide plate with 3D printing and to simulate screw placement in vitro,and to explore its feasibility in vertebral pedicle screw placement.METHODS:Lumbar spine CT data of 11 patients with degenerative lumbar spine were selected from April 2016 to July 2016 at Hebei General Hospital,and 3D reconstruction of L1,L3 and L5 vertebrae of each case was performed.Pre-experiment was conducted based on one patient's lumbar CT data:according to the principle of screw placement,the screw position and orientation were designed to prepare the best pedicle guide plate model.Afterwards,the screw placement in vitro was simulated,and was then cut by chainsaw to verify the accuracy of screw placement.RESULTS AND CONCLUSION:(1) A total of 30 pedicle guide plates were used,and 60 screws were inserted in the patients,and the placement process was successful.The guide plates adhered well,none appeared with screw perforating the pedicle cortex,and the screw position was accurate and reliable.(2) There were no significant changes in the transverse section and sagtial section angles of the left and right pedicle screws before and after placement (P ＞ 0.05).(3) These results suggest that the 3D-printed individualized pedicle guide plate holds a good accuracy of placement,which can be applied in the vertebral pedicle screw placement,but further clinical trials are needed.

Changes in APPL1 expression during renal fibrosis in a mouse model of renal ischemia-reperfusion injury / 中华麻醉学杂志

Objective To evaluate the changes in the expression of adaptor protein containing pleck-strin homobgy domain, phosphotyrosine-binding domain and a leucine zipper motif 1(APPL1)during renal fibrosis in a mouse model of renal ischemia-reperfusion(I∕R)injury. Methods Twenty-four male C57BL∕6 mice, aged 8 weeks, weighing 20-25 g, were divided into 2 groups(n=12 each)using a random number table: sham operation group(S group)and renal I∕R group.The model of renal I∕R injury was established by clipping the bilateral renal pedicles for 30 min followed by reperfusion in group I∕R.Six mice were selected at 2 days of reperfusion, and venous blood samples were collected for determination of serum concentrations of blood urea nitrogen and creatinine.The animals were then sacrificed, the renal specimens were obtained for microscopic examination of tubular necrosis with a light microscope, and the damage to the renal tubules was scored using a semi-quantitative method.Six mice were sacrificed at 14 days of reperfusion, and the renal specimens were obtained for assessment of the degree of renal fibrosis(using picric acid-sirius red staining) and for determination of the expression of collagen type 1, fibronectin and α-smooth muscle actin in renal tis-sues(by Western blot or immunofluorescence method). At 2 and 14 days of reperfusion, the expression of APPL1 in renal tissues was detected by Western blot and the expression of APPL1 mRNA in renal tissues by real-time polymerase chain reaction. Results Compared with group S, the serum concentrations of blood u-rea nitrogen and creatinine, scores of renal tubular damage and degree of renal fibrosis were significantly in-creased at 2 days of reperfusion, the expression of collagen type 1, fibronectin and α-smooth muscle actin in renal tissues was up-regulated at 14 days of reperfusion, and the expression of APPL1 protein and mRNA was up-regulated at 2 and 14 days of reperfusion in group I∕R(P<0.05). Conclusion Up-regulated expression of APPL1 may be involved in the process of renal fibrosis in a mouse model of renal I∕R injury.

Role of T-type calcium channels in up-regulation of spinal CaMKⅡ expression in rats with neuro-pathic pain / 中华麻醉学杂志

Objective To evaluate the role of T?type calcium channels in up?regulation of spinal Ca2+∕calmodulin?dependent protein kinase Ⅱ ( CaMKⅡ) expression in rats with neuropathic pain. Meth?ods Forty?eight male Sprague?Dawley rats, weighing 230-270 g, in which intrathecal catheters were suc?cessfully implanted, were divided into 4 groups ( n=12 each) using a random number table: sham opera?tion group (group S), neuropathic pain group (group NP), normal saline group (group NS), and T?type calcium channel blocker mibefradil group ( group M ) . The model of neuropathic pain was established by chronic compression of the dorsal root ganglion ( DRG) . Normal saline 20μl and mibefradil 200μg ( dilu?ted to 20μl in normal saline) were injected intrathecally at 5 days after compression of the DRG in NS and M groups, respectively. Before intrathecal catheter implantation ( T1 ) , before compression of the DRG ( T2 ) , at 5 days after compression of the DRG and before intrathecal administration ( T3 ) , and at 30, 60, 120 and 240 min after intrathecal administration ( T4?7 ) , the mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured. The rats were sacrificed after the last measure?ment of the pain threshold at T7 , and the lumbar enlargement segments of the spinal cord were harvested for determination of CaMKⅡ expression by Western blot. Results Compared with group S, the MWT was significantly decreased, and TWL was significantly shortened at T3?7 , and the expression of spinal CaMKⅡ was significantly up?regulated in NP and M groups (P0.05). Conclusion T?type calcium channels are opened, the intra?cellular free calcium ion concentrations are increased, and activated spinal CaMKⅡ is involved in the de?velopment of neuropathic pain in rats.