Evaluation of the cross-protection of the Vero cell-derived attenuated influenza vaccines with compound adjuvant, through intranasal immunization.

This study was to evaluate the sufficient safety and effect of the novel influenza vaccine program. It prepared new reassortant influenza virus, with high yield on Vero cells. According to the plaque counting, one dose LAIV was composed with 105 PFU of H1, H3, BY, and BV, respectively. Then mixed this LAIV with compound adjuvant, containing 500 µg/mL of carbopol971P and 50 µg/mL of tetanus toxin. That vaccination was called catt-flu. And it employed the GYZZ02 vaccine (commercialized freeze-dried LAIV, listed in China) as cohort analysis control. All mice received two doses of the vaccine, administered on days 0 and 14, respectively. That catt-flu program could induce more cross-protection with neutralizing antibody against heterogeneous types of influenza virus, not only based on HA but also NA protective antigen, through convenient nasal immunization, which had non-inferiority titter compared with the chicken embryo-derived GYZZ02 vaccine on safe and effect. The Vero cell-derived vaccine (LAIV) combined compound catt adjuvant (contain carbopol971P and tetanus toxin) could provide another safety and protective program of influenza vaccine by intranasal administration, as catt-flu program.

A Rare Case of Co-Infection with Nocardia farcinica, Pneumocystis jirovecii, and Aspergillus fumigatus Due to Tooth Extraction in a Mildly Immunosuppressed Patient.

We report a case of co-infection with Nocardia farcinica, Pneumocystis jirovecii, and Aspergillus fumigatus due to tooth extraction in a mildly immunosuppressed patient. This patient did not respond well to a meropenem-based regimen, and the number of lesions was significantly reduced after switching to imipenem. The patient's trough concentration was insufficient when using conventional doses of voriconazole for the treatment of pulmonary aspergillosis. After adding omeprazole, the concentration reached standard levels and symptoms improved. The patient eventually made a full recovery.

Evaluation of CT value with dual-energy CT in predicting cerebral hemorrhagic transformation after endovascular treatment in patients with acute ischemic stroke / 中华神经科杂志

Objective:To evaluate the value of dual-energy CT (DECT) mixed images CT in predicting hemorrhagic transformation (HT) after endovascular therapy (EVT) of acute ischemic stroke (AIS).Methods:From October 2018 to January 2020, the immediate dual-energy CT images of intracranial high attenuation (HA) regions in patients with AIS after endovascular treatment in Wuhan No.1 Hospital were retrospectively analyzed. According to the diagnostic criteria of CT or diffusion weighted image in 72 hours of follow-up, they were classified into HT group and non-HT group. The CT value of mixed images, contrast media, and virtual non-enhancement (VNC) and iodine concentration in the highest attenuation areas were measured. Intragroup correlation coefficient was used to evaluate the consistency among the readers; Mann-Whitney U test was used to compare the difference between the two groups of quantitative parameters; Spearman correlation analysis was uesd for evaluating correlation between mixed images CT value and contrast media CT value, VNC CT value, and iodine concentration. The receiver operating characteristic curve was used to analyze the quantitative parameters to predict the diagnostic efficacy of HT. Results:A total of 154 cases were enrolled, with 65 cases in the HT group and 89 cases in the non-HT group. The intraclass correlation coefficient of CT values of mixed images was 0.861 ( P<0.05). Comparing the non-HT group and the HT group,the CT value of mixed images [59.40(54.84, 63.05) HU vs 100.10(79.90, 122.40) HU, Z=-10.87, P<0.001],contrast agent CT value [24.90(20.75, 30.05) HU vs 66.60(47.10, 84.15) HU, Z=-10.85, P<0.001] and iodine concentration [1.10(1.00, 1.30) mg/ml vs 2.90(2.05, 3.65) mg/ml, Z=-10.85, P<0.001] both increased in the HT group, but there was no significant difference in VNC CT values between the two groups [33.60(31.80, 35.70) HU vs 34.30(30.90, 38.00) HU, Z=-0.50, P=0.62]. There was a highly significant correlation between the CT value of mixed images and iodine concentration ( r=0.99, P<0.01). Using CT value>72.60 HU as the diagnostic cutoff value for predicting HT, the sensitivity and specificity were 89.23% and 95.51%, respectively. Conclusions:The CT value of DECT mixed images after EVT can be used to predict HT within 72 hours. When DECT was not available, conventional CT scan′s intracranial HA density over 72.60 HU can be selected as the cutoff value for predicting HT.

Role of phenol red in the stabilization of the Sabin type 2 inactivated polio vaccine at various pH values.

To analyze the effects of phenol red at various pH values on the Sabin type 2 inactivated polio vaccine (sIPV2), several biophysical techniques were used to evaluate the particle size and capsid protein for conformation. sIPV2's size was assessed via transmission electron microscopy and dynamic light scattering. The effects of various pH values (from 4.0 to 7.0) on the biophysical characters of sIPV2 particles in solution were determined by dynamic light scattering and zeta potential. The results clearly indicated that aggregation and instability occurred in the solution of sIPV2 particles at a pH of 6.0. Under similar conditions, by dynamic light scattering and zeta potential, the virus particles in solution showed more dispersion and were stable with the addition of 0.05 mM phenol red. According to circular dichroism and intrinsic tryptophan fluorescence data, it was observed that the secondary and tertiary structures of the sIPV2 particles were more stable with the protection of phenol red. At a pH below 6.0, the sIPV2 solution with phenol red had more D-antigen content, which was confirmed by enzyme-linked immunosorbent assay and rat experiments. These results strongly suggested that phenol red improved the pH stability of the sIPV2. The study indicated the potential of phenol red in preserving vaccine potency of the sIPV2 at various pH values.

Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model.

Rabies is the most lethal zoonotic, vaccine-preventable viral disease in the world. Its treatment is complicated by insufficient vaccine supply and the requirement for four to five repeated injections, as commercially available inactivated rabies lack adjuvant and have low immunogenicity. In this study, we focused on the role of a Krebs cycle intermediate, succinate dehydrogenase (SDH), in the innate immune response to cytokine production. We formulated a novel nanoemulsion adjuvant, Golden03, which stabilizes mouse SDH activity and contains more coenzyme Q10 and succinic acid than the classic MF59 adjuvant. Mice were immunized on days 1, 3, and 7, with seroconversion rate results suggesting that Golden03 significantly enhanced vaccine-stimulated antibody production against the rabies virus. Neutralizing antibody concentration testing by RFFIT indicated that treatment with Golden03 could result in antibody levels of up to 0.74 IU/mL 5 days post infection (DPI). ELISPOT for IFN-γ in mouse spleen cells showed that Golden03 enhanced immune responses at 14 DPI, inducing a rapid and powerful cellular response compared to the control group. Furthermore, the Vaccine-Golden03 group displayed no obvious weight loss or death after intracranial injection with CVS-11. An additional advantage is that Golden03 allowed for a three-quarter reduction in dose, while maintaining its efficacy and rapid stimulation effect. We suggest that Golden03 could be developed as a potential adjuvant for use in human rabies vaccine.

Construction of influenza B virus vero cell adapted strain by genetic reassortment / 中华实验和临床病毒学杂志

Objective@#To construct influenza B virus Vero cell adapted strain by genetic recombination technology by using the influenza B virus Vero cell adapted strain as the parent strain.@*Methods@#The chick embryo and Vero cell were co-infected with influenza virus Vero cell adapted strain B/Malaysia/2506/2004 Va (Bv) and the vaccine strain B/massachusetts/2/2012 (BX-51B) recommended by WHO. The reassortants were screened with the anti-Bv serum. Plaque-purified reassortants were used to screen for Vero cell-adapted influenza B virus strains containing the surface antigen of the epidemic strain.@*Results@#A Vero cell-adapted influenza B virus strain was obtained with successive passage in Vero cells. The hemagglutination inhibition test and the one-way immunogold agar diffusion test both showed that the reassortant virus was homologous to NYMC BX-51B, and sequence analysis result showed that the reassortment virus has the same HA and NA gene with the vaccine strain.@*Conclusion@#B/Malaysia/2506/2004Va (Bv) can be used as a parent strain to prepare Vero cell vaccine against influenza B virus.

Immunogenicity and safety of Sabin IPV vaccine in Banna mini pigs / 中国实验动物学报

Objective To evaluate the immunogenicity and safety of inactivated poliovirus vaccine derived from Sabin strain (sIPV) in Banna mini pigs, and to provide experimental evidence for the new animal model. Methods sIPV vaccines which are listed at Institute of Medical Biology at Chinese Academy of Medical Sciences were used in this study. The groups of intramuscular sIPV and the wild strain IPV injections (IPV derived from wild strain, wIPV) were designed, and the saline group was used as a negative control group. The Banna mini pigs in various groups were immunized at 0, 1 and 2 months. Blood samples were collected before immunization and on days 30 after each immunization. Levels of neutralizing antibodies were tested for evaluating immunogenicity. The safety was evaluated by observation of the status and weight of mini pigs. Results After the three dose immunization schedules in the Banna mini pigs, the seroconversion rates of type Ⅰ,Ⅱ and Ⅲ sIPV experimental groups and wIPV group were all up to 100%. The neutralizing antibody levels in all the three types were much higher than the protective titer 1: 8. The weight of mini pigs increased after vaccination. Conclusions The sIPV vaccine has good immunogenicity and safety in Banna mini pigs. Banna mini pigs could be a new animal model for evaluation of sIPV vaccine.

Volume CT Perfusion in Unilateral Middle Cerebral Artery Stenosis / 中国医学影像学杂志

Purpose To evaluate the application value of volume CT perfusion (CTP) protocol with 128-slice CT scanner in patients with unilateral middle cerebral artery (MCA) stenosis or occlusion.Materials and Methods Thirty-five patients with severe unilateral MCA stenosis or occlusion who underwent cerebral volume CTP examination in Wuhan No.1 Hospital between July 2013 and December 2014 were evaluated.The volume CTP parameter maps of cerebral blood flow (CBF),cerebral blood volume (CBV),mean transit time (MTT) and time to peak (TTP) were analyzed.Meanwhile,the dynamic CT angiography (4D-CTA) images were obtained.Results In three patients,CBF,CBV and MTT were observed normal but TTP was delayed.In the other thirty-two patients,CBF in the affected side was lower than that in the contralateral side (but difference without significance:P＞0.05).The increased CBV,prolonged TTP and MTT were also detected in the affected side compared with the contralateral side (difference with significance:P＜0.05).McNemar test showed 4D-CTA and DSA diagnosis of middle cerebral artery occlusion were not significantly different (P＞0.05),and they had better consistency (Kappa=0.861,P＜0.05).Conclusion Brain volume CTP protocol with 128-slice CT scanner provides valuable information about cerebral artery abnormalities and hemodynamic changes in patients with severe stenosis or occlusion of MCA.It has great value for clinical application.

Alkaloids in stems and leaves of Stephania cepharantha / 中国中药杂志

<p><b>OBJECTIVE</b>To study the alkaloids in the stems and leaves of Stephania cepharantha.</p><p><b>METHOD</b>The dried stems and leaves of S. cepharantha were percolated with 95% ethanol and the solvent was removed by rotary evaporation to give a concentrate, and the concentrate was extracted by petroleum ether and chloroform. Column chromatograghy on MCI CHP 20P, silica gel, Rp-18, Sephadex LH-20 and polyamide were applied for the isolation and purification of the chloroform fraction. The structures were elucidated by their physicochemical properties and spectral data.</p><p><b>RESULT</b>Eleven alkaloids were obtained and identified as lysicamine (1), tetrahadropalmatine (2), palmatine (3), isocorydione (4), corydalmine (5), corypalmine (6), sinoracutine (7), sinoacutine (8), cepharamine (9), isocorydine (10) and corydine (11).</p><p><b>CONCLUSION</b>Compounds 2-7 were isolated from S. cepharantha for the first time, and compound 7 was isolated from the genus Stephania for the first time, compound 4 was isolated from the Menispermaceae family for the first time.</p>

Hasubanan type alkaloids in Stephania hernandifolia / 中国中药杂志

<p><b>OBJECTIVE</b>To study the hasubanan type alkaloids in Stephania hernandifolia.</p><p><b>METHOD</b>The dried herbs of S. hernandifolia. were extracted with 95% ethanol. After removal of the solvent, the residue was first partitioned between acid water and petroleum ether, then the aqueous layer was basified and extracted with chloroform to obtain crude alkaloids. Column chromatograghic methods with on silica gel, Rp-18, MCI CHP 20P, Sephadex LH-20 were applied for the isolation and purification of the crude alkaloid fraction. The structures were elucidated by their physicochemical properties and spectral data.</p><p><b>RESULT</b>Nine hasubanan type alkaloids were obtained and identified as aknadinine(1), longanone(2), stephasunoline (3), N-methylstephuline(4), epistephamiersine(5), prostephabyssine(6), aknadilactam(7), dihydroepistephamiersine(8), hasubanonine(9).</p><p><b>CONCLUSION</b>Compounds 2-8 were isolated from this plant for the first time.</p>