To study in vitro anti-influenza viral activities of Chinese traditional patent medicines for influenza prevention and treatment, neuraminidase (NA) activity assay was used to examine NA inhibitory activity of 33 Chinese traditional patent medicines through fluorimetric assay, and influenza virus induced cytopathic effect (CPE) inhibition assay was used to verify their anti-influenza viral activities in vitro. The assay results showed that most liquid preparations displayed relatively high NA inhibitory activities, such as Shuanghuanglian oral liquid, Qingkailing oral liquid, Qingre Jiedu oral liquid, and Reduning injection. Among liquid preparations, Shuanghuanglian oral liquid not only displayed the highest NA inhibitory effect, but also exhibited obvious in vitro anti-viral activity in CPE experiment. Among solid preparations, Shuanghuanglian powder for injection showed the highest activity on NA inhibition, and Fufang Yuxingcao tablet showed relatively strong anti-influenza viral activity in CPE cells. From the results, it can be concluded that most Chinese traditional patent medicines possessed NA inhibitory activity, but only a few of them displayed significant in vitro anti-influenza viral activities. These results will provide important information for the isolation of active constituents, and for the clinical uses of Chinese traditional patent medicines for influenza treatment and prevention.

To enhance the specificity of anti-TNF-α single chain Fv antibody (TNF-scFv) to inflamed site, we constructed a bispecific antibody BsDb that targets TNF-α and ED-B-containing fibronectin (B-FN) by covalently linking TNF-scFv and the anti-ED-B scFv L19 at the gene level via a flexible peptide linker deriving from human serum albumin. BsDb was successfully secreted from Pichia pastoris as functional protein, identified by immunoblotting, and purified to homogeneity with affinity chromatography. BsDb retained the immunoreactivity of its original antibodies TNF-scFv and L19, and showed a marked gain in antigen-binding affinity and in TNF-α-neutralizing ability, when compared to TNF-scFv and L19 that were produced in Escherichia coli. In the adjuvant-induced arthritis (AIA) mice model, BsDb showed selective accumulation and retention in the inflamed paws but rapid clearance from blood, resulting in high arthritic paw to blood ratios. These data indicate that BsDb is endowed with high specificity to inflamed site and low toxicity to normal tissues and holds great potential for in vivo application for the targeted therapy of RA and other chronic inflammatory diseases.
Animals ; Antibodies, Bispecific ; biosynthesis ; immunology ; Antibodies, Neutralizing ; biosynthesis ; immunology ; Escherichia coli ; Fibronectins ; chemistry ; immunology ; Humans ; Mice ; Single-Chain Antibodies ; biosynthesis ; immunology ; Tumor Necrosis Factor-alpha ; immunology

Objective To investigate the changes in expression of hippocampal neuronal gap function protein connexin 36 (Cx36) induced by postoperative cognitive dysfunction (POCD) in aged rats.Methods Ninety male SD rats aged 20 months weighing 500-600 g were randomly divided into 3 groups ( n =30 each):group normal control (group C); group sham operation (group S) and group POCD.POCD was induced by splenectomy.Cognitive function was assessed by using open field test and maze test on the 1st,3rd and 7th day after operation (T1,T2,T3 ).The ultrastructure of gap junction in the CA1 region of hippocampas was examined with thin-section transmission electron microscope.The expression of Cx36 was detected by immuno-histochemical method.Results POCD significantly decreased the number of grid cross,the rearing and correct responses and increased the time the animab spent in the central square and total reaction time at T1 in group POCD as compared with group C.Cx36 expression was significantly decreased at T1 in group POCD as compared with group C.The ultrastructure of gap junctions underwent significant change at T1 in group POCD.Conclusion Hippocampal neuronal Cx36 may be involved in the cognitive dysfunction after splenectomy in aged rats.

In order to enhance the specificity of TNF-α monoclonal antibody to inflamed site, a bispecific antibody BsDb that targets TNF-α and the extra-domain B (ED-B) of fibronectin (FN) was constructed by covalently linking the anti-TNF-α single chain Fv antibody (TNF-scFv) and the anti-ED-B scFv L19 via a flexible peptide linker deriving from human serum albumin (HSA). ED-B is an antigen specifically expressed at the inflamed site. BsDb is expressed in E. coli, identified by immunoblot, and purified with affinity chromatography. This was followed by further examination of its bioactivities and pharmacokinetics. We demonstrated that BsDb retained the immunoreactivity of its original antibodies as it could simultaneously bind to TNF-α and ED-B and neutralize the biological action of TNF-α. In the collagen-induced arthritis mice model, BsDb selectively accumulate in the inflamed joint with a maximal uptake of (12.2 ± 1.50)% ID/g in a single inflamed paw and retain in the inflamed paw for at least 72 h. In contrast, BsDb showed a short serum half-life of (0.50 ± 0.05) h and a rapid clearance from normal tissues. The findings reported herein indicate that BsDb has good specificity to the inflamed site and low toxicity to normal tissues. BsDb is therefore likely to have greater clinical applications in the treatment of rheumatoid arthritis and other autoimmune diseases. This laid a stable basis for its preclinical study.

Objective To investigate the clinical and pathological characteristics between types 1 and 2 endometrial uterine cancers.Methods The clinical materials of 9 437 patients with uterine cancer were collected with retrospective analysis from 62 hospitals during 2000 to 2010.Results The mean age of type 1 endometrial cancers was less than type 2.There were more young patients in type 1 endometrial cancers.The mean menopause age of type 2 endometrial cancers was greater than type 1.The mean age of menarche,obesity,diabetes,hypertension,infertility,and nulliparous were not significant differences between types 1 and 2 endometrial cancers.There were more patients with advanced tumor,deep myometrium invasion,estrogen receptor (ERs) negative,progesterone receptor (PR) negative,P53 positive,lymph vascular space involvement,cervical stromal invasion,adnexal metastasis,and lymph node metastasis in type 2 endometrial cancers.Conclusions Type 2 endometrial uterine cancers occurred in elder people with more pathological risk factors and more malignant biological activities.

Objective To investigate the antioxidative and antiaging effects of the bioactive extract from Agrocybe aegerita. Method Fruit flies and D-galactose induced aging mice were fed with the bioactive extract from Agrocybe aegerita. The lifespan of fruit fly and spleen index, brain index,SOD activity in serum and lipofuscin level in 1iver of the mice were measured, and its acute toxic effect was studied. Results The bioactive extract from Agrocybe aegerita could significantly increase the mean lifespan and half death time of fruit flies. The percentage of life prolongation was 41.81% compared with the control. Compared to the models, SOD activity in serum,spleen index and brain index of male mice fed with 800mg/(kg.d) of the bioactive extract from Agrocybe aegerita were respectively increased by 42.36%, 33.33% and 17.85%,while lipofuscin content of liver decreased by 50.06%. 20g/(kg.d) of the bioactive extract from Agrocybe aegerita was safe for mouse. Conclusion The bioactive extract from Agrocybe aegerita have obviously antioxidative and antiaging effects with little side effect.

Objective To study the effect of combination mode of blood purification on insulin resistance in MODS patients and discuss the best mode of blood purification to improve insulin resistance in MODS patients.Methods A total of 60 MODS pa-tients were selected and randomly divided into control group(single mode of blood purification)and treatment group(combination mode of blood purification),each group of 30 cases.Blood glucose (BG),glucose standard deviation (BGSD),coefficient of variation of blood glucose (BGCV),regular insulin dosage (Ins),fasting insulin (FINS),insulin resistance index (HOMA-IR),HbA1c,C-re-active protein (CRP)was observed before and after treatment.Results BG,HbA1c,FINS,CRP,HOMA-IR,Ins of experimental group was lower than that of control group (P <0.05).After treatment,BG,FINS,CRP,HOMA-IR,Ins was declined in experi-mental group (P <0.05).After treatment,HbA1c was not changed in experimental group (P >0.05 ).Conclusion Combination mode blood purification may be more effective to insulin resistance in MODS patients.

Objective To explore the efficacy of neoadjuvant chemoradiotherapy (CRT) followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC),and to investigate the correlation between a clinical complete response (cCR) and a pathologic complete response (pCR).Methods One hundred and fifty-eight patients with locally advanced thoracic ESCC from 2001 to 2013 were retrospectively analyzed.All patients received concurrent chemoradiotherapy followed by surgery.Platinumbased chemotherapy regimens were adopted in chemotherapy and a prescribed dose of 40 Gy in 20 fractions,5 fractions per week,was used in radiotherapy.The overall survival (OS) and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method,and pairwise comparisons and univariate prognostic analyses were performed using the log-rank test.Multivariable prognostic analyses were performed using the Cox regression model.Results The pCR rate was 41.1％ in all patients.After the treatment with neoadjuvant CRT,32(72.7％) out of 44 patients with a cCR had a pCR,but only 33(28.9％) out of 114 patients with a non-cCR had a pCR (P =0.000).The sensitivity,specificity,positive predictive value,and negative predictive value of a cCR in predicting a pCR were 49.2％,87.1％,72.7％,and 71.1％,respectively.The 3-year sample size was 91.The 3-year OS and DFS rates in all patients were 53.9％ and 48.6％,respectively.Patients with a cCR had significantly higher 3-year OS and DFS rates than those with a non-cCR (P =0.012;P =0.026),while patients with a pCR had significantly higher 3-year OS and DFS rates than those with a non-pCR (P =0.000;P =0.000).The multivariate analyses demonstrated that the pathologic response after CRT and chemotherapy regimen were the influencing factors for OS.The most common grade ≥3 acute adverse reaction was leucopenia (34.2％).Conclusions With a high pCR rate and tolerable adverse reactions,neoadjuvant CRT followed by surgery is a safe and effective option for locally advanced ESCC.The cCR rate after CRT is closely correlated with the pCR and OS rates.

Objective To explore the relationship among clinicians' work pressure,perceived social support and compassion fatigue,and to provide a new prospective for the localization studying of intervention and treatment to compassion fatigue.Methods Data of scale for occupational stressors on clinician,perceived social support scale and professional quality of life scale were collected from a sample of 533 clinicians and analyzed with structural equation modeling to study the relationship among clinicians' work pressure,perceived social support and compassion fatigue.Results (1)Work pressure(2.40±0.45),burnout (2.14±0.54) and secondary traumatic stress(1.93±0.60) scores of the clinicians with high perceived social support were significantly lower than that of the clinicians with low perceived social support (2.78±3.67,2.73± 0.59,2.32±0.71;t=7.68,-9.44,8.77,5.07;P＜0.01).Compassion satisfaction scores (4.15±0.63) of the clinicians with high perceived social support were significantly higher than that of the clinicians with low perceived social support (3.40±0.71,t =-9.44,P＜0.01).(2) According to relevant results,work pressure was significantly negative correlation with both perceived social support (r=-0.34,P＜0.01) and compassion satisfaction (r=-0.44,P＜0.01),and significantly positive correlation with both burnout (r=0.69,P＜0.01) and secondary traumatic stress(r=0.53,P＜0.01);while perceived social support was significantly positive correlation with compassion satisfaction (r=0.42,P＜0.01),and significantly negative correlation with burnout (r=-0.40,P＜0.01) and secondary traumatic stress(r=-0.26,P＜0.01).(3) According to the results of structural equation modeling,perceived social support played a partly mediating role in the effect of work pressure toward compassion satisfaction and fatigue with the intermediary effect of 55.4％ and 12.5％.Conclusion Perceived social support plays a mediation role between work pressure and compassion fatigue for clinicians,and better social support of the clinician is beneficial to clinicians mental health level.

In order to enhance the specificity of TNF-α monoclonal antibody to inflamed site, a bispecific antibody BsDb that targets TNF-α and the extra-domain B (ED-B) of fibronectin (FN) was constructed by covalently linking the anti-TNF-α single chain Fv antibody (TNF-scFv) and the anti-ED-B scFv L19 via a flexible peptide linker deriving from human serum albumin (HSA). ED-B is an antigen specifically expressed at the inflamed site. BsDb is expressed in E. coli, identified by immunoblot, and purified with affinity chromatography. This was followed by further examination of its bioactivities and pharmacokinetics. We demonstrated that BsDb retained the immunoreactivity of its original antibodies as it could simultaneously bind to TNF-α and ED-B and neutralize the biological action of TNF-α. In the collagen-induced arthritis mice model, BsDb selectively accumulate in the inflamed joint with a maximal uptake of (12.2 ± 1.50)% ID/g in a single inflamed paw and retain in the inflamed paw for at least 72 h. In contrast, BsDb showed a short serum half-life of (0.50 ± 0.05) h and a rapid clearance from normal tissues. The findings reported herein indicate that BsDb has good specificity to the inflamed site and low toxicity to normal tissues. BsDb is therefore likely to have greater clinical applications in the treatment of rheumatoid arthritis and other autoimmune diseases. This laid a stable basis for its preclinical study.
Animals ; Antibodies, Bispecific ; chemistry ; Antibodies, Monoclonal ; chemistry ; Arthritis, Experimental ; Escherichia coli ; Fibronectins ; chemistry ; Half-Life ; Humans ; Mice ; Single-Chain Antibodies ; chemistry ; Tumor Necrosis Factor-alpha ; chemistry