Objective To study the clinical significance of systemic lupus erythematosus disease activity index(SLEDAI) in the treatement of SLE. Methods Disease activity of every patient with SLE 10 days before admission and before discharging was assessed using the SLEDAI system. The patients were treated separately with prednisone, pulse methylprednisolone and/or pulse cyclophosphamide according to their conditions. Statistical analysis was carried out using SPSS software. Results ①The difference of SLEDAI between the patients before admission and discharging was significant (P

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

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.

Novel cancer immunotherapy can treat tumors through regulating innate immunity and adaptive immune system. cGMP-AMP synthase (cGAS) is a key regulator of innate immune response to both exogenous and endogenous DNA. After recognizing the cytoplasmic DNA, cGAS produces the second messenger cyclic GMP-AMP (cGAMP), which subsequently combines with the adaptor STING (also known as MITA, MPYS and ERIS) to mediate innate immunity by inducing the production of type I interferons and inflammatory cytokines. Recent studies have revealed that the cGAS/STING signaling pathway can be activated by tumor-derived DNA and by-products of genomic instability and affect the incidence and development of tumors, which plays a critical role in the natural antitumor immunity across cancer types and immune checkpoint blockade therapy. In this article, current understanding of cGAS/STING signaling pathway in tumors was summarized, the pivotal role in tumor immunity and radiotherapy was highlighted, and the potential targeted or alternative therapy of this signaling pathway was reviewed.

Objective To evaluate the differences of α-fetoprotein (AFP), ffeeβ-human chorionic gnnadotropin (HCG) indexes in 3 foreign median databases for antepartum risk screening, and establish the median databases of normal pregnant women in Wenzhou for antepartum screening of AFP, free-β-HCG indexes through the suitable median computational models. Methods The levels of AFP and free β-HCG of 20054 normal pregnant women in Wenzhou were detected by time-resolved fluorometry. The data in this paper were compared with the data of 2T-risk ( 2T), Lifecycle-2. 2 (LC2.2 ) and Lifecycle -3.0 (LC3.0) by double-factor ANOVA. The differences between the data in the paper and the data from Shenyang and Ningbo were analyzed. The median database of Wenzhou pregnant women was established by the suitable regression model, with the stability of nonlinear regression models of the 3 software assessed by model correcting fitting, distribution mean of model fitting logarithmic and standard deviation. Results The levels of AFP and freeβ- hCG reported here were 10% and 16% higher than the data of 2T-risk, 15% and 20% higher than that of LC 2. 2, 6% and 17% higher than that of LC 3.0 respectively. The differences were statistically significant. ( FAFP = 161. 757 ,P < 0. 01 ; Ffree-β-HCG = 58. 261, P < 0.01 ). The levels of AFP and free β- hCG in Wenzhou were 2% higher and 3% lower than that of Shenyang, 1% and 2% higher than that of Ningbo. There was no statistical difference of AFP levels among Wenzhou , Shenyang and Ningbo( FAFP = 0. 174 ,P =0. 840) while the differences of free-β-hCG were statistically significant( F<,free-β-HCG> = 13.303 ,P < 0. 01 ). The differences of quadratic equation regression model, exponent quadratic function regression model and exponent quadru-function regression model of 2T, LC-2. 2 and LC-3.0 were not remarkable. The exponent quadru-function regression model was the best. Conclusions There are significant differences between the data from Wenzhou, Shenyang and Ningbo and the data of T-2 risk, LC-2. 2, LC -3.0. The discrepancy is due to the ethnic and different parameters of regression models. So the model parameters and the median databases are urgently required in China. The differences of large sample size of AFP from Wenzhow, Shengyang and Ningbo are not significant, while the differences of free-β- hCG from Wenzhow, Shengyang and Ningbo is remained because of its instability. The levels from Wenzhow and Ningbo are near. It is suggested that the laboratories with small sample size can establish their own laboratory parameters using the reference obtained from large sample size under the same experimental conditions. There are no significant differences of stability among regression computational models in the 3 software. The exponent quadru-function regression model can be used to establish the median databases for the screening with the similar data distribution in the paper.

Objective To explore the relativity of preoperative health status and perioperative com-plication incidence of aged patients. Methods The chnical data of 3108 old aged people (60 and above 60 years old)who were operated from January 2006 to November 2007 was retrospectively analysed. General e-valuated preoperative health status, and summarized perioperative complication incidence. Results Before operation, 68.7% patients had one or more coexist disease, 41.1% patients had two or more coexist dis-eases, 38.7% had three coexist diseases in the meantime. After operation,one or more complications oc-curred in 21.4% (666/3108)patients, 2.8% (88/3108) patients died because of heart,brain,lung, kidney function failure. Conclusions Aged patients have more coexist diseases, the complications and death rates are higher than those in younger patients. The complications are correlated with preoperative health status and coexist diseases. Some factors could influence the patients rehabilitation,such as heart,brain,lung, kidney function, water-electrolyte balance and blood glucose change.

Objective To explore the prevalence of sialorrhea and its clinical correlation with dysphagia in Chinese patients with Parkinson′s disease ( PD ).Methods One hundred and sixteen consecutive patients with a clinical diagnosis of PD were selected.Demographic data included sex , age, years of education, age at onset of PD, clinical genotype, disease duration, treatment, Hoehn and Yahr (H&Y) stage.Sialorrhea was assessed using the Unified Parkinson′s Disease Rating Scale (UPDRS) Ⅱitem number 6.All patients were studied with videofluoroscopic study of swallowing ( VFSS).Results The prevalence rate of sialorrhea in PD was 59.5% (69/116, 95% CI 50.6%-68.4%).Males were more likely to develop sialorrhea than females (47/70 vs 22/46,χ2 =4.298, P=0.038).PD patients′sialorrhea correlated with oral dysphagia:with food leaking from the mouth ( liquid r=0.229, P=0.014; juice r=0.197, P=0.034;pudding viscosities r=0.231, P=0.013;solid food r=0.255, P=0.006), with more than 1 ml of oral food residues (liquid r=0.319, P<0.01;solid food r=0.185, P=0.047), with delay in food transfer to the root of the tongue (liquid r=0.279, P=0.002; juice r=0.209, P=0.024), and delayed swallow transfer ( pudding viscosities r=0.257, P=0.005).Sialorrhea score was not related to H&Y stage, clinical course and levodopa equivalent doses (LED).The prevalence rate of dysphagia in PD was 87.1%(95% CI 81.0% -93.2%).Liquid was more likely to cause pharyngeal dysphagia ( P=0.03).With the increase in H&Y stage , so did the oral and pharyngeal stages of dysphagia.Late and mid-course was more likely to develop oral and pharyngeal dysphagia than those with early clinical course .Conclusions Sialorrhea and dysphagia are common non-motor symptoms in PD patients.Sialorrhea is more prevalent in males and correlates with oral phase of dysphagia.Liquid is more likely to cause pharyngeal dysphagia.With increase in H&Y stage , so did oral and pharyngeal dysphagia.Even though late clinical course is more likely to develop oral and pharyngeal dysphagia than early clinical course , the comparison between late and intermediate clinical courses does not reach statistical significance .

Objective To explore the associations between vitamin D receptor ( VDR) Fok- Ⅰ and Apa- Ⅰ polymorphisms and myasthenia gravis (MG) in Chinese Han population.Methods Polymorphisms of VDR Fok- Ⅰ and Apa-Ⅰ were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.The frequencies of genotypes and hyplotypes were compared among 286 normal controls and 267 MG patients in different subgroups classified by gender,age of onset,presence of thymoma,and Osserman classification sat maximal severity in the follow-up.The association between the genotypes and maximal severity of MG and short-term glucocorticoid treatment were also investigated.Results There were no significant differences in frequencies of genotypes and hyplotypes of both Fok-Ⅰ and Apa-Ⅰ between MG group and control group,and among subgroups of MG.The Fok- Ⅰ showed no statistical difference between the patients with better and less improvement after short-term treatment of glucocorticoid.The frequency of Apa-Ⅰ alleles in the patients with better improvement (55/186,29.6% ) significantly differed from the less improved group ( 7/48,14.6%,OR = 2.46,95% CI 1.04-10.43,x2 = 4.400,P = 0.036).The patients with the genotype A A/Aa were more likely to improve better after the treatment(48/93,51.6%) than in the worse group(7/24,29.2%,OR =2.59,95% CI 0.98-14.60,x2 =3.858,P= 0.049).Conclusions Alleles and genotypes of VDR-Fok- Ⅰ and Apa-Ⅰ were not found to be related with MG onset and severity.MG patients with VDR-Apa-A allele may have better improvement short-term treatment of glucocorticoid.

Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load. The average deviation of spot position was 0.733+/-0.101 mm in IEF direction, and 0.925+/-0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241+/-88 spots were detected, 987+/-65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190+/-72 spots were detected, and 875+/-48 spots were matched with an average matching rate of 73.5%. A total of 864+/-34 spots were matched between tumors and controls. Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduction. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis. These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.
Amino Acid Sequence ; Bronchi ; pathology ; Carcinoma, Squamous Cell ; genetics ; pathology ; Databases as Topic ; Electrophoresis, Gel, Two-Dimensional ; methods ; Electrophoresis, Polyacrylamide Gel ; Epithelial Cells ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Image Processing, Computer-Assisted ; Isoelectric Focusing ; Lung Neoplasms ; genetics ; pathology ; Molecular Sequence Data ; Proteomics ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Objective To study the preventive effect of artemether (Art) in protecting the people from schistosome infection during flood fighting in schistosomiasis endemic area of Poyang Lake, Jiangxi Province. Methods From mid July to mid August in 1996, the water level in Poyang Lake rose due to torrential rains and 2 embankments, Zhedi and Jiangtongdi, which appeared in dangerous situation and were selected as the pilot spots. After those who went to fight against flood arrived at the pilots their sera were collected within 48 hours and were examined with indirect hemagglutination test (IHA), enzyme-linked immunosorbent assay (ELISA) and McAb-ELISA. Individuals with negative outcome in the 3 tests were then selected as the study subjects and were allocated randomly to the Art or the control group. The first dose of Art given to the individuals contacted with the infested water within 11-15 days was 6 mg/kg. If the individual continually contacted the infested water, the same dose of Art was given once every 15 days. After the individuals withdrew from the pilot, one more dose of Art was administered 7-15 days later. Placebo (starch) was given to individuals in the control group at the same period as in artemether group. Stool examinations were made in both groups 40-50 days after the last medication for evaluation of the preventive effect of artemether. Double blind method was used in the administration of both artemether and placebo. Results In Zhedi pilot, the individuals fought against flood for about 1 month. In Art group, 99 individuals receiving 3 doses of the drug completed the stool examination with egg-positive rate of 4% and no acute schistosomiasis was seen. In the control group, among 110 people who completed the observation, 44 were egg-positive with an infection rate of 40%, and 29 were identified as having acute schistosomiasis. In Jiangtondi, the studied individuals contacted the infested water for only about 4 hours. But in the control group 4 out of 102 individuals were egg-positive, while none of the 103 individuals in Art group receiving 2 doses of the drug showed schistosome infection. No apparent side effect was seen in the people treated with artemether.Conclusion After oral Art was given to the people fighting against flood in schistosomiasis endemic area of Poyang Lake, it was shown that the oral Art has a promising effect on controlling acute schistosomiasis and reducing the infection rate.