Bioinformatics-based design of a fusion vaccine with CTLA-4 variable region to combat Brucella

Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.

Long-term efficacy of endovascular vs open surgical repair for complicated type-B aortic dissection: a single-center retrospective study and meta-analysis

This study aimed to evaluate the long-term survival and risk factors of traditional open surgical repair (OSR) vs thoracic endovascular aneurysm repair (TEVAR) for complicated type-B aortic dissection (TBAD). A total of 118 inpatients (45 OSR vs 73 TEVAR) with TBAD were enrolled from January 2004 to January 2015. Kaplan-Meier curves and Cox proportional hazards analysis were performed to identify the long-term survival rate and independent predictors of survival, respectively. Meta-analysis was used to further explore the long-term efficacy of OSR and TEVAR in the eight included studies using Review Manager 5.2 software. An overall 10-year survival rate of 41.9% was found, and it was similar in the two groups (56.7% OSR vs 26.1% TEVAR; log-rank P=0.953). The risk factors of long-term survival were refractory hypertension (OR=11.1; 95%CI=1.428-86.372; P=0.021] and preoperative aortic diameter >55 mm (OR=4.5; 95%CI=1.842-11.346; P=0.001). Long-term survival rate did not differ significantly between OSR and TEVAR (hazard ratio=0.87; 95%CI=0.52-1.47; P=0.61). Compared with OSR, TEVAR did not show long-term advantages for patients with TBAD. Refractory hypertension and total aortic diameter >55 mm can be used to predict the long-term survival of TBAD in the Chinese Han population.

Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China

Invasive pulmonary fungal infection (IPFI) is a potentially fatal complication in patients with connective tissue disease (CTD). The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15%) CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17%) of cases with IPFI. Candida albicans (72.3%) accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05). Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI.

Voluntary exercise prior to traumatic brain injury alters miRNA expression in the injured mouse cerebral cortex

MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular changes that occur after traumatic brain injury (TBI). However, the changes and possible roles of miRNAs induced by voluntary exercise prior to TBI are still not known. In this report, the microarray method was used to demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decreased the mortality rate and improved the recovery of the righting reflex in TBI mice, and ii) differentially changed the levels of several miRNAs, upregulating some and downregulating others. Furthermore, we revealed global upregulation of miR-21, miR-92a, and miR-874 and downregulation of miR-138, let-7c, and miR-124 expression among the sham-non-runner, TBI-non-runner, and TBI-runner groups. Quantitative reverse transcription polymerase chain reaction data (RT-qPCR) indicated good consistency with the microarray results. Our microarray-based analysis of miRNA expression in mice cerebral cortex after TBI revealed that some miRNAs such as miR-21, miR-92a, miR-874, miR-138, let-7c, and miR-124 could be involved in the prevention and protection afforded by voluntary exercise in a TBI model.

A meta analysis of cetuximab plus oxaliplatin based chemotherapy regimen for metastatic colorectal cancer.

BACKGROUND: Oxaliplatin based chemotherapy regimen was one of the most used chemotherapy modality for metastatic colorectal cancer. The purpose of this meta‑analysis was to assess the clinical activity and toxicities of cetuximab plus oxaliplatin‑based chemotherapy regimen for metastatic colorectal Cancer. METHODS: We searched the clinical studies about the cetuximab plus oxaliplatin‑based chemotherapy regimen versus oxaliplatin‑based chemotherapy alone for metastatic colorectal cancer in the databases of PubMed, EMBASE, Cochran, and CNKI. The data of response and toxicities were extracted and pooled by random or fixed effects model. And publication bias was evaluated by begg’s funnel plot and egger’s regression test. RESULTS: Seven papers were included in this study. Adding cetuximab to oxaliplatin‑based chemotherapy regime can significant increase response rate in K‑RAS mutation metastatic colorectal patients (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.17–1.80, Z = 3.38, P = 0.001) and metastatic colorectal patients without knowing the K‑RAS status (OR: 1.36, 95% CI: 1.11–1.65, Z = 1.89, P = 0.003). But for patients with mutated K‑RAS, the improvement for objective response rate was not statistical significant (OR: 0.70, 95% CI: 0.49–1.01, Z = 3.00, P = 0.058) when adding cetuximab to oxaliplatin‑based chemotherapy regime. The pooled results indicating the rash and diarrhea risk was significantly increased in the combined treatment group (P < 0.05). The toxicity of peripheral neuritis was decreased by adding the cetuximab (P < 0.05). And other toxicities were not statistical different between the two groups (P > 0.05). Significant publication bias was found in toxicities evaluation. CONCLUSION: Cetuximab plus oxaliplatin‑based chemotherapy regimen significant increase the response rate for metastatic colorectal cancer. But the some toxicities such rash and diarrhea risk was also increased.

A meta‑analysis of bevacizumab combined with chemotherapy.

INTRODUCTION: Angiogenesis plays an important role in the biology of ovarian cancer. The clinical efficacy and side effects of bevacizumab, the vascular endothelial growth factor inhibitor, on survival and toxicity in women with this ovarian cancer, was not conclusive. We performed this systematic review and meta‑analysis in order to clarify the efficacy of bevacizumab combined with chemotherapy in the treatment of ovarian cancer. MATERIALS AND METHODS: We searched the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CNKI for clinical controlled trials of comparing bevacizumab combined with chemotherapy and chemotherapy alone in the treatment of ovarian cancer. The primary outcomes of eligible studies included median progression‑free survival (PFS), overall survival (OS), and toxicities such as enterobrosis, hypertension, albuminuria, congestive heart failure (CHF), neutrophils, thrombosis, and bleeding. The Hazard ratio (HR) and relative risk were used for the meta‑analysis and were expressed with 95% confidence intervals (CIs). All the statistical analyses were carried out by Stata 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX, USA). RESULTS: We included 5 studies with 1798 cases in the bevacizumab combined with the chemotherapy group and 1810 subjects in the chemotherapy alone group. The pooled results showed that bevacizumab + chemotherapy compared with chemotherapy alone can significant prolong the median PFS (HR, 0.64; 95% CI, 0.46–0.82; P < 0.05) but not the OS (HR, 0.84; 95% CI, 0.59–10.9; P > 0.05); the toxicity analysis showed that the enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding were significantly increased in the bevacizumab + chemotherapy group compared with chemotherapy alone (Pall < 0.05). But the CHF risk between the two groups was not statistical different (P > 0.05). CONCLUSION: Bevacizumab combined with chemotherapy prolonged the median PFS in patients with ovarian cancer but also increase the risk of developing enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding.

Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancer

Our objective was to investigate the efficacy and safety of capecitabine maintenance therapy (CMT) after capecitabine-based combination chemotherapy in patients with metastatic breast cancer. The clinical data of 139 metastatic breast cancer patients treated from March 2008 to May 2012 with capecitabine-based combination chemotherapy were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, we used CMT for 50 patients, while 37 patients were treated with a different (non-CMT) maintenance therapy. We compared time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety of the two groups, and a sub-group analysis was performed according to pathological characteristics. Sixty-four percent of the patients received a median of six cycles of a docetaxel+capecitabine combination chemotherapy regimen (range 1-45); the median TTP (MTTP) for the complete treatment was 9.43 months (95%CI=8.38-10.48 months) for the CMT group and 4.5 months (95%CI=4.22-4.78 months; P=0.004) for the non-CMT group. The MTTPs for the maintenance therapies administered after the initial capecitabine combined chemotherapy were 4.11 months (95%CI=3.34-4.87 months) for the CMT group and 2.0 months (95%CI=1.63-2.38 months) for the non-CMT group. Gastrointestinal side effects, decreased white blood cells and palmar-plantar erythrodysesthesia were the main adverse reactions experienced with the combination chemotherapies, CMT and non-CMT treatments. No significant differences in the incidence of adverse reactions were detected in the CMT and non-CMT patients. After initial disease control was achieved with the capecitabine-based combination chemotherapy, CMT can significantly prolong TTP rates with a favorable safety profile.

Lipopolysaccharide-induced dental pulp cell apoptosis and the expression of Bax and Bcl-2 in vitro

Lipopolysaccharide exerts many effects on many cell lines, including cytokine secretion, and cell apoptosis and necrosis. We investigated the in vitro effects of lipopolysaccharide on apoptosis of cultured human dental pulp cells and the expression of Bcl-2 and Bax. Dental pulp cells showed morphologies typical of apoptosis after exposure to lipopolysaccharide. Flow cytometry showed that the rate of apoptosis of human dental pulp cells increased with increasing lipopolysaccharide concentration. Compared with controls, lipopolysaccharide promoted pulp cell apoptosis (P < 0.05) from 0.1 to 100 μg/mL but not at 0.01 μg/mL. Cell apoptosis was statistically higher after exposure to lipopolysaccharide for 3 days compared with 1 day, but no difference was observed between 3 and 5 days. Immunohistochemistry showed that expression of Bax and Bcl-2 was enhanced by lipopolysaccharide at high concentrations, but no evident expression was observed at low concentrations (0.01 and 0.1 μg/mL) or in the control groups. In conclusion, lipopolysaccharide induced dental pulp cell apoptosis in a dose-dependent manner, but apoptosis did not increase with treatment duration. The expression of the apoptosis regulatory proteins Bax and Bcl-2 was also up-regulated in pulp cells after exposure to a high concentration of lipopolysaccharide.

Effects of a high molecular mass Convolvulus arvensis extract on tumor growth and angiogenesis

BACKGROUND: Plant materials represent promising sources of anti-cancer agents. We developed and tested a novel extract from the ubiquitous plant Convolvulus arvensis. MATERIALS AND METHODS: Convolvulus arvensis components were extracted in boiling water, and small molecules were removed by high-pressure filtration. The extract's biological activity was assessed by measuring its effects on S-180 fibrosarcoma growth in Kun Ming mice and on heparin-induced angiogenesis in chick embryos. We also examined the extract's effects on lymphocytes ex vivo and tumor cell growth in vitro. RESULTS: The extract (primarily proteins and polysaccharides) inhibited tumor growth in a dose-dependent fashion when administered orally. At the highest dose tested, 200 mg/kg/day, tumor growth was inhibited by roughly seventy percent. Subcutaneous or intraperitoneal administration at 50 mg/kg/day also inhibited tumor growth by over seventy percent. The extract's acute LD50 in Kun Ming mice was 500 mg/kg/day when injected, indicating that tumor growth inhibition occurred at non-toxic doses. It inhibited angiogenesis in chick embryos, improved lymphocyte survival ex vivo, and enhanced yeast phagocytosis, but did not kill tumor cells in culture. CONCLUSION: High molecular mass extract deserves further study as an anti-cancer agent.

Nationwide survey of human parasite in China.

A nationwide survey of human parasites in China was conducted during 1988-1992, with a coverage of 30 provinces/autonomous regions/municipalities (P/A/M). A total of 2,848 pilot sites in 726 counties were selected by random sampling, and 1,477,742 individuals residing on were surveyed by fecal examination. The status of paragonimiasis, hydatid diseases, cysticercosis and trichinellosis were summarized through data review. The overall infection rate of intestinal parasites was 62.6% whereas at provincial level, the highest infection rate (94.7%) was recovered in Hainan, and the lowest (17.5%) in Heilong-jiang. A high proportion (43.3%) of polyparasitism among the infected population (882,080) was revealed. Altogether 56 species of parasites comprising protozoa (19), trematode (16), cestodes (8), nematodes (12) and thorny-headed worm (1) were discovered. During the survey a new species and several new records were documented. The number of the population infected with common intestinal parasites was estimated. The diversities of parasite distribution were noted in different nationalities as well as in varied occupations.