Pre-emptive therapy is an effective approach for cytomegalovirus (CMV) control; however, refractory CMV still occurs in a considerable group of recipients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Until now, hardly any data have been available about the clinical characteristics and risk factors of refractory CMV, or its potential harmful impact on the clinical outcome following allo-HSCT. We studied transplant factors affecting refractory CMV in the 100 days after allo-HSCT, and the impact of refractory CMV on the risk of CMV disease and non-relapse mortality (NRM). We retrospectively studied 488 consecutive patients with CMV infection after allo-HSCT. Patients with refractory CMV in the 100 days after allo-HSCT had a higher incidence of CMV disease and NRM than those without refractory CMV (11.9% vs. 0.8% and 17.1% vs. 8.3%, respectively). Multivariate analysis showed that refractory CMV infection in the 100 days after allo-HSCT was an independent risk factor for CMV disease (hazard ratio (HR) 10.539, 95% CI 2.467-45.015, p 0.001), and that refractory CMV infection within 60-100 days after allo-HSCT was an independent risk factor for NRM (HR 8.435, 95% CI 1.511-47.099, p 0.015). Clinical factors impacting on the risk of refractory CMV infection included receiving transplants from human leukocyte antigen-mismatched family donors (HR 2.012, 95% CI 1.603-2.546, p <0.001) and acute graft-versus-host disease (HR 1.905, 95% CI 1.352-2.686, p <0.001). We conclude that patients with refractory CMV infection during the early stage after allo-HSCT are at high risk for both CMV disease and NRM.

Treatment of ducks congenitally infected with the duck hepatitis B virus (DHBV) using the guanosine analogue ganciclovir resulted in prompt and profound inhibition of viral DNA replication in serum and liver. By the end of the treatment period all the replicative intermediates, except the supercoiled DNA form, could not be detected. Within 2 weeks of cessation of treatment viral replication returned and, in some cases, rebound occurred. Sequential treatment with prednisolone followed by ganciclovir also resulted in inhibition of viral replication and, even though relapse was observed after therapy was discontinued, the rebound phenomenon was reduced. Ganciclovir significantly and selectively inhibited DHBV DNA replication but may be more efficacious if used in combination with compounds targeted to the viral supercoiled DNA form.

The results suggest that ER stress is involved in human and Ang II induced AAA formation in ApoE mice. TUDCA attenuates Ang II induced AAA formation in ApoE mice by inhibiting ER stress mediated apoptosis.

BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT.MethodsIn this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype- mismatched transplantation. The four SNP genotypes (−1661, −318, CT60 and +49) were determined by TaqMan SNP genotyping assays.ResultsALL recipients of donors with +49 GG showed significantly lower OS (67.7 vs. 90.3 %, P = 0.015) than those with GA+AA. Multivariate analyses showed that +49 GG was an independent risk factor for OS (HR: 0.306, 95 % CI 0.111–0.842, P = 0.022) .23 ALL patients receiving mDLI showed significantly lower OS with +49 GG donor than those with GA+AA (30.0 vs. 83.1 %, P = 0.003). The haplotype analysis revealed only three haplotypes in the donor population −1661/−318/CT60/+49 i.e., ACGG, ACAA and GTGA, the frequencies were 64.1, 19.4 and 16.5 %, respectively. Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcomes as those with +49 GG and +49 GA+AA.ConclusionIn summary, the CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival in ALL after allo-HSCT from the related HLA-haplotype-mismatched donor, knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.

We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT.

The present study was conducted to explore the efficacy of suicide gene therapy with thymidine kinase (TK) in combination with cytosine deaminase (CD) for breast cancer. The expression of CD/TK was detected in the infected cells by RT-PCR. The killing effect on MCF-7 cells following treatment was analyzed by MTT assay. The morphological characteristics of the cells were observed by electron microscopy, and the distribution of the cell cycle was analyzed by flow cytometry. Caspase‑3 and -8 activities were detected by absorption spectrometry. Cytotoxic assays showed that cells transfected with CD/TK became more sensitive to the prodrugs. Morphological features characteristic of apoptosis were noted in the MCF‑7 cells via electron microscopy. The experimental data showed that the proportion of MCF-7 cells during the different phases of the cell cycle varied significantly following treatment with the prodrugs. The activity of caspase‑3 gradually increased following treatment with increasing concentrations of the prodrugs. We conclude that the TK/ganciclovir and CD/5-fluorocytosine suicide gene system used here induces apoptosis in breast cancer cells, and provides a promising treatment modality for breast cancer.

improve the detection of ITC compared with routine pathological examination.Background: Accurate TNM staging plays an important role in the diagnosis, treatment, and prognosis of lung cancer. In current clinical practice, the staging of lung cancer is usually decided by physicians. We aim to develop an automated lung cancer staging system using machine learning and verify the staging correctness. Method: In this work, we constructed a feature generalizing and automatically extracting model using NLP techniques. The parameters required for Tumor (T), Lymph nodes (N) and Metastases (M) categories of the eighth edition of the International Lung Cancer Research Association (IASLC) TNM staging system were automatically extracted from de-identified electronic medical records of pathology, operation note, CT scan, PET/CT scan, cranial MRI, bone scan, and ultrasound. A technical solution using Bayesian reasoning network was developed for automated staging. The stage was automatically predicted while the reasoning basis was given. All the reports were reviewed by thoracic surgeons to obtain the gold standard for evaluation. Result: Five hundred de-identified reports were collected as training dataset to construct the model by learning from stage given by physicians. Five hundred and thirteen de-identified reports were collected as validation dataset. The current overall recall rate was 96.88%, and the agreement rate between machine prediction and physicians's diagnosis was 93.70%. Conclusion: Natural language processing is a useful technique for encoding medical reports in order to detect the TNM descriptors. Automatic lung cancer staging process using Bayesian reasoning network achieve acceptable accuracy. This system is extendable and can be applied to large database processing.

Background: KD025 is an inhibitor of ROCK2 in a pivotal clinical trial for chronic graft-versus-host disease (cGVHD). Inhibition of ROCK2 downregulates TH17 and Tfh cells while upregulating regulatory T (Treg) cells, helping to resolve the immune dysregulation seen in cG-VHD. In addition, KD025 decreases myofibroblast formation and proliferation, inhibiting the fibrotic components of cGVHD. Aims: KD025-208 is an open-label, Phase 2 study of KD025 in patients with steroid-dependent or refractory cGVHD.