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In the era of intensity-modulated radiotherapy (IMRT), it is important to analyse the prognostic value of deficient mismatch repair (dMMR) in nasopharyngeal carcinoma (NPC). In this study, in pretreatment biopsies of 69 patients with stage II–IVa NPC, the expression levels of MMR proteins, including MLH1, MSH2, MSH6 and PMS2, were assessed by immunohistochemistry (IHC). The median follow-up time was 37.5 months (3.1–87.4 months). 50.7% of cases (35/69) showed preserved expression of all 4 MMR proteins, which was interpreted as proficient mismatch repair (pMMR). Only 1.5% of cases (1/69) lost expression of all 4 MMR proteins, 26.1% of cases (18/69) have PMS2 loss alone and 21.7% of cases (15/69) lost expression of both PMS2 and MLH1. Thus, 49.3% of cases (34/69) lost expression of one or more MMR proteins, which was interpreted as dMMR. There was no significant difference (P > 0.05) in terms of sex, age, clinical stage, T category, N category or therapy regimens between the dMMR and pMMR groups. The multivariate Cox regression analysis revealed that dMMR was an independent significant prognostic factor for distant metastasis-free survival (DMFS) (dMMR vs pMMR: P = 0.01, HR = 0.25, 95% CI: 0.09~0.75). Therefore, NPC patients with dMMR had significantly superior DMFS compared with patients with pMMR. It can be expected that dMMR will become a new independent prognostic factor for NPC. more...

Background and Objective: The aim of this study was to investigate the value of programmed death ligand 1 (PD-L1) expression as a predictive biomarker for Miller/Payne grading before neoadjuvant chemotherapy (NACT) in breast cancer. Patients and Methods: The expression of PD-L1 in pretreatment biopsies of breast cancer was assessed by immunohistochemistry in tissue microarrays. The results were analyzed using SPSS 22.0 statistical software. Results: Of 53 female patients, 10 (18.9%) patients had a grade 5 (G5) response, and 12 (22.6%) patients showed PD-L1 expression, including 7 (13.2%) patients with staining in tumor cells (TCs) and 8 (15.1%) patients with staining in peritumoral lymphocytes (PTLCs). Logistic regression analysis revealed that G5 response to NACT was significantly associated with TCs or PTLCs PD-L1 positivity, whether with univariate analysis (TCs PD-L1: p = 0.00, OR 20.50, 95% CI 3.11–134.94; PTLCs PD-L1: p = 0.02, OR 6.50, 95% CI 1.27–33.20) or with multivariate analysis (TCs PD-L1: p = 0.00, OR 42.23, 95% CI 3.36–530.90; PTLCs PD-L1: p = 0.02, OR 9.07, 95% CI 1.37–60.02). The same trend was found in the luminal subgroup analysis (TCs PD-L1: p = 0.02, OR 23.43, 95% CI 1.66–331.58; PTLCs PD-L1: p = 0.01, OR 47.89, 95% CI 2.47–927.41). Conclusion: G5 response to NACT in breast cancer was significantly associated with TCs or PTLCs PD-L1-positive expression in pretreatment biopsies; it can be expected that PD-L1 will become a new independent biomarker of response to NACT in breast cancer. more...

The therapeutic strategies for advanced gastric cancer (GC) remain unsatisfying and limited. Therefore, it is still imperative to fully elucidate the mechanisms underlying GC aggressive progression. The prognostic value and biological functions of low density lipoprotein receptor class A domain containing protein 2 (LDLRAD2) in GC have never been studied yet. We found that LDLRAD2 expression was significantly upregulated in GC and closely correlated with poor prognosis in GC patients. Functionally, LDLRAD2 promoted epithelial-mesenchymal transition, migration and invasion, and metastasis of GC cells. Mechanistically, LDLRAD2 interacted with and inhibited Axin1 from binding to cytoplasmic β-catenin, which facilitated the nuclear translocation of β-catenin, thereby activating Wnt/β-catenin pathway. Inhibition of β-catenin activity markedly abolished LDLRAD2-induced migration, invasion and metastasis. Together, these results suggested that LDLRAD2 contributed to invasion and metastasis of GC through activating Wnt/β-catenin pathway. LDLRAD2/ Wnt/β-catenin axis may be a potential therapeutic target for GC treatment. more...

Background Severe complications associated with EV71 infections caused many infants death. However, the pathogenesis of EV71 infection in the severe cases remained poorly understood. Methods In this study we collected plasma and cerebrospinal fluid (CSF) specimens drawn in the acute and/or recovery phases from EV71-infected individuals, and plasma specimens from healthy children served as normal controls. We compared the levels of cytokines and chemokines determined by a Luminex-based cytokine bead array. Results The plasma levels of IL-1β and IL-6 were significantly higher in severe and critical cases than in mild patients and normal controls. Higher plasma levels of IL-6, IL-10, and IL-8 were evident in critical than severe cases. The CSF levels of IL-6, IL-8, and IP-10 were higher, and that of RANTES lower (compared to plasma), in severe and critical patients. Significantly lower CSF levels of cytokines and chemokines were recorded in the recovery than the acute phase in severe and critical cases treated with intravenous immunoglobulin (IVIG) and glucocorticoids. Only the CSF levels of IL-6, IP-10, and IL-8 were significantly correlated with white blood cell counts, and absolute neutrophil and monocyte counts, in severe cases. Furthermore, the CSF levels of IL-6 were correlated with temperature in both cases. Conclusions These data indicate that a major cytokine response and inflammation, in both plasma and the CNS, are features of disease caused by EV71 infection. Systemic inflammation caused by EV71 infection exacerbated the deterioration of the disease, and resulted in the disease progression to the critical illness stage. more...

To study the etiological agent of hand-foot-and-mouth disease (HFMD), and to genetically characterize enterovirus 71 (EV71) isolated from clinical specimens of HFMD patients in Nanjing in 2010.Throat swab specimens were collected from 248 inpatients with HFMD in Nanjing Children's Hospital and then viral isolation was performed. Real-time PCR was used for detection of EV71, coxsackievirus A16 (Cox A16) and other enteroviruses from the positive isolates. Twenty EV71 strains from different clinical types of cases were selected for entire VP1 coding gene amplification and sequencing, finally a phylogenetic tree was constructed among the 20 EV71 strains and EV71 representative strains of known genotypes and subgenotypes.From the 248 throat swabs specimens, 110 EV71 strains, 28 Cox A16 strains, and 8 other enterovirus strains were isolated and the positive rate was 44.35%, 11.29%, 3.23%, respectively. Then nucleotide sequencing was performed on the 20 EV71 strains. There was little difference in the nucleotide and the amino acid sequences among the 20 EV71 strains, the homology was 95.51%-100% and 98.32%-100%, respectively. The phylogenetic tree showed that all the 20 EV71 strains belonged to C4 subgenotype.EV71 was the main pathogen of HFMD in Nanjing in 2010 and all the analyzed isolates belonged to C4 serotype. No significant difference was found in sequence of VP1 region of EV71 isolated from different clinical types of cases. more...

Hemolysis is a common feature in patients with β-thalassemia major. As a result, autoimmune hemolytic anemia complicating β-thalassemia is easily overlooked. Here, the authors described the clinical features and management of 7 patients with β-thalassemia major and autoimmune hemolytic anemia. These patients had fever, cough, and tea-colored urine on admission. The laboratory investigations showed a significant drop in hemoglobin and increased serum bilirubin. Coombs' tests revealed that anti-immunoglobulin G (IgG) and anti-C3 was positive in 7 and 5 cases, respectively, whereas anti-Rh E alloantibody was positive in 3 cases. All the patients received corticosteroids treatments and blood transfusions. Patients with anti-Rh E alloantibodies also received immunoglobulin treatments. Six of the patients responded well to the management, but 1 patient developed recurrent autoimmune hemolytic anemia that required cyclosporin A treatment. All the patients remained well by following up for more than 6 months. more...

To study the clinical and molecular epidemiology characteristics of human Bocavirus 1-3 (HBoV1-3) in children for acute respiratory infection in Lanzhou area.Nasopharyngeal aspiration samples and throat swabs were collected from 524 children with ARTI at the First Hospital of Lanzhou University, Gansu Province, China, between December 2009 and November 2010. Nested PCR was employed to screening HBoV1-3, which amplified a 518-bp fragment of the partial NS1 gene. Furthermore, a standard reverse transcription-PCR was used to screen for other common respiratory viruses.The overall frequency of HBoV was 8.2% (43/524), lining up behind human rhinovirus, RSV, parainfluenza virus 3. Thirty of the HBoV-postive children(69.8%) were co-infected with other respiratory viruses. The prevalence of HBoV1 in ALRTI was obviously higher than that in AURI. The 2 HBoV2 NS1 sequences shared 99% and 100% nucleotide sequence identity with HBoV2 strain CU47TH respectively. Two cases of HBoV2 postive children appears gastrointestinal symptoms. The one HBoV3 NS1 sequences shared 99% nucleotide sequence identity with HBoV3 isolate 46-BJ07.The HBoV3 was detected at the first time in lanzhou area. HBoV1-3 infection exists in children with acute respiratory tract infections in Lanzhou region, HBoV1 were dominant. The mixed infection rate was higher. more...

To investigate the molecular epideiological and clinical feature of human metapneumovirus in children with acute respiratory tract infection in Nanjing city, China.Nasopharyngeal aspirates and nasopharyngeal swab were taken from 642 outpatients or hospitalized pediatric patients with acute at the Children Hospital of Nanjing, Jiangsu Province, China, between August 2009 and July 2010. Respiratory speciments were tested for the M gene of hMPV by reverse-transcription polymerase chain reaction (RT-PCR). All RT-PCR positive products were sequenced and phlogenetic analysis was conducted.hMPV was detected in 35 (5.5%) of the 642 children. Phylogenetic analysis revealed that 51.4% of the hMPV were B1, 31.4% were A2b. The peak of the positive rate was in April. The majority of the hMPV-positive patients(71.4%) were 0-1 years old. Of the 35 hMPV-positive patients, 15 (42.8%) were co-infected with other respiratory viruses, and human rhinovirus (HRV) were the most common additional respiratory virus. The most common clinical diagnosis was pneumonia (48.6%).Human metapneumovirus is an important pathogen of acute respiratory tract infection in children in Nanjing city. The subtype B1 was the predominating lineage in 2009-2010 in Nanjing city. No significant differences were found for clinical characteristics between genotype A and genotype B human metapneumovirus infection in children in Nanjing. more...

This study was purposed to detect the minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) by using real time quantitative PCR (RQ-PCR) . The Ig and TCR gene rearrangements were amplified by using 18 primer sets in B-ALL, 8 primer sets in T-ALL; the ALL-MRD levels were quantified by using RQ-PCR with SYBR green dye staining and clone specific Ig/TCR gene rearrangements as molecular markers. The results indicated that there were 8 cases showing gene rearrangements in 9 B-ALL patients, marker detection rate for all samples was 88.8%, the MRD level on day 33 during induction treatment decreased significantly. It is concluded that Ig/TCR gene rearrangements can be used as a marker to detect MRD in childhood ALL; the technique of QR-PCR with SYBR green dye staining is reliable, relatively sensitive and easy performable method which can be used in routine detection for childhood ALL. more...