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Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

ObjectiveHerein, we purposed to explore the association of sleep duration with chest pain among adults in US.MethodsThis research work enrolled 13,274 subjects in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The association of sleep duration with chest pain among adults in US was evaluated by Multivariable logistic regression.ResultsTo elucidate the association, we made adjustments for gender, BMI, diabetes, smoking status, drinking status, race, marital status, annual family income, hyperlipoidemia, Hypertension. Chest pain incidence decreased by 5% [OR = 0.95 (0.93, 0.98), p = 0.0004] for an increase in sleep duration by 1 h. A generalized additive model (GAM) was used to reseal a U-shaped relationship of sleep duration with incident chest pain. When duration of sleep was P < 0.0001]. However, when sleep duration was ≥6.5 h, chest pain incidence rose with escalating sleep duration [OR = 1.07 (1.03, 1.11) p = 0.0014].ConclusionsDuration of sleep was established to be independently linked with an increase in the occurrence of chest pain. Excessive sleep, as much as insufficient sleep, increases the risk of chest pain. Both excessive sleep and insufficient sleep are associated with an increased risk of chest pain.

Background Though the survival benefit of primary tumor operation for patients with signet ring cell carcinoma of the stomach is known, the specific characteristics of those patients who would profit from the operation are yet to be determined. To this end, a predictive model was developed to identify the conjecture that the survival profit from primary tumor operation would only be obtained by patients. Method The clinical data of the patients with signet ring cell carcinoma of the stomach were obtained from the Surveillance, Epidemiology, and End Results database, and then divided into operation and no-operation groups based on whether the patients underwent the primary tumor operation. To remove the confounding factors, propensity score matching was employed, and it was hypothesized that the patients who had been operated on and lived a longer life than the median cancer-specific survival time of those who hadn’t must have profited from the surgery. To discuss the independent factors of cancer-specific survival time in the beneficial group and the non-beneficial group, the Cox model was used, and based on the various vital predictive factors, a nomogram was drawn using logistic regression. Result The number of eligible patients was 12,484, with 43.9% (5483) of them having received surgery. After employing propensity score matching, the cancer-specific survival time of the operation group was found to be apparently longer (median: 21 vs. 5 months; p < 0.001) than the no-operation group. In the operation group, 4757 (86.7%) of the patients lived longer than five months (beneficial group). The six indexes (beneficial and non-beneficial group) included gender, age, Tumor Node Metastasis stage, histologic type, differentiation grade, and tumor position, and were used as predictors to draw the nomogram. The nomogram was used to divide the patients who had taken operations into two groups: the beneficial operation group and the non-beneficial operation group. The beneficial operation group, it was found, survived longer than the non-beneficial operation group (median cancer-specific survival time: 28 vs. 3 months, p < 0.001). Moreover, there was we could tell little difference in survival between the two groups (median cancer-specific survival time: 3 vs. 5 months). Conclusions The predictive model created to select suitable candidates for surgical treatment from patients with signet ring carcinoma of the stomach could be adopted to identify certain patients benefiting from the primary tumor operation.

Efficacy evaluation through human trials is crucial for advancing a vaccine candidate to clinics. Next-generation sequencing (NGS) can be used to quantify B cell repertoire response and trace antibody lineages during vaccination. Here, we demonstrate this application with a case study of Hecolin®, the licensed vaccine for hepatitis E virus (HEV). Four subjects are administered the vaccine following a standard three-dose schedule. Vaccine-induced antibodies exhibit a high degree of clonal diversity, recognize five conformational antigenic sites of the genotype 1 HEV p239 antigen, and cross-react with other genotypes. Unbiased repertoire sequencing is performed for seven time points over six months of vaccination, with maturation pathways characterize for a set of vaccine-induced antibodies. In addition to dynamic repertoire profiles, NGS analysis reveals differential patterns of HEV-specific antibody lineages and highlights the necessity of the long vaccine boost. Together, our study presents a quantitative strategy for vaccine evaluation in small-scale human studies., The authors provide a comprehensive characterization of the human antibody response to a licensed hepatitis E virus (HEV) vaccine, Hecolin, in four individuals over the course of six months post vaccination. They demonstrate diverse patterns of antibody response underlying the vaccine protection.

We reviewed the outcomes of 77 episodes of CD19 CAR-T therapy in 67 patients with B cell hematological malignancies from October 2016 to January 2020. Factors related to the grade of cytokine release syndrome (CRS) were explored by multivariate analysis, nonparametric test was conducted to explore the correlation between CRS and response. Kaplan-Meier curves were used to indicate survival profiles, and the correlation between CRS and survival was determined by the log-rank test.The rate of complete remission (CR) was 74.0% (57/77). CRS of any grade occurred in 68 of 77 episodes (grade 1: 32.5%, grade 2: 24.7%, grade 3: 22.1%, grade 4: 6.5%, grade 5: 2.6%). Patients with a history of transplantation had less severe CRS, and dose escalation-based infusion reduced the severity of CRS. Severe CRS was related to a higher CR rate but had no significant impact on event-free survival (EFS), relapse-free survival (RFS), or overall survival (OS).As a common adverse reaction of CAR-T therapy, the severity of CRS can be alleviated by dose escalation infusion, a history of transplantation was correlated with less severe CRS. Severe CRS was related to better response but was unrelated to long-term survival.

Background: For extremely low-birth-weight infants (ELBWIs), mechanical ventilation and total parenteral nutrition are generally required in the early stages and lose the protective effect of early gastrointestinal nutrition of colostrum. We conducted a prospective randomized controlled trial to explore the effectiveness of early colostrum oropharyngeal administration on the feeding status of ELBWIs on mechanical ventilation. Materials and Methods: We randomly divided mechanically ventilated ELBWIs into an intervention group and a control group. In the intervention group, we provided oropharyngeal administration of colostrum during mechanical ventilation. The first colostrum oropharyngeal administration ended within 24 hours of birth. In the control group, we gave colostrum only for gastrointestinal nutrition, and other interventions were the same as for the intervention group. We collected the 1st and 6th day of life airway secretions and urine specimens from both groups. We recorded feeding status, including corrected gestational age at onset of enteral nutrition, corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, corrected gestational age of sucking began, and corrected gestational age of per oral feeding. We also recorded growth of body mass, the incidence of feeding intolerance, and necrotizing enterocolitis (NEC). Results: On the 6th day of life, concentrations of secretory immunoglobulin A, and lactoferrin in airway secretions and urine of the intervention group were significantly higher than those of the control group (p < 0.05). The intervention group showed younger corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, the corrected gestational age of sucking began and per oral feeding than those in the control group (p < 0.05). The day of recovery to birth weight was earlier than those in the control group (p < 0.05). The rate of feeding intolerance and NEC incidence in the intervention group was significantly lower than in the control group (p < 0.05). Conclusions: Early oropharyngeal administration of colostrum improves immune function of the gastrointestinal tract and the systemic anti-infective capability in ELBWI on mechanical ventilation, promoting the maturity of gastrointestinal function, improving feeding condition, and reducing the risk of feeding intolerance and NEC.

Background: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). Methods: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. Results: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90–30.10%) and 24.2% (95% CI, 13.81–34.59%) for the MRD group and 16.80% (95% CI, 1.71–31.89%) and 28.70% (95% CI, 8.71–48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ2 = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24–71.36%) and 45.4% (95% CI, 33.44–57.36%), and 65.6% (95% CI, 47.18–84.02%) and 26.8% (95% CI, 7.59–46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ2 = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. Conclusion: Haploidentical SCT could be performed safely and feasibly for patients with MM in need. Key words: Allogeneic stem-cell transplantation; Multiple myeloma

The integrity of functional epitopes is a critical quality attribute for recombinant protein based vaccines since the presence of these native-like epitopes is the structural basis for vaccines to elicit functional antibodies. To demonstrate the quality and quantity of functional epitopes on vaccine antigens, a toolbox of assessing antigen characteristics is essential. Among the physicochemical, biophysical, immunochemical and in vivo potency analyses, the epitope-specific assays are most critical assessment of the antigen functionality. In this study, we used hepatitis E virus vaccine as an example to illustrated how the monoclonal antibody (mAb) based immunochemical assays were established for in-depth and multifaceted antigen characterization. A large panel of mAbs were developed and characterized using epitope clustering analysis. A subset of these mAbs recognizing non-overlapping epitopes were chosen to be used for assay development. Orthogonal methods, including surface plasma resonance-based BIAcore, solution competitive ELISA and sandwich ELISA, were developed for the antigenicity assessment. The sandwich ELISA with a pair of mAbs, recognizing two different epitopes, was used to assess the accelerated antigen stability, showing enhanced stability with adjuvant adsorption. Such a sandwich ELISA with robust performance has the potentials to be used for in vitro potency analysis to replace animal-based potency assay as product release test. In summary, using hepatitis E vaccine as an example, we demonstrated the importance and establishment of a mAb-based immunochemical toolbox for multifaceted antigen characterization. This is particularly important to demonstrate the successful reconstruction of the native-like and functional epitopes on a recombinant antigen post expression and purification. These epitope-specific and multifaceted assays serve as critical tools for process monitoring or lot consistency tests in support of vaccine development and manufacturing.

With the dramatic improvements in outcomes following alternative donor hematopoietic stem cell transplantation (HSCT), interest in the use of alternative donors in severe aplastic anemia (SAA) is increasing. We conducted a multicenter prospective study to explore the efficiency and safety of upfront HSCT from a 6-8/8 HLA-matched unrelated donor (MUD) or 6-7/8 HLA-matched related donor (MRD) in acquired SAA patients under 40 years. Between August 2014 and July 2017, 115 patients were enrolled, including 48 (41.7%) patients receiving grafts from an 8/8 MUD, 25 (21.7%) from a 6-7/8 MRD, and 42 (36.5%) from a 6-7/8 MUD. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was higher in the 6-7/8 MUD group than in the 8/8 MUD group (42.9% vs. 12.8%, P=0.001). The corresponding incidence in the 6-7/8 MRD group was comparable to that in the 8/8 MUD group (21.7% vs. 12.8%, P=0.332). There was no significant difference in the incidence of chronic GVHD (24.3%, 13.6%, and 17.9%, P=0.676), graft failure (2.4%, 8.0%, and 6.3%, P=0.551), overall survival (85.7%, 96.0%, and 87.5%, P=0.424), and failure-free survival (83.3%, 88.0%, and 83.3%, P=0.885) among the three groups (6-7/8 MUD, 6-7/8 MRD, and 8/8 MUD). In multivariate analysis, conditioning regimen without low-dose irradiation or busulfan was associated with an inferior failure-free survival (HR=2.973, P=0.042). In conclusion, after an intensified conditioning regimen with additional low-dose irradiation or busulfan, the outcome of HSCT from a 6-7/8 MRD or 6-7/8 MUD is comparable to that from an 8/8 MUD.

To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML).The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis.Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival，and no patient relapsed.UCBT is an effective treatment for children with JMML.单份非血缘脐血移植治疗幼年型粒单核细胞白血病的疗效分析.探讨非血缘脐血移植（UCBT）治疗幼年型粒单核细胞白血病（JMML）的临床疗效和安全性.回顾性分析2011年10月至2019年7月5例接受单份UCBT的JMML患儿的临床资料。5例患儿均为男性，中位发病年龄1.5（0.4-5.0）岁。全部患儿均采用清髓性不含ATG的预处理方案，并予以环孢素A联合霉酚酸酯方案预防移植物抗宿主病（GVHD）.5例患者中4例成功植入，1例原发性植入失败接受挽救性相合造血单倍体干细胞移植。2例Ⅲ-Ⅳ度急性GVHD均有效控制，无慢性GVHD发生。3例患儿无病生存，无1例复发.UCBT是治疗JMML的有效方法.

Hyperglycaemia is responsible for the major pathophysiological factor of diabetes-associated vascular endothelial injury, which mainly resulted from the disturbance of equilibrium between ROS generation and elimination. Eucalyptol was verified with exact anti-oxidation effects via stimulating the secretion of endogenous antioxidant enzymes against ROS. However, the volatility, instability and poor water solubility of eucalyptol limited its pharmacological activities in vivo. In this study, we developed carboxymethyl chitosan-coated lipid nanoparticles for eucalyptol (CMC/ELN) to facilitate oral administration. A thin lipid film dispersion method was used to prepare the ELN. After CMC coating, the diameter of ELN increased from 166 nm to 177 nm and charge reversal was observed. The nanocarrier enhanced the protective effects of eucalyptol both in the high level of glucose (HG)-damaged HUVECs and endothelial injury in type I diabetes mellitus (T1DM) rat model. Furthermore, the mechanism of eucalyptol on the promotion of Nrf2 and HO-1 and reduction on Keap1 expression have been verified both in the in vitro and in vivo model. Besides, the pharmacokinetics data were verified the promotion of the oral eucalyptol absorption by the nanocarrier. Taken together, we established an optimal oral delivery system that promoted oral administration of eucalyptol to exert protective effects on hyperglycaemia-induced vascular endothelial injury.

Background Hepatitis E virus (HEV)-caused acute viral hepatitis is a major threat to public health worldwide. Recently, an enzyme linked immunosorbent assay (ELISA) kit detecting the HEV antigen was reported to have good concordance with the HEV RNA load and showed good clinical performance. But the ELISA kits can barely satisfy the needs of community clinics. In this study, a fluorescent microbead-based immunoassay (FMIA) for detecting the HEV antigen was developed and evaluated. Methods A mouse anti-HEV monoclonal antibody (mAb) conjugated with fluorescent microbeads was used as capturing antibody and another mouse mAb was used as detection antibody. Overall, 150 serum samples were collected from HEV-infected patients (n = 50) and non-HEV cases (n = 100) to evaluate the performance of the FMIA. Results The FMIA results showed a strong linear correlation with the viral RNA load. The diagnostic sensitivity and specificity of the HEV antigen FMIA were 92.0% (46/50) and 100.0% (100/100), respectively, and the test was consistent (kappa = 0.937, p = 0.627) with the commercial HEV antigen ELISA. The FMIA also showed good consistency with the PCR results (kappa = 0.939, p = 0.134). Conclusions As a rapid point-of-care (POC) test, a FMIA that is developed with acceptable performance is suitable for acute hepatitis E diagnosis, especially in developing countries and regions, because of its reduced time and simplified operation.

Hepatitis E virus (HEV) is one of the major pathogens that cause acute viral hepatitis. The human (genotypes 1 and 2) and zoonotic (genotypes 3 and 4) groups of HEV present different epidemiology and clinical features. In this study, we developed a classification method for rapidly classifying HEV into human or zoonotic groups that combines a general antigen test with a zoonotic group-specific antigen test. Evaluation of serial samples from HEV-infected rhesus monkeys indicated that HEV antigen-positive samples can be classified using the antigen-based classification method. The antigen-based classification method was evaluated further on 55 genotyped samples from acute hepatitis E patients, including 9 human and 46 zoonotic groups. The novel method was completely consistent with the sequencing results: 9/9 for the human groups (100%, 95% confidence interval [CI] 66.4-100%) and 46/46 for the zoonotic groups (100%, 95% CI 92.3-100%). This method was also successfully used for the clustering of some samples that could not be clustered by sequencing. Compared with the sequencing-based method, this method is less time-consuming, less expensive, and less technically complex and is therefore ideal for large numbers of samples. In conclusion, this study provides a convenient and sensitive method for classifying different groups of HEV, and it has potentially important public health applications, especially in underdeveloped areas that cannot afford the high cost of nucleic acid testing.

To investigate the effects of cytomegalovirus (CMV) DNA load on immune reconstitution and clinical outcomes of patients after unrelated cord blood transplantation (UCBT).Eight-color flow cytometry was used to dynamically monitor the changes of peripheral blood lymphocyte subsets of 41 patients at one year after UCBT, and 10 healthy volunteers were enroled as controls. Patients were divided into two groups according to the DNA load of CMV (DNA copies1000/ml and DNA copies ≥1000/ml). Comparative analyse of the effect of CMV DNA load on lymphocyte subsets and transplantation outcomes were carried out after transplantation.The high CMV DNA load group showed a faster and expanded T cell reconstitution, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.38×10The high CMV DNA load induces a faster and long-lasting expansion of T cells, mainly as the expansion of CD8单份非血缘脐血移植术后巨细胞病毒的DNA负荷对免疫重建及移植结局的影响.探索巨细胞病毒（CMV）的DNA负荷对非血缘脐血移植（UCBT）后免疫重建和临床结局的影响。.8色流式细胞术动态监测41例患者UCBT后1年的外周血淋巴细胞亚群变化，同时纳入10例健康体检者作为正常人对照。根据CMV的DNA负荷水平（DNA拷贝1 000/ml和DNA拷贝≥1 000/ml）将患者分为2组，比较分析移植后CMV的DNA负荷对淋巴细胞亚群重建及移植结局的影响.CMV的DNA高负荷组呈现较快的T细胞重建，且移植后1年内的T细胞数均高于DNA低负荷组，2组间T细胞数在移植后1和9个月分别为0.38×10UCBT后CMV的DNA高负荷促进T细胞的扩增，主要表现为CD8

To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT).Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD.The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.非血缘脐血移植治疗高危难治AML1-ETO阳性急性髓细胞白血病的疗效分析.分析非血缘脐血移植（UCBT）治疗AML1-ETO+ 急性髓系白血病（AML）患者中的植入、移植物抗宿主病（GVHD）及生存等临床结果.2010年7月-2018年4月，单中心进行单份UCBT治疗高危难治性AML1-ETO+ AML患者45例。对所有患者均采用清髓性预处理方案，应用环孢素A（CSA）联合吗替麦考酚酯（MMF）预防GVHD.输注脐血总有核细胞（TNC）中位值为5.21（1.96-12.68）×10UCBT是高危难治性AML1-ETO+ AML的一种有效解救治疗措施.

Background Nepal is an endemic area for hepatitis E virus (HEV) epidemics. The research on viral hepatitis in Nepal is limited. Methods Serum samples from 170 patients presenting with symptoms of hepatitis were collected from April to May 2014 in Biratnagar, Nepal, and then transported to Xiamen, China, for further evaluation. All samples were tested for HEV RNA, HEV antigen, anti-HEV IgM, anti-HEV IgG and anti-HBc IgM, anti-HCV IgG, and anti-HAV IgM. Results Sixteen patients were identified as acute hepatitis E with the presence of ≥ 2 HEV acute phase markers (antigen, RNA, and anti-HEV IgM). HEV infection was the major cause of potential active viral hepatitis (59.2%, 16 of 27), followed by HBV (25.9%, 7 of 27, anti-HBc IgM positive), HAV (18.5%, 5 of 27, anti-HAV IgM positive), and HCV (3.7%, 1 of 27, anti-HCV antibodies). All 16 confirmed HE cases were positive for HEV antigen, while 5 cases were HEV RNA positive, as well as 15 anti-HEV IgM positive. The low positive rate of RNA might be related to the collection and/or the transportation of these samples. Conclusions This study showed that HEV is a major cause of acute hepatitis in developing countries and regions. Application of immunoassay diagnostic kits, especially the HEV antigen tests, showed great potential for HE detection in these countries and regions.

The enterically transmitted hepatitis E virus (HEV) adopts a unique strategy to exit cells by cloaking its capsid (encoded by the viral ORF2 gene) and circulating in the blood as “quasi-enveloped” particles. However, recent evidence suggests that the majority of the ORF2 protein present in the patient serum and supernatants of HEV-infected cell culture exists in a free form and is not associated with virus particles. The origin and biological functions of this secreted form of ORF2 (ORF2S) are unknown. Here we show that production of ORF2S results from translation initiated at the previously presumed AUG start codon for the capsid protein, whereas translation of the actual capsid protein (ORF2C) is initiated at a previously unrecognized internal AUG codon (15 codons downstream of the first AUG). The addition of 15 amino acids to the N terminus of the capsid protein creates a signal sequence that drives ORF2S secretion via the secretory pathway. Unlike ORF2C, ORF2S is glycosylated and exists as a dimer. Nonetheless, ORF2S exhibits substantial antigenic overlap with the capsid, but the epitopes predicted to bind the putative cell receptor are lost. Consistent with this, ORF2S does not block HEV cell entry but inhibits antibody-mediated neutralization. These results reveal a previously unrecognized aspect in HEV biology and shed new light on the immune evasion mechanisms and pathogenesis of this virus.

Background: A quantitative and accurate measurement of the range of hip joint flexion (RHF) is necessarily required in the evaluation of disordered or artificial hip joint function. This study aimed to assess a novel method to measure RHF more accurately and objectively. Methods: Lateral radiographs were taken of 31 supine men with hip joints extended or flexed. Relevant angles were measured directly from the radiographs. The change in the sacrofemoral angle (SFA) (the angle formed between the axis of the femur and the line tangent to the upper endplate of S1) from hip joint extension to hip joint flexion, was proposed as the RHF. The validity of this method was assessed via concomitant measurements of changes in the femur-horizontal angle (between the axis of the femur and the horizontal line) and the sacrum-horizontal angle (SHA) (between the line tangent to the upper endplate of S1 and the horizontal line), the difference of which should equal the change in the SFA. Results: The mean change in the SFA was 112.5 ± 7.4°, and was independent of participant age, height, weight, or body mass index. The mean changes in the femur-horizontal and SHAs were 123.0 ± 6.4° and 11.4 ± 3.0°, respectively. This confirmed that the change of SFA between hip joint extension and hip joint flexion was equal to the difference between the changes in the femur-horizontal and SHAs. Conclusions: Using the SFA, to evaluate RHF could prevent compromised measurements due to the movements of pelvis and lumbar spine during hip flexion, and is, therefore, a more accurate and objective method with reasonable reliability and validity.

Hepatitis E virus (HEV) is a serious public health problem. The commonly used tests that are specific for current HEV infection diagnosis include the detection of anti-HEV IgM and HEV RNA. Here, we report an improved enzyme-linked immunosorbent assay (ELISA) method for HEV antigen detection with a linear range equivalent to 6.3 × 10 3 to 9.2 × 10 5 RNA copies per ml. The monoclonal antibody (MAb) 12F12, a high-ability MAb that binds HEV virus, was selected as the capture antibody from a panel of 95 MAbs. The positive period of HEV antigenemia in infected monkeys using this test was, on average, 3 weeks longer than previously reported and covered the majority of the acute phase. The positive detection rates of IgM, RNA, and new antigen from the first serum samples collected from 16 confirmed acute hepatitis E patients were 81% (13/16), 81% (13/16), and 100% (16/16), respectively. In three patients, the initial serum specimens that tested negative for IgM, despite the presence of symptoms of acute hepatitis and elevated alanine aminotransferase (ALT) levels, were positive for HEV antigen and HEV RNA. In contrast, the serum samples of the three RNA-negative patients were antigen positive (and IgM positive), possibly due to the degradation of HEV nucleic acids. Our results suggest that this new antigen detection method has acceptable concordance with RNA detection and could serve as an important tool for diagnosing acute hepatitis E.

Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor cells to mimic the pattern of embryonic vasculogenesis, which was associated with invasion and metastasis. The grape seed proanthocyanidins (GSPs) had attracted much attention as a potential bioactive anti-carcinogenic agent. However, GSPs regulation of VM and its possible mechanisms in a triple-negative breast cancer cells (TNBCs) remain not clear. Therefore, we examined the effect of GSPs on VM information in HCC1937 cell model. In this study, we identified the VM structure via the three-dimensional (3D) matrix in vitro. Cell viability was measured using the CCK8 assay. The effects of GSPs on human triple-negative breast cancer cells (TNBCs) HCC1937 in terms of related proteins of VM information were determined using western blot analysis. In vitro, the tubular networks were found in highly invasive HCC1937 cells but not in the non-invasive MCF-7 cells when plated on matrigel. The number of vascular channels was significantly reduced when cells were exposed in GSPs (100 μg/ml) and GSPs (200 μg/ml) groups (all p

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide. Current methods for evaluating the neutralizing activity of HEV-specific antibodies include immunofluorescence focus assays (IFAs) and real-time PCR, which are insensitive and operationally complicated. Here, we developed a high-throughput neutralization assay by measuring secreted pORF2 levels using an HEV antigen enzyme-linked immunosorbent assay (ELISA) kit based on the highly replicating HEV genotype (gt) 3 strain Kernow. We evaluated the neutralizing activity of HEV-specific antibodies and the sera of vaccinated individuals (n = 15) by traditional IFA and the novel assay simultaneously. A linear regression analysis shows that there is a high degree of correlation between the two assays. Furthermore, the anti-HEV IgG levels exhibited moderate correlation with the neutralizing titers of the sera of vaccinated individuals, indicating that immunization with gt 1 can protect against gt 3 Kernow infection. We then determined specificity of the novel assay and the potential threshold of neutralizing capacity using anti-HEV IgG positive sera (n = 27) and anti-HEV IgG negative sera (n = 23). The neutralizing capacity of anti-HEV IgG positive sera was significantly stronger than that of anti-HEV IgG negative. In addition, ROC curve analysis shows that the potential threshold of neutralizing capacity of sera was 8.07, and the sensitivity and specificity of the novel assay was 88.6% and 100%, respectively. Our results suggest that the neutralization assay using the antigen ELISA kit could be a useful tool for HEV clinical research.

Deregulated microRNAs and their roles in cancer development have attracted much attention. Although miR-133a has been shown to be important in osteogenesis, its roles in osteosarcoma carcinogenesis and progression remain unknown. Hence, we focused on the expression and mechanisms of miR-133a in osteosarcoma development in this study. We found that miR-133a was downregulated in osteosarcoma cell lines and primary human osteosarcoma tissues, and its decrease was significantly correlated with tumor progression and prognosis of the patients. Functional studies revealed that restoration of miR-133a could reduce cell proliferation, promote cell apoptosis, and suppress tumorigenicity in osteosarcoma cell lines. Furthermore, bioinformatic prediction and experimental validation were applied to identify target genes of miR-133a, and the results revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of Bcl-xL and Mcl-1 expression. Taken together, our data elucidate the roles of miR-133a in osteosarcoma pathogenesis and implicate its potential in cancer therapy.

Cisplatin is widely used for the treatment of solid tumours including small cell lung cancers, but its success is often compromised by relapse and resistance to further treatment. Extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt are two major cell survival pathways that are upregulated and activated in lung cancer tissues. Phosphorylated ERK1/2 (p-ERK1/2) and Akt (p-Akt) can be further stimulated by chemotherapeutics in cancer cells. Although individually targeting the ERK1/2 or Akt pathway has been reported to sensitize cancer cells to therapy, the effect of concurrently blocking these two pathways on the sensitivity of lung cancer cells to cisplatin has not been investigated. In the present study, we aimed to determine whether the ERK1/2 and Akt pathways contribute to cisplatin resistance in human small cell lung cancer A549 cells. The results showed that cisplatin activates p-ERK1/2 and p-Akt in A549 cells. Blockade of either of these pathways with chemical inhibitors moderately sensitized A549 cells to cisplatin-induced apoptosis and reduced cell viability. Strikingly, concurrent inhibition of p-ERK1/2 and p-Akt significantly potentiated cisplatin cytotoxicity in vitro and in vivo. The sensitization of A549 cells to cisplatin cytotoxicity induced by p-Akt inhibition was mediated by the upregulation of PUMA, whereas that induced by p-ERK1/2 inhibition occurred by Bcl-2 downregulation. These data indicate that the cooperative effects of p-ERK1/2 and p-Akt on attenuating cisplatin cytotoxicity are mediated by PUMA and Bcl-2 regulation, and concurrently blocking these pathways may be an effective strategy for improving the efficacy of cisplatin as anticancer treatment.

The hepatitis E virus (HEV) is one of the main causes of enterically transmitted hepatitis worldwide. Although the mortality rates associated with HEV are generally low, they can be up to 28% in HEV-infected pregnant women, and the elderly are more susceptible. The reasons for this selective severity are unclear, partially because there is no suitable, easy-to-use model in which to study HEV infection. Non-human primates and standard swine have been identified as being sensitive to infection with HEV and have been used for HEV infection studies. However, studies in these animals have been limited by high housing costs and the difficulty of manipulating these animals. In the current study, we established a model of HEV infection using Bama miniature swine. The model is easy to use and is sensitive to infections with HEV genotypes 3 and 4, which are classified as zoonotic HEVs. In this model, infection of Bama miniature swine with HEV genotypes 3 and 4 caused the typical features. All Bama miniature swine that were infected with HEV genotypes 3 and 4 exhibited significant HEV viremia, shedding, anti-HEV antibody responses and partial liver inflammation. Bama miniature swine may serve as an alternative to standard swine models for the study of zoonotic HEV infection and HEV genotype specificity research.

Hepatitis E virus (HEV) is the aetiological agent of enterically transmitted hepatitis. The traditional methods for evaluating neutralizing antibody titres against HEV are real-time PCR and the immunofluorescence foci assay (IFA), which are poorly repeatable and operationally complicated, factors that limit their applicability to high-throughput assays. In this study, we developed a novel high-throughput neutralizing assay based on biotin-conjugated p239 (HEV recombinant capsid proteins, a.a. 368–606) and staining with allophycocyanin-conjugated streptavidin (streptavidin APC) to amplify the fluorescence signal. A linear regression analysis indicated that there was a high degree of correlation between IFA and the novel assay. Using this method, we quantitatively evaluated the neutralization of sera from HEV-infected and vaccinated macaques. The anti-HEV IgG level had good concordance with the neutralizing titres of macaque sera. However, the neutralization titres of the sera were also influenced by anti-HEV IgM responses. Further analysis also indicated that, although vaccination with HEV vaccine stimulated higher anti-HEV IgG and neutralization titres than infection with HEV in macaques, the proportions of neutralizing antibodies in the infected macaques’ sera were higher than in the vaccinated macaques with the same anti-HEV IgG levels. Thus, the infection more efficiently stimulated neutralizing antibody responses.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for children with high-risk acute lymphoblastic leukemia (ALL). Human leukocyte antigen (HLA)-haploidentical HSCT (haplo-HSCT) or umbilical cord blood transplantation (UCBT) are both important alternative sources of stem cells for those without an HLA-identical sibling donor or unrelated matched donor. We aimed to compare the therapeutic effects of single UCBT and unmanipulated haplo-HSCT in high-risk ALL children (n = 129). Hematopoietic recovery was significantly faster in haplo-HSCT recipients than in UCBT recipients. The 2-year cumulative incidences of relapse in the haplo-HSCT and UCBT groups were 16.1% and 24.1%, respectively (p = 0.169). The 2-year cumulative incidences of non-relapse mortality in the haplo-HSCT and UCBT groups were 12.8% and 18.8%, respectively (p = 0.277). The 2-year probabilities of overall survival in the haplo-HSCT and UCBT groups were 82.0% and 69.6%, respectively (p = 0.071), and the 2-year probability of disease-free survival in the haplo-HSCT group was higher than in the UCBT group (71.0% vs. 57.2%, p = 0.040). However, several variables (such as leukocyte count and cytogenetics at diagnosis) were different between the groups, and a possible center effect should also be considered. In addition, only mild and moderate chronic graft-versus-host disease (GVHD) was associated with significantly improved survival compared to those without chronic GVHD in multivariate analysis. Thus, our results show that both unmanipulated haplo-HSCT and UCBT are valid for high-risk ALL children lacking a HLA matched donor, and both strategies expand the donor pool for children in need.

Delays in the diagnosis of tuberculosis reflect a lack of access to care, and contribute to ongoing tuberculosis transmission in the community. The objective of this study was to evaluate the delay in tuberculosis testing and the associated risk factors in Shanghai, Shandong and Sichuan provinces in China.A prospective cohort study of 765 culture-positive pulmonary tuberculosis patients registered between December 2006 and December 2008. The delay between the onset of symptoms and tuberculosis diagnosis testing and patient information were recorded in a questionnaire and analysed.The median delay was 36 days and was significantly shorter in patients from Shanghai compared with other places (30 vs. 42 days, P0.001). Multivariate analysis revealed that cough in Shanghai patients, lowest income level, being married and presenting expectoration in Shandong and Sichuan patients, were associated with a delay in the diagnosis testing of tuberculosis of30 days. The only factor associated with a delay of90 days was, in Shandong and Sichuan provinces only, female gender. The presence of other pulmonary symptoms like haemoptysis and loss of weight, fever and chills could shorten these delays.Efforts to shorten delays in the diagnosis of tuberculosis must target vulnerable populations. The non-specific symptom of cough is a risk factor associated with longer delays. Training for healthcare workers in areas with a high incidence of tuberculosis, where a delayed diagnosis in coughers may enhance tuberculosis transmission in the community, is of paramount importance.

Patients with relapsed or refractory acute myeloid leukemia (rAML) have a poor prognosis if they do not undergo hematopoietic stem cell transplantation (HSCT). We describe a case herein of acute myeloid leukemia (AML) with monosomy 7 and EVI1(+)(-7/EVI1(+)) in a patient who failed to achieve a complete remission (CR) after two cycles of standard induction chemotherapy. He subsequently received decitabine (DAC) as "bridge therapy" and directly underwent unrelated cord blood transplantation (UCBT) due to the absence of an available sibling donor. Although DAC treatment did not induce CR, it did produce hematologic improvement and control disease progression with acceptable side effects, thus effectively bridging the time of donor search. Following UCBT, the marrow showed complete hematologic and cytogenetic remission. At present, 18 months after the transplantation, the patient's general condition is still good.

Background Acute coronary syndrome (ACS) is one of the most common forms of heart disease. Recent studies have shown that interleukin (IL)-8 plays a key role in the development of atherosclerotic plaques, but the relationship between the common genetic variants of IL-8 and ACS has not been extensively studied. Methods This case-control study in the Chinese Han population included 675 patients with ACS and 636 age- and sex-matched controls. We investigated IL-8 polymorphisms and their association with susceptibility to ACS. The investigation was replicated in the second study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay. Results IL-8 −251 A/T polymorphism was associated with increased susceptibility to ACS ( P = 0.004; odds ratio = 1.30; 95% confidence interval: 1.12–1.53). The second study yielded similar results. An increased IL-8 level was found in the plasma of acute myocardial infarction patients, suggesting that IL-8 −251 A/T may affect the expression of IL-8. Conclusion IL-8 −251 A/T polymorphism is associated with ACS risk in the Chinese Han population and the A allele of IL-8 −251 A/T may be an independent predictive factor for ACS.

This study was aimed to detect the FLT3 gene mutation in patients with de-novo acute myeloid leukemia (AML), and to investigate its prognostic value and clinical significance.Polymerase chain reaction (PCR) was used to detect FLT3 gene mutation, in bone marrow samples of 54 patients with de novo AML.The incidence of FLT3-ITD mutation in 54 de-novo AML patients was 22.22%, 10 out of 12(83.3%) AML patients were identified with normal karyotype, while 16.7% patients were identified as with abnormal karyotype. The peripheral blood white cell count and bone marrow blast cells were significantly higher in the patients with FLT3-ITD mutation than those in patients without FLT3-ITD mutation (P0.05), but there was no statistically significant difference in sex, age, CR rate of the first course induction chemotherapy, survival rate and so on between the two groups. Two cases had FLT3-TKD gene mutation; as compared with FLT3-TKD negative AML patients there was no statistical difference in sex, age, white blood cell count, the percentage of marrow blasts and CR rate of the first course of treatment at the initial diagnosis.FLT3-ITD mutation positive likely occurs in AML patients with normal karyotype, the FLT3-ITD mutation is associated with higher peripheral white cell count and higher percentage of bone marrow blast cells.

Natural-killer/T cell lymphoma (NKTCL) is a malignant proliferation of CD56+/cytoCD3+ lymphocytes and constitutes a heterogeneous group of aggressive lymphoma prevalent in Asian and South American populations. NKTCL represents a distinct clinicopathologic entity of non-Hodgkin’s lymphoma, characterized by male predominance, strong association with Epstein-Barr virus (EBV) infection, prominent tissue necrosis and aggressive clinical course. However, molecular pathogenesis of NKTCL remains largely elusive. Here we identified somatic mutations by whole-exome sequencing in 25 NKTCL patients and extended validation through targeted sequencing in an additional 80 cases. Functional experiments including RNA unwinding test, colony forming assay, cell proliferation assay and gene expression profiling were also performed. Overall, 50.5% of NKTCL patients displayed somatic mutations of RNA helicase family, tumor suppressors (TP53 and MGA), and/or epigenetic modifiers (MLL2, ARID1A, EP300 and ASXL3). Recurrent mutations were most frequently discovered in RNA helicase gene DDX3X (21/105 cases, 20.0%). Mutations of DDX3X were seldom overlapped with those of TP53. Functionally, DDX3X mutants exhibited reduced RNA unwinding activity and enhanced cell proliferation. Similar stimulatory effect on cell proliferation was observed in cells transfected with specific siRNA targeting DDX3X. Gene expression profiling revealed an association of DDX3X mutations with activation of NF-kB and MAPK pathways. The clinical follow-up data showed that DDX3X-mutated patients presented a poor prognosis. Our work suggests the heterogeneity of gene mutational spectrum of NKTCL and provides a potential therapeutic target for relevant cases. Disclosures No relevant conflicts of interest to declare.

Hepatitis E virus (HEV) is a serious public health problem that causes acute hepatitis in humans and is primarily transmitted through fecal and oral routes. The major anti-HEV antibody responses are against conformational epitopes located in a.a. 459–606 of HEV pORF2. All reported neutralization epitopes are present on the dimer domain constructed by this peptide. While looking for a neutralizing monoclonal antibody (MAb)-recognized linear epitope, we found a novel neutralizing linear epitope (L2) located in a.a. 423–437 of pORF2. Moreover, epitope L2 is proved non-immunodominant in the HEV-infection process. Using the hepatitis B virus core protein (HBc) as a carrier to display this novel linear epitope, we show herein that this epitope could induce a neutralizing antibody response against HEV in mice and could protect rhesus monkeys from HEV infection. Collectively, our results showed a novel non-immunodominant linear neutralizing epitope of hepatitis E virus, which provided additional insight of HEV vaccine.

The aim of this study was to investigate the role of F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in diagnosis and prognostic evaluation of secondary hemophagocytic syndrome (HPS). A total of 11 secondary HPS patients examined with 18F-FDG-PET/CT were retrospectively analyzed. The diagnostic value of F-18 FDG PET/CT for malignancy detection was assessed. The values of maximum standardized uptake value (SUV(max)) in spleen (SUVS(p)) and in bone marrow (SUVBM) were measured to analyze their relationship with various laboratorial parameters and clinical outcome of secondary HPS patients. The results showed that 4 out of the 11 patients had malignancies, the sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT for malignancy detection were 100%, 66.7% and 75% respectively, the SUV(max) of spleen and bone marrow showed no significant correlation with laboratorial parameters, a maximum SUVS(p) of 3.10 and a maximum SUVBM of 3.47 were the optimal cutoffs for predicting patients' outcome, the increased uptake of F-18 FDG in the BM and spleen were significantly associated with shorter survival time according to univariate analysis. It is concluded that 18F-FDG PET/CT may especially play an important role in diagnosis and predicting outcome of secondary HPS for the small sample size.

This study was aimed to investigate the effect of high mobility group box1(HMGB1) and/or stromal cell derived factor-1(SDF-1) on the migration of cord blood CD34⁺ cells, and to explore whether HMGB1 promotes cord blood CD34⁺ cell migration via SDF-1/CXCR4 axis. Cord blood mononuclear cells were isolated by Ficoll-Paque density centrifugation, CD34⁺ cells were collected by a positive immunoselection procedure (CD34 MicroBeads) according to the manufacturer's instructions, the purity of the isolated CD34⁺ cells was detected by flow cytometry. In vitro chemotaxis assays were performed using Transwell cell chambers to detect cells migration. 1 × 10⁵ cells/well cord blood CD34⁺ cells were added into the upper chambers. Different concentrations of HMGB1 and/or SDF-1 (0, 10, 25, 50, 100, 200 ng/ml) were used to detect the optimal concentrations of HMGB1 and/or SDF-1 for inducing migration of cord blood CD34⁺ cells. Freshly isolated cord blood CD34⁺ cells express CXCR4 (SDF-1 receptor), and HMGB1 receptor TLR-2,TLR-4 and RAGE. To explore which receptors were required for the synergy of HGMB1 and/or SDF-1 on cells migration, the anti-SDF-1, anti-CXCR4 and anti-RAGE antibodies were used to detect the effect of HGMB1 alone or with SDF-1 on cord blood CD34⁺ cells migration. The results showed that the purity of CD34⁺ cells isolated from cord blood mononuclear cells by magnetic cell sorting was 97.40 ± 1.26%, the 25 ng/ml SDF-1 did not induce migration of cord blood CD34⁺ cells, whereas the optimal migration was observed at 100 ng/ml. HMGB1 alone did not induce migration up to 100 ng/ml. The dose test found that the the best synergistic concentrations for cells migration were 100 ng/ml HMGB1 combined with 50 ng/ml SDF-1. The blocking test showed that both the anti-SDF-1 (4 µg/ml) and anti-CXCR4 (5 µg/ml) antibodies could block cell migration induced by HMGB1 or combined with SDF-1, but the cord blood CD34⁺ cells in the presence of anti-RAGE, anti-TLR-2 and anti-TLR-4 antibodies did not modify the response to SDF-1 in the presence of HMGB1. It is concluded that both HMGB1 and SDF-1 can induce cord blood CD34⁺ cells migration, HMGB1 enhances SDF-1-induced migration exclusively via CXCR4 and in a RAGE and TLR receptors-independent manner, the exact mechanism needs to be further explored.

This study was purposed to comparatively analyze the early T-lymphocyte subsets and T-cell receptor excision cycles (TREC) reconstruction in recipients with hematologic malignancies after myeloablative unrelated cord blood transplantation (UCBT) and sibling donor bone marrow and/or peripheral blood stem cell transplantation (BMT/PBSCT). The peripheral blood T lymphocyte subsets were detected using flow cytometry and TREC were detected using real-time quantitative PCR for 40 patients with hematologic malignancies in the first six months after myeloablative allogenic hematopoietic stem cell transplantation. The results showed that in the first month after transplantation, the absolute counts of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+) cells were lower significantly in the UCBT group than those in the BMT/PBSCT group. And later the absolute counts of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) cells were not different between two groups. The ratio of CD3(+)T subset in the peripheral blood lymphocytes of the UCBT recipients was lower, but the difference was not statistically significant within 2 months after transplantation. The ratio of CD3(+)CD4(+) cells in the patients received the UCBT and BMT/PBSCT decreased obviously since engraftment happened. The CD3(+)CD4(+) cells on the 2 months after transplantation fell to the lowest level, then gradually increased, but did not reach to the normal level until 6 months after transplantation. CD3(+)CD8(+)cells were well reconstituted, rising to normal at the engraftment after transplantation, with a low CD4(+): [KG-*2] CD8(+) ratio over the first 6 months after transplantation. Compared with the BMT/ PBSCT group, the naive T cells (CD3(+)CD4(+)CD45RA(+)CD62L(+)) were more in the first month after transplantation and the terminally differentiated effector memory T cells (CD3(+)CD4(+)CD45RA(+)CD62L(-)) were more at the 3 month after transplantation in the UCBT group, and those were significantly more than the normal control group. TREC were lower and did not recovered until 6 months after transplantation in the recipients of the two groups. It is concluded that compared with sibling donor's BMT/PBSCT, early T cell reconstitution significantly delayed after UCBT, but the terminally differentiated effector memory T cells are higher after transplantation, and thus play a anti-infective or anti-leukemia role.

Migraine sufferers have abnormal cerebral information processing and personality disorders, post-traumatic headache sufferers also have some personality changes. We therefore, studied intensity dependence of auditory evoked potentials, Plutchik-van Praag's depression inventory, Zuckerman's sensation seeking scales and Zuckerman-Kuhlman's personality questionnaire in patients suffering from migraine without aura (n = 26) and chronic post-traumatic headaches (n = 26) as well as in healthy volunteers (n = 30). The migraine group showed significantly increased neuroticism-anxiety than controls, increased intensity dependence of N1-P2, and decreased thrill and adventure score compared with the controls and post-traumatic headaches. The post-traumatic headache had significantly increased depression compared with the controls, and increased disinhibition compared with the controls and migraines. This study demonstrates that the two headache types have different neurophysiological and personality traits. The pronounced intensity dependence of N1-P2 suggests a cortical potentiation response, together with a decreased thrill and adventure seeking, favor a lower serotonergic innervation in migraine. While the elevated disinhibition and depression, as consequences, may be linked with the wide cortical neuronal/axonal degeneration in post-traumatic headache.

For most patients with severely ankylosed hips, traditional surgical approaches do not provide sufficient exposure during THAs. We report our experience with a combined anterior and posterior approach using a lateral incision for total hip arthroplasty (THA) in patients with severe, spontaneous bony hip ankylosis.Between January 2004 and December 2008, patients with severe, spontaneous bony hip ankylosis underwent THA via a combined anterior and posterior approach using a lateral incision.We included 47 patients (76 hips) with a mean age of 53 (range 22-72) years in our study. All surgeries were successful, and no significant postoperative complications occurred. The mean operative duration was 1.5 (range 1.3-1.7) hours, and mean blood loss was 490 (range 450-580) mL. The mean duration of follow-up was 5.5 (range 2-11) years. Harris hip score improved from 53 to 88 points postoperatively, and the outcome was good to excellent in 88.37% of cases. Heterotopic ossification occurred in 6 hips, and infection, which resolved with antibiotics, occurred in 1 patient.This combined anterior and posterior approach to THA using a lateral incision in patients with severe, spontaneous ankylosis provides very good exposure, protects the abduction unit and results in good to excellent postoperative recovery.Pour la plupart des patients atteints d'une grave ankylose de la hanche, les approches chirurgicales classiques n'exposent pas suffisamment l'articulation lors des interventions pour prothèse totale de la hanche (PTH). Nous faisons état de notre expérience d'une approche antéro-postérieure à l'aide d'une incision latérale pour la PTH chez des patients atteints d'une grave ankylose ostéoarticulaire spontanée de la hanche.Entre janvier 2004 et décembre 2008, nous avons effectué des interventions pour PTH par l'approche antéro-postérieure à l'aide d'une incision latérale chez des patients présentant une grave ankylose ostéoarticulaire spontanée de la hanche.Nous avons inclus dans notre étude 47 patients (76 hanches) âgés en moyenne de 53 (entre 22 et 72) ans. Toutes les interventions ont réussi et on n'a eu à déplorer aucune complication postopératoire significative. La durée moyenne de l'intervention a été de 1,5 (entre 1,3 et 1,7) heure et la perte de sang moyenne a été de 490 (entre 450 et 580) mL. La durée moyenne du suivi a été de 5,5 (entre 2 et 11) ans. Le score de Harris pour la hanche s'est amélioré, passant de 53 à 88 points après l'intervention, et les résultats ont été de bons à excellents dans 88,37 % des cas. On a observé une ossification hétérotopique dans 6 hanches, et 1 patient a présenté une infection traitée avec succès par antibiothérapie.Cette approche antéro-postérieure à l'aide d'une incision latérale pour la PTH chez des patients présentant une grave ankylose ostéoarticulaire spontanée offre une excellente visibilité. Elle protège le système d'abduction et permet un rétablissement postopératoire de bon à excellent.

There are different materials used for anterior cruciate ligament (ACL) reconstruction. It has been reported that both autologous grafts and allografts used in ACL reconstruction can cause bone tunnel enlargement. This study aimed to observe the characteristics of bone tunnel changes and possible causative factors following ACL reconstruction using Ligament Advanced Reinforcement System (LARS) artificial ligament.Forty-three patients underwent ACL reconstruction using LARS artificial ligament and were followed up for 3 years. X-ray and CT examinations were performed at 1, 3, 6, 12, 24, and 36 months after surgery, to measure the width of tibial and femoral tunnels. Knee function was evaluated according to the Lysholm scoring system. The anterior and posterior stability of the knee was measured using the KT-1000 arthrometer.According to the Peyrache grading method, grade 1 femoral bone tunnel enlargement was observed in three cases six months after surgery. No grade 2 or grade 3 bone tunnel enlargement was found. The bone tunnel enlargement in the three cases was close to the articular surface with an average tunnel enlargement of (2.5 ± 0.3) mm. Forty cases were evaluated as grade 0. The average tibial and femoral tunnel enlargements at the last follow-up were (0.8 ± 0.3) and (1.1 ± 0.3) mm, respectively. There was no statistically significant difference in bone tunnel width changes at different time points (P0.05). X-ray and CT measurements were consistent.There was no marked bone tunnel enlargement immediately following ACL reconstruction using LARS artificial ligament. Such enlargement may, however, result from varying grafting factors involving the LARS artificial ligament or from different fixation methods.

Nicardipine is a dihydropyridine-type Ca(2+) channel blocker with a powerful antihypertensive activity and a unique cerebrovascular profile. Recent studies have examined nicardipine for the treatment of patients with aneurysmal subarachnoid haemorrhage (SAH), but have shown inconsistent results. In the current study, a meta-analysis was performed to assess the clinical effectiveness of nicardipine in the prevention of cerebral vasospasm in patients who had suffered from aneurysmal SAH. Medline, EMBASE, and PubMed databases were searched for the controlled trials evaluating nicardipine for treating SAH after a ruptured aneurysm, without language restrictions. Moreover, a manual search of the bibliographies of relevant articles was also conducted. Two researchers of the present study independently performed the literature search and the data extraction. The meta-analyses were performed using the software RevMan 4.2.10 (provided by the Cochrane Collaboration, Oxford, UK). Five published manuscripts involving 1,154 patients were included in this meta-analysis. Nicardipine infusion reduced the risk of poor outcome (death, vegetative state, or dependency) and mortality, with an odds ratio (OR) of 0.58 [95 % confidence interval (CI) 0.37-0.90] and 0.45 (95 % CI 0.15-1.29), respectively. This meta-analysis suggests that nicardipine therapy reduces the likelihood of poor outcome and mortality in patients after aneurysmal SAH.

To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) with improved myeloablative conditioning regimen (total body irradiation (TBI)/cytosine arabinoside (Ara-c)/cyclophosphamide (CY) without antithymocyte globulin (ATG)) in adult patients with hematological malignancies.Forty consecutive adult patients with hematological malignancies received improved myeloablative unrelated CBT at a single center from September 2006 to May 2011. Their average age was (23 ± 6) years and the average weight (58 ± 9) kg. Thirty-five (87.5%) patients were high-risk and 15 (37.5%) at the advanced disease status at pre-transplantation. They received 1 (n = 23) or 2 (n = 17) cord blood units. Seventy-five percent of them were transplanted with 1/2-human leukocyte antigen mismatched unit. The conditioning regimen consisted of 12 Gy TBI, granulocyte colony-stimulating factor (G-CSF) plus Ara-c and CY without ATG. All patients received a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD).For the entire group of patients, the average cell doses infused were (4.1 ± 1.1)×10⁷ total nucleated cells/kg and (2.4 ± 1.0)×10⁵ CD34(+) cells/kg. All patients acquired engraftment with an implantation rate of 100%. The average time of absolute neutrophil count (ANC) ≥ 0.5×10⁹/L was (20 ± 5) days and the average time of platelet ≥ 20×10⁹/L was(38 ± 12) days. Acute GVHD occurred in 23 patients (57.5%) and 4 (10.0%) were of grade III-IV. Chronic GVHD occurred in 22.9% (8/35) evaluable patients. Relapse occurred in 12.5% (5/40) patients. During a median follow-up period of 19.8 (range 4.6 - 55.0) months, the transplantation-related mortality was 15.0% (6/40) within 100 days and 35.0% (14/40) within 1 year. The main causes of mortality were pneumonia and severe acute GVHD. Two-year overall survival (OS) or disease-free survival was 58.8% and 58.8%, respectively. Two-year OS for patients with advanced or complete remission disease was 48.6% and 63.8%, respectively.The TBI/Ara-c/CY myeloablative conditioning regimen is well-tolerated and capable of establishing sustained donor cell engraftment and decreasing the risks of transplant-related death in adults with hematologic malignancies. For the high-risk and advanced patients, it may reduce the occurrences of relapse and chronic GVHD.

Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

This study was purposed to investigate the amplification of CD3(-)CD56(+)NK cells in umbilical cord blood and their change of immunophenotype and cytotoxicity after stimulation with IL-2 and IL-15. Mononuclear cells were isolated from umbilical cord blood and cultured in serum-free medium supplemented with IL-2 or (and) IL-15 for 14 d. The subset level of CD3(-)CD56(+)NK cells and expression of CD16, CD62L, NKG2A, NKG2D, NCR44, NCR46, granzyme B and perforin were analyzed by flow cytometry. The cytotoxicity of NK cells to K562 was detected by WST-1 method. The results showed that NK cells stimulated with IL-2, IL-15 and IL-2/IL-15 were amplified by 10.78 ± 2.51, 10.42 ± 3.72, and 10.54 ± 6.24 times respectively after 14 d, there was no statistically significant difference between these three groups. The expression of CD16 decreased obviously in NK cells after amplification; there was significant difference between IL-2 and IL-15 groups. The expression of CD62L was not changed statistically after stimulation with cytokines, the IL-2 down-regulated the expressions of NKG2A and NCR46, while IL-15 showed the opposite effect. IL-2 or IL-15 displayed upregulation effect on the expression of NKG2D, perforin and NCR44, but there was statistically significant difference between effects of these two cytokines. IL-15 up-regulated the expression of granzyme B on NK cells. The cytotoxicity of NK cells stimulated and amplified by cytokines significantly increased, but there was no statistically significant difference between IL-2 and IL-15. It is concluded that IL-2 or IL-15 can effectively amplify umbilical cord blood NK cells under serum-free conditions. Although the immunophenotype associated with NK cells function showed different characteristics between them, however, cytotoxicity of NK cells increased obviously after amplification and there is no statistically significant difference between effect of these two cytokines, their synergistic effect is not obvious. The cytotoxicity of NK cells is the result from combined effect of all active molecules.

Seven major contaminations of the landfill were selected from northeast of China, and the migration and transformation of contaminations environmental medias were studied by using the multimedia multipathway and multireceptor risk assessment (3MRA) model. The results show, the order of the radical concentration of the seven contaminations is Ni2+BenzeneCdPbCr6+AsHg. The radical concentration of benzene, As and Hg in human is similar to that of ecology, respectively. The radical concentration of Cd and Ni2+ in human is higher than that of ecology, while the radical concentration of Cr6+ in ecology is higher than that of human. The risk and hazard quotient of the groundwater in the landfill is 5.06 x 10(-7), 2.3 x 10(-1), respectively.

To investigate the clinical features and treatment strategy for acute respiratory distress syndrome (ARDS) caused by phosgene.Individualized therapy was carried out in 17 cases of severe phosgene poison patients. Blood routine, electrolytes, blood gas analysis, hepatic and renal function tests and cardiac enzymes were examined before and after treatment.Vital signs, fluid, electrolytes and acid-base disturbances were improved after treatment. As compared to that of pre-treatment period, white blood cells [WBC, ×10(9)/L: 12.18 ± 4.76 vs. 21.93 ± 6.21], neutrophil percentage (0.87 ± 0.05 vs. 0.92 ± 0.03), hemoglobin (Hb, g/L: 128.12 ± 25.65 vs. 173.71 ± 23.53), blood platelet count [PLT,×10(9)/L:165.12 ± 31.70 vs. 254.47 ± 70.80], alanine transaminase (ALT, U/L: 70.71 ± 46.70 vs. 212.71 ± 141.34), aspartate aminotransferase (AST, U/L: 52.47 ± 34.68 vs. 82.41 ± 34.60), blood urea nitrogen (BUN, mmol/L: 5.83 ± 4.09 vs. 7.89 ± 5.96), serum creatinine (SCr, μmol/L: 48.13 ± 14.97 vs. 67.25 ± 24.29), lactate dehydrogenase (LDH, U/L: 280.10 ± 81.77 vs. 586.35 ± 186.71), creatine kinase (CK, U/L: 199.12 ± 106.75 vs. 683.00 ± 323.21), MB isoenzyme of creatine kinase (CK-MB, U/L: 26.94 ± 9.13 vs. 45.59 ± 11.21), serum chlorine anion [Cl(-), mmol/L: 95.88 ± 6.06 vs. 102.29 ± 7.28], respiratory rate (RR, beats/min: 20.88 ± 4.30 vs. 30.06 ± 5.78), heart rate (HR, beats/min: 82.76 ± 17.16 vs. 113.35 ± 16.90), blood pH value (7.34 ± 0.44 vs. 7.39 ± 0.03) were all decreased (P0.05 or P0.01). Serum sodium ion [Na(+),mmol/L:140.61 ± 6.69 vs. 134.06 ± 4.80], arterial partial pressure of oxygen [PO(2), mm Hg, 1 mm Hg = 0.133 kPa: 84.41 ± 30.58 vs. 59.88 ± 15.19] and pulse oxygen saturation [SpO(2): 0.91 ± 0.08 vs. 0.78 ± 0.15] were increased (P0.05 or P0.01). Sixteen patients totally recovered, 1 patient died, and the cure rate was 94.12%.Respiratory system could be mainly injured as the result of exposure to phosgene and leading to ARDS. Early initial combination therapies with corticosteroids and respiratory support should be addressed.

To examine prevalence and associated factors of diabetic retinopathy in patients with Type 2 diabetes mellitus in urban communities of Beijing.The community health care center-based study included subjects with diabetes mellitus and an age of 20 years to 80 years, who were recruited from 15 community health centers in urban Beijing. Diabetes mellitus was defined using the World Health Organization criteria. Fundus photographs were graded using the modified Airlie House classification system.Of 2,642 eligible patients, 2,007 (76.0%) subjects (1,199 women) with a mean age of 64.1 ± 9.0 years participated. The overall prevalence of diabetic retinopathy was 24.7 ± 1.0% (95% confidence interval [CI], 22.8-26.6). In binary logistic analysis, presence of diabetic retinopathy was associated with younger age (odds ratio [OR], 0.97; 95% CI, 0.95-0.98), longer duration of diabetes (OR, 1.10; 95% CI, 1.08-1.12), higher concentration of glycosylated hemoglobin HbA1c (OR, 1.23; 95% CI, 1.14-1.33), higher systolic blood pressure (OR, 1.01; 95% CI, 1.01-1.02), lower body mass index (OR, 0.95; 95% CI, 0.92-0.98), and elevated blood urea concentration (OR, 1.01; 95% CI, 1.00-1.01). Microalbuminuria was an additional associated factor (OR, 1.55; 95% CI, 1.16-2.08). Patients with microalbuminuria were 4.7 times more likely to have a severe or proliferating diabetic retinopathy than those without microalbuminuria.In the urban population of Beijing, prevalence of diabetic retinopathy in diabetic patients was 25%. As in whites, increased blood pressure besides elevated plasma glucose concentrations was highly significantly associated with diabetic retinopathy in Chinese. It suggests that in Chinese as also in whites, blood pressure control beside control of plasma glucose levels is important to prevent development or progression of diabetic retinopathy.

This study was aimed to retrospectively analyze and compare the clinical curative efficacy of patients with hematologic malignancies after G-CSF-mobilized sibling HLA-matched (sm) peripheral blood hematopoietic stem cell transplantation (sm-allo-PBHSCT) and sm-allo-PBHSCT combined with bone marrow transplantation (BMT). 100 patients received sm-allo-HSCT in a single center from October 2001 to October to 2010, included 38 patients received sm-allo-PBHSCT and 62 patients received sm-allo-PBHSCT combined with BMT. The myeloablative or reduced intensity conditioning regimens were chosen according to the condition of patients. All patients received standard cyclosporine (CsA) and mycophenolate mofetil (MMF) as prophylaxis for GVHD. The results showed that the rapid hematopoietic reconstitution was observed in all patients. The median time of ANC ≥ 0.5 × 10(9)/L in both groups were 12 days, the median time of platelet count ≥ 20 × 10(9)/L was 15 days in sm-allo-PBHSCT group and 16 days in sm-allo-PBHSCT + BMT group. The incidence of acute GVHD, acute GVHD of III-IV grade and chronic GVHD in sm-allo-PBHSCT and sm-allo-PBHSCT + BMT groups were 37.1% and 34.2%, 7.89% and 8.06%, 36.11% and 41.38% respectively, there were no statistical differences. The relapse rates were similar in two groups (sm-allo-PBHSCT 13.16% vs sm-allo-PBHSCT + BMT 12.9%). The 3-year disease-free survivals in sm-allo-PBHSC and sm-allo-PBHSCT + BMT groups were 57.1 ± 8.7% and 61.3 ± 6.4% respectively (p = 0.852). The 2-year overall survival of high-risk patients was 41.4 ± 12.8% in sm-allo-PBHSCT group, while 60.9 ± 9.6% in sm-allo-PBHSCT + BMT group (p = 0.071). It is concluded that the rhG-CSF mobilized sibling matched allo-PBHSCT + BMT is superior to the rhG-CSF mobilized sibling matched allo-PBHSCT in increasing the overall survival of high-risk hematologic malignancies.

To investigate the peripheral levels and clinical significance of Th17/Treg cell-associated cytokines in patients with acute graft versus host disease (aGVHD) or chronic GVHD (cGVHD), blood samples were collected from 39 hematopoietic stem-cell transplantation patients and 20 healthy donors. The patients included 10 patients with aGVHD, 13 patients with cGVHD and 16 patients without evidence of GVHD. Th17/Treg cell-associated cytokines such as IFNγ, IL-4, IL-6, IL-10, TGF-β(1), IL-17 and IL-23 were detected by ELISA. The results showed that the plasma levels of IFN-γ, IL-4, IL-6, IL-17 and IL-23 significantly increased in patients with aGVHD or cGVHD, compared with the patients without clinical signs of GVHD and the healthy donors (p0.05), while IL-10 and TGF-β(1) were obviously lower than that of them (p0.05). After aGVHD and cGVHD patients were treated effectively, the plasma levels of IL-6, IL-17 and IL-23 were significantly decreased, and IL-10, TGF-β(1) were significantly increased, while the levels of IFN-γ and IL-4 did not markedly change. The TGF-β(1) level were negatively correlated with IL-6 (r = -0.36, p0.05), IL-17 (r = -0.51, p0.05) and IL-23 (r = -0.44, p0.05) respectively, while there were positive correlations between IL-6 and IL-17 (r = 0.62, p0.05), IL-6 and IL-23 (r = 0.71, p0.05), IL-17 and IL-23 (r = 0.93, p0.05). It is concluded that Th17/Treg cell-associated cytokines may play an important role in the development of a/cGVHD, which helps to find novel targets for developing new strategies of GVHD treatment.

This study was aimed to investigate the influence of TLR2 and TLR4 agonists on the migration and adhesion activity of umbilical cord blood (UCB) CD34(+) cells and to explore the underlying mechanism. The expression of TLR2 and TLR4 on UCB CD34(+) cells was detected with flow cytometry. The effect of TLR2 agonist (PAM3CSK4) and TLR2 agonist (LPS) on the migration and adhesion ability of UCB CD34(+) cells was evaluated with chemotaxis and adhesion assays. The results indicated that expression levels of TLR2 and TLR4 were (14.2 ± 3.8)%, (19.6 ± 4.1)% respectively. Compared with the control group, the migration activity of UCB CD34(+) cells toward SDF-1 decreased significantly in LPS group (p0.01). The adhesion activity was not altered significantly in LPS group. However, both the migration activity towards SDF-1 and the adhesion activity of UCB CD34(+) cells were not changed significantly in PAM3CSK4 group. Further study found that LPS did not affect the expression level of CXCR4 on CD34(+) cells, but could inhibit the spontaneous migration ability of CD34(+) cells. It is concluded that TLR4 activation can decrease the chemotaxis function of CD34(+) cells towards SDF-1, which may associate with the decreased spontaneous migration ability of CD34(+) cells.