Meta-analysis of the prevalence of Giardia duodenalis in sheep and goats in China.

Giardia duodenum (G. duodenalis) can cause giardiasis and infect a variety of hosts. So far, there have been no detailed data regarding the positive rate of G. duodenalis in sheep and goats in China. Here, a systematic literature review was carried out to investigate the epidemiology of G. duodenalis in sheep and goats in China. To perform the meta-analysis, the databases CNKI, VIP, WanFang, PubMed, Web of science and ScienceDirect were employed for screening studies related to the prevalence of G. duodenalis in sheep and goats in China. The total prevalence of G. duodenalis in sheep and goats was estimated to be 7.00% (95% CI: 4.00-10.00). In the age subgroup, the prevalence of G. duodenalis in sheep and goats of >12 months (11.29%; 95% CI: 8.08-14.97) was higher than that in sheep and goats of ≤12 months (7.57%; 95% CI: 3.95-12.24). An analysis based on seasons showed that the prevalence of G. duodenalis in sheep and goats was higher in summer (11.90%; 95% CI: 0.50-35.05) than that in other seasons. The prevalence of G. duodenalis in sheep and goats after 2016 was 8.57% (95% CI: 5.34-11.79), which was higher than others. The highest prevalence of G. duodenalis in sheep and goats was 13.06% (95% CI: 6.26-19.86) recorded in Southwestern China. The prevalence of Giardia infection in sheep (7.28%; 95% CI: 2.30-14.73) was higher than that in goats (5.43%; 95% CI: 2.73-8.98). The NOAA's National Center for Environmental Information (https://gis.ncdc.noaa.gov/maps/ncei/cdo/monthly) was used to extract relevant geoclimatic data (latitude, longitude, elevation, temperature, precipitation, humidity, and climate). By analyzing the data of each subgroup, it was shown that region, genetype, and climate were potential risk factors for giardiasis prevalence in sheep and goats. Based on the analysis of common factors and geographical factors, it is recommended to strengthen effective management measures (e.g. ventilation and disinfection in warm and humid areas) and formulate relevant policies according to local conditions. Breeders should strengthen the detection of G. duodenalis in sheep and goats, customize corresponding control measures according to the diet and living habits of sheep and goats, and strengthen the protection of sheep and lamb calves, so as to reduce the incidence rate and reduce the economic loss of China's animal husbandry.

PD-L1 upregulation promotes drug-induced pulmonary fibrosis by inhibiting vimentin degradation.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and limited therapeutic options. The immune checkpoint PD1/PD-L1 axis is related to the pathogenesis of pulmonary fibrosis, and upregulated expression levels of PD-L1 have been demonstrated in IPF patients. However, the mechanism of PD-L1 in pulmonary fibrosis is not fully understood. Here, we demonstrated upregulated expression of PD-L1 in fibrotic lung tissues and sera of IPF patients. Bleomycin (BLM) treatment induced PD-L1 upregulation, EMT (Epithelial-Mesenchymal Transition) and fibrosis-like morphology changes in human pulmonary alveolar epithelial cells (HPAEpiCs). Silencing PD-L1 attenuated BLM-induced EMT and fibrosis-like morphology changes in HPAEpiCs. In addition, we identified that PD-L1 directly binds to vimentin and inhibits vimentin ubiquitination, thereby increasing vimentin levels in HPAEpiCs. Silencing of vimentin inhibited BLM- and PD-L1-induced fibrosis in HPAEpiCs. The correlation between PD-L1 and EMT or vimentin expression was further confirmed in clinical samples and animal models. Finally, we used BLM- and paraquat-induced pulmonary fibrosis animal models to confirm the anti-pulmonary fibrosis effects of PD-L1 silencing. Taken together, our findings suggest that upregulated PD-L1 stimulates EMT of alveolar epithelial cells by increasing vimentin levels by inhibiting vimentin ubiquitination, thereby contributing to pulmonary fibrosis.

PD-L1P146R is prognostic and a negative predictor of response to immunotherapy in gastric cancer.

Cancer cells evade immune detection via programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) interactions that inactivate T cells. PD-1/PD-L1 blockade has become an important therapy in the anti-cancer armamentarium. However, some patients do not benefit from PD-1/PD-L1 blockade despite expressing PD-L1. Here, we screened 101 gastric cancer (GC) patients at diagnosis and 141 healthy control subjects and reported one such subpopulation of GC patients with rs17718883 polymorphism in PD-L1, resulting in a nonsense P146R mutation. We detected rs17718883 in 44% of healthy control subjects, and rs17718883 was associated with a low susceptibility to GC and better prognosis in GC patients. Structural analysis suggests that the mutation weakens the PD-1:PD-L1 interaction. This was supported by co-culture experiments of T cells, with GC cells showing that the P146R substitution results in interferon (IFN)-γ secretion by T cells and enables T cells to suppress GC cell growth. Similar results with animal gastric tumor models were obtained in vivo. PD-1 monoclonal antibody treatment did not enhance the inhibitory effect of T cells on GC cells expressing PD-L1P146Rin vitro or in vivo. This study suggests that rs17718883 is common and may be used as a biomarker for exclusion from PD-1/PD-L1 blockade therapy.

Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter.

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION: The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.

Human leukocyte antigen disparities reduce relapse after hematopoietic stem cell transplantation in children with juvenile myelomonocytic leukemia: A single-center retrospective study from China.

BACKGROUND: HSCT is the only proven curative therapy for JMML. Matching donor and recipient HLA alleles is considered optimal to reduce the risk of GVHD after HSCT but is not always possible. Only a limited number of studies have compared the influence of HLA disparities on HSCT outcomes for patients with JMML. METHODS: We conducted a retrospective study among 47 children with JMML who received related or unrelated unmanipulated HSCT (March 2010-October 2018). Among our participants, 27 (57.4%) donor-recipient pairs had 0-1 HLA disparities (Group 1: HLA-matched or ≤1 allele/antigen mismatch donor) and 20 (42.6%) had ≥2 HLA disparities (Group 2: 2-3 mismatched/haploidentical donors). RESULTS: The median follow-up period was 26.0 months (range: 1-105 months), and the 5-year probabilities of DFS and RI for the whole cohort were 54.6 ± 7.7% and 34.8 ± 15.0%, respectively. Compared to Group 1, Group 2 patients had a significantly lower RI (5.3 ± 10.5% vs 55.5 ± 20.9%, P Ë‚ .001), though similar rates of grade II-IV acute GVHD (60.0 ± 22.4% vs 33.3 ± 18.2%, P = .08), grade III-IV acute GVHD (25.0 ± 19.5% vs 7.4 ± 10.1%, P = .08), chronic GVHD (30.0 ± 20.9% vs 34.9 ± 18.8%, P = .85), NRM (20.0 ± 18.0% vs 3.9 ± 7.7%, P = .07), and DFS (74.4 ± 9.9% vs 41.3 ± 10.0%, P = .08). CONCLUSIONS: Disease relapse remains the major cause of treatment failure in JMML patients, especially in patients receiving HLA-matched and limited HLA-mismatched HSCT. Our findings suggest that donor-recipient HLA disparities may improve the outcome of HSCT in children with JMML.

Comparison of the adhesion and endocytosis of calcium oxalate dihydrate to HK-2 cells before and after repair by Astragalus polysaccharide.

This work investigated the effects of repairing injured renal proximal tubular epithelial (HK-2) cells by using three Astragalus polysaccharides (APS) with different molecular weights and the adhesion and endocytosis of HK-2 cells to the calcium oxalate dihydrate (COD) nanocrystals before and after repair to develop new products that can protect against kidney stones. HK-2 cells cultured in vitro were injured with 2.6 mmol/L oxalic acid to establish a damaged cell model. Three kinds of APS (APS0, APS1, and APS2 with molecular weights of 11.03, 4.72, and 2.60 kDa, respectively) were used to repair the damaged cells. The changes in the adhesion and endocytosis of 100 nm COD crystals to cells before and after the repair were detected. After the repair of HK-2 cells by the APS, the speed of wound healing of the damaged HK-2 cells increased, and the amount of phosphatidylserine (PS) ectropion decreased. In addition, the proportion of cells with adhered COD crystals decreased, whereas the proportion of cells with internalized crystals increased. As a result of the repair activity, APS can inhibit the adhesion and promote the endocytosis of COD nanocrystals to damaged cells. APS1, which had a moderate molecular weight, displayed the strongest abilities to repair the cells, inhibit adhesion, and promote endocytosis. Thus, APS, particularly APS1, may serve as potential green drugs for preventing kidney stones.

Long non-coding RNAs: New biomarkers for prognosis and diagnosis of colon cancer.

Dysregulation of long non-coding RNAs has been found in many human cancers, including colorectal cancer that is still the third most prevalent cancer worldwide and related to poor prognosis; along with this, robust testimony has identified that long non-coding RNAs can take charge of tumor suppressor genes or oncogenes. This review summarizes nowadays research achievements on the character of long non-coding RNAs in the prognosis and diagnosis of colorectal cancer. On the basis of the results acquired in the last decade, some long non-coding RNAs are rising as biomarkers of colorectal cancer for prognosis, diagnosis, even prediction of therapeutic result, and have crucial effects in the regulation of colorectal cancer cell functions such as proliferation, invasion, apoptosis, metastasis, and drug resistant ability. Also, long non-coding RNAs, circulating in body fluids, could act as novel, affordable, lightly accessible, non-invasive detection tools for the personal health management of patients with colorectal cancer. Especially, circulating long non-coding RNA profiles may be demonstrating preferable prognostic and diagnostic capability and better accuracy than respective long non-coding RNAs in colorectal cancer.

The long-term outcome of reduced-intensity allogeneic stem cell transplantation from a matched related or unrelated donor, or haploidentical family donor in patients with leukemia: a retrospective analysis of data from the China RIC Cooperative Group.

This study compared 6-year follow-up data from patients undergoing reduced-intensity conditioning (RIC) transplantation with an HLA-matched related donor (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID) for leukemia. Four hundred and twenty-seven patients from the China RIC Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47 in the MUD groups. The conditioning regimen involved fludarabine combined with anti-lymphocyte globulin and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis was administered using cyclosporin A (CsA) and mycophenolate mofetil (MMF). Four hundred and nineteen patients achieved stable donor chimerism. The incidence of stage II-IV acute GVHD in the HID group was 44.3 %, significantly higher than that in the MRD (23.6 %) and MUD (19.1 %) groups. The 1-year transplantation-related mortality (TRM) rates were 44.3, 17.6, and 21.3, respectively. Event-free survival (EFS) at 6 years in the HID group was 36.7 %, significantly lower than that of the MRD and MUD groups (59.1 and 66.0 %, P < 0.001 and P = 0.001, respectively). For advanced leukemia, the relapse rate of the HID group was 18.5 %, lower than that of the MRD group (37.5 %, P = 0.05), but the EFS at 6 years was 31.7 and 30.4 % (P > 0.05), respectively. RIC transplantation with MRD and MUD had similar outcome in leukemia which is better than that with HID. RIC transplantation with HID had lower relapsed with higher TRM and GVHD rate, particularly in advanced leukemias. RIC transplantation with MRD and MUD had similar outcomes in leukemia and they were better than those with HID. RIC transplantation with HID had a lower relapse rate but higher TRM and GVHD rates, particularly in cases of advanced leukemia.

Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study.

We conducted a prospective, multicentre study to confirm the feasibility of haplo-identical transplantation in treatment of severe aplastic anaemia (SAA) as salvage therapy, by analysing the outcomes of 101 patients who received haplo-identical transplantation between June 2012 and October 2015. All cases surviving for more than 28 d achieved donor myeloid engraftment. The median time for myeloid engraftment was 12 (range, 9-25) days and 15 (range, 7-101) days for platelets, with a cumulative platelet engraftment incidence of 94·1 ± 0·1%. With a median follow-up of 18·3 (3·0-43·6) months, recipients from haplo-identical transplantation had more cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD, 33·7% vs. 4·2%, P < 0·001), more chronic GVHD (22·4% vs. 6·6%, P = 0·014) at 1 year, but similar grade III-IV aGVHD (7·9% vs. 2·1%, P = 0·157), 3-year estimated overall survival (OS, 89·0% vs. 91·0%, P = 0·555) and failure-free survival (FFS, 86·8% vs. 80·3%, P = 0·659) when compared with 48 patients who received contemporaneous transplantation from matched related donors. Multivariate analysis showed no significant difference in engraftment and survival between the two cohorts. Both OS and FFS for the entire population correlated significantly with grades III-IV aGVHD. In conclusion, haplo-identical transplantation is a feasible choice for SAA with favourable outcomes.

Damage of vascular endothelial barrier induced by explosive blast and its clinical significance.

In recent years, injuries induced by explosive blast have got more and more attention owing to weapon development and frequent terrorist activities. Tear, bleeding and edema of tissues and organs are the main manifestations of blast shock wave damage. Vascular endothelial barrier is the main defense of tissues and organs' integrity. This article aims to discuss possible mechanisms of endothelial barrier damage induced by explosive blast and main manifestations of blood brain barrier, bloodeair barrier, and intestinal vascular barrier impairments. In addition, the main regulatory factors of vascular permeability are also summarized so as to provide theoretical basis for prevention and cure of vascular endothelial barrier damage resulting from explosive blast.

[Meta-analysis on effect of compound Danshen injection in treating neonatal hypoxic-ischemic encephalopathy].

To systematically evaluate the clinical efficacy and safety of compound Danshen injection in treating hypoxic-ischemic encephalopathy (HIE) of newborns. Computer retrievals were made in PubMed, Embase, Cochrane Library, CBM, CNKI, VIP and China info (before May 2014) and relevant literature references, and manual retrievals were made for journals and conference papers, in order to collect randomized or semi-randomized controlled trials concerning compound Danshen injection in the treatment of neonatal HIE. The quality of included references was evaluated according to literatures recommended by Cochrane Handbook. RevMan 5. 3 software was applied in the statistical treatment. Finally, a total of 13 randomized controlled trials were included, covering 1,211 patients (including 639 patients in the compound Danshen injection-treated group and 572 patients in the control group). Meta-analysis results showed that the routine treatment combined with compound Danshen injection can improve the treatment efficiency of neonatal HIE [RR = 1.28; 95% CI (1.21-1.36)], reduce the mortality rate [RR = 0.42; 95% CI (0.23-0.75)] and the incidence of long-term neurological sequelae [RR = 0.48; 95% CI (0.35-0.65)], with statistical differences. No fatal side effect was observed in all of included trials. So far, limited evidences in this study proved that the application of compound Danshen injection in the treatment of neonatal HIE can enhance the clinical efficiency. However, because of the low quality of the included trials, more well-designed and large-scale multi-center randomized controlled trials shall be made in the future.

Characteristics of acute myeloid leukemia with myelodysplasia-related changes: A retrospective analysis in a cohort of Chinese patients.

We retrospectively analyzed 449 patients with AML under the WHO classification of AML 2008 and probed implications of this classification in diagnosis and treatment of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) among them. The clinical presentations, biological features, treatments, and prognosis of patients diagnosed with AML-MRC were analyzed and compared with those of AML not otherwise specified (AML-NOS). In all patients, 115 (25.6%) were diagnosed as AML-MRC including 64 males and 51 females with median onset age of 48 years (range from 17 to 78). Their complete remission (CR) rate was 60.9% and relapse rate was 57.1%. The observed median overall survival (OS) and disease-free survival (DFS) were 10 and 5 months, respectively, which was significantly shorter than those of AML-NOS patients (P < 0.05). The prognosis of AML-MRC patients with myelodysplastic syndrome (MDS)-related cytogenetics sole was similar to those with history of MDS or myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Patients with MDS-related cytogenetic abnormalities and/or history of MDS or MDS/MPN predisposed significantly shortened CR, OS, and DFS than AML-MRC patients with only multilineage dysplasia (MLD) and AML-NOS patients (P < 0.05). Multivariate analysis showed that age, cytogenetics, and history of MDS or MDS/MPN were independent prognostic factors. Patient diagnosed as AML-MRC presented distinctive clinical and biological features. Presence of MLD does not change the prognosis.

Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial.

BACKGROUND: Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukaemia. However, their efficacy has not been tested in a multicentre randomised controlled trial in a large population. We assessed the efficacy and safety of homoharringtonine-based induction treatment for management of newly diagnosed acute myeloid leukaemia. METHODS: This open-label, randomised, controlled, phase 3 study was done in 17 institutions in China between September, 2007, and July, 2011. Untreated patients aged 14-59 years with acute myeloid leukaemia were randomly assigned (by a computer-generated allocation schedule without stratification) to receive one of three induction regimens in a 1:1:1 ratio: homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and aclarubicin 20 mg/day on days 1-7 (HAA); homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and daunorubicin 40 mg/m(2) per day on days 1-3 (HAD); or daunorubicin 40-45 mg/m(2) per day on days 1-3 and cytarabine 100 mg/m(2) per day on days 1-7 (DA). Patients in complete remission were offered two cycles of intermediate-dose cytarabine (2 g/m(2) every 12 h on days 1-3). The primary endpoints were the proportion of patients who achieved complete remission after two cycles of induction treatment and event-free survival in the intention-to-treat population. The trial is registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-06000054. FINDINGS: We enrolled 620 patients, of whom 609 were included in the intention-to-treat analysis. 150 of 206 patients (73%) in the HAA group achieved complete remission versus 125 of 205 (61%) in the DA group (p=0.0108); 3-year event-free survival was 35.4% (95% CI 28.6-42.2) versus 23.1% (95% CI 17.4-29.3; p=0.0023). 133 of 198 patients (67%) in the HAD group had complete remission (vs DA, p=0·20) and 3-year event-free survival was 32.7% (95% CI 26.1-39.5; vs DA, p=0.08). Adverse events were much the same in all groups, except that more patients in the HAA (12 of 206 [5.8%]) and HAD (13 of 198 [6.6%]) groups died within 30 days than in the DA group (two of 205 [1%]; p=0.0067 vs HAA; p=0.0030 vs HAD). INTERPRETATION: A regimen of homoharringtonine, cytarabine, and aclarubicin is a treatment option for young, newly diagnosed patients with acute myeloid leukaemia. FUNDING: Chinese National High Tech Programme, Key Special Research Foundation of the Ministry of Science and Technology of China, National Nature Science Foundation of China, National Clinical Key Specialty Construction Project.

Safinamide alleviates hyperalgesia via inhibiting hyperexcitability of DRG neurons in a mouse model of Parkinson's disease.

Pain is a widespread non-motor symptom that presents significant treatment challenges in patients with Parkinson's disease (PD). Safinamide, a new drug recently introduced for PD treatment, has demonstrated analgesic effects on pain in PD patients, though the underlying mechanisms remain unclear. To investigate the analgesic and anti-PD effect of safinamide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was used, and rasagiline as positive control on motor symptoms. Notably, only safinamide alleviated hyperalgesia in MPTP mice. Whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons revealed hyperexcitability in MPTP mice, which safinamide counteracted in a concentration-dependent manner. The voltage clamp further demonstrated that sodium current in DRG neurons of MPTP mice was enhanced and safinamide reduced sodium current density. RT-qPCR identified upregulated Nav1.7 and Nav1.8 transcripts (Scn9a and Scn10a) in DRG neurons of MPTP mice. Our results suggest that safinamide could relieve hyperalgesia by inhibiting DRG neuron hyperexcitability in MPTP mice.

Diagnostic performance of a multiplexed gastrointestinal PCR panel for identifying diarrheal pathogens in children undergoing hematopoietic stem cell transplant.

BACKGROUND: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection. METHODS: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays. RESULTS: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%). CONCLUSIONS: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.

Allogeneic peripheral blood stem cell transplantation is a promising and safe choice for the treatment of refractory/relapsed acute myelogenous leukemia, even with a higher leukemia burden.

The prognosis of patients with refractory/relapsed acute myelogenous leukemia (rAML) is poor. Recent studies have shown that more transplant centers are choosing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for recipients, even with a higher leukemia burden. The purpose of the present study is to evaluate the outcome of rAML patients undergoing allo-PBSCT and to determine whether the disease status can predict the post-transplantation survival. The outcome of 58 patients (median age, 34 years; range, 14 to 52) with rAML who underwent allo-PBSCT in our institution from January 2000 until September 2011 was retrospectively studied. Thirty-three patients had complete remission (CR) before PBSCT, whereas 25 patients had no remission. Donors were matched related (31 patients) and unrelated (27 patients). Reduced-intensity conditioning was used for 18 patients with rAML, and myeloablative conditioning was used for others. Sixty-six consecutive non-rAML patients (median age, 33 years; range, 15 to 51) who received an allo-PBSCT at the same period were used as a control. Full donor-type engraftment was achieved in all patients. After a median follow-up of 61 months, the 5-year overall survival of rAML patients was 54.21% ± 7.06%, which was lower than non-rAML patients (71.82% ± 6.4%, P = .0386). However, the 5-year event-free survival for rAML and non-rAML patients had no statistical significance (53.54% ± 6.87% versus 62.07% ± 6.78%, P = .2626). The 5-year overall survival between rAML patients who had CR and no remission before PBSCT was 56.06% ± 9.2% and 51.85% ± 10.83%, respectively (P = .6408). These data demonstrate that allo-PBSCT is a promising and safe choice for the treatment of rAML, and the results were partially due to the rapid tapering of immunosuppressants in the early stage after PBSCT and prophylactic donor lymphocyte infusion. Meanwhile, the patients who did not achieve CR before PBSCT could also benefit from allo-PBSCT.

Super-Eddington accreting massive black holes as long-lived cosmological standards.

Super-Eddington accreting massive black holes (SEAMBHs) reach saturated luminosities above a certain accretion rate due to photon trapping and advection in slim accretion disks. We show that these SEAMBHs could provide a new tool for estimating cosmological distances if they are properly identified by hard x-ray observations, in particular by the slope of their 2-10 keV continuum. To verify this idea we obtained black hole mass estimates and x-ray data for a sample of 60 narrow line Seyfert 1 galaxies that we consider to be the most promising SEAMBH candidates. We demonstrate that the distances derived by the new method for the objects in the sample get closer to the standard luminosity distances as the hard x-ray continuum gets steeper. The results allow us to analyze the requirements for using the method in future samples of active black holes and to demonstrate that the expected uncertainty, given large enough samples, can make them into a useful, new cosmological ruler.

Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: a multicenter, randomized, crossover phase 3 study.

The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 µg/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 µg/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.

Synthesis and biopharmaceutical studies of JLTN as potential dasatinib prodrug.

Dasatinib was identified as a potent orally administered Src/Abl kinase inhibitor with excellent antiproliferative activity against Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. The low bioavailability of Dasatinib may be due to both incomplete oral absorption and first-pass metabolism. A prodrug, JLTN, was synthesized to minimize the first-pass effect of Dasatinib and improve the oral bioavailability following oral administration via targeting intestinal peptide transporter and enhancing chemical stability. Biological evaluation data indicated that there was a 150%-fold increase in oral bioavailability of this prodrug compared to the parent drug Dasatinib in monkeys.

[Association of polymorphisms of exon 2 of GOLA-DQA2 gene with blood immune traits in goats].

The polymorphisms of exon 2 of GOLA-DQA2 gene were analyzed by PCR-RFLP technique in Laiwu black goats, Lubo goats, and Boer goats; and the effects of genotypes of GOLA-DQA2 gene on blood immune traits were estimated. The results showed that four genotypes were detected in the three goats. Polymorphic sites were detected at base positions 77, 79, 80, and 169 in exon 2 of GOLA-DQA2 gene. The effects of breed were major effect. In Lubo goats, red blood count (RBC) with genotype AB was significantly higher than that with genotype BB (P<0.05), and white blood count (WBC) with genotype AB was significantly higher than that with genotype BC (P<0.05). Hematocrit (HCT) in Lubo goats with genotype AB was significantly higher than that with genotypes BB and BC (P<0.05). WBC-large cell ratio (W-LCR) in Lubo goats with genotype BC was significantly higher than that with genotype BB (P<0.05). In Laiwu black goats and Boer goats, there was certain degree of association between genotypes and blood immune traits, but it was not significant. Genotype AB and BC was an important factor affecting RBC, WBC, W-LCR, and so on. It was concluded from these results that GOLA-DQA2 was the gene affecting the blood immune traits, which provides a basis for disease resistance breeding of goats.