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Abstract Background Permanent left bundle branch area pacing (LBBAP) has been established as an effective means to correct left bundle branch block. Right bundle branch block (RBBB), emerge as a distinct form of cardiac conduction abnormality, can be seen in the context of LBBAP procedure. However, the correction potential of LBBAP in patients with RBBB remains largely unexplored. Objective The objective of this study was to evaluate the efficacy and safety of permanent LBBAP in patients with RBBB. Methods Ninety-two consecutive patients who underwent successful permanent LBBAP were recruited from May. 2019 to Dec. 2022 in Fuwai Central China Cardiovascular Hospital. Among them, 20 patients with RBBB were included in our analysis. These patients were followed up at 1, 3, 6 and 12 months post-LBBAP. The QRS duration (QRSd) on the V1 lead of the 12-lead elctrocardiogram was measured and compared before and after the LBBAP procedure. Additionally, mitral regurgitation, tricuspid regurgitation and cardiac function were assessed using transthoracic echocardiography, specifically focusing on left ventricular ejection fraction (LVEF) and mitral regurgitation severity. The acute pitfills and delayed complications associated with the LBBAP procedure were recorded to evaluate its safety. SPSS 23.0 was used to perform statistical analysis with Student’s t test or one way ANOVA or nonparametric tests (paired Wilcoxon test). A p value less than 0.05 was defined as significant. Results The demographic breakdown of the RBBB cohort revealed a mean age of 66.35 ± 11.55 years, 60% being male. Comorbidities were prevalent, including severe atrioventricular block (AVB) in 75%, sick sinus syndrome (SSS) in 20%, heart failure in 25%, atrial fibrillation in 30%, coronary heart diseases in 45%, hypertension in 35%, and diabetes mellitus in 15%. Regarding the LBBAP procedure, the average operation time was 106.53 ± 2.72 min, with 45% of patients (9 individuals) requiring temporary cardiac pacing during the surgery. Notably, the LBBAP procedure significantly narrow the QRS duration in RBBB patients, from 132.60 ± 31.49ms to 119.55 ± 18.58 ms (P = 0.046). Additionally, at the 12-month follow-up, we observed a marked improvement in LVEF, which increased significantly from 55.15 ± 10.84% to 58.5 ± 10.55% (P = 0.018). Furthermore, mitral regurgitation severity improved, with a median reduction from 4.46 (0.9, 7.3) to 2.29 (0, 3.49) cm2 (P = 0.033). Importantly, no cases of ventricular septum perforation or pericardial effusion were reported during the LBBAP procedure or during the follow-up period. Conclusion LBBAP provides an immediate reduction in QRS duration for patients suffering from RBBB, accompanied by improvements in mitral regurgitation and cardiac function as evident in the 12-month follow-up period.

Abstract Background For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT). Methods The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981). Results Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-β and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-β (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-β tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031). Conclusions For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.

Abstract Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing. Downregulation of filamin A is identified to induce softness via ZAP70-mediated YAP Y357 phosphorylation and activation. Despite the requirements of YAP in both cell types for softness induction, CTLs are more resistant to YAP inhibitors than malignant T cells, potentially due to the higher expression of the drug-resistant transporter, MDR1, in CTLs. As a result, moderate inhibition of YAP stiffens malignant T cells but spares CTLs, thus allowing CTLs to cytolyze malignant cells without autolysis. Our findings thus hint a mechanical force-based immunotherapeutic strategy against T cell leukemia.

Introduction Virtual objective structured clinical examination (OSCE) has been shown to influence the performance of nursing students. However, its specific effects, particularly students’ competence, stress, anxiety, confidence, satisfaction with virtual reality OSCE and examiners’ satisfaction, remain unclear.Method and analysis This study aims to assess the effects of virtual reality OSCE on nursing students’ education. The study follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol guidelines. A literature search is performed on electronic databases, namely, PubMed, Web of Science, CINAHL, EBSCO, EMBASE and the Cochrane Library. The inclusion criteria adhere to the PICOS principle, encompassing nursing students, including those studying in school and those engaged in hospital internship. This review includes studies on the use of virtual reality OSCE as an assessment tool, compared with traditional clinical examinations, such as in-person OSCE. The outcome assessments encompass (1) competence, (2) stress, (3) anxiety, (4) confidence, (5) student satisfaction with virtual reality OSCE and (6) examiners’ satisfaction. These studies are designed as randomised controlled trials (RCTs) or quasi-experimental research. The search time is from the inception of each database to 30 June 2023, without language restriction. Studies for inclusion are screened by two reviewers for data extraction dependently. Any dispute is resolved through discussion. Unresolved disputes are decided by consulting a third author. For the risk of bias (ROB) assessment, the Cochrane ROB tool for RCTs and the risk of bias in non-randomised studies of intervention tool are used. Moreover, RevMan V.5.3 is used for meta-analysis.Ethics and dissemination This study protocol does not include any clinical research and thus does not require ethical approval. Research findings are published in a peer-reviewed journal.PROSPERO registration number CRD42023437685.

Abstract Background The prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) are well known indicators for adverse outcomes in various diseases, but there is no evidence on their association with the risk of left atrial thrombus (LAT) in patients with valvular atrial fibrillation (VAF). Methods A comparative cross-sectional analytical study was conducted on 433 VAF patients. Demographics, clinical characteristics and echocardiographic data were collected and analyzed. Patients were grouped by the presence of LAT detected by transesophageal echocardiography. Results LAT were identified in 142 patients (32.79%). The restricted cubic splines showed an L-shaped relationship between PNI and LAT. The dose-response curve flattened out near the horizontal line with OR = 1 at the level of 49.63, indicating the risk of LAT did not decrease if PNI was greater than 49.63. GNRI was negative with the risk of LAT and tended to be protective when greater than 106.78. The best cut-off values of PNI and GNRI calculated by receiver operating characteristics curve to predict LAT were 46.4 (area under these curve [AUC]: 0.600, 95% confidence interval [CI]:0.541–0.658, P = 0.001) and 105.7 (AUC: 0.629, 95% CI:0.574–0.684, P

Abstract Background Inflammation has been implicated in the progressive exacerbation of valvular atrial fibrillation (VAF) and thrombogenesis. This study aimed to analyze the association of systemic inflammation as measured by six indices with left atrial thrombus (LAT) in patients with VAF. Methods This comparative cross-sectional analytical study included 434 patients with VAF. Logistic regression analysis was used to assess the predictive value of LAT using six inflammation indices: neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio (MLR), white blood cell-to-mean platelet volume ratio, neutrophil-to-mean platelet volume ratio, systemic immune inflammation index, and systemic inflammation response index. Receiver operating characteristic curves were plotted, and the area under these curves (AUC) were calculated to evaluate the discriminative ability of the indices. Results Transesophageal echocardiography revealed LAT in 143 (32.9%) patients. All six indices reflected a positive correlation with C-reactive protein levels. Multivariate logistic analysis revealed that these indices were independent predictors of LAT, and MLR appeared to perform best (odds ratio 12.006 [95% confidence interval (CI) 3.404–42.347]; P

Background:. Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients. Methods:. This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events. Results:. At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated. Conclusions:. Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high. Registration:. ClinicalTrials.gov, NCT04214951.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as one of the life-saving treatments for severe aplastic anemia (SAA), is widely used because of its great donor availability. Over decades, granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol (the so-called Beijing Protocol) has achieved favorable engraftment and survival outcomes. In this study, we modified the conventional Beijing Protocol: the full-dose Cyclophosphamide (Cy) (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and Low dose post-transplant Cy (PTCy) (14.5 mg/kg on days +3 and +4), hoping to reduce the incidence of severe acute graft-versus-host disease (aGVHD) and to guarantee successful and stable engraftment. Here we retrospectively reported and analyzed the data of first 17 patients with SAA who had received haplo-HSCT using this novel regimen between August 2020 and August 2022. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. Four (23.5%) patients developed grade II bladder toxicity, two (11.8%) patients developed grade II cardiotoxicity. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11–20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade III-IV aGVHD. The cumulative incidence of grade II and grade I aGVHD at 100 days was 23.5% (95% CI, 6.8%-49.9%) and 47.1% (95% CI, 23.0%-72.2%). Three patients (17.6%) developed chronic GVHD of skin, mouth, and eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival of 100%, which was defined as survival without treatment failures, such as death, graft failure, or relapse rate. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 17.6% (95% CI, 3.8%-43.4%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. In conclusion, the encouraging results of prolonged survival outcomes and reduced incidence of GVHD suggest promising effect of this novel regimen in haplo-HSCT for patients with SAA. Larger-sample prospective clinical trials are needed to confirm the effectiveness of this regimen.

As endocrine hormones, glucocorticoids (GCs) play a pivotal role in numerous physiological processes, including mammary growth and lactation, circulatory metabolism, and responses to external stimuli. In the dairy industry, milk production from cows or goats is important for newborns and economic benefits. However, the milk yields from ruminant animals are always affected by the extent of mammary development, mammary disease, stress, or changes in metabolism. Thus, it is necessary to clarify how GCs changes in ruminants affect ruminant mammary gland function and mammary disease. This review summarizes the findings identifying that GCs modulate mammary gland development before lactation, but the stress-induced excessive release of GCs leads to milk production loss. In addition, the manner of GCs release may change under different concentrations of metabolites or during mastitis or inflammatory challenge. Nevertheless, exogenous GCs administration to animals may alleviate the clinical symptoms of mastitis. This review demonstrates that GCs offer a fascinating contribution to both physiologic and pathogenic conditions of the mammary gland in ruminant animals. Characterizing and understanding these changes or functions of endogenous and exogenous GCs in animals will be crucial for developing more endocrine regulators and therapies for improving milk production in ruminants.

ObjectiveDiabetic kidney disease (DKD) is the most common chronic kidney disease (CKD) and has the highest prevalence of end-stage kidney disease (ESKD) globally, owing mostly to the rise in Type 2 diabetes mellitus (T2DM) correlated with obesity. Current research suggested that the immune response and inflammation may play a role in the pathophysiology of T2DM. The systemic immune-inflammation index (SII) is a novel and integrated inflammatory biomarker that has not yet been linked to DKD. We aimed to identify the potential relationship between SII and DKD.MethodsIn the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018, the current cross-sectional study was conducted among adults with T2DM. SII was calculated as the platelet count × neutrophil count/lymphocyte count. DKD was diagnosed with impaired glomerular filtration rate (< 60 mL/min/1.73 m2 assessed by using the Chronic Kidney Disease Epidemiology Collaboration algorithm), albuminuria (urine albumin to creatinine ratio ≥ 30 mg/g), or both in T2DM patients. To investigate the independent association between SII and DKD, weighted univariate and multivariable logistic regression analyses and subgroup analyses were performed.ResultsThe study involved 3937 patients in total, of whom 1510 (38.4%) had DKD for the diagnosis. After adjustment for covariates, multivariable logistic regression revealed that a high SII level was associated with increased likelihood of DKD (OR = 1.42, 95% CI: 1.10-1.83, P = 0.01). Subgroup analyses and interaction tests revealed that age, gender, estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), body mass index (BMI), hypertension, hyperlipidemia, anti-inflammation therapy (yes or no), metformin use (yes or no), and insulin use (yes or no) had no significant dependence on this positive relationship (all p for interaction >0.05).ConclusionsOur results indicate that the higher SII level is associated with DKD in T2DM patients. The SII could be a cost-effective and straightforward approach to detecting DKD. This needs to be verified in further prospective investigations.

Understanding human-induced changes in biodiversity and the environment can provide important references for managing and conservating freshwater fish. To date, most studies on the influence of urbanization on fish assemblage diversity have focused on large rivers, estuaries, and urban ponds; the process and mechanism of urbanization driving diversity changes in fish assemblages in headwater streams are unclear. We assessed the effects of urbanization on the taxonomic and functional alpha and beta diversity of fish assemblages in the headwater streams of the Xin’an River in China. Our results showed that compared with natural segments, urban segments had higher species richness and lower functional richness, which resulted from the gain of native invasive species and the loss of endemic species; fish assemblages also became taxonomically differentiated but functionally homogenized. In addition, ΔFD (difference value in functional beta diversity between urban and natural segments) was significantly positively correlated with ΔTD (difference value in taxonomic beta diversity between urban and natural segments), whereas only ΔFD was significantly negatively related to the urbanization indicators (e.g. urban land use and ammonia nitrogen concentration). Thus, a combination of taxonomic and functional diversity indices better reveals how fish biodiversity responds to urbanization. Our study provides evidence of urbanization-induced changes in fish assemblages as well as early warning signs for urban-disturbed ecosystems, both of which will benefit fish conservation in headwater streams.

Low-head dams are ubiquitous human disturbances that degrade aquatic ecosystem function worldwide. The localized effects of low-head dams have been relatively well documented; however, most previous studies have ignored the concealed process caused by native-invasive species. Based on fish assemblage data from the first-order streams of four basins in the Wannan Mountains, we used a quantitative approach to assess the effects of low-head dams on fish assemblages by distinguishing between native and native-invasive species using occurrence- and abundance-based data, respectively. Low-head dams significantly decreased native fish alpha diversity while favoring native-invasive fish. The opposite pattern between the two fish types partly masked changes in the whole fish assemblage. Meanwhile, the establishment of widespread native-invasive species and the loss of native species driven by low-head dams influenced the interaction network structure. The degree to which local fish assemblages were altered by low-head dams, i.e., beta diversity (β-diversity) was significantly higher for abundance-based approaches than for occurrence-based ones, suggesting that the latter underestimated the effects of low-head dams. Furthermore, the species contribution to β-diversity of native species was significantly higher than that of native-invasive species in both impoundments and free-flowing segments for abundance-based data. In communities or regions where native fish species are predominant, our results suggest that understanding which species contribute to β-diversity will offer new insights into the development of effective conservation strategies by taking the identities of native and native-invasive species into account.

Introduction: Patients with myocardial infarction (MI) and cardiogenic shock (CS) have poor outcomes in terms of morbidity and mortality. Many devices act as a ‘bridge’ in case of cardiogenic shock, by providing circulatory support and buy time so that the patient either recovers or receives a transplant or a long-term device. Materials and methods: This is a retrospective observational study where all patients (n = 286) getting admitted for MI and CS were included. The different variables are compared across the three groups [extracorporeal membrane oxygenation (ECMO), Intra-aortic balloon pump (IABP) and IABP + ECMO]. The fourth group (Impella) had only 6 patients and no statistical analysis has been done for the same, to avoid skewness of results. Results: There are a total of 286 patients in the study out of which ECMO was used in 99 patients, IABP in 138 patients, both IABP and ECMO in 43 patients, and Impella in 6 patients. The patients differed in terms of diagnosis category, pre-existing hypertension, pre-existing diabetes, pre-existing hyperlipidemia, pre-existing heart failure, and other co-morbidities. The groups also differed in terms of the cardiac findings like heart rate, left ventricular end-diastolic diameter (LVED), and left ventricular ejection fraction (LVEF). Stents were implanted more commonly among the IABP (22.5%) and IABP + ECMO group (25.6%) as compared to the ECMO group (6.1%), and the difference was statistically significant (p Value = 0.0012). The median time for device usage in ECMO group was 147 h, as compared to 130 h among IABP group and 144 h among IABP + ECMO group, and the difference was statistically significant between the ECMO and IABP group (p Value = 0.047). The median time for breathing machine assisted ventilation was also highest in the ECMO group (262 h), as compared to IABP (86 h) and IABP + ECMO group (177 h). Patients in the ECMO group had the higher heart rate than patients in IABP group (median heart rate: 95 vs 86 beats per minute). Left ventricular ejection fraction was highest in the IABP group (41% in IABP group Vs 24.5% in ECMO group & 35% in IABP + ECMO group). Conclusion: Though the three groups (IABP, ECMO and ECMO + IABP) were heterogenous, there was a clear advantage in terms of outcomes in the group in which more than one device was used. In conclusion we can say that all three devices have their own advantages and disadvantages, and they have a distinct hemodynamic footprint and thus should be used after detailed assessment of the patient.

Substantial damage to the bone marrow can be caused by exposure to radiation, which can then develop into severe thrombocytopenia. In this study, we investigated the in vivo impact of adipose-derived mesenchymal stem cells (ADSCs) on megakaryopoiesis and platelet recovery in irradiated mice. Radiation markedly reduced peripheral blood counts. Recovery of both platelets and WBCs was better in the ADSC-treated group compared with the saline group and the fibroblast group 21 days after irradiation. A significant increase in the total CFU and MK-CFU after irradiation was observed in the ADSC group compared with the saline group and the fibroblast group. Further, the proportion of CD41 + cells in the ADSC group was significantly higher than that in the saline group and the fibroblast group. ADSC treatment significantly improved the cellularity and decreased the apoptotic cells in the bone marrow while normal fibroblasts did not. Administration of ADSCs upregulated protein expression of phosphorylated Akt and Bcl-xL, whereas the expression of Bax, a protein related to apoptosis, was significantly lower in the ADSC group. In conclusion, this study suggests that ADSCs were capable of promoting platelet recovery, improving megakaryopoiesis, and inhibiting apoptosis of bone marrow cells in irradiated mice. The antiapoptotic effect of ADSCs is likely to be mediated via the PI3K/Akt pathway. These findings may provide a scientific basis for using ADSCs as a new therapy after irradiation.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as one of the life-saving treatments for severe aplastic anemia (SAA), is widely used because of its great donor availability. Over decades, granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol (the so-called Beijing Protocol) has achieved favorable engraftment and survival outcomes. In this study, we modified the conventional Beijing Protocol: the full-dose Cyclophosphamide (Cy) (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and Low dose post-transplant Cy (PTCy) (14.5 mg/kg on days +3 and +4), hoping to reduce the incidence of severe acute graft-versus-host disease (aGVHD) and to guarantee successful and stable engraftment. Here we retrospectively reported and analyzed the data of first 17 patients with SAA who had received haplo-HSCT using this novel regimen between August 2020 and August 2022. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. Four (23.5%) patients developed grade II bladder toxicity, two (11.8%) patients developed grade II cardiotoxicity. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11–20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade III-IV aGVHD. The cumulative incidence of grade II and grade I aGVHD at 100 days was 23.5% (95% CI, 6.8%-49.9%) and 47.1% (95% CI, 23.0%-72.2%). Three patients (17.6%) developed chronic GVHD of skin, mouth, and eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival of 100%, which was defined as survival without treatment failures, such as death, graft failure, or relapse rate. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 17.6% (95% CI, 3.8%-43.4%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. In conclusion, the encouraging results of prolonged survival outcomes and reduced incidence of GVHD suggest promising effect of this novel regimen in haplo-HSCT for patients with SAA. Larger-sample prospective clinical trials are needed to confirm the effectiveness of this regimen. [ABSTRACT FROM AUTHOR]

The physical fitness of college students in northern China, was systermetic evaluated with classified data by supervised SOM, then differences of classified data were validated with ANOVA. The relative importance of all physique indicators in each classified data were evaluated by PCA. BMI was considered as the supervised parameter in SOM analysis due to the reasonable and prevalent parameter reflecting health of physical health. The results were as follows: (1) The supervised SOM provided the intuitive and visual characteristics of classification for physical fitness data as well as the emphasis on BMI; (2) The differences of the classifications coupled with emphasized BMI were validated by ANOVA, and the relative importance indicators were pointed by PCA for each classification. Physique indicator showed heterogeneity in different classifications. Height and Pulup were relative important for male students, but Weight for female students; (3) the methods presented here were universally applicable, and the better performance could be promoted with much more data inputs. The results and the relevant methods of the study are valuable for deepening our understanding of BMI effects on physical fitness and can be used to develop a practical strategy for effective physical activities. [ABSTRACT FROM AUTHOR]

In this paper, Gd2O3 (amSiO2@CaTiO3:Pr nanoparticles with a novel core/shell structure featured by mesoporous, magnetic and long persistent luminescent properties have been synthesized via a facile template method. The as-prepared nanoparticles show ordered mesoporous characteristics, monodisperse spherical morphology and narrow size distribution, so they are expected to be suitable as a drug carrier. These nanoparticles exhibit bright red phosphorescence at 614 nm after UV irradiation and the persistent luminescence can persist for more than one hour. Moreover, they possess a prominent longitudinal relaxivity (r1 value of 6.43 mM-1s-1, which suggests that these nanoparticles can be used as MR imaging agents. The combination of long persistent luminescent and magnetic properties reveals the high imaging sensitivity, which suggests that these nanoparticles can be used for imaging in vivo with a high signal to noise ratio. Drug release results indicate that the nanoparticles hold excellent drug sustained properties. The cumulative released amount of drugs can also be easily monitored by the change of luminescence intensity. After modification with polyethylene glycol, the resulting nanoparticles demonstrate good biocompatibility and low toxicity. Furthermore, we can realize in vivo imaging for over 20 min using these nanoparticles. These results indicate the promising use of these nanoparticles as multifunctional traceable drug carriers in vivo. [ABSTRACT FROM AUTHOR]

We compared total body irradiation (TBI, 700 cGy)/cyclophosphamide (Cy, 3.6 g/m²)/simustine (250 mg/m²) plus antithymocyte globulin (ATG) (TBI/Cy plus ATG) with cytarabine (8 g/m²)/i.v. busulfan (Bu, 9.6 mg/kg)/Cy (3.6 g/m²)/simustine (250 mg/m²) plus ATG (modified Bu/Cy plus ATG) as preparative therapy in T cell-replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute leukemia. From August 2009 to August 2013, 38 consecutive patients using TBI/Cy plus ATG regimen for T cell-replete haplo-HSCT (TBI group) at our center were eligible, which contained 28 high-risk and 10 standard-risk patients. A nested case-control study was designed. Seventy-seven patients using modified Bu/Cy plus ATG regimen (Bu group) were randomly selected in a 1 to 3:1 ratio matching for age, disease and status, year of HSCT (±2 years), and length of follow-up. Only 1 graft failure occurred in the TBI group. The incidence and time of neutrophil and platelet engraftment were comparable between the 2 groups. Severe grades III/IV graft-versus-host disease was observed in 13.4% of Bu group and only 2.6% of TBI group (P = .083). More toxicity of the liver (37.7% versus 10.5%; P = .002) and more hemorrhagic cystitis occurred in the Bu group (49.3% versus 23.7%, P = .008). Diarrhea was more common in the TBI group (44.7% versus 22.1%; P = .031). No significant differences were found in the 2-year incidences of relapse (26.5% for TBI group versus 32.3% for Bu group, P = .742), 1-year transplant-related mortality (12.6% versus 16.2%, P = .862), 2-year overall survival (60.2% versus 57.0%, P = .937), and 2-year incidence of disease-free survival (57.9% versus 56.6%, P = .845) between the 2 groups. We conclude that the TBI/Cy plus ATG regimen seems to be feasible in T cell-replete haplo-HSCT, which promotes stable engraftment and a lower incidence of liver toxicity and hemorrhagic cystitis. However, longer follow-up is necessary to determine the late relapse rate and late toxicity. [ABSTRACT FROM AUTHOR]

Background: Liver cancer is one of the most frequent cancers in the world. Targeted therapy of cancer with specific inhibitors is developing and has shown promising antitumor efficacy. CCI-779 (temsirolimus), a specific inhibitor of mTOR (mammalian target of rapamycin), can block the mTOR signaling pathway. Here, we systematically examined the expression of mTOR and its downstream targets in liver cancer cells and normal liver cells, then investigated inhibitory effects of CCI-779 on mTOR signaling pathway and its role in regulating liver cancer cell growth. Methods: The expression of mTOR and its downstream targets in Bel-7402 liver cancer cells and HL-7702 normal liver cells were examined by western blot. The mTOR specific inhibitor (CCI-779) was used to treat Bel-7402 cells to identify its effects on Bel-7402 cell growth and activity of mTOR signaling pathway in vitro. Cell viability tests were performed after the treatment of CCI-779. Western blot was applied to assess the changes of mTOR pathway and flow cytometry was used to analyze cell cycle of Bel-7402 cells after the treatment of CCI-779. Results: mTOR, p70S6K, S6, and 4EBP1 were overexpressed in Bel-7402 cells compared with HL-7702 cells. Bel-7402 cells were sensitive to CCI-779. The survival rate of the cells treated with CCI-779 over 0.312 μM was significantly different compared with that of control (P < 0.05). CCI-779 inhibited the phosphorylation of mTOR (Ser2448), p70S6K (Thr389), S6 (Ser240/244), and 4EBP1 (Thr37/46) in different grades and the expressions of p70S6K, S6, and 4EBP1. As a result, CCI-779 induced a dose-dependent decrease in cell proliferation, G1/S arrest and damage of cell shape. Conclusions: Taken together, these data showed that CCI-779 can inhibit mTOR signaling and proliferation in Bel- 7402 liver cancer cells in vitro. It offers a therapeutic intervention through inhibition of mTOR as a potential strategy for liver cancer. [ABSTRACT FROM AUTHOR]