Computation-Driven Rational Design of Self-Assembled Short Peptides for Catalytic Hydrogen Production.

Self-assembling peptides represent a captivating area of study in nanotechnology and biomaterials. This interest is largely driven by their unique properties and the vast application potential across various fields such as catalytic functions. However, design complexities, including high-dimensional sequence space and structural diversity, pose significant challenges in the study of such systems. In this work, we explored the possibility of self-assembled peptides to catalyze the hydrolysis of hydrosilane for hydrogen production using ab initio calculations and carried out wet-lab experiments to confirm the feasibility of these catalytic reactions under ambient conditions. Further, we delved into the nuanced interplay between sequence, structural conformation, and catalytic activity by combining modeling with experimental techniques such as transmission electron microscopy and nuclear magnetic resonance and proposed a dual mode of the microstructure of the catalytic center. Our results reveal that although research in this area is still at an early stage, the development of self-assembled peptide catalysts for hydrogen production has the potential to provide a more sustainable and efficient alternative to conventional hydrogen production methods. In addition, this work also demonstrates that a computation-driven rational design supplemented by experimental validation is an effective protocol for conducting research on functional self-assembled peptides.

The association between neighborhood-level social fragmentation and distressing psychotic-like experiences in early adolescence: the moderating role of close friends.

BACKGROUND: Early exposure to neighborhood social fragmentation has been shown to be associated with schizophrenia. The impact of social fragmentation and friendships on distressing psychotic-like experiences (PLE) remains unknown. We investigate the relationships between neighborhood social fragmentation, number of friends, and distressing PLE among early adolescents. METHODS: Data were collected from the Adolescent Brain Cognitive Development Study. Generalized linear mixed models tested associations between social fragmentation and distressing PLE, as well as the moderating role of the number of total and close friends. RESULTS: Participants included 11 133 adolescents aged 9 to 10, with 52.3% being males. Greater neighborhood social fragmentation was associated with higher levels of distressing PLE (adjusted ß = 0.05; 95% CI: 0.01-0.09). The number of close but not total friends significantly interacted with social fragmentation to predict distressing PLE (adjusted ß = -0.02; 95% CI: -0.04 to <-0.01). Among those with fewer close friends, the association between neighborhood social fragmentation and distressing PLE was significant (adjusted ß = 0.07; 95% CI: 0.03-0.11). However, among those with more close friends, the association was non-significant (adjusted ß = 0.03; 95% CI: -0.01 to 0.07). CONCLUSIONS: Greater neighborhood social fragmentation is associated with higher levels of distressing PLE, particularly among those with fewer close friends. Further research is needed to disentangle aspects of the interaction between neighborhood characteristics and the quality of social interactions that may contribute to psychosis, which would have implications for developing effective interventions at the individual and community levels.

Research on Mask-Wearing Detection Algorithm Based on Improved YOLOv5.

COVID-19 is highly contagious, and proper wearing of a mask can hinder the spread of the virus. However, complex factors in natural scenes, including occlusion, dense, and small-scale targets, frequently lead to target misdetection and missed detection. To address these issues, this paper proposes a YOLOv5-based mask-wearing detection algorithm, YOLOv5-CBD. Firstly, the Coordinate Attention mechanism is introduced into the feature fusion process to stress critical features and decrease the impact of redundant features after feature fusion. Then, the original feature pyramid network module in the feature fusion module was replaced with a weighted bidirectional feature pyramid network to achieve efficient bidirectional cross-scale connectivity and weighted feature fusion. Finally, we combined Distance Intersection over Union with Non-Maximum Suppression to improve the missed detection of overlapping targets. Experiments show that the average detection accuracy of the YOLOv5-CBD model is 96.7%-an improvement of 2.1% compared to the baseline model (YOLOv5).

Accessory ossicles of the foot-an imaging conundrum.

Various anatomical variations can be found in the foot and ankle, including sesamoid bones and accessory ossicles. These are usually incidental findings and remain asymptomatic; however, they may cause complications resulting in painful syndromes or degenerative changes secondary to overuse or trauma. They can also lead to fractures or simulate fractures. These complications are challenging to diagnose on radiographs. Advanced imaging with US, CT, MRI, or Tc-99m bone scan is useful for definitive diagnosis. This study aims to illustrate how imaging modalities can be used to diagnose complications of common sesamoids and accessory ossicles of the ankle and foot (hallux sesamoids, os trigonum, accessory navicular, os supranaviculare, os peroneum, os intermetatarseum, and os calcaneus secundarius) and demonstrate the imaging differences between fractures and their mimics.

Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 141 risk genes for Alzheimer's disease dementia.

BACKGROUND: Transcriptome-wide association study (TWAS) is an influential tool for identifying genes associated with complex diseases whose genetic effects are likely mediated through transcriptome. TWAS utilizes reference genetic and transcriptomic data to estimate effect sizes of genetic variants on gene expression (i.e., effect sizes of a broad sense of expression quantitative trait loci, eQTL). These estimated effect sizes are employed as variant weights in gene-based association tests, facilitating the mapping of risk genes with genome-wide association study (GWAS) data. However, most existing TWAS of Alzheimer's disease (AD) dementia are limited to studying only cis-eQTL proximal to the test gene. To overcome this limitation, we applied the Bayesian Genome-wide TWAS (BGW-TWAS) method to leveraging both cis- and trans- eQTL of brain and blood tissues, in order to enhance mapping risk genes for AD dementia. METHODS: We first applied BGW-TWAS to the Genotype-Tissue Expression (GTEx) V8 dataset to estimate cis- and trans- eQTL effect sizes of the prefrontal cortex, cortex, and whole blood tissues. Estimated eQTL effect sizes were integrated with the summary data of the most recent GWAS of AD dementia to obtain BGW-TWAS (i.e., gene-based association test) p-values of AD dementia per gene per tissue type. Then we used the aggregated Cauchy association test to combine TWAS p-values across three tissues to obtain omnibus TWAS p-values per gene. RESULTS: We identified 85 significant genes in prefrontal cortex, 82 in cortex, and 76 in whole blood that were significantly associated with AD dementia. By combining BGW-TWAS p-values across these three tissues, we obtained 141 significant risk genes including 34 genes primarily due to trans-eQTL and 35 mapped risk genes in GWAS Catalog. With these 141 significant risk genes, we detected functional clusters comprised of both known mapped GWAS risk genes of AD in GWAS Catalog and our identified TWAS risk genes by protein-protein interaction network analysis, as well as several enriched phenotypes related to AD. CONCLUSION: We applied BGW-TWAS and aggregated Cauchy test methods to integrate both cis- and trans- eQTL data of brain and blood tissues with GWAS summary data, identifying 141 TWAS risk genes of AD dementia. These identified risk genes provide novel insights into the underlying biological mechanisms of AD dementia and potential gene targets for therapeutics development.

Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 93 risk genes for Alzheimer's disease dementia.

Background: Transcriptome-wide association study (TWAS) is an influential tool for identifying novel genes associated with complex diseases, where their genetic effects may be mediated through transcriptome. TWAS utilizes reference genetic and transcriptomic data to estimate genetic effect sizes on expression quantitative traits of target genes (i.e., effect sizes of a broad sense of expression quantitative trait loci, eQTL). These estimated effect sizes are then employed as variant weights in burden gene-based association test statistics, facilitating the mapping of risk genes for complex diseases with genome-wide association study (GWAS) data. However, most existing TWAS of Alzheimer's disease (AD) dementia have primarily focused on cis -eQTL, disregarding potential trans -eQTL. To overcome this limitation, we applied the Bayesian Genome-wide TWAS (BGW-TWAS) method which incorporated both cis - and trans -eQTL of brain and blood tissues to enhance mapping risk genes for AD dementia. Methods: We first applied BGW-TWAS to the Genotype-Tissue Expression (GTEx) V8 dataset to estimate cis - and trans -eQTL effect sizes of the prefrontal cortex, cortex, and whole blood tissues. Subsequently, estimated eQTL effect sizes were integrated with the summary data of the most recent GWAS of AD dementia to obtain BGW-TWAS (i.e., gene-based association test) p-values of AD dementia per tissue type. Finally, we used the aggregated Cauchy association test to combine TWAS p-values across three tissues to obtain omnibus TWAS p-values per gene. Results: We identified 37 genes in prefrontal cortex, 55 in cortex, and 51 in whole blood that were significantly associated with AD dementia. By combining BGW-TWAS p-values across these three tissues, we obtained 93 significant risk genes including 29 genes primarily due to trans -eQTL and 50 novel genes. Utilizing protein-protein interaction network and phenotype enrichment analyses with these 93 significant risk genes, we detected 5 functional clusters comprised of both known and novel AD risk genes and 7 enriched phenotypes. Conclusion: We applied BGW-TWAS and aggregated Cauchy test methods to integrate both cis - and trans -eQTL data of brain and blood tissues with GWAS summary data to identify risk genes of AD dementia. The risk genes we identified provide novel insights into the underlying biological pathways implicated in AD dementia.

A convenient and stable graph-based pressure estimation methodology for water distribution networks: Development and field validation.

Accurate estimation of unknown nodal pressures (nodal heads) is necessary for efficient operation and management of water distribution networks (WDNs), but existing methods such as hydraulic simulation and data interpolation can hardly reconcile estimation accuracy with model construction and maintenance costs. Recent developments in graph signal processing (GSP) techniques provide us with new tools to utilize information in WDN hydraulics and available measurements. In a pilot study, a graph-based head reconstruction (GHR) method was proposed, which used GSP to reconstruct the spatially slow-varying parts of nodal heads from a limited number of field measurements to approximate original heads. GHR has illustrated the effectiveness and ease of implementation of GSP-based methods. However, due to the ill-conditioning reconstruction process and inherent uncertainties, GHR may show unstable results with large errors if pressure meters are not installed at specific optimized locations, which limits its applicability. To solve this problem and discover a stable and convenient method that can support a wider range of applications, a graph-based head reconstruction method with improved stability (GHR-S) is proposed. GHR-S utilizes a rough estimation of unknown pressures as pseudo measurements, which provide additional constraints and avoid the occurrence of unreasonable results during the reconstruction process. A middle-sized network with synthetic data illustrates the stability, convenience, and accuracy of GHR-S with arbitrary meter locations and uncalibrated model parameters. GHR-S is also applied to a large real-life network with field measurements, and successfully estimates the unknown pressures of 83,000 nodes with only 58 measurements, showing its effectiveness in practical engineering.

Association between intracerebral hemorrhage and cholesterol levels, and molecular mechanism underlying low cholesterol inhibiting autophagy in cerebral arterial smooth muscle cells leading to cell necrosis.

BACKGROUND: An association between cholesterol and intracerebral hemorrhage (ICH) has been reported, but the mechanism is unclear. METHODS: In this cross-sectional study, participants aged 50-75 years were selected using multistage stratified cluster sampling. All samples completed a questionnaire (age, gender, medication, etc.) and were examined (blood lipid, height, blood pressure, etc.) for risk factors. Multivariable logistic regression was used to analyze the association between cholesterol levels and ICH risk, after adjusting for age, smoking, hypertension, and other factors. We cultured rat cerebral artery smooth muscle cells at different cholesterol concentrations. The autophagy pathway was identified by transcriptome sequencing. The results were then validated using real-time polymerase chain reaction and western blot. RESULTS: We included 39,595 patients, among whom 286 had ICH. The study showed that a low level of low-density lipoprotein cholesterol (LDL-C) was a risk factor of ICH (odds ratio 2.912, 95% confidence interval 1.460-5.806; P = 0.002). Cell experiments showed that lower cholesterol levels could significantly induce rat cerebral artery smooth muscle cell necrosis. In low-cholesterol groups, expression of the autophagy marker LC3 protein was significantly decreased and p62 protein was significantly increased. In western blot and comparison with the control group, the low cholesterol PI3K/Akt/mTOR signaling pathway was significantly activated in the autophagy pathway, resulting in its inhibition, which in turn led to smooth muscle cell death. CONCLUSION: Low cholesterol levels may inhibit autophagy through PI3K/Akt/mTOR signaling and induce arterial smooth muscle cell necrosis, thereby increasing the risk of ICH.

Prevalence of birth defects and risk-factor analysis from a population-based survey in Inner Mongolia, China.

BACKGROUND: Birth Defects are a series of diseases that seriously affect children's health. Birth defects are generally caused by several interrelated factors. The aims of the article is to estimate the prevalence rate and types of birth defects in Inner Mongolia, China, to compare socio-demographic characteristics among the children with birth defects and to analyze the association between risk factors and birth defects. METHODS: Data used in this study were obtained through baseline survey of Inner Mongolia Birth Defects Program, a population-based survey conducted from 2005 to 2008. The survey used cluster sampling method in all 12 administrative districts of Inner Mongolia. Sampling size is calculated according to local population size at a certain percentage. All live births, stillbirths and abortions born from October 2005 to September 2008, whose families lived in Inner Mongolia at least one year, were included. The cases of birth defects were diagnosed by the clinical doctors according to their experiences with further laboratory tests if needed. The inclusion criteria of the cases that had already dead were decided according to death records available at local cites. We calculated prevalence rate and 95% confidence intervals of different groups. Outcome variable was the occurrence of birth defects and associations between risk factors and birth defects were analyzed by using Poisson regression analysis. RESULTS: 976 children with birth defects were diagnosed. The prevalence rate of birth defects was 156.1 per 10000 births (95%CI: 146.3-165.8). The prevalence rate of neural tube defect (20.1 per 10000 births) including anencephaly(6.9 per 10000), spina bifida (10.6 per 10000), and encephalocele (2.7 per 10000) was the highest, followed by congenital heart disease (17.1 per 10000). The relative risk (RR) for maternal age less than 25 was 2.22 (95%CI: 2.05, 2.41). The RR of the ethnic Mongols was lower than Han Chinese (RR: 0.84; 95%CI: 0.80-0.89). The RR of the third and second pregnancy was significantly higher than the first pregnancy while a slight difference between the second and the first pregnancy was also found. Alcohol drinking of mothers, familial inheritance and living area were also found to be related to the occurrence of the birth defects. CONCLUSIONS: Relatively higher birth defect rates were found in Inner Mongolia. This study found that maternal age less than 25, alcohol drinking, familiar inheritance, lower education level of mothers, times of pregnancies and living in rural areas may increase the risk of birth defects. Ethnic Mongols were less likely to have birth defects than Han Chinese.

Management of an Extensive Intraparotid and Auricular Arteriovenous Malformation.

BACKGROUND Extracranial arteriovenous malformations (AVMs) of the parotid gland and auricle are rarely encountered. Management of these AVMs depends on the Schobinger stage and their flow characteristics. We present a rare case of an AVM involving the parotid and auricle concurrently. The clinical and imaging features of these high-flow vascular malformations and their treatment options are discussed and we provide a review of the literature. CASE REPORT A 40-year-old woman presented with a large 6.4×6.0×13.0 cm high-flow Schobinger stage II high-flow AVM of the parotid gland and auricle. Diagnostic imaging included magnetic resonance imaging (MRI) and conventional catheter angiogram, which defined the vascular anatomy and flow characteristics of the AVM. She was treated with preoperative endovascular embolization followed by surgical excision and free-tissue transfer reconstruction on the next day. The results were excellent, with no recurrence over 3.5 years of follow-up. CONCLUSIONS This is the second case reported in the literature of high-flow AVM concurrently involving the parotid gland and auricle, treated with perioperative embolization followed by surgical excision and grafting. Management of AVMs requires a multidisciplinary team approach and understanding of the natural history of the lesion. Although total surgical resection is the criterion standard for these AVMs, endovascular embolization is an alternative treatment that can be used as an adjunct to surgery. Furthermore, perioperative embolization can decrease the vascularity of the lesion and effectively reduce blood loss during AVM surgery.

The Willingness of the Elderly to Choose Nursing Care: Evidence From in China.

With the accelerating aging of the population and the worsening psychological conditions of older people, the traditional mode of family support for the elderly in China does not always meet the physical and psychological needs of the elderly, and more social support modes for the elderly are needed. Based on 3,513 valid questionnaires on the long-term care and protection needs of Chinese residents, this paper uses a logit regression model to analyze the factors influencing the willingness of the elderly to choose nursing care. The results show that intergenerational family support for the elderly is a significant psychological driver on the willingness of the elderly to choose nursing care. Compared with the elderly living with family, empty nesters or older people living alone are more inclined to select nursing care when they have difficulties taking care of themselves. The physical health of the elderly affects their willingness to choose nursing care, and elderly individuals with more hospitalizations are less likely to select nursing care. In addition, elderly females who are relatively young, have a high level of education, have a high income, have a nursing home near the residence, and are already covered by medical insurance are more willing to choose nursing care. The results of this study are of great importance for improving the medical services and aging care services for the elderly and providing theoretical support for alleviating the psychological and social pressure brought by population aging.

Maintaining the long-term accuracy of water distribution models with data assimilation methods: A comparative study.

The upgrading of water supply services is calling for more accurate and adaptive numerical models to give insight into actual water distribution systems (WDSs), which underlines the importance of carefully calibrating model parameters. Due to unavoidable uncertainties in the calibration process such as measurement errors, errors in model parameters assumed to be known, and local-optimum of calibration algorithms, calibrated parameters could still contain non-negligible latent errors, and the calibrated model may not able to maintain its long-term accuracy when operating conditions change. To solve this problem, there is growing interest in adopting data assimilation (DA) methods to utilize more comprehensive information in long-term measurements to reduce the impact of uncertainties and maintain the accuracy and stability of calibrated models. In this study, two traditional calibration methods and four DA methods were tested and compared in two WDSs with different structures, which aims to form a general understanding of the behavior and applicability of different methods. The calibration results show that DA methods perform better than traditional methods and are more robust to different types of uncertainties, which provide an effective way to maintain the long-term accuracy of WDS models to enable better management of WDSs. Ensemble-based DA methods such as Particle Filter (PF) and Inferential-Measurement Kalman Filter (IMKF) performed well in the real-life system. They avoid linear approximation and can better estimate the impact of uncertainties to assimilate accurate correction information of the parameters. Gradient-based DA methods such as Extended Kalman Filter (EKF) and Variational Bayesian Adaptive Kalman Filter (VBAKF) have lower computational demand, but they are found to be less robust when dealing with large system uncertainties and nonlinearities.

Analysis of clinical characteristics and prognostic factors associated with EBV-associated HLH in children.

Purpose Our aim is to analyze the clinical characteristics and prognostic factors of Epstein-Barr (EB) virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children. Methods Children with newly diagnosed HLH were retrospectively analyzed. Results Finally, a total of 95 children with HLH were enrolled in this study, including 43 (45.3%) with EBV-HLH and 52 (54.7%) with non-EBV-HLH. Laboratory tests showed that the levels of absolute neutrophil count (ANC) decrease (P = 0.031) and triglycerides (TG) increase (P = 0.036) in the EBV-HLH group were statistically significant compared with those in the non-EBV-HLH group, respectively. We found that the remission rate during induction period in the EBV-HLH group and non-EBV-HLH group was 75.8% and 89.3%, respectively. The correlation analysis showed that the elevated degree of total bilirubin (TBIL) (P = 0.042), triglyceride (TG) (P = 0.009), serum ferritin (SF) (P = 0.008) and interleukin-8 (IL-8) (P = 0.004) were related with the remission rate during induction in the EBV-HLH group. Further univariate analysis showed that the elevated degree of TBIL (P = 0.048) and TG (P = 0.019) were significant risk factors for the remission rate during induction in the EBV-HLH group. In the multivariate analysis, we observed that there was statistical significance for the degree of TG elevation (P = 0.015) between the two groups. The correlation analysis showed that the elevated degree of TBIL (P = 0.030), the elevated degree of SF (P = 0.020) and the elevated degree of interleukin-6 (P = 0.010) were related to the induction mortality of children with EBV-HLH. Conclusion TBIL and TG are valid indicators to assess the efficacy and prognosis of EVBHLH among children in induction period.

[Analysis of Clinical Characteristics and Prognosis in Children with Acute Megakaryoblastic Leukemia without Down Syndrome].

OBJECTIVE: To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL). METHODS: The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment. RESULTS: The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×109/L, the median hemoglobin was 67 g/L and median platelet was 16×109/L. An increase of primitive and naive megakaryocytes was found in the bone marrow sample. The immunophenotypes of bone marrow detected by flow cytometry in 19 children were all positive expressed for CD41, CD61. Genetic tests showed that five cases carrying EVI1, including one complicating with MLL/AF10, one patient carrying HOX11, one carrying GATA1, IKZF1 and DDX11 mutations, one patient carrying missense mutation of NRAS, one with missense mutation of KRAS and two cases with high expression of WT1. Karyotype analysis were performed in 11 cases of children, including four with normal karyotype, four with complex karyotypes, one with trisomy 8, one with 7/13 trisomy 21 without Down syndrome manifestations (considered as abnormal somatic karyotype) and one Robertsonian translocation carrier involving chromosomes 14 and 21. Ten children received treatment, including three cases with allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR), two cases with complete donor implantation, and one without implanted but hematopoietic recovered, these three children were followed up for 26, 15 and 12 months respectively and the minimal residual disease (MRD) were all less than 10-4. Another three cases achieving CR after chemotherapy but relapsed in 5, 10 and 12 months after the onset respectively, and all the three children were died eventually. One children died of pulmonary hemorrhage during chemotherapy and three children died from discontinuation of treatment after non remission. The remaining nine children died because of without chemotherapy treatment. CONCLUSION: Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.

Stable, active CO2 reduction to formate via redox-modulated stabilization of active sites.

Electrochemical reduction of CO2 (CO2R) to formic acid upgrades waste CO2; however, up to now, chemical and structural changes to the electrocatalyst have often led to the deterioration of performance over time. Here, we find that alloying p-block elements with differing electronegativities modulates the redox potential of active sites and stabilizes them throughout extended CO2R operation. Active Sn-Bi/SnO2 surfaces formed in situ on homogeneously alloyed Bi0.1Sn crystals stabilize the CO2R-to-formate pathway over 2400 h (100 days) of continuous operation at a current density of 100 mA cm-2. This performance is accompanied by a Faradaic efficiency of 95% and an overpotential of ~ -0.65 V. Operating experimental studies as well as computational investigations show that the stabilized active sites offer near-optimal binding energy to the key formate intermediate *OCHO. Using a cation-exchange membrane electrode assembly device, we demonstrate the stable production of concentrated HCOO- solution (3.4 molar, 15 wt%) over 100 h.

[Efficacy of BMMSCs on aGVHD and Its Correlation with SerumInflammatory Cytokines in Pediatric Patients with Severe Refractory Acute Graft-Versus-Host Disease].

OBJECTIVE: To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC. METHODS: 17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs. RESULTS: The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 106/kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P＞0.05). CONCLUSION: The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.

Diagnosis and treatment of juvenile myelomonocytic leukemia.

Objective: To investigate clinical features, diagnosis, treatment strategies and prognosis of juvenile myelomonocytic leukemia (JMML). Methods: The clinical data of 21 patients with JMML who were diagnosed in our hospital from January 2013 to May 2018 were retrospectively analyzed. Results: Among the 21 children with JMML, 16 were male and 5 were female. Out of the 21 children who were diagnosed with JMML, 7 were lost after treatment while the remaining 14 received A-3V chemotherapy regimen of South Korea. The effective response rate was 78.5%. The three-year overall survival (OS) rate and three-year disease-free survival (DFS) rate were (76.2 ± 14.8)% and (66.2 ± 14)%, respectively. Single factor analysis showed that PLT count ≤33×109/L, LDH level >500 U/L and HbF level >10% and chemotherapy only were the significant factors that lead to poor prognosis in children. Cox multivariate analysis showed that the choice of treatment options affected the prognosis of JMML children. By taking prognostic factors for long-term efficacy into account, patients with treatment strategy of chemotherapy alongside hematopoietic stem cell transplantation (HSCT) have a better prognosis. Conclusion: The PLT count, LDH level, HbF level and choice of treatment plan are important for the evaluation of prognosis for children with JMML. Although there is a lack of consistency in terms of donors but the A-3V scheme is relatively stable, so HSCT should be preferred for children with poor prognostic factors.

[Clinical Analysis of 164 Children of Blood Disease Complicated with Invasive Fungal Disease].

OBJECTIVE: To investigate the clinical characteristics, prevention and treatment of invasive fungal disease (IFD). METHODS: The clinical data of 164 patients who met the diagnostic criteria of IFD in our center from January 2012 to January 2015 were retrospectively analyzed. The incidence, clinical characteristics, related factors, treatment methods and prognosis were analyzed. RESULTS: Among 1289 cases of blood diseases, 164 cases suffered from IFD with inciduce of 12.7%. The main infection sites were as followed: lung, blood and gastrointestinal tract, with incidence of 84.2%, 5.5% and 3% respectively. The funge was found in 35 cases by detection; among fungi, the detected rate of candida albicans. aspergillus and candida glabrata was more high with 51.5%, 20% and 14.3% respectively. Among 164 childen with blood deseases complicated by IFD, 36 cases gained complete remission, 97 cases gained partial remission, 10 cases were stable, 11 cases were progressive and 10 cases died, the overall effective rate reached 81.1%. The univariate analysis showed that the gramulopenia, granulocyte recovery, long-term use of corticosteroid and immuno-suppressive agents, as well as different grades of diagnosis were significant factors affecting the efficacy of antifungal therapy for blood disease children with IFD, the multivariate analysis further showed that the granulocyte recovery and diagnosis grades were independent prognostic factors affecting the therapeutic efficacy for IFD children. The overall survival rate of IFD children with 12 weeks of antifungal treatnment was 81.7%, out of which the survival rate of IFD children at 12 weeks of treatment with itraconazole, voriconazole, amphotericin B and caspofungin was 81.4%, 80%, 69.4% and 97.1% respectively, there were significant differences in survival rate between each other by long rank test. In addition of caspofungin, the other 3 kinds of drugs had toxic side effects of different degrees, but IFD children could tolerated these effects after symptomatic treatment. CONCLUSION: The incidence of IFD in children with blood deseases in our hospital is 12.7%, the lung is most common infective site, moreover patogens of IFD mainly is candida. The promotion of granulocyte recovery and early stratified diagnosis can contribule to the treatment of IFD. For the IFD children with better economic condition, the caspofungin is a potent antifungal agent with high efficacy, low toxicity and better prognosis.

[Efficacy and Safety of MSC Infusion in Treatment of Children with Refractory LOHC: A Clinical Study].

OBJECTIVE: To study the curative effect and safety of menchymal stem cell infusion in treatment of children with refractory late-onset hemorrhagic cystitis(LOHC) after allogeneic HSCT. METHODS: Thirty cases of children with refractory LOHC after allo-HSCT in our department between December 2010 and July 2016 were analyzed retrospectively, out of 30 cases 7 received MSC treatment. The used MSC of all were four-to-five generation MSC from bone marrows of third party donors, and were infused into patients with (1.87±0.456)×106/kg MSCs once a week (1-4 times in total) until the hematuria and odynuria symptoms being improved. To observe whether unfavorable reactions occurred after MSC treatment, the patients accepted daily physical examination and regular assistant examination. The cytokine levels were also measured and dynamically detected in 2 cases before and after MSC treatment. RESULTS: In 30 children with refractory LOHC, the hematuria difficultly reached the remission after routine hydration, alkalizing and antiviral therapy, Among 25 cases who were received methylprednisolone, MTX and CTX therapy, 7 cases received MSC infusion for 1-4 times with dose of (1.87±0.456)×106/(kg·time) as a result, 7 cases of LOHC were cured. The TNF-α and IL-2R levels in 2 cases progressively decreased after MSC infusion, no occurence of fever, rash, embolism and so on were found in 7 cases received MSC infusion; the BKV detection showed that the viral load did not increase; the leukemia relapse or secondary cancer did not occure. CONCLUSION: The MSC treatment is safe and effective for refractory LOHC after allo-HSCT.

Draft Genome Sequence of a Thermophilic Desulfurization Bacterium, Geobacillus thermoglucosidasius Strain W-2.

Geobacillus thermoglucosidasius strain W-2 is a thermophilic bacterium isolated from a deep-subsurface oil reservoir in northern China, which is capable of degrading organosulfur compounds. Here, we report the draft genome sequence of G. thermoglucosidasius strain W-2, which may help to elucidate the genetic basis of biodegradation of organosulfur pollutants under heated conditions.