Real-world patient characteristics and treatment patterns of polycythemia vera in Taiwan between 2016 and 2017: a nationwide cross-sectional study.

Background: Polycythemia vera (PV) patients often experience constitutional symptoms and are at risk of thromboembolism as well as disease progression to myelofibrosis or acute myeloid leukemia. Not only is PV often overlooked but treatment options are also limited, however. Objectives: To explore the patient characteristics and treatment pattern of PV patients in Taiwan, and compare with other countries reported in the literature. Design: This is a nationwide cross-sectional study. Methods: The National Health Insurance Research Database in Taiwan, which covers 99% of the population, was utilized. Patients were identified during the cross-sectional period between 2016 and 2017, and their retrospective data were retrieved from 2001 to 2017. Results: A total of 2647 PV patients were identified between 1 January 2016 and 31 December 2017. This study described the demographic information of these patients, including number of patients by risk stratification and by sex, age at diagnosis, age at cross-sectional period, rate of bone marrow aspiration/biopsy at diagnosis, comorbidities, number of postdiagnosis thrombosis, number of disease progression, and death. The mortality rate of PV patients (4.1%) over 60 of age was higher than the general population of the same age group (2.8%). This study also compared the different treatment patterns between sexes and risk groups. Hydroxyurea was deferred to an older age, but conversely was prescribed at higher dose to younger patients. Alarmingly, a high proportion of patients did not receive phlebotomy or hydroxyurea for at least 2 years. Furthermore, discrepancies in prevalence, age at diagnosis, sex ratio, incidence of thrombosis and mortality were also found when compared with data reported in other countries. Conclusion: The clinical landscape of PV in Taiwan between 2016 and 2017 was examined. Distinctive patterns of phlebotomy and hydroxyurea were identified. Overall, these findings highlight the importance of understanding the patient characteristics and treatment patterns of PV in different regions to better inform clinical practice and improve patient outcomes.

Epitomizing biohydrogen production from microbes: Critical challenges vs opportunities.

Hydrogen is a clean and green biofuel choice for the future because it is carbon-free, non-toxic, and has high energy conversion efficiency. In exploiting hydrogen as the main energy, guidelines for implementing the hydrogen economy and roadmaps for the developments of hydrogen technology have been released by several countries. Besides, this review also unveils various hydrogen storage methods and applications of hydrogen in transportation industry. Biohydrogen productions from microbes, namely, fermentative bacteria, photosynthetic bacteria, cyanobacteria, and green microalgae, via biological metabolisms have received significant interests off late due to its sustainability and environmentally friendly potentials. Accordingly, the review is as well outlining the biohydrogen production processes by various microbes. Furthermore, several factors such as light intensity, pH, temperature and addition of supplementary nutrients to enhance the microbial biohydrogen production are highlighted at their respective optimum conditions. Despite the advantages, the amounts of biohydrogen being produced by microbes are still insufficient to be a competitive energy source in the market. In addition, several major obstacles have also directly hampered the commercialization effors of biohydrogen. Thus, this review uncovers the constraints of biohydrogen production from microbes such as microalgae and offers solutions associated with recent strategies to overcome the setbacks via genetic engineering, pretreatments of biomass, and introduction of nanoparticles as well as oxygen scavengers. The opportunities of exploiting microalgae as a suastainable source of biohydrogen production and the plausibility to produce biohydrogen from biowastes are accentuated. Lastly, this review addresses the future perspectives of biological methods to ensure the sustainability and economy viability of biohydrogen production.

Study on the preparation and luminescence properties of SrGe4 O9 :Mn4+ red phosphors for plant illumination.

In this study, SrGe4 O9 :Mn4+ red phosphors for plant illumination were prepared using a high-temperature solid-phase method. The samples were characterized and analyzed by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), fluorescence spectroscopy, and other techniques. The phase structure, apparent morphology, and luminescence properties of the SrGe4 O9 :Mn4+ red phosphors were investigated. The results indicated that the dopant Mn4+ was incorporated into the matrix structure by substituting some Ge4+ ions without any changes in the crystal structure of the SrGe4 O9 matrix. The samples comprised micron-scale particles and exhibited high purity and uniform distribution of elements. The SrGe4 O9 :Mn4+ phosphors exhibited relatively strong red light emission at 660 nm under the excitation of a 430-nm blue light, and the luminescence intensity was the highest when the Mn4+ doping amount was 1%. Proper doping of Ti4+ or Sn4+ could effectively improve the luminescence intensity of the SrGe4 O9 :Mn4+ phosphors. The light-emitting diode (LED) device packaging showed that the SrGe4 O9 :Mn4+ red phosphors could be used for plant growth illumination.

Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry / 中国实验血液学杂志

OBJECTIVE@#To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).@*METHODS@#The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.@*RESULTS@#Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.@*CONCLUSION@#Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

Medication guidelines for glucagon-like peptide-1 receptor agonist （2023 edition） / 中国药房

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

Clinical Study on the Relationship between Gene Mutation Profile and Prognosis in Pediatric Acute Lymphocyte Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.@*METHODS@#Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL.@*RESULTS@#227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ2= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×109/L vs 8.23×109/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).@*CONCLUSION@#Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.

Free sialic acid storage disorders with fetal hydrops in a neonate / 中国当代儿科杂志

A boy, aged 3 hours, was admitted due to a prenatal diagnosis of fetal hydrops at 3 hours after resuscitation for birth asphyxia. Prenatal examination at 5 months of gestation showed massive ascites in the fetus, and after birth, the boy had the manifestations of systemic hydroderma, massive ascites, coarse face, and hepatomegaly. Genetic testing revealed heterozygous mutations in the SLC17A5 gene, and there was a significant increase in urinary free sialic acid. Placental pathology showed extensive vacuolization in villous stromal cells, Hofbauer cells, cytotrophoblast cells, and syncytiotrophoblast cells in human placental chorionic villi. The boy was finally diagnosed with free sialic acid storage disorders (FSASDs). This is the first case of FSASDs with the initial symptom of fetal hydrops reported in China. The possibility of FSASDs should be considered for cases with non-immune hydrops fetalis, and examinations such as placental pathology and urinary free sialic acid may help with early diagnosis and clinical decision making.

IL-33 gene recombination and expression does not affect the phenotypic characteristics of rabies virus in vitro / 细胞与分子免疫学杂志

Objective To create a recombinant rabies virus overexpressing IL-33 and to clarify the effect of IL-33 overexpression on the phenotypic characteristics of recombinant virus in vitro. Methods The IL-33 gene was obtained and amplified from the brain of a highly virulent strain of rabies infected mouse. It was then inserted between the G and L genes of the parental virus LBNSE genome by reversing genetic manipulation and rescuing a recombinant virus overexpressing IL-33. BSR cells or mouse NA cells were infected with recombinant rabies virus (rLBNSE-IL33) and the parental strain LBNSE. Sequencing and fluorescent antibody virus neutralization assay was employed to detect the stability of recombinant virus at multiplicity of infection=0.01. Viral titres focal forming units (FFU) were detected to plot multi-step growth curves (multiplicity of infection=0.01). Cytotoxicity assay kit was used to detect cellular activity. ELISA was adopted to identify the IL-33 in the supernatant of infected cells of different multiplicity of infection. Results Rescued rLBNSE-IL33 overexpressing IL-33 remained stable for at least 10 consecutive generations and had virus titers of approximately 108 FFU/mL. rLBNSE-IL33 was able to express IL-33 at high levels in a dose-dependent manner, but no high expression of IL-33 was detected in the supernatant of cells infected by LBNSE. Examination of the titers of rLBNSE-IL33 and the parental strain LBNSE in BSR and NA cells over 5 days showed no significant differences and similar kinetic properties in growth. Overexpression of IL-33 had no significant effect on the proliferation and activity of infected cells. Conclusion Overexpression of IL-33 does not significantly affect the phenotypic characteristics of recombinant rabies virus in vitro.

Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases) / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL).@*METHODS@#The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed.@*RESULTS@#Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ［(3.92-470)×109/L］ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%.@*CONCLUSION@#B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

Exploring risk factors for combined coronary microvascular dysfunction in patients with ischemia and non-obstructive coronary artery disease / 中华核医学与分子影像杂志

Objective:To investigate the risk factors for combined coronary microvascular dysfunction (CMD) in patients with ischemia and non-obstructive coronary artery disease (INOCA).Methods:From October 2020 to May 2022, 100 INOCA patients with myocardial ischemic symptoms who underwent coronary angiography (CAG) suggestive of <50% stenosis in all three coronary arteries at the Tenth People′s Hospital of Tongji University were prospectively recruited. Myocardial perfusion imaging (MPI), transthoracic echocardiography and cadmium-zinc-telluride (CZT) SPECT coronary flow quantification were performed in the same month, and 93 INOCA patients (36 males and 57 females, age (63.0±10.9) years) were finally included. CMD was defined as coronary flow reserve (CFR)<2.5. Independent-sample t test, Mann-Whitney U test and χ2 test were used to compare MPI results and left ventricular volume parameters between CMD and non-CMD groups. ROC curve analysis was used to analyze the efficacy of each index in predicting CMD, and independent risk factors for CMD were screened by multivariate logistic regression analysis. Results:Among 93 INOCA patients, 29 were in the CMD group and 64 were in the non-CMD group. The age, proportion of hypertension, left ventricular mass index (LVMI), summed stress score (SSS), summed difference score (SDS), left ventricular internal diameter systolic (LVIDS), interventricular septum thickness (IVST), and left ventricular posterior wall thickness (LVPWT) in the CMD group were higher than those in the non-CMD group ( t values: 2.42-3.76, χ2=8.94, z values: -3.31, -3.41, all P<0.05). ROC curve analysis showed that LVMI, SSS, SDS, LVPWT, IVST and age were significant in predicting CMD (AUCs: 0.67-0.72). Multivariate logistic regression analysis showed that LVMI (odds ratio ( OR)=1.08, 95% CI: 1.01-1.17), SDS ( OR=5.37, 95% CI: 1.95-14.78), hypertension ( OR=5.68, 95% CI: 1.34-24.18) and age ( OR=1.10, 95% CI: 1.03-1.18) were risk factors for CMD. Conclusion:LVMI, SDS, hypertension and age are strongly associated with combined CMD in INOCA patients, which can be used for early risk stratification of INOCA patients.

Risk factors of cardiovascular and cerebrovascular diseases in young patients with hyperhomocysteinemia / 中国基层医药

Objective:To investigate the risk factors of cardiovascular and cerebrovascular diseases in young patients with hyperhomocysteinemia.Methods:A total of 260 patients younger than 45 years old who received treatment at the Department of Emergency, Seventh Medical Center, Chinese PLA General Hospital from January 2018 to January 2019 were included in this study. Among these patients, 126 patients with serum homocysteine levels ≥ 15.0 μmol/L were included in the hyperhomocysteinemia group, and 134 patients with serum homocysteine levels < 15.0 μmol/L were included in the control group. Height, body weight, body mass index, blood pressure, homocysteine, fasting blood glucose, blood uric acid, total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and N-terminal B-type natriuretic peptide were determined in each group. Changes in risk factors of cardiovascular and cerebrovascular diseases were compared between the hyperhomocysteinemia and control groups.Results:There were significant differences in body mass index [(26.42 ± 3.54) kg/m 2vs. (22.14 ± 3.22) kg/m 2, t = 10.21, P = 0.016], blood uric acid [(308.71 ± 78.44) μmol/L vs. (285.05 ± 92.09) μmol/L, t = 2.22, P = 0.027], the incidence of coronary heart disease (73/126 vs. 61/134, χ2 = 4.00, P = 0.045) and the incidence of stroke (19/126 vs. 6/134, χ2 = 8.39, P = 0.004) between the hyperhomocysteinemia and control groups. There were no significant differences in fasting blood glucose, blood lipid level, N-terminal B-type natriuretic peptide, and the incidences of diabetes mellitus and hypertension between the two groups (all P > 0.05). Conclusion:The related risk factors of cardiovascular and cerebrovascular diseases increase in young patients with hyperhomocysteinemia. The incidences of coronary heart disease and stroke are very high, and therefore timely intervention should be carried out.

Age-Associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

The effect of immune checkpoint blockade on COVID-19 immunity is unclear. In this study, we determine whether immune checkpoint blockade expanded age-associated B cells (ABCs) are similar to those present in other conditions, and whether they enhance or detract from the COVID-19 vaccine responses. First, we use single cell RNA sequencing (scRNAseq) to show that ABCs arising from distinct aetiologies have common transcriptional profiles and may be further subdivided according to expression of genes associated with different immune functions, including the autoimmune regulator (AIRE). Next, we perform detailed longitudinal profiling of the COVID-19 vaccination response in patients. Finally, we show that high pre-vaccination ABC frequency correlates with decreased levels of antigen-specific memory B cells, and reduced magnitude and longevity of neutralising capacity against authentic SARS-CoV-2 virus. Expansion of ABCs is a biomarker for individuals with cancer requiring additional or more frequent booster immunisation against COVID-19.

Guanxinning tablet inhibits the interaction between leukocyte integrin Mac-1 and platelet GPIbα for antithrombosis without increased bleeding risk.

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.

Incidence and predictors of idiopathic pneumonia syndrome in hematopoietic stem cell transplant patients: a nationwide registry study.

Idiopathic pneumonia syndrome (IPS) is a rare but deadly complication of hematopoietic stem cell transplantation (HSCT). This study characterized the incidence and risk factors for IPS after HSCT in Taiwan. Data from January 2009 to February 2019 was collected from the Taiwan Society of BMT national registry. Forty-three (1.1%) of 3924 HSCT patients who developed IPS were identified. Incidence of IPS was lower in patients who received autologous HSCT than patients who received allogeneic HSCT (0.68% vs 1.44%, P = 0.022). Multivariate analysis showed that use of TBI and intravenous busulfan in the conditioning regimen were each independent predictor of IPS after HSCT. In addition, development of IPS was significantly associated with increased risk of death in the first 120 days post-HSCT (HR, 2.09; 95% CI, 1.08 to 4.05, P = 0.029) and 2 years post-HSCT (HR, 1.65; 95% CI, 1.07 to 2.542, P = 0.023), but not beyond 2 years post-HSCT. However, survival outcomes did not differ significantly between patients with IPS who received autologous versus allogeneic HSCT (P = 0.52). In conclusion, despite the relatively low incidence of post-HSCT IPS in Taiwan, mortality remains high. The results of this study will help to identify high-risk patients for early intervention and guide future therapeutic research.

Current utilization of interferon alpha for the treatment of coronavirus disease 2019: A comprehensive review.

Recent studies have identified an association between perturbed type I interferon (IFN) responses and the severity of coronavirus disease 2019 (COVID-19). IFNα intervention may normalize the dysregulated innate immunity of COVID-19. However, details regarding its utilization and therapeutic evidence have yet to be systematically evaluated. The aim of this comprehensive review was to summarize the current utilization of IFNα for COVID-19 treatment and to explore the evidence on safety and efficacy. A comprehensive review of clinical studies in the literature prior to December 1st, 2021, was performed to identify the current utilization of IFNα, which included details on the route of administration, the number of patients who received the treatment, the severity at the initiation of treatment, age range, the time from the onset of symptoms to treatment, dose, frequency, and duration as well as safety and efficacy. Encouragingly, no evidence was found against the safety of IFNα treatment for COVID-19. Early intervention, either within five days from the onset of symptoms or at hospital admission, confers better clinical outcomes, whereas late intervention may result in prolonged hospitalization.

Influence of blood group and von Willebrand factor on population pharmacokinetics and dose individualization of recombinant factor VIII in Taiwanese patients with haemophilia A.

INTRODUCTION: The large interpatient variability in the pharmacokinetic (PK) parameters of recombinant Factor VIII (rFVIII) observed in haemophilia A hinders efficient and cost-beneficial prophylactic regimen initiation. Identification of factors influencing the PK of rFVIII may shed more light on personalised treatment. AIM: This study aimed to develop a population PK model in the Taiwanese haemophilia A and evaluate the current national health insurance (NHI) reimbursement guidelines of Taiwan for haemophilia treatment. METHODS: A population PK analysis was established based on 69 Taiwanese with moderate or severe haemophilia A. A nonlinear mixed-effects modelling (NONMEM® ) was used to estimate PK parameters and their variabilities. A Monte Carlo simulation was performed to evaluate different prophylactic regimens. RESULTS: A two-compartment model with first-order elimination best described the rFVIII data. Weight-based allometric scaling was related to clearance and central volume of distribution. Blood type and baseline von Willebrand factor (VWF) were significant covariates for clearance. For single dose simulations, a time achieving target level (> 1 IU/dL) was associated with increasing rFVIII dose and VWF level. The multiple dose simulations showed that > 96.4% of patients with high VWF level (> 200%) had predicted trough level > 1 IU/dL for all dosing regimens (15-40 IU/kg, two to three times weekly). However, for twice weekly dosing, lower percentage (47.62-62.20%) of patients with blood group O and low VWF level (< 50%) achieved a predicted trough level > 1 IU/dL. CONCLUSION: The population PK of rFVIII was successfully developed. Dose adjustment based on blood type and VWF level should be considered.

Combined monitoring of thrombelastography, coagulation function and mean platelet volume/platelet count ratio to evaluate the prognosis of patients with sepsis / 中华急诊医学杂志

Objective:To compare the value of difference between thromboelastogram (TEG), coagulation function and mean platelet volume (MPV)/platelet count (PLT) ratio in sepsis patients with short-term prognosis.Methods:A total of 271 patients with sepsis admitted to the Affiliated Hospital of Xuzhou Medical University from January 2020 to September 2021 were retrospectively analyzed. The clinical data of the patients were recorded, and the SOFA score and APACHE Ⅱ score were calculated. The patients were followed up within 28 days and were divided into the survival group and death group. The TEG, coagulation function and MPV/PLT ratio were compared between the two groups. The independent prognostic factors of Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio were confirmed by Logistic regression analysis. The combination of Angle + CI + AT-Ⅲ + D-Di +MPV/PLT ratio was established, and the ROC curve was drawn to evaluate the prognostic value of Angle, CI, AT-Ⅲ and D-Di combined with MPV/PLT ratio in patients with sepsis.Results:The mortality rate of patients with sepsis was 42.4%. The D-Di and MPV/PLT ratio of the death group were significantly higher than those of the survival group, and the differences were statistically significant. Angle, CI and AT-III in the death group were significantly lower than those in the survival group, and the differences were statistically significant. Logistic regression analysis showed that Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio were independent predictors of the prognosis of patients with sepsis (all P < 0.05) . The area under the curve of the combined detection of Angle, CI, AT-Ⅲ, D-DI and MPV/PLT ratio to evaluate the prognosis of sepsis at 28 days was 0.931, which was larger than that of Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio alone (0.755, 0.790, 0.776, 0.729 and 0.746). The sensitivity and specificity of the combination of Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio were 83.5% and 91.0%, which were also higher than those of the single index . Conclusions:Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio are independent prognostic predictors of patients with sepsis. The combination of Angle, CI, AT-Ⅲ, D-Di and MPV/PLT ratio has high sensitivity and specificity in evaluating the prognosis of sepsis.

Effect of hippocampal brain derived neurotrophic factor precursor in mice cognitive dysfuction induced by social isolation / 解剖学报

[Abstract] Objective To investigate the effect of hippocampal brain derived neurotrophic factor precursor (proBDNF) in cognitive dysfuction induced by social isolation. Methods Thirty C57BL / 6 J male mice (4-week old) were randomly divided into group house (GH,n = 15) and socially isolated (SI,n = 15) groups. The GH group (5 mice / cage) and SI group (1 mice / cage) were reared separately under the same conditions. The novel object recognition test and the novel place recognition test were used to evaluate the cognitive function. The expression of BDNF mRNA in the hippocampus was detected by Real-time PCR. The expression of BDNF and proBDNF in hippocampus was detected by Western blotting. Matrix metallopeptidase-9 (MMP-9) and tissue plasminogen activator (tPA) were extracellular enzymes that catalyzed the transformation of proBDNF into mature BDNF. Expression of MMP-9 and tPA mRNA in the hippocampus were detected by Real-time PCR. Results Compared with the GH group, the SI group showed significantly reduced discrimination ratio in the novel object recognition test and novel place recognition test. The result of Real-time PCR showed that there was no difference in the expression of BDNF mRNA between SI group and GH group. The result of Western blotting showed that the expression level of proBDNF in the hippocampus of SI group increased significantly compared with the GH group (P<0. 01),and no difference in BDNF expression was found between the two groups; Compared with the GH group, the BDNF/ proBDNF ratio in the hippocampus of SI group decreased. In addition, the result of Real-time PCR showed that the expression level of MMP-9 and tPA mRNA in the hippocampus of SI group decreased significantly compared with the GH group. Conclusion The social isolation-induced cognitive dysfuction in mice may be related to the up-regulation of proBDNF in the hippocampus.

The affinity maturation, characteristics and application of HIV-1 broadly neutralizing antibodies / 中华预防医学杂志

Hundreds of broadly neutralizing antibodies(bNAbs) were successfully isolated from long-term nonprogression(LTNP) of human immunodeficiency virus type 1(HIV-1) infected individuals. Some bNAbs were illustrated could reduce the viral load and the risk of HIV-1 infection. Today, HIV-1 bNAbs are at the center of vaccine development and passive immunization treatment. Usually, the activity of neutralizing antibodies depends on the epitope. The affinity of neutralizing antibodies also plays a vital role in its inhibitory effect. Multiple affinity maturation in vivo actually provides the broad and potent neutralizing activity of HIV-1 bNAbs. When high affinity HIV-1 bNAbs applied in clinic, it can help immune system to remove virus with lower dosage and fewer side effect. While affinity maturation, HIV-1 bNAbs shows unique characteristics, such as extensive of somatic hypermutation(SHM), in-frame insertion and deletion and long CDR 3 region of heavy chain. The key points in the progress that HIV-1 bNAbs affinity maturation will help us understand the relationship between antibodies neutralizing capability and its characteristics.It also potentially provide a reference to design effective HIV-1 immunogen.

Automatic diagnosis and assessment of bone metastases on bone scans based on deep learning / 中华核医学与分子影像杂志

Objective:To develop an approach for the automatic diagnosis of bone metastasis and to design a parameter of quantitative evaluation for tumor burden on bone scans based on deep learning technology.Methods:A total of 621 cases (389 males, 232 females, age: 12-93 years) of bone scan images from the Department of Nuclear Medicine in Tenth People′s Hospital of Tongji University from March 2018 to July 2019 were retrospectively analyzed. Images were divided into bone metastasis group and non-bone metastasis group. Eighty percent of the cases were randomly extracted from both groups as the training set, and the rest of cases were used as the test set. A deep residual convolutional neural network ResNet34 was used to construct the classification model and the segmentation model. The sensitivity, specificity and accuracy were calculated and the performance differences of the classification model in different age groups (15 cases of <50 years, 75 cases of ≥50 and <70 years, 33 cases of ≥70 years) were analyzed. The regions of metastatic bone lesions were automatically segmented by the segmentation model. The Dice coefficient was used to evaluate the effect of the segmentation model and the manual labeled results. Finally, the bone scans tumor burden index (BSTBI) was calculated to assess the tumor burden of bone metastases.Results:There were 280 cases with bone metastases and 341 cases with non-bone metastases, including 498 in training set and 123 in test set. The classification model could accurately identify bone metastases, with the sensitivity, specificity and accuracy of 92.59%(50/54), 85.51%(59/69) and 88.62%(109/123), respectively, and it performed best in the <50 years group (sensitivity, 2/2; specificity, 12/13; accuracy, 14/15). The specificity in the ≥70 years group (8/12) was the lowest. The Dice coefficient of bone metastatic area and bladder area were 0.739 and 0.925 in the segmentation model, which performed similarly in the three age groups. Preliminary results showed that the value of BSTBI increased with the increase of the number of bone metastatic lesions and the degree of 99Tc m-MDP uptake. The machine learning model in this study took (0.48±0.07) s for the entire analysis process from input to the final BSTBI calculation. Conclusions:The deep learning based on automatic diagnosis framework for bone metastases can automatically and accurately identify segment bone metastases and calculate tumor burden. It provides a new way for the interpretation of bone scans. The proposed BSTBI may be used as a quantitative evaluation indicator in the future to assess the tumor burden of bone metastases based on bone scans.