[Incidence of hypogammaglobulinaemia in children with steroid-dependent/frequently relapsing nephrotic syndrome treated with rituximab and its association with severe infections].

Objective: To investigate the incidence and influencing factors of hypogammaglobulinemia (HGG) in children with steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with rituximab (RTX), and its relationship with the risk of severe infections. Methods: The clinical data of children with SDNS/FRNS treated with RTX at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University from December 2020 to January 2023 were retrospectively analyzed. RTX treatment was performed using a B-cell-guided regimen (a single dose of 375 mg/m2, a maximum of 500 mg/dose, and an additional one dose when reassessment of peripheral blood CD19+B cells≥1%). Patients were divided into HGG and non-HGG groups according to the presence or absence of HGG during the follow-up period. A multivariate logistic regression model was used to analyze the influencing factors of HGG, and the predictive value of each influencing factor on HGG was assessed by plotting the receiver operating characteristic (ROC) curve. Results: A total of 59 SDNS/FRNS children (48 males and 11 females) were included, and aged [M (Q1, Q3)] 9.4 (6.5, 12.2) years at the time of the first RTX treatment, with a median application of 3 (2, 4) doses of RTX. During the follow-up period of 15.5 (9.9, 22.8) months, the HGG was present in 16 (27.1%) children, of which seven persisted for more than 1 year. Compared with non-HGG group, HGG group had a shorter duration of the disease [3.3 (2.1, 3.6) vs 4.6 (2.4, 8.0) years, P=0.030], younger age at the time of the first RTX treatment [6.2 (5.6, 7.4) vs 11.3 (8.8, 13.3) years, P<0.001], and lower serum IgG levels [5.9 (4.9, 6.4) vs 7.5 (6.1, 8.2) g/L, P<0.001]. Multivariate logistic regression analysis showed that young age at the time of the first RTX treatment (OR=0.52, 95%CI: 0.35-0.78, P=0.002) was an influencing factor of HGG. The area under the curve (AUC) for age at first RTX treatment to predict HGG was 0.887 (95%CI: 0.778-0.955, P<0.001), with an optimal cut-off value of 8.3 years. During the follow-up period, six children (10.2%) developed severe infectious, and there was no statistically significant difference in the incidence of serious infections between the HGG and non-HGG groups [12.5% (2/16) vs 9.3% (4/43), P=1.000]. Conclusions: HGG is frequent in children with SDNS/FRNS treated with RTX, and nearly half of HGG persists for more than 1 year. The possibility of HGG is greater in those≤8.3 years at the first RTX treatment, but HGG does not increase the risk of severe infections in children.

[Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells].

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

[Long-term mortality risk of valvular heart disease adults over 35 years old in Chinese communities].

Objective: To investigate the risk and influencing factors of long-term mortality of valvular heart disease (VHD) adults aged 35 years and over in Chinese communities. Methods: A cohort study was carried out. The data of the subjects who underwent echocardiography were collected from the Chinese Hypertension Survey between 2012 and 2015 and survival outcomes were followed up between 2018 and 2019. Kaplan-Meier survival curves were plotted and compared using log-rank test. Cox proportional hazards models were used to analyze the influence of VHD on mortality. Results: During an average follow-up time of (4.6±0.9) years, a total of 23 237 participants (10 881 males and 12 356 females) were pooled into the final analysis from 5 eastern, 5 central, and 4 western provinces, cities and autonomous regions in China, with a mean age of (56.9±13.2) years. Among the included participants, 1 004 had VHD (467 males and 537 females), with a mean age was of (68.1±12.6) years. In the Kaplan-Meier analysis, participants with VHD had a significantly increased risk of all-cause mortality (log-rank χ2=351.82, P<0.001) and cardiovascular mortality (log-rank χ2=284.14, P<0.001) compared with those without VHD. Multivariate Cox regression analysis showed that compared with those without VHD, the participants with rheumatic VHD had a 45% increased risk of all-cause mortality (HR=1.45, 95%CI: 1.12-1.89) and degenerative VHD increased the risk of cardiovascular mortality by 69% (HR=1.69, 95%CI: 1.19-2.38). The risk factors of cardiovascular mortality for VHD were age 55 years and over (55-<75 years: HR=4.93, 95%CI: 1.17-20.85;≥75 years: HR=11.92, 95%CI: 2.85-49.80) and diabetes mellitus (HR=1.71, 95%CI: 1.00-2.93). Conclusions: VHD is a risk factor of all-cause mortality and cardiovascular mortality among adults aged 35 years and over. Age 55 years and over and diabetes mellitus are adverse prognostic factors for patients with VHD.

[Study on long-term morphological stability of three-dimensional-printed photosensitive resin dental models].

Objective: To study the long-term morphological stability of three-dimensional (3D) printed photosensitive resin dental models under natural light and dark conditions. Methods: Eighty sets of resin dental models were made by the desktop 3D printer from one digital standard model set, and randomly divided into two groups, namely natural light group (40 sets) and dark group (40 sets). All resin models were stored in sealed bags, with 4 model sets from each group randomly collected after 1, 3, 5, 7, 14, 21, 28, 40, 60, or 90 days of storage and 3D scanned using an optical model scanner. The root-mean-square error (RMSE) was calculated to represent the mean deviation of the difference between the digital standard model and the scanned resin model. Meanwhile, three linear indexes (the width between the canines, the width between the first molars, and the arch length) of the resin dental model were measured and compared with the corresponding values of the standard model. RMSE and the linear measurements between the digital standard model and the scanned resin models were compared between the natural light group and the dark group and among models from different time points. Results: Compared with the digital standard model, the RMSE values of 96.9% (155/160) resin dental models were less than 0.1 mm within 90-day storage. Also, at the same time point, there was no significant difference in the RMSE between the natural light group and the dark group (P>0.05). 75.0% (360/480) of the absolute values of the linear differences (differences in inter-canine width, intra-molar width, and arch length between the digital standard model and the scanned resin model) were within 0.2 mm, and about 0.1% (3/480) of the linear differences were greater than 0.5 mm, and all of the linear differences were within 0.6 mm. Conclusions: 3D-printed resin dental models can be stored stably under natural light and dark conditions for a long time.

[Prevalence of albuminuria and its association with cardiovascular diseases in Chinese residents aged over 35 years].

Objective: To investigate the prevalence of albuminuria in Chinese residents aged >35 years and its potential association with cardiovascular disease (CVD). Methods: A total of 34 647 Chinese subjects aged ≥35 years were selected by stratified multi-stage random sampling from 2012 to 2015. Data were collected through questionnaires, physical examinations, and laboratory tests. Albuminuria was categorized into 3 types according to urinary albumin-to- creatinine ratio: normal (<30 mg/g), microalbuminuria (MAU, 30-300 mg/g), and macroalbuminuria (≥300 mg/g). Measurement data were expressed as x¯±s, and t-tests were used for comparisons between indicators. Qualitative data were expressed as rate or constituent ratio, and the χ2 test or Kruskal-Wallis test was used to examine differences. Logistic regression was used for multivariate analyses. SAS 9.4 software was used for statistical analyses, and P<0.05 was considered statistically significant. Results: The prevalence of abnormal albuminuria was 19.1%; the prevalence was 17.2% for MAU and lower in males (13.8%) than females (20.1%, P<0.01). The risk of CVD was higher among subjects with MAU (OR=1.23, 95%CI 1.12-1.35) and macroalbuminuria (OR=1.86, 95%CI 1.50-2.32). When MAU was complicated by hypertension and diabetes mellitus, the CVD risk was 1.76 times higher. Conclusions: The prevalence of MAU is high among Chinese subjects aged 35 years and over. Those with MAU have higher CVD risk, especially those with hypertension and diabetes mellitus.

[Impact of non-valvular atrial fibrillation on global cognitive function and executive function].

Objective: To explore the impact of non-valvular atrial fibrillation (AF) on the global cognitive function and executive function of patients without dementia, and to observe the differences between different types of AF. Methods: This research is a prospective and cross-sectional study. Non-dementia patients admitted to the department of neurology in the third people's hospital of Chengdu from July 2018 to July 2019 were included. Patients with non-valvular AF were included in the AF group and those with sinus rhythm were included in the control group. General clinical data and compared global cognitive function (mini-mental state examination (MMSE) and montreal cognitive assessment (MOCA)) and executive function (shape trails test (STT) and stroop color and word test (SCWT)) data were obtained and compared between 2 groups, and between different AF type groups. Results: A total of 386 participants were included, including 203 in AF group (52.6%), age was 68 (63, 71) years old, 119 were male (58.6%) and 183 in control group, age was 68 (63, 71) years old, 101 were male (55.2%). MMSE(28 (27, 29)) and MOCA (25 (22, 26)) scores were lower in AF group than those in control group (P<0.05), while STT-A time (84 (64, 140) s), STT-B time (248 (184, 351) s), STT time difference((159 (106, 245) s), SCWT-A time (50 (50, 50) s), SCWT-B time (55 (46, 63) s), SCWT-C time (100 (86, 120) s) and SCWT time interference (46 (34, 65) s) were higher than those in control group (P<0.05). Moreover, there was no difference in above indexes between paroxysmal AF and non-paroxysmal AF. Conclusion: The global cognitive function and executive function of patients with non-valvular AF are both decreased, while there is no obvious difference of the global cognitive function and executive function between paroxysmal AF and non-paroxysmal AF patients.

Band-selective Holstein polaron in Luttinger liquid material A0.3MoO3 (A = K, Rb).

(Quasi-)one-dimensional systems exhibit various fascinating properties such as Luttinger liquid behavior, Peierls transition, novel topological phases, and the accommodation of unique quasiparticles (e.g., spinon, holon, and soliton, etc.). Here we study molybdenum blue bronze A0.3MoO3 (A = K, Rb), a canonical quasi-one-dimensional charge-density-wave material, using laser-based angle-resolved photoemission spectroscopy. Our experiment suggests that the normal phase of A0.3MoO3 is a prototypical Luttinger liquid, from which the charge-density-wave emerges with decreasing temperature. Prominently, we observe strong renormalizations of band dispersions, which are recognized as the spectral function of Holstein polaron derived from band-selective electron-phonon coupling in the system. We argue that the strong electron-phonon coupling plays an important role in electronic properties and the charge-density-wave transition in blue bronzes. Our results not only reconcile the long-standing heavy debates on the electronic properties of blue bronzes but also provide a rare platform to study interesting excitations in Luttinger liquid materials.

[Dasatinib combined with multi-agent chemotherapy regimen in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a prospective study from a single center].

Objective: This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients. Methods: This prospective, single-arm, and open clinical study enrolled 30 adult Ph(+) ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results: All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS (P=0.004) , HRFS (P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS (P=0.030) and EFS (P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions: The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph(+) ALL patients. Clinical trial registration: ClinicalTrials.gov, NCT02523976.

Simple and rapid detection Aspergillus fumigatus by loop-mediated isothermal amplification coupled with lateral flow biosensor assay.

AIMS: We have developed a new diagnostic technique, termed loop-mediated isothermal amplification coupled with lateral flow biosensor (LAMP-LFB), which has been successfully applied to the detection of Aspergillus fumigatus. MATERIAL AND METHODS: A set of six LAMP primers was designed according to the A. fumigatus-specific anxC4 gene, which specifically recognized eight different regions of the target sequence. The LFB was employed for reporting the A. fumigatus-LAMP results, and the visual readouts were obtained within 2 min. The strains of A. fumigatus species and non-A. fumigatus species were used to test the assay's sensitivity and examine the analytical specificity of the target assay. Optimal LAMP conditions were 66°C for 50 min. The limit of detection is 100 fg. No cross-reactions were obtained, and the specificity of LAMP-LFB assay was 100%. The whole process of the assay, including 20 min of DNA preparation, 50 min of constant temperature amplification, and 2 min of detection by the sensor strip, took a total of 72 min (less than 75 min). Among 89 sputum specimens for clinical evaluation, 10 (11·23%) samples were A. fumigatus-positive by LAMP-LFB and traditional culture method, 9 (10·11%) samples were A. fumigatus-positive by PCR method. Compared with culture method, the diagnostic accuracy of LAMP-LFB method was 100%. CONCLUSIONS: The novel LAMP-LFB detection technology established in the current research is a rapid and reliable detection tool for A. fumigatus. SIGNIFICANCE AND IMPACT OF THE STUDY: This novel LAMP-LFB assay can quickly, specifically and sensitively detect A. fumigatus, thereby speeding up the detection process and increasing the detection rate. In addition, it can also be used as a new molecular method for detection of A. fumigatus in clinical and laboratory areas.

Diagnostic value of the combined detection of CEA, NSE and IL-18 for lung cancer and their relationship with apoptosis gene Bcl-2.

This study aims to investigate the value of the combined detection of carcinoembryonic antigen (CEA), Neuron-specific enolase (NSE) and the level of Interleukin-18 (IL-18) in the serum in the diagnosis of lung cancer. The correlation between these parameters and the expression levels of B-cell lymphoma-2 (Bcl-2) protein were also studied. Eighty patients with lung cancer were included in the lung cancer group. These patients underwent surgery in the Department of Oncology of Huai'an Second People's Hospital between February 2016 and February 2018. During the same period, another 80 patients with benign lung lesions were registered in the benign lesion group and 80 healthy people were enrolled in the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of CEA, NSE and IL-18. The diagnostic critical value of these factors was used as positive indicator. When CEA, NSE and IL-18 levels were positive at the same time, the combined detection was considered to be positive. WB was used to detect Bcl-2 expression level. We also analyzed the possible correlation between CEA, NSE, IL-18 levels and the Bcl-2 expression levels. The CEA, NSE and IL-18 expression levels in the serum of the lung cancer group were significantly higher than those in the benign lesion and the control groups (p<0.05). The area under ROC curve for CEA, NSE and IL-18 respectively was 0.770 (0.697-0.843), 0.829 (0.767-0.890), 0.721 (0.642-0.800) (p<0.001). IL-18 level was negatively correlated with the level of Bcl-2 mRNA in the tissue (r=-0.380, p<0.001). In conclusion, CEA, NSE and IL-18 have a good auxiliary diagnostic value in patients with lung cancer. The combined detection could improve the sensitivity and specificity of lung can¬cer diagnosis. There was a negative correlation between IL-18 and Bcl-2 levels which suggested a potential inhibitory role of IL-18 on the lung cancer cells apoptosis pathway.

[The association study of WWP2 gene polymorphisms with delayed encephalopathy after acute carbon monoxide poisoning].

Objective: To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods: From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ(2) test, and χ(2) test was used for association analysis. Results: For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group (P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups (P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion: It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

[Impact of duration of antibiotic therapy on the prognosis of patients with acute myeloid leukemia who had Gram-negative bloodstream infection in consolidation chemotherapy].

Objectives: To investigate the influence of duration of antibiotic therapy on the prognosis of patients with AML who had Gram-negative bloodstream infection during consolidation chemotherapy. Methods: Data were collected retrospectively from 591 patients enrolled from the registered "A Phase III study on optimizing treatment based on risk stratification for acute myeloid leukemia, ChiCTR-TRC-10001202" treatment protocol between September 2010 and January 2016 in different treatment cycles. Results: A total of 119 episodes of Gram-negative bloodstream infection occurred during consolidation chemotherapy. Excluding the 5 episodes in which fever lasted longer than 7 days, 114 episodes of infection were analyzed. The median neutrophil count was 0 (0-5.62)×10(9)/L, median neutropenia duration was 9 (3-26) days, median interval of antibiotics administration was 7 (4-14) days. Logistic regression analysis showed that there is no significant difference on 3-day recurrent fever rate and reinfection by the same type bacteria between antibiotics administration ≤7 days or >7 days (1.2% vs 3.0%, P=0.522, OR=0.400, 95% CI 0.024-6.591; 18.5% vs 21.2%, P=0.741, OR=0.844, 95% CI 0.309-2.307). Propensity score analysis confirmed there was no significant difference on same pathogen infection rate between antibiotics application time ≤ 7 days or >7 days (P=0.525, OR=0.663, 95% CI 0.187-2.352). No infection associated death occurred within 7 or 30 days in both groups. Conclusion: Discontinuation of therapy until sensitive antibiotics treated for 7 days does not increase the recurrent fever rate and the infection associated death rate. Indicating that, for AML who had Gram-negative bloodstream infection during consolidation chemotherapy, short courses of antibiotic therapy is a reasonable treatment option when the infection is controlled.

Induction of nuclear factor-κB signal-mediated apoptosis and autophagy by reactive oxygen species is associated with hydrogen peroxide-impaired growth performance of broilers.

The oxidative study has always been particularly topical in poultry science. However, little information about the occurrence of cellular apoptosis and autophagy through the reactive oxygen species (ROS) generation in nuclear factor-κB (NF-κB) signal pathway was reported in the liver of broilers exposed to hydrogen peroxide (H2O2). So we investigated the change of growth performance of broilers exposed to H2O2 and further explored the occurrence of apoptosis and autophagy, as well as the expression of NF-κB in these signaling pathways in the liver. A total of 320 1-day-old Arbor Acres male broiler chickens were raised on a basal diet and randomly divided into five treatments which were arranged as non-injected treatment (Control), physiological saline (0.75%) injected treatment (Saline) and H2O2 treatments (H2O2(0.74), H2O2(1.48) and H2O2(2.96)) received an intraperitoneal injection of H2O2 with 0.74, 1.48 and 2.96 mM/kg BW. The results showed that compared to those in the control and saline treatments, 2.96 mM/kg BW H2O2-treated broilers exhibited significantly higher feed/gain ratio at 22 to 42 days and 1 to 42 days, ROS formation, the contents of oxidation products, the mRNA expressions of caspases (3, 6, 8), microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I, autophagy-related gene 6, Bcl-2 associated X and protein expressions of total caspase-3 and total LC3-II, and significantly lower BW gain at 22 to 42 days and 1 to 42 days, the activities of total superoxide dismutase and glutathione peroxidase, the expression of NF-κB in the liver. Meanwhile, significantly higher feed/gain ratio at 1 to 42 days, ROS formation, the contents of protein carbonyl and malondialdehyde, the mRNA expression of caspase-3 and the protein expressions of total caspase-3 and total LC3-II, as well as significantly lower BW gain at 22 to 42 days and 1 to 42 days were observed in broilers received 1.48 mM/kg BW H2O2 treatment than those in control and saline treatments. These results indicated that oxidative stress induced by H2O2 had a negative effect on histomorphology and redox status in the liver of broilers, which was associated with a decline in growth performance of broilers. This may attribute to apoptosis and autophagy processes triggered by excessive ROS that suppress the NF-κB signaling pathway.

[Characteristics and prognosis in adult acute myeloid leukemia patients with MLL gene rearrangements].

Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M(3)) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10(9)/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients' partner genes weren't identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions: AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.

[Characteristics and prognosis in adult patients with early T-cell precursor acute lymphoblastic leukemia].

Objective: To analyze the clinical, laboratory characteristics and prognosis of adult early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Methods: The clinical data of 13 adult ETP-ALL patients from January 2009 to March 2017 were retrospectively analyzed and compared with non-ETP ALL patients. Results: 13 ETP-ALL patients (17.3%) were identified in 75 adult T-ALL patients, the median age of the patients was 35 years old (15 to 49 years) and 10 patients were male (76.9%). ETP-ALL patients had lower WBC count, LDH level, blasts in peripheral blood, lower incidence of thymic mass and higher PLT count compared to non-ETP ALL patients. The CR rate after one course induction chemotherapy for ETP-ALL and non-ETP ALL patients was 33.3% and 90.1%, respectively (χ(2)=26.521, P<0.001). The median overall survival(OS) was 11.33 (95%CI 0-28.46) and 25.69 (95%CI 11.98-39.41) months, respectively. The 3-year OS was 41.7% and 40.7%, respectively (P=0.699). The median event free survival (EFS) was 1.51 (95%CI 1.23-1.79) and 21.36 (95%CI 4.67-38.04) months, respectively. The 3-year EFS was 16.7% and 39.5%, respectively (P=0.002). The 3-year relapse free survival (RFS) was 53.0% and 52.0%, respectively (P=0.797). Multivariate analysis revealed that CNSL and allo-HSCT were independent risk factors affecting OS of T-ALL and ETP-ALL didn't affect the prognosis of T-ALL. Conclusion: To our knowledge, this study is the first report on characteristics and prognosis of adult ETP-ALL patients in China. At total of 13 T-ALL patients (17.3%) were classified as having ETP-ALL. These patients had a lower leukemia burden and lower CR rate after one course induction compared to non-ETP ALL patients. Allo-HSCT can improve the prognosis of ETP-ALL.

Random dopant fluctuations and statistical variability in n-channel junctionless FETs.

The influence of random dopant fluctuations on the statistical variability of the electrical characteristics of n-channel silicon junctionless nanowire transistor (JNT) has been studied using three dimensional quantum simulations based on the non-equilibrium Green's function (NEGF) formalism. Average randomly distributed body doping densities of 2 × 1019, 6 × 1019 and 1 × 1020 cm-3 have been considered employing an atomistic model for JNTs with gate lengths of 5, 10 and 15 nm. We demonstrate that by properly adjusting the doping density in the JNT, a near ideal statistical variability and electrical performance can be achieved, which can pave the way for the continuation of scaling in silicon CMOS technology.

Differences in photoreceptor recovery among patients and between different parts of the posterior pole in Vogt-Koyanagi-Harada disease.

PurposeTo investigate the recovery of photoreceptors following the treatment in Vogt-Koyanagi-Harada (VKH) disease.Patients and methodsThis was a retrospective study. We enrolled 28 patients with VKH (56 eyes). The clinical and optical coherence tomography (OCT) findings were recorded for 12 months after treatment. The patterns of photoreceptor recovery on OCT were defined: pattern F group=Foveal photoreceptor recovery visible first; pattern E group=Extrafoveal photoreceptor recovery visible first; and pattern S group=Simultaneous foveal and extrafoveal photoreceptor recovery.ResultsPhotoreceptor recovery varied in different parts of the fundus among patients. Among the 56 eyes, the ellipsoid zone (EZ) recovery of 10 eyes and the interdigitation zone (IZ) recovery of 17 eyes belonged to pattern F group. In most eyes (46 eyes for EZ and 26 eyes for IZ), the recovery of these structures were pattern S. Only in 10 eyes, the recovery of IZ was pattern E. The different patterns of recovery correlated with how promptly the patients had been treated and with the anatomical and visual outcomes at 12 months. Patients in pattern F group were characterized by delayed treatment, delayed recovery of EZ or IZ, and a less favourable prognosis at 12 months relative to other patients, while those in pattern E group had the most prompt treatment and recovery as well as a more favourable outcome at 12 months.ConclusionsIn VKH patients with delayed treatment, foveal photoreceptors tended to recover more rapidly than photoreceptors in other regions.

[Prediction of outcome in acute myeloid leukemia by measurement of WT1 expression as a basic marker of minimal residual disease].

Objective: To probe the potential utility of Wilms tumor 1 (WT1) as a marker of minimal residual disease (MRD) in acute myeloid leukemia (AML) to estimate the relapse-predicting cut-off value. Methods: Quantitative assessment of bone marrow WT1 mRNA level was preformed using real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) assay. The expression levels of WT1 dynamically measured with RQ-RT-PCR were retrospectively analyzed in 121 AML cases (not including acute promyelocytic leukemia) achieving complete remission (CR) after induction therapy followed by consolidation therapy. By comparing WT1 levels of patients with different post-therapy outcomes, the investigators used the receiver operating characteristic (ROC) curve to determine WT1 threshold so as to predict their clinical relapses. Then prognoses and the significance of intervention were analyzed between WT1 positive and negative patients according to the cut-off value of WT1. Results: According to ROC curve, WT1 level higher than 2.98% predicted the possibility of relapse. For simplicity and clinical application, 3.00% was used as the cut-off value of WT1 level for relapse. WT1 levels in 41 patients at diagnosis were detected, meanwhile 3 patients whose WT1 levels at diagnosis below 3.00% were excluded, then the median WT1 level of the rest 38 patients at diagnosis was 44.09% (range 7.19%-188.06%) . The median WT1 level in remission was 0.48% (352 samples, range 0-8.41%) . The median WT1 level at diagnosis was higher than that in remission. Excluding the 3 patients with WT1 level at diagnosis under 3.00%, the relapse rate of WT1 positive group (>3.00% during consolidation phase and follow-up) and WT1 negative group (≤3.00%) was 70.0% (14/20) and 12.2% (12/98) respectively (P<0.001) . The median time from WT1 positivity to clinical relapse was 58 days. Conclusions: WT1 expression level above 3.00% was associated with markedly high risk of relapse, which could be as a useful marker for monitoring MRD following consolidation therapy.

[Primary antifungal prophylaxis with posaconazole plays a pivotal role during chemotherapy of acute myeloid leukemia].

Objective: To evaluate the incidence of invasive fungal infections (IFI) and usage of intravenous antifungal drugs during remission induction chemotherapy in patients with acute myeloid leukemia (AML) under primary antifungal prophylaxis with posaconazole. Methods: Clinical records from newly diagnosed AML patients above 15 years old in one single center from February 2014 to January 2016 were retrospectively reviewed and analyzed, excluding acute promyelocytic leukemia. The incidence of IFI and usage of intravenous antifungal drugs were investigated between control group (not receiving any broad spectrum antifungal prophylaxis) and treatment group (receiving posaconazole as primary prophylaxis). Results: A total of 147 newly diagnosed AML patients were enrolled. Of them, 81 received prophylaxis with posaconazole, and 66 did not receive broad-spectrum antifungal treatment. 7 IFI occurred in posaconazole group, and all were possible cases; 19 IFI occurred in control group (3 proven, 4 probable, 12 possible). The incidence of IFI was significantly lower in treatment group than that in control group (8.6% vs 28.8%, χ(2)=10.138, P=0.001). Usage of intravenous antifungal drugs was significantly decreased in posaconazole group (18.5% vs 50.0%, χ(2)=16.390, P<0.001). Conclusion: Prophylaxis with posaconazole coulf prevent IFI and reduce usage of intravenous antifungal drugs significantly during remission induction chemotherapy in AML patients.

Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins.

OBJECTIVES: Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown. METHODS: We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in fracture callus from Itch knockout (KO) mice and their WT littermates were examined by qPCR. The effect of NF-κB on Itch expression in C2C12 osteoblast cells was determined by a chromatin immunoprecipitation (ChIP) assay. RESULTS: The expression levels of WW Domain Containing E3 Ubiquitin Protein Ligase 1 (Wwp1), SMAD Specific E3 Ubiquitin Protein Ligase 1 (Smurf1), SMAD Specific E3 Ubiquitin Protein Ligase 2 (Smurf2) and Itch were all significantly increased in the fracture callus of WT mice, which was associated with elevated expression of NF-κB members and total ubiquitinated proteins. Callus tissue isolated from Itch KO mice expressed higher levels of osteoblast-associated genes, including Runx2, a positive regulator of osteoblast differentiation, but osteoclast-associated genes were not increased. Both NF-κB RelA and RelB proteins were found to bind to the NF-κB binding site in the mouse Itch promoter. CONCLUSIONS: Our findings indicate that Itch depletion may have a strong positive effect on osteoblast differentiation in fracture callus. Thus, ubiquitin E3 ligase Itch could be a potential target for enhancing bone fracture healing.Cite this article: J. Liu, X. Li, H. Zhang, R. Gu, Z. Wang, Z. Gao, L. Xing. Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins. Bone Joint Res 2017;6:154-161. DOI: 10.1302/2046-3758.63.BJR-2016-0237.R1.