[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.

[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.

[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.

[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.

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.

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.

Immunomagnetic separation combined with colony immunoblotting for selective enrichment and detection of piliated Lactobacillus rhamnosus strains.

AIMS: Piliated Lactobacillus rhamnosus (pLR) strains have attracted much attention owing to their excellent mucus adhering capacity and immunomodulatory effects. Here, we aimed to develop a rapid, sensitive method for isolating pLR strains in complex ecosystems using immunomagnetic separation (IMS) with colony immunoblotting (CIB). METHODS AND RESULTS: Magnetic nanobeads (diameter: 180 nm) conjugated with anti-pLR SpaA pilin antibodies (anti-SpaA) were prepared and used to preconcentrate pLR strains in samples, followed by confirmation with anti-SpaA-based CIB analysis. Under optimized experimental conditions, IMS-CIB selectively recovered pLR strains from 107  CFU ml-1 of faecal microbiota samples spiked with 2·9 × 101 to 2·4 × 106  CFU ml-1 of pLR strains. No positive colonies were detected in samples without addition of pLR strains. The detection limit of IMS-CIB was 29 CFU pLR ml-1 of faecal microbiota, which is much lower than that of CIB without IMS preconcentration (2·0 × 104  CFU ml-1 ). CONCLUSIONS: IMS-CIB allowed selective preconcentration of pLR strains in highly heterogeneous bacterial suspensions and direct detection of pLR colonies, which remained readily available for subsequent isolation. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings established an effective method for selective enrichment and detection of pLR strains.

Intramedullary pressure changes in rats after spinal cord injury.

OBJECTIVES: The objectives of this study were to explore the change of intramedullary pressure over time in rats after different degrees of spinal cord contusion injury and to verify the hypothesis that the more serious the injury, the higher the intramedullary pressure. METHODS: The control group rats underwent laminectomy only, whereas the rats in the three experimental groups were subjected to mild, moderate or severe 10th thoracic cord (T10) contusion injury after laminectomy. In addition, an intramedullary pressure of T10 was measured by a Millar Mikro-Tip pressure catheter (Millar Incorporated Company, Houston, TX, USA) immediately in the control group or at different time points after injury in the experimental groups. RESULTS: The average intramedullary pressure of the rats in the control group was 6.88±1.67 mm Hg, whereas that of the rats in any injury group was significantly higher (P=0.000). There was statistical difference among the different time points in the mild or moderate injury group (P=0.007/0.017), but no in the severe (P=0.374). The curves of intramedullary pressure over time in the mild and moderate injury group were bimodal, peaking at 1 and 48 h after the injury. The intramedullary pressure after injury was positively correlated with the injury degree (r=0.438, P=0.000). CONCLUSIONS: The intramedullary pressure of the rats increased after traumatic spinal cord injury. If the injury was not serious, the intramedullary pressure fluctuated with time and peaked at 1 and 48 h after injury. If the injury was serious, the intramedullary pressure remained high. The more serious the injury, the higher the intramedullary pressure.

Myelotomy reduces spinal cord edema and inhibits aquaporin-4 and aquaporin-9 expression in rats with spinal cord injury.

OBJECTIVE: Spinal cord edema contributes to the pathophysiological mechanisms underlying spinal cord injury (SCI) and is associated with functional recovery after SCI. Early myelotomy may be a promising surgical intervention for reducing SCI-induced edema. However, it remains unclear whether myelotomy can reduce SCI-induced edema. In addition, aquaporin-4 (AQP4) and aquaporin-9 (AQP9) have important roles in the regulation of water homeostasis. Here, we aimed to determine the effects of myelotomy on AQP4 and AQP9 expression and spinal cord edema in a rat model of moderate SCI. METHODS: Rats were randomly assigned to three groups: the sham control group (n=22) receiving laminectomy alone; the contusion group (n=44) receiving laminectomy plus contusion; and the myelotomy group (n=44) receiving laminectomy plus contusion followed by myelotomy at 24 h. Functional recovery was estimated by the open-field and inclined plane tests. Spinal cord edema was determined by measuring the water content. The expression of AQP4 and AQP9 was determined by western blot. RESULTS: Compared with the contusion group, myelotomy significantly improved the Basso, Beattie and Bresnahan scores in the open-field test and resulted in a higher mean angle value in the incline plane test. Myelotomy significantly reduced SCI-induced edema at 4 and 6 days after SCI, which was accompanied by downregulation of AQP4 and AQP9 expression. CONCLUSION: Myelotomy improves locomotor function, reduces edema in rats with SCI and is associated with decreased expression of AQP4 and AQP9.

Arsenic trioxide induced apoptosis in retinoblastoma cells by abnormal expression of microRNA-376a.

Arsenic trioxide (ATO) has been demonstrated to induce apoptosis in retinoblastoma cells, however, mechanisms responsible for this phenomenon are not fully understood. In the present study, we determined whether ATO induced apoptosis by abnormal expression of microRNA. In an apoptosis model of retinoblastoma cells subjected to 4 µM ATO for 72 hours, we found 14 miRNAs changed more than 2-fold by using miRNA microarray analysis. Most of these aberrantly expressed miRNAs were confirmed by quantitative RT-PCR. MiR-376a, a significantly down-regulated miRNA, was selected for further study. The overexpression of miR-376a resulting from miR-376a mimic transfection significantly inhibited ATO-induced apoptosis. By contrast, miR-376a deficiency resulting from miR-376a inhibitor transfection aggravated ATO-induced apoptosis. Using bioinformatic algorithms, caspase-3, a key apoptosis executioner, was predicted as a putative target of miR-376a. The quantitative RT-PCR showed no effects of miR-376a mimic or inhibitor on caspase-3 mRNA level. However, the amount of caspase-3 proteins was reduced by miR-376a mimic, whereas increased by miR-376a inhibitor. Furthermore, the luciferase reporter assay confirmed caspase-3 to be a target of miR-376a, and the apoptosis caused by miR-376a inhibitor were abolished by a caspase-3 inhibitor. These results suggest that ATO -induced apoptosis in retinoblastoma cells is part mediated by decreasing expression of miR-376a, which subsequently increased caspase-3 expression.

Optimal time window of myelotomy in rats with acute traumatic spinal cord injury: a preliminary study.

OBJECTIVES: Pathophysiological mechanisms underlying spinal cord injury (SCI) partially involve edema and formation of a hematoma. Myelotomy seems to be a promising intervention. However, the appropriate timing of myelotomy is still unknown in SCI. Here we aimed to determine the timing of microsurgical myelotomy in an animal model of SCI. METHODS: The SCI model was contusion-induced with a new york university impactor. Sixty-five adult female rats were randomly divided into the following groups: laminectomy alone (the 'sham group', SG), laminectomy plus contusion (the 'contusion group', CG) or laminectomy plus contusion followed by myelotomy at 8, 24 or 48 h (8 h-MTG [myelotomy-treated group], 24 h-MTG or 48 h-MTG). Functional recovery was evaluated via the open field test and the inclined plane test every week after SCI. The percentage of spared white matter area (SWMA) and ultrastructure characteristics of the injured dorsolateral spinal cord were determined on the 42nd day after SCI. RESULTS: Compared with the CG, myelotomy at 8 h-MTG or 24 h-MTG greatly improved the BASSO-BEATTIE- BRESNAHAN scores (P<0.008), whereas the 48 h-MTG showed less efficacy (P=0.023). All myelotomy groups showed higher mean angle values in an inclined plane test (P<0.005) and had greater percentages of SWMA than the CG. Rats in the 24 h-MTG showed a higher intra-axonal fraction and myelin fraction than those in 48 h-MTG (P<0.005). CONCLUSION: Myelotomy up to 48 h after SCI improves recovery in rats. The potential time window of myelotomy may be between 8 and 24 h after SCI.

[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.

[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.

K/B×N serum transfer arthritis is delayed and less severe in leukaemia inhibitory factor (LIF)-deficient mice.

This study is investigating the role of leukaemia inhibitory factor (LIF) in the development of inflammation and joint damage in the mouse K/B×N serum transfer arthritis model. LIF knock-out (LIF(-/-)) mice were generated by mating heterozygote females (LIF(+/-)) with heterozygote males. Arthritis was induced in 8-20-week-old LIF knock-out mice (LIF(-/-)) by intraperitoneal injection of pooled K/B×N sera (50 µl) on days 0 and 2. Clinical disease was scored daily for 6 days. Safranin-O and haematoxylin-stained sections were scored for synovitis, joint space exudate, cartilage degradation and bone damage. RNA was extracted from ankle joints and used to investigate gene expression levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1, LIF, LIF receptor, oncostatin M (OSM), OSM receptor, IL-6 and their common receptor subunit gp130 by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results show that wild-type mice developed severe clinically overt polyarthritis. In contrast, LIF(-/-) mice showed a more than 50% reduction in clinical arthritis severity. Significantly lower histological scores were observed in LIF(-/-) mice compared to wild-type disease controls. LIF(-/-) mice had histopathological scores that were similar to normal healthy mice. IL-6 subfamily cytokine and receptor subunit expression remained unchanged. The expression levels for IL-6 were reduced significantly in all the diseased mice, whether wild-type or LIF(-/-) mice (P < 0·001), compared to healthy wild-type mice. We conclude that LIF contributes to the development of disease in the K/B×N serum transfer model of arthritis. These results provide further evidence for the role of LIF in inflammation and cartilage bone resorption and provide impetus to test the effects of LIF blockade as a therapeutic strategy in rheumatoid arthritis.

Association of the genes for tumor necrosis factor-α and myelin basic protein with delayed encephalopathy after acute carbon monoxide poisoning.

There is structural damage to myelin and secondary immune injury in the development of delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP). In order to assess the role of genetic factors in this mechanism, we studied the association between tumor necrosis factor-α308 (TNF-α308) and myelin basic protein (MBP) 5'-side tetranucleotide repetitive sequence (TGGA) n gene polymorphism and DEACMP. We selected 109 DEACMP patients from the Han population in the Northern Henan Province as the case group, and 115 patients without delayed encephalopathy (called the acute CO poisoning group or the control group). There were no significant differences in TNF-α308 and MBP 5'-side TGGA n genotype distribution and allele frequency between the DEACMP group and the acute CO poisoning group (all P > 0.05). When the population was stratified by gender, only the MBP 5'-side TGGA n allele frequency was significantly different, and the frequency of allele L in the DEACMP group was significantly higher than that of the acute CO poisoning group in males (χ(2) = 4.089, P = 0.043, odds ratio = 2.103, 95% confidence interval = 1.014-4.363). The results showed that there was association between MBP 5'-side TGGA n gene polymorphism and DEACMP, and that allele L could increase the risk of occurrence in male patients with DEACMP. DEACMP may be the result of interaction of environmental and genetic factors.

UCP2 -866G/A and Ala55Val, and UCP3 -55C/T polymorphisms in association with type 2 diabetes susceptibility: a meta-analysis study.

AIMS/HYPOTHESIS: A meta-analysis was performed to assess the association between the UCP2 -866G/A, UCP2 Ala55Val and UCP3 -55C/T polymorphisms and type 2 diabetes susceptibility. METHODS: A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further analyses were performed that stratified for ethnicity. RESULTS: We examined 17 publications. Stratified analysis for ethnicity and sensitivity analysis revealed that there was no heterogeneity between studies for these variants. Using an additive model, no significant association of the UCP2 -866G/A polymorphism with type 2 diabetes risk was observed, either in participants of Asian (OR 1.05, 95% CI 0.96, 1.16) or of European (OR 1.03, 95% CI 0.99, 1.07) descent. Neither the UCP2 Ala55Val nor the UCP3 -55C/T polymorphism showed any significant association with type 2 diabetes risk in Europeans (OR 1.04, 95% CI 0.98, 1.09 for Ala55Val; OR 1.04, 95% CI 1.00, 1.09 for -55C/T). In contrast, a statistically significant association was observed for both polymorphisms in participants of Asian descent (OR 1.23, 95% CI 1.12, 1.36 for Ala55Val; OR 1.15, 95% CI 1.03, 1.28 for -55C/T). CONCLUSIONS/INTERPRETATION: Our meta-analysis suggests that the UCP2 -866G/A polymorphism is unlikely to be associated with increased type 2 diabetes risk in the populations investigated. In contrast, our results indicate that the UCP2 Ala55Val and UCP3 -55C/T polymorphisms may indeed be risk factors for susceptibility to type 2 diabetes in individuals of Asian descent, but not in individuals of European descent. This conclusion warrants confirmation by further studies.

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.