A novel cuproptosis-related subtypes and gene signature associates with immunophenotype and predicts prognosis accurately in neuroblastoma.

Background: Neuroblastoma (NB) is the most frequent solid tumor in pediatrics, which accounts for roughly 15% of cancer-related mortality in children. NB exhibited genetic, morphologic, and clinical heterogeneity, which limited the efficacy of available therapeutic approaches. Recently, a new term 'cuproptosis' has been used to denote a unique biological process triggered by the action of copper. In this instance, selectively inducing copper death is likely to successfully overcome the limitations of conventional anticancer drugs. However, there is still a gap regarding the role of cuproptosis in cancer, especially in pediatric neuroblastoma. Methods: We characterized the specific expression of cuproptosis-related genes (CRGs) in NB samples based on publicly available mRNA expression profile data. Consensus clustering and Lasso-Cox regression analysis were applied for CRGs in three independent cohorts. ESTIMATE and Xcell algorithm was utilized to visualize TME score and immune cell subpopulations' relative abundances. Tumor Immune Dysfunction and Exclusion (TIDE) score was used to predict tumor response to immune checkpoint inhibitors. To decipher the underlying mechanism, GSVA was applied to explore enriched pathways associated with cuproptosis signature and Connectivity map (CMap) analysis for drug exploration. Finally, qPCR verified the expression levels of risk-genes in NB cell lines. In addition, PDHA1 was screened and further validated by immunofluorescence in human clinical samples and loss-of-function assays. Results: We initially classified NB patients according to CRGs and identified two cuproptosis-related subtypes that were associated with prognosis and immunophenotype. After this, a cuproptosis-related prognostic model was constructed and validated by LASSO regression in three independent cohorts. This model can accurately predict prognosis, immune infiltration, and immunotherapy responses. These genes also showed differential expression in various characteristic groups of all three datasets and NB cell lines. Loss-of-function experiments indicated that PDHA1 silencing significantly suppressed the proliferation, migration, and invasion, in turn, promoted cell cycle arrest at the S phase and apoptosis of NB cells. Conclusions: Taken together, this study may shed light on new research areas for NB patients from the cuproptosis perspective.

Immune-related gene signature associates with immune landscape and predicts prognosis accurately in patients with Wilms tumour.

Wilms tumour (WT) is the most common kidney malignancy in children. Chemoresistance is the leading cause of tumour recurrence and poses a substantial therapeutic challenge. Increasing evidence has underscored the role of the tumour immune microenvironment (TIM) in cancers and the potential for immunotherapy to improve prognosis. There remain no reliable molecular markers for reflecting the immune landscape and predicting patient survival in WT. Here, we examine differences in gene expression by high-throughput RNA sequencing, focused on differentially expressed immune-related genes (IRGs) based on the ImmPort database. Via univariate Cox regression analysis and Lasso-penalized Cox regression analysis, IRGs were screened out to establish an immune signature. Kaplan-Meier curves, time-related ROC analysis, univariate and multivariate Cox regression studies, and nomograms were used to evaluate the accuracy and prognostic significance of this signature. Furthermore, we found that the immune signature could reflect the immune status and the immune cell infiltration character played in the tumour microenvironment (TME) and showed significant association with immune checkpoint molecules, suggesting that the poor outcome may be partially explained by its immunosuppressive TME. Remarkably, TIDE, a computational method to model tumour immune evasion mechanisms, showed that this signature holds great potential for predicting immunotherapy responses in the TARGET-wt cohort. To decipher the underlying mechanism, GSEA was applied to explore enriched pathways and biological processes associated with immunophenotyping and Connectivity map (CMap) along with DeSigN analysis for drug exploration. Finally, four candidate immune genes were selected, and their expression levels in WT cell lines were monitored via qRT-PCR. Meanwhile, we validated the function of a critical gene, NRP2. Taken together, we established a novel immune signature that may serve as an effective prognostic signature and predictive biomarker for immunotherapy response in WT patients. This study may give light on therapeutic strategies for WT patients from an immunological viewpoint.

The Regulatory Network and Role of the circRNA-miRNA-mRNA ceRNA Network in the Progression and the Immune Response of Wilms Tumor Based on RNA-Seq.

Circular RNA (circRNA), which is a newly discovered non-coding RNA, has been documented to play important roles in miRNA sponges, and the dysregulation of which is involved in cancer development. However, circRNA expression profiles and their role in initiation and progression of Wilms tumor (WT) remain largely unclear at present. Here, we used paired WT samples and high-throughput RNA sequencing to identify differentially expressed circRNAs (DE-circRs) and mRNAs (DE-mRs). A total of 314 DE-circRs and 1612 DE-mRs were identified. The expression of a subset of differentially expressed genes was validated by qRT-PCR. A complete circRNA-miRNA-mRNA network was then constructed based on the common miRNA targets of DE-circRs and DE-mRs identified by miRanda prediction tool. The Gene set enrichment analysis (GSEA) indicated that several signaling pathways involving targeted DE-mRs within the ceRNA network were associated with cell cycle and immune response, which implies their participation in WT development to some extent. Subsequently, these targeted DE-mRs were subjected to implement PPI analysis and to identify 10 hub genes. Four hub genes were closely related to the survival of WT patients. We then filtered prognosis-related hub genes by Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a prognosis-related risk score system based on a three-gene signature, which showed good discrimination and predictive ability for WT patient survival. Additionally, we analyzed the mutational landscape of these genes and the associations between their expression levels and those of immune checkpoint molecules and further demonstrated their potential impact on the efficacy of immunotherapy. qRT-PCR and western blotting (WB) analysis were used to validate key differentially expressed molecules at the RNA and protein levels, respectively. Besides these, we selected a key circRNA, circEYA1, for function validation. Overall, the current study presents the full-scale expression profiles of circRNAs and the circRNA-related ceRNA network in WT for the first time, deepening our understanding of the roles and downstream regulatory mechanisms of circRNAs in WT development and progression. We further constructed a useful immune-related prognostic signature, which could improve clinical outcome prediction and guide individualized treatment.

[Effects of eye acupuncture on motor evoked potential and somatosensory evoked potential in patients with incomplete spinal cord injury based on neuroelectrophysiological technology].

OBJECTIVE: To observe the effects of eye acupuncture on motor evoked potential (MEP) and somatosensory evoked potential (SEP) in the patients with incomplete spinal cord injury so as to evaluate its clinical efficacy. METHODS: According to the random number table, 90 patients were divided into exercise therapy group, eye acupuncture group and eye acupuncture combined exercise therapy group (combined treatment group), 30 cases in each. In the exercise therapy group, patients were treated with the routine exercise and occupational therapy. Patients of the eye acupuncture group were treated with eye acupuncture at upper jiao region, lower jiao region, liver region and kidney region bilaterally. Patients of the combined treatment group were given the routine exercise and occupational therapy combined with eye acupuncture. All the treatments were conducted once daily, 7 days as one treatment course for 4 treatment courses. Before treatment and 4 weeks after treatment, the motor function, light touch sensation and pinprick sensation, injury grade and clinical efficacy were assessed separately, using the criteria developed by the American Spinal Injury Association. The modified Barthel index(MBI) was adopted to evaluate the activities of daily livings. By monitoring SEP and MEP, the neurophysiological conditions were assessed for spinal cord injury. RESULTS: The total effective rate was 56.7% (17/30), 66.7% (20/30) and 90.0% (27/30) in the exercise therapy group, the eye acupuncture group and the combined treatment group, respectively. The total effective rate in the combined treatment group was higher than those in the other two groups (P<0.05). Compared with those before treatment, the scores of motor function, light tough sensation and pinprick sensation were all increased after treatment in three groups (P<0.05), MBI score was increased in both the exercise therapy group and the combined treatment group (P<0.05), and the latency of SEP (N11, N20, N23, P38) and the Cortical (hand region), Csp, Cortical (leg region) and Lsp of MEP were all shortened in the three groups separately (P<0.05). After treatment, compared with the exercise therapy group, the score of motor function was increased (P<0.05), MBI score decreased (P<0.05) and MEP latency shortened (P<0.05) in the eye acupuncture group. After treatment, compared with the exercise therapy group and the eye acupuncture group, the scores of motor function, light touch sensation and pinprick sensation, as well as MBI score were all increased (P<0.05), and the latency of SEP (N11,N20,N23,P38) and MEP shortened (P<0.05) in the combined treatment group. CONCLUSION: In treatment of incomplete spinal cord injury, eye acupuncture combined with exercise therapy can significantly increase the excitability of sensory and motor nerve conduction in the spinal cord and cerebral cortex of patients, effectively promote the recovery of patients' motor and sensory function and improve the activities of daily living.

Programmed intermittent epidural bolus in parturients: A meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the efficacy and safety of programmed intermittent epidural bolus (PIEB) in parturients. METHODS: The PubMed, Embase, and the Cochrane Library (from inception to July 2021) were searched for identification of randomized placebo-controlled trials in which PIEB was applied in parturients. The outcomes were the effect of analgesia, satisfaction score, mode of delivery, duration of labor, neonatal condition, and adverse events. The pooled odds ratios (OR), weighted mean difference (WMD), and 95% confidence intervals (CIs) were calculated using random- and fixed-effects models. RESULTS: PIEB was found to be associated with decreased total consumption of ropivacaine (WMD = -15.83, 95% CI: -19.06 to -12.60, P < .00001; I2 = 61%; P for heterogeneity = .04), total consumption of sufentanil (WMD = -4.93, 95% CI: -6.87 to 2.98, P < .00001; I2 = 68%; P for heterogeneity = .05), numbers of patients who require patient-controlled epidural analgesia bolus (OR = 0.27, 95% CI: 0.14-0.51, P < .0001; I2 = 65%; P for heterogeneity = .01), the number of attempts (WMD = -4.12, 95% CI: -7.21 to -1.04, P = .009; I2 = 100%; P for heterogeneity < .00001), rate of breakthrough pain (OR = 0.47, 95% CI: 0.28-0.80, P = .005; I2 = 47%; P for heterogeneity = .09). Eight studies focus on the duration of analgesia. After by meta-analysis, we found that the pain visual analogue scale (VAS) score at 30 minutes, 2 hours, 4 hours, and 5 hours in PIEB group was significantly lower when compared with control group, (WMD = -0.15, 95% CI: -0.26 to -0.04, P = .006; I2 = 0%; P for heterogeneity = .64), (WMD = -0.79, 95% CI: -1.32 to 0.25, P = .004; I2 = 97%; P for heterogeneity < .00001), (WMD = -1.00, 95% CI: -1.08 to -0.91, P < .00001; I2 = 0%; P for heterogeneity = .67), (WMD = -1.81, 95% CI: -3.23 to -0.39, P = .01; I2 = 98%; P for heterogeneity < .00001), respectively. Nineteen studies discussed the mode of delivery between 2 groups. The results suggest that the rate of normal delivery is significantly higher in PIEB group compared with control group (OR = 1.37, 95% CI: 1.08-1.75, P = .01). The time of first and second stage of labor are significantly shorter in PIEB group compared with control group, the result is (WMD = -10.52, 95% CI: -14.74 to 4.76, P < .00001; I2 = 0%; P for heterogeneity = .86), (WMD = -1.48, 95% CI: -2.26 to -0.69, P = .0002; I2 = 35%; P for heterogeneity = .10), respectively. Thirteen studies concerned the satisfaction score of patients. The satisfaction score of patients in the PIEB group was significantly higher when compared with control group (WMD = 0.91, 95% CI: 0.42-1.39, P = .0003; I2 = 98%; P for heterogeneity < .00001). The Apgar score at 1, 5 minutes in PIEB group are significantly higher (WMD = 0.07, 95% CI: 0.02-0.13 P = .007; I2 = 55%; P for heterogeneity = .04), (WMD = -0.08, 95% CI: -0.12 to -0.05, P < .00001; I2 = 21%; P for heterogeneity = .27), respectively. CONCLUSIONS: PIEB is a good alternative for labor analgesia with better analgesic effect, maternal and infant outcome.

Clinical outcomes of individualized busulfan-dosing in hematopoietic stem cell transplantation in Chinese children undergoing with therapeutic drug monitoring.

To identify relationships between busulfan (Bu) exposure and outcomes of a cohort pediatric patients receiving hematopoietic stem cell transplantation (HSCT), along with a targeted busulfan-based conditioning regimen. We retrospectively evaluated targeted busulfan concentrations in 53 pediatric patients (age 0.4-16 years) who received busulfan 4 times daily according to recommended weight-based doses in a single-center analysis between 2018 and 2020. In this trial, individual busulfan pharmacokinetics were performed following dose 5 of the conditioning regimen. Twenty four of 53 patients (45.3%) studies did not require dose adjustments. Equal number of patients (24/53) required one dose adjustments while two-dose adjustment applied for 5 of 53 (9.4%). Twenty-one percent of the patients exhibited ll-lV aGVHD. The incidence of veno-occlusive disease (VOD) was in 3.8% of the 53 patients, while incidence of hemorrhagic cystitis (II-III) reached to 9.7%. Engraftment was successful in 98% of the 53 patients with relapse in 2% of cases. The probability of overall survival and disease-free survival at day 100 was 96% and 94%, respectively. In conclusion, therapeutic drug monitoring (TDM) and individualization of Bu dosage are essential to improve the efficacy and safety of busulfan-based regimen in Chinese pediatric HSCT recipients.

The novel HLA-B*35:501 allele, identified by sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*35:501 differs from HLA-B*35:02:01:01 by three nucleotides in exon 2.

[Establishment of an Animal Model of Vesicoureteral Reflux Renal Injury through Partial Bladder Outlet Obstruction].

OBJECTIVE: To establish an animal model of reflux renal damage through bladder outlet obstruction. METHODS: Sixty male C57BL/6 mice aged 6-8 weeks were randomly assigned to a control group, a sham operation group, and a partial bladder outlet obstruction (PBOO) group, with 20 mice in each group. Laparotomy were performed on the PBOO mice under anesthesia in order to separate the bladder necks and to perform guided partial ligation of the bladder neck with a metal rod of 0.3 mm diameter. Mice in the sham operation group had laparotomy and had their bladder necks separated without ligation. The control group did not receive any treatment. 7 days after the surgery, 12 surviving mice were randomly selected from each group to observe the general changes of the bladder, ureter, renal pelvis and kidney. Retrograde urography was performed through the bladder. Kidney tissues were extracted for histopathological analysis. The expression levels of Vimentin, proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were examined with Western blot, immunohistochemistry and immunofluorescence staining tests, respectively. RESULTS: Compared with the control and sham operation group, the bladder, ureter, and renal pelvis of the mice in the PBOO group were significantly enlarged, vesicoureteral reflux was more obvious, the kidney volume and mass increased ( P<0.001), and renal parenchyma became thinner ( P<0.000 1). Histopathological staining showed glomerular atrophy, renal tubule expansion, tubulointerstitial inflammatory cell infiltration, glomerular basement membrane hyperplasia and obvious interstitial fibrosis. Western blot, immunofluorescence and immunohistochemistry staining showed that the expression levels of Vimentin, PCNA and α-SMA in kidney tissue were elevated ( P<0.000 1). CONCLUSION: After PBOO, the bladder, ureter, and kidney of the mice showed obvious morphological alteration and presented reflux renal fibrosis-like damage. This can be used as an animal model to study the pathological alteration mechanism and therapeutic measures of renal fibrosis caused by bladder outlet obstruction.

MiR-29a-3p Enhances the Viability of Rat Neuronal Cells that Injured by Oxygen-Glucose Deprivation/Reoxygenation Treatment Through Targeting TNFRSF1A and Regulating NF-κB Signaling Pathway.

OBJECTIVE: We attempt to investigate the role of TNFRSF1A and its underlying mechanism in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in rat pheochromocytoma PC12 cells. METHODS: Public datasets GSE61616 and GSE106680 were downloaded from GEO database. PC12 cells were used to construct OGD/R models. QRT-PCR and western blot were implemented to test the relative mRNA and protein levels, respectively. The miRNA online prediction website TargetScan was used to predict TNFRSF1A upstream regulated miRNAs, which were then confirmed by luciferase reporter assay. The changes in cell viability and apoptosis were evaluated using cell counting kit 8 (CCK-8), lactose dehydrogenase (LDH), and flow cytometry assays. RESULTS: Bioinformatics analysis demonstrated that the expression of TNFRSF1A was upregulated in CI/RI and middle cerebral artery occlusion models compared with control, respectively. And a significant upregulation was also observed in OGD/R-damaged PC12 cells. Depletion of TNFRSF1A can notably enhance the cells proliferation after OGD/R treatment, while enlargement of TNFRSF1A presented the opposite outcomes. Moreover, miR-29a-3p was shown to be the upstream regulatory miRNA of TNFRSF1A. The levels of TNFRSF1A were inversely mediated by miR-29a-3p. Overexpression of miR-29a-3p can raise the cell viability, decrease the LDH activity, and reduce the apoptotic ratio in OGD/R-treated cells. Besides, TNFRSF1A can attenuate the protective effect of miR-29a-3p on OGD/R-treated cells. Furthermore, miR-29a-3p mimic inhibited, while overexpression of TNFRSF1A promoted the activation of NF-κB signaling pathway, and TNFRSF1A can attenuate the suppressive effect of miR-29a-3p on the NF-κB pathway. CONCLUSION: Our research illustrated that the potential regulatory role of miR-29a-3p/TNFRSF1A axis in neurons cells suffered from OGD/R, and their effects on NF-κB signaling pathway, providing a possible bio-target for protecting cells from OGD/R damage .

Migrant adolescents' behavioral problems compared to host adolescents and adolescents in their region of origin: a longitudinal study.

BACKGROUND: Since the 1990s, families from the ecologically hostile mountainous southern areas of Ningxia Province, China, have been migrating to the northern areas of the province. This study compared the prevalence of behavioral problems among migrant adolescents to those among host adolescents (adolescents from the northern areas) and adolescents in the region of origin (adolescents from the southern areas), to determine whether ecological migration is related to adolescent behavioral problems, and possible changes in such problems over time. METHODS: We used the Children and Adolescents Ecological Migration Survey on Mental Health, administered to 4805 students aged 12-16 years and their parents between 2012 and 2014 (W1), of whom 1753 students and their parents completed the follow-up between 2014 and 2017 (W2). Parents answered questions related to adolescent behavioral problems, main source of family income, parents' desire to reverse migrate, improved standard of living, and parents' educational attainment, while children completed the Eysenck Personality Questionnaire and a classroom environment questionnaire. RESULTS: The prevalence of behavioral problems among the migrant adolescents (28.04%) was significantly higher than among host adolescents (21.59%) or adolescents in the region of origin (24.37%; p < 0.001) at W1. After adjusting for gender and age, parents' work outside the home was the main source of family income (OR = 1.42, 95% CI = 1.13-1.78), and adolescents' learning burden (OR = 1.04, 95% CI = 1.01-1.06) in school negatively influenced behavioral problems. Strong student-teacher relationships (OR = 0.97,95% CI = 0.94-0.99) and parents who had no intention to move back to the original residence (OR = 0.70, 95% CI = 0.52-0.94) exerted a protective effect at W1; at W2, a protective effect was associated with improved living conditions (OR = 0.39-0.55, 95% CI = 0.25-0.84). The extent of behavioral problems among migrant adolescents significantly decreased after two years. CONCLUSION: Ecological migration will increase children's behavioral problems in the early stage, with various factors influencing the extent of these problems.

miR-339 Promotes Hypoxia-Induced Neuronal Apoptosis and Impairs Cell Viability by Targeting FGF9/CACNG2 and Mediating MAPK Pathway in Ischemic Stroke.

Ischemic stroke (IS) is a common cerebrovascular disease characterized by insufficient blood blow to the brain and the second leading cause of death as well as disability worldwide. Recent literatures have indicated that abnormal expression of miR-339 is closely related to IS. In this study, we attempted to assess the biological function of miR-339 and its underlying mechanism in IS. By accessing the GEO repository, the expression of miR-339, FGF9, and CACNG2 in middle cerebral artery occlusion (MCAO) and non-MCAO was evaluated. PC12 cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment were prepared to mimic in vitro the IS model. The levels of miR-339, FGF9, CACNG2, and MAPK-related markers were quantitatively measured by qRT-PCR and Western blot. CCK-8 and flow cytometry analyses were performed to examine cell viability and apoptosis, respectively. IS-related potential pathways were identified using KEGG enrichment analysis and GO annotations. Bioinformatics analysis and dual-luciferase reporter assay were used to predict and verify the possible target of miR-339. Our results showed that miR-339 expression was significantly increased in MCAO and OGD/R-treated PC12 cells. Overexpression of miR-339 inhibited cell viability of PC12 cells subjected to OGD/R treatment. FGF9 and CACMG2 are direct targets of miR-339 and can reverse the aggressive effect of miR-339 on the proliferation and apoptosis of OGD/R-treated PC12 cells. Moreover, miR-339 mediated the activation of the MAPK pathway, which was inhibited by the FGF9/CACNG2 axis in PC12 cells treated by OGD/R stimulation. In summary, these findings suggested that miR-339 might act as a disruptive molecule to accelerate the IS progression via targeting the FGF9/CACNG2 axis and mediating the MAPK pathway.

Serum Tumor Marker Carbohydrate Antigen 125 Levels and Carotid Atherosclerosis in Patients with Coronary Artery Disease.

OBJECTIVE: We assessed the correlation between serum carbohydrate antigen 125 (CA125) and carotid intima-media thickness (cIMT) in patients with coronary artery disease (CAD). METHODS: We collected 518 CAD patients from the cardiovascular disease center in our hospital, and all cIMT values were measured in patients with CAD. RESULTS: The serum CA125 concentrations were found to be increased in CAD patients with early carotid atherosclerosis compared with patients without early carotid atherosclerosis (20.1±7.72 vs. 17.7±6.41 U/mL, p<0.001). The cIMT values were increased in patients with higher serum CA-125 levels than those with lower serum CA-125 concentrations (1.16±0.32 vs. 0.98±0.29 mm, p<0.001). There was a positive correlation between serum CA125 and cIMT in CAD patients (r=0.262, p<0.001). Moreover, the serum CA125 concentrations also were positively correlated with cIMT in subjects with early carotid atherosclerosis and without early carotid atherosclerosis (r=0.255, p<0.001; r=0.189, p=0.002). We found that serum CA-125 concentrations were independently correlated with cIMT (beta = 0.293, p<0.001) in multiple linear regression analysis. CONCLUSIONS: We found that serum CA125 concentrations were positively correlated with cIMT in CAD patients, serum CA125 might be a potential biochemical marker for the estimation of atherosclerosis in patients with CAD.

Association of GCKR rs780094 polymorphism with circulating lipid levels in type 2 diabetes and hyperuricemia in Uygur Chinese.

To investigate the relationship between a GCKR rs780094 polymorphism and lipid profiles in the Xinjiang Uygur population in China. 980 type 2 diabetes mellitus (T2DM) patients, 1017 hyperuricemia (HUA) and 1185 healthy controls were included in this study. After genotyping of rs780094 by Sequenom Mass ARRAY system, chi-square test and logistic regression analysis were used for association analysis as well as a genotype-phenotype analysis. We found that the serum concentration of TC (P<0.001) was significantly higher and HDL-C (P<0.001) was lower in T2DM than in control participants. Subjects with HUA had a significantly higher TG (P=0.003) and lower HDL-C (P<0.001) than control participants. Additionally, under the recessive model, rs780094 was shown to be associated with the risk of HUA (P=0.015, OR=1.311), particularly in males (P=0.047, OR=1.330). Subsequent interaction analysis between rs780094 and lipid parameters showed that the TG level was positively correlated with HUA in the rs780094- AA+AG carriers (P=0.005). The TC concentrations showed to be associated with T2DM in the rs780094- AA+AG carriers (P<0.001). The association between lipid parameters and gender showed that significantly higher TG levels (P<0.001) and lower HDL-C levels (P<0.001) were observed in female HUA. Higher LDL-C levels were found in male HUA (P=0.015). Moreover, statistically higher TC levels and lower HDL-C levels were found both in male and female T2DM cases (TC: male: P<0.001, female: P=0.014. HDL-C: male: P<0.001, female: P<0.001.).To conclude, our results demonstrated that different genotypes of rs780094 had different effects on blood lipids in HUA and T2DM patients in a Uygur population. Gender was also one of the factors influencing blood lipid levels.

Trends and relationship between antimicrobial resistance and antibiotic use in Xinjiang Uyghur Autonomous Region, China: Based on a 3 year surveillance data, 2014-2016.

PURPOSES: The objective of the study was to identify the trends and relations between antimicrobial resistance (AMR) and antibiotic use in the Xinjiang Uyghur Autonomous Region in Western China from 2014 to 2016. METHODS: A retrospective, descriptive analysis of AMR prevalence, and trends and relations between AMR and antibiotic use during the 3-year period was performed. RESULTS: Third-generation cephalosporin-resistant Escherichia coli was the most prevalent resistant pathogen in terms of both resistance density and resistance proportion. A significant correlation was found between resistance density of third-generation cephalosporin-resistant Klebsiella pneumoniae and the use of beta-lactam-beta-lactamase inhibitor combinations (cc=0.63, p=0.03), quinolones (cc=0.60, p=0.04), and carbapenems (cc=0.76, p=0.004), among which only beta-lactam-beta-lactamase inhibitor combinations showed a significant correlation with third-generation cephalosporin-resistant E. coli (cc=0.63, p=0.03). For carbapenem-resistant Pseudomonas aeruginosa, not only carbapenem use (cc=0.65, p=0.02) but also penicillin (cc=0.76, p=0.004) and quinolone (cc=0.69, p=0.01) use showed significant correlation. A strong correlation was observed between the resistant proportion of third-generation cephalosporin-resistant E. coli and only the use of beta-lactam-beta-lactamase inhibitor combinations (cc=0.61, p=0.03). CONCLUSION: The association between antibiotic use and AMR, especially the implication of the difference in resistance density and resistance proportion, is crucial for local physicians and decision-makers to better use of antibiotics and allocate healthcare resources more effectively, as well as to better implement antimicrobial stewardship and effective infection control strategies.

Multivariate model for predicting semen cryopreservation outcomes in a human sperm bank.

Semen cryopreservation is widely used in assisted reproductive technologies, but it reduces sperm quality dramatically. The aim of this study was to develop a model using basal semen quality to predict the outcome of postthaw semen parameters and improve the efficiency of cryopreservation in a human sperm bank. Basal semen parameters of 180 samples were evaluated in the first stage, and a multiple logistic regression analysis involving a backward elimination selection procedure was applied to select independent predictors. After a comprehensive analysis of all results, we developed a new model to assess the freezability of sperm. Progressive motility (PR), straight-line velocity (VSL) and average path velocity (VAP) were included in our model. A greater area under the receiver operating characteristic curve was obtained in our model when compared with other indicators. In the second stage of our study, samples that satisfied the new model were selected to undergo freeze-thawing. Compared with the first stage, the rate of good freezability was increased significantly (94% vs 67%, P = 0.003). By determining basal semen quality, we have developed a new model to improve the efficiency of cryopreservation in a human sperm bank.

Association Between KCNQ1 Genetic Variants and Type 2 Diabetes in the Uyghur Population.

OBJECTIVE: To investigate the association between KCNQ1 gene polymorphisms and type 2 diabetes (T2D) in an admixed ethnic minority, Uyghur population, living in the Northwest region of China. MATERIALS AND METHODS: We genotyped three tagging single-nucleotide polymorphisms rs2283171, rs11023485, and rs2283208 of the KCNQ1 gene in 1006 T2D participants and 1004 controls and conducted association analysis. RESULTS: The frequencies of the AG and GG genotypes and the G allele of rs2283171 were higher in the control group (51.4%, 22%, and 47.7%, respectively) than in the case group (49%, 17.6%, and 42.1%, respectively). The minor G allele decreased the risk of T2D with a per-allele odds ratio of 0.79 (95% CI: 0.70-0.90) for the additive genetic model in univariate analysis (p = 0.0001). After adjustment for the covariates of age, gender, smoking, alcohol use, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), triglyceride (TG), and total cholesterol (TC), the diabetic protective effect of the rs2283171-G allele remained. No difference was observed in the frequency distributions of the rs11023485 and rs2283208 genotypes between the two groups. CONCLUSION: We identified a novel association between rs2283171 of KCNQ1 and T2D in the Uyghur population. Further association and functional studies are required to identify the causal functional variant that is in linkage disequilibrium with this polymorphism.

[Diagnostic value of R-banding Technique, Dual-color Fluore- scence In Situ Hybridization and Quantitative Real-time PCR in Acute Promyelocytic Leukemia].

OBJECTIVE: To explore the diagnostic value of R-banding technique (RT), dual-color fluorescence in situ hybridization (D-FISH) and quantitative real-time PCR (RT-PCR) for acute promyelocytic leukemia. METHODS: The cytogenetic characteristics and PML/RARα fusion gene in 340 patients with suspectable APL were analyzed by using 3 detection methods. MICM (morphology, immunology, cytogenetic and molecular biology) was used as diagnostic standard of APL, and the diagnostic value of RT, D-FISH and RT-PCR was evaluated by comparing the detection results of RT, D-FISH and RT-PCR as well as their combination. RESULTS: For the diagnosis of APL, the sensitivity of RT, D-FISH and RT-PCR was 81.3% (78/96), 95.0% (91/96) and 96.9% (93/96) respectively. RT failed to detect 18 cases, the results of D-FISH showed 5 cases with false positive and 2 cases with false negative, the RT-PCR showed 4 cases with false positive, 3 cases with false negative. The sensitivity and specificity of combined detection of 3 methods were 99.97% and 100% respectively. CONCLUSION: The 3 detection methods alone all have certain defects for diagnosis of APL, but their combined detection is helpful to improve the definitive diagnostic rate and can decrease misdiagnosis rate and missed diagnostic rate.

Assessment of the Relationship Between Red Cell Distribution Width and Multiple Sclerosis.

Accumulating data have shown that immune and inflammatory factors are involved in the pathogenesis of multiple sclerosis (MS), and loss of polyunsaturated fatty acids from plasma and blood cell membranes has also been reported in patients with MS, contributing to the variation of erythrocyte deformability. Therefore, the aim of this investigation was to assess the association between red blood cell distribution width (RDW) and MS. A total of 109 patients with MS and 130 healthy individuals were enrolled into the study, and MS patients receiving treatment of subcutaneous recombinant Rebif (IFN-ß1a) were followed retrospectively. Complete blood cell counts and Expanded Disability Status Scale (EDSS) score were evaluated in patients with MS before and after treatment. RDW values were significantly higher in patients with MS compared with the controls (13.6 ± 0.89 vs 12.8 ± 0.38, P < 0.001); a positive correlation between RDW and EDSS score was observed in patients with MS (r = 0.789, P < 0.001). Significant differences in the value of RDW and EDSS score were observed between treatment-naive patients and treated patients (13.6 ± 0.95 vs 12.7 ± 0.44, P < 0.001; 3.6 ± 1.39 vs 1.5 ± 0.60, P < 0.001). RDW was associated independently with MS in logistic regression analysis (odds ratio = 7.007; 95% confidence interval [CI] 3.461-14.187; P < 0.001), and receiver-operating characteristics (ROC) analysis showed that a RDW measurement >13.11% evaluated MS with a sensitivity of 70.0% and a specificity of 84.7%, and the area under the ROC curve for RDW was calculated as 0.80 (95% CI 0.739-0.859, P < 0.001). The level of RDW was decreased in treatment responders with the reduction of EDSS score; a strong relationship was also observed in treatment responders between RDW and EDSS score (r = 0.733, P < 0.001), and covariance analysis indicated RDW values decreased significantly in treatment responders (P = 0.025). Our results suggest that elevated RDW values are associated with EDSS score in patients with MS, and the relationship is remarkably influenced by Rebif treatment; RDW may be a useful marker to estimate disability status and treatment effectiveness in patients with MS.

Association between Serum Fructosamine and Kidney Function in Nondiabetic Individuals without Chronic Kidney Disease.

BACKGROUND: Serum fructosamine (SF) has been considered to be an indicator that estimates glycemic control in patients with diabetes mellitus (DM). There is increasing evidence that SF concentration and oxidative stress are significantly elevated in patients with chronic kidney disease (CKD). However, the data about SF and its association with kidney function are lacking in nondiabetic individuals without CKD. We included 1891 nondiabetic individuals who had not been diagnosed with CKD to determine the association between SF and kidney function. MATERIAL AND METHODS: We conducted a retrospective analysis on the basis of the biochemistry database in nondiabetic individuals without CKD. RESULTS: When eligible participants were stratified in accordance with SF quartiles, from the bottom to the top quartile of SF, a significant decrease of estimated glomerular filtration rate (GFR) was observed in baseline data. SF concentration was negatively associated with estimated GFR (r=-0.066, P=0.004) in the Pearson correlation analysis. Estimated GFR was associated with SF levels independently of glucose (GLU), total cholesterol (TC), triglyceride (TG), and total protein (TP) in multivariable logistic regression analysis (OR=0.984; CI 95% 0.977-0.991; P<0.001). CONCLUSIONS: We suggest that mild elevation of SF concentration is associated with estimated GFR in nondiabetic individuals without CKD. These findings indicate that SF may underlie CKD in nondiabetic individuals.