Genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangzhou, China.

BACKGROUND: G6PD deficiency is a common inherited disorder worldwide and has a higher incidence rate in southern China. Many variants of G6PD result from point mutations in the G6PD gene, leading to decreased enzyme activity. This study aimed to analyse the genotypic and phenotypic characteristics of G6PD deficiency in Guangzhou, China. METHODS: In this study, a total of 20,208 unrelated participants were screened from 2020 to 2022. G6PD deficiency was further analysed by quantitative enzymatic assay and G6PD mutation analysis. The unidentified genotype of the participants was further ascertained by direct DNA sequencing. RESULTS: A total of 12 G6PD mutations were identified. Canton (c.1376G>T) and Kaiping (c.1388G>A) were the most common variants, and different mutations led to varying levels of G6PD enzyme activity. Comparing the enzyme activities of the 6 missense mutations between the sexes, we found significant differences (P < 0.05) in the enzyme activities of both male hemizygotes and female heterozygotes. Two previously unreported mutations (c.1438A>T and c.946G>A) were identified. CONCLUSIONS: This study provided detailed genotypes of G6PD deficiency in Guangzhou, which could be valuable for diagnosing and researching G6PD deficiency in this area.

Space-time mapping on the sagittal axis in congenital blindness.

Previous evolutionary perspectives proposed that the space-time mapping on the sagittal axis originates from visuo-locomotion coupling when walking/running forward. Accordingly, the congenitally blind could not have developed a sagittal mental timeline if the latter depends on such a visuo-locomotion coupling. However, this conclusion was reached in only a single empirical study (Rinaldi et al. in J Exp Psychol General 147:444-450, 2018), and its theoretical underpinnings are not entirely convincing as locally static and continuous auditory input undergoes a relatively similar change as function of self-locomotion, but this type of sensory-locomotion coupling is spared even in congenital blindness. Therefore, the present study systematically explored whether the congenitally blind show space-time mappings on the sagittal axis using different paradigms in three experiments. In Experiment 1, using a typical implicit RT task, the congenitally blind showed the same preferred space-time mapping in the sagittal dimension as normally sighted participants did. In Experiment 2, this space-time mapping occurred even automatically when temporal relations were task-irrelevant in a naming task. In Experiment 3, in an explicit space-time mapping task, the congenitally blind were more likely to locate the past behind and the future in front of their bodies. Moreover, most blind participants used spatial metaphors for their space-time mapping on the sagittal axis. These results supported the conclusion that the congenitally blind have a sagittal mental timeline, and that their sensory-locomotion coupling experience was either more similar to that of sighted participants or not critical for the space-time mapping. The present study, thus, also helps to clarify the origin of the sagittal mental timeline.

Does walking/running experience shape the sagittal mental time line?

A growing body of evidence suggested that time could be separately represented either on the lateral or sagittal axis. And the lateral mental time line has an origin associated with sensorimotor experience, e.g., reading/writing. However, it is still not clear whether the sagittal mental time line also originates from sensorimotor experience, e.g., walking/running. To address this question, we examined how the movement experience affected the space-time mapping on the lateral and sagittal axes using the virtual reality technique in two experiments. The results showed that the virtual movement experience had significant effects on the space-time mapping on the lateral axis (Experiment 1), but not on the sagittal axis (Experiment 2). This finding supported that the space-time mapping on the lateral axis does originate from sensorimotor experience, while the space-time mapping on the sagittal axis more likely originates from spatial metaphors in languages or other cultural experiences.

Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring.

We describe here a minimally invasive glucose biosensor based on a microneedle array electrode fabricated from an epoxy-based negative photoresist (SU8 50) and designed for continuous measurement in the dermal compartment with minimal pain. These minimally invasive, continuous monitoring sensor devices (MICoMS) were produced by casting the structures in SU8 50, crosslinking and then metallising them with platinum or silver to obtain the working and reference electrodes, respectively. The metallised microneedle array electrodes were subsequently functionalised by entrapping glucose oxidase in electropolymerised polyphenol (PP) film. Sensor performance in vitro showed that glucose concentrations down to 0.5 mM could be measured with a response times (T90) of 15 s. The effect of sterilisation by Co60 irradiation was evaluated. In preparation for further clinical studies, these sensors were tested in vivo in a healthy volunteer for a period of 3-6 h. The sensor currents were compared against point measurements obtained with a commercial capillary blood glucometer. The epoxy MICoMS devices showed currents values that could be correlated with these. Graphical Abstract Microneedle arrays for continuous glucose monitoring in dermal interstitial fluid.

Exploring Appropriate Reference Intervals and Clinical Decision Limits for Glucose-6-Phosphate Dehydrogenase Activity in Individuals From Guangzhou, China.

Background: Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China. Methods: We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups. Results: In Guangzhou, the RIs for the G6PD activities were 11.20-20.04 U/g Hb in male and 12.29-23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: <10% of the NMM, female: <30% of the NMM), medium hemolysis-risk CDLs (male: 10%-45% of the NMM, female: 30%-79% of the NMM), and low hemolysis-risk CDLs (male: ≥ 45% of the NMM, female: ≥ 79% of the NMM). Conclusions: Collectively, our findings contribute to a more accurate evaluation of G6PD-activity levels within the local population and provide valuable insights for clinical decision-making. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes.

PVT1 promotes resistance to 5-FU in colon cancer via the miR-486-5p/CDK4 axis.

Drug resistance in tumors is a major issue, limiting the curative efficacy of currently available cancer chemotherapeutics. 5-Fluorouracil (5-FU) is a commonly applied therapeutic drug in colon cancer patient regimens; however, the majority of patients develop resistance to 5-FU in the later stages of the disease, rendering this chemotherapy ineffective. Drug resistance is the main factor underlying the poor prognosis of patients with colon cancer. In recent years, a number of studies have confirmed that long non-coding (lnc)RNAs may play vital roles in tumor resistance. In the present study, the Gene Expression Omnibus (GEO) and lncRNADisease2 databases were screened for colon cancer-associated expression patterns of lncRNA plasmacytoma variant translocation 1 (PVT1). Subsequently, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in PVT1 expression in resistant cell lines, and a Cell Counting Kit-8 (CCK-8) assay kit was used to assess the effects of PVT1 knockdown on the half maximal inhibitory concentrations of parental and 5-FU-resistant HCT116 cells. Subsequently, CCK-8, clone formation, and flow cytometric assays were performed to investigate the effects of PVT1 knockdown on the sensitivity of HCT116-5FU-resistant cells to 5-FU. Dual-luciferase assay, RNA pull-down and RNA immunoprecipitation assays verified the interactive regulation of PVT1, miR-486-5p and cyclin dependent kinase 4 (CDK4). PVT1 was highly expressed in HCT116-5FU-resistant cells, as compared to its expression in HCT116 parental cells. PVT1 knockdown significantly reduced the resistance of HCT116-5FU-resistant cells to 5-FU. In addition, PVT1 upregulated CDK4 expression by adsorbing miR-486-5p; however, CDK4 overexpression restored the effects of miR-486-5p inhibition on HCT116-5-FU-resistant cells. Additionally, PVT1 knockdown partially rescued CDK4 overexpression in HCT116-5-FU-resistant cells. On the whole, the findings of the present study suggest that PVT1 promotes the resistance of colon cancer cells to 5-FU by regulating the miR-486-5p/CDK4 axis. Therefore, PVT1 may prove to be a potential target for counteracting resistance to 5-FU in colon cancer therapy.

Value of Transabdominal Combined Transvaginal Color Doppler Ultrasonography in the Distinguish between Uterine Adenomyoma and Uterine Fibroids.

Objective: To investigate the value of transabdominal combined transvaginal color Doppler ultrasonography in the diagnosis of uterine adenomyoma. Methods: A total of 80 patients with suspected uterine adenomyoma in our hospital from January 2019 to December 2021 were selected as the study subjects. All of them were examined by transabdominal color Doppler ultrasound (TA-CDUS) and transvaginal color Doppler ultrasound (TV-CDUS), and the postoperative pathological examination results were taken as the gold standard to analyze the diagnostic efficacy of different examination methods for uterine adenomyoma. Results: By postoperative pathological biopsy, 46 cases (57.50%) were diagnosed as positive and 34 cases (42.50%) were diagnosed as negative, including 29 cases of uterine adenomyoma and 5 other cases. The sensitivity, accuracy, and negative predictive value of TA-CDUS combined with TV-CDUS in the diagnosis of adenomyoma were higher than those of TA-CDUS (P < 0.05), and the Kappa value between TA-CDUS and pathological diagnosis was 0.923, which was higher than the 0.615 between TV-CDUS and pathological diagnosis. TA-CDUS combined with TV-CDUS showed that there were significant differences in the distribution of Adier blood flow grades between patients with uterine adenomyoma and uterine fibroids (P < 0.05), and the Adier blood flow grades of patients with uterine adenomyoma were mainly grade 0 and grade I; and the resistance index (RI), peak systolic velocity (Vs), and pulsatile index (PI) in patients with uterine adenomyoma were higher than those in patients with uterine fibroids (P < 0.05). Conclusion: Compared with TA-CDUS, TA-CDUS combined with TV-CDUS is more sensitive and accurate in the diagnosis of uterine adenomyoma and has a good consistency with pathological diagnosis results. Attention should be paid to the blood flow parameter values in the differential diagnosis of uterine fibroids.

[Modeling of p53 signaling pathway based on S-system equations].

p53, as a transcription factor, is an important tumor suppressor gene and plays the key role in the p53-dependent gene regulatory network. Therefore, it is important to understand its biological function at the level of the whole system. In this paper, based on KEGG database and related literatures in English and Chinese, the interaction mode and quantitative relationship of the related molecules involved in p53 signaling pathway were extracted. By using S-system equations and 'Simulink' toolbox of Matlab7.0, a dynamic model of p53 signaling pathway was developed, and the dynamic regulatory characteristics of p53 signaling pathway were analyzed on model simulation. The results were in accord with the literatures and could reflect quantitatively the complex regulatory relationship between the interacting molecules involved in p53 signaling pathway. In addition, model simulation helped us find and identify the key molecules in this signaling pathway. Thus, this model can be used as a basis for the follow-up study of the relationship by precise and quantitative assessment.

Up-Regulation of MicroRNA-21 Indicates Poor Prognosis and Promotes Cell Proliferation in Esophageal Squamous Cell Carcinoma via Upregulation of lncRNA SNHG1.

INTRODUCTION: MicroRNA-21 (miRNA-21) and lncRNA SNHG1 (small nucleolar RNA host gene 1) are known to be aberrantly upregulated and promote tumor progression in various cancers. Nevertheless, very few studies have determined the roles of tissue and circulating miRNA-21 and SNHG1 in ESCC patients. Particularly, knowledge about the characteristics of miRNA-21 and SNHG1 expression and their correlations with survival rates, as well as their interaction with each other remains inadequate in ESCC. METHODS: Thse expression level of miRNA-21 and SNHG1 of tissues, serum and cell lines were detected by qRT-PCR, and the characteristics of their expression and clinicopathology were analyzed. Then, the diagnostic and prognosis value of serum and tissue miRNA-21 and SNHG1 were evaluated, respectively. In addition, the interaction with each other between miRNA-21 and SNHG1, as well as the effect on ESCC cell proliferation were further clarified. RESULTS: The expression level of miRNA-21 and SNHG1 are significantly upregulated in tissues, serum and cell lines of ESCC, and tissue miRNA-21 and SNHG1 significantly correlates with lymph node metastasis, TNM stage, tumor size, and poor overall survival in ESCC patients. The receiver operating characteristic (ROC) curves show that areas under the ROC curve (AUC) for serum miRNA-21 and SNHG1 are 0.928 and 0.850, respectively. Pearson correlation coefficient indicated that the expression levels of miRNA-21 and SNHG1 in frozen cancerous tissues are significantly associated with their respective serum levels. Further, Cox univariate and multivariate analyses reveal that miRNA-21 and SNHG1 are independent prognostic factors for overall survival (OS) and disease-free survival (DFS) in ESCC patients. In addition, our in vitro data revealed a novel regulatory pathway, in which miRNA-21 is probably a unidirectional upstream positive regulator of SNHG1 in ESCC cells, and the interaction between miRNA-21 and SNHG1 plays an important role in the proliferation of ESCC cells. DISCUSSION: In summary, our data show that SNHG1 may be a novel downstream target of miRNA-21 and not vice versa in ESCC cells and contributes significantly toward the proliferation of ESCC cells. These findings suggest that miRNA-21 and SNHG1 may serve as potential diagnostic, prognostic biomarkers and therapeutic targets for ESCC patients.

Hospitalization costs of treating colorectal cancer in China: A retrospective analysis.

BACKGROUND: The objective of this study was to explore the influence factors of hospitalization costs of treating colorectal cancer in China. And the study provides new estimates on hospitalization costs and length of hospital stay for patients with colorectal cancer in China. METHODS: Data for inpatient hospitalization associated with colorectal cancer were obtained from a 3-tier hospital in Guangdong Province and were analyzed post hoc. We conducted descriptive statistical methods, Wilcoxon rank-sum tests (for 2 groups) and the Kruskal-Wallis test (for more than 2 groups) to analyze the hospitalization costs of treating colorectal cancer. RESULTS: The analysis included 8021 patients (female: 40.54%; mean age; 61.80 ±â€Š13.28 years; male: 59.46%; mean age: 61.80 ±â€Š13.28 years). The overall mean length of hospital stay was 11.35 days. Over the 5 years, the mean length of hospital stay showed a small decrease from 12.22 days in 2012 to 10.69 days in 2016, while per-day costs showed a trend of increase between 2012 and 2015 (increase from < 1190.94 to < 1382.50). The mean length of hospital stay was statistically significant difference was found for sexes (P = .039) and insurance status (P < .001). The mean hospitalization costs were < 16,279.58. Mean hospitalization costs were different among the UEBMI, the URBMI and the Unspecified (< 17,114.58, < 15,555.05, and < 17,735.30, respectively; P < .001). CONCLUSION: The study showed that hospitalization costs increase were associated with a small decreasing length of hospital stay and increasing per-day hospitalization costs. Moreover, the proportion of the hospitalization costs reimbursed by insurances increased. For inpatients with UEBMI, it possibly lead to over treatment and the medical expense rise which result in medical resources waste and significant society costs. The rising hospitalization costs may lead to a remarkably increased financial burden in the future in China.

Breast cancer laterality and molecular subtype likely share a common risk factor.

BACKGROUND: To investigate the epidemiological features of breast cancer laterality and molecular subtypes in southern China. MATERIALS AND METHODS: A total of 2,049 cases who were diagnosed with unilateral breast cancer in the past 5 years were classified based on laterality and molecular subtypes. Molecular subtypes were defined in accordance with the 2013 St. Gallen recommendations. RESULTS: Breast cancer was more likely to be diagnosed in the left breast than in the right at a rate of around 5%. In the case of invasive carcinomas, the right breast was more commonly affected than the left in young (<40 years old) patients (left-to-right [L:R] ratio 0.80, 95% CI 0.65, 0.98), whereas the opposite trend was found in old (≥40 years old) patients (L:R ratio 1.06, 95% CI 1.02, 1.73). Except for invasive mucinous and invasive medullary breast cancers, the other histological types occurred more frequently on the left side than on the right. In situ cancer with a defined subtype was likely to be diagnosed as luminal B(HER-2+). Except for invasive medullary and invasive nonspecific cancers, other invasive carcinomas with a defined subtype were most likely to be diagnosed as luminal B(HER-2-). The age of ≥40 years was a risk factor for luminal B(HER-2+), and a significant correlation was present between the right breast and luminal B(HER-2+). CONCLUSION: We explored the risk factors of breast cancer laterality and various molecular subtypes and found that age may be a predictor of breast cancer laterality. We found that age and laterality are the probable risk factors of the luminal B(HER-2+) type of breast cancer. These results provide a basis for the epidemiological characterization of breast cancer.

Occurrence, fate, and mass balance of different classes of pharmaceuticals and personal care products in an anaerobic-anoxic-oxic wastewater treatment plant in Xiamen, China.

In this study, the occurrence and fate of 49 pharmaceuticals and personal care products (PPCPs) were investigated in an anaerobic-anoxic-oxic (A2/O) wastewater treatment plant (WWTP) for seven consecutive days using 24-h composite sampling technique. Special emphasis was placed to understand the distribution of PPCPs in dissolved and adsorbed phase, and to evaluate PPCP fate in different treatment units. Among the 49 PPCPs, 40 PPCPs in influent, 36 in effluent, 29 in sludge and 23 in suspended solids were detected at least once during sampling. Non-steroidal anti-inflammatory drugs (NSAIDs) and a stimulant were predominant PPCPs in influent whereas antibiotics were predominant in sludge, effluent and suspended solids. Removal efficiencies from the aqueous phase based on the dissolved PPCPs showed variable contribution in removing different PPCPs under screen and grit chamber, anaerobic treatment, anoxic treatment, oxic treatment and sedimentation-UV treatments, with the highest removal percentage by anaerobic process in terms of both individual and overall treatment. Mass load analysis showed that 352 g PPCPs enter the WWTP daily while 14.5 g and 58.1 g were discharged through effluent and excess sludge to the receiving sea water and soil applications, respectively. Mass balance analysis based on both aqueous and suspended PPCPs showed 280 g (79.4%) mass of influent PPCPs was lost along the wastewater treatment processes, mainly due to degradation/transformation.