Risk Factors Analysis and Pathogen Distribution of Urinary Tract Infection in Patients Undergoing Cutaneous Ureterostomy After Radical Cystectomy for Bladder Cancer.

BACKGROUND: Postoperative urinary tract infection is a common complication that not only significantly prolongs the hospital stay and amplifies the economic burden on patients, but also affects their quality of life and prognosis. This study aimed to investigate risk factors and distribution of pathogenic bacteria in urinary tract infections among bladder cancer patients who underwent cutaneous ureterostomy following radical cystectomy. METHODS: A total of 137 bladder cancer patients, who underwent cutaneous ureterostomy after radical cystectomy at our hospital from November 2018 to October 2022, were enrolled in this retrospective study. Univariate and multivariate logistic regression analyses were employed to investigate the risk factors associated with postoperative urinary tract infection and the distribution of pathogenic bacteria among the infected patients. RESULTS: The results of both univariate and multivariate analyses confirmed that age, proficiency in ostomy knowledge, frequency of ureteral stent tube replacement, ureteral stent tube dislodgement, urine immersion at the outer end of the ureteral stent tube, and the interval of ostomy bag replacement were independent risk factors for urinary tract infection after radical cystectomy and cutaneous ureterostomy in bladder cancer patients. A total of 55 pathogenic bacteria were isolated from 52 patients with infections. Predominantly, these were gram-negative bacteria (34 strains, 61.8%), with Proteus mirabilis having the highest proportion. CONCLUSION: Urinary tract infections after radical cystectomy and cutaneous ureterostomy predominantly involve gram-negative bacteria. This is correlated with factors such as the age of bladder cancer patients, the level of nursing education, the duration of ureteral stent tubes and ostomy bag usage, as well as issues related to impaired urine drainage.

Baseline serum uric acid level is associated with progression-free survival, disease control rate, and safety in postoperative patients with colorectal cancer treated by FOLFOX, FOLFIRI, or XELOX.

Background: High serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy. Patients and Methods: We conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center. Results: Data from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety. Conclusions: These findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.

Quantification of immunosuppressants from one 3.2 mm dried blood spot by a novel cold-induced phase separation based LC-MS/MS method.

Dried blood spots (DBS) have been regarded as a promising alternative for therapeutic drug monitoring (TDM) of immunosuppressants (ISDs) for over fifteen years. Nonetheless, there are still three main issues impeding its preference: (i) the requirement of relatively large disc; (ii) the controversial and intricate desorption approaches; (iii) the lack of feasible extraction strategies. For improvement, this work described a new LC-MS/MS method realizing quantification of four ISDs from one piece of 3.2 mm DBS. During sample pretreatment, a modified approach (infiltrating the DBS in pure water before adding acetonitrile and zinc sulfate as protein-precipitators) was developed to completely dissociate the targets from filter paper. Afterward, effective enrichment and purification of the targets were achieved by using cold-induced phase separation technique. Benefiting from these novelties, the method exhibited satisfying throughput (15 min for sample preparation), applicability (consuming only one 3.2 mm disc), reliability (82.3-107.8% for accuracy and <14.3% for precision) and sensitivity (lower limit of quantification of 0.5, 7.6, 0.7 and 0.8 ng mL-1 for tacrolimus, cyclosporine A, everolimus and sirolimus, respectively). Without hematocrit correction, the method showed favorable interchangeability to the certified whole blood method through analyzing 120 paired clinical samples. By taking ±20% of the mean as the limit of acceptance for cross validation, over 90% of the detection met the criterion. It can be expected the developed method is able to further promote the popularization of DBS-based TDM for ISDs in practice.

Cold-induced phase separation for the simple and reliable extraction of sex hormones for subsequent LC-MS/MS analysis.

Sex hormones, including androgens, estrogens, and progestogens, are important biomarkers for various diseases. Quantification of sex hormones is typically conducted by LC-MS/MS. At present, most methods require liquid-liquid extraction or solid phase extraction for sample preparation. However, these pretreatments are prone to compromise LC-MS/MS throughput. To improve on the current standard practices, we investigated cold-induced phase separation for sex hormone extraction. After protein precipitation with acetonitrile and adjusting the solution constitution with water, samples were stored at -30°C for 10 min to generate two distinct phases: an acetonitrile-rich layer on top of a water-rich layer. During this process, the hydrophobic sex hormones spontaneously separate into the upper layer. This simple and reliable cold-induced phase separation-based LC-MS/MS methodology was used here to simultaneously detect estrone, estradiol, estriol, testosterone, androstenedione, dehydroepiandrosterone, progesterone, and 17-hydroxyprogesterone in serum. Validation of this method indicated satisfactory performance, including acceptable linearity, accuracy, precision, and tractability. Compared with the mainstream liquid-liquid extraction-based method, this new method exhibits significant progress in throughput, which shortens the time cost of sample preparation from 90 to 40 min. We propose that this method can be an excellent alternative for sex hormone analysis in routine clinical laboratories.

Complementarity in Requirements Tracing.

Complementarity between activities reveals that doing any one of them increases the returns to doing the others. In other words, complementarity leads to the synergistic effect that the whole is greater than the sum of its parts. Identifying and exploiting complementarity can benefit many cybernetic activities, where human-machine interactions are inherent and dominant. One such activity is requirements tracing that helps stakeholders to track the status of their goals. Although various kinds of support for human analysts in requirements tracing have been proposed, little is known about the nature of complementarity when different tracing practices are involved. In this paper, we explore the role of complementarity by considering together the tagging-to-trace (T2T) and learning-to-trace (L2T) activities. We present a novel approach to examining which T2T and L2T practices enhance the qualities of each other. Our approach also uncovers the environmental factors which the complementarity is sensitive to. Applying our approach to the logs of 140 analyst-tracing units offers operational insights into the rigorous detection of complementarity and shows the importance of understanding the cybernetic conditions under which the requirements tracing practices may in fact be complementary.

[Plasma metabonomics of Guifu Dihuang Wan in the treatment of yang deficiency].

OBJECTIVE: To assess the effect of Guifu Dihuang Wan (GFDHW) in the treatment of yang deficiency and explore the underlying molecular mechanism. METHODS: Sixty-two participants without diseases were randomized into control group (n=31) and experimental group (n=31) and were given lifestyle intervention additional GFDHW treatment for a month. NMR technology was used for metabonomics analysis. RESULTS: Intervention with GFDHW resulted in significantly decreased conversion scores of yang deficiency in the experimental group compared with the control group (P<0.005). The concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate were increased in the plasma of yang-deficient subjects after lifestyle intervention. GFDHW treatment with lifestyle intervention significantly increased the concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate and also the levels of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol. CONCLUSION: GFDHW treatment improves yang deficiency possibly by increasing the concentrations of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol and promoting energy metabolism of the body.

BDNF promotes human neural stem cell growth via GSK-3ß-mediated crosstalk with the wnt/ß-catenin signaling pathway.

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/ß-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3ß expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and ß-catenin components were all downregulated, whereas GSK-3ß was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3'-oxime (BIO), a small molecule inhibitor of GSK-3ß. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/ß-catenin signaling pathway, and that this interaction may be mediated by GSK-3ß.

A Clustering-Based Approach to Enriching Code Foraging Environment.

Developers often spend valuable time navigating and seeking relevant code in software maintenance. Currently, there is a lack of theoretical foundations to guide tool design and evaluation to best shape the code base to developers. This paper contributes a unified code navigation theory in light of the optimal food-foraging principles. We further develop a novel framework for automatically assessing the foraging mechanisms in the context of program investigation. We use the framework to examine to what extent the clustering of software entities affects code foraging. Our quantitative analysis of long-lived open-source projects suggests that clustering enriches the software environment and improves foraging efficiency. Our qualitative inquiry reveals concrete insights into real developer's behavior. Our research opens the avenue toward building a new set of ecologically valid code navigation tools.

Optimal Group Size for Software Change Tasks: A Social Information Foraging Perspective.

Group size is a key factor in collaborative software development and many other cybernetic applications where task assignments are important. While methods exist to estimate its value for proprietary projects, little is known about how group size affects distributed and decentralized cybernetic applications and in particular open source software (OSS) development. This paper presents a novel approach in which we frame developers' collective resolution of OSS change tasks as a social information foraging problem. This new perspective enables us to predict the optimal group size and quantify group size's effect on individual performance. We test the theory with data mined from two projects: 1) Firefox and 2) Mylyn. This paper not only uncovers the mismatch of optimal and actual group sizes, but also reveals the association of optimality with improved productivity. In addition, the social-level productivity gain is observed as project evolves. We show this paper's impact by extending the frontiers of knowledge in two areas: 1) social coding and 2) recommendation systems.

Expression pattern of ß-catenin during the development of human fetal spinal cord.

Development of the human fetal spinal cord is a very complicated process involving numerous signaling pathways including Wnt signaling pathways. These pathways are critical for the development and function of the mammalian nervous system. ß-Catenin is a key molecule in the canonical Wnt signaling pathway. However, the distributions of ß-catenin during development of the human fetal spinal cord have not been well characterized. Therefore, in this study, we performed immunohistochemical analysis of the ß-catenin distribution in the developing human spinal cord from 35 fetuses at three weeks to eight months of gestation. As early as E3W and E4W, ß-catenin was mainly expressed in the internal limiting membrane of the neural tube and neuroepithelium (E: Embryos; W: Weeks). During developmental stages, ß-catenin was widely expressed in various structures and cells including the neuroepithelium, internal limiting membrane, mantle layer, marginal layer, basal plate, alar plate, ependyma, gray matter, white matter, neurons with multiple processes, glial cells, and nerve fibers. This study clarifies the morphological developmental characteristics of the human fetal spinal cord as well as the distribution and expression pattern of ß-catenin in chronological and spatial aspects. Our results suggest that the Wnt÷ß-catenin signaling pathway might play a crucial role in various stages of the formation and differentiation of the human fetal spinal cord.

Expression pattern of NeuN and GFAP during human fetal spinal cord development.

PURPOSE: The development of the human embryonic spinal cord is very complicated, and many cell types are involved in the process. However, the morphological characteristics of neuronal and glial cells during the development of the human fetal spinal cord have not been described. We investigated the systemic distributions and expression pattern of the cell type-specific markers Neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) during the development of the human fetal spinal cord, in order to clarify the detailed developmental changes of neuronal and glial cells in chronological and spatial aspects. METHODS: A total of 35 fetuses, aged 3 weeks to 8 months of gestation (E3W-E8M), were studied. The markers used for immunohistochemical study were NeuN and GFAP. RESULTS: The intracellular makers NeuN and GFAP were widely detected expression in different structures and cells during the development of the human fetal spinal cord, including the following: central canal, neuroepithelial layer, internal limiting membrane, mantle layer, marginal layer, basal plate, alar plate, ependymal layer, gray matter, white matter, neuron, astrocytes, and nerve fibers. However, there was an absence of GFAP in astrocytes during early fetal spinal cord development until E9W, and the appearance of GFAP-positive reactivity was later than that of neurons. CONCLUSIONS: We consider that NeuN and GFAP can be used to identify neuronal and glial cells during the development of the human fetal spinal cord, and their distribution differs both chronologically and spatially. These characteristic expression patterns would give us a clue to better understand the developmental characteristics of the human spinal cord.