BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Development of a Deep-Learning Model for Diagnosing Lumbar Spinal Stenosis Based on CT Images.

STUDY DESIGN: Retrospective study. OBJECTIVES: This study aimed to develop an initial deep-learning (DL) model based on computerized tomography (CT) scans for diagnosing lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging is commonly used for diagnosing lumbar spinal stenosis due to its high soft tissue resolution, but CT is more portable, cost-effective, and has wider regional coverage. Using DL models to improve the accuracy of CT diagnosis can effectively reduce missed diagnoses and misdiagnoses in clinical practice. MATERIALS AND METHODS: Axial lumbar spine CT scans obtained between March 2022 and September 2023 were included. The data set was divided into a training set (62.3%), a validation set (22.9%), and a control set (14.8%). All data were labeled by two spine surgeons using the widely accepted grading system for lumbar spinal stenosis. The training and validation sets were used to annotate the regions of interest by the two spine surgeons. First, a region of interest detection model and a convolutional neural network classifier were trained using the training set. After training, the model was preliminarily evaluated using a validation set. Finally, the performance of the DL model was evaluated on the control set, and a comparison was made between the model and the classification performance of specialists with varying levels of experience. RESULTS: The central stenosis grading accuracies of DL Model Version 1 and DL Model Version 2 were 88% and 83%, respectively. The lateral recess grading accuracies of DL Model Version 1 and DL Model Version 2 were 75% and 71%, respectively. CONCLUSIONS: Our preliminarily developed DL system for assessing the degree of lumbar spinal stenosis in CT, including the central canal and lateral recess, has shown similar accuracy to experienced specialist physicians. This holds great value for further development and clinical application.

[Estimation and Critical Source Area Identification of Non-point Source Pollution Based on Improved Export Coefficient Models: A Case Study of the Upper Beiyun River Basin].

Non-point source pollution(NSP) poses a great threat to water ecosystem health. The quantitative estimation of spatial distribution characteristics and accurate identification of critical source areas(CSAs) of NSP are the basis for its efficient and accurate control. The export coefficient model(ECM) has been widely used to assess NSP, but this model should be improved because it ignores pollutant loss in transport processes. In this study, the ECM, which refines the physical transport processes of pollutants through quantifying the loss rate of pollutants in runoff, sediment, and infiltration, was improved to assess NSP and identify CSAs. The simulation accuracy among Johnes ECM, frequent ECM, and improved ECM were analyzed, and the effects of the three models on the simulation results of both spatial distribution characteristics and CSAs were explored. The study showed that:① the simulation error of the improved ECM(-6.79%) was significantly lower than that of the Johnes ECM(50.44%) and the frequent ECM(-84.01%), and this improved ECM increased the simulation accuracy of NSP. ② The spatial distribution characteristics and CSAs of NSP obtained from Johnes, frequent, and improved ECMs were significantly different, and the simulation results of improved ECM were more consistent with the spatial characteristics of NSP in the watershed. The NSP was high in the southeast and low in the northwest of the basin, and the NSP mainly came from urban and cultivated land. ③ Based on the improved ECM, the CSAs of NSP in the basin were mainly distributed in Changping, Shahe, Shigezhuang, the north of Wenquan, and the west of Malianwa Street, accounting for 6.71% of the area. This study can provide an effective tool and scientific reference for the assessment and control of NSP in data-limited regions.

Complications and radiographic changes after implantation of interspinous process devices: average eight-year follow-up.

PURPOSE: This study aims to evaluate complications, clinical outcomes, and radiographic results following Coflex implantation. METHODS: We retrospectively studied 66 patients who had decompressive surgery combined with Coflex implantation to treat lumbar spinal stenosis. All imaging data were collected and examined for imaging changes. Clinical outcomes, included Oswestry Disability Index (ODI), back and leg visual analog scale (VAS) scores, were evaluated before surgery, six months after surgery and at the last follow-up. The number of complications occurring after five years of follow-up was counted. All reoperation cases were meticulously recorded. RESULTS: 66 patients were followed up for 5-14 years. The VAS and ODI scores were significantly improved compared with baseline. Heterotopic Ossification (HO) was detectable in 59 (89.4%). 26 (39.4%) patients had osteolysis at the contact site of Coflex with the spinous process. Coflex loosening was detected in 39 (60%) patients. Spinous process anastomosis was found in 34 (51.5%) patients. There was a statistically significant difference in the VAS score of back pain between patients with and without spinous process anastomosis. Nine cases of lumbar spinal restenosis were observed, and prosthesis fracture was observed in one case. CONCLUSION: Our study identified various imaging changes after Coflex implantation, and majority of them did not affect clinical outcomes. The majority of patients had HO, but osteolysis and Coflex loosening were relatively rare. The VAS score for back pain of these patients was higher if they have spinous process anastomosis. After five-year follow-up, we found lumbar spinal restenosis and prosthesis fracture cases.

[Effects of Green, Blue, and Blue-green Roofs on Runoff Quality].

Roofs occupy a great proportion of urban impervious surfaces, and the implementation of eco-roof construction in urban areas is beneficial to alleviate the ecological and environmental problems caused by rapid urbanization. In this study, different eco-roofs (i.e., 68.6%-90.7%, and 39.8%-54.5%, respectively. However, all the eco-roofs were sources of NO-3-N, DCr, DFe, and DNi. The blue roof was a sink of DCu (with a pollutant load reduction rate of 21.9%) and did not affect the cumulative load of PO3-4-P in runoff. However, the green roof and blue-green roof were the sources of PO3-4-P and DCu. The RQI value of the blue roof was the highest, followed by that of the blue-green roof and green roof. The RQI value of the green roof was significantly lower than that of the blue and blue-green roofs (P<0.05). These results indicated that the runoff quality of the blue roof was the best, whereas that of the green roof was the worst. Adding a storage layer to the green roofs could significantly improve the runoff quality. The results of this study provide scientific references for the selection and design of eco-roof facilities.

Superior pancreatic lymphadenectomy with portal vein priority via posterior common hepatic artery approach in laparoscopic radical gastrectomy.

BACKGROUND: D2 lymph node dissection for advanced gastric cancer is advocated, and station 8p lymph node should be considered in selected patients, which is, however, technically difficult. AIM: To introduce a new and easy-to-perform procedure for dissection of the lymph nodes superior to the pancreas. METHODS: A series of patients who underwent laparoscopic gastrectomy for gastric cancer were retrospectively included with utilization of a new procedure for superior pancreatic lymphadenectomy (LND) with portal vein priority via the posterior common hepatic artery approach (SPLD-PPPH) based on a newly defined portal triangle. The surgical outcome of the patients, as well as the efficacy and safety of SPLD-PPPH are reported. RESULTS: A total of 51 patients were included with most of them being male (n = 34, 66.7%). According to the 8th edition of AJCC TNM staging, there were four (7.8%) patients in stage I, 13 (25.5%) in stage II, 33 (64.7%) in stage III and one (2.0%) in stage IV. The average duration for LND was about 1 h (67.7 ± 6.9 min). After surgery, four patients developed morbidities, but all were treated successfully with no perioperative mortality. Among the 51 patients included, the percentage of patients who had lymph node metastasis at station 8p was 9.8%. Of note, with a total of 14 lymph nodes harvested at station 8p, the incidence of nodal metastasis was 14.3%. CONCLUSION: About one in 10 patients with advanced gastric cancer had nodal metastasis at station 8p. The new approach of SPLD-PPPH is safe and effective for D2+ LND during laparoscopic radical gastrectomy.

[Analysis of Spatial-Temporal Variation Characteristics of Potential Non-point Source Pollution Risks in the Upper Beiyun River Basin Using Different Weighting Methods].

Non-point source pollution has become an important factor affecting the aquatic ecological environment and human health, and the analysis of spatial-temporal variations in non-point source pollution risks is an important prerequisite for pollution control. Based on land-use and land-cover data from 1980 to 2020, the potential non-point source pollution index (PNPI) model was applied in the upper Beiyun River Basin using different weighting methods. The results showed that:① The potential risk of non-point source pollution is high in the southeast and low in the northwest of the basin. Between 1980 and 2020, the total area of extremely high-risk and high-risk non-point source pollution regions showed a decreasing trend, and the main types of land use for extremely high-risk and high-risk regions gradually evolved from paddy fields, drylands, and orchards to urban and rural residential land; ② The weighting of the land use index determined by the mean-square deviation decision, entropy, coefficient of variation, and expert scoring methods was largest among the three PNPI indices, with average weightings of 0.46, 0.53, 0.45, and 0.48, respectively. However, the weightings for runoff and distance indices determined by different weighting methods were notably different, and the proportions of regions with different levels of non-point source pollution risk also varied; ③ The exponential function method, which describes the relationship between source factors and transport factors by constructing the exponential functions of land use, runoff, and distance indices, provided results that are more consistent with the spatial distribution characteristics of non-point source pollution risk in the basin. The proportions of extremely low-risk and extremely high-risk regions are 54.22% and 6.23%, respectively. These results provide scientific reference for risk analysis and the control of non-point source pollution in this basin.

[Effect of glucose on biofilm and the gene ica expression in Staphylococcus epidermidis with different biofilm-forming capability].

The infection of S. epidermidis, an opportunistic human pathogen, depends on biofilm formation, and biofilm formation is closely related to environment. Researches in the thesis focused on two strains of S. epidermidis with different capability of biofilm formation. To find the mechanism of response to environment on biofilm formation, biofilm formation and expression of ica, icaR, AtlE in theses S. epidermidis cultivated in different grow environment and in media with glucose for different time were assayed. Glucose can induce the biofilm formation by inducing ica gene, but the inducing do not need continued ica expression, and other genes also contribute to the regulation; anti-ODN specially binding icaADBC can withstand biofilm inducing from glucose. These results suggest that biofilm formation closely related to growth environment, which is a complex regulation mechanism. Biofilm formation is closely related to bacteria energy metabolism and cell wall synthesis. Some crucial factors in the complex and integrated regulation system have not been known yet.

[Effect of glucose analogs on bofilm and expressions of related genes in Staphylococcus epidermidis].

Staphylococcus epidermidis, an opportunistic human pathogen, has become the most important cause of nosocomial infections in recent years. Its infection is mainly due to the ability to form biofilm on indwelling medical devices. To investigate the response mechanism of S. epidermidis to environment in biofilm formation and find efficient anti-biofilm methods, we investigated effects of two glucose analogs, 2-Deoxy-D-glucose (2DG) and Methyl-D-glucoside (MG), on biofilm formation, expression of related gene and changes of surface protein in S. epidermidis 97-337 with high biofilm formation capability and pathogenicity. The effect of MG on biofilm formation was more complex than that of 2-DG which is a strong inhibitor in S. epidermidis 97-337 growth. MG can induce biofilm formation of S. epidermidi 97-337 in low concentration and exhibited strong inhibition only in high concentration, and distinctly inhibited the primary attachment to poly-material. In S. epidermidi 97-337 cultured in media with MG, expressions of ica and AtlE were not be changed obviously in mRNA level, but mRNA expression of agr gene increased distinctly, and MG disturbed component of surface proteins of S. epidermidi 97-337. Glucose analogies MG can inhibit S. epidermidi 97-337 biofilm formation, and MG inhibition in initiating attachment dramatically contributes to it. MG inhibition effects result not from regulating the expression of ica and AtlE genes but from changing the protein components on surface by regulating agr gene expression, and it can be presumed that MG's competitive character in bacteria glycose metabolism is crucial factor for these effects.

Genome-based analysis of virulence genes in a non-biofilm-forming Staphylococcus epidermidis strain (ATCC 12228).

Staphylococcus epidermidis strains are diverse in their pathogenicity; some are invasive and cause serious nosocomial infections, whereas others are non-pathogenic commensal organisms. To analyse the implications of different virulence factors in Staphylococcus epidermidis infections, the complete genome of Staphylococcus epidermidis strain ATCC 12228, a non-biofilm forming, non-infection associated strain used for detection of residual antibiotics in food products, was sequenced. This strain showed low virulence by mouse and rat experimental infections. The genome consists of a single 2499 279 bp chromosome and six plasmids. The chromosomal G + C content is 32.1% and 2419 protein coding sequences (CDS) are predicted, among which 230 are putative novel genes. Compared to the virulence factors in Staphylococcus aureus, aside from delta-haemolysin and beta-haemolysin, other toxin genes were not found. In contrast, the majority of adhesin genes are intact in ATCC 12228. Most strikingly, the ica operon coding for the enzymes synthesizing interbacterial cellular polysaccharide is missing in ATCC 12228 and rearrangements of adjacent genes are shown. No mec genes, IS256, IS257, were found in ATCC 12228. It is suggested that the absence of the ica operon is a genetic marker in commensal Staphylococcus epidermidis strains which are less likely to become invasive.