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Abstract There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.

The placement of ureteral stents plays a crucial role in the treatment of ureteral strictures, therefore requiring high material performance standards. In addition, depending on the etiology of ureteral strictures, there are significant differences in the retention time of ureteral stents, thus requiring different degradation rates for the stents. Therefore, it is crucial to develop stent materials with high performance and controllable degradation rates. This study explores the potential of Zn-2Cu-0.5Fe-xMn alloy as a ureteral stent material, utilizing the antibacterial effect of copper ions, the strengthening effect of Fe element on Zn-based alloys, and the accelerated degradation effect of Mn element. The research found that with the increase in Mn content, the average grain size of the alloy and the size of (Fe, Mn)Zn13 phase gradually increased, leading to a decrease in hardness. The corrosion rate of the alloy increased with the increase in Mn content, attributed to changes in grain size and standard electrode potential differences between elements. Due to the antibacterial effects of Zn ions and Cu ions, the Zn-2Cu-0.5Fe-xMn alloy exhibits good anti-stone formation capabilities. Furthermore, the alloy also demonstrates acceptable cytotoxicity. Therefore, the Zn-2Cu-0.5Fe-xMn alloy is expected to become an important implant material in urological surgery.

The stability of slopes might be influenced by numerous uncertainty factors. In this study, three uncertainty factors are considered in the slope stability analysis, which are locations of weak structural surfaces, structures of soil-rock mixtures, saptial variability of shear strength parameters. One new uncertainty analysis method considering these three uncertainty factors is proposed. And three geostatistical simulation algorithms are used to simulate three uncertainty factors, which are single normal equation simulation, sequential indicator simulation, sequential Gaussian simulation, respectively. When the uncertainty geology model is established, the finite element shear strength reduction method is carried out to calculate the factor of safety. This method is used to the stability analysis of Dahua landslide. The results of the Mont Carlo simulations showed that this method can effectively evaluate the influence of these three uncertainty factors on the slope stability. And the deformation pattern of Dahua landslide has been obtained by this method, which is retrogressive landslide. Then, the influence of the weak structural surfaces’ dip angle to the stability of slopes is discussed. Results show that when there are more vertical weak surfaces the more unstable of the slope.

Previous studies have found that climate change and underlying surface change are the most direct and important drivers of the streamflow change in the Yellow River Basin. However, there are significant spatial differences in climate and underlying surface in the Yellow River Basin, especially in the Loess Plateau, attribution analysis of runoff evolution in the Loess Plateau from the perspective of spatial heterogeneity was rarely reported. Therefore, in order to further reveal the causes of runoff evolution in the Loess Plateau, this study have quantitatively revealed the spatial differences of climate and underlying surface changes driving streamflow changes in 34 main Loess Plateau basins from 1956 to 2020 basing on the Budyko equation with fixed parameters. Results show that the streamflow on the Loess Plateau decreased significantly from 1956 to 2020, and streamflow decreased by 17.19 mm (26.95%) after abrupt change in 1990. The sensitivity coefficients of streamflow change on the Loess Plateau to precipitation, potential evapotranspiration and underlying surface parameters are 0.30, −0.08 and −69.26 respectively. The contributions of precipitation, potential evapotranspiration and underlying surface change to streamflow change were 26.24%, 2.15% and 73.01%, respectively, and showed significant spatiotemporal differences. The spatial variability of streamflow is mainly controlled by underlying surface. For 29 of the whole 34 tributaries, underlying surface change was the dominant driver of streamflow change with the contribution of 52.50%–98.22%. The temporal variability of streamflow on the Loess Plateau is mainly controlled by precipitation. The wetter the climate is, the more sensitive of the streamflow changes are to climate change. And the smaller the underlying surface parameters are, the more sensitive the streamflow changes are to the underlying surface change. The results further deepen our understanding for the response of streamflow to climate and underlying surface changes in the Loess Plateau and can provide theoretical support for systematic regulation of basin water resources in the future.

Abstract Objective This study aims to investigate the efficacy and safety of intraoperative real time ultrasound-assisted flexible ureteroscopic holmium laser incision and internal drainage in the treatment of parapelvic cysts, and to review recently published relevant literature. Method This is a retrospective study in which the clinical data of 47 patients who underwent flexible ureteroscopic holmium laser incision and internal drainage of parapelvic cysts in our center from March 2017 to March 2021 were retrospectively analyzed. A literature search was conducted to review and summarize relevant reports on endoscopic treatment of parapelvic cysts published in the past 10 years. Results Among 47 patients with parapelvic cysts who underwent flexible ureteroscopic holmium laser incision and internal drainage, 12 (25.53%) cases had a typical cyst wall bulging into the collecting system under flexible ureteroscope. As the cyst wall was thin and translucent in these cases, ultrasound was not used during the operation. The cysts of the remaining 35 patients were located with the aid of intraoperative real time ultrasound, and all underwent successful operation. No serious surgical complications occurred after surgery. The patients were followed up for 12–24 months after operation. The cyst in one case was observed larger than its original size before operation, so recurrence was considered. In another two cases, the diameters of the cysts were more than half of their original diameters before operation. Thus, the efficacy was poor in the three cases. For the remaining 44 cases, there was no obvious cyst observed or the diameter of the cysts was less than half their preoperative level. Conclusion The approach of ultrasound-assisted flexible ureteroscopic holmium laser incision and internal drainage in the treatment of parapelvic cysts is safe and effective, which helps to solve the problem of localization of atypical parapelvic cysts on endoscopic findings.

PurposeWe aimed to explore the relationship between serum phosphate concentration and 90-day mortality in critically ill children receiving continuous renal replacement therapy (CRRT).MethodsData from the medical records of children aged 2.4 mmol/L (hyperphosphatemia), with the normal phosphate group serving as the comparator group. The correlation of the serum phosphate concentration before and during CRRT with the 90-day mortality after CRRT initiation was analyzed using logistic regression.ResultsA total of 177 children were included in our study. The mean serum phosphate concentration before CRRT was 1.46 mmol/L (quartiles: 1.04, 2.20). The 90-day mortality rate was increased in children with a serum phosphate concentration >2.4 mmol/L before CRRT (adjusted odds ratio [aOR] 3.74, 95% confidence interval [CI] 1.42–9.86, P = 0.008). The mean serum phosphate concentration during CRRT was 1.2 mmol/L (quartiles: 0.91, 1.49). The 90-day mortality rate was increased in children with a mean serum phosphate concentration >2.4 mmol/L during CRRT (aOR 7.34, 95% CI 1.59–33.88, P = 0.011).ConclusionHyperphosphatemia before and during CRRT predicts a higher 90-day mortality rate.

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder. How to stratify high risk patients is one of the current challenges for the treatment of HLH. HLH patients usually fulfill multiple but not all eight diagnostic criteria. Different combinations of the fulfilled criteria may naturally cluster into previously undescribed subsets or phenotypes that may have different pathophysiology and demonstrate different risks for a poor outcome. The objectives of this study were to identify HLH subgroups according to the fulfillment of diagnostic criteria and evaluate the risk of multiple organ dysfunction syndrome (MODS) and 30-day mortality for subgroups. We retrospectively collect medical records of patients with discharge diagnosis of HLH between June 2015 and October 2018 from a tertiary children’s hospital in China. Latent class analysis was used to identify class defining variables from HLH diagnostic items, and subgroups were defined according to different combinations of the class defining variables. Results Triglyceride and fibrinogen were identified as the class defining variables. When evaluated in combinations, patients with hypertriglyceridemia and normal fibrinogen levels during hospitalization had the lowest risks for MODS (27.8%, OR = 1) and 30-day mortality (18.8%, OR = 1), and patients with normal triglyceride and hypofibrinogenemia had the highest risks for MODS (86.2%, OR = 16.24, P = 0.0002) and 30-day mortality (57.1%, OR = 5.78, P = 0.0187). The fulfillment status of hypertriglyceridemia and hypofibrinogenemia within 72 h of hospital admission was also associated with the risk of adverse outcomes. Conclusions The fulfillment status of hypertriglyceridemia and hypofibrinogenemia were associated with the risks of MODS and 30-day mortality among pediatric HLH patients. Further studies are needed to validate this association and investigate its clinical utility in the severity evaluation for HLH.

Background and aimsDeciding when to suspect hemophagocytic lymphohistiocytosis (HLH) and perform diagnostic tests in patients with acute infection of Epstein-Barr virus (EBV) is challenging, given the high prevalence of EBV infection, the life-threatening risk of EBV-HLH, the relatively low incidence of EBV-HLH, and the wide spectrum of disease presentations. The aim of this study was to develop an EBV-HLH screening model for pediatric patients diagnosed with acute infection of EBV.MethodsAn inpatient cohort with 3183 pediatric patients who were diagnosed with active infection of EBV was used to construct and validate the EBV-HLH screening score model. The model parameters were selected from common laboratory parameters using the method of Akaike Information Criterion-optimal selection through cross-validation under logistic regression. Performance of the score was evaluated and compared with the performance of screening methods using the number of cytopenias lineages.ResultsThe EBV-HLH screening score has five parameters, including hemoglobin, platelet, neutrophil, albumin, and lactate dehydrogenase. Using a cut-of value of 29, the scoring model had a sensitivity of 89.2% and a specificity of 89.5% in the validation set. The false negative rate, false positive rate, positive predictive value, and negative predictive value in the validation set was 10.8%, 10.5%, 26.8%, and 99.5%, respectively, similar to that of the training set.ConclusionsWith five common laboratory parameters, the EBV-HLH score provides a simple tool to assist the identification of EBV patients who require further evaluation of HLH. Further studies are needed to evaluate the generalizability of the score and optimize the diagnose process for EBV-HLH.

Increasing evidence has demonstrated that ischemic preconditioning (IPC) increases cerebral tolerance to subsequent prolonged ischemic insults. However, the exact mechanisms underlying the process have not been fully explored. In the current study, we aim to investigate whether NLRP3 inflammasome and cell pyroptosis are involved in the neuroprotective mechanism of IPC after ischemic stroke. In vitro, IPC was set up by exposing BV-2 cells to 10 min of oxygen–glucose deprivation (OGD). In vivo, IPC was performed by a transient cerebral ischemia of 10 min occlusion of the middle cerebral artery (MCA) in mice. We found that the NLRP3 inflammasome was activated and cell pyroptosis was induced at 6 h and 24 h post-stroke in an ischemic brain. IPC treatment increased cell viability under OGD state, reduced the infarct size, and attenuated the neurological deficits of mice. However, the effects NLRP3 inflammasome activation and pyroptosis after stroke were attenuated by IPC, which decreased the expression of NLRP3, ASC, cleaved caspase 1, and GSDMD-N and reduced the production of IL-1β and IL-18. In addition, confocal immunofluorescence staining of Annexin V-mCherry and SYTOX green was inhibited by IPC. These findings suggest a more enhanced link between IPC and inflammatory signature and cell death, highlighting that the NLRP3 inflammasome may act as a promising target for the prevention and treatment of ischemic stroke.

A new signal processing method named orthogonal signal phase multiplication (OSPM) is proposed, which is used to improve the precision of vibration measurement in a phase-modulating self-mixing interferometer (SMI). The modulated signal is acquired by an electro-optic modulator, which is placed in the external cavity. Higher measurement precision is realized by performing the phase multiplication algorithm on the orthogonal signals extracted from the harmonic components of the signal spectrum. Theoretically, the displacement reconstruction precision of OSPM is higher than that of conventional modulation methods, and it can be continuously improved by increasing the multiplication times. The feasibility and performance of the proposed method are verified by simulated signals and confirmed by experiments; the absolute error is less than 11 nm, and relative error is less than 0.75%, within the amplitude range from 661 nm to 2013 nm. This method does not involve additional optical elements, and its effectiveness meet the requirements for real-time high-precision measurements.

BackgroundExtracorporeal membrane oxygenation (ECMO) has been increasingly used as rescue therapy for severe pediatric acute respiratory distress syndrome (PARDS) over the past decade. However, a contemporary comparison of venovenous (VV) and venoarterial (VA) ECMO in PARDS has yet to be well described. Therefore, the objective of our study was to assess the difference between VV and VA ECMO in efficacy and safety for infection-associated severe PARDS patients.MethodsThis prospective multicenter cohort study included patients with infection-associated severe PARDS who received VV or VA ECMO in pediatric intensive care units (PICUs) of eight university hospitals in China between December 2018 to June 2021. The primary outcome was in-hospital mortality. Secondary outcomes included ECMO weaning rate, duration of ECMO and mechanical ventilation (MV), ECMO-related complications, and hospitalization costs.ResultsA total of 94 patients with 26 (27.66%) VV ECMO and 68 (72.34%) VA ECMO were enrolled. Compared to the VA ECMO patients, VV ECMO patients displayed a significantly lower in-hospital mortality (50 vs. 26.92%, p = 0.044) and proportion of neurologic complications, shorter duration of ECMO and MV, but the rate of successfully weaned from ECMO, bleeding, bloodstream infection complications and pump failure were similar. By contrast, oxygenator failure was more frequent in patients receiving VV ECMO. No significant intergroup difference was observed for the hospitalization costs.ConclusionThese positive findings showed the conferred survival advantage and safety of VV ECMO compared with VA ECMO, suggesting that VV ECMO may be an effective initial treatment for patients with infection-associated severe PARDS.

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare and life-threatening disorder. Early mortality remains significantly high among patients with HLH. Our aim was to investigate clinical features and risk factors associated with 7-day and 30-day mortality among pediatric HLH patients. We retrospectively collected medical records of patients with discharge diagnosis of HLH between August 2014 and October 2018 from a tertiary children’s hospital in China. The main outcome measures were the 7-day and 30-day outcome after hospital admission. The associations between symptoms, concomitant diagnoses, laboratory test results, and the risk of 7-day and 30-day mortality were examined. Results Among 160 pediatric HLH patients, 18 (11.3%) patients were deceased within 7 days after admission, and 46 (28.8%) patients were deceased within 30 days. The identified strong risk factors (OR > 10 and p

Cell-based assays (CBAs) and radioimmunoprecipitation assay (RIPA) are the most sensitive methods for identifying anti-acetylcholine receptor (AChR) antibody in myasthenia gravis (MG). But CBAs are limited in clinical practice by transient transfection. We established a stable cell line (KL525) expressing clustered AChR by infecting HEK 293T cells with dual lentiviral vectors expressing the genes encoding the human AChR α1, β1, δ, ϵ and the clustering protein rapsyn. We verified the stable expression of human clustered AChR by immunofluorescence, immunoblotting, and real-time PCR. Fluorescence-activated cell sorting (FACS) was used to detect anti-AChR antibodies in 103 MG patients and 58 healthy individuals. The positive results of MG patients reported by the KL525 was 80.6% (83/103), 29.1% higher than the 51.4% (53/103) of RIPA. 58 healthy individuals tested by both the KL525 CBA and RIPA were all negative. In summary, the stable expression of clustered AChR in our cell line makes it highly sensitive and advantageous for broad clinical application in CBAs.

The difficulties and challenges of applying the HLH-2004 diagnostic criteria to early identification and diagnosis of haemophagocytic lymphohistiocytosis have been fully addressed in previous studies. However, the distribution of the diagnostic time lag of haemophagocytic lymphohistiocytosis and related patient characteristics remain unclear. This study investigated the time lags between symptom onset and diagnosis and between hospital admission and diagnosis among pediatric patients with haemophagocytic lymphohistiocytosis, and identified factors that associated with a shorter or longer diagnostic time lag. The cohort of patients with haemophagocytic lymphohistiocytosis was drawn from a tertiary children's hospital and consisted of 122 pediatric patients. The distributions of symptom-to-diagnosis and admission-to-diagnosis time lags were assessed. Clinical characteristics within 48 h of admission and the fulfillment of HLH-2004 diagnostic criteria were compared among admission-to-diagnosis time lag categories. Logistic regression analyses were conducted to identify factors associated with an admission-to-diagnosis time lag >3 days. The median interval from first symptom onset to HLH diagnosis was 12 days (range 4–71 days) and the median interval from hospital admission to HLH diagnosis was 2 days (range 0–23 days). The following factors were negatively associated with admission-to-diagnosis > 3 days: Epstein–Barr virus infection; admission through pediatric intensive care unit; diagnosis established without NK-cell activity and soluble CD25 tests; the performance of all readily available diagnostic tests for HLH (within 48 and 72 h); concurrent fever, splenomegaly, and cytopenias within 48 h; hemophagocytosis, hypertriglyceridemia and/or hypofibrinogenemia within 48 h; and elevated ferritin, total bilirubin, alanine aminotransferase, and prothrombin time within 48 h. Our findings suggest that performance of adequate diagnostic tests for HLH is essential for early diagnosis of HLH. Once suspected, immediate and adequate diagnostic tests for HLH should be arranged for PICU patients. Improvements in diagnostic procedures and monitoring plans are needed to promote early diagnosis of HLH.

An improved method combining multiple reflections with the phase-modulation technique (MR-PM) is proposed to construct a self-mixing interferometer with high accuracy. The phase modulation is performed by using an electro-optic modulator that is placed in the external cavity. To broaden the harmonic components spectrum of the self-mixing signal, the multiple-reflection technique is employed. By extracting orthogonal signals from the spectrum, phase demodulation is implemented to realize displacement reconstruction. The principle and signal processing approach are described in detail. A series of simulations and experiments indicate that the measurement accuracy of the system can be effectively improved with the increase in reflection times. The vibration with an amplitude of 44 nm has been proved to be measurable with a reconstruction error less than 3 nm. Due to the advantages of high accuracy and broad measurement range, the proposed method will play a significant role in the field of non-contact nanometer vibration measurement.

Summary: Short-term memory (STM) is crucial for animals to hold information for a small period of time. Persistent or recurrent neural activity, together with neural oscillations, is known to encode the STM at the cellular level. However, the coding mechanisms at the microcircuitry level remain a mystery. Here, we performed two-photon imaging on behaving mice to monitor the activity of neuronal microcircuitry. We discovered a neuronal subpopulation in the medial prefrontal cortex (mPFC) that exhibited emergent properties in a context-dependent manner underlying a STM-like behavior paradigm. These neuronal subpopulations exclusively comprise excitatory neurons and mainly represent a group of neurons with stronger functional connections. Microcircuitry plasticity was maintained for minutes and was absent in an animal model of Alzheimer’s disease (AD). Thus, these results point to a functional coding mechanism that relies on the emergent behavior of a functionally defined neuronal assembly to encode STM.

Bisphenol A is used in the production of many plastic products, but has adverse health effects and is therefore being replaced. Here the authors show that its substitute, fluorene-9-bisphenol, is released from commercial plastic bottles into drinking water, and has anti-oestrogenic effects in mice.

With low mature Triassic Chang 7 Member shale samples from the Ordos Basin as study object, the 3-D porosity evolution with temperature increase and its main controlling factors are analyzed based on the physical modeling under high temperature & pressure and nano-CT scanning data. More and more nano-pores were developed in Chang 7 Member organic-rich shale with the increase of maturity. The porosity calculated from the nano-CT scanning model increased from 0.56% to 2.06%, more than 250% times larger, when temperature increased from 20 °C to 550 °C. The process of porosity evolution can be divided into three phases. Firstly, porosity decreased rapidly from immature to low mature stage because of weak hydrocarbon generation and strong compaction; Secondly, porosity increased rapidly when the maturity increased from low mature stage to mature and post-mature stage, organic matter cracked into hydrocarbon (HC) massively, and clay minerals transformed intensively; Thirdly, porosity system kept stable when the shale entered into post-mature stage and the intensity of both HC generation and clay mineral transformation decreased. Organic matter thermal evolution, clay mineral transformation and brittle mineral transformation make different contribution to the porosity of shale, and the ratio is 6:3:1 respectively. It is inferred abundant organic matter pores occur when Ro is over 1.2%. Key words: lacustrine shale, porosity evolution, clay mineral, nano-CT, Ordos Basin, Triassic Chang 7 Member

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP). In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate Fmr1 knockout (KO) rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO). Electrophysiological analysis revealed that the theta-burst stimulation (TBS)–induced long-term potentiation (LTP) and the low-frequency stimulus (LFS)–induced long-term depression (LTD) were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG)–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.