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Background: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. Methods: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. Results: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384–73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045–28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48–49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25–25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48–12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09–27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798–0.934) with a sensitivity of 0.761 and specificity of 0.869. Conclusion: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely. [ABSTRACT FROM AUTHOR]

Background: Recently, chronic kidney disease (CKD)-mineral and bone disorder (MBD) has become one of common complications occurring in CKD patients. Therefore, development of a new treatment for CKD-MBD is very important in the clinic. In China, Fucoidan (FPS), a natural compound of Laminaria japonica has been frequently used to improve renal dysfunction in CKD. However, it remains elusive whether FPS can ameliorate CKD-MBD. FGF23-Klotho signaling axis is reported to be useful for regulating mineral and bone metabolic disorder in CKD-MBD. This study thereby aimed to clarify therapeutic effects of FPS in the CKD-MBD model rats and its underlying mechanisms in vivo and in vitro, compared to Calcitriol (CTR). Methods: All male rats were divided into four groups: Sham, CKD-MBD, FPS and CTR. The CKD-MBD rat models were induced by adenine administration and uninephrectomy, and received either FPS or CTR or vehicle after induction of renal injury for 21 days. The changes in parameters related to renal dysfunction and renal tubulointerstitial damage, calcium-phosphorus metabolic disorder and bone lesion were analyzed, respectively. Furthermore, at sacrifice, the kidneys and bone were isolated for histomorphometry, immunohistochemistry and Western blot. In vitro, the murine NRK-52E cells were used to investigate regulative actions of FPS or CTR on FGF23-Klotho signaling axis, ERK1/2-SGK1-NHERF-1-NaPi-2a pathway and Klotho deficiency. Results: Using the modified CKD-MBD rat model and the cultured NRK-52E cells, we indicated that FPS and CTR alleviated renal dysfunction and renal tubulointerstitial damage, improved calcium-phosphorus metabolic disorder and bone lesion, and regulated FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. In addition, using the shRNA-Klotho plasmid-transfected cells, we also detected, FPS accurately activated ERK1/2-SGK1-NHERF-1-NaPi-2a pathway through Klotho loss reversal. Conclusion: In this study, we emphatically demonstrated that FPS, a natural anti-renal dysfunction drug, similar to CTR, improves renal injury-related calcium-phosphorus metabolic disorder and bone abnormality in the CKD-MBD model rats. More importantly, we firstly found that beneficial effects in vivo and in vitro of FPS on phosphorus reabsorption are closely associated with regulation of FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. This study provided pharmacological evidences that FPS directly contributes to the treatment of CKD-MBD. [ABSTRACT FROM AUTHOR]

Constructing and operating cascade reservoirs significantly contribute to comprehensive basin water resource management, while altering natural hydrological regimes of rivers, which imposes negative impacts on riverine ecology. The main aim of this study is to synergistically optimize the objectives of increasing hydropower generation and alleviating hydrological regime alteration for cascade reservoirs. This study first proposed a dynamic time warping scenario backward reduction (DTW-SBR) framework to extract streamflow scenarios from the historical streamflow series regarded as benchmarks for calculating deviation degrees of hydrological regimes. Then a multi-objective long-term operation model considering the hydrological regime and hydroelectricity was formed for minimizing the deviation degrees of hydrological regimes at the downstream section (O1) and maximizing the hydropower generation of cascade reservoirs (O2). The non-dominated sorting genetic algorithm-II (NSGA-II) combined with the long-term conventional operation (CO) rules of cascade reservoirs was adopted to produce the Pareto-front solutions to derive the recommended policies for guiding the long-term operation of cascade reservoirs. The six large reservoirs in the middle reaches of the Jinsha River, China with a 10-day runoff dataset spanning from 1953 to 2015 constitute a case study. The results showed that nine streamflow scenarios were extracted for calculating the O1 by the DTW-SBR framework, which could reflect the intra- and inter- annual variability of hydrological regimes at the Panzhihua hydrological station. The Pareto-front solutions obtained by the NSGA-II revealed competitive relationships between the O1 and O2. As compared to the long-term CO rules of cascade reservoirs, the O1 value could be reduced by up to 42,312 (corresponding rate of 10.51%) and the O2 value could be improved by up to 1752 × 108 kW·h (corresponding rate of 5.14%). Based on the inclination to be dominated by different objectives, three typical operation schemes, A, B and C, were chosen from the Pareto-front solutions; Scheme A could be considered as the recommended solution, which simultaneously reduced the O1 value by 23,965 with the rate of 5.95% and increased the O2 value by 1752 × 108 kW·h with the rate of 5.14%, as compared to the long-term CO rules. This study can provide references on boosting the synergies of hydropower production and hydrological regime restoration for the long-term ecological operation of cascade reservoirs. [ABSTRACT FROM AUTHOR]

Purpose: The prognosis of patients with leptomeningeal metastasis (LM) remains poor. Circulating tumour DNA (ctDNA) has been proven to be abundantly present in cerebrospinal fluid (CSF); hence, its clinical implication as a biomarker needs to be further verified. Methods: We conducted a retrospective study of 35 lung adenocarcinoma (LUAD) patients with LM, and matched CSF and plasma samples were collected from all patients. All paired samples underwent next-generation sequencing (NGS) of 139 lung cancer-associated genes. The clinical characteristics and genetic profiling of LM were analysed in association with survival prognosis. Results: LM showed genetic heterogeneity, in which CSF had a higher detection rate of ctDNA (P = 0.003), a higher median mutation count (P < 0.0001), a higher frequency of driver mutations (P < 0.01), and more copy number variation (CNV) alterations (P < 0.001) than plasma. The mutation frequencies of the EGFR, TP53, CDKN2A, MYC and CDKN2B genes were easier to detect in CSF than in LUAD tissue (P < 0.05), possibly reflecting the underlying mechanism of LM metastasis. CSF ctDNA is helpful for analysing the mechanism of EGFR-TKI resistance. In cohort 1, which comprised patients who received 1/2 EGFR-TKIs before the diagnosis of LM, TP53 and CDKN2A were the most common EGFR-independent resistant mutations. In cohort 2, comprising those who progressed after osimertinib and developed LM, 7 patients (43.75%) had EGFR CNV detected in CSF but not plasma. Furthermore, patient characteristics and various genes were included for interactive survival analysis. Patients with EGFR-mutated LUAD (P = 0.042) had a higher median OS, and CSF ctDNA mutation with TERT (P = 0.013) indicated a lower median OS. Last, we reported an LM case in which CSF ctDNA dynamic changes were well correlated with clinical treatment. Conclusions: CSF ctDNA could provide a more comprehensive genetic landscape of LM, indicating the potential metastasis-related and EGFR-TKI resistance mechanisms of LM patients. In addition, genotyping of CSF combined with clinical outcomes can predict the prognosis of LUAD patients with LM. [ABSTRACT FROM AUTHOR]

Purpose: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. Methods: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. Results: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794–0.944), 0.92 (95% CI 0.795–1.000), and 0.86 (95% CI 0.744–0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. Conclusion: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner. [ABSTRACT FROM AUTHOR]

This study investigates and compares the effects of the Coronavirus disease 2019 (COVID-19) pandemic, the Chicago mercantile exchange (CME)'s negative price suggestion on prices and trading activities in the crude oil futures market to discuss the cause of negative crude oil futures prices. Through event studies, the empirical results show that the COVID–19 pandemic no longer impacts crude oil futures prices in April, 2020 after controlled market risk, while the CME's negative prices suggestion can explain the crude oil futures price changes around and even after April 8, 2020 to some degree. Moreover, this study uncovers anomalies in prices and trading activities by analyzing returns, trading volume, open interest, and illiquidity measures using vector autoregressive (VAR) models. The results imply that CME's allowing negative prices strengthens the price impact on trading volume and makes illiquidity risk matter. This study's results coincide with the following lawsuit evidence of market manipulation. [ABSTRACT FROM AUTHOR]

Purpose: Leptomeningeal carcinomatosis (LC) is a rare complication of non-small cell lung cancer (NSCLC) with highly mortality. Cerebrospinal fluid (CSF) as a special kind of tumor microenvironment (TME) better represents alterations than plasma. However, the clinical value of protein profiles of exosome in CSF as liquid biopsy remains unclear. Methods: In this study, CSF samples of NSCLC patients with (LC group) or without (NSCLC group) LC were collected and compared to patients without tumors (normal group). CSF exosomes were isolated by ultracentrifugation and protein profiles were performed by label-free proteomics. Differentially expressed proteins (DEPs) were detected by bioinformatics tools and verified by parallel reaction monitoring (PRM). Results: A total of 814 proteins were detected. Bioinformatics analysis revealed their shared function in the complement activation, extracellular region, and complement and coagulation cascades. Between LC and NSCLC group, 72 DEPs were found among which FN1 demonstrated the highest betweenness centrality (BC) after protein-protein interaction network analysis. Conclusion: We investigated the application of label free and PRM based proteomics to detect key proteins related to LC. FN1 may serve as potential indicator to classify LC and NSCLC. Extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are important in the process of LC. These data is promising for early prediction and diagnosis of LC. [ABSTRACT FROM AUTHOR]

Background: Neurobrucellosis (NB) presents a challenge for rapid and specific diagnosis. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has showed power in detection of causative pathogens, even some infrequent and unexpected pathogens. In this study, we presented 8 cases of NB diagnosed by the NGS of CSF. Methods: Between August 1, 2018 and September 30, 2020, NGS was used to detect causative pathogens in clinically suspected central nervous system (CNS) infections. Data on demographics, clinical features, and laboratory tests, imaging results and NGS results were collected and reviewed. Results: Among the presented 8 patients, Brucella was rapidly detected using NGS of CSF within 1–4 days, despite those eight patients had variable medical history, disease course, clinical manifestations, laboratory tests and imaging findings. NGS showed the sequence reads corresponded to Brucella species were 8 to 448, with genomic coverage of 0.02 to 0.87%. The relative abundance was 0.13% to 82.40% and sequencing depth was 1.06 to 1.24. Consequently, patients were administered with 3 to 6 months of doxycycline, ceftriaxone and rifampicin, double or triple combination, supplemented with symptomatic therapy and were fully recovered except for case 1. Conclusion: NGS of CSF provides a powerful tool in detection of Brucella in a prompt and specific manner, and can be considered for first-line diagnostic use in practice. [ABSTRACT FROM AUTHOR]

The hosts of OH megamaser (OHM) are luminous infrared galaxies (LIRGs), in fact 1/3 of them are ultra-luminous infrared galaxies (ULIRGs), which imply that OHM phenomena should be related to the infrared radiation field. In this paper, we investigate the far infrared (FIR) properties of OHM host galaxies, through detailed infrared data covering broad bands. All known OHM sources and one control sample of (U)LIRGs without maser detections (non-OHM sources) are cross-identified with AKARI and Herschel photometric catalogs. Comparative analysis on the spectral energy distribution (SED) with broad coverage from J to 350 μ m (taken from 2MASS, WISE, Spitzer, and AKARI and Herschel archive data) shows that the OHM sources tend to have higher FIR luminosities than those of the non-OHM sources, which are more pronounced in the SED range covered by the AKARI. These are consistent with our statistical results of the FIR luminosities distribution of both the samples, which show that the OHM sources tend to have higher FIR luminosities, especially, at short FIR wavelength (i.e., the 65 and 90 μ m). However, the non-OHM sources tend to have much stronger emission than those of OHM sources at both the near infrared (NIR) and middle infrared (MIR) bands. The statistic analysis of the color–color properties at MIR and FIR bands shows that the OHM sources have much cooler MIR and warmer FIR colors than non-OHM sources. These clues could help us to choose OHM candidates for future OHM surveys with the Five-hundred-meter Aperture Spherical radio Telescope (FAST), where the OHM detection rate may exceed 40%. Further, one significant correlation of L OH ∝ L T FIR 1.18 ± 0.11 can be found between the maser luminosity and total FIR luminosity of OHM LIRGs. Combined with previous studies, we suggest that the OHM is dominantly pumped by the FIR, instead of NIR and MIR radiation fields. [ABSTRACT FROM AUTHOR]

Background: Leptomeningeal metastases (LM) were rare in gastric cancer (GC), and GC patients with LM (GCLM) generally suffer from poor prognosis. Nevertheless, the clinical utility of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) was underinvestigated in GCLM. Methods: We retrospectively studied 15 GCLM patients, and all patients had paired primary tumor tissue samples and post-LM CSF samples while 5 patients also had post-LM plasma samples. All samples were analyzed using next-generation sequencing (NGS), and the molecular and clinical features were correlated with clinical outcomes. Results: CSF had higher mutation allele frequency (P = 0.015), more somatic mutations (P = 0.032), and more copy-number variations (P < 0.001) than tumor or plasma samples. Multiple genetic alterations and aberrant signal pathways were enriched in post-LM CSF, including CCNE1 amplification and cell cycle-related genes, and CCNE1 amplification was significantly associated with patients' overall survival (P = 0.0062). More potential LM progression-related markers were detected in CSF samples than in tumor samples, including PREX2 mutation (P = 0.014), IGF1R mutation (P = 0.034), AR mutation (P = 0.038), SMARCB1 deletion (P < 0.001), SMAD4 deletion (P = 0.0034), and TGF-beta pathway aberration (P = 0.0038). Additionally, improvement in intracranial pressure (P < 0.001), improvement in CSF cytology (P = 0.0038), and relatively low levels of CSF ctDNA (P = 0.0098) were significantly associated with better PFS. Lastly, we reported a GCLM case whose CSF ctDNA dynamic changes were well correlated with his clinical assessment. Conclusions: CSF ctDNA could more sensitively detect molecular markers and metastasis-related mechanisms than tumor tissues in GCLM patients, and our study sheds light on utilizing CSF ctDNA in prognostic estimation and clinical assessment in GCLM. [ABSTRACT FROM AUTHOR]

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Purpose: There is a lack of research on the composition of destination attributes of memorable tourism experiences (MTEs) and their impact on tourist loyalty in Chinese rural tourism. Based on the extended SOR (stimulus-organism-response) theory, this study constructs a model of destination attributes (gastronomy, accommodation, physiography, and rural lifestyle) of MTEs on tourists' recommend intention and revisit intention under the chain mediating effect of positive arousal and memory in Chinese rural tourism. Methods: Through the judgment sampling method, this study distributed questionnaires to the subjects who met the sampling standard in all provincial administrative regions in China. Finally, 270 valid questionnaires from 29 provincial administrative regions were obtained and the proposed hypotheses were verified using a structural equation model. Results: The results show that gastronomy, accommodation, physiography and rural lifestyle are all destination attributes of MTEs in Chinese rural tourism, and all have a positive impact on positive arousal. In addition, they are positively correlated with recommend intention and revisit intention through the chain mediating effect of positive arousal and memory. Conclusion: This study explored the impact mechanism of destination attributes of MTEs on tourist destination loyalty in the field of Chinese rural tourism to enrich findings pertaining to the study of MTEs in different contexts. Four destination attributes of MTEs were proposed and verified, and this study also confirmed that destination attributes of MTEs vary with respect to the research context. The new destination attribute of MTEs was discovered. The research results showed that managers can deliver MTEs to tourists through optimizing gastronomy, accommodation, physiography and rural lifestyle, thus generating positive arousal, deepening their memory and then gaining their loyalty. In addition, the extended SOR theory proved that it could effectively and comprehensively explain the influencing mechanism of MTEs on tourist loyalty. [ABSTRACT FROM AUTHOR]

The unique energy conversion characteristics of metal halide perovskite (MHP) materials, which can be hardly observed in conventional semiconductors and metal oxides, have boosted their promising application in detecting and sensing devices, in addition to their famous optoelectronic functions. Herein, the recent progresses of the state‐of‐the‐art applications of MHPs are focused on X‐ray diagnosis, cardiac detection, bionic retina, artificial synapse, cell imaging, and others. Owing to their emerging electrical properties with multifield coupled response effect, and photoelectric, electro‐optical, and all‐optical conversion functions, MHPs demonstrate promising prospects in the diagnosis and treatment of various diseases. As functional optoelectronic materials, MHPs provide a new platform for future biomedical devices. This review article is expected to present the current status on, and further promote the application of MHP materials in detecting and sensing devices. [ABSTRACT FROM AUTHOR]

Background: Neurosyphilis refers to infection of the central nervous system by Treponema pallidum. The clinical presentation is variable and nonspecific. Neuroimaging findings are complex and that the diagnosis is based on clinical presentation, cerebrospinal fluid (CSF) parameters, and serologic and CSF evidence of syphilis. To date, there is no case report describing Treponema pallidum detected by metagenomic next-generation sequencing (mNGS) in CSF. Case presentation: In this report, we describe a case of neurosyphilis in a HIV-negative, 29-year-old man, who was admitted to our hospital with an epileptic seizure and progressive cognitive impairment. Brain magnetic resonance imaging (MRI) revealed fluid-attenuated inversion recovery (FLAIR) high signal intensities in bilateral medial and anterior temporal lobes, insula, right pulvinar of the thalami, precuneus, frontal and temporo-occipital lobes. Laboratory examination showed positive results by means of nontreponemal or specific treponemal test in serum and CSF. mNGS of the CSF was also performed to identify Treponema pallidum for the first time. Conclusions: This case underscores the importance of considering neurosyphilis as a potential cause of mesiotemporal abnormality. In addition, the rapid improvement and wide usability of mNGS technology will bring new breakthroughs in the clinical diagnosis of neurosyphilis. [ABSTRACT FROM AUTHOR]

Background: Fucoidan (FPS) has been widely used to treat renal fibrosis (RF) in patients with diabetic kidney disease (DKD); however, the precise therapeutic mechanisms remain unclear. Recently, research focusing on inflammation-derived podocyte pyroptosis in DKD has attracted increasing attention. This phenomenon is mediated by the activation of the nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to RF during DKD progression. Therefore, we designed a series of experiments to investigate the ameliorative effects of FPS on RF in DKD and the mechanisms that are responsible for its effect on NLRP3 inflammasome-mediated podocyte pyroptosis in the diabetic kidney. Methods: The modified DKD rat models were subjected to uninephrectomy, intraperitoneal injection of streptozotocin, and a high-fat diet. Following induction of renal injury, the animals received either FPS, rapamycin (RAP), or a vehicle for 4 weeks. For in vitro research, we exposed murine podocytes to high glucose and MCC950, an NLRP3 inflammasome inhibitor, with or without FPS or RAP. Changes in the parameters related to RF and inflammatory podocyte injury were analyzed in vivo. Changes in podocyte pyroptosis, NLRP3 inflammasome activation, and activation of the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/NLRP3 signaling axis involved in these changes were analyzed in vivo and in vitro. Results: FPS and RAP ameliorated RF and inflammatory podocyte injury in the DKD model rats. Moreover, FPS and RAP attenuated podocyte pyroptosis, inhibited NLRP3 inflammasome activation, and regulated the AMPK/mTORC1/NLRP3 signaling axis in vivo and in vitro. Notably, our data showed that the regulative effects of FPS, both in vivo and in vitro , on the key signaling molecules, such as p-AMPK and p-raptor, in the AMPK/mTORC1/NLRP3 signaling axis were superior to those of RAP, but similar to those of metformin, an AMPK agonist, in vitro. Conclusion: We confirmed that FPS, similar to RAP, can alleviate RF in DKD by inhibiting NLRP3 inflammasome-mediated podocyte pyroptosis via regulation of the AMPK/mTORC1/NLRP3 signaling axis in the diabetic kidney. Our findings provide an in-depth understanding of the pathogenesis of RF, which will aid in identifying precise targets that can be used for DKD treatment. [ABSTRACT FROM AUTHOR]

Background: The proximal renal tubule plays a critical role in diabetic kidney disease (DKD) progression. Early glomerular disease in DKD triggers a cascade of injuries resulting in renal tubulointerstitial disease. These pathophysiological responses are collectively described as diabetic tubulopathy (DT). Thus, therapeutic strategies targeting DT hold significant promise for early DKD treatment. Shenkang injection (SKI) has been widely used to treat renal tubulointerstitial fibrosis in patients with chronic kidney disease in China. However, it is still unknown whether SKI can alleviate DT. We designed a series of experiments to investigate the beneficial effects of SKI in DT and the mechanisms that are responsible for its effect on epithelial-to-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress-induced apoptosis in DT. Methods: The modified DKD rat models were induced by uni-nephrectomy, streptozotocin intraperitoneal injection, and a high-fat diet. Following the induction of renal injury, these animals received either SKI, rosiglitazone (ROS), or vehicle, for 42 days. For in vitro research, we exposed NRK-52E cells to high glucose (HG) and 4-phenylbutyric acid (4-PBA) with or without SKI or ROS. Changes in parameters related to renal tubular injury and EMT were analyzed in vivo. Changes in the proportion of apoptotic renal tubular cells and ER stress, and the signaling pathways involved in these changes, were analyzed both in vivo and in vitro. Results: SKI and ROS improved the general condition, the renal morphological appearance and the key biochemical parameters, and attenuated renal injury and EMT in the rat model of DKD. In addition, SKI and ROS alleviated apoptosis, inhibited ER stress, and suppressed PERK-eIF2α-ATF4-CHOP signaling pathway activation both in vivo and in vitro. Notably, our data showed that the regulatory in vitro effects of SKI on PERK-eIF2α-ATF4-CHOP signaling were similar to those of 4-PBA, a specific inhibitor of ER stress. Conclusion: This study confirmed that SKI can alleviate DT in a similar manner as ROS, and SKI achieves this effect by inhibiting EMT and ER stress-induced apoptosis. Our findings thereby provide novel information relating to the clinical value of SKI in the treatment of DT. [ABSTRACT FROM AUTHOR]

It is very difficult to diagnose and distinguish tuberculous meningitis, and the current laboratory methods are unsubstantial in developing countries. The study is aimed at creating a scoring system on the basis of basic laboratory and clinical achievements that could be used as diagnostic aid for tuberculous meningitis for Chinese patients. A retrospective study of cases was conducted for comparison between clinical characteristics and laboratory features of 241 patients on admission who conformed to inclusion criteria of tuberculous meningitis (n = 141) or bacterial meningitis (n = 100). Logistic regression was employed to establish a diagnostic formula to distinguish between tuberculous meningitis and bacterial meningitis. The receiver operating characteristic curve analysis was applied to determine the best diagnostic critical point of the diagnostic formula. It was found that five variables (disease course, white blood cell count, serum sodium, total white cell count of cerebrospinal fluid, and neutrophil proportion in cerebrospinal fluid) were independently associated with tuberculous meningitis. The 87% sensitivity and 94% specificity were included in the diagnostic scoring system derived from these variables. Especially in the case of limited microbial resources, doctors can use this diagnostic scoring system to distinguish tuberculous meningitis from bacterial meningitis. [ABSTRACT FROM AUTHOR]

It is very difficult to diagnose and distinguish tuberculous meningitis, and the current laboratory methods are unsubstantial in developing countries. The study is aimed at creating a scoring system on the basis of basic laboratory and clinical achievements that could be used as diagnostic aid for tuberculous meningitis for Chinese patients. A retrospective study of cases was conducted for comparison between clinical characteristics and laboratory features of 241 patients on admission who conformed to inclusion criteria of tuberculous meningitis (n = 141) or bacterial meningitis (n = 100). Logistic regression was employed to establish a diagnostic formula to distinguish between tuberculous meningitis and bacterial meningitis. The receiver operating characteristic curve analysis was applied to determine the best diagnostic critical point of the diagnostic formula. It was found that five variables (disease course, white blood cell count, serum sodium, total white cell count of cerebrospinal fluid, and neutrophil proportion in cerebrospinal fluid) were independently associated with tuberculous meningitis. The 87% sensitivity and 94% specificity were included in the diagnostic scoring system derived from these variables. Especially in the case of limited microbial resources, doctors can use this diagnostic scoring system to distinguish tuberculous meningitis from bacterial meningitis. [ABSTRACT FROM AUTHOR]

Background: The total flavones of Abelmoschus manihot (TFA), a compound that is extracted from Abelmoschus manihot , has been widely used in China to reduce podocyte injury in diabetic kidney disease (DKD). However, the mechanisms underlying the therapeutic action of this compound have yet to be elucidated. Podocyte pyroptosis is characterized by activation of the NLRP3 inflammasome and plays an important role in inflammation-mediated diabetic kidneys. Regulation of the PTEN/PI3K/Akt pathway is an effective strategy for improving podocyte damage in DKD. Previous research has also shown that N6-methyladenosine (m6A) modification is involved in DKD and that m6A-modified PTEN regulates the PI3K/Akt pathway. In this study, we investigated whether TFA alleviates podocyte pyroptosis and injury by targeting m6A modification-mediated NLRP3-inflammasome activation and PTEN/PI3K/Akt signaling. Methods: We used MPC-5 cells under high glucose (HG) conditions to investigate the key molecules that are involved in podocyte pyroptosis and injury, including activation of the NLRP3 inflammasome and the PTEN/PI3K/Akt pathway. We detected alterations in the levels of three methyltransferases that are involved in m6A modification. We also investigated changes in the levels of these key molecules in podocytes with the overexpression or knockdown of methyltransferase-like (METTL)3. Results: Analysis showed that TFA and MCC950 protected podocytes against HG-induced pyroptosis and injury by reducing the protein expression levels of gasdermin D, interleukin-1β, and interleukin-18, and by increasing the protein expression levels of nephrin, ZO-1, WT1 and podocalyxin. TFA and 740Y-P inhibited activation of the NLRP3 inflammasome via the PI3K/Akt pathway by inhibiting the protein levels of NIMA-related kinase7, NLRP3, ASC, and caspase-1, and by increasing the protein expression levels of p-PI3K and p-Akt. TFA improved pyroptosis and injury in HG-stimulated podocytes by regulating METTL3-dependent m6A modification. Conclusion: Collectively, our data indicated that TFA could ameliorate pyroptosis and injury in podocytes under HG conditions by adjusting METTL3-dependent m6A modification and regulating NLRP3-inflammasome activation and PTEN/PI3K/Akt signaling. This study provides a better understanding of how TFA can protect podocytes in DKD. [ABSTRACT FROM AUTHOR]

Background: Recently, progression of chronic renal failure (CRF) has been closely associated with gut microbiota dysbiosis and intestinal metabolite-derived microinflammation. In China, total flavones of Abelmoschus manihot (TFA), a component of Abelmoschus manihot , has been widely used to delay CRF progression in clinics for the past two decades. However, the overall therapeutic mechanisms remain obscure. In this study, we designed experiments to investigate the renoprotective effects of TFA in CRF progression and its underlying mechanisms involved in gut microbiota and microinflammation, compared with febuxostat (FEB), a potent non-purine selective inhibitor of xanthine oxidase. Methods: In vivo , the CRF rat models were induced by uninephrectomy, potassium oxonate, and proinflammatory diet, and received either TFA suspension, FEB, or vehicle after modeling for 28 days. In vitro , the RAW 264.7 cells were exposed to lipopolysaccharide (LPS) with or without TFA or FEB. Changes in parameters related to renal injury, gut microbiota dysbiosis, gut-derived metabolites, and microinflammation were analyzed in vivo. Changes in macrophage polarization and autophagy and its related signaling were analyzed both in vivo and in vitro. Results: For the modified CRF model rats, the administration of TFA and FEB improved renal injury, including renal dysfunction and renal tubulointerstitial lesions; remodeled gut microbiota dysbiosis, including decreased Bacteroidales and Lactobacillales and increased Erysipelotrichales ; regulated gut-derived metabolites, including d-amino acid oxidase, serine racemase, d-serine, and l-serine; inhibited microinflammation, including interleukin 1β (IL1β), tumor necrosis factor-α, and nuclear factor-κB; and modulated macrophage polarization, including markers of M1/M2 macrophages. More importantly, TFA and FEB reversed the expression of beclin1 (BECN1) and phosphorylation of p62 protein and light chain 3 (LC3) conversion in the kidneys by activating the adenosine monophosphate-activated protein kinase-sirtuin 1 (AMPK-SIRT1) signaling. Further, TFA and FEB have similar effects on macrophage polarization and autophagy and its related signaling in vitro. Conclusion: In this study, we demonstrated that TFA, similar to FEB, exerts its renoprotective effects partially by therapeutically remodeling gut microbiota dysbiosis and inhibiting intestinal metabolite-derived microinflammation. This is achieved by adjusting autophagy-mediated macrophage polarization through AMPK-SIRT1 signaling. These findings provide more accurate information on the role of TFA in delaying CRF progression. [ABSTRACT FROM AUTHOR]

Background: This study profiled the somatic genes mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM).Methods: A total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were bioinformatically analyzed by (Database for Annotation, Visualization and Integrated Discovery) DAVID software.Results: The most common mutated gene was TP53 (54/62; 87.10%), followed by EGFR (44/62; 70.97%), PTEN (39/62; 62.90%), CDKN2A (32/62; 51.61%), APC (27/62: 43.55%), TET2 (27/62; 43.55%), GNAQ (18/62; 29.03%), NOTCH1 (17/62; 27.42%), VHL (17/62; 27.42%), FLT3 (16/62; 25.81%), PTCH1 (15/62; 24.19%), BRCA2 (13/62; 20.97%), KDR (10/62; 16.13%), KIT (9/62; 14.52%), MLH1 (9/62; 14.52%), ATM (8/62; 12.90%), CBL (8/62; 12.90%), and DNMT3A (7/62; 11.29%). The mutated genes were enriched in the PI3K-Akt signaling pathway by the KEGG pathway analysis. Furthermore, the CNVs of these genes were also identified in these 62 samples. The mutated genes in CSF samples receiving intrathecal chemotherapy and systemic therapy were enriched in the ERK1/2 signaling pathway.Conclusions: This study identified genes mutations in all CSF ctDNA samples, indicating that these mutated genes may be acted as a kind of biomarker for diagnosis of NM, and these mutated genes may affect meningeal metastasis through PI3K-Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC.Methods: A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time.Results: The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA.Conclusions: This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of meningeal carcinomatosis (MC) treated by intrathecal chemotherapy (IC) and analyzes the prognostic factors.Methods: The clinical and follow-up data of 33 MC patients was collected and retrospectively analyzed. Potential prognostic factors such as age, gender, primary cancer, transfer time, presence of brain metastasis, intracranial pressure, protein, glucose, vascular endothelial growth factor (VEGF), eastern cooperative oncology group (ECOG) performance status (PS), systemic treatment and IC were discussed.Results: The most common clinical manifestation of MC was high intracranial pressure (30 cases). The negative rate of cerebrospinal fluid cytology was 50% after MC patients treated by IC. The remission rate of IC and no-IC group was 71.4% and 15.7%, respectively, of which the stability rate was 92.8% and 57.8% with significant difference. The median survival time was 5.200 months (95% CI 0.000-11.491) and the survival rate of 3, 6, 12 months were respectively 71.6%, 49.2%, 30.7%.Conclusion: IC can relieve the symptoms of MC and extend life expectancy. Early treatment can improve prognosis. Presence of brain metastasis, ECOG PS and IC were correlated with prognosis of patients, whereas IC is an independent prognostic factor. [ABSTRACT FROM AUTHOR]

Purpose: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyze the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes. Methods: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated. Results: Of the 11 patients, seven were males, and a mean age at presentation of 63 years (range: 47-79 years). The major clinical features include cognitive decline (9/11), epilepsy (10/11), mental and behavioral disorders (6/11), involuntary movement (4/11), sleep disorders (2/11), hearing loss (1/11), disturbance of consciousness (4/11) and fever (3/11). GABA-B receptor antibody was positive in serum and/or cerebrospinal fluid in 11 patients. Small-cell lung cancer was detected in five patients. Electroencephalogram monitoring demonstrated abnormal discharge in 10 cases. Epileptiform activities were found in five patients. Four patients showed abnormality in hippocampal region, parahippocampal gyrus, temporal and occipital lobe on magnetic resonance imaging. Ten patients accepted first-line immune therapy. Five patients with small-cell lung cancer received oncologic treatment. During a median follow-up of 11 months, eight patients showed a good outcome, two patients (cases 8 and 9) with tumors had a poor one and one patient (case 10) died of status epilepticus. Conclusion: Anti-GABAB receptor encephalitis is an uncommon autoimmune disease, which has been known to be often associated with cancer. Generally, patients associated with GABABR GABA-B receptor antibody encephalitis respond well to immunotherapy, especially if started early. [ABSTRACT FROM AUTHOR]

A novel broadband CPW-fed 2-iteration fractal antenna based on the circular patch and the equilateral triangle slot is designed for RF energy harvesting. The simulated and measured results show that the proposed antenna offers an impedance bandwidth of 162% from 0.88 to 8.45 GHz and a peak gain of 8.7 dBi. Afterwards, the single-stage voltage multiplier rectifier with a T shape LC matching network to reduce the reflection losses is used to realize RF-to-DC conversion in energy harvesting; here, it is also integrated with the fractal antenna to form the rectenna. Accumulating RF power from 2G (GSM), 3G (the third generation), 4G-LTE and WLAN frequency-bands, the measured results across an optimized load resistor of 4.7-kΩ show that the maximum rectenna efficiency is 51.8%, 46.1% and 45.08% at the center frequency of 2.4 GHz, 2.1 GHz and 1.9 GHz, respectively. Additionally, the measured peak conversion efficiency of the system is 24.03% at 2.4 GHz. [ABSTRACT FROM AUTHOR]

This article studies the optimization of space station short-term mission planning (STMP) problems. The domain knowledge including description and the concept definitions of the STMP problem are presented, an STMP constraint satisfaction model is developed, and then an iterative conflict-repair method with the resolving strategies is proposed to satisfy complicated constraints. A genetic algorithm (GA) is adopted to optimize the STMP problem. The proposed approach is evaluated using a test case with 15 missions, 13 devices and three astronauts. The results show that the established STMP constraint satisfaction model is effective, and the iterative conflict-repair method can make the plan satisfy all constraints considered and can effectively improve the optimization performance of the GA. [ABSTRACT FROM AUTHOR]

Background: Conventional hyperbaric spinal anaesthesia solution (SAS) with 8% glucose and low-dose bupivacaine may reduce the incidence of hypotension in caesarean section compared to standard doses, and marginally hyperbaric SAS (≤0.8% glucose) can induce a lower block level and a lower incidence of hypotension in nonobstetric patients than conventional 8% glucose SAS.Objective: The objective of this study was to evaluate the clinical efficacy of marginally hyperbaric low-dose bupivacaine solutions used for spinal anaesthesia during caesarean section.Design: A randomised, controlled clinical trial.Setting: Single medical centre.Patients: One hundred twenty women scheduled for elective caesarean section were randomised into four groups.Interventions: Caesarean section after combined spinal-epidural anaesthesia using hyperbaric preparations of low-dose SAS (7.2 mg bupivacaine and 2 μg 1.6 ml sufentanil in one of the following: 8%, 0.8%, 0.5% or 0.33% glucose solution.Main Outcome Measures: The dermatomal sensory block and degree of motor block of the lower extremities and adverse effects of anaesthesia were recorded.Results: The maximum cephalad sensory block level and the incidence of hypotension decreased as the density of SAS fell (T1, T2, T4 and T6, P < 0.001; 48.3, 30, 13.3 and 10.3%, P = 0.003). The incidence of shivering reduced with decreasing density of SAS (P < 0.05). There was no significant difference in the quality of anaesthesia (efficacy of motor block and sensory block) between the groups (P > 0.05).Conclusion: Compared with conventional 8% glucose hyperbaric SAS, marginally hyperbaric (0.5 or 0.33% glucose) low-dose bupivacaine solutions led to a significantly lower height of cephalad spread and incidence of hypotension with no impact on the efficacy of spinal anaesthesia for caesarean section. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the mechanism underlying the cardioprotection bestowed by chronic intermittent hypobaric hypoxia (CIHH ) against ischemia/reperfusion (I/R) injury in developing rats. Neonatal male rats were subjected to CIHH treatments that simulated an altitude of 3000 m a.s.l. for 28 days (CIHH28) and 42 days (CIHH42), respectively, or no treatment (control). The left ventricular function of isolated hearts was evaluated. The ultra-microstructure, superoxide dismutase (SOD) activity and total anti-oxidation capacity (TAC) of the myocardium were determined. The basic left ventricular function remained unchanged in CIHH rats, except for an increased coronary flow. The recovery of cardiac function from I/R, however, was much better in CIHH rats than in control rats. Compared to control rats, CIHH rats had much higher SOD levels and TAC, and the ultra-microstructure damage to mitochondria was considerably less. The cardiac protection of CIHH was canceled out by glibenclamide, an inhibitor of the ATP-sensitive potassium (K) channel, 5-hydroxydecanoate, an inhibitor of mitochondrial K (mitoK), and atractyloside, an opener of the mitochondrial permeability transition pore (MPTP). To the contrary, diazoxide, an opener of mitoK, and cyclosporin A, a blocker of MPTP opening, induced cardioprotection in control rats. These results suggest that CIHH protects the heart against I/R injury in developing rats through opening of the K channel and inhibiting of opening of the MPTP. [ABSTRACT FROM AUTHOR]

The air transport industry crucially depends on traffic forecasting for supporting management decisions. In this study, a singular spectrum analysis (SSA)-based ensemble forecasting modeling approach is proposed. The original air passenger time series is first decomposed into three components: trend, seasonal oscillations, and irregular component. The trend is predicted by generalized regression neural network (GRNN), whereas seasonal oscillations are predicted by radial basis function networks (RNFNs). The empirical results of Hong Kong (HK) air passenger data show a significant improvement of the proposed ensemble method in comparison to other results of competing models. [ABSTRACT FROM AUTHOR]

Background Cryptococcal meningitis (CM) is the most common fungal infection of central nervous system, caused by Cryptococcus neoformans infection of the meninges. The development and prognosis of CM depend on the patient's own immune function to some extent, and are relative to the imbalance of helper T lymphocyte (Th1/Th2). This study aims to explore the hidden role of the local Th1/ Th2 immune response in the pathophysiological process of CM. Methods The levels of Th1 cytokines interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and Th2 cytokine interleukin-10 (IL-10) in the cerebrospinal fluid (CSF) were detected by enzyme - linked immunosorbent assay (ELISA). CSF cytology changes were monitored dynamically to understand the outcome status of patients with CM. Results The levels of IFN - γ and TNF - α in CM patients [(11.17 ± 1.50) and (18.74 ± 2.97) pg/ml, respectively] were significantly lower than that in control patients [(17.69 ± 2.34) and (28.83 ± 3.55) pg/ml; P = 0.000, for all]. However, the levels of IL-10 in CM patients [(43.65 ± 10.12) pg/ml] were significantly higher than that in control patients [(7.80 ± 1.30) pg/ml, P = 0.000]. The CSF IFN-γ and TNF-α levels in acute phase of CM patients [(11.17 ± 1.50) pg/ml and (18.74 ± 2.97) pg/ml, respectively] were significantly lower than that in stable phase of CM patients [(17.70 ± 2.34) and (22.93 ± 1.53) pg/ml;P = 0.000, for all]. On the other hand, the levels of IL-10 were significantly higher in the acute phase than that in stable phase [(43.65 ± 10.12) and (22.93 ± 7.39) pg/ml, respectively; P = 0.000]. The ratios of Th1/Th2 were used to assess the contribution of Th1/Th2 immunity in acute and stable phase of CM patients. The ratios of IFN-γ/IL-10 and TNF-α/IL-10 measured in acute phase of CM patients were significantly lower than that in control patients (P = 0.000, for all). These ratios in acute phase patients were also significantly lower than that in stable phase patients (P = 0.000, for all). Conclusions In acute phase, the Th2 response is dominant in patients with CM. However, the immune response shifts towards to Th1 response in the stable phase, providing direct evidence that the imbalance of Th1-Th2 cytokines is related to the pathogenesis of CM. [ABSTRACT FROM AUTHOR]

This paper examines the proxy variables of investor sentiment in Chinese stock market carefully, and tries to construct an investor sentiment index indirectly. We use cross correlation analysis to examine lead-lag relationship between the proxy variables and HS300 index. The results show that net added accounts (NAA), SSE share turnover (TURN), and closed-end fund discount (CEFD) are leading variables to stock market. The average first day return of IPOs (RIPO) and relative degree of active trading in equity market (RDAT) are contemporary variables, while number of IPOs (NIPO) is a lagging variable of stock market. Using the sentiment proxy variables with most possible leading order, and forward selection stepwise regression method, the empirical results on monthly stock returns reveal that three leading proxy variables can be used to form a sentiment index. And the out of sample tests prove that this sentiment index has good predictive power of Chinese stock market, and it is robust. [ABSTRACT FROM AUTHOR]

In the analysis of existing methods of Petri net modeling and FPGA implementation of the models, this paper firstly discussed the Petri net modeling of parallel computing. This method included decomposing the parallel computing task into multiple parallel processing units, and modeling the system by using IOPT net. Then it proposed the double layer structure, which contained monitoring layer and of algorithm layer, in order to map the Petri net model to FPGA implementation. This implementation method was an effective solution to the problem that transitions of Petri nets model could only represent the simple addition and subtraction operations. A matrix multiplication application shows that the above methods are correct and generic. Finally, it gave further research directions. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, selectively involving the upper and lower motor neurons. Glutamate excitotoxicity and oxidative stress are important mechanisms for the pathogenesis of ALS. Nuclear-factor erythroid 2-related factor 2 (Nrf2) is a master transcriptional regulator of many cytoprotective genes. Nrf2 signal pathway could induce a series of antioxidant enzyme, anti-inflammatory and antitoxic protein. The expression of these antioxidant enzymes and antioxidant proteins in nervous system exhibited broad neuroprotection against injury by glutamate. Diallyl trisulfide (DATS) was previously shown to induce many Nrf2 target genes in non-nervous cells. Our studies have shown that DATS at 50 m M caused activation of Nrf2 and Nrf2 target gene in rat spinal cord explants. DATS also protected motor neurons against glutamate-induced excitotoxicity. These have identified DATS as a promising neuroprotective agent and suggest that the activation of Nrf2 signal pathway may be a new strategy in neurodegeneration disease. [ABSTRACT FROM AUTHOR]

Outcomes among patients with diabetes mellitus (DM) was unclear. Cohort study of patients with DM who underwent coronary angiography and were For patients with CAD and DM, the HbA1c was a routine test. [Extracted from the article]

Background: Recently, chronic kidney disease (CKD)-mineral and bone disorder (MBD) has become one of common complications occurring in CKD patients. Therefore, development of a new treatment for CKD–MBD is very important in the clinic. In China, Fucoidan (FPS), a natural compound of Laminaria japonica has been frequently used to improve renal dysfunction in CKD. However, it remains elusive whether FPS can ameliorate CKD–MBD. FGF23-Klotho signaling axis is reported to be useful for regulating mineral and bone metabolic disorder in CKD–MBD. This study thereby aimed to clarify therapeutic effects of FPS in the CKD–MBD model rats and its underlying mechanisms in vivo and in vitro , compared to Calcitriol (CTR). Methods: All male rats were divided into four groups: Sham, CKD–MBD, FPS and CTR. The CKD–MBD rat models were induced by adenine administration and uninephrectomy, and received either FPS or CTR or vehicle after induction of renal injury for 21 days. The changes in parameters related to renal dysfunction and renal tubulointerstitial damage, calcium-phosphorus metabolic disorder and bone lesion were analyzed, respectively. Furthermore, at sacrifice, the kidneys and bone were isolated for histomorphometry, immunohistochemistry and Western blot. In vitro , the murine NRK-52E cells were used to investigate regulative actions of FPS or CTR on FGF23-Klotho signaling axis, ERK1/2-SGK1-NHERF-1-NaPi-2a pathway and Klotho deficiency. Results: Using the modified CKD–MBD rat model and the cultured NRK-52E cells, we indicated that FPS and CTR alleviated renal dysfunction and renal tubulointerstitial damage, improved calcium-phosphorus metabolic disorder and bone lesion, and regulated FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. In addition, using the shRNA-Klotho plasmid-transfected cells, we also detected, FPS accurately activated ERK1/2-SGK1-NHERF-1-NaPi-2a pathway through Klotho loss reversal. Conclusion: In this study, we emphatically demonstrated that FPS, a natural anti-renal dysfunction drug, similar to CTR, improves renal injury-related calcium-phosphorus metabolic disorder and bone abnormality in the CKD–MBD model rats. More importantly, we firstly found that beneficial effects in vivo and in vitro of FPS on phosphorus reabsorption are closely associated with regulation of FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. This study provided pharmacological evidences that FPS directly contributes to the treatment of CKD–MBD. [ABSTRACT FROM AUTHOR]

Objectives: Stroke is one of the rare but devastating complications after hip fracture in the elderly. By far, there is still scarce data on postoperative stroke in elderly patients with hip fractures. Methods: This was a retrospective study of prospectively collected data. Between October 2014 to December 2018, patients aged above 65 years who underwent operative treatment for hip fractures were included. Inpatient medical surveillance and scheduled telephone follow-up at 1, 3, 6, and 12 months after operation was conducted to identify who developed an incident stroke. Variables of interests were extracted from patients' inpatient medical records. Univariate analysis and multivariate logistic regression analysis were used to identify the independent risk factors associated with stroke. Results: During the study period, a total of 3743 patients were included, among whom 56 were found to have a stroke after operation, representing an incidence of 1.5% (95% CI, 1.1 to 1.9%). The multivariate analyses showed that advanced age (1-year increment; OR, 1.32; 95% CI, 1.08 to 1.48), history of previous stroke (OR, 4.79; 95% CI, 1.86 to 6.56), ASA III and above (OR, 2.62; 95% CI, 1.27 to 3.68), long-term use of aspirin (OR, 3.63; 95% CI, 1.41 to 4.78), and elevated RDW level (each increment of 1%, OR, 1.21; 95% CI, 1.02 to 1.36) were independently associated with postoperative stroke. Conclusions: Although most are not modifiable, these risk factors help in counseling patients regarding the risk of postoperative stroke, individual risk stratification, and targeted optimization of medical conditions and should be firmly kept in treating surgeon's mind. [ABSTRACT FROM AUTHOR]

Background: The inflammatory or non-inflammatory changes caused by the virus entering the nervous system and related tissues are central nervous system virus infections. Viral infection is a common infectious disease of the central nervous system, of which herpes simplex virus encephalitis is the most common. However, conventional laboratory techniques to detect an infectious agent are difficult to achieve etiological diagnosis. Case presentation: Here we present a patient with severe and progressive encephalitis, requiring diagnosis of the specific pathogen to guide clinical treatments. Conclusions: Application of next-generation sequencing provided a quick and definite diagnosis of the etiology of encephalitis and enabled our patient to be treated appropriately. [ABSTRACT FROM AUTHOR]

Background: It is usually very complicated to treat meningeal carcinomatosis, and it is important to treat it as soon as possible.Case Presentation: The 19-Del mutation was found in the exon for the epidermal growth factor receptor gene in the pleural effusion of a patient on March 11th, 2015. He took 250 mg of oral gefitinib once a day for 11 months beginning in December of 2015. On the 3rd of November 2016, he arrived at the hospital and presented with dizziness, headache and transient blurred vision. At this time, he began to take 4 mg of oral zoledronic acid once a month to prevent bone metastases. The result of a cytology exam of the cerebrospinal fluid showed that the man had meningeal carcinomatosis. The 19-Del mutation and the 20-T790 M mutation in the exon of the epidermal growth factor receptor gene was found by the next generation sequencing of the CSF. Then, he discontinued taking gefitinib and began to take 90-100 mg of oral AZD9291 once a day in November 2016. After adjusting the medication dose based on the NGS, his headache was noticeably reduced, and his condition gradually stabilized.Conclusions: Cerebrospinal fluid ctDNA detection by next generation sequencing may become a suitable biomarker to monitor clinical treatment response in meningeal carcinomatosis. [ABSTRACT FROM AUTHOR]

In this paper, the RF energy harvesting system and RF‐based wireless power transfer system are proposed and designed for battery‐less self‐sustaining application. For energy harvesting, the designed antenna array improves the received RF power effectively and also can harvest RF energy in multi‐frequency bands. For wireless power transfer, the proposed helical antenna realizes the system design in miniaturization. Subsequently, the T shape LC matching network are designed between the antenna and the rectifying circuit to obtain more power transmission. The measured results show that the proposed Wi‐Fi rectifier and 433 MHz rectifier offer a maximum conversion efficiency of 66.8% and 76% in case of the input power is −3 dBm and 0 dBm, respectively. Finally, the performance of the RF‐based wireless power transfer system and RF energy harvesting system are attested by experimentally measurement, the measured results indicate that these systems can be used to power electronic. [ABSTRACT FROM AUTHOR]