Peripheral Inflammatory and Immune Landscape in Multiple System Atrophy: A Cross-Sectional Study.

BACKGROUND: Neuroinflammation might contribute to the pathogenesis of multiple systemic atrophy (MSA). However, specific alterations in the peripheral inflammatory and immune profiles of patients with MSA remain unclear. OBJECTIVES: To determine the peripheral inflammatory and immune profiles of patients with MSA and their potential value as biomarkers for facilitating clinical diagnosis and monitoring disease severity. METHODS: This cross-sectional study included 235, 240, and 235 patients with MSA, patients with Parkinson's disease (PD), and healthy controls (HCs), respectively. Inflammatory and immune parameters were measured in peripheral blood, differences between groups were assessed, and clusters were analyzed. Associations between the parameters and clinical characteristics of MSA were assessed using Spearman and partial correlation analyses. RESULTS: Significant differences were observed especially in monocytes, neutrophils-to-lymphocyte ratio (NLR) and neutrophils-to-lymphocyte ratio (MPV) between MSA patients and HCs (P < 0.01). Monocytes and uric acid (UA) levels were also significantly different between the MSA and PD patients (P < 0.05). The combination of NLR and MPV distinguished MSA-P patients from HCs (areas under the curve = 0.824). In addition, complement components C4 and C3 were significantly correlated with the Scale Outcomes in PD for Autonomic Symptoms and Wexner scale, whereas immunoglobulin G (IgG) was significantly correlated with scores of Unified Multiple System Atrophy Rating Scale (P < 0.05). CONCLUSIONS: In MSA patients, monocytes, NLR and MPV might serve as potential diagnostic biomarkers, whereas MLR, C3, C4, and IgG significantly correlate with disease severity. © 2023 International Parkinson and Movement Disorder Society.

Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.

Tubular epithelial cells (TECs) play critical roles in the development of diabetic nephropathy (DN), and can activate macrophages through the secretion of exosomes. However, the mechanism(s) of TEC-exosomes in macrophage activation under DN remains unknown. By mass spectrometry, 1,644 differentially expressed proteins, especially Dll4, were detected in the urine exosomes of DN patients compared with controls, which was confirmed by western blot assay. Elevated Epsin1 and Dll4/N1ICD expression was observed in kidney tissues in both DN patients and db/db mice and was positively associated with tubulointerstitial damage. Exosomes from high glucose (HG)-treated tubular cells (HK-2) with Epsin1 knockdown (KD) ameliorated macrophage activation, TNF-α, and IL-6 expression, and tubulointerstitial damage in C57BL/6 mice in vivo. In an in vitro study, enriched Dll4 was confirmed in HK-2 cells stimulated with HG, which was captured by THP-1 cells and promoted M1 macrophage activation. In addition, Epsin1 modulated the content of Dll4 in TEC-exosomes stimulated with HG. TEC-exosomes with Epsin1-KD significantly inhibited N1ICD activation and iNOS expression in THP-1 cells compared with incubation with HG alone. These findings suggested that Epsin1 could modulate tubular-macrophage crosstalk in DN by mediating exosomal sorting of Dll4 and Notch1 activation.

Renal outcomes after contrast exposure in patients with diabetes who use sodium-glucose cotransporter 2 inhibitors.

BACKGROUND: Contrast-induced nephropathy has become increasingly prevalent as the age and prevalence of comorbidities in the general population have increased. Most cases of contrast-induced nephropathy are reversible; however, some may progress to acute kidney disease, and subsequently, to chronic kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known for their renoprotective effects. However, whether the use of these inhibitors affects the risk of contrast-induced kidney injury remains unclear. METHODS: Data were collected from the Taipei Medical University Clinical Research Database. We included patients with diabetes who had contrast exposure between 2016 and 2020 because of computed tomography or coronary angiography. The primary outcome was the risk of a major adverse kidney event (MAKE), which encompassed acute kidney disease, chronic kidney disease progression, and the need for renal replacement therapy. Overlap weighting was performed to reduce the effects of potential confounders. RESULTS: This study included 12 421 patients, who were divided into two groups: SGLT2i users (n = 920) and nonusers (n = 11 501). The follow-up period after contrast exposure was 6 months. The risk of a MAKE was lower in SGLT2i users than in nonusers (incidence, 36.9 vs. 49.9 per 1000 person-months, respectively; P = .0011). Furthermore, the incidence of acute kidney disease or chronic kidney disease progression was significantly lower in the SGLT2i users than in nonusers. However, no significant between-group difference was noted in the incidence of other MAKEs. CONCLUSIONS: SGLT2i may be safely used in diabetic patients needing contrast exposure. The risk of a MAKE may be lower in SGLT2i users than in nonusers.

Reconstruction of OFDM Signals Using a Dual Discriminator CGAN with BiLSTM and Transformer.

Communication signal reconstruction technology represents a critical area of research within communication countermeasures and signal processing. Considering traditional OFDM signal reconstruction methods' intricacy and suboptimal reconstruction performance, a dual discriminator CGAN model incorporating LSTM and Transformer is proposed. When reconstructing OFDM signals using the traditional CNN network, it becomes challenging to extract intricate temporal information. Therefore, the BiLSTM network is incorporated into the first discriminator to capture timing details of the IQ (In-phase and Quadrature-phase) sequence and constellation map information of the AP (Amplitude and Phase) sequence. Subsequently, following the addition of fixed position coding, these data are fed into the core network constructed based on the Transformer Encoder for further learning. Simultaneously, to capture the correlation between the two IQ signals, the VIT (Vision in Transformer) concept is incorporated into the second discriminator. The IQ sequence is treated as a single-channel two-dimensional image and segmented into pixel blocks containing IQ sequence through Conv2d. Fixed position coding is added and sent to the Transformer core network for learning. The generator network transforms input noise data into a dimensional space aligned with the IQ signal and embedding vector dimensions. It appends identical position encoding information to the IQ sequence before sending it to the Transformer network. The experimental results demonstrate that, under commonly utilized OFDM modulation formats such as BPSK, QPSK, and 16QAM, the time series waveform, constellation diagram, and spectral diagram exhibit high-quality reconstruction. Our algorithm achieves improved signal quality while managing complexity compared to other reconstruction methods.

No Correlation between Plasma GPNMB Levels and Multiple System Atrophy in Chinese Cohorts.

BACKGROUND: Glycoprotein nonmetastatic melanoma protein B (GPNMB) has been demonstrated to mediate pathogenicity in Parkinson's disease (PD) through interactions with α-synuclein, and plasma GPNMB tended to be a novel biomarker for PD. OBJECTIVE: The goal of this study was to investigate whether plasma GPNMB could act as a potential biomarker for the clinical diagnosis and severity monitoring of multiple system atrophy (MSA), another typical synucleinopathy. METHODS: Plasma GPNMB levels in patients with MSA, patients with PD, and healthy control subjects (HCs) were quantified using enzyme-linked immunosorbent assays. RESULTS: A total of 204 patients with MSA, 65 patients with PD, and 207 HCs were enrolled. The plasma GPNMB levels in patients with MSA were similar to those in HCs (P = 0.251) but were significantly lower than those in patients with PD (P = 0.003). Moreover, there was no significant correlation detected between the plasma GPNMB levels and disease severity scores of patients with MSA. CONCLUSIONS: No evidence was detected for the biomarker potential of plasma GPNMB in MSA. © 2023 International Parkinson and Movement Disorder Society.

Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFß-dependent Smad/YAP/TAZ signaling.

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-ß (TGFß)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFß through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFß axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.

Independent and joint associations of aerobic and muscle-strengthening exercise with mental health in adolescents: A cross-sectional analysis before and during COVID-19 using the 2015-2021 National Youth Risk Behavior Survey.

PURPOSE: COVID-19 led to social isolation that may have compromised adolescent mental health. This study examined the independent and joint associations of aerobic physical activity (PA) and muscle-strengthening exercise (MSE) with mental health problems in adolescents. METHODS: Participants were US adolescents who completed the 2015-2021 National Youth Risk Behavior Survey (N = 61,298; 45.7% female). Data were collected between 2015 and 2021 and analyzed in 2023. Outcomes were binary response items asking about feeling sad/hopeless, having difficulty concentrating, remembering, or making decisions, and having a suicidal ideation. Preventive exposure variables were items asking about frequencies of aerobic PA and MSE with responses dichotomized to align with recommendations. Independent and joint associations were examined using robust Poisson regression with covariates selected using double selection lasso. Structural equation models examined the associations treating PA and MSE as continuous predictors and poor mental health as a latent dependent variable. RESULTS: Meeting either recommendation alone associated with a 4-10% lower prevalence of mental health problems (APR = 0.90-0.96, p < 0.05), and meeting both recommendations associated with a 15%-20% lower prevalence of mental health problems (APR = 0.80-0.85, p < 0.001). Although categorical joint associations were stronger in males (p < 0.05), multiplicative interactions were observed in females using continuous variables for PA and MSE (ß = -0.09, p < 0.001). CONCLUSION: Meeting aerobic PA and MSE recommendations associated with lower prevalence of mental health problems. Participation in MSE below recommended levels may be beneficial for females when combined with aerobic PA. Future research should examine these associations by acquiring contextual information and device-based assessments.

Association of rurality, type of primary caregiver and place of death with end-of-life medical expenditures among the oldest-old population in China.

BACKGROUND: Understanding whether the type of primary caregiver and end-of-life (EOL) care location are associated with EOL medical expenditures is crucial to inform global debates on policies for efficient and effective EOL care. This study aims to assess trends in the type of primary caregiver and place of death stratified by rural‒urban status among the oldest-old population from 1998-2018 in China. A secondary objective is to determine the associations between rurality, the type of primary caregiver, place of death and EOL medical expenditures.  METHODS: A total of 20,149 deaths of people aged 80 years or older were derived from the Chinese Longitudinal Health Longevity Survey (CLHLS). Cochran-Armitage tests and Cuzick's tests were used to test trends in the type of primary caregiver and place of death over time, respectively. Tobit models were used to estimate the marginal associations of rurality, type of primary caregiver, and place of death with EOL medical expenditures because CLHLS sets 100,000 Chinese yuan (approximately US$15,286) as the upper limit of the outcome variable.  RESULTS: Of the 20,149 oldest-old people, the median age at death was 97 years old, 12,490 (weighted, 58.6%, hereafter) were female, and 8,235 lived in urban areas. From 1998-2018, the prevalence of informal caregivers significantly increased from 94.3% to 96.2%, and home death significantly increased from 86.0% to 89.5%. The proportion of people receiving help from informal caregivers significantly increased in urban decedents (16.5%) but decreased in rural decedents (-4.0%), while home death rates significantly increased among both urban (15.3%) and rural (1.8%) decedents. In the adjusted models, rural decedents spent less than urban decedents did (marginal difference [95% CI]: $-229 [$-378, $-80]). Those who died in hospitals spent more than those who died at home ($798 [$518, $1077]). No difference in medical expenditures by type of primary caregiver was observed. CONCLUSIONS: Over the past two decades, the increases in informal caregiver utilization and home deaths were unequal, leading to substantially higher EOL medical expenditures among urban decedents and deceased individuals who died at hospitals than among their counterparts who lived in rural areas and died at home.

Hierarchical Controlled Hybrid Quantum Communication Based on Six-Qubit Entangled States in IoT.

The rapid development and extensive application of the Internet of Things (IoT) have brought new challenges and opportunities to the field of communication. By integrating quantum secure communication with the IoT, we can provide a higher level of security and privacy protection to counteract security threats in the IoT. In this paper, a hybrid quantum communication scheme using six-qubit entangled states as a channel is proposed for specific IoT application scenarios. This scheme achieves hierarchical control of communication protocols on a single quantum channel. In the proposed scheme, device A transmits data to device B through quantum teleportation, while device B issues control commands to device A through remote quantum state preparation technology. These two tasks are controlled by control nodes C and D, respectively. The transmission of information from device A to device B is a relatively less important task, which can be solely controlled by control node C. On the other hand, issuing control commands from device B to device A is a more crucial task requiring joint control from control nodes C and D. This paper describes the proposed scheme and conducts simulation experiments using IBM's Qiskit Aer quantum computing simulator. The results demonstrate that the fidelity of the quantum teleportation protocol (QTP) and the remote state preparation protocol (RSP) reach an impressive value of 0.999, fully validating the scheme's feasibility. Furthermore, the factors affecting the fidelity of the hybrid communication protocol in an IoT environment with specific quantum noise are analyzed. By combining the security of quantum communication with the application scenarios of the IoT, this paper presents a new possibility for IoT communication.

A Scheme for Quantum Teleportation and Remote Quantum State Preparation of IoT Multiple Devices.

With the continuous development of the Internet of Things (IoT) technology, the industry's awareness of the security of the IoT is also increasing, and the adoption of quantum communication technology can significantly improve the communication security of various devices in the IoT. This paper proposes a scheme of controlled remote quantum state preparation and quantum teleportation based on multiple communication parties, and a nine-qubit entanglement channel is used to achieve secure communication of multiple devices in the IoT. The channel preparation, measurement operation, and unitary operation of the scheme were successfully simulated on the IBM Quantum platform, and the entanglement degree and reliability of the channel were verified through 8192 shots. The scheme's application in the IoT was analyzed, and the steps and examples of the scheme in the secure communication of multiple devices in the IoT are discussed. By simulating two different attack modes, the effect of the attack on the communication scheme in the IoT was deduced, and the scheme's high security and anti-interference ability was analyzed. Compared with other schemes from the two aspects of principle and transmission efficiency, it is highlighted that the advantages of the proposed scheme are that it overcomes the single fixed one-way or two-way transmission protocol form of quantum teleportation in the past and can realize quantum communication with multiple devices, ensuring both security and transmission efficiency.

Low-dose arecoline regulates distinct core signaling pathways in oral submucous fibrosis and oral squamous cell carcinoma.

BACKGROUND: Betel nut chewing plays a role in the pathogenesis of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). As the major active ingredient of the betel nut, the effect of arecoline and its underlying mechanism to OSF and OSCC pathogenesis remain unclear. METHODS: Next-generation sequencing-based transcriptome and dRRBS analysis were performed on OSF and OSCC cells under low-dose arecoline exposure. Functional analyses were performed to compare the different roles of arecoline during OSF and OSCC pathogenesis, and key genes were identified. RESULTS: In this study, we identified that low-dose arecoline promoted cell proliferation of both NFs and OSCC cells via the acceleration of cell cycle progression, while high-dose arecoline was cytotoxic to both NFs and OSCC cells. We performed for the first time the transcriptome and methylome landscapes of NFs and OSCC cells under low-dose arecoline exposure. We found distinct transcriptome and methylome profiles mediated by low-dose arecoline in OSF and OSCC cells, as well as specific genes and signaling pathways associated with metabolic disorders induced by low-dose arecoline exposure. Additionally, low-dose arecoline displayed different functions at different stages, participating in the modulation of the extracellular matrix via Wnt signaling in NFs and epigenetic regulation in OSCC cells. After exposure to low-dose arecoline, the node roles of FMOD in NFs and histone gene clusters in OSCC cells were found. Meanwhile, some key methylated genes induced by arecoline were also identified, like PTPRM and FOXD3 in NFs, SALL3 and IRF8 in OSCC cells, indicating early molecular events mediated by arecoline during OSF and OSCC pathogenesis. CONCLUSIONS: This study elucidated the contribution of low-dose arecoline to OSF and OSCC pathogenesis and identified key molecular events that could be targeted for further functional studies and their potential as biomarkers.

Epac activation ameliorates tubulointerstitial inflammation in diabetic nephropathy.

Tubulointerstitial inflammation plays an important role in the progression of diabetic nephropathy (DN), and tubular epithelial cells (TECs) are crucial promoters of the inflammatory cascade. Exchange protein activated by cAMP (Epac) has been shown to suppress the angiotensin II (Ang-II)-induced release of inflammatory cytokines in tubular cells. However, the role of Epac in TEC-mediated tubulointerstitial inflammation in DN remains unknown. We found that administering the Epac agonist 8-pCPT-2'-O-Me-cAMP (8-O-cAMP) to db/db mice inhibited tubulointerstitial inflammation characterized by macrophage infiltration and increased inflammatory cytokine release and consequently alleviated tubulointerstitial fibrosis in the kidney. Furthermore, 8-O-cAMP administration restored CCAAT/enhancer binding protein ß (C/EBP-ß) expression and further upregulated the expression of Suppressor of cytokine signaling 3 (SOCS3), while inhibiting p-STAT3, MCP-1, IL-6, and TNF-α expression in the kidney cortex in db/db mice. And in vitro study showed that macrophage migration and MCP-1 expression induced by high glucose (HG, 30 mM) were notably reduced by 8-O-cAMP in human renal proximal tubule epithelial (HK-2) cells. In addition, 8-O-cAMP treatment restored C/EBP-ß expression in HK-2 cells and promoted C/EBP-ß translocation to the nucleus, where it transcriptionally upregulated SOCS3 expression, subsequently inhibiting STAT3 phosphorylation. Under HG conditions, siRNA-mediated knockdown of C/EBP-ß or SOCS3 in HK-2 cells partially blocked the inhibitory effect of Epac activation on the release of MCP-1. In contrast, SOCS3 overexpression inhibited HG-induced activation of STAT3 and MCP-1 expression in HK-2 cells. These findings indicate that Epac activation via 8-O-cAMP ameliorates tubulointerstitial inflammation in DN through the C/EBP-ß/SOCS3/STAT3 pathway.

Activation of UCP2 by anethole trithione suppresses neuroinflammation after intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating disease, in which neuroinflammation substantially contributes to brain injury. Uncoupling protein 2 (UCP2) is a member of the mitochondrial anion carrier family, which uncouples oxidative phosphorylation from ATP synthesis by facilitating proton leak across the mitochondrial inner membrane. UCP2 has been reported to modulate inflammation. In this study we investigated whether and how UCP2 modulated neuroinflammation through microglia/macrophages following ICH in vitro and in vivo. We used an in vitro neuroinflammation model in murine BV2 microglia to mimic microglial activation following ICH. ICH in vivo model was established in mice through collagenase infusion into the left striatum. ICH mice were treated with anetholetrithione (ADT, 50 mg· kg-1 ·d-1, ip) or the classical protonophoric uncoupler FCCP (injected into hemorrhagic striatum). We showed that the expression and mitochondrial location of microglial UCP2 were not changed in both in vitro and in vivo ICH models. Knockdown of UCP2 exacerbated neuroinflammation in BV2 microglia and mouse ICH models, suggesting that endogenous UCP2 inhibited neuroinflammation and therefore played a protective role following ICH. ADT enhanced mitochondrial ROS production thus inducing mitochondrial uncoupling and activating UCP2 in microglia. ADT robustly suppressed neuroinflammation, attenuated brain edema and improved neurological deficits following ICH, and these effects were countered by striatal knockdown of UCP2. ADT enhanced AMP-activated protein kinase (AMPK) activation in the hemorrhagic brain, which was abrogated by striatal knockdown of UCP2. Moreover, striatal knockdown of AMPK abolished the suppression of neuroinflammation by ADT following ICH. On the other hand, FCCP-induced mitochondrial uncoupling was independent of UCP2 in microglia; and striatal knockdown of UCP2 did not abrogate the suppression of neuroinflammation by FCCP in ICH mice. In conclusion, the uncoupling activity is essential for suppression of neuroinflammation by UCP2. We prove for the first time the concept that activators of endogenous UCP2 such as anetholetrithione are a new class of uncouplers with translational significance.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Transthoracic, thoracoabdominal, and transabdominal surgical approaches for gastric cardia adenocarcinomas: a survival evaluation based on a cohort of 7103 patients.

BACKGROUND: This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. METHODS: A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan-Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. RESULTS: There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages. CONCLUSION: Thoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Performance of the renal resistive index and usual clinical indicators in predicting persistent AKI.

BACKGROUND: Early recognition of persistent acute kidney injury (AKI) could optimize management and prevent deterioration of kidney function. The Doppler-based renal resistive index (RI) has shown promising results for predicting persistent AKI in preliminary studies. Here, we aimed to evaluate the performance of renal RI, clinical indicators, and their combinations to predict short-term kidney prognosis in septic shock patients. METHOD: We performed a retrospective study based on data from a prospective study in a single-center general ICU between November 2017 and October 2018. Patients with septic shock were included. Clinical indicators were evaluated immediately at inclusion, and renal RI was measured within the first 12 h of ICU admission after hemodynamic stabilization. Persistent AKI was defined as AKI without recovery within 72 h. A multivariable logistic regression was used to select significant variables associated with persistent AKI. The discriminative power was evaluated by a receiver operating characteristic curve analysis. RESULT: Overall, 102 patients were included, 39 of whom had persistent AKI. Renal RI was higher in the persistent AKI patients than in those without persistent AKI: 0.70 ± 0.05 vs. 0.66 ± 0.05; p = 0.001. The performance of RI to predict persistent AKI was poor, with an area under the receiver operating characteristic curve (AUROC) of 0.699 [95% confidence interval (CI) 0.600-0.786]. A clinical prediction model combining serum creatinine at inclusion and the nonrenal SOFA score showed a better prediction ability for nonrecovery, with an AUROC of 0.877 (95% CI 0.797-0.933, p = 0.0012). The addition of renal RI to this model did not improve the predictive performance. CONCLUSION: The Doppler-based renal resistive index performed poorly in predicting persistent AKI and did not improve the clinical prediction provided by a combination of serum creatinine at inclusion and the nonrenal SOFA score in patients with septic shock.

State of Charge Estimation of Lithium-Ion Batteries Based on an Adaptive Iterative Extended Kalman Filter for AUVs.

As a power source for autonomous underwater vehicles (AUVs), lithium-ion batteries play an important role in ensuring AUVs' electric power propulsion performance. An accurate state of charge (SOC) estimation method is the key to achieving energy optimization for lithium-ion batteries. Due to the complicated ocean environments, traditional filtering methods cannot effectively estimate the SOC of lithium-ion batteries in an AUV. Based on the standard extended Kalman filter (EKF), an adaptive iterative extended Kalman filter (AIEKF) method for the SOC in an AUV is proposed to address the traditional filter's problems, such as low accuracy and large errors. In this method, the adaptive update is introduced to deal with the uncertain noise from the lithium-ion battery. The iteration is used to improve the convergence speed and to reduce the computational burden. Compared with the EKF, iterative extended Kalman filter (IEKF) and adaptive extended Kalman filter (AEKF), the proposed AIEKF has a higher estimation accuracy and anti-interference capability, which is suitable for the AUV's SOC estimation. In addition, based on the second-order equivalent circuit model of the lithium-ion battery, a forgetting factor recursive least squares (FFRLS) method is proposed to deal with the multi-variability problem. In the end, four different methods, including EKF, IEKF, AEKF, and the proposed AIEKF, are compared in computational time. The experiment results show that the proposed method has high accuracy and fast estimation speed, meaning that it has good application potential in AUVs.

Awareness for Endoscopic Screening Among Accompanying Children of Hospitalized Esophageal Cancer Patients in Henan.

The free generalized endoscopic screening for diagnosis of early esophageal cancer and precancerous lesion could not be satisfactorily implemented in China. At present, the decision to accept endoscopic screening at their own expense may largely depend on the public awareness. This study was aimed to investigate the awareness and other influencing factors associated with the accompanying children of esophageal cancer patients after their hospitalization. In this cross-sectional study, from April to June 2016, 233 children of accompanying patients, who were admitted within the last 1 year due to esophageal cancer in three affiliated hospitals of Zhengzhou University and Anyang Tumor Hospital, were enrolled. In addition, telephone surveys were conducted to investigate their awareness about endoscopic screening. One child was corresponded to an esophageal cancer patient. About half (47.6%, 111/233) of the children were unaware that endoscopic screening could detect early esophageal cancer and precancerous lesion. There was no significant difference in their awareness rates between hospitals with different administration levels. Besides, the males who had a lower family income and lower education level showed a poor awareness rate (P < 0.05). The overall awareness rate among the accompanying children of patients on endoscopic screening was rather low in Henan province (China). Hence, the health education and awareness on the importance of endoscopic screening for early detection of esophageal cancer should be promoted among children accompanying the patients. More attention should be focused towards the subject group, particularly among those male children with lower educational level and family income.

SYT7 acts as an oncogene and a potential therapeutic target and was regulated by ΔNp63α in HNSCC.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) are one of the most common types of head and neck cancer, and it is urgent to find effective treatment for advanced patients. Exploring developing and progressing mechanisms of HNSCC could provide a theoretical basis to find new therapeutic targets. METHODS: In our research, we performed a whole-gene expression profile microarray analysis to identify differential expression genes between squamous cell carcinoma cells and ΔNp63 alpha (ΔNp63α) knockdown cells. As a result, an important gene Synaptotagmin VII (SYT7) was screened out. RESULTS: SYT7 knockdown affected the proliferation, apoptosis and cell cycle of squamous cell carcinoma cells. The rescue experiment in vitro with ΔNp63α and SYT7 double knockdown resulted in partial reversion of ΔNp63α-induced phenotypes. This was also confirmed by experiments in vivo. CONCLUSIONS: Taken together, we found that ΔNp63α could inhibit the occurrence and progression of HNSCC throughout downregulating the expression of SYT7. Therefore, SYT7/ΔNp63α axis could be a potential therapeutic target for clinical treatment of HNSCC.

Identification of four key prognostic genes and three potential drugs in human papillomavirus negative head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a common tumor worldwide with poor prognosis. The pathogenesis of human papillomavirus (HPV)-positive and HPV-negative HNSCCs differs. However, few studies have considered the HPV status when identifying biomarkers for HNSCC. Thus, the identification of biomarkers for HPV-positive and HPV-negative HNSCCs is urgently needed. METHODS: Three microarray datasets from Gene Expression Omnibus (GEO) were analyzed, and the differentially expressed genes (DEGs) were obtained. Then, functional enrichment pathway analysis was performed and protein-protein interaction (PPI) networks were constructed. The expression of hub genes at both the mRNA and protein level was determined in Oncomine, The Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA). In addition, survival analysis of the patient stratified by HPV status and the expression levels of key genes were performed based on TCGA data. The role of AREG, STAG3, CAV1 and C19orf57 in cancer were analyzed through Gene set enrichment analysis (GSEA). The top ten small molecule drugs were identified and the therapeutic value of zonisamide, NVP-AUY922, PP-2 and fostamatinib was further evaluated in six HPV-negative HNSCC cell lines. Finally, the therapeutic value of NVP-AUY922 was tested in vivo based on three HPV-negative HNSCC models, and statistical analysis was performed. RESULTS: In total, 47 DEGs were obtained, 11 of which were identified as hub genes. Biological process analysis indicated that the hub genes were associated with the G1/S transition of the mitotic cell cycle. Survival analysis uncovered that the prognostic value of AREG, STAG3, C19orf57 and CAV1 differed between HPV-positive and HPV-negative patients. Gene set enrichment analysis (GSEA) showed the role of AREG, STAG3 and CAV1 in dysregulated pathways of tumor. Ten small molecules were identified as potential drugs specifically for HPV-positive or HPV-negative patients; three-NVP-AUY922, fostamatinib and PP-2-greatly inhibited the proliferation of six HPV-negative HNSCC cell lines in vitro, and NVP-AUY922 inhibited three HPV-negative HNSCC xenografts in vivo. CONCLUSIONS: In conclusion, AREG, STAG3, C19orf57 and CAV1 are key prognostic factors and potential therapeutic targets in HPV-negative HNSCC. NVP-AUY922, fostamatinib and PP-2 may be effective drugs for HPV-negative HNSCC.