Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study.

BACKGROUND: Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. METHODS: Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. RESULTS: Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3 ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). CONCLUSION: FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.

4-Octyl itaconate attenuates glycemic deterioration by regulating macrophage polarization in mouse models of type 1 diabetes.

BACKGROUND: Pancreatic beta cell dysfunction and activated macrophage infiltration are early features in type 1 diabetes pathogenesis. A tricarboxylic acid cycle metabolite that can strongly activate NF-E2-related factor 2 (Nrf2) in macrophages, itaconate is important in a series of inflammatory-associated diseases via anti-inflammatory and antioxidant properties. However, its role in type 1 diabetes is unclear. We used 4-octyl itaconate (OI), the cell-permeable itaconate derivate, to explore its preventative and therapeutic effects in mouse models of type 1 diabetes and the potential mechanism of macrophage phenotype reprogramming. METHODS: The mouse models of streptozotocin (STZ)-induced type 1 diabetes and spontaneous autoimmune diabetes were used to evaluate the preventative and therapeutic effects of OI, which were performed by measuring blood glucose, insulin level, pro- and anti-inflammatory cytokine secretion, histopathology examination, flow cytometry, and islet proteomics. The protective effect and mechanism of OI were examined via peritoneal macrophages isolated from STZ-induced diabetic mice and co-cultured MIN6 cells with OI-pre-treated inflammatory macrophages in vitro. Moreover, the inflammatory status of peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients was evaluated after OI treatment. RESULTS: OI ameliorated glycemic deterioration, increased systemic insulin level, and improved glucose metabolism in STZ-induced diabetic mice and non-obese diabetic (NOD) mice. OI intervention significantly restored the islet insulitis and beta cell function. OI did not alter the macrophage count but significantly downregulated the proportion of M1 macrophages. Additionally, OI significantly inhibited MAPK activation in macrophages to attenuate the macrophage inflammatory response, eventually improving beta cell dysfunction in vitro. Furthermore, we detected higher IL-1ß production upon lipopolysaccharide stimulation in the PBMCs from type 1 diabetes patients, which was attenuated by OI treatment. CONCLUSIONS: These results provided the first evidence to date that OI can prevent the progression of glycemic deterioration, excessive inflammation, and beta cell dysfunction predominantly mediated by restricting macrophage M1 polarization in mouse models of type 1 diabetes.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages.

Phagocytosis is a pivotal process by which macrophages eliminate microorganisms after recognition by pathogen sensors. Here we unexpectedly found that the self ligand and cell surface receptor SLAM functioned not only as a costimulatory molecule but also as a microbial sensor that controlled the killing of gram-negative bacteria by macrophages. SLAM regulated activity of the NADPH oxidase NOX2 complex and phagolysosomal maturation after entering the phagosome, following interaction with the bacterial outer membrane proteins OmpC and OmpF. SLAM recruited a complex containing the intracellular class III phosphatidylinositol kinase Vps34, its regulatory protein kinase Vps15 and the autophagy-associated molecule beclin-1 to the phagosome, which was responsible for inducing the accumulation of phosphatidylinositol-3-phosphate, a regulator of both NOX2 function and phagosomal or endosomal fusion. Thus, SLAM connects the gram-negative bacterial phagosome to ubiquitous cellular machinery responsible for the control of bacterial killing.

Acute pancreatitis in pregnancy: a 10-year, multi-center, retrospective study in Beijing.

OBJECTIVE: Acute pancreatitis in pregnancy (APIP) is a rare and serious complication during pregnancy. It has acute onset and is difficult to diagnose and treat. The aim of the present study was to describe the etiology, clinical manifestations, and maternofetal outcomes of APIP. METHODS: We retrospectively reviewed 32 pregnant women who were treated at three tertiary care hospitals in Beijing, China. The correlation between the causes of APIP, severity, laboratory indices, and outcomes was analyzed. RESULTS: The most common causes of APIP were hypertriglyceridemia (56.2%,18/32) and gallstones (28.1%, 9/32). Hypertriglyceridemia-induced APIP was associated with a higher rate of severe acute pancreatitis (P = 0.025). Serum level of triglycerides showed a positive correlation with the severity of APIP (P = 0.039). The most frequent presentation of APIP was abdominal pain (93.7%, 30/32). There were no maternal or fetal deaths in our study. Apgar scores at 1 min, 5 min, and 10 min of the premature neonates was correlated with the severity of APIP of the mother (P = 0.022; 0.002; 0.002). CONCLUSION: High level of triglycerides may serve as a useful marker of the severity of APIP. The severity of APIP was associated with higher risk of neonate asphyxia. Appropriate timing of termination of pregnancy is a key imperative for APIP patients.

Expression of peripheral monocytic programmed death ligand-1 in severe sepsis combined with HBV-related cirrhosis. A pilot observational study.

INTRODUCTION: Hepatitis B virus (HBV)-related liver cirrhosis (LC) complicated with severe sepsis (SS) leads to HBV-related acute-on-chronic liver failure (HBV-ACLF). Programmed cell death ligand-1 (PD-L1)-associated immunosuppression is involved in both LC and SS. This study aimed to examine the expression and clinical relevance of PD-L1 on peripheral CD14+ monocytes in sepsis-induced HBV-ACLF. MATERIAL AND METHODS: PD-L1 expression on peripheral CD14+ monocytes among the healthy control (HC), LC and LC + SS groups was examined using flow cytometry analysis and compared. In the LC + SS group, an SS-induced ACLF subgroup was identified. LC + SS patients were followed up for 28 days. The correlations between monocytic PD-L1 expression and illness severity scores and the prognostic value of monocytic PD-L1 expression in SS-induced HBV-ACLF patients was examined. RESULTS: There were 17, 30 and 70 participants in the HC, LC and LC + SS groups, respectively. The monocytic PD-L1 expression was higher in the LC group compared with the HC group and in the LC + SS group compared with the LC group. The monocytic PD-L1 expression was positively correlated with the illness severity scores in LC + SS patients and predicted 28-day mortality of SS-induced HBV-ACLF patients (n = 59). CONCLUSIONS: Severe sepsis exhibits a superimposed effect of monocytic PD-L1 up-regulation on the basis of liver cirrhosis, and monocytic PD-L1 expression predicts 28-day mortality of SS-induced HBV-ACLF.

Enhanced Attention Using Head-mounted Virtual Reality.

Some evidence suggests that experiencing a given scenario using virtual reality (VR) may engage greater attentional resources than experiencing the same scenario on a 2D computer monitor. However, the underlying neural processes associated with these VR-related effects, especially those pertaining to current consumer-friendly head-mounted displays of virtual reality (HMD-VR), remain unclear. Here, two experiments were conducted to compare task performance and EEG-based neural metrics captured during a perceptual discrimination task presented on two different viewing platforms. Forty participants (20-25 years old) completed this task using both an HMD-VR and traditional computer monitor in a within-group, randomized design. Although Experiment I (n = 20) was solely behavioral in design, Experiment II (n = 20) utilized combined EEG recordings to interrogate the neural correlates underlying potential performance differences across platforms. These experiments revealed that (1) there was no significant difference in the amount of arousal measured between platforms and (2) selective attention abilities in HMD-VR environment were enhanced from both a behavioral and neural perspective. These findings suggest that the allocation of attentional resources in HMD-VR may be superior to approaches more typically used to assess these abilities (e.g., desktop/laptop/tablet computers with 2D screens).

14.85 µW Analog Front-End for Photoplethysmography Acquisition with 142-dBΩ Gain and 64.2-pArms Noise.

A low-power, high-gain, and low-noise analog front-end (AFE) for wearable photoplethysmography (PPG) acquisition systems is designed and fabricated in a 0.35 µm CMOS process. A high transimpedance gain of 142 dBΩ and a low input-referred noise of only 64.2 pArms was achieved. A Sub-Hz filter was integrated using a pseudo resistor, resulting in a small silicon area. To mitigate the saturation problem caused by background light (BGL), a BGL cancellation loop and a new simple automatic gain control block are used to enhance the dynamic range and improve the linearity of the AFE. The measurement results show that a DC photocurrent component up-to-10 µA can be rejected and the PPG output swing can reach 1.42 Vpp at THD < 1%. The chip consumes a total power of 14.85 µW using a single 3.3-V power supply. In this work, the small area and efficiently integrated blocks were used to implement the PPG AFE and the silicon area is minimized to 0.8 mm × 0.8 mm.

Removal of Motion Artifacts in Photoplethysmograph Sensors during Intensive Exercise for Accurate Heart Rate Calculation Based on Frequency Estimation and Notch Filtering.

With photoplethysmograph (PPG) sensors showing increasing potential in wearable health monitoring, the challenging problem of motion artifact (MA) removal during intensive exercise has become a popular research topic. In this study, a novel method that combines heart rate frequency (HRF) estimation and notch filtering is proposed. The proposed method applies a cascaded adaptive noise cancellation (ANC) based on the least mean squares (LMS)-Newton algorithm for preliminary motion artifacts reduction, and further adopts special heart rate frequency tracking and correction schemes for accurate HRF estimation. Finally, notch filters are employed to restore the PPG signal with estimated HRF based on its quasi-periodicity. On an open source data set that features intensive running exercise, the proposed method achieves a competitive mean average absolute error (AAE) result of 0.92 bpm for HR estimation. The practical experiments are carried out with the PPG evaluation platform developed by ourselves. Under three different intensive motion patterns, a 0.89 bpm average AAE result is achieved with the average correlation coefficient between recovered PPG signal and reference PPG signal reaching 0.86. The experimental results demonstrate the effectiveness of the proposed method for accurate HR estimation and robust MA removal in PPG during intensive exercise.

Abundance of ammonia-oxidizing bacteria and archaea under different ventilation strategies during cattle manure composting.

Composting of cattle manure was conducted under four ventilation strategies, i.e., no-aeration (A-00), continuous aeration (B-44), non-aeration for 14 d and then aeration for 42 d (C-04), aeration for 14 d and then no-aeration for 42 d (D-40). Physicochemical parameters and potential ammonia oxidation (PAO) indicated that continuous and intermittent ventilation provide favourable conditions for ammonia-oxidizing bacteria (AOB) and archaea (AOA) to oxidize ammonia. Quantitative PCR (qPCR) analysis showed AOB amoA gene abundance of all treatments on every sampling day ranged from 2.25 × 105 to 2.76 × 109copies/g, was significantly lower than that of archaeal amoA gene from 2.71 × 108 to 9.05 × 1011copies/g. There was also a significantly positive relationship between PAO rates and AOB (r2 ≥ 0.066, p < 0.05) and AOA (r2 ≥ 0.300, p < 0.05) abundance. These data suggested that ammonia oxidation is driven by both AOA and AOB in cattle manure composting.

The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.

The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome of C. rodentium infections in Rag(-/-) mice. Surprisingly, the pathology and immune responses in the lamina propria of C. rodentium-infected Slamf6(-/-) Rag(-/-) mice were markedly reduced as compared with those of Rag(-/-) mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower in Slamf6(-/-) Rag(-/-) mice than in Rag(-/-) animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 to Rag(-/-) mice ameliorated the infection compared with a control antibody. We conclude that Slamf6-mediated interactions of colonic innate immune cells with specific Gram(-) bacteria reduce mucosal protection and enhance inflammation, contributing to lethal colitis that is caused by C. rodentium infections in Rag(-/-) mice.

The effects of phosphodiesterase-5 inhibitor sildenafil against post-resuscitation myocardial and intestinal microcirculatory dysfunction by attenuating apoptosis and regulating microRNAs expression: essential role of nitric oxide syntheses signaling.

BACKGROUND: Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. Sildenafil has been shown to attenuate postresuscitation myocardial dysfunction in piget models of ventricular fibrillation. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by attenuating apoptosis and regulating miRNA expressions, furthermore, ameliorating the severity of post-microcirculatory dysfunction. METHODS: Twenty-four male pigs (weighing 30 ± 2 kg) were randomly divided into groups, sildenafil pretreatment (n = 8), saline (n = 8) and sham operation (sham, n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil, administered once intraperitoneally 30 min prior to ventricular fibrillation (VF). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC). Surviving pigs were euthanatized at 24 h after ROSC, and hearts were removed for analysis by electron microscopy, western blotting, quantitative real-time polymerase chain reaction (PCR), and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Intestinal microcirculatory blood flow was visualized by a sidestream dark-field imaging device at baseline and 0.5, 1, 2, 4, and 6 h after ROSC. RESULTS: Compared with the saline group, the sildenafil group had a higher 24-hour survival (7/8 versus 3/8 survivors, p < 0.05) and a better outcome in hemodynamic parameters. The protective effect of sildenafil also correlated with reduced cardiomyocyte apoptosis, as evidenced by reduced TUNEL-positive cells, increased anti-apoptotic Bcl-2/Bax ratio and inhibited caspase-3 activity in myocardium. Additionally, sildenafil treatment inhibited the increases in the microRNA-1 levels and alleviated the decreases in the microRNA-133a levels which negatively regulates pro-apoptotic genes. At 6 h after ROSC, post-resuscitation perfused vessel density and microcirculatory flow index were significantly lower in the saline group than in the sildenafil group. CONCLUSIONS: The major findings of this study are as follows: (1) sildenafil improved post-resuscitation perfusion of the heart, and thus reduced cardiac myocyte apoptosis and improved cardiac function; (2) sildenafil treatment inhibited the increases in the microRNA-1 levels, but alleviated the decreases in the microRNA-133a levels.

Association of a functional variant in the Wnt co-receptor LRP6 with early onset ileal Crohn's disease.

Ileal Crohn's Disease (CD), a chronic small intestinal inflammatory disorder, is characterized by reduced levels of the antimicrobial peptides DEFA5 (HD-5) and DEFA6 (HD-6). Both of these α-defensins are exclusively produced in Paneth cells (PCs) at small intestinal crypt bases. Different ileal CD-associated genes including NOD2, ATG16L1, and recently the ß-catenin-dependant Wnt transcription factor TCF7L2 have been linked to impaired PC antimicrobial function. The Wnt pathway influences gut mucosal homeostasis and PC maturation, besides directly controlling HD-5/6 gene expression. The herein reported candidate gene study focuses on another crucial Wnt factor, the co-receptor low density lipoprotein receptor-related protein 6 (LRP6). We analysed exonic single nucleotide polymorphisms (SNPs) in a large cohort (Oxford: n = 1,893) and prospectively tested 2 additional European sample sets (Leuven: n = 688, Vienna: n = 1,628). We revealed an association of a non-synonymous SNP (rs2302685; Ile1062Val) with early onset ileal CD (OR 1.8; p = 0.00034; for homozygous carriers: OR 4.1; p = 0.00004) and additionally with penetrating ileal CD behaviour (OR 1.3; p = 0.00917). In contrast, it was not linked to adult onset ileal CD, colonic CD, or ulcerative colitis. Since the rare variant is known to impair LRP6 activity, we investigated its role in patient mucosa. Overall, LRP6 mRNA was diminished in patients independently from the genotype. Analysing the mRNA levels of PC product in biopsies from genotyped individuals (15 controls, 32 ileal, and 12 exclusively colonic CD), we found particularly low defensin levels in ileal CD patients who were carrying the variant. In addition, we confirmed a direct relationship between LRP6 activity and the transcriptional expression of HD-5 using transient transfection. Taken together, we identified LRP6 as a new candidate gene in ileal CD. Impairments in Wnt signalling and Paneth cell biology seem to represent pathophysiological hallmarks in small intestinal inflammation and should therefore be considered as interesting targets for new therapeutic approaches.

Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System.

Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

TCF-1-mediated Wnt signaling regulates Paneth cell innate immune defense effectors HD-5 and -6: implications for Crohn's disease.

Wnt signaling regulates small intestinal stem cell maintenance and Paneth cell differentiation. In patients with ileal Crohn's disease (CD), a decrease of Paneth cell α-defensins has been observed that is partially caused by impaired TCF-4 and LRP6 function. Here we show reduced expression of the Wnt signaling effector TCF-1 (also known as TCF-7) in patients with ileal CD. Reporter gene assays and in vitro promoter binding analysis revealed that TCF-1 activates α-defensin HD-5 and HD-6 transcription in cooperation with ß-catenin and that activation is mediated by three distinct TCF binding sites. EMSA analysis showed binding of TCF-1 to the respective motifs. In ileal CD patients, TCF-1 mRNA expression levels were significantly reduced. Moreover, we found specifically reduced expression of active TCF-1 mRNA isoforms. Tcf-1 knockout mice exhibited reduced cryptdin expression in the jejunum, which was not consistently seen at other small intestinal locations. Our data provide evidence that TCF-1-mediated Wnt signaling is disturbed in small intestinal CD, which might contribute to the observed barrier dysfunction in the disease.

Cutting edge: Slamf8 is a negative regulator of Nox2 activity in macrophages.

Slamf8 (CD353) is a cell surface receptor that is expressed upon activation of macrophages (MΦs) by IFN-γ or bacteria. In this article, we report that a very high NADPH oxidase (Nox2) enzyme activity was found in Slamf8(-/-) MΦs in response to Escherichia coli or Staphylococcus aureus, as well as to PMA. The elevated Nox2 activity in Slamf8(-/-) MΦs was also demonstrated in E. coli or S. aureus phagosomes by using a pH indicator system and was further confirmed by a reduction in the enzyme activity after transfection of the receptor into Slamf8-deficient primary MΦs or RAW 264.7 cells. Upon exposure to bacteria or PMA, protein kinase C activity in Slamf8(-/-) MΦs is increased. This results in an enhanced phosphorylation of p40phox, one key component of the Nox2 enzyme complex, which, in turn, leads to greater Nox2 activity. Taken together, the data show that, in response to inflammation-associated stimuli, the inducible receptor Slamf8 negatively regulates inflammatory responses.

The protective effects of a phosphodiesterase 5 inhibitor, sildenafil, on postresuscitation cardiac dysfunction of cardiac arrest: metabolic evidence from microdialysis.

INTRODUCTION: Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism. METHODS: Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously, and the experiment was terminated 24 hours after resuscitation. RESULTS: After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P < 0.05). Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05). Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05). Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively). Furthermore, 24 hours after ROSC, the sildenafil group had marked elevations in activity of left ventricular Na(+)-K(+)-ATPase and Ca(2+)-ATPase compared with the SA group (P = 0.03, P = 0.04, respectively). CONCLUSIONS: Sildenafil could reduce the severity of postresuscitation myocardial dysfunction, and it produced better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat postresuscitation myocardial dysfunction.

Beneficial effects of pioglitazone on retardation of persistent atrial fibrillation progression in diabetes mellitus patients.

This study aimed to explore the effects of pioglitazone treatment on progression from persistent atrial fibrillation (AF) to permanent atrial fibrillation in diabetes mellitus (DM) patients and to investigate the possible mechanisms involved in those effects.A total of 146 diabetes mellitus (DM) patients with firstly identified persistent AF were selected. Seventy patients were randomized into the pioglitazone (30 mg/day) group and 76 into the placebo group. Pro-collagen type I carboxyterminal peptide (PICP), advanced glycation end products (AGEs), and angiotensin II were assayed and left atrial diameter (LA diameter) was measured at the first presence of persistent AF, and at 6 and 14 months of follow-up. The time point of identification of permanent AF and the incidence of permanent AF in the patients were all recorded.Thirty-seven (49%) of the 76 patients in the placebo group and 21 (30%) of the 70 patients in the pioglitazone group progressed to permanent AF (P = 0.028). No significant differences existed in the follow-up time (20.5 ± 3.97 months for pioglitazone group versus 20.9 ± 4.14 months for placebo group) between the two groups (P = 0.535). In the pioglitazone group, no significant change was found in angiotensin II level. The PICP level did not change significantly at 6-months of follow-up, but decreased significantly at 14-months of follow-up (P = 0.032). The AGE (P = 0.037 at 6-month follow-up, P < 0.035 at 14-month follow-up) level was significantly lower at both 6 and 14-months of followup.By lowering the PICP level, pioglitazone treatment may decrease the incidence of permanent AF in DM patients with persistent AF, which may be associated with the suppressing effect of pioglitazone on AGEs.

Self-Adaptive Perception of Object's Deformability with Multiple Deformation Attributes Utilizing Biomimetic Mechanoreceptors.

The perception of object's deformability in unstructured interactions relies on both kinesthetic and cutaneous cues to adapt the uncertainties of an object. However, the existing tactile sensors cannot provide adequate cutaneous cues to self-adaptively estimate the material softness, especially in non-standard contact scenarios where the interacting object deviates from the assumption of an elastic half-infinite body. This paper proposes an innovative design of a tactile sensor that integrates the capabilities of two slow-adapting mechanoreceptors within a soft medium, allowing self-decoupled sensing of local pressure and strain at specific locations within the contact interface. By leveraging these localized cutaneous cues, the sensor can accurately and self-adaptively measure the material softness of an object, accommodating variations in thicknesses and applied forces. Furthermore, when combined with a kinesthetic cue from the robot, the sensor can enhance tactile expression by the synergy of two relevant deformation attributes, including material softness and compliance. It is demonstrated that the biomimetic fusion of tactile information can fully comprehend the deformability of an object, hence facilitating robotic decision-making and dexterous manipulation.

An Energy-Efficient FD-fNIRS Readout Circuit Employing a Mixer-First Analog Frontend and a Σ-Δ Phase-to-Digital Converter.

This paper presents a low-power frequency-domain functional near-infrared spectroscopy (FD-fNIRS) readout circuit for the absolute value measurement of tissue optical characteristics. The paper proposes a mixer-first analog front-end (AFE) structure and a 1-bit Σ-Δ phase-to-digital converter (PDC) to reduce the required circuit bandwidth and the laser modulation frequency, thereby saving power while maintaining high resolution. The proposed chip achieves sub-0.01° phase resolution and consumes 6.8 mW of power. Nine optical solid phantoms are produced to evaluate the chip. Compared to a self-built high-precision measurement platform that combines a network analyzer with an avalanche photodiode (APD) module, the maximum measuring errors of the absorption coefficient and reduced scattering coefficient are 10.6% and 12.3%, respectively.