Dysrhythmic saliva microbiota in mobile phone addicts with sleep disorders and restored by acupuncture.

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

An AIE-active tetra-aryl imidazole-derived chemodosimeter for turn-on recognition of hydrazine and its bioimaging in living cells.

A new chemodosimeter SWJT-31 with an aggregation-induced emission (AIE) effect was designed and constructed. Upon increasing the water fraction in the solution, it exhibited typical AIE, which showed bright red fluorescence at 610 nm. SWJT-31 could sensitively and specifically recognize hydrazine by the TICT effect with an LOD of 33.8 nM, which was much lower than the standard of the USEPA. A portable test strip prepared using SWJT-31 was also developed for the visual detection of hydrazine. Eventually, it was successfully used for the detection of hydrazine in water samples and HeLa cells.

Electro-scalp acupuncture regulates the expression of CYP27a1/b1, CYP24a and related inflammatory cytokines in ischemic cortex of rats with middle cerebral artery occlusion. / ç”µå¤´é’ˆè°ƒæŽ§å¤§è„‘ä¸­åŠ¨è„‰æ “å¡žå¤§é¼ ç¼ºè¡€å¤§è„‘çš®å±‚åŒºCYP27a1/b1、CYP24aåŠç›¸å ³ç‚Žæ€§ç»†èƒžå› å­è¡¨è¾¾çš„ç ”ç©¶.

OBJECTIVES: To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke. METHODS: Sixty SD rats were randomly divided into sham-operation, model, vitamin D3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D3 group were given 1, 25-VitD3 solution (3 ng·100 g-1·d-1) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1ß and IL-4 in the cerebral cortex of ischemic area were detected by Western blot. RESULTS: Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were increased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased (P<0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were decreased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased (P<0.01) in the ESA and vitamin D3 groups. CONCLUSIONS: ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D3, inhibiting vitamin D3 degradation, and regulating Th1/Th2 balance.

An unexpected role of EasDaf: catalyzing the conversion of chanoclavine aldehyde to chanoclavine acid.

Ergot alkaloids (EAs) are a diverse group of indole alkaloids known for their complex structures, significant pharmacological effects, and toxicity to plants. The biosynthesis of these compounds begins with chanoclavine-I aldehyde (CC aldehyde, 2), an important intermediate produced by the enzyme EasDaf or its counterpart FgaDH from chanoclavine-I (CC, 1). However, how CC aldehyde 2 is converted to chanoclavine-I acid (CC acid, 3), first isolated from Ipomoea violacea several decades ago, is still unclear. In this study, we provide in vitro biochemical evidence showing that EasDaf not only converts CC 1 to CC aldehyde 2 but also directly transforms CC 1 into CC acid 3 through two sequential oxidations. Molecular docking and site-directed mutagenesis experiments confirmed the crucial role of two amino acids, Y166 and S153, within the active site, which suggests that Y166 acts as a general base for hydride transfer, while S153 facilitates proton transfer, thereby increasing the acidity of the reaction. KEY POINTS: • EAs possess complicated skeletons and are widely used in several clinical diseases • EasDaf belongs to the short-chain dehydrogenases/reductases (SDRs) and converted CC or CC aldehyde to CC acid • The catalytic mechanism of EasDaf for dehydrogenation was analyzed by molecular docking and site mutations.

Artificial Intelligence-Assisted Multiparameter Size Discrimination of Silver Nanoparticles through Electrochemical Collision.

Single particle collision is an important tool for size analysis at the individual particle level; however, due to complex dynamic behaviors of nanoparticles on the surface of an electrode, the accuracy of size discrimination is limited. A silver (Ag) nanoparticle (NP) was chosen as the research target, and the dynamic behavior of Ag NPs was simplified by enhancing adsorption between Ag NP and Au ultramicroelectrode (UME) in alkaline media. Immediately after, accurate dynamic and thermodynamic information on single Ag NP was accurately extracted from collision events, including current intensity, transferred charge, and duration time. On the basis that there were differences between parameters of different-sized Ag NPs, multiparameter size discrimination was proposed, which improved the accuracy compared to single-parameter discrimination. More intriguingly, multiparameter analysis was combined with artificial intelligence, a tool adept at processing multidimensional data, for the first time. Finally, artificial intelligence-assisted multiparameter size discrimination was successfully used to intelligently distinguish mixed Ag NPs, with an optimal accuracy of more than 95%. To sum up, the artificial intelligence-assisted multiparameter method showed an excellent ability to quickly achieve the most accurate size discrimination of nanoparticles at the level of individual particle and provide an effective guidance for the application of nanoparticles.

Role of cyclophilin A in aggravation of myocardial ischemia reperfusion injury via regulation of apoptosis mediated by thioredoxin-interacting protein.

BACKGROUND: The progression and persistence of myocardial ischemia/reperfusion injury (MI/RI) are strongly linked to local inflammatory responses and oxidative stress. Cyclophilin A (CypA), a pro-inflammatory factor, is involved in various cardiovascular diseases. However, the role and mechanism of action of CypA in MI/RI are still not fully understood. METHODS: We used the Gene Expression Omnibus (GEO) database for bioinformatic analysis. We collected blood samples from patients and controls for detecting the levels of serum CypA using enzyme-linked immunosorbent assay (ELISA) kits. We then developed a myocardial ischemia/reperfusion (I/R) injury model in wild-type (WT) mice and Ppia-/- mice. We utilized echocardiography, hemodynamic measurements, hematoxylin and eosin (H&E) staining, immunohistochemistry, enzyme-linked immunosorbent assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to determine the role of CypA in myocardial I/R injury. Finally, we conducted an in vitrostudy, cell transfection, flow cytometry, RNA interference, and a co-immunoprecipitation assay to clarify the mechanism of CypA in aggravating cardiomyocyte apoptosis. RESULTS: We found that CypA inhibited TXNIP degradation to enhance oxidative stress-induced cardiomyocyte apoptosis during MI/RI. By comparing and analyzing CypA expression in patients with coronary atherosclerotic heart disease and in healthy controls, we found that CypA was upregulated in patients with Coronary Atmospheric Heart Disease, and its expression was positively correlated with Gensini scores. In addition, CypA deficiency decreased cytokine expression, oxidative stress, and cardiomyocyte apoptosis in I/R-treated mice, eventually alleviating cardiac dysfunction. CypA knockdown also reduced H2O2-induced apoptosis in H9c2 cells. Mechanistically, we found that CypA inhibited K48-linked ubiquitination mediated by atrophin-interacting protein 4 (AIP4) and proteasomal degradation of TXNIP, a thioredoxin-binding protein that mediates oxidative stress and induces apoptosis. CONCLUSION: These findings highlight the critical role CypA plays in myocardial injury caused by oxidative stress-induced apoptosis, indicating that CypA can be a viable biomarker and a therapeutic target candidate for MI/RI.

Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), and Eosinophil-to-Lymphocyte Ratio (ELR) as Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD).

Purpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed. Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799-0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability. Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.

Different clinical diagnosis end up in the same pathological diagnosis of intravascular leiomyomatosis: Two case reports.

RATIONALE: Intravascular/intravenous leiomyomatosis (IVL) is a peculiar variant of uterine leiomyoma that is classified as a histologically benign smooth muscle tumor with a biological behavior similar to that of a malignant tumor. It is characterized by the proliferation of leiomyomas spreading along the uterine and extrauterine venous circulation. PATIENT CONCERNS: Herein, we present 2 cases of IVL who had completely different clinical manifestations to stress the need for constant vigilance of IVL diagnosis and the understanding of uterine leiomyoma heterogenicity. Case 1 was registered for fever without specific triggering factors, irregular menstruation and clinically diagnosed uterine diverticula, while no information about fibroids was mentioned. Case 2 was characterized by an aggressively growing abdominal mass. With a large space-occupying lesion in the right abdominopelvic cavity and no imaging evidence of involvement of the iliac vein or above vein, the patient was initially diagnosed with multiple myomata. DIAGNOSES: Both patients' diagnoses were confirmed as IVL by histopathology. To our knowledge, the mass of case 1 is the minimum IVL in the English literature. INTERVENTIONS: Subtotal hysterectomy with bilateral salpingectomy was performed on the former, while total hysterectomy with bilateral salpingectomy was performed on the latter. OUTCOMES: Both patients were comfortable, and no relapse occurred. LESSONS: Two cases in the study showed 2 different proceeding stages of the same disease and corroborated multiple pathogeneses, which have been mentioned in the available literature on IVL. Our work provides both supplement for clinical data to facilitate further research and better understanding of special types of fibroids to clinicians.

Effectiveness of lipid-lowering therapy on mortality and major adverse cardiovascular event outcomes in patients undergoing percutaneous coronary intervention: a network meta-analysis of randomised controlled trials.

BACKGROUND: Emergency percutaneous coronary intervention (PCI) can quickly restore myocardial perfusion after acute coronary syndrome. Whether and which lipid-lowering regimens are effective in reducing major adverse cardiovascular events (MACEs) and mortality risk after PCI remain unclear. OBJECTIVE: This study assessed the benefits of different lipid-lowering regimens on the risk of MACEs and mortality in the post-PCI population by network meta-analysis. METHODS: Public databases, including PubMed, Embase and the Cochrane Library, were searched from inception to August 2022. Randomised controlled trials (RCTs) on lipid-lowering regimens in post-PCI populations were included and analysed. The outcomes were the incidence of all-cause mortality and MACEs, whether reported as dichotomous variables or as HRs. RESULTS: Thirty-nine RCTs were included. For MACEs, alirocumab plus rosuvastatin (OR: 0.18; 95% CI: 0.07 to 0.44), evolocumab plus ezetimibe and statins (OR: 0.19; 95% CI: 0.06 to 0.59), eicosapentaenoic acid (EPA) plus pitavastatin (HR: 0.67; 95% CI: 0.49 to 0.96) and icosapent ethyl plus statins (HR: 0.73; 95% CI: 0.62 to 0.86) had significant advantages and relatively high rankings. For mortality, rosuvastatin (OR: 0.30; 95% CI: 0.11 to 0.84), ezetimibe plus statins (OR: 0.55; 95% CI: 0.43 to 0.89) and icosapent ethyl plus statins (OR: 0.66; 95% CI: 0.45 to 0.96) had significant advantages compared with the control. CONCLUSION: EPA, especially icosapent ethyl, plus statins had a beneficial effect on reducing the risk of MACEs and mortality in post-PCI patients. Proprotein convertase subtilisin/kexin type-9 inhibitors plus statins were able to reduce the risk of MACEs, but the risk of mortality remained unclear. PROSPERO REGISTRATION NUMBER: CRD42018099600.

[Effects of Combined Application of Different Nitrogen Fertilizers and Biochar on Cadmium Uptake by Pakchoi (Brassica chinensis L.) in Cadmium Contaminated Soil].

Nitrogen is an essential nutrient element for crop growth, and biochar is a good material for soil remediation. In this study, a pakchoi (Brassica chinensis L.) pot experiment was conducted to investigate the effects of the combined application of three nitrogen fertilizers, including urea, ammonium sulfate, calcium nitrate, and biochar on pakchoi growth and cadmium (Cd) uptake from cropland soil contaminated by Cd. The results showed that the application of nitrogen fertilizers and biochar prompted pakchoi growth, and the biomass of pakchoi in the treatments of single applications of urea, ammonium sulfate, calcium nitrate, and biochar were significantly increased by 5.02%-32.9%, as compared with that in the control treatment without nitrogen fertilizer application. The biomass of pakchoi in the treatments of the combined application of nitrogen fertilizers and biochar were significantly increased by 8.84%-50.8%, as compared with that in the treatment of the single application of nitrogen fertilizer. Compared with that under the control treatment without nitrogen fertilizer application, the single application of urea significantly reduced soil pH by 0.27 and significantly increased the content of soil available Cd by 30.0%. The single application of ammonium sulfate significantly reduced soil pH by 0.33 and significantly increased Cd content in pakchoi by 29.2%, as compared with that in the control treatment. The single application of calcium nitrate had no significant effect on soil pH or Cd content in pakchoi, whereas the single application of biochar significantly increased soil pH by 0.35 and significantly decreased the content of soil available Cd and content of Cd in pakchoi by 57.4% and 53.7%, respectively, as compared with that in the control treatment. Soil pH in the treatments of the combined application of nitrogen fertilizers and biochar was significantly increased by 0.14-0.28, the contents of soil available Cd were decreased by 16.5%-30.1%, and the contents of Cd in pakchoi were reduced by 15.3%-28.6%, as compared with that in the treatment of single application of nitrogen fertilizers. In general, the application of biochar could adjust the effects of different nitrogen fertilizers on Cd availability in the contaminated soil. During the remediation process of heavy metal-contaminated cropland, nitrogen fertilizer should be selected and applied reasonably to obtain the maximum economic and environmental benefits.

[Effects of electro-scalp acupuncture on inflammatory response and microglial polarization in the ischemic cortex of rats with ischemic stroke].

OBJECTIVE: To observe the effects of electro-scalp acupuncture （ESA） on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1ß, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke. METHODS: Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD3 group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD3 group were treated with intragastric administration of 1,25-dihydroxyvitamin D3 (1,25-VitD3) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1ß, and IL-10 in the ischemic cortex. RESULTS: Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1ß in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD3 group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1ß in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD3 group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1ß, and IL-10 in the ischemic cortex (P<0.01, P<0.05). CONCLUSION: ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.

[Study on alleviating neuroinflammatory injury in ischemic stroke rats by electrical stimulation with scalp acupuncture based on IFN-γ mediated JAK/STAT1 signaling pathway].

OBJECTIVE: To explore the molecular mechanism of electrical stimulation with scalp acupuncture (ESA) in alleviating neuroinflammatory injury in ischemic stroke rats based on interferon γ (IFN-γ)-mediated Janus kinase/signal transduction and transcriptional activator 1 (JAK/STAT1) signaling pathway. METHODS: Fifty-six SD rats aged 7 weeks were randomly divided into normal, model, ESA and inhibitor groups, with 14 rats in each group. The middle cerebral artery embolization rat model was established by means of thread embolization. Rats in the inhibitor group were intraperitoneally injected with the inhibitor PJ34 (5 mg/mL, 25 mg/kg) once a day for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. The percentage of cerebral infarction volume was detected by TTC staining. The positive expressions of interleukin (IL)-6 and IL-10 in cerebral cortex were detected by immunohistochemistry. The protein expression levels of IFN-γ, JAK1, JAK2 and phosphorylated (p)-STAT1 in rats cerebral cortex were detected by Western blot. RESULTS: Compared with the normal group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were increased (P<0.01), while the expression level of IL-10 was decreased (P<0.01) in the model group. Compared with the model group, the neurological deficit score and neurobehavioral score after treatment were significantly decreased (P<0.01), the percentage of cerebral infarction volume was decreased (P<0.01), the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were decreased (P<0.01), while the expression level of IL-10 was increased (P<0.01) in the ESA and inhibitor groups. ESA was superior to inhibitors in improving neurological deficit score and down-regulating p-STAT1 expression (P<0.05, P<0.01), and was inferior to inhibitor in reducing the percentage of cerebral infarction volume as well as down-regulating IFN-γ and JAK1 (P<0.01, P<0.05). CONCLUSION: Down-regulating the expression of IFN-γ and inhibiting the activity of JAK/STAT1 signaling pathway may be one of the mechanisms by which ESA alleviates neuroinflammatory injury in ischemic stroke rats.

Pathophysiological interpretation of fetal heart rate tracings in clinical practice.

The onset of regular, strong, and progressive uterine contractions may result in both mechanical (compression of the fetal head and/or umbilical cord) and hypoxic (repetitive and sustained compression of the umbilical cord or reduction in uteroplacental oxygenation) stresses to a human fetus. Most fetuses are able to mount effective compensatory responses to avoid hypoxic-ischemic encephalopathy and perinatal death secondary to the onset of anaerobic metabolism within the myocardium, culminating in myocardial lactic acidosis. In addition, the presence of fetal hemoglobin, which has a higher affinity for oxygen even at low partial pressures of oxygen than the adult hemoglobin, especially increased amounts of fetal hemoglobin (ie, 180-220 g/L in fetuses vs 110-140 g/L in adults), helps the fetus to withstand hypoxic stresses during labor. Different national and international guidelines are currently being used for intrapartum fetal heart rate interpretation. These traditional classification systems for fetal heart rate interpretation during labor are based on grouping certain features of fetal heart rate (ie, baseline fetal heart rate, baseline variability, accelerations, and decelerations) into different categories (eg, category I, II, and III tracings, "normal, suspicious, and pathologic" or "normal, intermediary, and abnormal"). These guidelines differ from each other because of the features included within different categories and because of their arbitrary time limits stipulated for each feature to warrant an obstetrical intervention. This approach fails to individualize care because the "ranges of normality" for stipulated parameters apply to the population of human fetuses and not to the individual fetus in question. Moreover, different fetuses have different reserves and compensatory responses and different intrauterine environments (presence of meconium staining of amniotic fluid, intrauterine inflammation, and the nature of uterine activity). Pathophysiological interpretation of fetal heart rate tracing is based on the application of the knowledge of fetal responses to intrapartum mechanical and/or hypoxic stress in clinical practice. Both experimental animal studies and observational human studies suggest that, just like adults undertaking a treadmill exercise, human fetuses show predictable compensatory responses to a progressively evolving intrapartum hypoxic stress. These responses include the onset of decelerations to reduce myocardial workload and preserve aerobic metabolism, loss of accelerations to abolish nonessential somatic body movements, and catecholamine-mediated increases in the baseline fetal heart rate and effective redistribution and centralization to protect the fetal central organs (ie, the heart, brain, and adrenal glands), which are essential for intrauterine survival. Moreover, it is essential to incorporate the clinical context (progress of labor, fetal size and reserves, presence of meconium staining of amniotic fluid and intrauterine inflammation, and fetal anemia) and understand the features suggestive of fetal compromise in nonhypoxic pathways (eg, chorioamnionitis and fetomaternal hemorrhage). It is important to appreciate that the timely recognition of the speed of onset of intrapartum hypoxia (ie, acute, subacute, and gradually evolving) and preexisting uteroplacental insufficiency (ie, chronic hypoxia) on fetal heart rate tracing is crucial to improve perinatal outcomes.

Optimizing the management of acute, prolonged decelerations and fetal bradycardia based on the understanding of fetal pathophysiology.

Any acute and profound reduction in fetal oxygenation increases the risk of anaerobic metabolism in the fetal myocardium and, hence, the risk of lactic acidosis. On the contrary, in a gradually evolving hypoxic stress, there is sufficient time to mount a catecholamine-mediated increase in the fetal heart rate to increase the cardiac output and redistribute oxygenated blood to maintain an aerobic metabolism in the fetal central organs. When the hypoxic stress is sudden, profound, and sustained, it is not possible to continue to maintain central organ perfusion by peripheral vasoconstriction and centralization. In case of acute deprivation of oxygen, the immediate chemoreflex response via the vagus nerve helps reduce fetal myocardial workload by a sudden drop of the baseline fetal heart rate. If this drop in the fetal heart rate continues for >2 minutes (American College of Obstetricians and Gynecologists' guideline) or 3 minutes (National Institute for Health and Care Excellence or physiological guideline), it is termed a prolonged deceleration, which occurs because of myocardial hypoxia, after the initial chemoreflex. The revised International Federation of Gynecology and Obstetrics guideline (2015) considers the prolonged deceleration to be a "pathologic" feature after 5 minutes. Acute intrapartum accidents (placental abruption, umbilical cord prolapse, and uterine rupture) should be excluded immediately, and if they are present, an urgent birth should be accomplished. If a reversible cause is found (maternal hypotension, uterine hypertonus or hyperstimulation, and sustained umbilical cord compression), immediate conservative measures (also called intrauterine fetal resuscitation) should be undertaken to reverse the underlying cause. In reversible causes of acute hypoxia, if the fetal heart rate variability is normal before the onset of deceleration, and normal within the first 3 minutes of the prolonged deceleration, then there is an increased likelihood of recovery of the fetal heart rate to its antecedent baseline within 9 minutes with the reversal of the underlying cause of acute and profound reduction in fetal oxygenation. The continuation of the prolonged deceleration for >10 minutes is termed "terminal bradycardia," and this increases the risk of hypoxic-ischemic injury to the deep gray matter of the brain (the thalami and the basal ganglia), predisposing to dyskinetic cerebral palsy. Therefore, any acute fetal hypoxia, which manifests as a prolonged deceleration on the fetal heart rate tracing, should be considered an intrapartum emergency requiring an immediate intervention to optimize perinatal outcome. In uterine hypertonus or hyperstimulation, if the prolonged deceleration persists despite stopping the uterotonic agent, then acute tocolysis is recommended to rapidly restore fetal oxygenation. Regular clinical audit of the management of acute hypoxia, including the "the onset of bradycardia to delivery interval," may help identify organizational and system issues, which may contribute to poor perinatal outcomes.

Effects of Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting on Clinical Outcomes in Patients with Reduced Ejection Fraction Heart Failure and Coronary Heart Disease: A Meta-Analysis.

OBJECTIVE: To clarify the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on the clinical outcomes of patients with coronary heart disease (CHD) complicated with reduced ejection fraction heart failure (HFrEF) through meta-analysis. METHODS: Three major literature databases - PubMed, Web of Science, and Cochrane - were searched by search terms and the literature retrieval time was publications dating from January 2007 to December 2021. To search for observational studies and randomized controlled trials (RCT) comparing the efficacy of PCI and CABG in patients with CHD and HFrEF, the abstract or full text of the literature was read and the final included literature was determined, according to inclusion and exclusion criteria. The quality of the included literature was evaluated using the Ottawa scale and data extraction was further completed. Data analysis was made using RevMan5.4 and R4.1 software; relevant forest plots and funnel plots were made, according to the extracted data. Egger's test was used to evaluate whether the data had publication bias. Outcomes were the major adverse cardiovascular events (MACE). RESULTS: A total of 10 studies were included and 11,032 subjects were included, made up of 5,521 cases of PCI and 5,511 cases of CABG. The results showed no significant difference between the two groups in cardiac mortality (CM) (RR=1.13, 95% CI 0.98-1.30, P = 0.10) and in overall all-cause mortality (ACM) (RR=1.12, 95% CI 0.92-1.37, P = 0.25). In the subgroup analysis of ACM, in the subgroups with left ventricular ejection fraction (LVEF) less than 35% and exceeding 35% and less than 50% (RR=1.12, 95% CI 0.92-1.37, P = 0.25) between the two groups, there was no statistical difference. However, among other MACE, compared with the PCI group, the CABG group had a lower risk of MACE (RR=1.58, 95%CI 1.49-1.70, P < 0.00001), myocardial infarction (MI) (RR=1.99, 95% CI 1.02-3.88, P = 0.04), heart failure (HF) (RR=1.29, 95% CI 1.17-1.43, P < 0.00001) and revascularization (RR=2.74, 95% CI 1.93-3.90, P < 0.00001). Finally in the CABG group, the risk of stroke or transient ischemic attack (TIA) was higher (RR=0.71, 95% CI 0.58-0.86, P = 0.0006) than the PCI group. CONCLUSIONS: The mortality rates of PCI and CABG were similar in patients with CHD complicated with HFrEF. Compared with PCI, CABG had a lower incidence of MACE, MI, HF, and revascularization, and a higher incidence of stroke or TIA.

Acupuncture ameliorates Mobile Phone Addiction with sleep disorders and restores salivary metabolites rhythm.

Objectives: Mobile Phone Addiction (MPA) is a novel behavioral addiction resulting in circadian rhythm disorders that severely affect mental and physical health. The purpose of this study is to detect rhythmic salivary metabolites in MPA with sleep disorder (MPASD) subjects and investigate the effects of acupuncture. Methods: Six MPASD patients and six healthy controls among the volunteers were enrolled by MPA Tendency Scale (MPATS) and Pittsburgh Sleep Quality Index (PSQI), then the salivary samples of MPASD and healthy controls were collected every 4-h for three consecutive days. Acupuncture was administered for 7 days to MPASD subjects, then saliva samples were collected again. Salivary metabolomes were analyzed with the method of LC-MS. Result: According to our investigation, 70 (57.85%) MPA patients and 56 (46.28%) MPASD patients were identified among 121 volunteers. The symptoms of the 6 MPASD subjects were significantly alleviated after acupuncture intervention. The number of rhythmic saliva metabolites dropped sharply in MPASD subjects and restored after acupuncture. Representative rhythmic saliva metabolites including melatonin, 2'-deoxyuridine, thymidine, thymidine 3',5'-cyclic monophosphate lost rhythm and restored after acupuncture, which may attribute to promising MPASD treatment and diagnosis biomarkers. The rhythmic saliva metabolites of healthy controls were mainly enriched in neuroactive ligand-receptor interaction, whereas polyketide sugar unit biosynthesis was mainly enriched in MPASD patients. Conclusion: This study revealed circadian rhythm characteristics of salivary metabolites in MPASD and that acupuncture could ameliorate MPASD by restoring part of the dysrhythmia salivary metabolites.

Current Lifetime of Single-Nanoparticle Electrochemical Collision for In Situ Monitoring Nanoparticles Agglomeration and Aggregation.

In situ monitoring of the agglomeration/aggregation process of nanoparticles (NPs) is crucial because it seriously affects cell entry, biosafety, catalytic performance of NPs, and so on. Nevertheless, it remains hard to monitor the solution phase agglomeration/aggregation of NPs via conventional techniques such as electron microscopy, which requires sample pretreatment and cannot represent native state NPs in solution. Considering that single-nanoparticle electrochemical collision (SNEC) is powerful to detect NPs in solution at the single-particle level, and the current lifetime, which refers to the time that current intensity decays to 1/e of the original value, is skilled in distinguishing different sized NPs, herein, a current lifetime-based SNEC has been developed to distinguish a single Au NP (d = 18 nm) from its agglomeration/aggregation. Based on this, the agglomeration/aggregation process of small-sized NPs and the discrimination of agglomeration vs aggregation have been carefully investigated at the single-particle level. Results showed that the agglomeration/aggregation of Au NPs (d = 18 nm) in 0.8 mM HClO4 climbed from 19% to 69% over two hours, whereas there was no visible granular sediment, and Au NPs tended to agglomerate rather than aggregate irreversibly under normal conditions. Hence, the proposed current lifetime-based SNEC could serve as a complementary method to in situ monitor the agglomeration/aggregation of small-sized NPs in solution at the single-particle level and provide effective guidance for the practical application of NPs.

Predictive Value of the Fibrinogen to Gamma-Glutamine Transferase Ratio in the Long-Term Outcome in Patients with Coronary Heart Disease: A Retrospective Cohort Study.

Background: The ratio of fibrinogen to γ -glutamine transferase (FGR) was used to predict long-term prognosis in patients with coronary heart disease (CHD). Methods: A total of 5638 patients with CHD who were hospitalized from January 2008 to December 2016 were retrospectively enrolled in the study. The mean follow-up time was 35.9 ± 22.5 months. The follow-up endpoints were major cardiac and cerebrovascular adverse events (MACCE). The optimal FGR cut-off value was determined and divided into high- and low-FGR groups according to the receiver operating characteristic (ROC) curve. Statistical methods were used to compare the differences between the two groups and their prognoses to determine whether FGR can predict prognosis in patients with CHD. The traditional predictors were incorporated into the logistic regression model to observe the correlation between these indicators and all-cause mortality (ACM) events. We compared the prediction performance of FGR and traditional predictors on the occurrence of ACM events by ROC curves. Results: The optimal cut-off value was determined via a ROC analysis (FGR = 1.22, p = 0.002), and subjects were classified into high and low FGR groups. The follow-up found that the incidence of MACCE in the high FGR group was higher than that in the low FGR group. The COX multivariate regression model showed that high FGR was independently correlated with the occurrence of MACCE. In addition, the Kaplan-Meier survival curve showed that the risk of events was significantly increased in the group with high FGR. With increases in the FGR ratio, the risk of MACCE was increased. The ROC curve revealed that the risk of ACM was statistically different between the FGR and the traditional risk factor model (p = 0.002), (Fibrinogen (p = 0.008), γ -glutamine transferase (GGT) (p = 0.004), and N-terminal pro brain natriuretic peptide (NT-ProBNP) (p = 0.024)). The comparison between other different models were not statistically significant (p > 0.05). The area under the FGR model curve was larger than that of the traditional risk factors, fibrinogen, GGT and NT-ProBNP models. Conclusions: High FGR can increase the risk of MACCE in patients with CHD; additionally, it can be used as a new biomarker for long-term prognosis in CHD patients. Clinical Trial Registration: All details of this study are registered on the website (http://www.chictr.org.cn), registration number: ChiCTR-ORC-16010153.

What affects the direct economic burden of non-communicable diseases on middle-aged and older adult people in Shaanxi Province?

Non-communicable diseases (NCDs) are the leading cause of death worldwide. NCDs affect the health status and the quality of life. In addition, continuous NCDs treatment expenses place a heavy economic burden on families and cause huge economic losses to the society. The prevention and treatment of NCDs and reduction of their economic burden are key public health issues. Considering middle-aged and older adult people as the focus, their basic socio-demographic characteristics and health behavior status of this group, and a pooled cross-sections regression model was then used to analyze the main factors affecting the direct economic burden. The results showed that from 2013 to 2018, the prevalence of NCDs among the middle-aged and older adult people in Shaanxi province as well as the direct economic burden of NCDs increased. The effect factors primarily included sex, age, employment status, income level, type of medical insurance, urban or rural residency, level of the health care-providing institutions, visiting times of 2-week, and length of hospital stay. Several measures can be taken to control the onset of NCDs and reduce their direct economic burden.

Predictive Value of the Modified GRACE Scoring System for All-Cause Mortality in Patients with Acute Myocardial Infarction.

Background: To establish a modified Global Registry of Acute Coronary Events (GRACE) scoring system with an improved predictive performance compared with the traditional GRACE scoring system. Methods: We identified 5512 patients who were hospitalized with a definite diagnosis of acute myocardial infarction (AMI) from January 1, 2015, to December 31, 2020, at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University through the hospital's electronic medical record system. A total of 4561 patients were enrolled after the inclusion and exclusion criteria were applied. The mean follow-up was 51.8 ± 23.4 months. The patients were divided into dead and alive groups by endpoint events. The differences between the two groups were compared using the two-sample t test and chi-square test. Adjusted traditional risk factors as well as LogBNP (B-type natriuretic peptide precursor, BNP) and the modified GRACE scoring system were included in a multifactorial COX regression model. The predictive performance of the traditional and modified GRACE scoring systems was compared by (Receiver Operating Characteristic) ROC curves. Results: Significant differences in age, heart rate, creatinine, uric acid, LogBNP, traditional GRACE score, and modified GRACE score were found between the dead and alive groups by the two-sample t test. Comparison of the two groups by the chi-square test revealed that the dead group had a higher incidence of males; higher cardiac function class; a previous history of hypertension, diabetes, coronary artery disease (CAD), or cerebrovascular disease; a history of smoking; the need for intra-aortic balloon pump (IABP) support; and more patients taking aspirin, clopidogrel, ticagrelor, and ß -blockers. The results were analyzed by a multifactorial COX regression model, and after adjusting for confounders, age, cardiac function class, history of CAD, use of aspirin and ß -blockers, and the modified GRACE scoring system were found to be associated with all-cause mortality (ACM) in patients with AMI. The ROC curve was used to compare the predictive performance of the conventional GRACE scoring system with that of the modified GRACE scoring system, and it was found that the modified GRACE scoring system (Area Under Curve (AUC) = 0.809, p < 0.001, 95% (Confidence Interval) CI (0.789-0.829)) was significantly better than the traditional GRACE scoring system (AUC = 0.786, p < 0.001, 95% CI (0.764-0.808)), the comparison between the two scores was statistically significant (p < 0.001). The change in the C statistic after 10-fold crossover internal validation of the modified GRACE score was not significant, and the integrated discrimination improvement (IDI) between the old and new models was calculated with IDI = 0.019 > 0, suggesting that the modified GRACE score has a positive improvement on the traditional GRACE score. Conclusions: The modified GRACE scoring system, established by combining B-type natriuretic peptide precursor (BNP) and the traditional GRACE scoring system, was independently associated with ACM in patients with AMI, with a larger AUC and higher predictive value than the traditional GRACE scoring system. Clinical Trial Registration: NCT02737956.