Efficacy and safety of Piwei Peiyuan Prescription in the treatment of chronic atrophic gastritis: A multicenter, double-blind, double-simulated, randomized, controlled clinical trial.

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.

Predicting ventilator-associated pneumonia in elderly patients requiring mechanical ventilation through the detection in tracheal aspirates.

OBJECTIVE: In this study, we evaluated the clinical utility of tracheal aspirates α-amylase (AM), pepsin, and lipid-laden macrophage index (LLMI) in the early diagnosis of ventilator-associated pneumonia (VAP) in elderly patients on mechanical ventilation. METHODS: Within 96 hours of tracheal intubation, tracheal aspirate specimens were collected from elderly patients on mechanical ventilation; AM, pepsin, and LLMI were detected, and we analyzed the potential of each index individually and in combination in diagnosing VAP. RESULTS: Patients with VAP had significantly higher levels of AM, pepsin, and LLMI compared to those without VAP (P < 0.001), and there was a positive correlation between the number of pre-intubation risk factors of aspiration and the detection value of each index in patients with VAP (P < 0.001). The area under a receiver operating characteristic (ROC) curve (AUC) of AM, pepsin, and LLMI in diagnosis of VAP were 0.821 (95% CI:0.713-0.904), 0.802 (95% CI:0.693-0.892), and 0.621 (95% CI:0.583-0.824), the sensitivities were 0.8815, 0.7632, and 0.6973, the specificities were 0.8495, 0.8602, and 0.6291, and the cutoff values were 4,321.5 U/L, 126.61 ng/ml, and 173.5, respectively. The AUC for the combination of indexes in diagnosing VAP was 0.905 (95% CI:0.812-0.934), and the sensitivity and specificity were 0.9211 and 0.9332, respectively. In the tracheal aspirate specimens, the detection rate of AM ≥ cutoff was the highest, while it was the lowest for LLMI (P < 0.001). The detection rates of AM ≥ cutoff and pepsin ≥ cutoff were higher within 48 hours after intubation than within 48-96 hours after intubation (P < 0.001). In contrast, the detection rate of LLMI ≥ cutoff was higher within 48-96 hours after intubation than within 48 hours after intubation (P < 0.001). The risk factors for VAP identified using logistic multivariate analysis included pre-intubation aspiration risk factors (≥3), MDR bacteria growth in tracheal aspirates, and tracheal aspirate AM ≥ 4,321.5 U/L, pepsin ≥ 126.61 ng/ml, and LLMI ≥ 173.5. CONCLUSION: The detection of AM, pepsin, and LLMI in tracheal aspirates has promising clinical utility as an early warning biomarker of VAP in elderly patients undergoing mechanical ventilation.

O-GlcNAcylation of NLRP3 Contributes to Lipopolysaccharide-Induced Pyroptosis of Human Gingival Fibroblasts.

Periodontitis is a leading chronic oral disorder and poses a serious burden on public health. O-GlcNAc glycosylation (O-GlcNAcylation) is regulated only by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) and participates in the regulation of human gingival fibroblasts (HGFs) function. Hence, the purpose of this study is to investigate whether HGFs cell function and periodontitis pathogenesis are regulated by O-GlcNAcylation. Herein, we first established cell model of periodontitis induced by lipopolysaccharide (LPS). The cell viability was measured with CCK-8 assay. Pyroptosis was measured by flow cytometry and western blot. The inflammatory factors levels were detected with ELISA kits. Afterward, our findings indicated that LPS elevated the O-GlcNAcylation level of HGFs and inhibition of O-GlcNAcylation improved LPS-induced pyroptosis of HGFs. Mechanistically, LPS heightened the expression of OGT to induce the O-GlcNAcylation of NLRP3. Subsequently, we certified that Thr542 was the O-GlcNAcylation site of NLRP3. More importantly, upregulation of NLRP3 reversed the effects of OGT knockdown on LPS-induced pyroptosis. In general, the current research demonstrated that LPS contributed to the pyroptosis of HGFs by enhancing the OGT expression to promote O-GlcNAcylation of NLRP3, which suggested that O-GlcNAcylation of NLRP3 was a driving factor for periodontitis and offered a novel insight into the treatment of this disease.

Association Between Visceral Fat, Blood Pressure and Arterial Stiffness in Patients with HFpEF: A Mediation Analysis.

Purpose: To investigate the association of visceral fat with arterial stiffness of heart failure patients with preserved ejection fraction (HFpEF) and to evaluate the extent to which this association is mediated by blood pressure (BP). Patients and Methods: This cross-sectional descriptive study (clinicaltrials.gov identifier: NCT04535726) recruited 94 patients with HFpEF totally from October to December 2020. The obesity-related measurements included visceral fat area (VFA), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WC/HC), abdominal circumference (AC), body fat mass and fat percentage. Brachial-ankle pulse wave velocity (baPWV) was used to estimate the degree of arterial stiffness. Mediation analysis was performed to reveal whether the effect of visceral fat area on arterial stiffness can be mediated by BP in patients with HFpEF and the extent to which this association was mediated by BP. Results: About 93.6% of HFpEF patients were accompanied with abdominal obesity. Patients in baPWV ≥1800cm/s group were older, with a higher incidence of type 2 diabetes mellitus (T2DM), hypertension and abdominal obesity. VFA, systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) were correlated with baPWV in total group. Adjusted for age ≥75 years old, gender, smoking, T2DM, calcium channel blocker and statins, the mediation effect of systolic SBP and PP on the VFA-baPWV association were 53.3% (indirect effect was 2.28, 95% CI 0.62-4.73) and 48.4% (indirect effect was 2.07, 95% CI 0.51-4.38), respectively. DBP failed to mediate the association between VFA and baPWV (indirect effect was 0.50, 95% CI -0.41-2.14). Conclusion: The association of visceral fat with baPWV in HFpEF patients may be partly accounted for SBP or PP. Elevated SBP and PP might be important potential targets for preventing arterial stiffness in HFpEF patients.

Serum uric acid: A risk factor for right ventricular dysfunction and prognosis in heart failure with preserved ejection fraction.

Background: Hyperuricemia and right ventricular dysfunction (RVD) are both widespread in heart failure with preserved ejection fraction (HFpEF) patients. RVD is associated with a poor prognosis in HFpEF. The correlation between serum uric acid (UA) levels and right ventricular function is unclear. The prognostic performance of UA in patients with HFpEF needs further validation. Methods and results: A total of 210 patients with HFpEF were included in the study and divided into two groups according to UA level: the normal UA group (≤7 mg/dl) and the high UA group (>7 mg/dl). The variables examined included clinical characteristics, echocardiography, and serum biochemical parameters. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (TAPSV). Baseline characteristics were compared between the two groups, and the correlation between baseline UA and RVD was assessed using multifactorial binary logistic regression. Kaplan-Meier curves were used to describe all-cause mortality and heart failure readmission. Results showed that right ventricular function parameters were worse in the high UA group. After adjusting for UA, left ventricular posterior wall thickness (LVPWT), N-terminal B-type natriuretic peptide (NT-proBNP), atrial fibrillation (AF), and low-density lipoprotein cholesterol (LDL-C), UA (odds ratio = 2.028; p < 0.001) was independently associated with RVD, and UA >7 mg/dl (HR = 2.98; p < 0.001) was associated with heart failure readmission in patients with HFpEF. Conclusion: Elevated serum UA is closely associated with RVD and significantly associated with the heart failure readmission rate in patients with HFpEF.

Preparation of Superhydrophobic Materials and Establishment of Anticorrosive Coatings on the Tinplate Substrate by Alkylation of Graphene Oxide.

Corrosion of structural parts not only reduces the service life of the equipment but also causes safety accidents, so building a long-lasting anti-corrosion coating on its surface is the key to solving this problem. Under the action of alkali catalysis, n-octyltriethoxysilane (OTES), dimethyldimethoxysilane (DMDMS), and perfluorodecyltrimethoxysilane (FTMS) hydrolyzed and polycondensed co-modified graphene oxide (GO), modified to synthesize a self-cleaning superhydrophobic material fluorosilane-modified graphene oxide (FGO). The structure, film morphology, and properties of FGO were systematically characterized. The results showed that the newly synthesized FGO was successfully modified by long-chain fluorocarbon groups and silanes. FGO presented an uneven and rough morphology on the substrate surface, the water contact angle was 151.3°, and the rolling angle was 3.9°, which caused the coating to exhibit excellent self-cleaning function. Meanwhile, the epoxy polymer/fluorosilane-modified graphene oxide (E-FGO) composite coating adhered to the carbon structural steel's surface, and its corrosion resistance was detected by the Tafel curve and EIS impedance. It was found that the current density of the 10 wt% E-FGO coating (Icorr) was the lowest (1.087 × 10-10 A/cm2), which was approximately 3 orders of magnitude lower than that of the unmodified epoxy coating. This was primarily due to the introduction of FGO, which formed a continuous physical barrier in the composite coating and gave the composite coating excellent hydrophobicity. This method might provide new ideas for advances in steel corrosion resistance in the marine sector.

Berberine ameliorates depression-like behavior in CUMS mice by activating TPH1 and inhibiting IDO1-associated with tryptophan metabolism.

Berberine, which is a potential antidepressant, exhibits definite efficiency in modulating the gut microbiota. Depressive behaviors in mice induced using chronic unpredictable mild stress (CUMS) stimulation were evaluated by behavioral experiments. The markers of neurons and synapses were measured using immunohistochemical staining. An enzyme-linked immunosorbent assay was adopted to analyze serum inflammatory cytokines levels and neurotransmitters were evaluated by LC-MS/MS. Untargeted metabolomics of tryptophan metabolism was further performed using LC-MS/MS. The target enzymes of berberine involved in tryptophan metabolism were assayed using AutoDock and GRMACS softwares. Then, antibiotics was utilized to induce intestinal flora disturbance. Berberine improved the depressive behaviors of mice in a microbiota-dependent manner. Increased neurons and synaptic plasticity were observed following berberine treatment. Meanwhile, berberine decreased serum levels of TNF-α, IL-1ß, and IL-4 and increased levels of IL-10. Moreover, berberine induced retraction of the abnormal neurotransmitters and metabolomics assays revealed that berberine promoted tryptophan biotransformation into serotonin and inhibited the kynurenine metabolism pathway, which was attributed to the potential agonist of tryptophan 5-hydroxylase 1 (TPH1) and inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1). In conclusion, berberine improves depressive symptoms in CUMS-stimulated mice by targeting both TPH1 and IDO1, which are involved in tryptophan metabolism.

Non-invasive global myocardial work index as a new surrogate of ventricular-arterial coupling in hypertensive patients with preserved left ventricular ejection fraction.

Objective: As a new method of left ventricular-arterial coupling (VAC), the non-invasive myocardial work index (MWI) may provide more useful information than the classical methods of arterial elastance/left ventricular (LV) elastance index (the ratio of effective arterial elastance (Ea) over end-systolic elastance [Ea/Ees]). This research aims to investigate if MWI might be better associated with hypertension-mediated organ damage (HMOD) and diastolic dysfunction than Ea/Ees in hypertension. Methods: We prospectively enrolled 104 hypertensives and 69 normotensives. All subjects had speckle-tracking echocardiography for myocardial work, conventional echocardiography, and brachial-ankle pulse wave velocity (baPWV) measurements. The global work index (GWI) is a myocardial work component. The correlation between GWI and HMOD, as well as diastolic dysfunction, was analyzed. The receiver operating characteristic (ROC) curve was utilized for evaluating the GWI predicting efficacy. Results: The global work index was significantly higher in hypertensives than in normotensives (2,021.69 ± 348.02 vs. 1,757.45 ± 225.86 mmHg%, respectively, p < 0.001). Higher GWI was a risk factor on its own for increased baPWV, pulse pressure (PP), echocardiographic LV hypertrophy (LVH), and left atrial volume index (LAVI) (p = 0.030, p < 0.001, p = 0.018 p = 0.031, respectively), taking into account the sex, age, mean arterial pressure (MAP), body mass index (BMI), and antihypertensive therapy. However, no considerable associations were found between Ea/Ees and HMOD parameters and the diastolic dysfunction markers. The GWI area under the ROC curve for increased PP and baPWV, echocardiographic LVH, and increased LAVI were 0.799, 0.770, 0.674, and 0.679, respectively (p < 0.05). Conclusions: The global work index but not traditionally echocardiographic-derived Ea/Ees of VAC is independently related to HMOD and diastolic impairment in hypertensives with preserved LV ejection fraction. The GWI may be a potential marker for evaluating the VAC in hypertension.

Neutrophils to high-density lipoprotein cholesterol ratio as a new prognostic marker in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a retrospective study.

BACKGROUND: Neutrophils and high-density lipoprotein cholesterol (HDL-c) play critical roles in the pathogenesis of acute myocardial infarction. We aimed to investigate the value of neutrophils count to high-density lipoprotein cholesterol ratio (NHR) in predicting occurrence of in-hospital adverse events in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI). METHODS: We retrospectively analyzed 532 patients who had been diagnosed with acute STEMI and treated with PPCI. Demographic and clinical data, admission laboratory parameters and NHR values were recorded. Major adverse cardiac events (MACE) were defined as stent thrombosis, cardiac rupture, cardiac arrest, ventricular aneurysm, malignant arrhythmia and cardiac death. Based on the receiver operating characteristic (ROC) analysis, all patients were divided into 2 groups based on the cut-off NHR value (NHR ≤ 11.28, NHR > 11.28). Cox regression analyses and the Kaplan-Meier survival curve were used to assess the prognostic ability of NHR in in-hospital MACE. RESULTS: MACE was observed in 72 patients (13.5%) during in-hospital follow-up. NHR was significantly higher in MACE group compared to MACE-free group (10.93 [6.26-13.97] vs. 8.13 [5.89-11.16]; P = 0.001). The incidence of in-hospital MACE was significantly higher in the NHR > 11.28 group than in NHR ≤ 11.28 group (24.8% vs. 9.6%; P < 0.001). In multivariable Cox regression analyses, ALT, Killip III-IV and increased NHR (hazard ratio, 2.211; 95% confidence interval,1.092-4.479; P = 0.027) were identified as independent predictive factors of occurrence of in-hospital MACE. Higher NHR group had worse cumulative survival compared with the lower group. CONCLUSIONS: NHR value on admission, which is an easily calculated and universally available maker, may be useful in in-hospital risk classification of STEMI patients undergoing PPCI.

Hydraulic constraints determine the distribution of heteromorphic leaves along plant vertical height.

As an interesting and important trait of some drought-tolerant species, heteromorphic leaves are distributed differentially along plant vertical heights. However, the underpinning mechanism for the formation of heteromorphic leaves remains unclear. We hypothesize that heteromorphic leaves are caused by the hydraulic constraints possibly due to the compensation of the changes in functional traits in response to water transport capacity or the reduction of ineffective water loss. In this study, differences in water transport capacity, morphological traits, anatomical structures, and cellular water relations among three typical types of heteromorphic leaves (i.e., lanceolate, ovate, and broad-ovate) of Populus euphratica Oliv. (a dominant species of desert riparian forest in Central and West Asia) and their relationships were analyzed in order to explore the forming mechanism of heteromorphic leaves. The results showed that the lanceolate, ovate, and broad-ovate leaves were growing in the lower, intermediate, and higher positions from the ground, respectively. Morphological traits, anatomical structures, cellular water relations, and water transport capacity significantly varied among the three types of heteromorphic leaves (P< 0.01). Drought stress in broad-ovate leaves was significantly higher than that in ovate and lanceolate leaves (P< 0.01). Water transport capacity has significant correlations with morphological traits, anatomical structures, and cellular water relations (R 2 ≥ 0.30; P< 0.01). Our results indicated that heteromorphic leaves were used as an important adaptive strategy for P. euphratica to alleviate the increase of hydraulic constraints along vertical heights.

Elevated Blood Urea Nitrogen to Serum Albumin Ratio Is an Adverse Prognostic Predictor for Patients Undergoing Cardiac Surgery.

Background: Elevated blood urea nitrogen (BUN) and reduced albumin have been prominently correlated with unfavorable outcomes in patients with cardiovascular diseases. However, whether combination BUN and albumin levels could predict the adverse outcomes of cardiac surgery patients remains to be confirmed. Here, we investigated the prognostic effect of the preoperative BUN to serum albumin ratio (BAR) in cardiac surgery patients. Methods: Data were obtained from the Medical Information Mart for Intensive Care (MIMIC) III and eICU databases and classified into a training cohort and validation cohort. The BAR (mg/g) was calculated by initial BUN (mg/dl)/serum albumin (g/dl). The primary outcome was in-hospital mortality. Secondary outcomes were 1-year mortality, prolonged length at intensive care unit, and duration of hospital stay. The associations of BAR with outcomes were explored by multivariate regression analysis and subgroup analyses. Then, C statistics were performed to assess the added prognostic impact of BAR beyond a baseline risk model. Results: Patients with in-hospital death had significantly higher levels of BAR. Multivariate regression analysis identified BAR, as a categorical or continuous variable, as an independent factor for adverse outcomes of cardiac surgery (all p < 0.05). Subgroup analyses demonstrated a significant relationship between elevated BAR and in-hospital mortality in different subclasses. The addition of BAR to a baseline model provided additional prognostic information benefits for assessing primary outcome. Results were concordant in the external validation cohort. Conclusions: Increased preoperative BAR is a potent predictor of unfavorable outcomes in patients undergoing cardiac surgery.

Vagus nerve stimulated by microbiota-derived hydrogen sulfide mediates the regulation of berberine on microglia in transient middle cerebral artery occlusion rats.

Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.

Involvement of Huanglian Jiedu Decoction on Microglia with Abnormal Sphingolipid Metabolism in Alzheimer's Disease.

Background: Abnormal sphingolipid metabolism is closely related to the occurrence and development of Alzheimer's disease (AD). With heat-clearing and detoxifying effects, Huanglian Jiedu decoction (HLJDD) has been used to treat dementia and improve learning and memory impairments. Purpose: To study the therapeutic effect of HLJDD on AD as it relates to sphingolipid metabolism. Methods: The level of sphingolipids in the brains of APP/PS1 mice and in the supernatant of ß-amyloid (Aß)25-35-induced BV2 microglia was detected by HPLC-QTOF-MS and HPLC-QTRAP-MS techniques, respectively. The co-expression of ionized calcium-binding adapter molecule 1 (Iba1) and Aß as well as four enzymes related to sphingolipid metabolism, including serine palmitoyltransferase 2 (SPTLC2), cer synthase 2 (CERS2), sphingomyelin phosphodiesterase 1 (SMPD1), and sphingomyelin synthase 1 (SGMS1), in the brains of APP/PS1 mice were evaluated by immunofluorescence double labelling. In addition, real-time quantitative reverse transcription-polymerase chain reaction was conducted to determine the mRNA expression of SPTLC2, CERS2, SMPD1, SGMS1, galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2) in Aß25-35-stimulated BV2 microglia. Results: Abnormal sphingolipid metabolism was observed both in APP/PS1 mouse brain tissues and Aß25-35-stimulated BV2 cells. The levels of sphingosine, sphinganine, sphingosine-1-phosphate, sphinganine-1-phosphate and sphingomyelin were significantly reduced, while the levels of ceramide-1-phosphate, ceramide, lactosylceramide and hexosylceramide significantly increased in Aß25-35-stimulated BV2 cells. In AD mice, more microglia were clustered in the Aß-positive region. The decreased level of SGMS1 and increased levels of CERS2, SPTLC and SMPD1 were also found. In addition, the expressions of SPTLC2, CERS2, and SMPD1 in Aß25-35-stimulated BV2 cells were increased significantly, while the expressions of GALC, SPHK2, and SGMS1 were decreased. These changes all showed a significant correction after HLJDD treatment. Conclusion: HLJDD is a good candidate for treating AD. This study provides a novel perspective on the potential roles of the sphingolipid metabolism in AD.

Impact of Brachial-Ankle Pulse Wave Velocity on Myocardial Work by Non-invasive Left Ventricular Pressure-Strain in Non-hypertensive and Hypertensive Patients With Preserved Left Ventricular Ejection Fraction.

OBJECTIVE: Data regarding the influence of arterial stiffness on myocardial work (MW) has been scarce. This study was performed to investigate the association between brachial-ankle pulse wave velocity (baPWV) and MW by non-invasive left ventricular pressure-strain in a population of non-hypertensive and hypertensive individuals. METHODS: Two hundred and eight participants (104 hypertensive and 104 non-hypertensive individuals) were prospectively enrolled into the study. All participants underwent conventional echocardiography, as well as 2D speckle-tracking echocardiography to assess MW by non-invasive left ventricular pressure-strain and global longitudinal strain (GLS). baPWV measurements were made at the same day as the echocardiography. Then, participants were categorized according to baPWV tertiles. Correlation between baPWV and MW were analyzed. Predicting ability of baPWV for abnormal WM was analyzed using receiver operating characteristic (ROC) curve. RESULTS: The median baPWV from the low to high tertile groups were 1286.5 (1197.5-1343.5), 1490.0 (1444.5-1544.0), and 1803.8(1708.3-1972.0) cm/s, respectively. In simple linear regression analysis, baPWV had a significant positive association with global work index (GWI), global constructed work (GCW), and global wasted work (GWW), and a negative association with global work efficiency (GWE). The association remained significant after adjusting for major confounding factors in multiple linear regression analysis. The areas under the ROC curve of baPWV for predicting abnormal GWI, GCW, GWW, and GWE were 0.653, 0.666, 0.725, and 0.688, respectively (all p < 0.05). CONCLUSIONS: BaPWV is significantly associated with all four components of MW using non-invasive left ventricular pressure-strain method in a mixed population of non-hypertensive and hypertensive individuals.

Nutritional indices at admission are associated with mortality rates of patients in the intensive care unit.

BACKGROUND: Malnutrition is a common occurrence in critically ill patients, and has been related to poor prognosis in various diseases. Here, we assess the prognostic value of malnutrition using nutritional indices in intensive care units (ICU) patients. METHODS: We retrieved information on 2060 patients from the Medical Information Mart for Intensive Care III, and randomized the patients into training and validation cohorts, at a ratio of 7:3. We estimated their nutritional indices using prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) score. Both multivariate regression analysis and the Kaplan-Meier (KM) survival curve were used to examine the prognostic role of nutritional indices in ICU mortality. Then we evaluated the additional predictive significance of each nutritional index beyond the baseline model including conventional risk factors. RESULTS: Multivariate regression analysis revealed that PNI, GNRI, and CONUT were independent predictors of in-hospital and 1-year mortality (all P < 0.001). KM curves showed higher 1-year mortality rates in having nutritional risk patients (PNI ≤ 38 or GNRI ≤ 98 or CONUT ≥ 2). Moreover, subgroup analyses revealed a significant association between each nutritional index and 1-year mortality in patients with different comorbidities. We also observed a pronounced additional impact on the predictive value of 1-year mortality when PNI, GNRI, and CONUT were separately added to the baseline model. The additional role of each nutritional index was further verified in the validation cohort. CONCLUSIONS: Our results revealed that the nutritional indices at admission are significantly correlated with increased mortality rates in ICU adult patients.

A Kinematic Data Based Lower Limb Motor Function Evaluation Method for Post-Stroke Rehabilitation.

Recent studies have demonstrated that home-based rehabilitation for stroke patients has excellent potential in reducing the cost and enhancing rehabilitation efficiency. Nonetheless, a timely and accurate rehabilitation assessment is required to attain efficacy and provide feedback to both clinicians and patients. In this paper, a lower limb motor function assessment approach based on limb kinematic data has been presented. The kinematic characteristics of lower limbs were quantified into specific evaluation parameters, which were calculated during a set of selected rehabilitation exercises. A body area network composed of two triaxial accelerometers was used to acquire the limb kinematic data of twenty stroke patients and six healthy subjects. While a referenced template was developed using the data from healthy subjects, an empirical score was obtained to evaluate the lower-limb motor function of stroke patients from the calculated parameters. The results have demonstrated that the scoring has a statistically significant strong correlation with the Brunnstrom stage classification, which provides a practical quantitative evaluation approach for home-based rehabilitation for lower limbs of stroke patients.Clinical Relevance- The proposed quality assessment method provides practical technical support for performing early support discharge rehabilitation.

Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds.

BACKGROUND: Molecular targeted therapy for non-small cell lung carcinoma (NSCLC) is restricted due to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This study evaluated the effects of dual targeting of MEK and PI3K in human EGFR-TKI resistant NSCLC cell lines. METHODS: EGFR-TKI resistant NSCLC cell lines H1975, H460, and A549, with different mutation and amplification status in EGFR, K-RAS, PIK3CA, and MET genes, were treated with a MEK162 (MEK inhibitor) and BKM120 (PI3K inhibitor) combination or a BIBW2992 (EGFR inhibitor) and ARQ197 (MET inhibitor) combination and assayed for cell proliferation, apoptosis, and cell cycle distribution. RESULTS: Dual targeting of MEK and PI3K efficiently inhibited the cell proliferation, induced apoptosis and the G0/G1 cell cycle, and decreased the phosphorylation of ERK1/2, AKT, S6, and 4E-BP1. H460 cells with K-RAS and PIK3CA mutation were most sensitive to MEK162 and BKM120 combinations. H1975 cells with EGFR and PIK3CA mutation and MET amplification were sensitive to BIBW2992 and ARQ197 combinations. CONCLUSION: Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics.

Cephalometric craniofacial features of patients with Sagliker syndrome: a primary analysis of our experience.

BACKGROUND: Sagliker syndrome (SS) is characterized by a severe uglifying facial appearance resulting from untreated or inadequately treated secondary hyperparathyroidism (SHPT). To date, the craniofacial morphology of patients with SS has yet to be analyzed. The present research sought to cephalometrically evaluate the craniofacial features of patients with SS and to perform an in-depth analysis of their serum biochemical parameters, with the aim of furthering the theoretical basis for the early diagnosis and prevention of SS. METHODS: A retrospective chart review of 9 patients who fulfilled the diagnostic criteria for SS were included in this study, and their serum biochemical parameters were collected. After subjecting standard lateral cephalometric radiographic images to correction for distortions caused by magnification followed by digitization, we conducted a cephalometric analysis. Student's two-tailed t tests or Mann-Whitney U tests were used to analyze the data. Thirty-three patients with patients with SHPT alone were also included as controls. RESULTS: The lower anterior facial height (ANS-ME) and total anterior facial height (N-Me) measurements of patients with SS were significantly increased compared to those of the controls. The angles between the Frankfort horizontal, palatal, and occlusal planes and the mandibular plane, were greater in the SS group than in the control group, as was the gonial angle. Patients with SS also exhibited a significantly larger maxillary protrusion angle and relative position of the maxilla to the mandible. Most patients with SS had class II malocclusion, whereas most of the controls exhibited normal occlusion. Soft tissue largely followed the same pattern as craniofacial changes. Our investigation also showed that among patients with SHPT, female sex, longer duration of dialysis, and higher serum levels of alkaline phosphatase and intact parathyroid hormone were associated with development to SS. CONCLUSIONS: Patients with SS show facial and biochemical differences compared to patients with SHPT. Female sex, long dialysis duration, and high serum levels of intact parathyroid hormone and alkaline phosphatase may be potential risk factors for SS.

Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics.

BACKGROUND: S. baicalensis, a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer's disease. AIM OF THE STUDY: To elucidate the mechanism by which S. baicalensis modulates lipid metabolism and explore the medicinal effects of S. baicalensis at a holistic level. MATERIALS AND METHODS: The potential active ingredients of S. baicalensis and targets involved in regulating lipid metabolism were identified using a network pharmacology approach. Metabolomics was utilized to compare lipids that were altered after S. baicalensis treatment in order to identify significantly altered metabolites, and crucial targets and compounds were validated by molecular docking. RESULTS: Steroid biosynthesis, sphingolipid metabolism, the PPAR signaling pathway and glycerolipid metabolism were enriched and predicted to be potential pathways upon which S. baicalensis acts. Further metabolomics assays revealed 14 significantly different metabolites were identified as lipid metabolism-associated elements. After the pathway enrichment analysis of the metabolites, cholesterol metabolism and sphingolipid metabolism were identified as the most relevant pathways. Based on the results of the pathway analysis, sphingolipid and cholesterol biosynthesis and glycerophospholipid metabolism were regarded as key pathways in which S. baicalensis is involved to regulate lipid metabolism. CONCLUSION: According to our metabolomics results, S. baicalensis may exert its therapeutic effects by regulating the cholesterol biosynthesis and sphingolipid metabolism pathways. Upon further analysis of the altered metabolites in certain pathways, agents downstream of squalene were significantly upregulated; however, the substrate of SQLE was surprisingly increased. By combining evidence from molecular docking, we speculated that baicalin, a major ingredient of S. baicalensis, may suppress cholesterol biosynthesis by inhibiting SQLE and LSS, which are important enzymes in the cholesterol biosynthesis pathway. In summary, this study provides new insights into the therapeutic effects of S. baicalensis on lipid metabolism using network pharmacology and lipidomics.

Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics.

Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.