ABSTRACT
BACKGROUND: As a central hub in cognitive and emotional brain circuits, the striatum is considered likely to be integrally involved in the psychopathology of bipolar disorder (BD). However, it remains unclear how alterations in striatal function contribute to distinct symptomatology of BD during different mood states. METHODS: Behavioral assessment (i.e., emotional symptoms and cognitive performance) and neuroimaging data were collected from 125 participants comprising 31 (hypo)manic, 31 depressive, and 31 euthymic patients with BD, and 32 healthy control participants. We compared the functional connectivity (FC) of striatal subregions across BD mood states with healthy control participants and then used a multivariate data-driven approach to explore dimensional associations between striatal connectivity and behavioral performance. Finally, we compared the FC and behavioral composite scores, which reflect the individual weighted representation of the associations, among different mood states. RESULTS: Patients in all mood states exhibited increased FC between the bilateral ventral rostral putamen and ventrolateral thalamus. Bipolar (hypo)mania uniquely exhibited increased ventral rostral putamen connectivity and superior ventral striatum connectivity. One latent component was identified, whereby increased FCs of striatal subregions were associated with distinct psychopathological symptomatology (more manic symptoms, elevated positive mood, less depressive symptoms, and worse cognitive performance). Patients with bipolar (hypo)mania had the highest FC and behavioral composite scores while bipolar patients with depression had the lowest scores. CONCLUSIONS: Our data demonstrated both trait features of BD and state features specific to bipolar (hypo)mania. The findings underscored the fundamental role of the striatum in the pathophysiological processes underlying specific symptomatology across all mood states.
Subject(s)
Affect , Bipolar Disorder , Corpus Striatum , Magnetic Resonance Imaging , Humans , Bipolar Disorder/physiopathology , Bipolar Disorder/diagnostic imaging , Male , Female , Adult , Affect/physiology , Corpus Striatum/physiopathology , Corpus Striatum/diagnostic imaging , Middle Aged , Mania/physiopathology , Ventral Striatum/physiopathology , Ventral Striatum/diagnostic imaging , Neural Pathways/physiopathology , Young AdultABSTRACT
Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. In this naturalistic prospective study (NCT03294525), we aimed to investigate relationships among subcortical functional connectivity (FC), mood symptom profiles and treatment outcome in MDD using multivariate methods. Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) correlation analysis to explore the association between subcortical FC and mood symptom profiles. FC score, reflecting the weighted representation of each individual in this association, was computed. Replication analysis was undertaken in an independent sample (n = 74). We also investigated the relationship between FC score and treatment outcome in the main sample. A distinctive subcortical connectivity pattern was found to be associated with negative affect. In general, higher FC between the caudate, putamen and thalamus was associated with greater negative affect. This association was partly replicated in the independent sample (similarity between the two samples: r = 0.66 for subcortical connectivity, r = 0.75 for mood symptom profile). Lower FC score predicted both remission and response to treatment after 8 weeks of antidepressant monotherapy. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical FC with negative affect. However, while the FC score significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.
Subject(s)
Depressive Disorder, Major , Humans , Affect , Antidepressive Agents/therapeutic use , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/drug therapy , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce and inconsistent. METHODS: Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis. RESULTS: A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients. CONCLUSIONS: Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.
Subject(s)
Bipolar Disorder , Humans , Mania , Brain Mapping/methods , Neural Pathways/diagnostic imaging , Magnetic Resonance Imaging/methods , BrainABSTRACT
Based on the successful establishment of a rat model of chronic restraint stress, we used multiple algorithms to quantify the morphological changes of rat hypothalamic microglia from various perspectives, providing a pathomorphological basis for the subsequent study of molecular mechanisms of hypothalamic stress injury, such as neuroinflammation. To verify the successful establishment of the chronic stress model, an enzyme-linked immunosorbent assay was performed to detect serum glucocorticoid levels. Microglia labeled with Iba1 in frozen sections of rat hypothalamus were scanned and photographed at multiple levels using confocal microscopy. Subsequently, images were processed for external contouring and skeletonization, and morphological indices of microglia were calculated and analyzed using fractal, skeleton, and Sholl analysis. In addition, the co-expression of CD68 (a marker that can reflect phagocytic activity) and Iba1 was observed by immunofluorescence technique. Compared with the control group, microglia in the chronic stress group displayed reduced fractal dimension and lacunarity, increased density and circularity, enlarged soma areas, and shortened and reduced branches. Sholl analysis confirmed the reduced complexity of microglia following chronic stress. Meanwhile, microglia CD68 increased significantly, indicating that the microglia in the chronic stress group have greater phagocytosis activity. In summary, chronic restraint stress promoted the conversion of microglia in the rat hypothalamus to a less complex form, manifested as larger soma, shorter and fewer branches, more uniform and dense texture, and increased circularity; indeed, the shape of these microglia resembled that of amoeba and they displayed strong phagocytosis activity.
Subject(s)
Hypothalamus , Microglia , Rats , AnimalsABSTRACT
BACKGROUND: The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further investigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the different relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs). METHODS: Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic resonance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clinical assessment. A seed-based approach was used to evaluate the intrinsic FC alterations in three core neurocognitive networks (the default mode network [DMN], the central executive network [CEN] and the salience network [SN]). Finally, we examined the relationship between FC and cognitive performance by using linear regression analyses. RESULTS: Decreased FC was observed within the DMN, in the DMN-SN and DMN-CEN and increased FC was observed in the SN-CEN in BD. The alteration direction of regional FC was consistent with that of FC at the brain network level. Decreased FC between the left posterior cingulate cortex and right anterior cingulate cortex was associated with longer WCST completion time in BD patients (but not in HCs). CONCLUSIONS: These findings emphasize the dominant role of the DMN in the psychopathology of BD and provide evidence that cognitive deficits in BD may be associated with aberrant FC between the anterior and posterior DMN.
Subject(s)
Bipolar Disorder , Humans , Bipolar Disorder/complications , Bipolar Disorder/diagnostic imaging , Executive Function , Neural Pathways/diagnostic imaging , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain Mapping/methods , CognitionABSTRACT
BACKGROUND: The fetal immune system and consequent elevated risk of asthma in childhood may be impacted by maternal anxiety during pregnancy. Limited studies have evaluated whether there was a sensitive period and cumulative effect of the relationship between prenatal anxiety and children's asthma. METHODS: 3131 mother-child pairs made up the study's sample from the Ma'anshan Birth Cohort Study in China. Maternal anxiety status was repeated three times using the pregnancy-related anxiety questionnaire in the 1st, 2nd and 3rd trimesters of pregnancy. Diagnostic information on asthma was collected three times at 24, 36, and 48 months of age. RESULTS: After adjusting for confounders, children born to mothers with anxiety in the 1st, 2nd and 3rd trimesters of pregnancy all had an elevated risk of total asthma from 12 to 48 months of age. After further adjusting prenatal anxiety in the other trimesters, no association was observed between prenatal anxiety in any trimester and preschoolers' asthma. Children of mothers with persistently high anxiety score trajectory during pregnancy had an elevated risk of total asthma and high prevalence trajectory of asthma. Cumulative effects analysis showed that the more frequent the mother's anxiety, the higher the risk of her offspring developing a high prevalence trajectory of asthma from 12 to 48 months of age. The results of the subgroup analysis by age showed similar associations overall. CONCLUSIONS: Maternal antenatal anxiety was associated with an elevated risk of preschool children's asthma, and a possible cumulative effect was observed. Maternal mental health conditions during pregnancy should receive constant attention throughout pregnancy, not just during one period.
Subject(s)
Asthma , Prenatal Exposure Delayed Effects , Humans , Child, Preschool , Female , Pregnancy , Cohort Studies , Prenatal Exposure Delayed Effects/epidemiology , Asthma/epidemiology , Anxiety/epidemiology , ParturitionABSTRACT
Four new diastereoisomeric neolignan glycosides (1-4) along with nine known lignan glycosides (5-13) were isolated from the root bark of Lycium chinense Mill. Their structures with absolute configurations were elucidated on the basis of NMR spectroscopy, ECD, Mo2(OAc)4-induced ECD spectra, enzymatic hydrolysis and acid hydrolysis. The isolated compounds were evaluated for their α-glucosidase inhibitory activity. Compounds 8 and 13 exhibited moderate inhibitory activities against α-glucosidase with IC50 values of 26.82 ± 2.71 and 43.14 ± 2.81 µg/mL.
Subject(s)
Lignans , Lycium , Lignans/pharmacology , Glycosides/chemistry , Lycium/chemistry , alpha-Glucosidases , Molecular Structure , Plant Bark/chemistryABSTRACT
BACKGROUND: A recent study revealed disrupted topological organization of whole-brain networks in patients with major depressive disorder (MDD); however, these results were mostly driven by recurrent MDD patients, rather than first-episode drug-naïve (FEDN) patients. Furthermore, few longitudinal studies have explored the effects of antidepressant therapy on the topological organization of whole-brain networks. METHODS: We collected clinical and neuroimaging data from 159 FEDN MDD patients and 152 normal controls (NCs). A total of 115 MDD patients completed an eight-week antidepressant treatment procedure. Topological features of brain networks were calculated using graph theory-based methods and compared between FEDN MDD patients and NCs, as well as before and after treatment. RESULTS: Decreased global efficiency, local efficiency, small-worldness, and modularity were found in pretreatment FEDN MDD patients compared with NCs. Nodal degrees, betweenness, and efficiency decreased in several networks compared with NCs. After antidepressant treatment, the global efficiency increased, while the local efficiency, the clustering coefficient of the network, the path length, and the normalized characteristic path length decreased. Moreover, the reduction rate of the normalized characteristic path length was positively correlated with the reduction rate of retardation factor scores. LIMITATIONS: The interaction effects of groups and time on the topological features were not explored because of absence of the eighth-week data of NC group. CONCLUSIONS: The topological architecture of functional brain networks is disrupted in FEDN MDD patients. After antidepressant therapy, the global efficiency shifted toward recovery, but the local efficiency deteriorated, suggesting a correlation between recovery of retardation symptoms and global efficiency.
Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/drug therapy , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain Mapping , Antidepressive Agents/therapeutic useABSTRACT
OBJECTIVE: Bulimia nervosa (BN) is an eating disorder associated with the dysfunction of intrinsic brain networks. However, whether the network disruptions in BN patients manifest as dysconnectivity or imbalances of network modular segregation remains unclear. METHOD: We collected data from 41 women with BN and 41 matched healthy control (HC) women. We performed graph theory analysis based on resting-state functional magnetic resonance imaging (RS-fMRI) data; then, we computed the participation coefficient (PC) among brain modules to characterize the modular segregation for the BN and HC groups. The number of intra- and inter-modular connections was calculated to explain the PC changes. Additionally, we examined the potential associations of the measures mentioned above with clinical variables within the BN group. RESULTS: Compared with the HC group, the BN group showed significantly decreased PC in the fronto-parietal network (FPN), cingulo-opercular network (CON), and cerebellum (Cere). Additionally, the number of intra-modular connections of the default mode network (DMN) and the number of the inter-modular connections between the DMN and CON, FPN and Cere, and CON and Cere in the BN group were lower than those in the HC group. The nodal level analysis showed that the BN group had a decreased PC of the anterior prefrontal cortex (aPFC), dorsal frontal cortex (dFC), inferior parietal lobule (IPL), thalamus, and angular gyrus. Further, these metrics were significantly correlated with clinical variables in the BN group. DISCUSSION: These findings may provide novel insights to capture atypical topologies associated with pathophysiology mechanisms and clinical symptoms underlying BN.
Subject(s)
Bulimia Nervosa , Feeding and Eating Disorders , Humans , Female , Bulimia Nervosa/diagnostic imaging , Magnetic Resonance Imaging , Brain/diagnostic imaging , Prefrontal Cortex , Brain MappingABSTRACT
BACKGROUND: Although early esophageal squamous cell carcinoma (EESCC) with cirrhosis is a relatively rare clinical phenomenon, the management of EESCC in cirrhotic patients continues to be a challenge. AIM: To evaluate the feasibility, safety, efficacy and long-term survival outcomes of endoscopic submucosal tunnel dissection (ESTD) for treating EESCC in patients with cirrhosis. METHODS: This was a single-center retrospective cohort study. We examined 590 EESCC patients who underwent ESTD between July 14, 2014, and May 26, 2021, from a large-scale tertiary hospital. After excluding 25 patients with unclear lesion areas or pathological results, the remaining 565 patients were matched at a ratio of 1:3 by using propensity score matching. A total of 25 EESCC patients with comorbid liver cirrhosis and 75 matched EESCC patients were ultimately included in the analysis. Parametric and nonparametric statistical methods were used to compare the differences between the two groups. The Kaplan-Meier method was used to create survival curves, and differences in survival curves were compared by the log-rank test. RESULTS: Among 25 patients with liver cirrhosis and 75 matched noncirrhotic patients, there were no significant differences in intraoperative bleeding (P = 0.234), 30-d post-ESTD bleeding (P = 0.099), disease-specific survival (P = 0.075), or recurrence-free survival (P = 0.8196). The mean hospitalization time and costs were significantly longer (P = 0.007) and higher (P = 0.023) in the cirrhosis group than in the noncirrhosis group. The overall survival rate was significantly lower in the cirrhosis group (P = 0.001). CONCLUSION: ESTD is technically feasible, safe, and effective for patients with EESCC and liver cirrhosis. EESCC patients with Child-Pugh A disease seem to be good candidates for ESTD.
ABSTRACT
BACKGROUND: Peripheral T-cell lymphoma (PTCL), an aggressive and rare disease that belongs to a heterogeneous group of mature T-cell lymphomas, develops rapidly and has a poor prognosis. Early detection and treatment are essential to improve patient cure and survival rates. Here, we report a rare case of PTCL with clinical presentation of noncirrhotic portal hypertension, which provides a basis for early vigilance of lymphomas in the future. CASE SUMMARY: A 65-year-old Chinese woman was admitted to our hospital because of abdominal distension for 3 months and pitting oedema of both lower limbs for 2 months. Physical examinations and associated auxiliary examinations showed the presence of hepatosplenomegaly, and her hepatic venous pressure gradient was 10 mmHg. Immunohistochemical analysis of the liver biopsy confirmed the diagnosis of PTCL. The patient underwent combination therapy with dexamethasone, VP-16, and chidamide. Unfortunately, after 41 days of chemotherapy, the patient died of multiple organ failure. CONCLUSION: PCTL accompanied by noncirrhotic portal hypertension is rarely reported. This case report discusses the diagnosis of a patient according to the literature.
ABSTRACT
The present study investigated the chemical constituents from Uncaria sessilifructus and their neuroprotective activities. The compounds were separated and purified from the 90% ethanol extract of U. sessilifructus by various chromatographic methods, including silica gel, Sephadex LH-20, and semi-preparative HPLC. Seven compounds were obtained, and their structures were identified as uncanidine J(1), uncanidine K(2), 17-O-ethylhirsutine(3), tetrahydroalstonine(4), akuammigine(5), hirsutine(6), and hirsuteine(7) by physicochemical properties and various spectral techniques, including UV, IR, MS, and NMR. Compounds 1 and 2 are two new compounds. Compound 3 is a new natural product, and compound 4 was isolated from U. sessilifructus for the first time. In addition, the isolated compounds were evaluated for their neuroprotective effects on oxygen and glucose deprivation/reoxygenation(OGD/R) injury in primary cortical neurons in rats. The results showed that compounds 1-7 had different degrees of protective effects on OGD/R injury. The EC_(50) values of compounds 2-4 were(0.17±0.03),(1.70±0.38), and(1.79±0.23) µmol·L~(-1), respectively.
Subject(s)
Biological Products , Drugs, Chinese Herbal , Neuroprotective Agents , Secologanin Tryptamine Alkaloids , Uncaria , Animals , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Ethanol , Glucose , Indole Alkaloids , Neuroprotective Agents/pharmacology , Oxygen , Rats , Silica Gel , Uncaria/chemistryABSTRACT
Image-guided tumor ablation eliminates tumor cells by physical or chemical stimulation, which shows less invasive and more precise in local tumor treatment. Tumor ablation provides a treatment option for medically inoperable patients. Currently, clinical ablation techniques are widely used in clinical practice, including cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). Previous clinical studies indicated that ablation treatment activated immune responses besides killing tumor cells directly, such as short-term anti-tumor response, immunosuppression reduction, specific and non-specific immune enhancement, and the reduction or disappearance of distant tumor foci. However, tumor ablation transiently induced immune response. The combination of ablation and immunotherapy is expected to achieve better therapeutic results in clinical application. In this paper, we provided a summary of the principle, clinical application status, and immune effects of tumor ablation technologies for tumor treatment. Moreover, we discussed the clinical application of different combination of ablation techniques with immunotherapy and proposed possible solutions for the challenges encountered by combined therapy. It is hoped to provide a new idea and reference for the clinical application of combinate treatment of tumor ablation and immunotherapy.
Subject(s)
Ablation Techniques , Catheter Ablation , Neoplasms , Radiofrequency Ablation , Catheter Ablation/methods , Humans , Immunotherapy , Neoplasms/therapy , Radiofrequency Ablation/methodsABSTRACT
Boron is an essential element for autoinducer-2 (AI-2) synthesis of quorum sensing (QS) system, which affects bacterial collective behavior. As a living biocatalyst, biofilms can stably catalyze the activity of intracellular enzymes. However, it is unclear how boron affects biofilm formation in E. coli, particularly recombinant E. coli with intracellular enzymes. This study screened different boron derivatives to explore their effect on biofilm formation. The stress response of biofilm formation to boron was illuminated by analyzing AI-2 activity, extracellular polymeric substances (EPS) composition, gene expression levels, etc. Results showed that boron derivatives promote AI-2 activity in QS system. After treatment with H3BO3 (0.6 mM), the AI-2 activity increased by 65.99%, while boron derivatives increased the biomass biofilms in the order H3BO3 > NaBO2 > Na2B4O7 > NaBO3. Moreover, treatment with H3BO3 (0.6 mM) increased biomass by 88.54%. Meanwhile, AI-2 activity had a linear correlation with polysaccharides and protein of EPS at 0−0.6 mM H3BO3 and NaBO2 (R2 > 0.8). Furthermore, H3BO3 upregulated the expression levels of biofilm formation genes, quorum sensing genes, and flagellar movement genes. These findings demonstrated that boron promoted biofilm formation by upregulating the expression levels of biofilm-related genes, improving the QS system AI-2 activity, and increasing EPS secretion in E. coli.
Subject(s)
Escherichia coli , Quorum Sensing , Bacteria/metabolism , Bacterial Proteins/metabolism , Biofilms , Boron , Escherichia coli/metabolism , Homoserine/pharmacology , Lactones/metabolism , Lactones/pharmacology , Quorum Sensing/geneticsABSTRACT
BACKGROUND: Pre-operative non-invasive histological evaluation of hepatocellular carcinoma (HCC) remains a challenge. Tumor perfusion is significantly associated with the development and aggressiveness of HCC. The purpose of the study was to evaluate the clinical value of quantitative liver perfusion parameters and corresponding histogram parameters derived from traditional triphasic enhanced computed tomography (CT) scans in predicting histological grade of HCC. METHODS: Totally, 52 patients with HCC were enrolled in this retrospective study and underwent triple-phase enhanced CT imaging. The blood perfusion parameters were derived from triple-phase CT scans. The relationship of liver perfusion parameters and corresponding histogram parameters with the histological grade of HCC was analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal ability of the parameters to predict the tumor histological grade. RESULTS: The variance of arterial enhancement fraction (AEF) was significantly higher in HCCs without poorly differentiated components (NP-HCCs) than in HCCs with poorly differentiated components (P-HCCs). The difference in hepatic blood flow (HF) between total tumor and total liver flow (ΔHF = HFtumor - HFliver) and relative flow (rHF = ΔHF/HFliver) were significantly higher in NP-HCCs than in P-HCCs. The difference in portal vein blood supply perfusion (PVP) between tumor and liver tissue (ΔPVP) and the ΔPVP/liver PVP ratio (rPVP) were significantly higher in patients with NP-HCCs than in patients with P-HCCs. The area under ROC (AUC) of ΔPVP and rPVP were both 0.697 with a high sensitivity of 84.2% and specificity of only 56.2%. The ΔHF and rHF had a higher specificity of 87.5% with an AUC of 0.681 and 0.673, respectively. The combination of rHF and rPVP showed the highest AUC of 0.732 with a sensitivity of 57.9% and specificity of 93.8%. The combined parameter of ΔHF and rPVP, rHF and rPVP had the highest positive predictive value of 0.903, and that of rPVP and ΔPVP had the highest negative predictive value of 0.781. CONCLUSION: Liver perfusion parameters and corresponding histogram parameters (including ΔHF, rHF, ΔPVP, rPVP, and AEFvariance) in patients with HCC derived from traditional triphasic CT scans may be helpful to non-invasively and pre-operatively predict the degree of the differentiation of HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/diagnostic imaging , Contrast Media , Humans , Liver Neoplasms/diagnostic imaging , Perfusion , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: The determinants of pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF) have been poorly investigated in patients with cardiovascular diseases (CVD). METHODS: From July 1 2017 to March 31 2019, a total of 149 consecutive HFpEF patients hospitalized with CVD were enrolled in this prospective cross-sectional study. A systolic pulmonary artery pressure (PASP) > 35 mmHg estimated by echocardiography was defined as PH-HFpEF. Logistic regression was performed to establish predictors of PH in HFpEF patients. RESULTS: Overall, the mean age of participants was 72 ± 11 years, and 74 (49.7%) patients were females. A total of 59 (39.6%) patients were diagnosed with PH-HFpEF by echocardiography. The left atrial diameter (LAD) was related to the ratio of the transmitral flow velocities/mitral annulus tissue velocities in early diastole (E/E') and the left ventricular diameter in systole (LVDs). N-Terminal pro B-type natriuretic peptide (NT-proBNP) was not found to be associated with LAD and impaired diastolic or systolic function of the left ventricle. Multivariable logistic regression showed that atrial fibrillation (AF) increased the risk of PH-HFpEF incidence 3.46-fold with a 95% confidence interval (CI) of 1.44-8.32, P = 0.005. Meanwhile, LAD ≥ 45 mm resulted in a 3.43-fold increased risk, 95% CI: 1.51-7.75, P = 0.003. However, the significance levels of NT-proBNP, age and LVEF were underpowered in the regression model. Two variables, AF and LAD ≥ 45 mm, predicted the PH-HFpEF incidence (C-statistic = 0.773, 95% CI: 0.695-0.852, P < 0.001). CONCLUSIONS: Two parameters associated with electrical and anatomical remodelling of the left atrium were related to the incidence of PH in HFpEF patients with CVD.
ABSTRACT
Developing circular economy is the only way to improve the efficiency of resource utilization. Whole-cell catalysis is an effective method to recycle enzymes, improve catalytic efficiency, and reduce production costs. The enzyme, α-L-rhamnosidase has considerable application prospects in the field of biocatalysis as it can hydrolyze a variety of α-L rhamnoses. In the present study, the genes for α-L-rhamnosidase (rhaB1) and enhanced fluorescent protein (EGFP) were co-expressed using a bi-promoter expression vector pRSFDuet1 and their enzymatic properties were evaluated. To our knowledge, this study has established an effective rhamnosidase-fluorescent indicator and whole-cell catalytic system for the first time. Moreover, we analyzed the change in the activity of the crude rhaB1-EGFP as well as its whole-cell during the biocatalysis process using fluorescence intensity. Recombinant rhaB1-EGFP as a product which contains rhaB1 and EGFP showed higher thermal stability, pH stability, and conversion efficiency than rhaB1, and its optimum temperature for rutin catalysis was ideal for industrial applications. Moreover, under the optimal conditions of a rutin concentration of 0.05 g/L, pH of 6.0, temperature of 40 °C, a yield of 92.5% was obtained. Furthermore, we demonstrated the relationship between the fluorescence intensity and enzyme activity. This study established a highly efficient whole-cell catalytic system whose activity can be evaluated by fluorescence intensity, providing a reference for enzyme recycling.
Subject(s)
Biocatalysis , Glycoside Hydrolases , Hydrogen-Ion Concentration , Recombinant Proteins , Rutin , TemperatureABSTRACT
BACKGROUND: Adverse events during endoscopic submucosal dissection (ESD) of superficial esophageal neoplasms, such as perforation and bleeding, have been well-documented. However, the Mallory-Weiss Tear (MWT) during esophageal ESD remains under investigation. AIM: To investigate the incidence and risk factors of the MWT during esophageal ESD. METHODS: From June 2014 to July 2017, patients with superficial esophageal neoplasms who received ESD in our institution were retrospectively analyzed. The clinicopathological characteristics of the patients were collected. Patients were divided into an MWT group and non-MWT group based on whether MWT occurred during ESD. The incidence of MWTs was determined, and the risk factors for MWT were then further explored. RESULTS: A total of 337 patients with 373 lesions treated by ESD were analyzed. Twenty patients developed MWTs during ESD (5.4%). Multivariate analysis identified that female sex (OR = 5.36, 95%CI: 1.47-19.50, P = 0.011) and procedure time longer than 88.5 min (OR = 3.953, 95%CI: 1.497-10.417, P = 0.005) were independent risk factors for an MWT during ESD. The cutoff value of the procedure time for an MWT was 88.5 min (sensitivity, 65.0%; specificity, 70.8%). Seven of the MWT patients received endoscopic hemostasis. All patients recovered satisfactorily without surgery for the laceration. CONCLUSION: The incidence of MWTs during esophageal ESD was much higher than expected. Although most cases have a benign course, fatal conditions may occur. We recommend inspection of the stomach during and after the ESD procedure for timely management in cases of bleeding MWTs or even perforation outside of the procedure region.
Subject(s)
Endoscopic Mucosal Resection/adverse effects , Esophageal Neoplasms/surgery , Esophagoscopy/adverse effects , Intraoperative Complications/epidemiology , Mallory-Weiss Syndrome/epidemiology , Adult , Aged , Aged, 80 and over , Esophageal Mucosa/diagnostic imaging , Esophageal Mucosa/pathology , Esophageal Mucosa/surgery , Esophageal Neoplasms/pathology , Female , Humans , Incidence , Intraoperative Complications/diagnostic imaging , Intraoperative Complications/etiology , Male , Mallory-Weiss Syndrome/diagnostic imaging , Mallory-Weiss Syndrome/etiology , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Current research has identified several risk factors for refractory benign esophageal strictures (RBES), but research is scarce on the prediction of RBES in benign esophageal strictures patients. Meanwhile, the long-term outcomes of RBES remain unclear. The aim of this study was to develop and validate a model to determine the progression of RBES in patients with benign esophageal strictures. And we also explored the long-term outcomes and safety in patients with RBES. AIM: To develop and validate a model to determine the progression of RBES in patients with benign esophageal strictures, based on the demographic data and endoscopic findings. METHODS: A total of 507 benign esophageal stricture patients treated by dilation alone or in combination with stenting were retrospectively enrolled between January 2009 and February 2018. The primary outcome was to establish a risk-scoring model predicting RBES in benign esophageal strictures. The secondary outcome was to explore the clinical effectiveness and adverse events in patients with RBES. RESULTS: In the study, age, etiology, and number and length of strictures were the independent risk factors for the refractory performance of benign esophageal strictures. According to risk factors of benign esophageal strictures, a risk-scoring model for predicting RBES in benign esophageal strictures was established: The risk score ranged from 0 to 8 points, and the risk scores were divided into low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-8 points). The proportions of RBES in the corresponding risk categories were 1.0%, 12.2%, and 76.0%, respectively. Among 507 patients, 57 had RBES (39 males; median age, 60 years). The success rate of dilation treatment (51.2%, 21/41) was higher than that of stent placement (37.5%, 6/16). CONCLUSION: In this study, 11.3% (57/507) patients had RBES at our hospital. The risk-scoring model predicting RBES in benign esophageal strictures could predict the long-term outcome of patients with strictures ahead.