Comprehensive Bile Acid Profiling of ABCB4-mutated Patients and the Prognostic Role of Taurine-conjugated 3α,6α,7α,12α-Tetrahydroxylated Bile Acid in Cholestasis.

Background and Aims: We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid (tauro-THBA) in cholestasis. Methods: Serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS). The concentration of tauro-THBA was compared between ABCB4-mutated patients with different prognoses. The areas under the curve (AUCs) of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve (ROC), with another patient cohort for further verification. Results: The overall hydrophobicity indices of bile acids in ABCB4-mutated patients (12.99±3.25 m) were significantly lower than those of healthy controls (14.02±1.74 m, p<0.000). That was due to markedly increased bile acid modifications including conjugation, sulfation, and ketonization. Differences in the tauro-THBA concentration in ABCB4-mutated patients with different prognoses were not significant. ROC analysis indicated that levels of tauro-THBA of <60 nM yielded an AUC of 0.900 with a sensitivity of 80% and specificity of 87.5% for ABCB11-mutated patients with different prognoses (p=0.0192). Of the 15 patients with good prognosis, 14 were classified correctly and four of the five patients with a poor prognosis were classified correctly (14:15 vs. 1:5, p=0.005) with tauro-THBA as a classifier. Conclusions: Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gamma-glutamyl transferase intrahepatic cholestasis patients.

Exploring the Catalytic Flexibility and Reversibility of Plant Glycosyltransferase HtUGT72AS1 for Glycodiversification of Phenolic Compounds.

Plant bioactive metabolites such as flavonoids are usually present in glycosylated forms by the attachment of various sugar groups. In this study, a catalytically flexible and reversible glycosyltransferase (HtUGT72AS1) was cloned and characterized from Helleborus thibetanus. HtUGT72AS1 could directly accept six sugar donors (UDP-glucose/-arabinose/-galactose/-xylose/-N-acetylglucosamine/-rhamnose) to catalyze the 3-OH glycosylation of flavonols. It also catalyzed the 4' and 7-OH glycosylation of other types of flavonoids, which lacked the 3-OH group. Additionally, the HtUGT72AS1-catalyzed reaction was highly reversible when using 2-chloro-4-nitrophenyl glycosides as substrates, which could be used for one-pot or coupled production of bioactive glycosides. It is the first reported UGT for the synthesis of arabinosides and galactosides using a transglycosylation platform. Based on structural modeling and mutagenetic analysis, the mutation of Tyr377 to Ara enhanced the catalytic efficiency of HtUGT72AS1 toward UDP-N-acetylglucosamine, and the V146S mutant gained an improvement in the regioselectivity toward 7-OH of flavonoids.

Feasibility for the application of expanded endoscopic resection criteria in mucosal undifferentiated gastric cancer.

BACKGROUND & AIM: The indication of endoscopic submucosal dissection (ESD) for mucosal undifferentiated early gastric cancer (EGC) remains controversial because of risk of lymph node metastasis (LNM). The aim of this study was to identify risk factors for lymph node metastasis (LNM) in mucosal undifferentiated EGC, and further to confirm feasibility of the ESD for the treatment of mucosal undifferentiated EGC. METHODS: We retrospectively reviewed data of patients who underwent surgical resection with lymph node dissection of T1a stage primary gastric adenocarcinoma at three medical centers between 2012 and 2022. We evaluated the frequency of lymph node metastasis and the associated risk factors, as well as the lymph node metastasis rate in the expanded indication of mucosal undifferentiated EGC. RESULTS: A total of 100 surgically treated patients with mucosal undifferentiated EGC were enrolled. LNM was irrelevant to the age, tumor size, location, and macroscopic type (all P > 0.05), while it was significantly associated with lymphovascular invasion (LVI, P ＜0.001). And logistic regression analysis showed that the LVI was the only significant risk factors for LNM (OR: 0.34, 95%CI: 0.06-0.204; P ＜0.001). Of 44 mucosal undifferentiated EGC patients satisfying the expanded indication of ESD, 3 patients (6.8%) showed LN metastasis, all of them with undifferentiated cancer without ulceration, less than 2.0 cm in size. CONCLUSIONS: Because LNM is present in mucosal undifferentiated EGC patients who satisfied the expanded indication of ESD, ESD cannot be considered a better choice than surgery for all undifferentiated EGC patients. LVI was significant risk factors for LNM in patients with mucosal undifferentiated EGC.

Evaluation of Doppler indices (MCA & UA) and fetal outcomes: a retrospective case-control study in women with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is associated with an increased risk of adverse outcomes. The fetal middle cerebral artery (MCA) and umbilical artery (UA) blood flow detected by ultrasound are recommended to evaluate the oxygenation of the fetus. It is necessary to analyze the relationship between MCA & UA doppler indices or cerebroplacental ratio (CPR) and fetal outcomes and describe MCA and UA blood flow values across gestation. METHODS: Hospital-based retrospective case-control study during 2016 to 2020. 800 singleton pregnant women: 400 normotensive control, 219 gestational hypertension (GH), and 181 preeclampsia (PE)/eclampsia (EC). An analysis of the outcomes of mothers and neonates was performed. The fetal MCA and UA blood flow values across gestation were established, and MCA-resistance index (RI) and CPR were used to predict fetal distress and small for gestational age (SGA). RESULTS: In the normotensive control, GH and PE/EC groups, the mean gestational age (GA) was 38.9 ± 1.2 weeks, 39.0 ± 1.0 weeks, and 38.6 ± 1.3 weeks respectively, and the mean birth weight (BW) was 3.195 ± 0.387 kilograms, 3.198 ± 0.428 kilograms, and 2.987 ± 0.544 kilograms respectively. There were differences in GA, BW, fetal distress, SGA and intraventricular hemorrhage I-II between the hypertension group and normotensive control group (p < 0.05). The MCA-RI (sensitivity: 70.1%, specificity: 64.3%) and MCA-RI (sensitivity: 52.4%, specificity: 84.6%) were the best indices to predict fetal distress and SGA, respectively during GA of 35-40 weeks. CONCLUSIONS: Fetal MCA blood flow values and CPR are of great benefit for obstetricians to evaluate the status of fetus evidentially in singleton pregnancy.

Hybrid Au-star@Prussian blue for high-performance towards bimodal imaging and photothermal treatment.

In recent years, branched or star-shaped Au nanostructures composed of core and protruding arms have attracted much attention due to their unique optical properties and morphology. As the clinically adapted nanoagent, prussian blue (PB) has recently gained widespread attention in cancer theranostics with potential applications in magnetic resonance (MR) imaging. In this article, we propose a hybrid star gold nanostructure（Au-star@PB）as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI)/ photoacoustic imaging（PAI） and photothermal therapy (PTT) of tumors. Importantly, the Au-star@PB nanoparticles function as effective MRI/PA contrast agents in vivo by increasing T1-weighted MR/PAI signal intensity and as effective PTT agents in vivo by decreasing the tumor volume in MCF-7 tumor bearing BALB / c mouse model as well as in vitro by lessening tumor cells growth rate. Interestingly, we found the main photothermal effect of Au-star@PB is derived from Au-star, but not PB. In summary, the hybrid structure of Au-star@PB NPs with good biological safety, significant photostability, dual imaging capability, and high therapeutic efficiency, might offer a novel avenue for the future diagnosis and treatment of cancer.

Effect of Cerebral Ischemic Strokes in Different Cerebral Artery Regions on Left Ventricular Function.

Objectives: The relationship between cerebral ischemic stroke and left ventricular function evaluated by echocardiography has been emphasized. Whether lesions in different cerebral artery regions would result in left ventricular dysfunction remains uncertain. Methods: Patients were divided into middle cerebral artery (MCA) (n = 79), posterior cerebral artery (PCA) (n = 64), basilar artery (BA) regions (n = 66), and no-ischemic stroke group (n = 209). We retrospectively collected demographic characteristics, hematologic parameters, and ECG results, and a comparison of echocardiographic parameters was performed to determine the relationship between ischemic stroke and left ventricular function. Results: A total of 418 patients were included. Demographic characteristics did not significantly differ between the ischemic stroke and non-ischemic stroke groups, except for a history of drinking (p < 0.001). Homocysteine levels in the MCA group were higher than those in the PCA and BA groups (p < 0.05). The highly sensitive C-reactive protein (hs-CRP) level was higher in the ischemic stroke group than in the non-ischemic stroke one (p = 0.001). A higher incidence of ST-T changes in the ECG and lower levels of potassium and magnesium in the ischemic stroke group were found. Significant differences in diastolic function between groups were noted, and the early mitral inflow velocity, annular early diastolic velocity, and ratio between the mitral annular early diastolic velocity and mitral annulus atrial inflow velocity in the MCA group were lower than those in the BA group (p < 0.05). Conclusions: Ischemic strokes exhibited a negative effect on left ventricular diastolic function by echocardiography, especially in MCA region infarcts. These results are of great importance for neurologists as they highlight the need for left ventricular function evaluation after stroke to regulate therapy strategies in time.

A diagnostic test: diagnostic value of gastrointestinal endoscopy narrow-band imaging (NBI) for colorectal laterally spreading tumor (LST) and submucosal invasion.

Background: Endoscopic ultrasonography is an effective endoscopic examination method for determining the depth of colorectal cancer invasion. Narrow-band imaging (NBI) techniques increase the contrast of vascular structures and more clearly highlight subtle structures on mucosal surfaces, thereby improving the accuracy of endoscopic assessment. This study investigated the diagnostic efficacy of NBI in colorectal laterally spreading tumor (LST) and its submucosal invasion. Methods: A total of 224 patients with colorectal LST admitted to the Affiliated Hospital of Putian University from January 2015 to December 2021 were enrolled in this study. The patients were divided into NBI and endoscopic ultrasonography groups according to the different examination methods they received. Subsequently, the clinicopathological characteristics of the patients were collected, and the rates of submucosal invasion of the four subtypes (LST-G-H, LST-G-NM, LST-NG-F, LST-NG-PD) were compared between the two groups. Also, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of judging the depth of LST lesions of the two examination methods were compared, taking the results of pathological tissue examination as the gold standard. Results: This study enrolled 224 patients with LST (mean onset age: 57.98±6.48 years), including 123 males and 101 females. In terms of tumor location, 21 cases were located in the cecum, 22 cases in the ascending colon, 38 cases in the transverse colon, 11 cases in the descending colon, 12 cases in the descending sigmoid junction, 23 cases in the sigmoid colon, and 97 cases in the rectum. The sizes of the tumors ranged from 18.81 to 52.88 mm. Moreover, there were 21 cases of lesion infiltration into the submucosa, and the infiltration rate was 9.38%. Furthermore, the accuracy of NBI in diagnosing colorectal LST was significantly higher than that of endoscopic ultrasonography (87.05% vs. 57.14%); NBI was more accurate than endoscopic ultrasonography in the preoperative diagnosis of LST lesion depth in the rectal, non-rectal, granular (LST-G), non-granular (LST-NG), <40, and ≥40 mm groups. Conclusions: Gastrointestinal NBI has a superior accuracy rate and value than endoscopic ultrasonography in diagnosing colorectal LST, tumor lesion depth, and submucosal invasion. Therefore, gastrointestinal NBI deserves to be promoted in clinical work.

Reference intervals for preterm thyroid function during the fifth to seventh day of life.

BACKGROUND: Due to the lack of reference intervals for serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in preterm neonates during the 5th to 7th day of life, we performed a retrospective study using the chemiluminescence immunoassay system. METHODS: A total of 2040 preterm neonates with a gestational age (GA) of 26-35 weeks in the neonatal intensive care unit from 2014 to 2019 were included. Their serum FT3, FT4 and TSH values were calculated and analyzed to establish reference intervals for preterm neonates stratified by GA. The comparisons of FT3, FT4 and TSH were made by sex (males and females) and gestational age (26-28 weeks; 29-32 weeks; 33-35 weeks). RESULTS: The reference intervals for FT3, FT4 and TSH in preterm neonates with a GA of 26-35 weeks were (1.65~5.21) pmol/L, (8.64~25.41) pmol/L, and (0.406~12.468) mlU/L, respectively. There were significant differences between serum FT3 and FT4 values and GA, while TSH levels were not significantly different (P < 0.01). The serum FT3 values of males were lower than those of females, especially in the 29-32 weeks group. No significant differences in serum values between sexes were found in FT4 or TSH (P > 0.05). CONCLUSION: Reference intervals of thyroid function tests were established to determine the early diagnostic criteria of thyroid diseases for neonates with a GA of 26-35 weeks and to avoid unnecessary retesting and interventions. The reference intervals of FT4 can be used as an indicator to regulate the doses of thyroid hormone supplement in the treatments of congenital hypothyroidism.

Different posterior hippocampus and default mode network modulation in young APOE ε4 carriers: a functional connectome-informed phenotype longitudinal study.

To determine the functional connectome change pattern based on subregions of the hippocampus in young APOEε4 carriers during a 3-year follow-up. All the participants (n = 213) were tested for resting-state functional MRI, neuropsychological scales, and APOE genotype. The age- and sex-matched APOE ε4/ε3 (23.9 ± 3.2 years old, 6 female/7 male) carriers and APOE ε3/ε3 (22.9 ± 1.6 years old, 7 female/12 male) carriers were finally followed up. The hippocampus and its anterior/middle/posterior subregion-based functional connectivity (FC) patterns were compared between APOEε4 and APOEε3 groups by a two-sample t-test at baseline and mixed-effect analysis at follow-up. The effective connectivity (EC) patterns among the altered regions of interaction effect were examined in the APOEε4 groups. APOEε4 carries displayed saliently enhanced FC in the right anterior/middle hippocampus and core regions of the default mode network (DMN) (P < 0.05 by Gaussian Random Fields (GRF) correction). However, the APOEε4-by-time interaction was evident in the middle/posterior hippocampus with connection to the lateral temporal lobe and anterior cingulate cortex (ACC) (P < 0.05 by GRF correction). Moreover, the APOEε4 group at follow-up showed increased EC separately from both the left middle hippocampus and lateral temporal lobe to the left posterior hippocampus, and its changes of FC/EC significantly correlated with altered memory function. The posterior hippocampus might be especially vulnerable to early modulation in young APOEε4 carriers. Its connection with the lateral temporal lobe, rather than with DMN, might be the early compensative mechanism of memory function regulation influenced by APOE ε4 in the young adults.

Network-level functional connectivity alterations in chemotherapy treated breast cancer patients: a longitudinal resting state functional MRI study.

BACKGROUND: Previous studies have found abnormal structural and functional brain alterations in breast cancer survivors undergoing chemotherapy. However, the network-level brain changes following chemotherapy remain unknown. The purpose of this study was to investigate the dynamic changes of large-scale within- and between-network functional connectivity in chemotherapy-treated breast cancer patients. METHODS: Seventeen breast cancer patients were evaluated with resting state functional MRI (rs-fMRI), neuropsychological tests and blood examination before postoperative chemotherapy (t0), one week after completing chemotherapy (t1) and six months after completing chemotherapy (t2). Nineteen age- and education level-matched healthy controls (HC) were also recruited. Independent components analysis (ICA) was performed to assess network component using rs-fMRI data. The functional network changes were then correlated with cognitive assessment scores and blood biochemical indexes. RESULTS: One-way repeated measures ANOVA revealed significantly changed within-network functional connectivity in the anterior and posterior default mode network (ADMN and PDMN), left and right frontoparietal network (LFPN and RFPN), visual network and self-referential network. Post-hoc test showed that decreased within-network functional connectivity in ADMN, PDMN, LFPN, RFPN, SRN and central network one week after chemotherapy and increased six months after chemotherapy (all P < 0.05). As for the between-network functional connectivity, the PDMN- sensorimotor network connectivity showed the same tendency. Most of these within- and between-network functional connectivity changes were negatively associated with blood biochemical indexes and cognitive assessment scores (all P < 0.05). CONCLUSIONS: These results indicated that chemotherapy may induce widespread abnormalities in resting state networks, which may serve as a potential biomarker of chemotherapy related cognitive impairment, providing insights for further functional recovery treatment.

Impacts of AD-Related ABCA7 and CLU Variants on Default Mode Network Connectivity in Healthy Middle-Age Adults.

OBJECTIVE: To investigate the impact of Alzheimer's disease (AD)-related risk gene (ATP-binding cassette A7-ABCA7 and Clusterin-CLU) on the functional connectivity pattern of default mode network (DMN) in healthy middle-age adults. METHODS: A total of 147 healthy middle-aged volunteers were enrolled in this study. All subjects completed MRI scans, neuropsychological assessments, and AD-related genotyped analysis. All subjects were divided into high, middle and low risk groups according to the score of risk genotypes, which included CLU (rs11136000, rs2279590, rs9331888, and rs9331949) and ABCA7 (rs3764650 and rs4147929). The genetic effects of CLU, ABCA7, and CLU × ABCA7 on DMN functional connectivity pattern were further explored. Moreover, the genetic effect of Apolipoprotein ε4 (APOEε4) was also considered. Finally, correlation analysis was performed between the signals of brain regions with genetic effect and neuropsychological test scores. RESULTS: Compared with the low-risk group, the high-risk group of CLU showed decreased functional connectivity in posterior cingulate cortex (PCC) and the left middle frontal cortex (P < 0.05, GRF correction). As for the interaction between the CLU and ABCA7, all the subjects were divided into high, middle, and low risk group; the middle-risk group was divided into CLU and ABCA7-dominated middle-risk group. The function connectivity pattern of DMN among the three or four groups were distributed in the bilateral medial prefrontal cortex (MPFC) and bilateral superior frontal gyrus (SFG) (P < 0.05, GRF correction). When APOEε4 carriers were excluded, the CLU-predominant middle-risk group displayed the decreased functional connectivity in MPFC when compared with the low-risk group, while ABCA7-prodominant middle-risk group displayed decreased functional connectivity in cuneus when compared with the high-risk group (all P < 0.05, GRF correction). The z values of left middle frontal cortex were positively correlated with the scores of Serial Dotting Test (SDT) in high-risk group of CLU, while z values of MPFC and cuneus were positively correlated to the scores of Montreal Cognitive Assessment (MoCA) in low-risk group of three or four groups. CONCLUSION: The functional connectivity of MPFC-PCC might be modulated by the interaction of CLU and ABCA7. Moreover, APOEε4 might be interacted with ABCA7 and CLU modulation in the middle-aged carriers.

Impacts of FKBP5 variants on large-scale brain network connectivity in healthy adults.

BACKGROUND: FK506 binding protein 5 (FKBP5) rs1360780 polymorphism has been identified as a molecular genetic marker associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The impact of FKBP5 rs1360780 on the large-scale brain network connectivity in healthy adults is still unknown. METHODS: 479 healthy volunteers (age: 20-80years) completed MRI scans, neuropsychological assessments and blood analysis.All subjects were divided into CC, CT and TT genotypes. Within and between network connectivities (10 sub-networks) were calculated using resting state functional MRI (rs-fMRI) data. The genetic effects and gene-gender/age interaction on large-scale network connectivity were explored. RESULTS: Compared with CC and CT groups, TT group showed increased intra-connectivity in default mode network (DMN) and increased inter-connectivity mainly distributed among the network of DMN, salience network (SAN), dorsal attention network (DAN), ventral attention network (VAN), subcortical network (SUB), and visual network (VIS). Gene-by-gender and gene-by-age interaction were found in inter-connectivity of DAN to VIS and DMN to FPN, respectively. The altered connectivities correlated with anxiety status test score. LIMITATIONS: Plasma adrenocorticotropic hormone (ACTH) or cortisol were not measured,or else, we could estimate the hypothalamic-pituitary-adrenal (HPA) axis activity which may strengthen our results. CONCLUSIONS: FKBP5 rs1360780 modulates the large-scale brain network connectivity in healthy adults. TT carriers showed the increased intra- and inter-connectivities mainly distributed among the network of DMN, SAN, DAN, VAN, SUB and VIS.

Gut dysbiosis-influence on amygdala-based functional activity in patients with end stage renal disease: a preliminary study.

Patients with end-stage renal disease (ESRD) are notably accompanied by cognitive disorder and anxiety or depressive symptom. We aimed to explore the linkages of the amygdala-based MR parameters, cognitive and mood performance, systematic inflammation and gut microbiota in ESRD. This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 43.9 ± 13.8 years) and 19 age- and sex-matched healthy control (HC) (12 males and 7 females, mean age of 44.1 ± 10.0 years). All subjects underwent cognitive assessment, inflammatory factor and stool microbiota analysis, and brain MRI analysis [amygdala-based functional connectivity and voxel-based morphometry (VBM)]. ERSD was separated by different microbiota strains. All factors were compared between ESRD and HC, as well as between ESRD subgroups. Pearson correlation analysis and causal mediation analysis were conducted to further investigate the relationship among the factors derived from the gut microbiota, brain and systemic inflammation. ESRD displayed gut dysbiosis and increased systemic inflammation when compared to HC (all P < 0.05). Meanwhile, ESRD showed smaller VBM in amygdala, decreased functional connectivity in left amygdala - right inferior parietal lobe [P < 0.05, Gaussian Random Field (GRF) corrected] and worse cognitive or mood performance. Moreover, ESRD-B (Prevutella mainly), when compared to ESRD-A (Bacteroides mainly), displayed increased interleukin-6, self-rating anxiety scale and functional connectivity in left amygdala - bilateral anterior cingulate cortex / medial superior frontal cortex (P < 0.05, GRF corrected). Furthermore, the correlation network of ESRD showed that both gut dysbiosis and amygdala-based alteration were correlated with cognitive performance and systemic inflammation. Causal mediation analysis validated that the disrupted distribution of Roseburia indirectly regulated the amygdala-based functional connectivity through tumor necrosis factor-alpha. The gut dysbiosis induced by ESRD was closely related to pro-inflammatory cytokines, amygdala-based phenotype, and mood performance. The lower abundance in Roseburia indirectly modulated amygdala-based functional connectivity pattern by tumor necrosis factor-alpha, which might provide a new way in diagnosis and treatment in patients of ESRD with depressive/anxious mood.

Postchemotherapy hippocampal functional connectivity patterns in patients with breast cancer: a longitudinal resting state functional MR imaging study.

The hippocampus plays a key role in cognitive function and emotion regulation due to its wide connection with the whole brain. This study examined the acute effect of chemotherapy on hippocampal and subfield functional connectivity and neuropsychological status in breast cancer patients (BC). This IRB approved study included 29 BC and 25 age matched healthy controls (HCs) who underwent resting state functional magnetic resonance imaging (Rs-fMRI), neuropsychological tests and blood examinations at baseline and one week after completing chemotherapy or in the same time interval. Within-group comparisons and group-by-time interactions analysis of hippocampus- and subregion- based functional connectivity were performed between the two groups. Functional connectivity changes were correlated with changes of blood examination and neuropsychological test scores in the BC group. The BC group had higher depression and anxiety scores, poorer performance on visual mobility, auditory memory and executive function than HCs (p < 0.05), and significantly abnormal estrodiol, total cholesterol and triglycerides (p < 0.05). BC survivors showed significant hippocampal functional connectivity changes mainly in the left insula, temporal lobe (Gaussian Random Field theory correction, P < 0.001) and the left inferior frontal gyrus (P < 0.01). The functional connections from the anterior hippocampus to the left temporal lobe were greater than the posterior hippocampus (P < 0.05). The hippocampus functional connectivity alterations were closely related to changes in depression scores, estrodiol and triglycerides (all p < 0.05). Chemotherapy induced especially anterior hippocampal functional connectivity abnormality, which is related to depression symptom, estrodiol and triglycerides disorders.

The gut microbiota-inflammation-brain axis in end-stage renal disease: perspectives from default mode network.

The gut-brain axis in end-stage renal disease (ESRD) is attracting more and more attention. However, the mechanism of gut-brain axis based cognitive disorders in ESRD patients remains unclear. The purpose of this study was to investigate the linkages between the gut microbiota, inflammatory cytokines, brain default mode network (DMN) and cognitive function in ESRD patients. Methods: This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 44 ± 14 years) and 19 healthy controls (HCs) (12 males and 7 females, mean age of 44 ± 10 years). All subjects underwent stool microbiota analysis, blood inflammatory cytokines examination, brain MRI scans and cognitive assessments. Resting state functional MRI (rs-fMRI) data were used to construct DMN and graph theory was applied to characterize network topological properties. Two samples t-test was applied for the comparisons between ESRD and HCs. Correlation analysis and mediation analysis were conducted among factors with significant group differences. Results: ESRD patients displayed gut microbiota alterations, increased systemic inflammation and worse cognitive performance compared to HCs (all p < 0.05). Graph analysis revealed disrupted DMN topological organization, aberrant nodal centralities and functional connectivities (FCs) in ESRD patients relative to HCs (all p < 0.05, FDR corrected). Significant correlations were found between gut microbiota, inflammatory cytokines, DMN network measures and cognitive assessments. Mediation analysis found that gut microbiota alteration impaired DMN connectivity by increasing systemic inflammation. Conclusion: The present study first revealed gut microbiota alterations, systemic inflammation, DMN dissociation and cognitive dysfunction in ESRD patients simultaneously and further illuminated their inner relationship.

Machinability of enamel under grinding process using diamond dental burrs.

Enamel grinding is a critical dental surgery process. However, tooth damage during the process remains a significant problem. Grinding forces, burr wear, and surface quality were characterised in relation to grinding speed, enamel orientation, grinding depth, and burr grit grain size. Results indicated that enamel rod orientation, grinding depth, and grinding speed critically affected enamel grinding. Occlusal surface grinding resulted in significantly higher normal forces, surface roughness, and marginally greater tangential forces than axial surface grinding. Damage to enamel machined surfaces indicated the significant impact of diamond grit size and rod orientation. Burr wear was primarily diamond grit peeling off and breakage. Surface roughness of axial and occlusal sections was largely influenced by grinding speed and diamond grit size. Improving the surface quality of machined enamel surfaces could be realised using fine burrs, reducing the grinding speed and grinding depth, and adjusting the feed direction vertical to the rod orientation. Enamel surface quality and roughness could be improved by reducing brittle failure and circular runout during the grinding process, respectively.

Incidence of portal vein thrombosis after splenectomy and its influence on transjugular intrahepatic portosystemic shunt stent patency.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is widely accepted as an alternative to surgery for management of complications of portal hypertension. TIPS has been used to treat portal vein thrombosis (PVT) in many centers since the 1990s. Although TIPS has good therapeutic effects on the formation of PVT, the effect of PVT on TIPS stenting has rarely been reported. Patients with splenectomy and pericardial devascu-larization have a high incidence of PVT, which can markedly affect TIPS stent patency and increase the risk of recurrent symptoms associated with shunt stenosis or occlusion. AIM: To investigate the incidence of PVT after splenectomy and its influence on the patency rate of TIPS in patients with cirrhosis and portal hypertension. METHODS: Four hundred and eighty-six patients with portal hypertension for refractory ascites and/or variceal bleeding who required TIPS placement between January 2010 and January 2016 were included in this retrospective analysis. Patients without prior splenectomy were defined as group A (n = 289) and those with prior splenectomy as group B (n = 197). The incidence of PVT before TIPS was compared between the two groups. After TIPS placement, primary patency rate was compared using Kaplan-Meier analysis at 3, 6, 9 and 12 mo, and 2 and 3 years. The clinical outcomes were analyzed. RESULTS: Before TIPS procedure, the incidence of PVT in group A was lower than in group B (P = 0.003), and TIPS technical success rate in group A was higher than in group B (P = 0.016). The primary patency rate in group A tended to be higher than in group B at 3, 6, 9 and 12 mo, 2 years and 3 years (P = 0.006, P = 0.011, P = 0.023, P = 0.032, P = 0.037 and P = 0.028, respectively). Recurrence of bleeding and ascites rate in group A was lower than in group B at 3 mo (P ≤ 0.001 and P = 0.001), 6 mo (P = 0.003 and P = 0.005), 9 mo (P = 0.005 and P = 0.012), 12 mo (P = 0.008 and P = 0.024), 2 years (P = 0.011 and P = 0.018) and 3 years (P = 0.016 and P = 0.017), respectively. During 3-years follow-up, the 1-, 2- and 3-year survival rate in group A were higher than in group B (P = 0.008, P = 0.021, P = 0.018, respectively), but there was no difference of the incidence of hepatic encephalopathy (P = 0.527). CONCLUSION: Patients with prior splenectomy have a high incidence of PVT, which potentially increases the risk of recurrent symptoms associated with shunt stenosis or occlusion.

Uric Acid Has Different Effects on Spontaneous Brain Activities of Males and Females: A Cross-Sectional Resting-State Functional MR Imaging Study.

OBJECTIVE: To explore the relationship among serum uric acid (SUA) levels in different states of disease, human cognition, and spontaneous brain activities by resting-state functional MRI (rs-fMRI). METHODS: We prospectively recruited 100 subjects (age 58 ± 11 years, 55 females) who underwent fasting blood sampling, cognitive tests and rs-fMRI scans. The subjects were divided into two groups by sex and each sex group was further stratified into three subgroups according to SUA level in different states of disease. The amplitude of low-frequency fluctuation (ALFF) method was applied to assess spontaneous brain activity among groups. Pearson's correlation analysis was used to investigate the relationships between the mean ALFF values (mALFF) and cognitive tests. RESULTS: A total of 97 patients completed the study protocol successfully. Significant differences in age, education level, number connection test (NCT), and word fluency were observed among the three subgroups in males (all P < 0.05). Results of group-by-sex interaction were distributed in bilateral pallidum and putamen [voxel P-value < 0.001, cluster P-value < 0.05, Gaussian random field (GRF)-corrected]. The tendency of the SUA effect on mALFF was different in males and females, particularly in corresponding High SUA subgroups (that is pre-hyperuricemia, both P < 0.001). Among the male subjects, mALFF values of the bilateral pallidum and putamen negatively correlated with attention/executive function. CONCLUSION: Our results suggest that elevated SUA levels have different effects on spontaneous brain activities and cognitive function in males and females. Males with pre-hyperuricemia and hyperuricemia are more susceptible to changes in spontaneous brain activities and lower neuropsychological assessment scores, particularly in word fluency tests and NCT, compared to females.

Neuroinflammation, Gut Microbiome, and Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that develops insidiously and causes dementia finally. There are also clinical complications in advanced dementia, such as eating problems, infections, which will lead to the decline of patients' life quality, and the rising cost of care for AD to our society. AD will be important public health challenge. Early detection of AD may be a key issue to prevent, delay, and stop the disease. Gut microbiome and neuroinflammation are closely related with nervous system diseases, although the specific mechanism is not clear. This review introduces the relationship between neuroinflammation, gut microbiome, and AD.

The quantification and assessment of depression and anxiety in patients with postoperative gastroparesis syndrome.

BACKGROUND: This study aimed to analyze the stage-situation depression and anxiety as well as independent influential factors in patients with postsurgical gastroparesis syndrome (PGS) and to provide dependent indications for treatment. PATIENTS AND METHODS: The self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to test the depression and anxiety of 53 patients with PGS, who were treated in the Department of Gastroenterological Surgery of Gansu Provincial Hospital from January 2012 to October 2016. A comparison between the SDS or SAS scores of patients with PGS and without PGS was undertaken; then, we retrospectively analyzed the factors influencing depression and anxiety in PGS patients. RESULTS: The patients with PGS' mean scores of depression and anxiety were 49.92±11.37 and 50.91±6.57, respectively, which were higher than that of patients without PGS in the Chinese population (P<0.05). The results of multivariate logistic regression analysis indicated that the independent influential factors of depression and anxiety in patients with PGS included course of disease, pancreatic juice leakage, preoperative outflow tract obstruction, postoperative abdominal infection, and anastomotic complication (P<0.05). Patients with a disease course longer than 30 days; with pancreatic juice leakage; and who suffered from preoperative outflow tract obstruction, postoperative abdominal infection, and anastomotic complication had higher ratios of depression and anxiety. CONCLUSION: Depression and anxiety are clearly evident in patients with PGS, and we should pay attention to this phenomenon and provide appropriate treatment.