Reduced functional connectivity induced by longitudinal alterations of structure and perfusion may be associated with cognitive impairment in patients on maintenance hemodialysis.

Hemodialysis (HD) leads to cognitive impairment; however, the pathophysiology of maintenance HD remains unclear. This study aimed to investigate the longitudinal alterations in gray matter volume (GMV) and cerebral blood flow (CBF) in patients on HD at follow-up compared with baseline, examine the alterations in functional connectivity (FC) by defining co-changed brain regions as seed points, and investigate the correlation between the co-changed brain regions and neuropsychological test scores. Twenty-seven patients with HD and 30 healthy controls were enrolled in this study. All participants underwent high-resolution T1-weighted imaging, arterial spin labeling, and functional MR imaging to measure GMV, CBF, and FC. The patients on HD were assessed at baseline and 3 years subsequently. The right and left medial superior frontal gyrus (SFGmed.L) exhibited significantly lower GMV and CBF in patients on HD at follow-up compared with baseline and lower FC between the SFGmed.L and left middle temporal gyrus (MTG.L). FC between the SFGmed.L and MTG.L was positively correlated with neuropsychological test scores in the HD group at follow-up. Reduced GMV and CBF may result in decreased FC between the SFGmed.L and MTG.L, which may be associated with cognitive impairment in patients on maintenance HD. Our findings provide unique insights into the pathological mechanisms of patients on maintenance HD with cognitive impairment.

Preimplantation genetic testing in the current era, a review.

BACKGROUND: Preimplantation genetic testing (PGT), also referred to as preimplantation genetic diagnosis (PGD), is an advanced reproductive technology used during in vitro fertilization (IVF) cycles to identify genetic abnormalities in embryos prior to their implantation. PGT is used to screen embryos for chromosomal abnormalities, monogenic disorders, and structural rearrangements. DEVELOPMENT OF PGT: Over the past few decades, PGT has undergone tremendous development, resulting in three primary forms: PGT-A, PGT-M, and PGT-SR. PGT-A is utilized for screening embryos for aneuploidies, PGT-M is used to detect disorders caused by a single gene, and PGT-SR is used to detect chromosomal abnormalities caused by structural rearrangements in the genome. PURPOSE OF REVIEW: In this review, we thoroughly summarized and reviewed PGT and discussed its pros and cons down to the minutest aspects. Additionally, recent studies that highlight the advancements of PGT in the current era, including their future perspectives, were reviewed. CONCLUSIONS: This comprehensive review aims to provide new insights into the understanding of techniques used in PGT, thereby contributing to the field of reproductive genetics.

Association between white matter hyperintensities and altered cerebral blood flow in maintenance hemodialysis patients: a longitudinal study.

OBJECTIVES: To explore changes in cerebral blood flow (CBF) and white matter in hemodialysis patients. METHODS: Thirty-three hemodialysis patients who underwent two brain MRI at an interval of three years and 33 age- and sex-matched healthy controls (HC) underwent structural and arterial spin-labeling MRI examinations. Intergroup differences in CBF in the gray matter, white matter, and whole matter, and regional white matter hyperintensities (WMH) were analyzed. Based on the changes in CBF between the baseline and follow-up groups, the hemodialysis patients were divided into two subgroups: an increased CBF group and a decreased CBF group. Differences in CBF and WMH between the subgroups and HC were analyzed. RESULTS: Patients undergoing hemodialysis exhibited increased cerebral watershed (CW) WMH, deep WMH, and periventricular WMH (P < 0.01). The CBF of patients with decreased CBF was higher than that of HC at baseline (,P < 0.01) and lower than that of HC at follow-up (P < 0.01). Compared with the increased CBF group, obvious development of deep WMH was found in the decreased CBF group for the gray matter, white matter, and whole matter (P < 0.01). CONCLUSIONS: WMH in hemodialysis patients were distributed in the deep white matter, periventricular white matter and CW, and progressed with the extension of hemodialysis duration. CBF in hemodialysis patients could manifest as both increased and decreased, and WMH in patients with decreased CBF developed severely with prolongation of hemodialysis duration. ADVANCES IN KNOWLEDGE: These findings provide a basis for exploring neuropathological changes of hemodialysis patients.

Transjugular intrahepatic portosystemic shunt for portal hypertension with chronic portal vein occlusion.

PURPOSE: This study aims to evaluate the long-term patency of transjugular intrahepatic portosystemic shunt (TIPS) and determine the predictors of shunt dysfunction in patients with chronic portal vein occlusion (CPVO). METHOD: This retrospective study was conducted from December 2010 to December 2020 in patients with portal hypertension and CPVO. Patients were followed up from initial TIPS insertion to December 2022 or death. Details of TIPS procedure, adverse events and clinical outcomes were recorded. The cumulative rate of shunt patency was calculated by the Kaplan-Meier method and compared by using the log-rank test. Independent predictors of shunt dysfunction were calculated with the Cox regression model. A nomogram comprising independent variables was developed to enhance the predictive accuracy of shunt patency. RESULTS: One hundred six patients (mean age, 45.3 years ± 13.6; 71 males and 35 females) were enrolled in the study. TIPS procedure was technically successful in 100 of 106 patients (94.3 %). The primary shunt patency rates for all 100 patients were 78.9 %, 74.7 %, 67.2 %, and 62.4 % at 6, 12, 24, and 36 months, respectively, and the overall shunt patency rates were 88.9 %, 86.8 %, 83.6 %, and 81.2 % at 6, 12, 24, and 36 months, respectively. Independent predictor of shunt dysfunction were inadequate inflow from superior mesenteric vein or splenic vein (the maximum diameter < 8 mm) and platelet count ≥ 300 × 109/L. The developed nomogram is a simple tool for accurately predicting shunt patency. CONCLUSIONS: In patients with CPVO, inadequate inflow and high platelet count are important factors for TIPS dysfunction.

Association of aberrant structural-functional network coupling with cognitive decline in patients with non-dialysis-dependent stage 5 chronic kidney disease.

Background: Cognitive decline exists in the chronic kidney disease (CKD) population and is particularly severe in patients with stage 5 CKD, but the mechanisms underlying this relationship are unclear. Structural-functional coupling, an integrated measure that combines functional and structural networks, offers the possibility of exploring changes in network relationships in patients with stage 5 CKD. This study aimed to investigate the brain network topology and structural-functional coupling characteristics in patients with non-dialysis-dependent stage 5 CKD (CKD 5ND) and the correlation between network changes and cognitive scores. Methods: We prospectively performed diffusion tensor and resting-state functional magnetic resonance (rs-fMRI) imaging on 40 patients with CKD 5ND disease and 47 healthy controls (HCs). Graph theory analysis of functional and structural connectivity (SC) was performed. Small-world properties and network efficiency properties were calculated, including characteristic path length (Lp), clustering coefficient (Cp), normalized clustering coefficient (Gamma), normalized characteristic path length (Lambda), small-worldness (Sigma), global efficiency (Eglob), and local efficiency (Eloc). The SC-functional connectivity (FC) coupling characteristics and the association between Montreal Cognitive Assessment (MoCA) scores and graph-theoretical features were analyzed. Results: For SC, the Sigma (P=0.009), Cp (P=0.01), Eglob (P<0.001), and Eloc (P=0.01) were significantly lower in patients with CKD 5ND than in HCs, while Lp (P<0.001) and Lambda (P<0.001) were significantly higher in the patients than in the HCs. For FC, the Sigma (P=0.008), Gamma (P=0.009), Eglob (P=0.04), and Eloc (P<0.0001) were lower in patients with CKD 5ND than in HCs; however, the Lp (P=0.02) was higher in the patients than in the HCs. SC-SC coupling (P<0.001) was greater in patients with CKD 5ND than in HCs. The structural (Cp, Eloc, Eglob) and functional network parameters (Sigma, Gamma, Eglob) of the patients with CKD 5ND were positively correlated with MoCA scores; however, the Lp of both structural and functional networks was negatively correlated with MoCA scores. Conclusions: All patients with CKD 5ND included in the study exhibited changes in their structural and functional brain network topology closely related to mild cognitive impairment. SC-SC coupling was elevated in the patients compared with that in the controls. This may provide vital information for understanding and revealing the underlying mechanisms of cognitive impairment in patients with CKD 5ND.

6-mm shunt transjugular intrahepatic portosystemic shunt in patients with severe liver atrophy and variceal bleeding.

OBJECTIVES: We proposed a strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt (TIPS) and to assess its effectiveness compared to a conventional 8-mm shunt for TIPS-induced hepatic encephalopathy (HE). METHODS: Patients were reviewed retrospectively using propensity score matching (1:1) and divided into 6-mm and 8-mm shunt groups based on shunt diameter. The stent patency, HE incidence, and rebleeding rate between the two groups were then compared. RESULTS: From January 2018 to June 2021, both 6-mm shunt group and 8-mm shunt group included 58 patients. The 6-mm shunt group had significantly smaller liver volumes (879.3 ± 237.1 vs. 1008.8 ± 293.0; p = 0.010), and the median stent patency times were 30.7 and 33.8 months in the 6-mm and 8-mm groups, respectively (p = 0.124). No statistically significant difference was found between the two groups in the 1-year (8.6% vs. 3.4%; p = 0.242) and 2-year (17.2% vs. 12.1%; p = 0.242) rebleeding rates. The 1-year cumulative incidences of overt HE were 12.1% and 27.6% in the 6-mm and 8-mm groups, respectively (p = 0.040), and the 2-year cumulative overt HE incidences in these groups were 19.0% and 36.2%, respectively (p = 0.038). Notably, patients with a 6-mm shunt also experienced less hepatic impairment. CONCLUSIONS: For patients with variceal bleeding and a small liver volume, the 6-mm shunt significantly reduced the incidence of overt HE, protected perioperative liver function, and did not affect stent patency or rebleeding rate. CLINICAL RELEVANCE STATEMENT: For patients with variceal bleeding with small liver volume, the 6-mm transjugular intrahepatic portosystemic shunt (TIPS) significantly reduced the incidence of overt hepatic encephalopathy after TIPS, protected perioperative liver function, and did not affect stent patency and rebleeding rate. KEY POINTS: • A strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt for patients with variceal bleeding and a small liver volume was proposed. • The 6-mm transjugular intrahepatic portosystemic shunt significantly reduced the incidence of overt hepatic encephalopathy. • The 6-mm transjugular intrahepatic portosystemic shunt did not affect stent patency or rebleeding rate.

Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab or Lenvatinib for Unresectable Hepatocellular Carcinoma: A Propensity Score Matched Study.

Purpose: Combined transarterial chemoembolization (TACE) and Lenvatinib (LEN) treatment (LEN-TACE) has been shown to be beneficial. We aimed to evaluate retrospectively Atezolizumab plus Bevacizumab (Atezo/Bev)-TACE compared with LEN-TACE as a first-line therapy for unresectable HCC. Patients and Methods: From October 2020 to October 2022, data from 98 consecutive HCC patients were analyzed. After propensity score matching, two cohorts of 34 patients who received either Atezo/Bev-TACE or LEN-TACE were studied. We compared overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR) and disease control rate (DCR) based on RECIST 1.1 and mRECIST, as well as safety outcome between the two cohorts. Results: The 6-month and 12-month OS rates were 85.3% (95% CI 73.5-97.0) and 75.4% (95% CI 53.6-85.7) in the Atezo/Bev-TACE group, and 88.2% (95% CI 76.5-97.1) and 79.2% (95% CI 63.6-90.9) in the LEN-TACE group, respectively. The hazard ratio for death in the Atezo/Bev-TACE group compared to the LEN-TACE group was 1.09 (95% CI 0.47-2.51; P = 0.837). The median PFS was 7.03 months (95% CI 3.89-10.17) in the Atezo/Bev-TACE group and 6.03 months (95% CI 0-14.14) in the LEN-TACE group (HR 1.21; 95% CI 0.66-2.21; P = 0.545). No significant difference in ORR and DCR between the two groups was observed either according to RECIST 1.1 or mRECIST standards. Incidence rates of hand-foot skin reaction (35.3% vs 5.9%, P = 0.003) and proteinuria (17.9% vs 2.9%, P = 0.046) were significantly higher in the LEN-TACE group. Conclusion: Atezo/Bev-TACE and LEN-TACE showed comparable efficacy and safety as first-line therapies for unresectable HCC patients.

Safety, efficacy, and survival of drug-eluting beads-transarterial chemoembolization vs. conventional-transarterial chemoembolization in advanced HCC patients with main portal vein tumor thrombus.

OBJECTIVES: To compare the efficacy, overall survival (OS) and safety of drug-eluting beads-TACE (DEB-TACE) and C-TACE as initial treatment in advanced hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (mPVTT). METHODS: The medical records of consecutive advanced HCC patients with mPVTT who underwent initial DEB-TACE or C-TACE from September 2015 to October 2021 were retrospectively evaluated. Treatment crossover was allowed in this retrospective research. The adverse events, disease control rate (DCR), time to tumor progression (TTP) and OS of patients who underwent DEB-TACE were compared with those of patients who underwent C-TACE. RESULTS: Eighty-three patients were included: 42 patients in DEB-TACE group and 41 patients in C-TACE group. DEB-TACE could be safely performed in HCC patients with mPVTT, and they gained a better DCR than those submitted to the C-TACE (76.2% vs. 53.7%, P = 0.031), which might have resulted in longer TTP (median TTP: 9.0 months vs. 3.0 months, P < 0.001). Furthermore, DEB-TACE showed significant OS benefits compared with C-TACE (median OS: 12.0 months vs. 5.0 months, P < 0.001). DEB-TACE, absence of arterioportal shunts (APS), leisons with capsular non-infiltration were found to be independent prognostic factors for better OS. Furthermore, subgroup analysis proved that patients with good DCR gained longer OS in DEB-TACE group. CONCLUSIONS: DEB-TACE could be safely performed and improve the DCR of HCC patients with mPVTT, which resulting in longer TTP and OS, compared with C-TACE.

Idarubicin versus epirubicin in drug-eluting beads-transarterial chemoembolization for treating hepatocellular carcinoma: A real-world retrospective study.

The purpose of this study was to compare the efficacy and safety of idarubicin-loaded drug-eluting beads-transarterial chemoembolization (IDA-TACE) and epirubicin-loaded drug-eluting beads-TACE (EPI-TACE) in treating hepatocellular carcinoma (HCC). All patients with HCC treated with TACE in our hospital between June 2020 and January 2022 were screened. The included patients were divided into the IDA-TACE group and EPI-TACE group to compare overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events. There were 55 patients each in the IDA-TACE and EPI-TACE groups. Compared with the EPI-TACE group, the median TTP in the IDA-TACE group was not significantly different (10.50 vs. 9.23 months; HR 0.68; 95% CI 0.40-1.16; P = 0.154), whereas the survival status in the IDA-TACE group tended to be better (neither achieved; HR 0.47; 95% CI 0.22-1.02; P = 0.055). Based on the Barcelona Clinic Liver Cancer staging system for subgroup analysis, considering stage C patients, the IDA-TACE group performed significantly better in terms of ORR (77.1% vs. 54.3%, P = 0.044), median TTP (10.93 vs. 5.20 months; HR 0.46; 95% CI 0.24-0.89; P = 0.021), and median OS (not achieved vs. 17.80 months; HR 0.41; 95% CI 0.18-0.93; P = 0.033). Considering stage B patients, there were no significant differences between the IDA-TACE and EPI-TACE groups in terms of ORR (80.0% vs. 80.0%, P = 1.000), median TTP (10.20 vs. 11.2 months; HR 1.41; 95% CI 0.54-3.65; P = 0.483), or median OS (neither achieved, HR 0.47; 95% CI 0.04-5.24; P = 0.543). Notably, leukopenia was more common in the IDA-TACE group (20.0%, P = 0.052), and fever was more common in the EPI-TACE group (49.1%, P = 0.010). IDA-TACE was more effective than EPI-TACE in treating advanced-stage HCC and comparable in treating intermediate-stage HCC.

Dysfunctional Coupling of Cerebral Blood Flow and Susceptibility Value in the Bilateral Hippocampus is Associated with Cognitive Decline in Nondialysis Patients with CKD.

SIGNIFICANCE STATEMENT: Patients with end stage CKD often develop cognitive decline, but whether this is related to the underlying disease or to hemodialysis remains unclear. We performed three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping prospectively in 40 patients with stage 1-4 CKD, 47 nondialysis patients with stage 5 CKD, and 44 healthy controls. Our magnetic resonance imaging data demonstrate that changes in cerebral blood flow-susceptibility coupling might underlie this cognitive decline, perhaps in the hippocampus and thalamus. These results suggest that magnetic resonance imaging parameters are potential biomarkers of cognitive decline in patients with CKD. Moreover, our findings may lead to discovery of novel therapeutic targets to prevent cognitive decline in patients with CKD. BACKGROUND: Cerebral blood flow (CBF) and susceptibility values reflect vascular and iron metabolism, providing mechanistic insights into conditions of health and disease. Nondialysis patients with CKD show a cognitive decline, but the pathophysiological mechanisms underlying this remain unclear. METHODS: Three-dimensional pseudocontinuous arterial spin labeling and quantitative susceptibility mapping were prospectively performed in 40 patients with stage 1-4 CKD (CKD 1-4), 47 nondialysis patients with stage 5 CKD (CKD 5ND), and 44 healthy controls (HCs). Voxel-based global and regional analyses of CBF, susceptibility values, and vascular-susceptibility coupling were performed. Furthermore, the association between clinical performance and cerebral perfusion and iron deposition was analyzed. RESULTS: For CBF, patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than HCs. Patients with CKD 5ND had higher normalized CBF in the hippocampus and thalamus than those with CKD 1-4. The susceptibility values in the hippocampus and thalamus were lower in patients with CKD 5ND than in HCs. Patients with CKD 5ND had higher susceptibility value in the caudate nucleus than those with CKD 1-4. More importantly, patients with CKD 5ND had lower CBF-susceptibility coupling than HCs. In addition, CBF and susceptibility values were significantly associated with clinical performance. CONCLUSIONS: Our findings demonstrate a new neuropathological mechanism in patients with CKD, which leads to regional changes in CBF-susceptibility coupling. These changes are related to cognitive decline, providing potential imaging markers for assessing clinical disability and cognitive decline in these patients.

Administration of Huperzine A microspheres ameliorates myocardial ischemic injury via α7nAChR-dependent JAK2/STAT3 signaling pathway.

Acetylcholinesterase (AChE) inhibitor (AChEI) is well established as first-line agents for relieving the symptoms of Alzheimer's disease (AD). Injectable sustained-release formulation of AChEI may be suitable for treating AD patients. However, it needs to know whether continuous inhibition of AChE could deteriorate or attenuate myocardial damage if myocardial ischemia (MI) occurs. Huperzine A microspheres (HAM) are a sustained-release formulation releasing sustainably huperzine A (an AChEI) for more than 7 days after a single dose of HAM. This study aimed to investigate the myocardial damage in an isoprenaline (ISO)-induced MI mice model during HAM treatment. The heart injury was evaluated by assaying serum CK-MB, Tn-I and observing histopathological changes. The levels of proinflammatory cytokines in serum were detected. The level of p-P65 and the expression of proteins in the JAK2/STAT3 signaling pathway were assayed with Western blot. Administration with a single dose of HAM resulted in inhibiting the MI-induced increases of CK-MB and Tn-I, alleviating the damage of heart tissue, and decreasing the levels of TNF-α and IL-6. In addition, HAM decreased the levels of p-P65, p-JAK2, and p-STAT3 in heart tissue. The effects of HAM could be weakened or abolished by the specific α7nAChR antagonist. These findings suggest that continuous AChE inhibition could protect the heart from ischemic damage during administration of sustained-release formulation of AChEI, which is associated with the anti-inflammatory effect of HAM by regulating α7nAChR-dependent JAK2/STAT3 signaling pathway.

Association between susceptibility value and cerebral blood flow in the bilateral putamen in patients undergoing hemodialysis.

Hemodialysis (HD) is the most regularly applied replacement therapy for end-stage renal disease, but it may result in brain injuries. The correlation between cerebral blood flow (CBF) alteration and iron deposition has not been investigated in patients undergoing HD. Ferritin level may be a dominant factor in CBF and iron deposition change. We hypothesize that ferritin level might be the key mediator between iron deposition and CBF alteration. The correlation in the putamen was estimated between the susceptibility values and CBF in patients undergoing HD. Compared with healthy controls, patients showed more altered global susceptibility values and CBF. The susceptibility value was negatively correlated with CBF in the putamen in patients. Moreover, the susceptibility value was negatively correlated with ferritin level and positively correlated with serum iron level in the putamen of patients. CBF was positively correlated with ferritin level and negatively correlated with serum iron level in the putamen of patients. These findings indicate that iron dyshomeostasis and vascular damage might exist in the putamen in patients. The results revealed that iron dyshomeostasis and vascular damage in the putamen may be potential neural mechanisms for neurodegenerative processes in patients undergoing HD.

DEM-TACE as the initial treatment could improve the clinical efficacy of the hepatocellular carcinoma with portal vein tumor thrombus: a retrospective controlled study.

BACKGROUND: Conventional-transarterial chemoembolization (C-TACE) was proven to improve overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT), drug-eluting microsphere-TACE (DEM-TACE) was supposed to provide more benefit than C-TACE in this respect. PURPOSE: To compare the safety and efficacy between DEM-TACE and C-TACE as the initial treatment in HCC patients with PVTT and to identify prognostic factors of OS. METHODS: The medical records of advanced HCC patients with PVTT who underwent DEM-TACE or C-TACE as the initial thearpy from September 2015 with mean follow-up time 14.9 ± 1.2 (95% CI 12.6-17.2) months were retrospectively evaluated. A total of 97 patients were included, 49 patients in the DEM-TACE group and 48 in the C-TACE group. Adverse events (AEs) related to TACE were compared. Tumor and PVTT radiologic response, time to tumor progression (TTP) and OS were calculated and compared in both groups. RESULTS: Patients in DEM-TACE group had a better radiologic response (Tumr response: 89.8% vs. 75.0%; PVTT response: 85.7% vs. 70.8%; overall response: 79.6% vs. 58.3%, P = 0.024) and longer TTP (7.0 months vs. 4.0 months, P = 0.040) than patients in C-TACE group. A lower incidence of abdominal pain was found in the DEM-TACE group than in C-TACE group (21 vs. 31, P = 0.032), but there were no significant differences between DEM-TACE and C-TACE patients in any other AEs reported. When compared to C-TACE, DEM-TACE also showed significant OS benefits (12.0 months vs. 9.0 months, P = 0.027). DEM-TACE treatment, the absence of arterioportal shunt (APS), lower AFP value and better PVTT radiologic response were the independent prognostic factors for OS in univariate/multivariate analyses, which provided us with a guide for better patient selection. CONCLUSIONS: Based on our retrospective study, DEM-TACE can be performed safely and might be superior to C-TACE as the initial treatment for HCC patients with PVTT. TRIAL REGISTRATION: Retrospectively registered.

Retraction Notice to: MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting paternally expressed gene 3.

[This retracts the article DOI: 10.1016/j.omtn.2021.02.020.].

Degradation of iopamidol by UV365/NaClO: Roles of reactive species, degradation mechanism, and toxicology.

The degradation of iopamidol (IPM) was investigated using a UV365/NaClO system. The reactive species (HO·, ClO·, ozone, Cl·, and Cl2-·) in the system were identified, and the changing trends of the percentage contributions of these reactive species to IPM removal under various conditions were systematically evaluated. The results showed that ClO· and HO· played the most significant roles in the apparent pseudo-first-order rate constants of IPM degradation (kobs, min-1) in the control experiment, and their percentage contributions to kobs were 41.31% and 34.45%, respectively. In addition, Cl· and Cl2-· together contributed 22% to the kobs. Furthermore, the contribution of ozone to the IPM removal could be neglected. The concentrations of these species increased significantly when the concentration of NaClO was increased from 50 µM to 200 µM, while the percentage contribution of ClO· to kobs was greatly increased. The concentrations and percentage contributions of HO· and ClO· decreased significantly as the solution pH increased from 5 to 9, with Cl2-· playing a greater role in the degradation of IPM under alkaline conditions. While Cl- or HCO3-/CO32- significantly promoted the generation of Cl2-· or CO3-·, neither had an obvious effect on kobs, suggesting that Cl2-· and CO3-· should have a certain reactivity with IPM. Compared with that of Cl2-·, the percentage contribution of ClO· and Cl· to kobs was more likely to be inhibited by NOM. In addition, the organic and inorganic oxidation products of IPM were detected. The oxidation mechanisms of IPM degradation in the UV365/NaClO system, such as the H-extraction reaction, deiodination, substitution reaction, amide hydrolysis, and amine oxidation, were proposed according to the obtained 15 organic products. No effect on acute toxicity towards Vibrio fischeri and Photobacterium phosphoreum was detected during the oxidation of IPM by the UV365/NaClO system. Furthermore, the engineering feasibility of the oxidation system was demonstrated, by the effective degradation of IPM in actual water. However, HOI rapidly accumulated during the removal of IPM in the UV365/NaClO system, which poses certain environmental risks and will needs to be investigated.

The etiology of poststroke-depression: a hypothesis involving HPA axis.

Approximately, one in three ischemic stroke survivors suffered from depression, namely, post-stroke depression (PSD). PSD affects functional rehabilitation and may lead to poor quality of life of patients. There are numerous explanations about the etiologies of PSD. Here, we speculated that PSD are likely to be the result of specific changes in brain pathology. We hypothesized that the stroke-induced hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis plays an important role in PSD. Stroke initiates a complex sequence of events in neuroendocrine system including HPA axis. The HPA axis is involved in the pathophysiology of depression, especially, the overactivity of the HPA axis occurs in major depressive disorder. This review summarizes the possible etiologies of PSD, focusing on the stroke-induced activation of HPA axis, mainly including the stress followed by severe brain damage and the proinflammatory cytokines release. The role of hyperactive of HPA axis in PSD was discussed in detail, which includes the role of high level corticotropin-releasing hormone in PSD, the effects of glucocorticoids on the alterations in specific brain structures, the expression of enzymes, excitotoxicity, the change in intestinal permeability, and the activation of microglia. The relationship between neuroendocrine regulation and inflammation was also described. Finally, the therapy of PSD by regulating HPA axis, neuroendocrine, and immunity was discussed briefly. Nevertheless, the change of HPA axis and the occurring of PSD maybe interact and promote on each other, and future investigations should explore this hypothesis in more depth.

Continuous Activation of Dopamine Receptors Alleviates LPS-Induced Liver Injury in Mice via ß-arrestin2 Dependent Akt/NF-κB Pathway.

Many studies showed that dopamine receptors (DRs) agonists have anti-inflammatory effects. Rotigotine, a non-ergot dopamine receptor agonist, mainly actives DRD2/DRD3/DRD1. Rotigotine extended-release microspheres (RoMS) are a sustained-release formulation that can release sustainably rotigotine for more than 7 days after a single dose of RoMS. This study aimed to investigate whether RoMS can attenuate the lipopolysaccharide (LPS)-induced liver injury of mice. The liver injury was evaluated by assaying serum transaminase and observing histopathological changes. The levels of pro-inflammatory cytokines in serum were also detected. Western blot was employed to assay the expression of proteins in the Akt/NF-κB pathway. The results showed that pre-administration with a single dose of RoMS could inhibit the increase of serum transaminase induced by LPS, alleviate the pathological damage of liver tissue, and decrease the levels of tumor necrosis factor-α and interleukin-6. In addition, RoMS decreased Toll-like receptor 4 protein expression in liver tissue. RoMS mitigated liver injury by activating DRs and negatively regulating the ß-arrestin2-dependent Akt/NF-κB signaling pathway. The effects of RoMS could be weakened or abolished by the specific DRD2 antagonist, R121. In conclusion, activation of DRs inhibited the releases of pro-inflammatory cytokines and alleviated the immune-mediated liver injury induced by LPS in mice. The anti-inflammatory mechanism of RoMS may be related to the regulation of the ß-arrestin2-dependent Akt/NF-κB signaling pathway.

Identification of circRNAs involved in the development of hepatocellular carcinoma after insufficient radiofrequency ablation.

Previous studies have reported that circular RNAs (circRNAs) play a key role in the pathogenesis and progression of various diseases. In the present study, we aimed to identify potential circRNAs associated with the progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (IRFA). A xenograft mouse IRFA model was initially established, and immunohistochemical staining (IHC) and polymerase chain reaction (PCR) were performed to confirm the expression of programmed cell death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor-1 (VEGFR-1). CircRNA expression alterations were screened by next-generation sequencing (RNA-seq). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to predict the function of genes coding differentially expressed circRNAs. The selected circRNAs were validated utilizing PCR and Sanger sequencing. The relationships between circRNAs, microRNAs, PD-L1, and VEGFR-1 were predicted by bioinformatics. Overall, a total of 612 circRNAs were differentially expressed in IRFA-treated subcutaneous tumorigenesis tissue. Among them, 435 circRNAs were significantly upregulated and 177 circRNAs were downregulated. GO and KEGG analyses were employed to predict the functions of these circRNAs. Thereafter, quantitative reverse transcription PCR (qRT-PCR) assays determined that these seven circRNAs were overexpressed in the IRFA group, which was consistent with the RNA-seq results. Based on the bioinformatic analysis, seven circRNAs confirmed by Sanger sequencing were predicted to likely regulate PD-L1 and VEGFR-1 expression levels by functioning as sponges for microRNAs (miRNAs) and forming a circRNA-miRNA-PD-L1/VEGFR-1 regulatory network. Finally, IHC and qRT-PCR of PD-L1 and VEGFR-1 confirmed the activation of this pathway. Taken together, we report that differentially expressed circRNAs might simultaneously regulate PD-L1 and VEGFR-1 in the IRFA tissues, which provides a novel view of circRNAs in HCC progression after the IRFA procedure.

DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.

Long-term hemodialysis may affect enlarged perivascular spaces in maintenance hemodialysis patients: evidence from a pilot MRI study.

BACKGROUND: Hemodialysis (HD) causes various nervous system abnormalities. Alterations in white matter (WM) microstructure after long-term HD have been reported in a few previous studies; however, no studies have been performed to investigate enlarged perivascular spaces (PVS) in WM regions. We measured cerebral blood flow (CBF) and white matter volume (WMV) in HD patients to assess enlarged PVS severity in the WM across the whole brain and suggest possible explanations for this. METHODS: Fifty-one HD patients and 51 age-, sex-, and education-matched healthy controls (HCs) were recruited. The number of enlarged PVS in the centrum semiovale (CS), cerebral watershed (CW), and basal ganglia (BG) regions were assessed by T2-weighted MRI. CBF was estimated by arterial spin labeling (ASL), which is a non-invasive perfusion imaging technique. WMV was assessed by the computational anatomy toolbox (CAT12), which is a statistical analysis package. Differences in descriptive variables (two-tailed t-tests, χ2 tests, Mann-Whitney U tests, and Friedman M tests), an intra-class correlation between radiologists, the relationship between enlarged PVS number and HD duration, normalized CBF and WMV (multiple regression), and group differences in CBF and WMV {voxel-wise t-tests with age and sex as covariates [cluster size >50 voxels, false discovery rate (FDR) corrected, P<0.05]} were assessed. RESULTS: HD patients displayed a more significant number of CS-PVS and CW-PVS in WM regions compared with the HCs, but there was no significant difference in the number of BG-PVS. The number of CS-PVS and CW-PVS were positively associated with HD duration. The number of CW-PVS was positively associated with CBF changes and WMV alteration in HD patients. Meanwhile, significant differences in the blood pressure (BP) readings pre-HD, intra-HD, and post-HD were observed in HD patients. Compared with the HCs, the HD patients showed higher CBF in the CS, CW, and BG regions (P<0.05). Hence, decreased WMV in the CS, CW, and BG regions were shown in the HD patients compared with the HCs (P<0.05). CONCLUSIONS: Enlarged CS-PVS and CW-PVS on MRI might be a feature of long-term HD patients. Enlarged CW-PVS number is associated with higher CBF in the CW region and lower WMV in the CW region in HD patients.