Niemann-Pick disease type B and heterogeneous manifestations of its liver involvement： A case report / 临床肝胆病杂志

This article reports a case with the chief complaint of “hepatosplenomegaly to be investigated” and a confirmed diagnosis of Niemann-Pick disease type B after various tests， and a literature review was conducted to summarize the heterogeneous manifestations of liver involvement in type B Niemann-Pick disease， in order to improve the clinical management of difficult and rare liver diseases.

Boosting CO2 Photoreduction to Formate or CO with High Selectivity over a Covalent Organic Framework Covalently Anchored on Graphene Oxide.

Covalent organic frameworks (COFs) have been widely studied in photocatalytic CO2 reduction reaction (CO2 RR). However, pristine COFs usually exhibit low catalytic efficiency owing to the fast recombination of photogenerated electrons and holes. In this study, we fabricated a stable COF-based composite (GO-COF-366-Co) by covalently anchoring COF-366-Co on the surface of graphene oxide (GO) for the photocatalytic CO2 reduction. Interestingly, in absolute acetonitrile (CH3 CN), GO-COF-366-Co shows a high selectivity of 94.4 % for the photoreduction of CO2 to formate, with a formate yield of 15.8 mmol/g, which is approximately four times higher than that using the pristine COF-366-Co. By contrast, in CH3 CN/H2 O (v : v=4 : 1), the main product for the photocatalytic CO2 reduction over GO-COF-366-Co is CO (96.1 %), with a CO yield as high as 52.2 mmol/g, which is also approximately four times higher than that using the pristine COF-366-Co. Photoelectrochemical experiments demonstrate the covalent bonding of COF-366-Co and GO to form the GO-COF-366-Co composite facilitates charge separation and transfer significantly, thereby accounting for the enhanced catalytic activity. In addition, theoretical calculations and in situ Fourier transform infrared spectroscopy reveal H2 O can stabilize the *COOH intermediate to further form a *CO intermediate via O-H(aq)⋅⋅⋅O(*COOH) hydrogen bonding, thus explaining the regulated photocatalytic performance.

Study of GCN repeats of PHOX2B gene among individuals from southwest China and diagnosis of two patients with Congenital central hypoventilation syndrome / 中华医学遗传学杂志

OBJECTIVE@#To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS).@*METHODS@#The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively.@*RESULTS@#Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN)7, (GCN)13, (GCN)14, (GCN)15 and (GCN)20. The frequency of the (GCN)20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN)7/(GCN)20, (GCN)13/(GCN)20, (GCN)14/(GCN)20, (GCN)15/(GCN)20, (GCN)20/(GCN)20. The homozygous genotypes were all (GCN)20/(GCN)20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN)20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the,Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN)20/(GCN)25 and (GCN)20/(GCN)30, respectively.@*CONCLUSION@#It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.

Self-Reported Neurological Symptoms Two Years After Hospital Discharge Among COVID-19 Survivors.

Background: The acute stage of COVID-19 often presents with neurological manifestations. Objective: This study aims to investigate the long-term neurological effects on survivors. Methods: This study recruited 1,546 COVID-19 survivors from Wuhan, including 1,119 nonsevere cases and 427 severe survivors. Participants were interviewed two years after discharge to report their neurological symptoms. The neurological symptoms of COVID-19 were compared between survivors of severe and nonsevere COVID-19. Results: Among the 1,546 COVID-19 survivors, 44.24% discovered at least one neurological symptom. The most prevalent self-reported symptom was fatigue (28.33%), memory deficit (13.26%), attention deficit (9.96%), myalgia (8.34%), dizziness (3.82%), and headache (2.52%). Severe cases had higher incidences of fatigue, myalgia, memory deficit, attention deficit than nonsevere cases. Older age, severe COVID-19, and comorbidity burden were associated with long-term neurological symptoms. Conclusion: Neurological symptoms are common among COVID-19 survivors, especially in severe cases.

Effect of Naoluoxintong formula and its split prescriptions on cerebral vascular regeneration in rats with the cerebral ischemia-reperfusion.

OBJECTIVE: To observe regulatory effect of Naoluoxintong formula (, NLXT) and its split prescriptions on vascular regeneration of rats suffering from cerebral ischemia-reperfusion (IR) syndrome of Qi deficiency with blood stasis (QDBS). METHODS: NLXT is the representative prescription of Yiqi Huoxue Tongluo decoction, and NLXT is divided into Yiqi herbs and Huoxue Tongluo herbs according to their efficacies. One hundred and eight specific-pathogen-free, clean-grade, Sprague-Dawley male rats were selected to prepare the classical rat model with QDBS due to middle artery ischemia-reperfusion using the multi-factor compound simulation approach. The animals were classified into sham operation (S), model (M), Nimodping (NMDP), NLXT, YQ and HXTL groups, each having 18 rats. Cerebral ischemia was reperfused after 2 h, and 24 h later, they were administered traditional Chinese medicine treatment for 14 d twice a day. Angiogenesis changes after NLXT administration to middle cerebral artery occlusion-reperfusion (MCAO/R) rats with QDBS were analyzed using the neurological deficit score and hematoxylin-eosin staining. Cerebral infarct area by 2,3,5-Triphenyltetrazolium chloride was detected, and the ultrastructure of the blood vessel in the ischemic frontoparietal cortex was observed by transmission electron microscopy. Angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), platelet endothelial cell adhesion molecule-1 (CD31), angiopoietin receptor 2 (Tie2), and P38 mitogen-activated protein kinase (MAPK) protein levels in the frontal and parietal cortex were quantified by immunofluorescence, reverse transcription-polymerase chain reaction, and Western blotting assays. RESULTS: Relative to the S group, VEGFA and VEGFR2 levels in the frontal and parietal cortex of group M were increased, and Ang1, Ang2, Tie2, CD31, and p38 MAPK levels remarkably increased (P < 0.05); cerebral infarct area was significant and pathological morphology and ultrastructure damage was obvious. Relative to the group M, VEGFA, VEGFR2, CD31, Ang1, Ang2, and Tie2 expression of group NLXT and NMDP remarkably elevated (P < 0.05) and infarct focus, pathological morphology and ultrastructure were significantly improved; VEGFA and VEGFR2 levels in the groups YQ and HXTL increased, and Ang1, Ang2, CD31, and Tie2 levels remarkably increased (P < 0.05); p38 MAPK levels in the three treatment groups decreased (P < 0.05). Relative to the group NLXT, the expression levels of p38 MAPK in group YQ and group HXTL were significantly increased, and the expression levels of other indicators were significantly decreased (P < 0.05). CONCLUSION: NLXT can promote the angiogenesis of the rat model of MCAO/R with QDBS by activating VEGFA and inhibiting P38 MAPK, and the effect is better than that of split prescription groups.

The effect of triple-dose-intravenous tranexamic acid on blood loss in patients undergoing total hip arthroplasty without affecting blood coagulopathy: A prospective thromboelastographic analysis.

OBJECTIVE: This study aimed to assess the safety and efficacy of triple-dose intravenous tranexamic acid (TXA) in patients following total hip arthroplasty (THA) using thromboelastography (TEG). METHODS: One hundred thirty patients undergoing THA were prospectively enrolled in the study. According to the intravenous infusion TXA dose, patients were divided into single-dose (n=65; mean age=60.8 ± 8.1 years) and triple-dose groups (n=65; mean age=61.8 ± 8.6 years). Complete blood count (CBC), conventional coagulation tests (CCT), and TEG were conducted 1 day before the operation, on postoperative day 1 (POD1), and postoperative day 7 (POD7). Color Doppler ultrasonography was performed 1 day before the operation and on POD7. Drainage blood loss, total blood loss (TBL), hidden blood loss (HBL), deep vein thrombosis (DVT) incidence, and blood transfusion rates were calculated and recorded. The CCT, CBC, and TEG parameters were compared between the 2 groups. RESULTS: Single- and triple-dose groups had significantly different hematocrit on POD7 (P < .05). No significant differences were found in CCT and hemoglobin at any corresponding time point between the 2 groups (P > .05). Despite the reaction time (R) on POD1 (P < .05), there were no significant differences in other TEG parameters at any other time point between the 2 groups (P > 0.05). For drainage blood loss and TBL, the triple-dose group had lesser blood loss than the single-dose group (P < .05). However, no significant differences were found for blood transfusion rate, HBL, or incidence of DVT (P > .05). CONCLUSION: Compared with single-dose, triple-dose TXA can be more effective in decreasing blood loss without increasing DVT incidence in patients undergoing THA. Although there is a notable disparity in the R time on POD1, the administration of triple-dose TXA does not substantially impact the coagulation status as assessed by TEG and CCT.

Socioeconomic differences in the perception of inequalities in healthcare utilization and health in South Korea.

This study investigated the lay perception of inequalities in society, healthcare utilization, and health in Korea. We also examined the association between socioeconomic status (SES) and perception of inequalities. Data from an online survey on the perception of health and healthcare inequalities related to cancer conducted between October 19, 2021, and November 12, 2021, were used. Data of 3,769 participants aged 20 to 74 years from 17 provinces were analyzed. We examined the perceived level of inequalities according to SES or residential area using frequency analysis, a t-test or analysis of variance (ANOVA), multiple linear regression analysis, and multiple logistic regression analysis. The mean score for perception of social inequality was 5.99 [Standard Deviation (SD) = 1.95] and that for perception of healthcare utilization inequality was 4.75 (SD = 1.96). The perception rate of health inequality according to SES and residential area was approximately 59 % and 61 %, respectively. Higher the income level, lower the level of perception of social inequalities ß = -0.22, p < 0.01). Higher the education level, higher the level of perception of healthcare utilization inequalities (ß = 0.21, p < 0.01). Higher the education level, higher the level of perception of health inequalities according to SES or residential area [adjusted odds ratio (aOR): 2.33 (95 % CI: 1.48, 3.66); aOR: 2.73 (95 % CI: 1.73, 4.31)]. Socioeconomic inequalities were observed in the perception of inequalities in healthcare utilization and health. Policymakers should establish policies to bridge the gap between perceived healthcare utilization inequalities and health inequalities. Future research should investigate the perception of healthcare utilization and health inequalities.

[Clinical Comparison of the Efficacy of Systemic Thrombolysis,Catheter-Directed Thrombolysis,and AngioJet Percutaneous Mechanical Thrombectomy in Acute Lower Extremity Deep Venous Thrombosis].

Objective To compare the clinical effects of three treatment methods including systemic thrombolysis(ST),catheter-directed thrombolysis(CDT),and AngioJet percutaneous mechanical thrombectomy(PMT)in acute lower extremity deep venous thrombosis(LEDVT). Methods The data of 82 patients diagnosed with LEDVT in the Department of Vascular and Gland Surgery of the First Affiliated Hospital of Hebei North University from January 2017 to December 2020 were collected.The patients were assigned into a ST group(n=50),a CDT group(n=16),and a PMT group(n=16)according to different treatment methods.The efficacy and safety were compared among the three groups. Results Compared with that before treatment,the circumferential diameter difference of both lower limbs on days 1,2,and 3 of treatment in the ST,CDT,and PMT groups reduced(all P<0.001).The PMT group showed smaller circumferential diameter difference of lower limbs on days 1,2,and 3 of treatment than the ST group(all P<0.001)and smaller circumferential diameter difference of the lower patellar margin on day 1 of treatment than the CDT group(P<0.001).The PMT group showed higher diminution rate for swelling of the affected limb at the upper and lower edges of the patella than the ST group(P<0.001)and higher diminution rate for swelling at the upper edge of the patella than the CDT group(P=0.026).The incidence of complications after treatment showed no significant differences among the three groups(all P>0.05).The median of hospital stay in the PMT group was shorter than that in the ST and CDT groups(P=0.002,P=0.001).The PMT group had higher thrombus clearance rate than the ST group(P=0.002)and no significant difference in the thrombus clearance rate from the CDT group(P=0.361).The vascular recanalization rates in the PMT(all P<0.001)and CDT(P<0.001,P=0.002,P=0.009)groups 3,6,and 12 months after treatment were higher than those in ST group,and there were no significant differences between PMT and CDT groups(P=0.341,P=0.210,P=0.341). Conclusions ST,CDT,and PMT demonstrated significant efficacy in the treatment of LEDVT,and PMT was superior to ST and CDT in terms of circumferential diameter difference of the lower limbs,diminution rate for swelling of the affected limb,thrombus clearance rate,length of hospital stay,and long-term vascular recanalization.There was no obvious difference in safety among the three therapies.

Mechanochromic and Selective Vapochromic Solid-State Luminescence of a Dinuclear Cuprous Complex.

The unraveling of the stimuli-responsive mechanism is crucial to the design and precise synthesis of stimuli-responsive luminescent materials. We report herein the mechanochromic and selective vapochromic solid-state luminescence properties of a new bimetallic cuprous complex [{Cu(bpmtzH)}2(µ-dppm)2](ClO4)2 (1), and the corresponding response mechanisms are elucidated by investigating its two different solvated polymorphs 1·2CH2Cl2 (1-g) and 1·2CHCl3 (1-c). Green-emissive 1-g and cyan-emissive 1-c can be interconverted upon alternate exposure to CHCl3 and CH2Cl2 vapors, which is principally attributable to a combined alteration of both intermolecular NHbpmtzH···OClO3- hydrogen bonds and intramolecular "triazolyl/phenyl" π···π interactions induced by different solvents. Solid-state luminescence mechanochromism present in 1-g and 1-c is mainly ascribed to the grinding-induced breakage of the NHbpmtzH···OClO3- hydrogen bonds. It is suggested that intramolecular π···π-triazolyl/phenyl interactions are affected by different solvents but not by grinding. The results provide new insights into the design and precise synthesis of multi-stimuli-responsive luminescent materials by the comprehensive use of intermolecular hydrogen bonds and intramolecular π···π interactions.

Water-Etched Approach to Hierarchically Porous Metal-Organic Frameworks with High Stability.

The development of hierarchically porous metal-organic frameworks (MOFs) with high stability is desirable to expand their applications but remains challenging. Herein, an anionic sodalite-type microporous MOF (Yb-TTCA; TTCA3- = triphenylene-2,6,10-tricarboxylate) was synthesized, which shows outstanding catalytic activities for the cycloaddition of CO2 into cyclic carbonates. Moreover, the microporous Yb-TTCA can be transformed into a hierarchical micro- and mesoporous Yb-TTCA by water treatment with the mesopore sizes of 2 to 12 nm. The hierarchically porous Yb-TTCA (HP-Yb-TTCA) not only exhibits a high thermal stability up to 500 °C but also shows a high chemical stability in aqueous solutions with pH values ranging from 2 to 12. In addition, the HP-Yb-TTCA displays enhanced performance for the removal of organic dyes in comparison with microporous Yb-TTCA. This work provides a facile way to construct hierarchically porous MOF materials.

Preoperative Prevalence and Risk Factors For Calf Muscular Vein Thrombosis in Elderly Patients with Hip Fracture.

OBJECTIVE: Increasing evidence has shown that calf muscular vein thrombosis (CMVT) can develop into proximal deep vein thrombosis, even causing pulmonary embolism. However, opinions about the prevalence and risk factors are still controversial. This study aimed to investigate the prevalence and risk factors for CMVT in elderly patients with hip fractures to facilitate their preoperative management. METHODS: We included 419 elderly patients with hip fracture who were treated in the orthopaedic department of our hospital from June 2017 to December 2020. The patients were divided into CMVT and non-CMVT groups based on color Doppler ultrasound screening of the venous system in the lower extremities. Clinical data, such as age, sex, body mass index, time from injury to admission, and laboratory data were collected. Univariate and multivariate logistic regression analyses were performed to determine independent risk factors for CMVT. A receiver operating characteristic curve was used to analyze the predictive effectiveness of the model. Finally, the clinical utility of the model was analyzed using decision curve analysis and clinical impact curves. RESULTS: The prevalence of preoperative CMVT was 30.5% (128/419). Independent predictors of preoperative CMVT identified by univariate and multivariate logistic regression analyses were sex, time from injury to admission, American Society of Anesthesiologists (ASA) classification, C-reactive protein (CRP) level, and D-dimer level (p < 0.05). The area under curve (AUC) was 0.750 (95% CI: 0.699-0.800, p < 0.001) and the sensitivity and specificity were 0.698 and 0.711, respectively, which meant the prediction model has a good efficacy in the prediction of CMVT risk. In addition, the fitting degree of the prediction model was also good (Hosmer-Lemeshow χ2 = 8.447, p > 0.05). The clinical utility of the model was verified using decision curve analysis and clinical impact curves. CONCLUSION: Sex, time from injury to admission, ASA classification, CRP level, and D-dimer levels are independent preoperative predictors of CMVT in elderly patients with hip fractures. Measures should be taken for patients with these risk factors to prevent the occurrence and deterioration of CMVT.

Associations of Blood and Cerebrospinal Fluid Aß and tau Levels with Renal Function.

Amyloid ß (Aß) and tau play pivotal roles in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that brain-derived Aß and tau can be cleared through transport into the periphery, and the kidneys may be vital organs involved in the clearance of Aß and tau. However, the effects of deficiency in the clearance of Aß and tau by the kidneys on brain AD-type pathologies in humans remain largely unknown. In this study, we first recruited 41 patients with chronic kidney disease (CKD) and 40 age- and sex-matched controls with normal renal function to analyze the associations of the estimated glomerular filtration rate (eGFR) with plasma Aß and tau levels. To analyze the associations of eGFR with cerebrospinal fluid (CSF) AD biomarkers, we recruited 42 cognitively normal CKD patients and 150 cognitively normal controls with CSF samples. Compared with controls with normal renal function, CKD patients had higher plasma levels of Aß40, Aß42 and total tau (T-tau), lower CSF levels of Aß40 and Aß42 and higher levels of CSF T-tau/Aß42 and phosphorylated tau (P-tau)/Aß42. Plasma Aß40, Aß42, and T-tau levels were negatively correlated with eGFR. In addition, eGFR was negatively correlated with CSF levels of T-tau, T-tau/Aß42, and P-tau/Aß42 but positively correlated with Mini-Mental State Examination (MMSE) scores. Thus, this study showed that the decline in renal function was correlated with abnormal AD biomarkers and cognitive decline, which provides human evidence that renal function may be involved in the pathogenesis of AD.

Prevalence of incidental thyroid abnormalities in patients with degenerative cervical spondylosis: a retrospective cross-sectional magnetic resonance imaging study.

Background: Incidental thyroid abnormalities found on magnetic resonance imaging (MRI) of the neck are not uncommon. This study aimed to investigate the prevalence of incidental thyroid abnormalities in the cervical spine MRI of the degenerative cervical spondylosis (DCS) population indicated for surgery and to identify patients who require additional workup based on the recommendations of the American College of Radiology (ACR). Methods: All consecutive patients with DCS and indications for cervical spine surgery from October 2014 to May 2019 in the Affiliated Hospital of Xuzhou Medical University were reviewed. All MRI scans of the cervical spine routinely include the thyroid. Cervical spine MRI scans were retrospectively evaluated for the prevalence, size, morphologic characteristics, and location of incidental thyroid abnormalities. Results: A total of 1,313 patients were included in the analysis, 98 (7.5%) of whom were found to have incidental thyroid abnormalities. The most frequent thyroid abnormality was thyroid nodules (5.3%), followed by goiters (1.4%). Other thyroid abnormalities included Hashimoto thyroiditis (0.4%) and thyroid cancer (0.5%). There was a statistically significant difference in age and sex between patients with DCS with and without incidental thyroid abnormalities (P=0.018 and P=0.007). Stratified by age, the results showed that the highest incidence of incidental thyroid abnormalities was found in patients aged 71 to 80 years (12.4%). Eighteen patients (1.4%) needed further ultrasound (US) and relevant workups. Conclusions: Incidental thyroid abnormalities are common in cervical MRI, with a prevalence of 7.5% identified in patients with DCS. Incidental thyroid abnormalities are large or have suspicious imaging features, and further evaluation with a dedicated thyroid US examination should be completed before cervical spine surgery is undertaken.

Intraindividual variance of lower limb rotation in patients with bilateral knee osteoarthritis.

Purpose: To determine the side-to-side difference in intraindividual rotation alignment of patients with bilateral varus-type knee osteoarthritis (OA) and compare it with control subjects. Methods: This retrospective study enrolled 60 patients with bilateral varus-type knee OA and 50 control subjects. All cases underwent bilateral lower limb CT angiography. Bilateral femoral and tibial rotation alignment were measured, and the overall lower limb rotation was calculated by two different methods. Method 1 was calculated by subtracting angle of the femoral torsion from the tibial torsion and method 2 was determined by relative rotation of the femoral neck angle to bimalleolar angle. The intraindividual variance and differences between the two groups were analyzed. Results: Both OA and control samples showed significant differences between right and left for all measurements. Femoral torsion for control group was 10.4 ± 5.5°, tibial torsion was -22.1 ± 6.1°, and overall leg rotation by method 1 was -15.6 ± 7.2° and method 2 was -11.7 ± 8.2°. Femoral torsion, tibial torsion, method 1, and method 2 in the patients with OA were 8.2 ± 6.3°, -18.6 ± 4.1°, -14.9 ± 7.9°, and -10.4 ± 7.6°, respectively. Patients with OA showed a more pronounced retroversion in the femur (p = 0.008) and more internal rotation in the tibia (p < 0.001). No statistical significance of both methods was found between the two groups. Patients with OA had a greater median side-to-side absolute difference in all measurements, though the differences of both two methods of overall lower limb rotation were not statistically significant. Conclusions: The discrepancy of side-to-side differences of bilateral lower limb rotation ought to be noticed with caution in diagnosing and treating rotational deformities of the lower limb, especially for patients with bilateral knee OA.

Hypertensive retinopathy and cardiovascular disease risk: 6 population-based cohorts meta-analysis.

Background: The cardiovascular risk associated with different levels of hypertensive retinopathy, including mild, remains unclear. We performed an individual participant meta-analysis from 6 population-based cohort studies to determine the relationship of hypertensive retinopathy with incident cardiovascular outcomes. Methods: We identified cohort studies that objectively assessed hypertensive retinopathy from photographs, documented incident cardiovascular outcomes, and were population-based. Six studies contributed data from 11,013 individuals at baseline with 5-13 years follow-up. Participants were recruited if they had hypertension and did not have confounding conditions such as diabetic retinopathy. Main outcome measures were incident coronary heart disease (CHD), stroke and a composite endpoint of cardiovascular disease (CHD or stroke). Pooled estimates of incident risk ratios (IRR) were obtained after adjusting for age, gender, systolic blood pressure, serum total cholesterol, high density lipoprotein and smoking. Results: Among eligible participants with hypertension and without diabetes, there were 1018/9662 (10.5%) incident CHD events, 708/11,013 (6.4%) incident stroke events and 1317/9378 (14.0%) incident CVD events. Mild hypertensive retinopathy was associated with increased risk of CVD (IRR 1.13, 95% CI 1.00 to 1.27) and CHD (IRR 1.17, 95% CI 1.02 to 1.34) but not stroke; moderate hypertensive retinopathy was associated with increased risk of CVD (IRR 1.25 95% CI 1.02 to 1.53) but not stroke or CHD individually. Conclusions: In persons with hypertension, both mild and moderate hypertensive retinopathy were associated with higher CVD risk.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Efficacy and safety of early anticoagulation after endovascular treatment in patients with atrial fibrillation.

BACKGROUND: The timing for initiating anticoagulant therapy in acute ischaemic stroke (AIS) patients with atrial fibrillation who recanalised after endovascular treatment (EVT) is unclear. The objective of this study was to evaluate the effect of early anticoagulation after successful recanalisation in AIS patients with atrial fibrillation. METHODS: Patients with anterior circulation large vessel occlusion and atrial fibrillation who were successfully recanalised by EVT within 24 hours after stroke in the Registration Study for Critical Care of Acute Ischemic Stroke after Recanalization registry were analysed. Early anticoagulation was defined as the initiation of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) within 72 hours after EVT. Ultra-early anticoagulation was defined if it was initiated within 24 hours. The primary efficacy outcome was the score on the modified Rankin Scale (mRS) at day 90, and the primary safety outcome was symptomatic intracranial haemorrhage within 90 days. RESULTS: Overall, 257 patients were enrolled, of whom 141 (54.9%) initiated anticoagulation within 72 hours after EVT, including 111 within 24 hours. A significant shift towards better mRS scores at day 90 was associated with early anticoagulation (adjusted common OR 2.08 (95% CI 1.27 to 3.41)). Symptomatic intracranial haemorrhage was comparable between patients treated with early and routine anticoagulation (adjusted OR 0.20 (95% CI 0.02 to 2.18)). Comparison of different early anticoagulation regimens showed that ultra-early anticoagulation was more significantly associated with favourable functional outcomes (adjusted common OR 2.03 (95% CI 1.20 to 3.44)) and reduced the incidence of asymptomatic intracranial haemorrhage (OR 0.37 (95% CI 0.14 to 0.94)). CONCLUSIONS: In AIS patients with atrial fibrillation, early anticoagulation with UFH or LMWH after successful recanalisation is associated with favourable functional outcomes without increasing the risk of symptomatic intracranial haemorrhages. TRIAL REGISTRATION NUMBER: ChiCTR1900022154.

Ion recognition properties of 2,2'-bibenzimidazole regulated by ammonium-modified pillar[5]arenes.

With the increasing issues of environmental degradation and health problem, the selective detection of toxic ions has attracted considerable attention from researchers. Chemical fluorescent sensors with the advantages of facile operation, high sensitivity, rapid response, and easy visualization are emerging as powerful detection tools towards ions. However, the selective recognition of ions is always hindered by the presence of other interfering substances. Herein, we show that supramolecular host-guest interaction based on a pillar[5]arene provides a new opportunity to regulate the ionic recognition properties of guest molecules. A pillar[5]arene-based host-guest complex HG was constructed through the host-guest interaction between ammonium functionalized pillar[5]arene (HAP5) and 2,2'-bibenzimidazole (G). The host-gust complex HG can realize the successive, highly selective, and sensitive detection of specific ions. It was found that only in the presence of HAP5, the sensitivity towards cations was evidently enhanced, and selective successive recognition for I- and HSO4- was achieved. Those results indicate that the introduction of HAP5 can effectively improve the ion recognition performance of 2,2'-bibenzimidazole, so it is a feasible strategy using supramolecular host-guest interaction to regulate the ionic recognition properties of guest molecules.

CD8+ lymphocytes do not impact SIV reservoir establishment under ART.

Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While reservoir formation begins during acute infection, the mechanisms responsible for its establishment remain unclear. CD8+ T cells are important during the initial control of viral replication. Here we examined the effect of CD8+ T cells on formation of the latent reservoir in simian immunodeficiency virus (SIV)-infected macaques by performing experimental CD8+ depletion either before infection or before early (that is, day 14 post-infection) ART initiation. We found that CD8+ depletion resulted in slower decline of viremia, indicating that CD8+ lymphocytes reduce the average lifespan of productively infected cells during acute infection and early ART, presumably through SIV-specific cytotoxic T lymphocyte (CTL) activity. However, CD8+ depletion did not change the frequency of infected CD4+ T cells in the blood or lymph node as measured by the total cell-associated viral DNA or intact provirus DNA assay. In addition, the size of the persistent reservoir remained the same when measuring the kinetics of virus rebound after ART interruption. These data indicate that during early SIV infection, the viral reservoir that persists under ART is established largely independent of CTL control.