Highly efficient catalytic transfer hydrogenation for the conversion of nitrobenzene to aniline over PdO/TiO2: The key role of in situ switching from PdO to Pd.

The reduction of nitrobenzene to aniline is very important for both pollution control and chemical synthesis. Nevertheless, difficulties still remain in developing a catalytic system having high efficiency and selectivity for the production of aniline. Herein, it was found that PdO nanoparticles highly dispersed on TiO2 support (PdO/TiO2) functioned as a highly efficient catalyst for the reduction of nitrobenzene in the presence of NaBH4. Under favorable conditions, 95% of the added nitrobenzene (1 mmol/L) was reduced within 1 min with an ultra-low apparent activation energy of 10.8 kJ/mol by using 0.5%PdO/TiO2 as catalysts and 2 mmol/L of NaBH4 as reductants, and the selectivity to aniline even reached up to 98%. The active hydrogen species were perceived as dominant species during the hydrogenation of nitrobenzene by the results of isotope labeling experiments and ESR spectroscopic. A mechanism was proposed as follows: PdO activates the nitro groups and leads to in-situ generation of Pd, and the generated Pd acts as the reduction sites to produce active hydrogen species. In this catalytic system, nitrobenzene prefers to be adsorbed on the PdO nanoparticles of the PdO/TiO2 composite. Subsequently, the addition of NaBH4 results in in-situ generation of a Pd/PdO/TiO2 composite from the PdO/TiO2 composite, and the Pd nanoclusters would activate NaBH4 to generate active hydrogen species to attack the adsorbed nitro groups. This work will open up a new approach for the catalytic transfer hydrogenation of nitrobenzene to aniline in green chemistry.

Endoscopic polidocanol foam sclerobanding for the treatment of grade II-III internal hemorrhoids: A prospective, multi-center, randomized study.

BACKGROUND: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain. AIM: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL. METHODS: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range. RESULTS: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]. CONCLUSION: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure.

π-π conjugated PDI supramolecular regulating the photoluminescence of imine-COFs for sensitive smartphone visual detection of levofloxacin.

As the contamination and enrichment in food chain of levofloxacin (LV) antibiotics have caused a significant threat to life safety, the instant detection of LV has become an urgent need. Here, a PDI-functionalized imine-based covalent organic framework (PDI-COF300) was prepared by the electrostatic self-assembly method as fluorescent probe for smartphone visual detection of LV, which exhibited excellent fluorescence quantum yield (82.68%), greater stability, high sensitivity with detection limit of 0.303 µM. Based on the results of molecular docking and Stern-Volmer equation, the LV detection by PDI-COF300 was mainly a static quenching process through π-π stacked hydrophobic interactions and fluorescence resonance energy transfer. Besides, PDI-COF300 was applied to LV detection in environmental medium and milk samples with recoveries from 85.56% to 108.34% and relative standard deviations <2.70%. This work also provided a new general strategy for using PDI-COF in smartphone devices and fluorescent papers for LV fluorescence detection and microanalysis.

Annular optical trapping of metallic nanoparticles using the azimuthally polarized beam.

The unique physical and chemical properties make metallic nanoparticles promising for broad applications in many fields. Exploring the dynamics of metallic nanoparticles in optical traps is crucial for exploiting optical tweezers to advance the applications of metallic particles. In this paper, we present a detailed study of the annular optical trapping of gold nanoparticles with azimuthal polarization. Theoretical analysis based on the T-matrix method shows that the gold nanoparticles experience optical forces pointing to the equilibrium position along the radial direction, while there is no force along the azimuthal direction at this equilibrium position. Therefore, a tightly focused azimuthally polarized beam captures gold nanoparticles in an annular region. Experimental measurements of the motion trajectory of the confined gold nanoparticles reveal a donut profile consistent with the theoretical predictions. Our work reported in this paper is expected to deepen our understanding of the interactions between metallic nanoparticles and light and promote the application of metallic nanoparticles.

Suicide among patients with oral cancer: A population-based study.

BACKGROUND: Patients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. METHODS: Surveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. RESULTS: Totally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. CONCLUSION: As oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

Wrapping stem cells with wireless electrical nanopatches for traumatic brain injury therapy.

Electrical stimulation holds promise for enhancing neuronal differentiation of neural stem cells to treat traumatic brain injury. However, once the stem cells leave the stimulating material and migrate post transplantation, electrical stimulation on them is diminished. Here, we wrap the stem cells with wireless electrical nanopatches, the conductive graphene nanosheets. Under electromagnetic induction, electrical stimulation can thus be applied in-situ to individual nanopatch-wrapped stem cells on demand, stimulating their neuronal differentiation through a MAPK/ERK signaling pathway. Consequently, 41% of the nanopatch-wrapped stem cells differentiate into functional neurons in 5 days, as opposed to only 16.3% of the unwrapped ones. The brain injury male mice implanted with the nanopatch-wrapped stem cells and exposed to a rotating magnetic field 30 min/day exhibit significant recovery of brain tissues, behaviors, and cognitions, within 28 days. This study opens up an avenue to individualized electrical stimulation of transplanted stem cells for treating neurodegenerative diseases.

Efficacy and long-term outcomes of single-balloon enteroscopy-assisted treatment for biliary obstruction after choledochojejunostomy.

BACKGROUND: To evaluate the long-term efficacy of single-balloon enteroscopy endoscopic retrograde cholangiography (SBE-ERC) for the treatment of biliary obstruction and to analyze the factors affecting the recurrence of benign bilioenteric anastomotic stricture after SBE-ERC treatment. METHODS: The clinical data of patients with biliary diseases treated with SBE-ERC after choledochojejunostomy in our hospital from January 2015 to December 2021 were analyzed retrospectively for the success rates of diagnosis and treatment and the incidence of complications. Patients who were diagnosed with benign bilioenteric anastomotic stricture were followed up. The independent factors affecting recurrence were obtained by univariate and multivariate analyses using the Kaplan‒Meier method and Cox proportional hazard regression model. RESULTS: A total of 289 SBE-ERCs were performed in 165 patients. The overall success rate was 83.0% (240/289). The incidence of postoperative complications was 5.2% (15/289). The 108 successfully treated patients diagnosed with benign bilioenteric anastomotic stricture were followed up. Twenty-six percent (29/108) of patients had recurrent stricture after SBE-ERC. The biliary patency rates at 1 year, 2 years and 5 years after SBE-ERC were 90.1%, 69.3%, and 53.9%, respectively. Single-factor analysis revealed the absence of intrahepatic biliary gas imaging during endoscopy ( χ 2 =5.366, P = 0.021), a diameter of balloon dilatation during the last endoscopic treatment less than 0.8 cm ( χ 2 =4.552, P = 0.033), and the presence of a thread in the anastomosis ( χ 2 =8.921, P = 0.003) as risk factors for recurrence. A non-indwelling biliary plastic stent ( χ 2 =14.868, P < 0.001) and undergoing only one ERCP treatment ( χ 2 =13.313, P = 0.001) were risk factors for the recurrence of benign stricture after SBE-ERC resection. Multivariate analysis revealed that the absence of a stent (HR = 0.15, 95% CI 0.06-0.40, P = 0.001), absence of intrahepatic biliary gas imaging during endoscopy (HR = 0.39, 95% CI 0.17-0.91, P = 0.03) and the presence of a thread in the anastomosis (HR = 3.69, 95% CI 1.59-8.57, P = 0.002) were independent risk factors for stricture recurrence. CONCLUSIONS: Treating biliary disease after choledochojejunostomy with SBE-ERC is safe and effective, with a good immediate technical success rate and an acceptable incidence of complications. SBE-ERC has long-term efficacy in the treatment of benign bilioenteric anastomotic stricture. The absence of intrahepatic biliary gas imaging during endoscopy, non-indwelling biliary stents and the existence of anastomotic threads are independent risk factors for the recurrence of benign bilioenteric anastomotic stricture.

Fast, faster, and the fastest structured illumination microscopy.

Parallel acquisition-readout structured-illumination microscopy (PAR-SIM) was designed for high-speed raw data acquisition. By utilizing an xy-scan galvo mirror set, the raw data is projected onto different areas of the camera, enabling a fundamentally stupendous information spatial-temporal flux.

Diagnostic Accuracy of Ultra-Low Dose CT Compared to Standard Dose CT for Identification of Fresh Rib Fractures by Deep Learning Algorithm.

The present study aimed to evaluate the diagnostic accuracy of ultra-low dose computed tomography (ULD-CT) compared to standard dose computed tomography (SD-CT) in discerning recent rib fractures using a deep learning algorithm detection of rib fractures (DLADRF). A total of 158 patients undergoing forensic diagnosis for rib fractures were included in this study: 50 underwent SD-CT, and 108 were assessed using ULD-CT. Junior and senior radiologists independently evaluated the images to identify and characterize the rib fractures. The sensitivity of rib fracture diagnosis by radiologists and radiologist + DLADRF was better using SD-CT than ULD-CT. However, the diagnosis sensitivity of DLADRF using ULD-CT alone was slightly more than SD-CT. Nonetheless, no substantial differences were observed in specificity, positive predictive value, and negative predictive value between SD-CT and ULD-CT by the same radiologist, radiologist + DLADRF, and DLADRF (P > 0.05). The area under the curve (AUC) of receiver operating characteristic indicated that senior radiologist + DLADRF was significantly better than senior and junior radiologists, junior radiologists + DLADRF, and DLADRF alone using SD-CT or ULD-CT (all P < 0.05). Also, junior radiologists + DLADRF was better with ULD-CT than senior and junior radiologists (P < 0.05). The AUC of the rib fracture diagnosed by senior radiologists did not differ from DLADRF using ULD-CT. Also, no significant differences were observed between junior + AI and senior and between junior and DLADRF using SD-CT. DLADRF enhanced the diagnostic performance of radiologists in detecting recent rib fractures. The diagnostic outcomes between SD-CT and ULD-CT across radiologists' experience and DLADRF did not differ significantly.

A Cascade C(sp3)-H Annulation Involving C(alkyl),C(alkyl)-Palladacycle Intermediates.

C-H bond functionalization involving C,C-palladacycle intermediates provides a unique platform for developing novel reactions. However, the vast majority of studies have been limited to the transformations of C(aryl),C-palladacycles. In sharp contrast, catalytic reactions involving C(alkyl),C(alkyl)-palladacycles have rarely been reported. Herein, we disclose an unprecedented cascade C(sp3)-H annulation involving C(alkyl),C(alkyl)-palladacycles. In this protocol, alkene-tethered cycloalkenyl bromides undergo intramolecular Heck/C(sp3)-H activation to generate C(alkyl),C(alkyl)-palladacycles, which can be captured by α-bromoacrylic acids to afford tricyclic fused pyridinediones. In addition, this strategy can also be applied to indole-tethered cycloalkenyl bromides to construct pentacyclic fused pyridinediones via suquential Heck dearomatization/C(sp3)-H activation/decarboxylative cyclization. Notably, the removal of α-bromoacrylic acids in the reaction of alkene-tethered cycloalkenyl bromides can build an interesting tricyclic skeleton containing a four-membered ring. Preliminary mechanistic experiments indicate that five-membered C(alkyl),C(alkyl)-palladacycles serve as the key intermediates. Meanwhile, density functional theory (DFT) calculations have provided insights into the reaction pathway.

Steric Effect and Intrinsic Electrophilicity and Nucleophilicity from a Conceptual Density Functional Theory and Information-Theoretic Approach as Quantitative Probes of Chemical Reactions.

Appreciating reactivity in terms of physicochemical effects for chemical processes is one of the most important undertakings in chemistry. While transition state (TS) theory provides the framework enabling the reliable calculation of the barrier height for a given elementary step, analytical tools are necessary to gain insight into key factors governing the different processes during chemical reactions. In this contribution, we partition the potential energy surface of an elementary step along the intrinsic coordinate into three segments, the so-called Pre-TS, TS, and Post-TS regions, and then determine the most important factors dictating each segment. This analysis is based on the use of both reactivity descriptors from conceptual density functional theory and concepts from the information-theoretic approach in density functional theory. We found that in both Pre-TS and Post-TS regions, steric effects are the dominant factors, whereas in the TS region, it is the intrinsic electrophilic and nucleophilic propensity of the transition state structure that governs the reactivity. The wide applicability of our approach is shown by a validation for a total of 37 organic and inorganic reactions. This work thus, in our view, provides a novel perspective on how chemical reactivity can be quantified at different stages of chemical reactions.

In vitro tungsten bioaccessibility in Chinese residential soils: Implications for human health risk assessments and soil screening level derivation.

Tungsten (W) contamination presents emerging environmental challenges, necessitating the need to establish soil screening levels (SSLs), especially for residential soils. This study assessed the health exposure risk and derived national and regional residential SSLs for W in Chinese residential soils, incorporating machine-learning prediction of in-vitro soil W bioaccessibility. We analyzed 204 residential soil samples collected across 24 provinces, recording a wide range of W concentrations (0.01-3063.2 mg/kg). Synchrotron-based X-ray fluorescence spectroscopy, chemical extractions, and random forest modeling indicated that the key determinants of soil W bioaccessibility were soil pH, cation exchange capacity, organic matter, and clay contents. Monte Carlo simulations demonstrated that soil W contamination predominantly results in noncarcinogenic health risks to residents via oral exposure, especially in mining-affected regions. A national residential SSL (NRSSL) of 35.5 mg/kg and regional residential SSLs (RRSSLs) of 34.5-49.2 mg/kg were established. Incorporating predicted bioaccessibility increased the NRSSL to 73.8 mg/kg and the RRSSLs to 69.8-112.5 mg/kg. Southern China, which is rich in W ore, exhibited lower RRSSLs, underscoring a need for enhanced safety management. Our framework and findings provide a robust scientific foundation for future soil contamination risk assessment studies, and we present customized SSLs that can guide targeted W risk control strategies.

Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment.

Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.

Causal benefits of 25 dietary intakes on epigenetic ageing: a Mendelian randomisation study.

DNA methylation GrimAge acceleration (DMGA) and intrinsic epigenetic age acceleration (IEAA) are important physiological markers for assessing the ageing process. Evidence from cross-sectional studies suggests that some dietary intake is associated with DMGA and IEAA. However, the causal relationship between them has yet to be elucidated. This Mendelian randomisation study uses genetic variants associated with different dietary intakes as instrumental variables to explore the causal benefits of multiple dietary intakes on DMGA and IEAA. Cheese intake, dark chocolate intake, average weekly red wine intake, dried fruit intake, fresh fruit intake, porridge intake, cereal intake, and liver intake had a negative causal association with DMGA, and poultry intake and doughnut intake had a positive causal association with DMGA (p < 0.05). Muesli and bran cereal intake had a negative causal association with IEAA, and pineapple intake had a positive causal association with IEAA (p < 0.05). Dietary intake positively causally associated with IEAA or DMGA may have accelerated biological ageing; conversely, dietary intake negatively causally associated with IEAA or DMGA may have contributed to delaying biological ageing. Based on genetic evidence, this study demonstrated some significant causal benefits of dietary intake on DMGA and IEAA, suggesting the possibility of intervening in DNA methylation acceleration and epigenetic age acceleration by adjusting these food intakes, thereby promoting health and delaying ageing. However, the findings of this study are exploratory and preliminary and need to be supported and validated by evidence from further clinical studies and mechanistic studies.

Empagliflozin rescues pro-arrhythmic and Ca2+ homeostatic effects of transverse aortic constriction in intact murine hearts.

We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2-6 weeks) challenge resulted in reduced late Na+ currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na+/Ca2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30-90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Isoproterenol shortened APD80 in sham-operated and TAC-only hearts, shortening CaTD80 and Decay30-90 but sparing TTP100 and Ca2+ transient alternans in all groups. All groups showed similar APD80, and TAC-only hearts showed greater CaTD80, heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts.

Extracellular vesicles as carriers for mitochondria: Biological functions and clinical applications.

In recent years, research has increasingly focused on the biogenesis of extracellular vesicles (EVs) and the sorting mechanisms for their contents. Mitochondria can be selectively loaded into EVs, serving as a way to maintain cellular mitochondrial homeostasis. EV-mediated mitochondrial transfer has also been shown to greatly impact the function of target cells. Based on the mechanism of EV-mediated mitochondrial transfer, therapies can be developed to treat human diseases. This review summarizes the recent advances in the biogenesis and molecular composition of EVs. It also highlights the sorting and trafficking mechanisms of mitochondrial components into EVs. Furthermore, it explores the current role of EV-mediated mitochondrial transfer in the development of human diseases, as well as its diagnostic and therapeutic applications.

The complete chloroplast genome sequence of Nostolachma jenkinsii (Hook.f.) Deb & J.Lahiri, an endangered coffeeae plant.

Nostolachma jenkinsii (Hook.f.) Deb & J.Lahiri, a member of the Rubiaceae family, is an endangered wild plant species with potential economic value. In this research, the complete chloroplast genome of N. jenkinsii was sequenced to gain insight into its genome feature and better understand the phylogenetic relationships among the Rubiaceae species. The chloroplast genome, with a total length of 155,036 bp, comprises two inverted repeats (IR) regions spanning 25,692 bp each, a large single-copy (LSC) region measuring 85,437 bp, and a short single-copy (SSC) region measuring 18,215 bp. There is an overall 37% GC content in the chloroplast genome. By annotation analysis,. 54 tRNA genes, 10 rRNA genes, and 107 protein-coding genes were all annotated in N. jenkinsii. Furthermore, we applied phylogenetic analysis that revealed a close relationship between N. jenkinsii, D. fruticosa and D. dubia, placing them together within the Rubiaceae family.

Endoscopic variceal ligation combined with sclerotherapy for management of gastroesophageal variceal bleeding in pediatric patients: a single-center retrospective study.

Objectives: Portal hypertension (PH) frequently gives rise to severe and life-threatening complications, including hemorrhage accompanied by the rupture of esophageal and gastric varices. In contrast to the guidelines for the management of PH in adults, the optimal endoscopic management of variceal bleeding for secondary prophylaxis in children remains unclear. The present study evaluated the efficacy and safety of endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST) to control gastroesophageal variceal bleeding in children. Methods: This retrospective study included children with gastroesophageal variceal bleeding who underwent EST or EVL at Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between February 2013 and March 2020. Short-term hemostasis rate and long-term rebleeding rate were evaluated. Adverse events related to the procedures, such as esophageal ulcer, esophageal stricture, abnormal embolization, pneumonia and perforation, were also recorded. Results: EVL (n = 8) and EST (n = 13) were performed successfully in all pediatric patients diagnosed with moderate to severe esophageal varices concurrent with gastric varices. Hemostasis was achieved during episodes of upper gastrointestinal bleeding. The mean volume of each single aliquot of cyanoacrylate injected was 0.3 ± 0.1 ml (range: 0.1-0.5 ml). Varices were eradicated in six (75%) of the eight patients who underwent EVL after a median 2 (range: 1-4) procedures and a median time of 3.40 months (range: 1.10-13.33 months). Eleven (52.4%) of the 21 patients developed rebleeding events, with the mean duration of hemostasis being 11.1 ± 11.6 months (range 1.0-39.2 months). No treatment-related complications, for example, distal embolism, occurred except for abdominal pain in one patient (4.8%). Conclusions: EST, alone or in combination with EVL, is an effective and safe method of managing gastroesophageal variceal hemorrhage in children undergoing secondary prophylaxis.

Heterogeneity of cerebral atrophic rate in mild cognitive impairment and its interactive association with proteins related to microglia activity on longitudinal cognitive changes.

BACKGROUND: Heterogeneity of cerebral atrophic rate commonly exists in mild cognitive impairment (MCI), which may be associated with microglia-involved neuropathology and have an influence on cognitive outcomes. OBJECTIVE: We aim to explore the heterogeneity of cerebral atrophic rate among MCI and its association with plasma proteins related to microglia activity, with further investigation of their interaction effects on long-term cognition. SUBJECTS: A total of 630 MCI subjects in the ADNI database were included, of which 260 subjects were available with baseline data on plasma proteins. METHODS: Group-based multi-trajectory modeling (GBMT) was used to identify the latent classes with heterogeneous cerebral atrophic rates. Associations between latent classes and plasma proteins related to microglia activity were investigated with generalized linear models. Linear mixed effect models (LME) were implemented to explore the interaction effects between proteins related to microglia activity and identified latent classes on longitudinal cognitive changes. RESULTS: Two latent classes were identified and labeled as the slow-atrophy class and the fast-atrophy class. Associations were found between such heterogeneity of atrophic rates and plasma proteins related to microglia activity, especially AXL receptor tyrosine kinase (AXL), CD40 antigen (CD40), and tumor necrosis factor receptor-like 2 (TNF-R2). Interaction effects on longitudinal cognitive changes showed that higher CD40 was associated with faster cognitive decline in the slow-atrophy class and higher AXL or TNF-R2 was associated with slower cognitive decline in the fast-atrophy class. CONCLUSIONS: Heterogeneity of atrophic rates at the MCI stage is associated with several plasma proteins related to microglia activity, which show either protective or adverse effects on long-term cognition depending on the variability of atrophic rates.