Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis.

The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.

Effects of socioeconomic status and regional inequality on the association between PM2.5 and its components and cardiometabolic multimorbidity: A multicenter population-based survey in eastern China.

BACKGROUND: Despite evidence linking fine particulate matter (PM2.5) to cardiometabolic multimorbidity (CMM), the impact of its components remains unclear. Socioeconomic status (SES) and regional disparities may confound their association. We aim to evaluate the associations between PM2.5 components and CMM and explore how socioeconomic status and regional disparities affect these relationships. METHODS: We recruited 108,941 participants aged 35-76 years from ten cities in eastern China. Individual exposure was assessed using Tracking Air Pollution in China (TAP) data, including PM2.5 and five components: ammonium (NH4+), black carbon (BC), nitrates (NO3-), organic matter (OM), and sulfates (SO42-). Generalized linear models and quantile g-computation models were employed to quantify the effects of PM2.5 components on CMM and to identify key components. Stratified analyses were performed to investigate the modifying effect of SES and regional disparities. RESULTS: For each increase in interquartile range (IQR), BC (odds ratio [OR] 1.37, 95 % CI 1.29-1.47), OM (1.38, 1.29-1.48), NH4+ (1.31, 1.21-1.40), NO3- (1.34, 1.25-1.44), and SO42- (1.28, 1.20-1.38) were positively associated with CMM. Joint exposure to five components was significantly positively associated with CMM (OR: 1.27, 95 % CI: 1.21-1.33), with SO42- having the highest estimated weight, followed by NO3- and BC. These associations were stronger for participants from low socio-economic status and poor regions. CONCLUSION: In summary, we found a stronger hazard effect of PM2.5 and its components on CMM, compared to those suffering from CMDs, particularly among participants with low socioeconomic status and in poor regions. SO42- may be a primary contributor to the association between PM2.5 components and CMM. These findings underscore the importance of prioritizing CMM and targeting SO42-related pollution sources in health policies, particularly amid China's aging population, reducing environmental health inequalities is critical.

High-efficiency color-tunable ultralong room-temperature phosphorescence from organic-inorganic metal halides via synergistic inter/intramolecular interactions.

Materials exhibiting highly efficient, ultralong and multicolor-tunable room-temperature phosphorescence (RTP) are of practical importance for emerging applications. However, these are still very scarce and remain a formidable challenge. Herein, using precise structure design, several novel organic-inorganic metal-halide hybrids with efficient and ultralong RTP have been developed based on an identical organic cation (A). The original organic salt (ACl) exhibits red RTP properties with low phosphorescence efficiency. However, after embedding metals into the organic salt, the changed crystal structure endows the resultant metal-halide hybrids with excellent RTP properties. In particular, A2ZnCl4·H2O exhibits the highest RTP efficiency of up to 56.56% with a long lifetime of up to 159 ms. It is found that multiple inter/intramolecular interactions and the strong heavy-atom effect of the rigid metal-halide hybrids can suppress molecular motion and promote the ISC process, resulting in highly stable and localized triplet excitons followed by highly efficient RTP. More crucially, multicolor-tunable fluorescence and RTP achieved by tuning the metal and halogen endow these materials with wide application prospects in the fields of multilevel information encryption and dynamic optical data storage. The findings promote the development of phosphorescent metal-halide hybrids for potential high-tech applications.

Tadpole-Like Polar Molecule Encapsulated in a Two-in-One Supramolecular Cage: Molecular Motion, Phase Transition and Ferroelectricity.

Molecule-inclusive closed cage compounds present a unique platform for molecular motion in an isolated environment. This study showcases the incorporation of a tadpole-like polar molecule (1-propyl-1H-imidazole, PIm) into a supramolecular cage formed by duad semicage p-tert-butylcalix[4]arene. The ferroelectric phase transition as well as the cage-confined motion of encapsulated PIm was studied in detail. The unusual quadrastable state of the PIm in the paraelectric phase allows for the modulation of dipolar polarization over a broad temperature/frequency range. This compound represents the first example of a clathrate molecular ferroelectric featuring a molecule-inclusive supramolecular cage, and it also contributes to the understanding of cage-confined molecular dynamics.

Clinical and pathological predictors of engraftment for patient-derived xenografts in lung adenocarcinoma.

Patient-derived xenografts (PDXs) are increasingly utilized in preclinical drug efficacy studies due to their ability to retain the molecular, histological, and drug response characteristics of patient tumors. This study aimed to investigate the factors influencing the successful engraftment of PDXs. Lung adenocarcinoma PDXs were established using freshly resected tumor tissues obtained through surgery. Radiological data of pulmonary nodules from this PDX cohort were analyzed, categorizing them into solid tumors and tumors with ground-glass opacity (GGO) based on preoperative CT images. Gene mutation status was obtained from next generation sequencing data and MassARRAY panel. A total of 254 resected primary lung adenocarcinomas were utilized for PDX establishment, with successful initial engraftment in 58 cases (22.8 %); stable engraftment defined as at least three serial passages was observed in 43 cases (16.9 %). The stable engraftment rates of PDXs from solid tumors and tumors with GGO were 22.1 % (42 of 190 cases) and 1.6 % (1 of 64 cases), respectively (P < 0.001). Adenocarcinomas with advanced stage, poor differentiation, solid histologic subtype, and KRAS or TP53 gene mutations were associated with stable PDX engraftment. Avoiding tumors with GGO features could enhance the cost-effectiveness of establishing PDX models from early-stage resected lung adenocarcinomas.

Serum cystatin C, monocyte/high-density lipoprotein-C ratio, and uric acid for the diagnosis of coronary heart disease and heart failure.

BACKGROUND: Coronary heart disease (CHD) and heart failure (HF) are the major causes of morbidity and mortality worldwide. Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis. However, conventional diagnostic methods such as electrocardiography, echocardiography, and cardiac biomarkers have certain limitations, such as low sensitivity, specificity, availability, and cost-effectiveness. Therefore, there is a need for simple, noninvasive, and reliable biomarkers to diagnose CHD and HF. AIM: To investigate serum cystatin C (Cys-C), monocyte/high-density lipoprotein cholesterol ratio (MHR), and uric acid (UA) diagnostic values for CHD and HF. METHODS: We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023. The patients were divided into CHD (n = 20), HF (n = 20), CHD + HF (n = 20), and control groups (n = 20). The serum levels of Cys-C, MHR, and UA were measured using immunonephelometry and an enzymatic method, respectively, and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Serum levels of Cys-C, MHR, and UA were significantly higher in the CHD, HF, and CHD + HF groups than those in the control group. The serum levels of Cys-C, MHR, and UA were significantly higher in the CHD + HF group than those in the CHD or HF group. The ROC curve analysis showed that serum Cys-C, MHR, and UA had good diagnostic performance for CHD and HF, with areas under the curve ranging from 0.78 to 0.93. The optimal cutoff values of serum Cys-C, MHR, and UA for diagnosing CHD, HF, and CHD+HF were 1.2 mg/L, 0.9 × 109, and 389 µmol/L; 1.4 mg/L, 1.0 × 109, and 449 µmol/L; and 1.6 mg/L, 1.1 × 109, and 508 µmol/L, respectively. CONCLUSION: Serum Cys-C, MHR, and UA are useful biomarkers for diagnosing CHD and HF, and CHD+HF. These can provide information for decision-making and risk stratification in patients with CHD and HF.

Accuracy of FreeStyle Libre flash glucose monitoring in patients with type 2 diabetes who migrated from highlands to plains.

BACKGROUND: The FreeStyle Libre flash glucose monitoring (FGM) system entered the Chinese market in 2017 to complement the self-monitoring of blood glucose. Due to its increased usage in clinics, the number of studies investigating its accuracy has increased. However, its accuracy has not been investigated in highland popu-lations in China. AIM: To evaluate measurements recorded using the FreeStyle Libre FGM system compared with capillary blood glucose measured using the enzyme electrode method in patients with type 2 diabetes (T2D) who had migrated within 3 mo from highlands to plains. METHODS: Overall, 68 patients with T2D, selected from those who had recently migrated from highlands to plains (within 3 mo), were hospitalized at the Department of Endocrinology from August to October 2017 and underwent continuous glucose monitoring (CGM) with the FreeStyle Libre FGM system for 14 d. Throughout the study period, fingertip capillary blood glucose was measured daily using the enzyme electrode method (Super GL, China), and blood glucose levels were read from the scanning probe during fasting and 2 h after all three meals. Moreover, the time interval between reading the data from the scanning probe and collecting fingertip capillary blood was controlled to < 5 min. The accuracy of the FGM system was evaluated according to the CGM guidelines. Subsequently, the factors influencing the mean absolute relative difference (MARD) of this system were analyzed by a multiple linear regression method. RESULTS: Pearson's correlation analysis showed that the fingertip and scanned glucose levels were positively correlated (R = 0.86, P = 0.00). The aggregated MARD of scanned glucose was 14.28 ± 13.40%. Parker's error analysis showed that 99.30% of the data pairs were located in areas A and B. According to the probe wear time of the FreeStyle Libre FGM system, MARD1 d and MARD2-14 d were 16.55% and 14.35%, respectively (t = 1.23, P = 0.22). Multiple stepwise regression analysis showed that MARD did not correlate with blood glucose when the largest amplitude of glycemic excursion (LAGE) was < 5.80 mmol/L but negatively correlated with blood glucose when the LAGE was ≥ 5.80 mmol/L. CONCLUSION: The FreeStyle Libre FGM system has good accuracy in patients with T2D who had recently migrated from highlands to plains. This system might be ideal for avoiding the effects of high hematocrit on blood glucose monitoring in populations that recently migrated to plains. MARD is mainly influenced by glucose levels and fluctuations, and the accuracy of the system is higher when the blood glucose fluctuation is small. In case of higher blood glucose level fluctuations, deviation in the scanned glucose levels is the highest at extremely low blood glucose levels.

Flow2GNN: Flexible Two-Way Flow Message Passing for Enhancing GNNs Beyond Homophily.

Message passing (MP) is crucial for effective graph neural networks (GNNs). Most local message-passing schemes have been shown to underperform on heterophily graphs due to the perturbation of updated representations caused by local redundant heterophily information. However, our experiment findings indicate that the distribution of heterophily information during MP can be disrupted by disentangling local neighborhoods. This finding can be applied to other GNNs, improving their performance on heterophily graphs in a more flexible manner compared to most heterophily GNNs with complex designs. This article proposes a new type of simple message-passing neural network called Flow2GNN. It uses a two-way flow message-passing scheme to enhance the ability of GNNs by disentangling and redistributing heterophily information in the topology space and the attribute space. Our proposed message-passing scheme consists of two steps in topology space and attribute space. First, we introduce a new disentangled operator with binary elements that disentangle topology information in-flow and out-flow between connected nodes. Second, we use an adaptive aggregation model that adjusts the flow amount between homophily and heterophily attribute information. Furthermore, we rigorously prove that disentangling in message-passing can reduce the generalization gap, offering a deeper understanding of how our model enhances other GNNs. The extensive experiment results show that the proposed model, Flow2GNN, not only outperforms state-of-the-art GNNs, but also helps improve the performance of other commonly used GNNs on heterophily graphs, including GCN, GAT, GCNII, and H 2 GCN, specifically for GCN, with up to a 25.88% improvement on the Wisconsin dataset.

Edaravone combined with hyperbaric oxygen therapy in delayed encephalopathy after acute carbon monoxide poisoning: A meta-analysis.

BACKGROUND: The use of both edaravone (EDA) and hyperbaric oxygen therapy (HBOT) is increasingly prevalent in the treatment of delayed encephalopathy after carbon monoxide poisoning (DEACMP). This meta-analysis aims to evaluate the efficacy of using EDA and HBOT in combination with HBOT alone in the treatment of DEACMP. METHODS: We searched and included all randomized controlled trials (RCTs) published before November 6, 2023, from 12 Chinese and English databases and clinical trial centers in China and the United States. The main outcome indicator was the total effective rate. The secondary outcome indicators included the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Hasegawa Dementia Scale (HDS), Fugl-Meyer Assessment (FMA), Superoxide Dismutase (SOD), and Malondialdehyde (MDA). Statistical measures utilized include risk ratios (RR), weighted mean difference (WMD), and 95 % confidence intervals (95 % CI). RESULTS: Thirty studies involving a combined total of 2075 participants were ultimately incorporated. It was observed that the combination of EDA with HBOT for the treatment of DEACMP demonstrated an improvement in the total effective rate (RR: 1.25; 95 % CI: 1.20-1.31; P < 0.01), MMSE (WMD: 3.67; 95 % CI: 2.59-4.76; P < 0.01), MoCA (WMD: 4.38; 95 % CI: 4.00-4.76; P < 0.01), BI (WMD: 10.94; 95 % CI: 5.23-16.66; P < 0.01), HDS (WMD: 6.80; 95 % CI: 4.05-9.55; P < 0.01), FMA (WMD: 8.91; 95 % CI: 7.22-10.60; P < 0.01), SOD (WMD: 18.45; 95 % CI: 16.93-19.98; P < 0.01); and a reduction in NIHSS (WMD: -4.12; 95 % CI: -4.93 to -3.30; P < 0.01) and MDA (WMD: -3.05; 95 % CI: -3.43 to -2.68; P < 0.01). CONCLUSION: Low-quality evidence suggests that for DEACMP, compared to using HBOT alone, the combined use of EDA and HBOT may be associated with better cognition and activity of daily living. In the future, conducting more meticulously designed multicenter and large-sample RCTs to substantiate our conclusions is essential.

A mussel-inspired, antibacterial, antioxidant, injectable composite hydrogel for the sustain delivery of salvianolic acid B for the treatment of frozen shoulder.

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Heterogeneity of fibroblast activation protein expression in the microenvironment of an intracranial tumor cohort: head-to-head comparison of gallium-68 FAP inhibitor-04 (68Ga-FAPi-04) and fluoride-18 fluoroethyl-L-tyrosine (18F-FET) in positron emission tomography-computed tomography imaging.

Background: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) can interact with tumor parenchymal cells to promote tumor growth and migration. Fibroblast activation protein (FAP) expressed by CAFs can be targeted with positron emission tomography (PET) tracers, but studies on FAP expression patterns in intracranial tumors remain scarce. We aimed to evaluate FAP expression patterns in intracranial tumors with gallium-68 FAP inhibitor-04 (68Ga-FAPi-04) and immunohistochemical staining and to observe the interactions between CAFs and tumor cells with a head-to-head comparison of 68Ga-FAPi-04 and fluoride-18 fluoroethyl-L-tyrosine (18F-FET) for PET quantification analysis. Methods: We prospectively enrolled 22 adult patients with intracranial mass lesions. 68Ga-FAPi-04 and 18F-FET PET-computed tomography (PET/CT) brain imaging were applied before surgery. Maximal tumor-to-brain ratio (TBRmax), metabolic tumor volume (MTV), and total lesion tracer uptake (TLU) was obtained, and different thresholds were used for 68Ga-FAPi-04-positive lesion delineation owing to the lack of relevant guidelines. The MTV and TLU ratios of both tracers were calculated. Linear regression was applied to observe the differential efficacy of semiquantitative PET parameters. Results: A total of 22 patients with a mean age of 50±13 years (range, 27-69 years) were enrolled. Heterogeneous patterns of 68Ga-FAPi-04 uptake [median of maximal standardized uptake value (SUVmax) =3.8; range, 0.1-19.1] were found. More malignant tumors, including brain metastasis, glioblastoma, and medulloblastoma, generally exhibited more significant 68Ga-FAPi-04 uptake than did the less malignant tumors, while the SUVmax and TBRmax exhibited nonsignificant differences across three intracranial lesion groups of primary brain tumor, brain metastasis, and noncancerous disease (SUVmax: P=0.092; TBRmax: P=0.189). Immunohistochemistry staining showed different stromal FAP expression status in various intracranial lesions. In 15 patients with positive 68Ga-FAPi-04 intracranial tumor uptake, the MTVFAPi:MTVFET ratio had differential efficacy in various types of intracranial tumors [95% confidence interval (CI): 0.572-7.712; P=0.027], and further quantification analyses confirmed the differential ability of the MTVFAPi:MTVFET ratio (95% CI: -0.045 to 11.013, P=0.052; 95% CI: 0.044-17.903, P=0.049; 95% CI: -1.131 to 30.596, P=0.065) with different isocontour volumetric thresholds. Conclusions: This head-to-head study demonstrated heterogeneous FAP expression in intracranial tumors. The FAP expression volume percentage in tumor parenchyma may therefore offer benefit with respect to differentiating between intracranial tumor types.

[Effects of Replacing Chemical Nitrogen Fertilizer with Organic Fertilizer on Active Organic Carbon Fractions, Enzyme Activities, and Crop Yield in Yellow Soil].

Taking the typical yellow soil in Guizhou as the research object, four treatments were set up： no fertilization （CK）, single application of chemical fertilizer （NP）, 50% organic fertilizer instead of chemical nitrogen fertilizer [1/2（NPM）], and 100% organic fertilizer instead of chemical nitrogen fertilizer （M）. The effects of organic fertilizer instead of chemical nitrogen fertilizer on organic carbon and its active components, soil carbon pool management index, soil enzyme activity, and maize and soybean yield in yellow soil were studied in order to provide theoretical basis for scientific fertilization and soil quality improvement in this area. The results showed that the replacement of chemical nitrogen fertilizer by organic fertilizer significantly increased soil pH, organic carbon （SOC）, total nitrogen （TN） content, and C/N ratio. Compared with those in the CK and NP treatments, the content and distribution ratio of soil active organic carbon components and soil carbon pool management index （CPMI） were improved by replacing chemical nitrogen fertilizer with organic fertilizer, and the effect of replacing chemical nitrogen fertilizer with 50% organic fertilizer was the best. Compared with those in the NP treatment, the 1/2 （NPM） treatment significantly increased the contents of soil readily oxidizable organic carbon （ROC333, ROC167）, dissolved organic carbon （DOC）, and microbial biomass carbon （MBC） by 22.90%, 8.10%, 29.32%, and 23.22%, respectively. Compared with those under the CK and NP treatments, organic fertilizer instead of chemical nitrogen fertilizer increased soil enzyme activities. The activities of catalase, urease, sucrase, and phosphatase in the 1/2 （NPM） treatment were significantly increased by 21.89%, 8.24%, 34.91%, and 18.78%, respectively, compared with those in the NP treatment. Compared with that of the NP treatment, the maize yield of the 1/2 （NPM） and M treatments was significantly increased by 44.15% and 17.39%, respectively. There was no significant difference in soybean yield among different fertilization treatments. Correlation analysis showed that soil SOC was significantly positively correlated with ROC333, ROC167, ROC33, DOC, MBC, and soil active organic carbon components, and CPMI was significantly positively correlated with soil organic carbon and its active components （P<0.01）. Corn yield was significantly positively correlated with soil enzyme activity, CPMI, total organic carbon, and its active components （P<0.05）. Therefore, from the perspective of yield increase and soil fertility, 50% organic fertilizer instead of chemical nitrogen fertilizer was conducive to improving soil quality and soil fertility, which is the key fertilization technology to achieve a high yield of crops in the yellow soil area of Anshun, Guizhou.

Peripheral blood MR1 tetramer-positive mucosal-associated invariant T-cell function is modulated by mammalian target of rapamycin complex 1 in patients with active tuberculosis.

Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.

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.

Advances in the role of circulating tumor cell heterogeneity in metastatic small cell lung cancer.

Small cell lung cancer (SCLC), a highly aggressive malignancy, is rapidly at an extensive stage once diagnosed and is one of the leading causes of death from malignancy. In the past decade, the treatment of SCLC has largely remained unchanged, and chemotherapy remains the cornerstone of SCLC treatment. The therapeutic value of adding immune checkpoint inhibitors to chemotherapy for SCLC is low, and only a few SCLC patients have shown a response to immune checkpoint inhibitors. Circulating tumor cells (CTCs) are tumor cells shed from solid tumor masses into the peripheral circulation and are key to tumor metastasis. Single-cell sequencing has revealed that the genetic profiles of individual CTCs are highly heterogeneous and contribute to the poor outcome and prognosis of SCLC patients. Theoretically, phenotypic analysis of CTCs may be able to predict the diagnostic significance of new potential targets for metastatic tumors. In this paper, we will discuss in depth the heterogeneity of CTCs in SCLC and the value of CTCs for the diagnosis and prognosis of SCLC and as relevant tumor markers in metastatic SCLC.

Morphological Changes of Peri-Coronary Adipose Tissue Together with Elevated NLR in Acute Myocardial Infarction Patients in-Hospital.

Background: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI. Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests. Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (-74.84±6.93 HU vs -79.04±8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (-78.46±8.56HU vs -83.13±8.34 HU) and LCXs (-73.83±10.63 HU vs -81.38±7.88 HU) of lesion related vessel in stable angina. Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.

Indole Lactic Acid in Plasma and Urine: A Potential Biomarker for Chronic Kidney Disease and Inflammatory.

Purpose: We aimed to explore changes in plasma and urine indole lactic acid (ILA) levels and the relationship between inflammation and ILA in chronic kidney disease (CKD) patients and healthy people. Patients and Methods: Forty-seven CKD patients and 30 healthy individuals were included in this study. One-way ANOVA was used for variables with normal distribution and homogeneous variance. A rank-sum test was performed for non-normally distributed variables. Correlation analyses were performed using Pearson's or Spearman correlation analyses. Independent relationship between patients and CKD was analyzed using ordinal and binary logistic regressions. Receiver operating characteristic (ROC) curve was used. Results: Plasma and urine ILA levels were positively correlated (r = 0.51, P < 0.01). Plasma ILA was positively correlated with BMI, age, creatinine, BUN, triglycerides, and uric acid and negatively correlated with hemoglobin levels. Urine ILA levels were positively correlated with age, creatinine, BUN, and uric acid and negatively correlated with hemoglobin and albumin levels. Ordered logistic regression analysis showed that CKD was significantly correlated with plasma ILA (OR=4.49, P < 0.01), urinary ILA (OR=2.14,P < 0.01), urea levels (OR=1.43, P < 0.01) and hemoglobin levels (OR=0.95, P < 0.01) were significantly related. ROC curves indicated that plasma and urinary ILA were reliable predictors of CKD. CKD was correlated with plasma, urine ILA (OR=5.92, P < 0.01; OR=2.79, P < 0.01) and Hs-CRP (OR=2.45, P < 0.01). Conclusion: Plasma and urine ILA can potentially be used as biomarkers of CKD and inflammatory status.

Fluoride-Mediated Aryne 1,2-Difunctionalization Involving C═S Bond Heterolysis.

We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the C═S π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.

Imparting Ultrahigh Strength to Polymers via a New Concept Strategy of Construction of up to Duodecuple Hydrogen Bonding among Macromolecular Chains.

Interconnecting macromolecules via multiple hydrogen bonds (H-bonds) can simultaneously strengthen and toughen polymers, but material synthesis becomes extremely difficult with increasing number of H-bonding donors and acceptors; therefore, most reports are limited to triple and quadruple H-bonds. Herein, this bottleneck is overcome by adopting a quartet-wise approach of constructing H-bonds instead of the traditional pairwise method. Thus, large multiple hydrogen bonds can be easily established, and the supramolecular interactions are further reinforced. Especially, when such multiple H-bond motifs are embedded in polymers, four macromolecular chains-rather than two as usual-are tied, distributing the applied stress over a larger volume and more significantly improving the overall mechanical properties. Proof-of-concept studies indicate that the proposed intermolecular multiple H-bonds (up to duodecuple) are readily introduced in polyurethane. A record-high tensile strength (105.2 MPa) is achieved alongside outstanding toughness (352.1 MJ m-3), fracture energy (480.7 kJ m-2), and fatigue threshold (2978.4 J m-2). Meantime, the polyurethane has acquired excellent self-healability and recyclability. This strategy is also applicable to nonpolar polymers, such as polydimethylsiloxane, whose strength (15.3 MPa) and toughness (50.3 MJ m-3) are among the highest reported to date for silicones. This new technique has good expandability and can be used to develop even more and stronger polymers.