Preparation, pharmacokinetics and anti-obesity effects on dogs of nuciferine liposomes.

BACKGROUND: Nuciferine (NUC), a natural compound extracted from lotus leaves, has been proven to have anti-obesity effects. However, the development and application of NUC as an anti-obesity drug in dogs are hindered due to its poor water solubility and low bioavailability. OBJECTIVE: To promote the development of NUC-related products for anti-obesity in dogs, this study prepared NUC into a liposome formulation and evaluated its characteristics, pharmacokinetics in dogs, and anti-obesity effects on high-fat diet dogs. METHODS: NUC liposomes were prepared by the ethanol injection method, using NUC, egg lecithin, and ß-sitosterol as raw materials. The characteristics and release rate in vitro of liposomes were evaluated by particle size analyser and dialysis method, respectively. The pharmacokinetics in dogs after oral administration of NUC-liposomes was carried out by the high-performance liquid chromatography (HPLC) method. Moreover, we investigated the anti-obesity effect of NUC-liposomes on obese dogs fed with a high-fat diet. RESULTS: NUC-liposome was successfully prepared, with an EE of (79.31 ± 1.06)%, a particle size of (81.25 ± 3.14) nm, a zeta potential of (-18.75 ± 0.23) mV, and a PDI of 0.175 ± 0.031. The cumulative release rate in vitro of NUC from NUC-liposomes was slower than that of NUC. The T1/2 and relative bioavailability of NUC-liposomes in dogs increased, and CL reduced compared with NUC. In addition, the preventive effect of NUC-liposomes on obesity in high-fat diet dogs is stronger than that of NUC. CONCLUSIONS: The liposome formulation of NUC was conducive to improve its relative bioavailability and anti-obesity effect in dogs.

INHBA promotes tumor growth and induces resistance to PD-L1 blockade by suppressing IFN-γ signaling.

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. In this study we investigated the effects and mechanisms of tumor intrinsic INHBA on carcinogenesis, tumor immunity and PD-L1 blockade. Bioinformatic analysis on the TCGA database revealed that INHBA expression levels were elevated in 33 cancer types, including breast cancer (BRCA) and colon adenocarcinoma (COAD). In addition, survival analysis also corroborated that INHBA expression was negatively correlated with the prognosis of many types of cancer patients. We demonstrated that gain or loss function of Inhba did not alter in vitro growth of colorectal cancer CT26 cells, but had striking impact on mouse tumor models including CT26, MC38, B16 and 4T1 models. By using the TIMER 2.0 tool, we figured out that in most cancer types, Inhba expression in tumors was inversely associated with the infiltration of CD4+ T and CD8+ T cells. In CT26 tumor-bearing mice, overexpression of tumor INHBA eliminated the anti-tumor effect of the PD-L1 antibody atezolizumab, whereas INHBA deficiency enhanced the efficacy of atezolizumab. We revealed that tumor INHBA significantly downregulated the interferon-γ (IFN-γ) signaling pathway. Tumor INHBA overexpression led to lower expression of PD-L1 induced by IFN-γ, resulting in poor responsiveness to anti-PD-L1 treatment. On the other hand, decreased secretion of IFN-γ-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment (TME). Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy with garetosmab or atezolizumab. We demonstrate that INHBA and activin A are involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway, which can be considered as potential targets to improve the responsive rate of PD-1/PD-L1 blockade.

PTEN regulated by gga-miR-20a-5p is involved in chicken macrophages inflammatory response to APEC infection via autophagy.

Colibacillosis, a bacterial disease caused by avian pathogenic E. coli (APEC), is a prevalent condition in the poultry industry, resulting in substantial economic losses annually. Previously, we identified PTEN as a crucial candidate gene that may play a significant role in chicken's immune response to APEC infection. Bioinformatics analysis indicated that the PTEN protein was unstable, hydrophilic and nuclear localization, with multiple putative phosphorylation sites and a high degree of similarity to duck and goose PTEN. Moreover, PTEN exhibited high expression levels in various tissues such as the stomach, cecum, small intestine, spleen, thymus, harderian gland, muscle, cerebrum, cerebellum, lung, and liver in comparison to heart tissue. Overexpression of PTEN resulted in a significant promotion of the expression level of pro-apoptosis genes and inflammatory mediators, as well as the production of NO, with or without APEC infection, which led to cellular injury. Furthermore, overexpression of PTEN was found to regulate the expression levels of autophagy related genes, regardless of APEC infection. Additionally, PTEN was a target gene of gga-miR-20a-5p and regulated by gga-miR-20a-5p upon APEC infection. Taken together, these findings establish a foundation for investigating the biological function of chicken PTEN, providing a potential target for future treatments against APEC infection as well as the breeding of genetically resistant poultry.

Electrochemical Activation Inducing Rocksalt-to-Spinel Transformation for Prolonged Service Life of LiMn2O4 Cathodes.

LiMn2O4 spinel is emerging as a promising cathode material for lithium-ion batteries, largely due to its open framework that facilitates Li+ diffusion and excellent rate performance. However, the charge-discharge cycling of the LiMn2O4 cathode leads to severe structural degradation and rapid capacity decay. Here, an electrochemical activation strategy is introduced, employing a facile galvano-potentiostatic charging operation, to restore the lost capacity of LiMn2O4 cathode without damaging the battery configuration. With an electrochemical activation strategy, the cycle life of the LiMn2O4 cathode is extended from an initial 1500 to an impressive 14 000 cycles at a 5C rate with Li metal as the anode, while increasing the total discharge energy by ten times. Remarkably, the electrochemical activation enhances the diffusion kinetics of Li+, with the diffusion coefficient experiencing a 37.2% increase. Further investigation reveals that this improvement in capacity and diffusion kinetics results from a transformation of the redox-inert LiMnO2 rocksalt layer on the surface of degraded cathodes back into active spinel. This transformation is confirmed through electron microscopy and corroborated by density functional theory simulations. Moreover, the viability of this electrochemical activation strategy has been demonstrated in pouch cell configurations with Li metal as the anode, underscoring its potential for broader application.

GFPBW1, a ß-glucan from Grifola frondosa as vaccine adjuvant: APCs activation and maturation.

Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous ß-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 µg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 µg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

Nodule-in-nodule architecture of hepatocellular carcinomas: enhancement patterns in the hepatobiliary phase and pathological features.

PURPOSE: This study aimed to evaluate the enhancement patterns in the hepatobiliary phase (HBP) and pathological features of nodule-in-nodule-type hepatocellular carcinoma (NIN-HCC) patients. METHODS: In this single-institution retrospective study, 27 consecutive cirrhosis patients with 29 histologically confirmed NIN-HCCs who underwent preoperative examination via Gd-EOB-DTPA-enhanced MRI were enrolled from January 2016 to September 2023. Two blinded radiologists assessed the imaging features of both the inner and outer nodules in NIN-HCCs to reach a consensus on the Liver Imaging Reporting & Data System (LI-RADS) categories of the lesions. Based on the different enhancement patterns of the inner and outer nodules in the HBP, NIN-HCCs were classified into different groups and further divided into different types. Imaging features and LI-RADS categories were subsequently compared among the groups. Pathological findings for NIN-HCCs were also evaluated. RESULTS: Among 29 NIN-HCCs, all inner nodules showed hypervascularity, with a maximum diameter of 13.2 ± 5.5 mm; 51.7% (15/29) showed "wash-in with washout" enhancement; and 48.3% (14/29) showed "wash-in without washout" enhancement. All outer nodules showed hypovascularity, with a maximum diameter of 25.6 ± 7.3 mm, and 51.9% (14/29) showed a washout appearance on PVP. Among all the lesions, the maximum diameter was 27.5 ± 6.8 mm; 12 (41.4%) lesions were LR-4, and 17 (58.6%) lesions were LR-5. NIN-HCCs were classified into hypointense (62.1%, 18/29) and isointense (37.9%, 11/29) groups based on the signal intensity of the outer nodules in the HBP. In the hypointense group, 2 (6.9%) of the inner nodules were hypointense (type A), 11 (37.9%) were isointense (type B), and 5 (17.2%) were hyperintense (type C) compared to the background hypointense outer nodules. In the isointense group, 9 (31.0%) of the inner nodules were hypointense (type D), 2 (6.9%) were isointense (type E), and no (0%) was hyperintense (type F) compared to the background isointense outer nodules. There were no significant differences in the diameter, dynamic enhancement patterns of the inner or outer nodules, or LI-RADS scores of the lesions between the hypointense group and the isointense group (all P > 0.05). Histologically, the inner nodules of NIN-HCCs were mainly composed of moderately differentiated HCC (75.9% 22/29), whereas the outer nodules consisted of either well-differentiated HCC or high-grade dysplastic nodules (HGDNs). CONCLUSIONS: NIN-HCCs exhibit specific MRI findings closely associated with their pathological features. The spectrum of HBP enhancement patterns provides valuable insights into the underlying cell biological mechanisms of these lesions. NIN-HCC subtypes may be used as a morphologic marker in the early stage of multistep hepatocarcinogenesis.

Meta-Modulation: A General Learning Framework for Cross-Task Adaptation.

Building learning systems possessing adaptive flexibility to different tasks is critical and challenging. In this article, we propose a novel and general meta-learning framework, called meta-modulation (MeMo), to foster the adaptation capability of a base learner across different tasks where only a few training data are available per task. For one independent task, MeMo proceeds like a "feedback regulation system", which achieves an adaptive modulation on the so-called definitive embeddings of query data to maximize the corresponding task objective. Specifically, we devise a type of efficient feedback information, definitive embedding feedback (DEF), to mathematize and quantify the unsuitability between the few training data and the base learner as well as the promising adjustment direction to reduce this unsuitability. The DEFs are encoded into high-level representation and temporarily stored as task-specific modulator templates by a modulation encoder. For coming query data, we develop an attention mechanism acting upon these modulator templates and combine both task/data-level modulation to generate the final data-specific meta-modulator. This meta-modulator is then used to modulate the query's embedding for correct decision-making. Our framework is scalable for various base learner models like multi-layer perceptron (MLP), long short-term memory (LSTM), convolutional neural network (CNN), and transformer, and applicable to different learning problems like language modeling and image recognition. Experimental results on a 2-D point synthetic dataset and various benchmarks in language and vision domains demonstrate the effectiveness and competitiveness of our framework.

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. PATIENTS AND METHODS: A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. RESULTS: In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. CONCLUSIONS: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

Prevalence and Clustering of Cardiovascular Disease Risk Factors among Adults Along the Lancang-Mekong River: A Cross-Sectional Study from Low- and Middle-Income Countries.

Background: Progress in cardiovascular health is increasingly concentrated in high-income countries, while the burden of cardiovascular disease (CVD) is high in low- and middle-income countries, a clear health inequity that must be urgently addressed. Objective: This study aims to evaluate the prevalence and clustering of CVD risk factors in the three Lancang-Mekong regions. Methods: We conducted a population-based cross-sectional survey from January 2021 to March 2023 in China, Laos, and Cambodia. We compared the prevalence and clustering of CVD risk factors-including hypertension, dyslipidemia, diabetes mellitus, overweight/obesity, current smoking status, current drinking status, inadequate vegetable and fruit intake, and insufficient physical activity-across the three regions, further stratifying the data by gender and age. Multivariate logistic regression models were performed to explore factors influencing the aggregation of CVD risk factors (≥2, ≥3, ≥4). Results: A total of 11,005 adults were included in the study. Hypertension emerged as the primary metabolic risk factor in Laos (36.8%) and Cambodia (23.5%), whereas overweight/obesity was the primary risk factor in China (37.6%). In terms of behavioral risk factors, participants in all three regions showed insufficient vegetable and fruit intake. The prevalence of individuals without CVD risk factors was 10% in China, 1.9% in Laos, and 5.2% in Cambodia. Meanwhile, the prevalence of two or more risk factors was 64.6% in China, 79.2% in Laos, and 76.0% in Cambodia. Multivariate logistic regression models revealed that the propensity for CVD risk factors clustering was higher in men and increased with age in all three countries. Conclusions: CVD risk factors and multiple clustering are pressing health threats among adults in low- and middle-income areas along the Lancang-Mekong River Basin. This study highlights the urgent need for proactive tailored strategies to control CVD risk factors.

Overexpression of YTHDF3 increases the specific productivity of the recombinant protein in CHO cells by promoting the translation process.

Due to their high-quality characteristics, Chinese hamster ovary (CHO) cells have become the most widely used and reliable host cells for the production of recombinant therapeutic proteins in the biomedical field. Previous studies have shown that the m6A reader YTHDF3, which contains the YTH domain, can affect a variety of biological processes by regulating the translation and stability of target mRNAs. This study investigates the effect of YTHDF3 on transgenic CHO cells. The results indicate that stable overexpression of YTHDF3 significantly enhances recombinant protein expression without affecting host cell growth. Transcriptome sequencing indicated that several genes, including translation initiation factor, translation extension factor, and ribosome assembly factor, were upregulated in CHO cells overexpressing YTHDF3. In addition, cycloheximide experiments confirmed that YTHDF3 enhanced transgene expression by promoting translation in CHO cells. In conclusion, the findings in this study provide a novel approach for mammalian cell engineering to increase protein productivity by regulating m6A.

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.

Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal membrane rupture at parturition remains unknown. Here, we reveal that versican (VCAN) is the major hyalectan in the amnion, where its cleavage increases at parturition with spontaneous rupture of membrane. We further reveal that ADAMTS4 is a crucial proteolytic enzyme for VCAN cleavage in the amnion. Inflammatory factors may enhance VCAN cleavage by inducing ADAMTS4 expression and inhibiting ADAMTS4 endocytosis in amnion fibroblasts. In turn, versikine, the VCAN cleavage product, induces inflammatory factors in amnion fibroblasts, thereby forming a feedforward loop between inflammation and VCAN degradation. Mouse studies show that intra-amniotic injection of ADAMTS4 induces preterm birth along with increased VCAN degradation and proinflammatory factors abundance in the fetal membranes. Conclusively, there is enhanced VCAN cleavage by ADAMTS4 in the amnion at parturition, which can be reenforced by inflammation.

A Highly Selective Implantable Electrochemical Fiber Sensor for Real-Time Monitoring of Blood Homovanillic Acid.

Homovanillic acid (HVA) is a major dopamine metabolite, and blood HVA is considered as central nervous system (CNS) dopamine biomarker, which reflects the progression of dopamine-associated CNS diseases and the behavioral response to therapeutic drugs. However, facing blood various active substances interference, particularly structurally similar catecholamines and their metabolites, real-time and accurate monitoring of blood HVA remains a challenge. Herein, a highly selective implantable electrochemical fiber sensor based on a molecularly imprinted polymer is reported to accurately monitor HVA in vivo. The sensor exhibits high selectivity, with a response intensity to HVA 12.6 times greater than that of catecholamines and their metabolites, achieving 97.8% accuracy in vivo. The sensor injected into the rat caudal vein tracked the real-time changes of blood HVA, which paralleled the brain dopamine fluctuations and indicated the behavioral response to dopamine increase. This study provides a universal design strategy for improving the selectivity of implantable electrochemical sensors.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification.

Objective: This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue. Methods: A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis. Results: Six potential active components, namely quercetin, ß-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment. Conclusion: Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Tenecteplase Plus Butyphthalide for Stroke Within 4.5-6 Hours of Onset (EXIT-BT): a Phase 2 Study.

To date, the benefit of intravenous thrombolysis is confined to within 4.5 h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25 mg/kg) plus NBP or NBP within 4.5 to 6 h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcome defined as a modified Rankin Scale score of 0 to 1 at 90 days. 100 patients diagnosed by non-contrast CT (NCCT) were enrolled, including 50 in TNK group and 50 in control group. sICH occurred in 2.0% (1/50) in TNK group and 0.0% (0/49) in control group with no difference (unadjusted P = 0.998). The proportion of excellent functional outcome was 77.6% (38/49) in TNK group and 69.4% (34/49) in control group with non-significance (absolute difference 8.2%, P = 0.36). A significant decrease in NIHSS score at 24 h (P = 0.004) and more early neurological improvement (20.4% vs 4.1%; P = 0.026) was observed in TNK vs control group, but there was no difference in other secondary outcomes. This phase 2 study suggests that intravenous TNK with adjuvant NBP seems safe, feasible and may improve early neurological function in AIS patients within 4.5 to 6 h of symptom onset selected using NCCT.Clinical Trials Registration: This trial was registered with ClinicalTrials.gov (NCT05189509).

Interface-Stabilized Fiber Sensor for Real-Time Monitoring of Amniotic Fluid During Pregnancy.

Diseases in pregnancy endanger millions of fetuses worldwide every year. The onset of these diseases can be early warned by the dynamic abnormalities of biochemicals in amniotic fluid, thus requiring real-time monitoring. However, when continuously penetrated by detection devices, the amnion is prone to loss of robustness and rupture, which is difficult to regenerate. Here, an interface-stabilized fiber sensor is presented for real-time monitoring of biochemical dynamics in amniotic fluid during pregnancy. The sensor is seamlessly integrated into the amnion through tissue adhesion, amniotic regeneration, and uniform stress distribution, posing no risk to the amniotic fluid environment. The sensor demonstrates a response performance of less than 0.3% fluctuation under complex dynamic conditions and an accuracy of more than 98% from the second to the third trimester. By applying it to early warning of diseases such as intrauterine hypoxia, intrauterine infection, and fetal growth restriction, fetal survival increases to 95% with timely intervention.

Clinical effectiveness of valve-sparing aortic root replacement in the treatment of patients with dilated aortic root after operation for tetralogy of Fallot / 中国胸心血管外科临床杂志

@#Objective     To evaluate the clinical effectiveness of valve-sparing aortic root replacement (VSARR) in the treatment of patients with dilated aortic root after operation for tetralogy of Fallot (TOF). Methods     A retrospective analysis was conducted on clinical data of TOF patients with aortic root dilation who underwent VSARR in our hospital from 2016 to 2022. Results     Finally 14 patients were collected, including 8 males and 6 females, with a median age of 22 years ranging from 12-48 years. Among them, 5 patients had severe aortic valve regurgitation, 4 moderate regurgitation, and 5 mild or no regurgitation. Six patients had sinus of valsalva dilation, and 8 significant dilation of the ascending aorta. One patient had residual shunt due to ventricular septal defect, and 9 severe pulmonary valve regurgitation. The David procedure was performed in 10 patients, Yacoub procedure in 2 patients, and Florida sleeve in 2 patients. There was no perioperative mortality in the group. The median follow-up time was 2.9 years (ranging from 0.4 to 6.0 years). One patient had mild aortic valve regurgitation, and the rest had minimal or no regurgitation. One patient had mild stenosis of the left ventricular outflow tract, and the rest patients had no obvious stenosis. Conclusion     VSARR is a satisfactory treatment for aortic root dilation in patients with TOF, with no significant increase in the incidence of left ventricular outflow tract stenosis or aortic regurgitation during mid-term follow-up.

Effect of LINC00894 gene on proliferation and metastasis of gastric cancer cells via miR-205-5p/ZEB1 axis / 安徽医科大学学报

Objective To investigate the effects of long non-coding RNA 00894(LINC00894)gene on prolifera-tion and metastasis of human gastric cancer cells,and to verify the regulatory relationship of LINC00894,miR-205-5p and ZEB1 in gastric cancer.Methods The expression level of LINC00894 in gastric cancer cell lines,normal gastric lines,clinical gastric cancer and normal gastric tissue samples were determined by RT-qPCR.Through fol-low-up,the relationship between the expression level of LINC00894 and the prognosis of gastric cancer patients was explored.LINC00894 knockdown cell lines and overexpression cell lines were constructed,and the knockdown and overexpression efficiency was detected by RT-qPCR.Cell proliferation and metastatic capacity were determined by CCK 8,clone formation and Transwell assays.Dual-luciferase reporter assays,RT-qPCR assays and Western blot assays were used to examine the targeted regulatory relationships of LINC00894,miR-205-5p and ZEB1.Results The expression of LINC00894 gene in gastric cancer tissues or cells was significantly higher than that in normal gas-tric tissues or cells,moreover,gastric cancer patients with high LINC00894 gene expression had a worse prognosis.The knockdown of LINC00894 inhibited the viability,clonogenesis,migration and invasion ability of gastric cancer cells,and conversely,the overexpression of LINC00894 obtained the opposite results.LINC00894 promoted ZEB1 expression by targeted downregulation of miR-205-5p expression.LINC00894 promoted the expression of ZEB1 by targeting miR-205-5p and down-regulating its expression.Conclusion LINC00894 serves as an oncogene in gastric cancer and may promote proliferation and metastasis of gastric cancer cells via regulating miR-205-5p/ZEB1 axis.

Analysis of coping styles of patients with Crohn's disease and its related influencing factors / 沈阳医学院学报

Objective:To investigate the current situation of coping styles in Crohn's disease patients and its related influencing factors.Methods:A total of 80 patients with Crohn's disease admitted to our hospital from Apri 2021 to Dec 2022 were selected to evaluate their coping styles with a simple coping style questionnaire,and relevant data were collected.The factors affecting the coping styles of Crohn's disease were analyzed by multivariable logistic regression.Results:Among the 80 patients,29 cases were negative coping,the incidence was 36.25% .There were 51 patients with positive coping(63.75% ).Educational level,simplified Crohn's disease activity index(CDAI)score,adverse psychology,social support and type D personality were associated with negative coping(P＜0.05).Gender,age,family history,working status,monthly family income,place of residence,and marital status were not associated with negative coping in patients with Crohn's disease(P＞0.05).Multivariable logistic regression analysis showed that education level of high school or below(OR=2.945,95% CI:1.139-7.614),higher CDAI score(OR=11.999,95% CI:4.387-32.815),poor psychology(OR=5.950,95% CI:2.180-16.239),low social support(OR=3.598,95% CI:1.370-9.448)and type D personality(OR=3.208,95% CI:1.118-8.904)were risk factors for negative coping in patients with Crohn's disease(P＜0.05).Conclusions:The incidence of negative coping in patients with Crohn's disease is higher,which is related to high school education or below,high CDAI score,poor psychology,low social support,and type D personality.Therefore,clinical measures can be taken to promote patients to actively cope with the disease.

Literature Case Analysis of 44 Patients with Thrombocytopenia Induced by Clopidogrel / 医药导报

Objective To investigate the characteristics of clopidogrel-associated thrombocytopenia to provide references for clinically safe drug use.Methods The case reports of thrombocytopenia induced by clopidogrel published in PubMed,Embase,CNKI,Wanfang and VIP were searched from the establishment of each database to November 2022,and their occurrence was collated and analysed.Results A total of 44 cases from 43 articles were identified and included in the analysis.There were 30 males(68.2％)and 14 females(31.8％).Ages ranged from 37 to 88(65.0±11.4)years,of which 30(68.2％)were ≥60 years old.Thrombocytopenia was found from 8 h to 9 months after medication,of which 29 cases(65.9％)appeared within two weeks.There were 31 cases(70.5％)with severe thrombocytopenia and 38 cases(86.4％)with complications,of which 24 cases(63.2％)with bleeding and 19 cases(50.0％)with thrombotic thrombocytopenic purpura(TTP).The platelet countof41 cases(93.2％)returned to normal after drug withdrawal and symptomatic treatment,and 3 cases(6.8％)died finally.Conclusion Clopidogrel related thrombocytopenia is mainly severe thrombocytopenia,and often accompanied by bleeding or thrombotic thrombocytopenic purpura(TTP),but the overall outcome is good.Platelet count should be regularly monitored within the first two weeks after medication.Clopidogrel should be stopped and symptomatic treatment should be given in case of any abnormality.