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The rapid development of the Internet of Things (IoT) has accelerated the advancement of indoor photovoltaics (IPVs) that directly power wireless IoT devices. The interest in lead-free perovskites for IPVs stems from their similar optoelectronic properties to high-performance lead halide perovskites, but without concerns about toxic lead leakage in indoor environments. However, currently prevalent lead-free perovskite IPVs, especially tin halide perovskites (THPs), still exhibit inferior performance, arising from their uncontrollable crystallization. Here, a novel adhesive bonding strategy is proposed for precisely regulating heterogeneous nucleation kinetics of THPs by introducing alkali metal fluorides. These ionic adhesives boost the work of adhesion at the buried interface between substrates and perovskite film, subsequently reducing the contact angle and energy barrier for heterogeneous nucleation, resulting in high-quality THP films. The resulting THP solar cells achieve an efficiency of 20.12% under indoor illumination at 1000 lux, exceeding all types of lead-free perovskite IPVs and successfully powering radio frequency identification-based sensors.
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Background: Studies on survival and prognostic factors in individuals with remnant gastric cancer (RGC) after gastric cancer (GC) are rare. It is debatable whether prognosis of RGC after GC is worse than that of only primary GC (OPGC). The objective of this study is to compare the survival outcomes between post-GC RGC and OPGC undergoing surgical resection and to identify the prognostic factors of disease-specific survival (DSS) for RGC. Methods: We retrospectively collected data from the Surveillance, Epidemiology, and End Results (SEER) database among patients who underwent GC surgery in 1988-2020. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier (KM) survival analysis was performed to compare their overall survival (OS) and DSS. Multivariable Cox analyses were performed to identify the independent prognostic factors of DSS for post-GC RGC by estimating hazard ratios (HRs) with 95% confidence intervals (CIs). Results: There were 76 patients with RGC and 32,763 patients with OPGC included and analyzed. After balancing the baseline characteristics by PSM, no significant difference existed between OPGC and RGC groups in both OS (P=0.65) and DSS (P=0.28). Fixed-time analyses also showed no difference between the two groups for the 5-year (60.0%, RGC vs. 53.3%, OPGC, P=0.38) and 10-year DSS (56.7%, RGC vs. 48.3%, OPGC, P=0.34). Multivariable analysis revealed that area of lower income ($75,000+ vs. <$55,000, HR =0.21, 95% CI: 0.05-0.89, P=0.03), cardiac tumor [middle vs. cardia, HR =0.16, 95% CI: 0.03-0.77, P=0.02; distal vs. cardia, HR =0.10, 95% CI: 0.02-0.58, P=0.01; not otherwise specified (NOS) vs. cardia, HR =0.11, 95% CI: 0.03-0.51, P=0.004], deeper invasion (T3-4 vs. Tis-2, HR =5.19, 95% CI: 1.21-22.15, P=0.03), higher grade (G3 vs. G1-2, HR =7.35, 95% CI: 1.41-38.48, P=0.02) and not receiving chemotherapy (yes vs. no/unknown, HR =0.16, 95% CI: 0.04-0.60, P=0.007) were independent risk factors for postsurgical DSS in patients with post-GC RGC. Conclusions: The prognosis of post-GC RGC was comparable to that of OPGC following surgical resection. The independent prognostic factors for RGC are similar to those established for OPGC. Our findings suggest that RGC following first GC might be the same entity to OPGC and curative resection should be considered in selected patients.
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BACKGROUND: Diabetes mellitus (DM) can aggravate lung ischemia-reperfusion (I/R) injury and is a significant risk factor for recipient mortality after lung transplantation. Metformin protects against I/R injury in a variety of organs. However, the effect of metformin on diabetic lung I/R injury remains unclear. Therefore, this study aimed to observe the effect and mechanism of metformin on lung I/R injury following lung transplantation in type 2 diabetic rats. METHODS: Sprague-Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion. RESULTS: Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C. CONCLUSIONS: Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.
Subject(s)
AMP-Activated Protein Kinases , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Lung Transplantation , Metformin , Necroptosis , Reperfusion Injury , Animals , Rats , AMP-Activated Protein Kinases/drug effects , AMP-Activated Protein Kinases/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Hypoglycemic Agents/pharmacology , Lung/pathology , Lung/drug effects , Lung/metabolism , Lung Injury/prevention & control , Lung Injury/etiology , Lung Injury/metabolism , Metformin/pharmacology , Necroptosis/drug effects , Oxidative Stress/drug effects , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Reperfusion Injury/prevention & control , Signal Transduction/drug effectsABSTRACT
This study aimed to explore the mechanism of Shexiang Tongxin Dropping Pills(STDP) in treating diabetic cardiomyopathy(DCM) based on network pharmacology, molecular docking, and animal experiments. BATMAN, TCMSP, and GeneCards were searched for the active ingredients and targets of STDP against DCM. STRING and Cytoscape were used to build the protein-protein interaction(PPI) network and "drug-active ingredient-target" network. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of the targets were carried out based on DAVID. The molecular docking of key receptor proteins with corresponding active ingredients was performed using AutoDock Vina. The rat model of DCM was established by a high-fat diet combined with intraperitoneal injection of streptozotocin. Rats were assigned into control, model, low-(20 mg·kg~(-1)) and high-dose(40 mg·kg~(-1)) STDP, and metformin(200 mg·kg~(-1)) groups. After 8 weeks of continuous administration, the cardiac function, myocardial pathological changes, and myocardial collagen fiber deposition of rats in each group were detected by echocardiography, hematoxylin-eosin(HE) staining, and Sirius red staining, respectively. The myocardial hypertrophy was detected by WGA staining. The expression levels of p38 mitogen-activated protein kinase(p38), phosphorylation-p38(p-p38), c-Jun N-terminal kinase(JNK), phosphorylation-JNK(p-JNK), caspase-3, and C-caspase-3 in the myocardial tissue of rats in each group were measured by Western blot. The network pharmacology predicted 199 active ingredients and 1 655 targets of STDP and 463 targets of DCM. One hundred and thirty-four potential targets of STDP for treating DCM were obtained, and the AGE-RAGE signaling pathway in diabetic complications was screened out. Molecular docking results showed that miltirone, dehydromiltirone, and tryptanthrin had strong binding affinity with RAGE. The results of animal experiments confirmed that STDP effectively protected the cardiac function of DCM rats. Compared with the DCM model group, the STDP groups showed significantly down-regulated protein levels of p-p38, p-JNK, and C-caspase-3. To sum up, STDP may protect the cardiac function of DCM rats by regulating the AGE-RAGE signaling pathway.
Subject(s)
Diabetic Cardiomyopathies , Drugs, Chinese Herbal , Molecular Docking Simulation , Network Pharmacology , Animals , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/genetics , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/administration & dosage , Rats , Male , Rats, Sprague-Dawley , HumansABSTRACT
OBJECTIVE: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). METHODS: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. RESULTS: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). CONCLUSION: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.
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Low-toxicity tin halide perovskites with excellent optoelectronic properties are promising candidates for photodetection. However, tin halide perovskite photodetectors have suffered from high dark current owing to uncontrollable Sn2+ oxidation. Here, 2-cyanoethan-1-aminium iodide (CNI) is introduced in CH(NH2)2SnI3 (FASnI3) perovskite films to inhibit Sn2+ oxidation by the strong coordination interaction between the cyano group (C≡N) and Sn2+. Consequently, FASnI3-CNI films exhibit reduced nonradiative recombination and lower trap density. The self-powered photodetector based on FASnI3-CNI exhibits low dark current (1.04 × 10-9 A cm-2), high detectivity (2.2 × 1013 Jones at 785 nm), fast response speed (2.62 µs), and good stability. Mechanism studies show the increase in the activation energy required for thermal emission and generated carriers, leading to a lower dark current in the FASnI3-CNI photodetector. In addition, flexible photodetectors based on FASnI3-CNI, exhibiting high detectivity and fast response speed, are employed in wearable electronics to monitor the human heart rate under weak light and zero bias conditions. Finally, the FASnI3-CNI perovskite photodetectors are integrated with a 32 × 32 thin-film transistor backplane, capable of ultraweak light (170 nW cm-2) real-time imaging with high contrast, and zero power consumption, demonstrating the great potential for image sensor applications.
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Tin halide perovskites (THPs) have demonstrated exceptional potential for various applications owing to their low toxicity and excellent optoelectronic properties. However, the crystallization kinetics of THPs are less controllable than its lead counterpart because of the higher Lewis acidity of Sn2+, leading to THP films with poor morphology and rampant defects. Here, a colloidal zeta potential modulation approach is developed to improve the crystallization kinetics of THP films inspired by the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. After adding 3-aminopyrrolidine dihydro iodate (APDI2) in the precursor solution to change the zeta potential of the pristine colloids, the total interaction potential energy between colloidal particles with APDI2 could be controllably reduced, resulting in a higher coagulation probability and a lower critical nuclei concentration. In situ laser light scattering measurements confirmed the increased nucleation rate of the THP colloids with APDI2. The resulting film with APDI2 shows a pinhole-free morphology with fewer defects, achieving an impressive efficiency of 15.13 %.
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Graph Neural Networks (GNNs) are often viewed as black boxes due to their lack of transparency, which hinders their application in critical fields. Many explanation methods have been proposed to address the interpretability issue of GNNs. These explanation methods reveal explanatory information about graphs from different perspectives. However, the explanatory information may also pose an attack risk to GNN models. In this work, we will explore this problem from the explanatory subgraph perspective. To this end, we utilize a powerful GNN explanation method called SubgraphX and deploy it locally to obtain explanatory subgraphs from given graphs. Then we propose methods for conducting evasion attacks and backdoor attacks based on the local explainer. In evasion attacks, the attacker gets explanatory subgraphs of test graphs from the local explainer and replace their explanatory subgraphs with an explanatory subgraph of other labels, making the target model misclassify test graphs as wrong labels. In backdoor attacks, the attacker employs the local explainer to select an explanatory trigger and locate suitable injection locations. We validate the effectiveness of our proposed attacks on state-of-art GNN models and different datasets. The results also demonstrate that our proposed backdoor attack is more efficient, adaptable, and concealed than previous backdoor attacks.
Subject(s)
Neural Networks, ComputerABSTRACT
BACKGROUND: Gastric cancer (GC) constitutes a major global health problem, of which remnant gastric cancer (RGC) occurs less frequently. The rate of RGCs after gastrectomy for GC is increasing recently due to improved survival and screening, however, their incidence and risk have not been reported in the U.S. POPULATION: The objective of this study was to evaluate the incidence and elevated risk of RGC after GC gastrectomy in this population, and to identify the risk factors. METHODS: Patients underwent gastrectomy for first primary GC in 2000-2015 and those who developed RGC were identified from Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray regression was used to estimate the cumulative incidence and to identify risk factors. Standardized incidence ratios (SIRs) were calculated by Poisson regression to compare the risk with the general population. RESULTS: Among 21,566 patients included in the cohort, 227 developed RGC. The 20-year cumulative incidence of RGC was 1.88%. Multivariate analysis revealed that older age, invasion depth, male sex, marital status, and lower income are independent risk factors for RGC development. SIR was 7.70 overall and > 4.5 in each stratum. CONCLUSIONS: Cumulative incidence and risk for RGCs increased continuously in patients underwent GC gastrectomy. Close and lifelong endoscopy surveillance should be recommended for patients who received GC gastrectomy, especially those with high-risk factors.
Subject(s)
Gastric Stump , Stomach Neoplasms , Humans , Male , Incidence , Stomach Neoplasms/epidemiology , Stomach Neoplasms/surgery , Stomach Neoplasms/diagnosis , Retrospective Studies , Gastrectomy/adverse effects , Gastrectomy/methodsABSTRACT
Our purpose of this study was to explore the application effect of respiratory flora regulation in bronchiolitis obliterans after lung transplantation, and its regulatory effect on the microbial environment of the lesion and the IL-10/STAT3 signaling pathway. 25 clean-grade C57BL/6 male mice and 5 BALB/c male mice were selected for orthotopic tracheal transplantation and postoperative respiratory flora regulation in a hospital animal room from Jan 2019 to Dec 2021. Next, the changes in the microbial environment and the IL-10/STAT3 signaling pathway before and after respiratory flora regulation were compared, so as to evaluate the regulatory effect of this method. The Simpson index did not show a significant difference before and after respiratory flora regulation intervention (P>0.05). However, the Chao1, ACE, Shannon, and Actinobacteria dominant indices were higher after the intervention. There were significant changes in the abundance of Proteobacteria, Bacteroidetes, Acidobacteria, Firmicutes, Propionibacterium, Corynebacterium, Staphylococcus, and Streptococcus after the intervention (P<0.05). Additionally, IL-10 and STAT3 levels were higher after the intervention and showed significant differences (P<0.05) compared to before. Regulating the respiratory tract flora can improve the microbial environment of bronchiolitis obliterans post-lung transplantation. This helps balance the respiratory flora, increase IL-10 and STAT3 levels, and aid in the recovery of inflammatory responses.
Subject(s)
Bronchiolitis Obliterans , Lung Transplantation , Microbiota , Animals , Male , Mice , Bronchiolitis Obliterans/pathology , Interleukin-10 , Lung Transplantation/adverse effects , Mice, Inbred BALB C , Mice, Inbred C57BLABSTRACT
PURPOSE: Survival after local resection (LR) versus radical resection (RR) has been revealed comparable for patients with rectal and duodenal gastrointestinal stromal tumors (GISTs), but is unknown for jejunoileal (JI) GISTs. This study aimed to compare the long-term survival between patients with JI GISTs who underwent LR and RR, and to find out the prognostic factors for JI GISTs. METHODS: Patients diagnosed with JI GISTs in 1975-2019 were identified from Surveillance, Epidemiology, and End Results (SEER) database and grouped according to surgical modality. Propensity score matching (PSM) was performed to balance the LR and RR groups. Overall survival (OS) and disease-specific survival (DSS) were compared in the full and matched cohorts using Kaplan-Meier (KM) analysis. Subgroup sensitivity analyses were also performed. Risk factors associated with DSS were analyzed in multivariate Cox analysis following model selection. RESULTS: 1107 patients diagnosed with JI GISTs were included in the study cohort. After PSM, OS and DSS were comparable in LR and RR groups. Consistently, the two groups had similar DSS in all subgroup analyses. Moreover, multivariate Cox analysis identified lymphadenectomy, older age, larger tumor size, distant metastasis, high and unknown mitotic rate, but not LR, as independent prognostic risk factors for JI GISTs. CONCLUSIONS: We conducted the first population-based comparison between the effect of different surgical modes on survival for patients with JI GISTs. LR can be carried out safely without compromising oncological outcome, and should be considered as a treatment option in selected patients with JI GISTs.
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Duodenal Neoplasms , Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Duodenal Neoplasms/pathology , Duodenal Neoplasms/surgery , Propensity Score , Pancreaticoduodenectomy/adverse effects , Retrospective Studies , PrognosisABSTRACT
Objective: Coronary heart disease is incurable and prone to recurrence, and long-term dependence on medication and good nursing management to improve the prognosis. The effect of clopidogrel in the treatment of coronary heart disease is affected by many factors, so paying more attention to details in the process of patient care is conducive to creating more ideal recovery conditions for patients. The purpose of this study is to conduct detailed intervention for coronary heart disease (CHD) after clopidogrel treatment, and to analyze the clinical efficacy of this intervention mode on CHD patients and the relief of angina pectoris. Methods: A total of 120 patients with coronary heart disease who were diagnosed and treated in our hospital from May 2020 to March 2022 were selected as the research objects and divided into a detail group (n=60) and a routine group (n=60) according to the computer randomization method, All research subjects were given clopidogrel intervention, followed by routine intervention in the routine group, and detailed intervention in the detail group. Detailed intervention includes specific measures such as psychological intervention, life intervention, health education, medical assessments, personalized care. The control of angina pectoris of the subjects was analyzed, and the daily life, motor function, quality of life score, negative emotion score and complications were observed. Results: The dimension score of TS [(83.50±5.14) points vs (77.42±4.35) points], DP [(85.59±5.78) points vs (80.14±5.43) points], PL [(79.62±5.19) points vs (74.18±5.04) points], AS [(90.69±6.35) points vs (85.57±6.12) points], AF[(83.54±5.22) points vs (77.51±5.16) points] in the detail group were higher than those of conventional group (P < .001). The differences in daily life, motor function of the subjects before the intervention were not comparable (P > .05), and the scores of daily life [(86.14±5.52) points vs (65.48±5.17) points] and motor function [(88.97±5.34) points vs (70.58±5.46) points] in the detail group at 4 weeks after intervention were higher than those in the routine group (P < .001). The quality of life in the detail group [mental state of (17.56±2.12) points vs (20.13±2.09) points, mental health of (15.62±2.34) points vs (18.09±2.06) points, social function of (15.86±2.41) points vs (18.11±2.14) points, emotional function of (14.36±3.45) points vs (16.78±3.69) points] were lower than those of the conventional group (P < .001). The negative mood scores [SAS score of (41.70±3.14) points vs (67.14±3.25) points, SDS score of (39.59±4.11) points vs (60.58±4.54) points] in the detail group were lower than those of the conventional group (P < .001). In addition, the total incidence of complications (3.33% vs 13.33%) in the detail group was significantly lower than that in the regular group (P < .001). Conclusions: Detailed intervention after clopidogrel treatment in CHD patients can significantly improve the efficacy of patients, reduce angina pectoris, and at the same time can effectively improve various physical functions and relieve their negative emotions, which is worthy of being widely used in clinical practice. Better control of angina pectoris is beneficial to reduce the frequency of hospital admission and save medical resources. The sample size of this study is small, and the sample size will be further expanded in the future to improve the scientific conclusion.
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Objective: Epstein-Barr virus (EBV) is a virus that is ubiquitous in humans. To investigate the association between EBV infection and lung cancer risk to reveal whether it is involved in the development and development of lung cancer. Although there has been discussion of EBV and lung cancer in the past. Through this study, we hope to deepen our understanding of the causes of lung cancer and provide new clues and targets for the prevention, early diagnosis and treatment of lung cancer. This study is also beneficial to the development of medical science and public health. First of all, the research results are expected to be incorporated into lung cancer prevention and treatment strategies and policies, so as to provide better treatment decisions for lung cancer patients and improve the survival rate and quality of life of patients. At the same time, communicating the research results to the public can help raise awareness of lung cancer risk factors. By encouraging healthy lifestyles and screening measures, the public can reduce their risk of lung cancer. In addition, this study also provides an important foundation for subsequent academic research and scientific exploration. It provides valuable information and inspiration for in-depth understanding of lung cancer and other related fields. Overall, this study makes an important contribution to both medical science and public health. Method: By September 26, 2022, an online database was used to conduct a literature search in English. Random effects models were employed to estimate the prevalence of EBV with 95% confidence intervals (CIs). Additionally, the pooled odds ratio (OR) and 95%CI were calculated from case-control studies to determine the association between EBV and lung cancer. Results: In this study of 886 patients with lung cancer, the overall prevalence of EBV infection was found to be 44.36% (95%CI: 4.08-16.9). Fourteen studies were included in the analysis, all of which used a case-control design and involved comparisons of tumors with adjacent or non-adjacent normal and non-cancerous controls. There was a significant difference in the prevalence of EBV infection in lung cancer tissues between China and other regions, with an odds ratio (OR) of 9.36 (95% confidence interval: 4.00-21.94, P<0.001, I²=73.5%). This suggests that the association between EBV infection and lung cancer cases is stronger in China than in other regions. Additionally, the prevalence of EBV infection varied across different pathological types of lung cancer, with rates of 81.08% for pulmonary lymphoepithelioma-like carcinoma (LELC),this a rare subtype of non-small cell lung cancer (NSCLC).34.78% for non-small cell lung cancer, and 21.17% for small cell lung cancer. The statistical analysis indicated that EBV infection was most significantly associated with cancer risk in LELC, while non-small cell lung cancer was more strongly associated with EBV than small cell lung cancer. Conclusion: The study found that EBV infection increases the risk of lung cancer by more than four times, and this risk is associated with the pathological type, lymphatic infiltration, and degree of differentiation of the lung cancer, particularly in the rare subtype of pulmonary lymphoepithelioma in non-small cell lung cancer(NSCLC). Additionally, there are racial and regional differences in the correlation between EBV-infected lung cancer, with the Asian population showing greater susceptibility. The study used normal or abnormal tissue adjacent to the tumor as a control, which is considered a more accurate method for determining the relationship between EBV infection and lung cancer.
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The aim of our study is to disclose the role and underlying molecular mechanisms of circular RNA ubiquitin protein ligase E3 component n-recognin 4 (circ-UBR4) in atherosclerosis (AS). Our data showed that circ-UBR4 expression was upregulated in AS patients and oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) compared with healthy volunteer and untreated VSMCs. In addition, ox-LDL stimulated proliferation, migration, and inflammation but decreased apoptosis in VSMCs, which were overturned by the inhibition of circ-UBR4. miR-515-5p was sponged by circ-UBR4, and its inhibitor reversed the inhibitory effect of circ-UBR4 knockdown on proliferation, migration, and inflammation in ox-LDL-induced VSMCs. Insulin-like growth factor2 (IGF2) was a functional target of miR-515-5p, and overexpression of IGF2 reversed the suppressive effect of miR-515-5p on ox-LDL-stimulated VSMCs proliferation, migration, and inflammation. Collectively, circ-UBR4 knockdown decreased proliferation, migration, and inflammation but stimulated apoptosis in ox-LDL-induced VSMCs by targeting the miR-515-5p/IGF2 axis.
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Background: Due to its nutritional advantages over total gastrectomy, proximal gastrectomy (PG) with anti-reflux techniques has gained significant attention in East Asian countries in recent years. The double flap technique (DFT) and modified side overlap and fundoplication by Yamashita (mSOFY) are two promising anti-reflux interventions following PG. However, anastomotic stenosis after DFT and gastroesophageal reflux after mSOFY have been reported in several patients. To address these concerns, a hybrid reconstruction procedure was designed, namely, right-sided overlap with single flap valvulopasty (ROSF), for proximal gastrectomy, with the aim of reducing anastomotic stricture and reflux. Among the 38 patients who underwent ROSF at our hospital, one developed Stooler grade II anastomotic stenosis. Herein, we present the successful management of this patient through endoscopic stricturotomy (ES). Case summary: A 72-year-old female complaining of "epigastric pain and discomfort for more than 1 month" was diagnosed with adenocarcinoma of the esophagogastric junction (Siewert type II). She underwent laparoscopic-assisted PG and ROSF procedures at our hospital and recovered well after surgery. However, she started experiencing progressive difficulty in eating and vomiting approximately 3 weeks after the intervention. Endoscopy revealed Stooler grade II esophagogastric anastomotic stenosis. ES with insulated tip (IT) Knife nano was eventually performed, and the patient was able to resume a normal diet without experiencing any discomfort during the 5-month follow-up period. Conclusion: Endoscopic stricturotomy using IT Knife nano successfully treated anastomotic stenosis following ROSF with no associated complications. Thus, ES to treat anastomotic stenosis after PG with valvulopasty can be considered a safe option and should be performed in centers with the required expertise.
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ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine compound, is fragrant, invigorates the qi, unblocks pulses, activates the blood circulation, removes blood stasis, and relieves pain. It is used clinically to treat coronary heart disease and angina pectoris. Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality from cardiovascular events. Endothelial dysfunction and inflammation have been verified as its underlying causes. STDP can ameliorate CMD, but the mechanism has not been fully elucidated. AIM OF THE STUDY: To explore the effects of STDP on M1 macrophage polarization-induced inflammation and endothelial dysfunction as an inhibitor of CMD, and to determine its mechanisms of action. MATERIALS AND METHODS: The CMD rat model was established by left anterior descending artery (LAD) ligation. The efficacy of STDP against CMD was evaluated by echocardiography, optical microangiography, Evans blue staining, and histological examination. The OGD/R-induced endothelial injury model, the endothelial injury-induced sterile inflammation model, the Dectin-1 overexpression model, and the Dectin-1-overexpressing RAW264.7 macrophage supernatant-stimulated HUVEC-induced secondary injury of endothelial function model were established to confirm the efficacy of STDP against M1 macrophage polarization-induced inflammation and endothelial dysfunction. RESULTS: STDP blunted the deterioration of cardiac function and ameliorated CMD by reducing inflammatory cell infiltration and endothelial dysfunction in CMD rats. Endothelial injury and Dectin-1 overexpression induced M1 macrophage polarization and inflammation. Mechanically, STDP hindered M1 macrophage polarization and inflammation by inhibiting the Dectin-1/Syk/IRF5 pathway both in vivo and in vitro. STDP alleviated endothelial dysfunction induced by Dectin-1 overexpression in macrophages. CONCLUSION: STDP can alleviate M1 macrophage polarization-induced inflammation and endothelial dysfunction against CMD via the Dectin-1/Syk/IRF5 pathway. Dectin-1-associated M1 macrophage polarization might be developed as a novel target for ameliorating CMD.
Subject(s)
Myocardial Ischemia , Vascular Diseases , Rats , Animals , Macrophages , Inflammation/drug therapy , Inflammation/metabolism , Myocardial Ischemia/metabolism , Vascular Diseases/metabolism , Interferon Regulatory Factors/metabolismABSTRACT
Purpose: The pain caused by spinal cord injury (SCI) poses a major burden on patients, and pain management is becoming a focus of treatment. Few reports have described changes in the brain after SCI. Particularly, the exact mechanism through which brain regions affect post-injury pain remains unclear. In this study, we aimed to determine the potential therapeutic mechanisms of pain. A mouse model of spinal cord contusion was established, and molecular expression in the anterior cingulate cortex (ACC) and periaqueductal gray (PAG) in the brain and animal behavior was observed after local injection of human umbilical cord mesenchymal stem cells (HU-MSCs) at the site of SCI. Method: Sixty-three female C57BL/6J mice were divided into four groups: a sham operation group (n = 15); a spinal injury group (SCI, n = 16); an SCI + HU-MSCs group (n = 16) and an SCI + PBS group (n = 16), in which the SCI site was injected with HU-MSCs/phosphate buffer. The BMS score was determined, and the von Frey test and Hargreaves test were used to assess behavior every week after surgery. Mice were sacrificed in the fourth week after operation, and samples were collected. The expression of CGRP, Substance P, C-Fos and KCC2 in the ACC and PAG were observed with immunohistochemistry. Chromic cyanine staining was used to observe transverse sections of the injured spinal cord. Result: In the ACC and PAG after SCI, the expression of CGRP, SP and C-Fos increased, and the expression of KCC2 decreased, whereas after HU-MSC injection, the expression of CGRP, SP and C-Fos decreased, and the expression of KCC2 increased. The SCI + HU-MSC group showed better exercise ability from 2 to 4 weeks after surgery than the SCI/SCI + PBS groups (P < 0.001). Local injection of HU-MSCs significantly improved the mechanical hyperalgesia caused by SCI in the fourth week after surgery (P < 0.0001), and sensation was significantly recovered 2 weeks after surgery (P < 0.0001); no improvement in thermal hypersensitivity was observed (P > 0.05). The HU-MSC group retained more white matter than the SCI/SCI + PBS groups (P < 0.0001). Conclusion: Local transplantation of HU-MSCs at the site of SCI partially relieves the neuropathic pain and promotes recovery of motor function. These findings suggest a feasible direction for the future treatment of SCI.
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The neuromorphic systems for sound perception is under highly demanding for the future bioinspired electronics and humanoid robots. However, the sound perception based on volume, tone and timbre remains unknown. Herein, organic optoelectronic synapses (OOSs) are constructed for unprecedented sound recognition. The volume, tone and timbre of sound can be regulated appropriately by the input signal of voltages, frequencies and light intensities of OOSs, according to the amplitude, frequency, and waveform of the sound. The quantitative relation between recognition factor (ζ) and postsynaptic current (I = Ilight - Idark) is established to achieve sound perception. Interestingly, the bell sound for University of Chinese Academy of Sciences is recognized with an accuracy of 99.8%. The mechanism studies reveal that the impedance of the interfacial layers play a critical role in the synaptic performances. This contribution presents unprecedented artificial synapses for sound perception at hardware levels.
ABSTRACT
BACKGROUND: There is no standard reconstruction method following proximal gastrectomy, of which gastroesophageal reflux and anastomotic complications are of great concern. Though several techniques have been devised to overcome these postoperative complications, such as double tract reconstruction, double-flap technique and side overlap fundoplication by Yamashita, none of them is considered a perfect solution. Herein, we designed a novel method of esophagogastrostomy after laparoscopic proximal gastrectomy (LPG), named right-sided overlap and single-flap valvuloplasty (ROSF). METHODS: Between March 2021 and December 2021, 20 consecutive patients underwent LPG-ROSF at Department of Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University. Surgical outcomes and postoperative complications were recorded. All patients were followed-up until December 2022. Endoscopy and assessment of gastrointestinal symptoms were performed 1 year after surgery. Nutrition-related parameters including total body weight, hemoglobin, lymphocyte count, serum total protein, serum albumin and serum prealbumin were evaluated 1 year after surgery and compared with those before surgery. RESULTS: The mean surgery time and anastomosis time was 285.3 ± 71.3 and 61.3 ± 11.2 min respectively. None of the patients had gastrointestinal early postoperative complications. Symptomatic reflux was observed in one patient (5%) while reflux esophagitis (Los Angeles Grade A) was observed in another patient (5%). Four patients (20%) had mild dysphagia (Visick score = II) but none of them had anastomotic stenosis. There were no significant changes in nutritional status postoperatively. CONCLUSIONS: ROSF can be safely performed after LPG and has satisfactory outcomes in preventing reflux and stenosis, and maintaining nutritional status. This technique requires further validation.