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The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell-ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin-collagen interplay reinforces the central role of integrins in mediating cell-ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell-ECM interactions, which may facilitate the development of novel therapeutic horizons.
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Objective: To investigate the prevalence and risk factors of functional dyspepsia (FD) and irritable bowel syndrome (IBS) among college students in China. Methods: An online questionnaire survey of college students aged 17-35 from across China was conducted. The online questionnaire survey was supplemented by an offline survey. A total of 2025 valid samples were included for statistical analysis. χ 2 test and logistic regression were performed for statistical analysis. Results: The prevalence of FD among college students who met the Rome â £ diagnostic criteria was 5.5% (112/2025), with most of them, or 66.1% (74/112), suffering from postprandial discomfort syndrome (PDS). Smoking (odds ratio [ OR]=2.334, 95% confidence interval [ CI]: 1.187-4.589, P=0.014), depression ( OR=2.447, 95% CI: 1.421-4.214, P=0.001), and insomnia ( OR=1.947, 95% CI: 1.291-2.937, P=0.001) were positively correlated with the prevalence of FD. The prevalence of IBS was 1.9% (38/2025), with IBS-diarrhea dominant (IBS-D) being the most important subtype that accounted for 44.7%. Anxiety ( OR=3.63, 95% CI: 1.34-9.88, P=0.012) and insomnia ( OR=2.35, 95% CI: 1.18-4.68, P=0.015) were positively correlated with the prevalence of IBS. Conclusion: Based on Rome â £ criteria, IBS and FD are not uncommon among Chinese university students. Psychological disorders and some related lifestyle factors may be related to the development of the disease. In the future, more series of studies based on different diagnostic criteria, different regions, and multiple factors should be conducted in China.
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Dispepsia , Síndrome del Colon Irritable , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/epidemiología , Dispepsia/diagnóstico , Dispepsia/epidemiología , Dispepsia/etiología , Prevalencia , Ciudad de Roma , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Encuestas y Cuestionarios , EstudiantesRESUMEN
The purpose of the present study is to investigate the effect of L-cysteine on colonic motility and the underlying mechanism. Immunohistochemical staining and Western blot were used to detect the localization of the H2S-generating enzymes cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE). Organ bath system was used to observe the muscle contractile activities. Whole-cell patch-clamp technique was applied to record ionic channels currents in colonic smooth muscle cells. The results showed that both CBS and CSE were localized in mucosa, longitudinal and circular muscle and enteric neurons. L-cysteine had a dual effect on colonic contraction, and the excitatory effect was blocked by pretreatment with CBS inhibitor aminooxyacetate acid (AOAA) and CSE inhibitor propargylglycine (PAG); L-cysteine concentration-dependently inhibited L-type calcium channel current (ICa,L) without changing the characteristic of L-type calcium channel (P < 0.01); In contrast, the exogenous H2S donor NaHS increased ICa,L at concentration of 100 µmol/L, but inhibited ICa,L and modified the channel characteristics at concentration of 300 µmol/L (P < 0.05); Furthermore, L-cysteine had no effect on large conductance calcium channel current (IBKCa), but NaHS significantly inhibited IBKCa (P < 0.05). These results suggest that L-cysteine has a potential dual effect on colonic smooth muscle and the inhibitory effect might be directly mediated by L-type calcium channel while the excitatory effect might be mediated by endogenous H2S.
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Cisteína/farmacología , Sulfuro de Hidrógeno , Cistationina betasintasa , Cistationina gamma-Liasa , Músculo LisoRESUMEN
Infrasound widely exists in nature, our living condition, productive and traffic environment. Gastrointestinal tract is relatively sensitive to infrasound. However, the effect of infrasound on gastrointestinal function is unclear. Therefore, the purpose of our study was to observe the effects of infrasound on gastric motility and gastric morphology and to assess the expression of nitric oxide synthase (NOS) in gastric antrum after exposure to infrasound of 8 Hz - 130 dB for 2 hours per day for 14 consecutive days. Gastric motility was assessed by gastric fluid-emptying rate. Gastric morphology was evaluated by HE. The expression of NOS was measured by tissue microarray technology. The results would contribute to understand the role of infrasound in gastroenterology, and help to explain the mechanism of infrasound on gastroenterology.
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Motilidad Gastrointestinal , Óxido Nítrico Sintasa/metabolismo , Sonido/efectos adversos , Estómago , Animales , Regulación Enzimológica de la Expresión Génica , Masculino , RatasRESUMEN
It is important to real-timely monitor and control the temperature of cell physiological solution in patch clamp experiments, which can eliminate the uncertainty due to temperature and improve the measurement accuracy. This paper studies the influence of different ions at different concentrations in the physiological solution on precision of a temperature model by using near infrared spectroscopy and chemometrics method. Firstly, we prepared twelve sample solutions respectively with the solutes of CaCl2, KCl and NaCl at four kinds of concentrations, and collected the spectra of different solutions at the setting temperature range 20-40 degrees C, the range of the spectra is 9 615-5 714 cm(-1). Then we divided the spectra of each solution at different temperatures into two parts (a training set and a prediction set) by three methods. Interval partial least squares method was used to select an effective wavelength range and develop calibration models between the spectra in the selected range and temperature velues. The experimental results show that RMSEP of CaCl2 solution with 0.25 g x mL(-1) is maximum, the result of the three tests are 0.386 3, 0.303 7 and 0.337 2 degrees C, RMSEP of NaCl with 0.005 g x mL(-1) solution is minimum, the result of the three tests are 0.220 8, 0.155 3 and 0.145 2 degrees C. The experimental results indicate that Ca2+ has the greatest influence on the accuracy of the temperature model of the cell physiological solution, then K+, and Na+ has the least influence. And with the ionic concentration increasing, the model accuracy decreases. Therefore; when we build the temperature model of cell physiological solution, it is necessary to change the proportion of the three kinds of main ions in cell physiological solution reasonably in order to correct the effects of different ionic concentrations in physiological solution and improve the accuracy of temperature measurements by near infrared spectroscopy.
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Soluciones Farmacéuticas , Temperatura , Calibración , Iones , Análisis de los Mínimos Cuadrados , Modelos Teóricos , Sodio , Cloruro de Sodio , Soluciones , Espectroscopía Infrarroja CortaRESUMEN
The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 µA and 0 µA. When the working current was higher than 0 µA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 µA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.
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Potenciales de Acción , Campos Magnéticos , Neuronas/citología , Canales de Sodio/fisiología , Animales , Potenciales de la Membrana , Ratones , Técnicas de Placa-Clamp , Transmisión SinápticaRESUMEN
OBJECTIVES: To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke. METHODS: Sixty SD rats were randomly divided into sham-operation, model, vitamin D3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D3 group were given 1, 25-VitD3 solution (3 ng·100 g-1·d-1) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1ß and IL-4 in the cerebral cortex of ischemic area were detected by Western blot. RESULTS: Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were increased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased (P<0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were decreased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased (P<0.01) in the ESA and vitamin D3 groups. CONCLUSIONS: ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D3, inhibiting vitamin D3 degradation, and regulating Th1/Th2 balance.
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Infarto de la Arteria Cerebral Media , Vitamina D3 24-Hidroxilasa , Animales , Humanos , Masculino , Ratas , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/metabolismo , Puntos de Acupuntura , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Corteza Cerebral/metabolismo , Colestanotriol 26-Monooxigenasa/genética , Colestanotriol 26-Monooxigenasa/metabolismo , Citocinas/metabolismo , Citocinas/genética , Electroacupuntura , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Vitamina D3 24-Hidroxilasa/genética , Vitamina D3 24-Hidroxilasa/metabolismoRESUMEN
OBJECTIVES: To observe the effect of electroacupuncture (EA) of scalp acupoint (Dingnieqian-xiexian, MS6) on expression of retinoid-related orphan receptor γT (ROR γ t), interleukin (IL)-17A, IL-10, transfor-ming growth factor-ß1 (TGF-ß1), IL-6, IL-21, and IL-17A+ Thelper cells(Th) 17 and forkhead transcription factor P3 (FOXP3)+ regulatory T cells (Treg) differentiation of ischemic cortex in ischemic stroke rats, so as to explore its molecular mechanisms underlying relief of inflammatory injury of ischemic stroke. METHODS: A total of 120 male SD rats were randomly assigned to sham operation, model, EA, inhibitor, agonist and EA+agonist groups, with 15 rats in each group. The ischemic stroke model was established by occlusion of the left middle cerebral artery according to Longa's methods. For rats of the EA group and EA+agonist group, EA (2 Hz/100 Hz, 1 mA) was applied to bilateral MS6 for 30 min, once daily for 7 days. Rats of the inhibitor group received intraperitoneal injection of solution of SR1001 (RORγt inhibitor) (2.5 mg/mL, 10 mg/kg), once daily for 7 days. Rats of the agonist and EA+agonist groups received intraperitoneal injection of solution of SR1078 (RORγt agonist) (5 mg/mL, 5 mg/kg) before EA, once daily for 7 days. Rats of the sham operation and model groups were grabbed and fixed in the same way with the other groups. The Zea-longa's score, modified neurological severity score (mNSS) and the neurobehavioral score were assessed before and after the intervention. At the end of experiments, the ischemic cortex tissue was collected. The 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction. The expression of RORγt mRNA was detected by real-time quantitative PCRï¼the protein expression levels of RORγt, IL-17A, IL-10 and TGF-ß1 were detected by Western blotï¼the immunoactivity of IL-6 and IL-21 were detected by immunohistochemistryï¼the fluorescence areas of IL-17A+Th17 and FOXP3+Treg cells were measured by immunofluorescence and their ratio was calculated in the tissue of ischemic cortex. RESULTS: Relevant to the sham operation group, the model group had a significant increase in the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg (P<0.01), and an obvious decrease in the expression levels of TGF-ß1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity (P<0.01). In contrast to the model group, both EA and inhibitor groups had a significant decrease in the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg (P<0.01, P<0.05), and a marked increase in the expression levels of TGF-ß1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity (P<0.05, P<0.01), while the above indicators of the agonist group were all reversed (P<0.01, P<0.05). Comparison between the agonist and EA+agonist groups showed that the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg were significantly lower (P<0.01, P<0.05), and the expression of TGF-ß1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity were obviously higher (P<0.01, P<0.05) in the EA+agonist group than in the agonist group, suggesting that EA intervention can effectively weaken the effects of RORγt agonist. CONCLUSIONS: EA of scalp acupoint MS6 can effectively improve the neurological function, behavior reaction and reduce cerebral infarct volume in ischemic stroke rats, which may be associated with its functions in down-regulating the expression of RORγt and promoting the balance of IL-17A+Th17/FOXP3+Treg to alleviate inflammatory injury after ischemic stroke.
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Isquemia Encefálica , Electroacupuntura , Accidente Cerebrovascular Isquémico , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Isquemia Encefálica/genética , Isquemia Encefálica/terapia , Interleucina-10 , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Interleucina-17/genética , Interleucina-6 , Puntos de Acupuntura , Cuero Cabelludo , Linfocitos T Reguladores , Factor de Crecimiento Transformador beta1 , Infarto Cerebral , Factores de Transcripción Forkhead , ARN MensajeroRESUMEN
OBJECTIVE: To observe the effects of electro-scalp acupuncture ï¼ESAï¼ on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1ß, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke. METHODS: Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD3 group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD3 group were treated with intragastric administration of 1,25-dihydroxyvitamin D3 (1,25-VitD3) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1ß, and IL-10 in the ischemic cortex. RESULTS: Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1ß in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD3 group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1ß in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD3 group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1ß, and IL-10 in the ischemic cortex (P<0.01, P<0.05). CONCLUSION: ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.
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Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Masculino , Animales , Ratas , Ratas Sprague-Dawley , Interleucina-10 , Interleucina-6/genética , Microglía , Cuero Cabelludo , Vitaminas , Infarto de la Arteria Cerebral MediaRESUMEN
OBJECTIVE: To explore the molecular mechanism of electrical stimulation with scalp acupuncture (ESA) in alleviating neuroinflammatory injury in ischemic stroke rats based on interferon γ (IFN-γ)-mediated Janus kinase/signal transduction and transcriptional activator 1 (JAK/STAT1) signaling pathway. METHODS: Fifty-six SD rats aged 7 weeks were randomly divided into normal, model, ESA and inhibitor groups, with 14 rats in each group. The middle cerebral artery embolization rat model was established by means of thread embolization. Rats in the inhibitor group were intraperitoneally injected with the inhibitor PJ34 (5 mg/mL, 25 mg/kg) once a day for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. The percentage of cerebral infarction volume was detected by TTC staining. The positive expressions of interleukin (IL)-6 and IL-10 in cerebral cortex were detected by immunohistochemistry. The protein expression levels of IFN-γ, JAK1, JAK2 and phosphorylated (p)-STAT1 in rats cerebral cortex were detected by Western blot. RESULTS: Compared with the normal group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were increased (P<0.01), while the expression level of IL-10 was decreased (P<0.01) in the model group. Compared with the model group, the neurological deficit score and neurobehavioral score after treatment were significantly decreased (P<0.01), the percentage of cerebral infarction volume was decreased (P<0.01), the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were decreased (P<0.01), while the expression level of IL-10 was increased (P<0.01) in the ESA and inhibitor groups. ESA was superior to inhibitors in improving neurological deficit score and down-regulating p-STAT1 expression (P<0.05, P<0.01), and was inferior to inhibitor in reducing the percentage of cerebral infarction volume as well as down-regulating IFN-γ and JAK1 (P<0.01, P<0.05). CONCLUSION: Down-regulating the expression of IFN-γ and inhibiting the activity of JAK/STAT1 signaling pathway may be one of the mechanisms by which ESA alleviates neuroinflammatory injury in ischemic stroke rats.
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Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Animales , Ratas , Ratas Sprague-Dawley , Interleucina-10 , Interferón gamma/genética , Interleucina-6 , Cuero Cabelludo , Transducción de Señal , Estimulación Eléctrica , Infarto CerebralRESUMEN
In recent years, research on the mechanism of bone destruction in rheumatoid arthritis (RA) has remained in the initial stages, and the mechanism has not been fully elucidated to date. Recent studies have shown that long noncoding RNAs (lncRNAs) participate in RA bone destruction via autophagy, but the specific regulatory mechanism of lncRNA-mediated autophagy is unclear. Therefore, in this article, we review the mechanisms of lncRNA-mediated autophagy in fibroblast-like synoviocytes and chondrocytes in RA bone destruction. We explain that lncRNAs mediate autophagy and participate in many specific pathological processes of RA bone destruction by regulating signalling pathways and the expression of target genes. Specific lncRNAs can be used as markers for molecular diagnosis, mechanistic regulation, treatment and prognosis of RA.
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Artritis Reumatoide , ARN Largo no Codificante , Sinoviocitos , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Artritis Reumatoide/metabolismo , Sinoviocitos/metabolismo , Transducción de Señal , Fibroblastos/metabolismo , Autofagia/genética , Proliferación Celular/genética , Células CultivadasRESUMEN
Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.
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Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Masculino , Humanos , Persona de Mediana Edad , Femenino , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Úlcera/etiología , Stents Liberadores de Fármacos/efectos adversos , Aspirina/efectos adversos , Hemorragia/inducido químicamenteRESUMEN
BACKGROUND: Previous studies have shown that moxibustion on Tianshu (ST25) and Qihai (CV6) is effective for treating Crohn's disease. However, the mechanism of moxibustion has not been clearly elucidated. AIM: The purpose of this study was to investigate the effect of moxibustion on the inhibition of colonic epithelial cell apoptosis and on tumor necrosis factor alpha (TNF-alpha) and tumor necrosis factor receptor TNF receptor-1 (TNFR1) and TNFR2 and to determine the mechanism of its protective effect using Crohn's disease (CD) model rats. METHODS AND RESULTS: The experimental CD rat models were established by the administration of trinitrobenzene sulfonic acid. In the herbs-partitioned moxibustion (HPM) and mild-warm moxibustion (MWM) groups, moxibustion was administered to Tianshu (ST25) and Qihai (CV6) acupoints once daily for 14 days. In the salicylazosulfapyridine (SASP) group, SASP was administered twice daily for 14 days. A normal control (NC) group and a model control (MC) group were also studied. The levels of TNF-alpha and its mRNA, TNFR1 as well as the rate of colonic epithelial cell apoptosis were significantly decreased in the HPM, MWM and SASP groups compared with the MC group. The HPM and MWM groups had lower mRNA expression and lower protein levels of TNF-alpha compared to the SASP group. The HPM and MWM groups exhibited less apoptosis than the SASP group. CONCLUSIONS: Moxibustion may inhibit colonic epithelial cell apoptosis by reducing the high expression of TNF-alpha and TNFR1 to protect the defective colonic epithelial barrier in CD model rats.
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Colon/metabolismo , Enfermedad de Crohn/terapia , Mucosa Intestinal/metabolismo , Moxibustión/métodos , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Apoptosis , Colon/patología , Citometría de Flujo , Regulación de la Expresión Génica , Etiquetado Corte-Fin in Situ , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
OBJECTIVE: To investigate the application experience and clinical effects of hand-assisted laparoscopic radical resection for rectal cancer. METHODS: The clinical data of 156 patients with rectal cancer treated with hand-assisted laparoscopic surgery between August 2009 and April 2011 were analyzed retrospectively. RESULTS: The operative procedures of 156 patients were completed successfully and 1 case was converted to laparotomy (0.6%). The mean operation time was (125 ± 35) minutes; the mean intraoperative blood loss was (118 ± 60) ml; the mean time of bowel function recovery was (60 ± 8) hours; the median postoperative hospital stay was (9.5 ± 2.2) days. The mean number of lymph nodes dissection was (14 ± 5). Five patients (3.2%) had postoperative complications. All the patients were followed up. There had been no local recurrence or trocar site implantation metastasis. CONCLUSION: Hand-assisted laparoscopic surgery approach for the curative resection of rectal cancer is safe and effective and has broad prospects in clinical application.
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Laparoscopía/métodos , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To observe the effect of scalp acupuncture on the expression of argarginine vasopressin receptor-1a(V1aR), phosphorylated calmodulin-dependent protein kinase â ¡(p-CaMKâ ¡), and aquaporin 4(AQP4) at hypothalamus in middle cerebral artery occlusion (MCAO) rats, so as to explore the molecular mechanisms of scalp acupuncture reducing encepha-ledema in acute ischemic stroke. METHODS: A total of 96 male SD rats were randomly divided into normalï¼ model, inhibitor and scalp acupuncture groups, with 24 rats in each group. The MCAO model was established by thread occlusion method. The inhibitor group was intraperitoneally injected with V1aR inhibitor (30 µg/kg)ï¼once a day for 7 consecutive days. In the scalp acupuncture group, acupuncture was applied to bilateral "parietal and temporal anterior oblique line", with rapid insertion of 2 needles at 15° to 20°, twisting at 100 r/min for 1 min, and retaining the needles for 30 min, once a day for 7 consecutive days. The neurologic deficit score (NDS) and neurological score (NS) were evaluated before and after intervention. The positive expression of p-CaMKâ ¡ and AQP4 proteins in hypothalamus was detected by immunohistochemistry. The water content of left brain tissue was determined by BIIiot method. The expression of V1aR mRNA in hypothalamus was detected by real-time PCR. RESULTS: Compared with the normal group, the NDS, NS, hypothalamic V1aR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKâ ¡ and AQP4 positive expression levels were significantly increased (P<0.01) in the model group. Compared with the model group, the NDS, NS, hypothalamic V1aR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKâ ¡ and AQP4 positive expression levels were significantly decreased (P<0.01) in the inhibitor and scalp acupuncture groups. CONCLUSION: Regulating the signaling pathway of V1aR/CaMKâ ¡/AQP4 in hypothalamus may be one of the molecular mechanisms of scalp acupuncture reducing encephaledema in acute ischemic stroke.
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Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Animales , Masculino , Ratas , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Infarto Cerebral , Hipotálamo , Ratas Sprague-Dawley , ARN Mensajero , Cuero Cabelludo , Transducción de Señal , AguaRESUMEN
As a neurological disease with high morbidity, disability, and mortality, the pathological mechanism underlying stroke involves complex processes such as neuroinflammation, oxidative stress, apoptosis, autophagy, and excitotoxicity; but the related research on these molecular mechanisms has not been effectively applied in clinical practice. As a form of iron-dependent regulated cell death, ferroptosis was first discovered in the pathological process of cancer, but recent studies have shown that ferroptosis is closely related to the onset and development of stroke. Therefore, a deeper understanding of the relationship between ferroptosis and stroke may lead to more effective treatment strategies. Herein, we reviewed the mechanism(s) underlying the onset of ferroptosis in stroke, the potential role of ferroptosis in stroke, and the crosstalk between ferroptosis and other pathological mechanisms. This will further deepen our understanding of ferroptosis and provide new approaches to the treatment of stroke.
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OBJECTIVE: To observe the impact of electro-scalp acupuncture (ESA) on the neural function and inflammatory response of ischemic cortex in the model rats with ischemic stroke and explore the anti-inflammation mechanism of ESA in treatment of ischemic stroke from the perspective of modulating the interleukin 12 (IL-12) mediated JAK (Janus kinase)/STAT (signal transduction and transcription activator) signal pathway. METHODS: Ninety male SD rats were randomized into a normal group (n =16) and a model preparation group (n=74). In the model preparation group, the model of middle cerebral artery occlusion (MCAO) was duplicated with suture-occlusion method. After modeled successfully, 48 rats with neurological deficit score of 1-3 were divided into a model group, an inhibitor group and an ESA group, 16 rats in each one. In the inhibitor group, IL-12 inhibitor (apilimod, 5 mg/kg) was used via intragastric administration. In the ESA group, the anterior oblique line of vertex-temporal (MS6) was stimulated bilaterally with electric acupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in current intensity. The needles were retained for 30 min. The treatment was given once daily and for 7 days in above two intervention groups. Before and after intervention, the neurological deficit score (NDS) and neurobehavioral score (NBS) were assessed in each group. HE staining method was adopted to observe the morphological manifestations of ischemic cortical lesion; the concentrations of IL-12 and IL-12R of the brain tissue in the ischemic cortical lesion were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of STAT4 and Tbx21 were detected by real-time PCR technique; and the protein expression of IL-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-4 were detected using immunohistochemistry. RESULTS: NDS and NBS in the model group, the inhibitor group and the ESA group were all higher than those in the normal group before intervention (P<0.01). After intervention, NDS and NBS in the model group were higher than the normal group (P<0.01); the two scores were all reduced when compared with those before intervention in the inhibitor group and the ESA group (P<0.01), and lower than those of the model group (P<0.01). NDS in the ESA group was lower than the inhibitor group (P<0.05). In the model group, the cells were shrunk and vacuolated in the ischemic cortical lesion. Many normal cells were visible in the ESA group and the inhibitor group. Compared with the normal group, the concentrations of IL-12 and IL-12R , the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in brain tissue of ischemic cortical lesion were all increased in the model group (P<0.01), while the protein expression level of IL-4 decreased (P<0.01). The concentrations of IL-12 and IL-12R, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ were all reduced (P<0.01), while the protein expression level of IL-4 increased (P<0.01) in the ESA group and the inhibitor group when compared with the model group. The concentration of IL-12, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in the ESA group were all higher than those of the inhibitor group (P<0.05); while the concentration of IL-12R and the protein expression level of IL-4 were lower than the inhibitor group (P<0.05). CONCLUSION: Electro-scalp acupuncture may improve the neurological function of the rats with ischemic stroke. The modulation to IL-12 mediated JAK/STAT signaling pathway is the potential molecular mechanism of this therapy for the inflammatory response in ischemic cortical lesion.
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Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Cuero Cabelludo/metabolismo , Interleucina-2 , Interleucina-4 , Quinasas Janus/genética , Quinasas Janus/metabolismo , Transducción de Señal , Interleucina-12 , ARN MensajeroRESUMEN
BACKGROUND: Obesity is associated with an increased risk of developing Crohn's disease (CD), higher disease activity, and comparatively worse clinical outcomes. AIM: To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals. METHODS: First, we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis. We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in mesenteric adipose tissue-derived exosomes and the colon. Next, we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6 (ATF6) axis. Finally, we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid (TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways. RESULTS: High-fat diet was found to aggravate TNBS-induced colitis in mice. The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased. The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway. This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p. CONCLUSION: Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice, which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.
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Colitis , Exosomas , MicroARNs , ARN Largo no Codificante , Factor de Transcripción Activador 6 , Tejido Adiposo/metabolismo , Animales , Colitis/inducido químicamente , Colitis/complicaciones , Colitis/genética , Dieta Alta en Grasa/efectos adversos , Exosomas/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Obesidad/metabolismo , ARN Largo no Codificante/metabolismoRESUMEN
BACKGROUND: Irritable bowel syndrome (IBS) is a common functional bowel disease that shares features with many organic diseases and cannot be accurately diagnosed by symptom-based criteria. Alarm symptoms have long been applied in the clinical diagnosis of IBS. However, no study has explored the predictive value of alarm symptoms in suspected IBS patients based on the latest Rome IV criteria. AIM: To investigate the predictive value of alarm symptoms in suspected IBS patients based on the Rome IV criteria. METHODS: In this multicenter cross-sectional study, we collected data from 730 suspected IBS patients evaluated at 3 tertiary care centers from August 2018 to August 2019. Patients with IBS-like symptoms who completed colonoscopy during the study period were initially identified by investigators through medical records. Eligible patients completed questionnaires, underwent laboratory tests, and were assigned to the IBS or organic disease group according to colonoscopy findings and pathology results (if a biopsy was taken). Independent risk factors for organic disease were explored by logistic regression analysis, and the positive predictive value (PPV) and missed diagnosis rate were calculated. RESULTS: The incidence of alarm symptoms in suspected IBS patients was 75.34%. Anemia [odds ratio (OR) = 2.825, 95% confidence interval (CI): 1.273-6.267, P = 0.011], fecal occult blood [OR = 1.940 (95%CI: 1.041-3.613), P = 0.037], unintended weight loss (P = 0.009), female sex [OR = 0.560 (95%CI: 0.330-0.949), P = 0.031] and marital status (P = 0.030) were independently correlated with organic disease. The prevalence of organic disease was 10.41% in suspected IBS patients. The PPV of alarm symptoms for organic disease was highest for anemia (22.92%), fecal occult blood (19.35%) and unintended weight loss (16.48%), and it was 100% when these three factors were combined. The PPV and missed diagnosis rate for diagnosing IBS were 91.67% and 74.77% when all alarm symptoms were combined with Rome IV and 92.09% and 34.10% when only fecal occult blood, unintended weight loss and anemia were combined with Rome IV, respectively. CONCLUSION: Anemia, fecal occult blood and unintended weight loss have high predictive value for organic disease in suspected IBS patients and can help identify patients requiring further examination but are not recommended as exclusion criteria for IBS.
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BACKGROUND: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) is a safe and accurate technique to confirm the diagnosis of pancreatic cancers. Recently, numerous studies comparing the diagnostic efficacy of smear cytology (SC) and liquid-based cytology (LBC) for pancreatic lesions yielded mixed results. AIM: To compare and identify the better cytology method for EUS-FNA in pancreatic lesions. METHODS: A comprehensive search of PubMed, Embase, and Cochrane was undertaken through July 18, 2020. The primary endpoint was diagnostic accuracy (sensitivity and specificity). Secondary outcomes included sample adequacy and post procedure complications. In addition, factors affecting diagnostic efficacy were discussed. RESULTS: Data on a total of 1121 comparisons from 10 studies met the inclusion criteria. Pooled rates of sensitivity for SC and LBC were 78% (67%-87%) vs 75% (67%-81%), respectively. In any case, both SC and LBC exhibited a high specificity close to 100%. Inadequate samples more often appeared in LBC compared with SC. However, the LBC samples exhibited a better visual field than SC. Very few post procedure complications were observed. CONCLUSION: Our data suggested that for EUS-FNA in pancreatic lesions (particularly solid lesions), SC with Rapid On-Site Evaluation represents a superior diagnostic technique. If Rapid On-Site Evaluation is unavailable, LBC may replace smears. The diagnostic accuracy of LBC depends on different LBC techniques.