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IL-33 has been associated with pro- and anticancer functions in cancer. However, its role in pancreatic cancer metastasis remains unknown. This study aimed to explore the role of miR-548t-5p/IL-33 axis in the metastasis of pancreatic cancer. Luciferase activity assay, qRT-PCR, Western blot and ELISA were performed to prove whether IL-33 is the target of miR-548t-5p. In vivo metastasis assay and cellular transwell assay were performed to explore the role of miR-548t-5p/IL-33 axis in the invasion and metastasis of pancreatic cancer. Co-culture experiments and immunohistochemistry were performed to observe whether IL-33 affects cell invasion and metastasis dependent on the involvement of M2 macrophages. THP-1 cell induction experiment and flow cytometry were performed to explore the effect of IL-33 on macrophage polarization. CCK-8, colony formation, cell apoptosis, cell cycle, cell wound healing and transwell assay were performed to investigate the effect of IL-33 induced M2 macrophages on cell malignant biological behavior by coculturing pancreatic cancer cells with the conditioned medium (CM) from macrophages. We found that miR-548t-5p regulated the expression and secretion of IL-33 in pancreatic cancer cells by directly targeting IL-33 mRNA. IL-33 secreted by cancer cells promoted the recruitment and activation of macrophages to a M2-like phenotype. In turn, IL-33 induced M2 macrophages promoted the migration and invasion of cancer cells. Moreover, IL-33 affected pancreatic cancer cell invasion dependent on the involvement of M2 macrophages in the co-culture system. Thus, our study suggested that manipulation of this IL-33-dependent crosstalk has a therapeutic potential for the treatment of pancreatic cancer metastasis.

Asunto(s)

Carcinoma Ductal Pancreático , Regulación Neoplásica de la Expresión Génica , Interleucina-33 , Macrófagos , MicroARNs , Neoplasias Pancreáticas , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Interleucina-33/metabolismo , Interleucina-33/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Macrófagos/metabolismo , Animales , Línea Celular Tumoral , Metástasis de la Neoplasia , Movimiento Celular/genética , Invasividad Neoplásica , Ratones , Apoptosis/genética , Técnicas de Cocultivo , Ratones Desnudos , Proliferación Celular/genética , Células THP-1

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The skin secretion of Andrias davidianus (SSAD) is a novel biological adhesive raw material under development. This material exhibits robust adhesion while maintaining the flexibility of the wound. It also has the potential for large-scale production, making it promising for practical application explore. Hence, in-depth research on methods to fine-tune SSAD properties is of great importance to promote its practical applications. Herein, we aim to enhance the adhesive and healing properties of SSAD by incorporating functional components. To achieve this goal, we selected 3,4-dihydroxy-l-phenylalanine and vaccarin as the functional components and mixed them with SSAD, resulting in a new bioadhesive, namely, a formulation termed "enhanced SSAD" (ESSAD). We found that the ESSAD exhibited superior adhesive properties, and its adhesive strength was improved compared with the SSAD. Moreover, ESSAD demonstrated a remarkable ability to promote wound healing. This study presents an SSAD-based bioadhesive formulation with enhanced properties, affirming the feasibility of developing SSAD-based adhesive materials with excellent performance and providing new evidence for the application of SSAD. This study also aims to show that SSAD can be mixed with other substances, and addition of effective components to SSAD can be studied to further adjust or improve its performance.

Asunto(s)

Adhesivos Tisulares , Cicatrización de Heridas , Humanos , Adhesivos/farmacología , Piel , Adhesivos Tisulares/farmacología , Adherencias Tisulares , Moco , Hidrogeles

RESUMEN

The abnormal accumulation of fused in sarcoma (FUS) is a pathological hallmark in a proportion of patients with frontotemporal dementia and amyotrophic lateral sclerosis. Therefore, the clearance of FUS aggregates is a possible therapeutic strategy for FUS-associated neurodegenerative diseases. This study reports that curcumin can strongly suppress FUS droplet formation and stress granule aggregation of FUS. Fluorescence spectra and isothermal titration calorimetry showed that curcumin can bind FUS through hydrophobic interactions, thereby reducing the ß-sheet content of FUS. Aggregated FUS sequesters pyruvate kinase, leading to reduced ATP levels. However, results from a metabolomics study revealed that curcumin changed the metabolism pattern and differentially expressed metabolites were enriched in glycolysis. Curcumin attenuated FUS aggregation-mediated sequestration of pyruvate kinase and restored cellular metabolism, consequently increasing ATP levels. These results indicate that curcumin is a potent inhibitor of FUS liquid-liquid phase separation and provide novel insights into the effect of curcumin in ameliorating abnormal metabolism.

Asunto(s)

Curcumina , Demencia Frontotemporal , Sarcoma , Humanos , Piruvato Quinasa/genética , Piruvato Quinasa/metabolismo , Curcumina/farmacología , Demencia Frontotemporal/metabolismo , Adenosina Trifosfato , Mutación , Proteína FUS de Unión a ARN/química , Proteína FUS de Unión a ARN/genética , Proteína FUS de Unión a ARN/metabolismo

RESUMEN

The biological effects of magnetic fields (MFs) have been a controversial issue. Fortunately, in recent years, there has been increasing evidence that MFs do affect biological systems. However, the physical mechanism remains unclear. Here, we show that MFs (16 T) reduce apoptosis in cell lines by inhibiting liquid-liquid phase separation (LLPS) of Tau-441, suggesting that the MF effect on LLPS may be one of the mechanisms for understanding the "mysterious" magnetobiological effects. The LLPS of Tau-441 occurred in the cytoplasm after induction with arsenite. The phase-separated droplets of Tau-441 recruited hexokinase (HK), resulting in a decrease in the amount of free HK in the cytoplasm. In cells, HK and Bax compete to bind to the voltage-dependent anion channel (VDAC I) on the mitochondrial membrane. A decrease in the number of free HK molecules increased the chance of Bax binding to VDAC I, leading to increased Bax-mediated apoptosis. In the presence of a static MF, LLPS was marked inhibited and HK recruitment was reduced, resulting in an increased probability of HK binding to VDAC I and a decreased probability of Bax binding to VDAC I, thus reducing Bax-mediated apoptosis. Our findings revealed a new physical mechanism for understanding magnetobiological effects from the perspective of LLPS. In addition, these results show the potential applications of physical environments, such as MFs in this study, in the treatment of LLPS-related diseases.

RESUMEN

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Asunto(s)

COVID-19 , Enfermedades Neurodegenerativas , Humanos , Proteínas Amiloidogénicas , Péptidos beta-Amiloides/química , Amiloide/metabolismo

RESUMEN

Regulator of G-protein signaling 22 (RGS22) is specifically expressed in the testis and in tumors of epithelial origin, but the expression and role of RGS22 in pancreatic cancer are unclear. In this study, 52 pairs of pancreatic ductal adenocarcinoma (PDAC) and adjacent non-neoplastic tissue samples with the corresponding clinical data were used to examine the expression of RGS22 and its relationship with PDAC prognosis. The findings showed that the expression of RGS22 was higher in the PDAC tissues than in the adjacent non-tumorous tissues and its expression was associated with the degree of blood vessel invasion. The in vitro experiments with PDAC cell lines and a normal control cell line showed that the proliferation, invasion, and metastasis of PDAC cells were suppressed by RGS22 overexpression and enhanced by RGS22 knockdown. The in vivo effect of RGS22 on PDAC xenografts was studied using subcutaneous implantation of tumor cells in BALB/cA-nu mice, and the results corroborated the in vitro findings. Analysis of the regulators of RGS22 showed that it was positively regulated by the transcription factor Yin Yang-1 (YY1). Thus, YY1-mediated RGS22 regulation suppressed the proliferation, migration, and invasion of PDAC.

RESUMEN

Staphylococcus aureus (S. aureus) infection, especially its drug-resistant bacterial infection, is a great challenge often faced by clinicians and patients, and it is also one of the most important threats to public health. Finding a safe and effective antibacterial agent is of great significance for the prevention and treatment of S. aureus infection. Lysozyme is known to have antibacterial effects against Gram-positive bacteria including S. aureus. Here, high-quality lysozyme with a purity of more than 99% and an activity of more than 60, 000 U/mg was prepared from egg white, which showed excellent antibacterial activity against three strains of S. aureus, especially against MRSA. Furthermore, an antibacterial cream loaded with lysozyme was prepared and tested in scald wound healing. The lysozyme-loaded cream exhibited the effect of preventing wound infection and promoting wound healing on scalds, and no toxicity was found in animal organs. Overall, lysozyme showed great application potential in the prevention and treatment of infections caused by S. aureus and scalded wound healing. The most remarkable discovery in this work is the unexpectedly powerful inhibitory effect of lysozyme on the drug-resistant bacterial, especially MRSA, which is usually very difficult to deal with using normal antibacterial drugs.

Asunto(s)

Quemaduras , Fármacos Dermatológicos , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Animales , Staphylococcus aureus , Pruebas de Sensibilidad Microbiana , Muramidasa/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Cicatrización de Heridas , Fármacos Dermatológicos/farmacología , Quemaduras/tratamiento farmacológico

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Objective: In order to explore the mechanism of neonatal spontaneous breathing, the difference of oxygen and carbon dioxide between umbilical cord arteries and veins before the start of spontaneous breathing after birth has been analyzed among people. In this part, the related information is analyzed individually. Methods: After all fetal parents signed the informed consent before birth, and before the newborn was born and did not breathe, the umbilical cord was exposed as quickly as possible, and the heparinized arterial indwelling needle was inserted into the umbilical artery and umbilical vein in the direction of newborn and placenta, and then blood was taken continuously. Although dozens of mothers were selected,but only 3 cases were collected from Pua and Puv blood samplers at the same time for blood gas analysis and determination, and the differences and dynamic changes of umbilical vein and umbilical artery were calculated and analyzed. Results: In all 3 none spontaneous breathing newborns,PuvO2 was significantly higher than PuaO2 at the same time (P<0.01), with an average difference of (24.17±7.09) mmHg; while PuvCO2 was significantly lower than PuaCO2 (all P<0.01), with an average difference of (-7.67±3.70) mmHg.The difference of Puv-uaO2 was significantly higher than those of Puv-uaCO2 (P<0.05). Conclusion: PuaO2 decreases gradually with time (heartbeat frequency) before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

Asunto(s)

Dióxido de Carbono , Arterias Umbilicales , China , Femenino , Humanos , Recién Nacido , Oxígeno , Presión Parcial , Embarazo

RESUMEN

Objective: The objective is to find the characteristics of arterial blood sample waveform in different respiration models. Methods: Six post-operative patients with normal heart function and negative Allen test, were 4 male and 2 female, (59.00±16.64)year, (71.67±0.37)kg, left ventricular ejection fraction(LVEF) (61.33±2.16)%, had been placed the arterial catheterization and central venous catheterization for continuous collecting arterial in 3 different kinds of respiration models: normal breathing, no breathing and deep breathing. We selected two breaths cycles of waveform from each patient for data calculations of magnitudes and time interval. Compare the adjacent highest and lowest values of patients to verify whether there are periodic wave-like signal changes in arterial and venous blood gas in the three breathing states. In addition, statistical t-test analysis was performed on the change amplitude of the periodic wave-like signal of the patient's arterial and venous blood gas to compare whether there is a difference. Results: The heart beat numbers for drawing blood into pipe were 15-16, and all covered more than 2 breathing cycles. There were significant changes of arterial PaO2 (i.e. the highest high values compare to the next lowest values, P<0.05) in three different breathing models(normal, no breathing and high breathing), the magnitudes of which were (9.96±5.18)mmHg, (5.33±1.55)mmHg and (13.13±7.55)mmHg, with (8.09±2.43)%, (5.29±2.19)% and (10.40±2.68)% from their mean respectively. PO2 in venous blood gas did not show wavy changes under normal breathing, 20 s breath holding and high tidal volume ventilation. The amplitudes were (1.63 ± 0.41) mmHg, (1.13 ± 0.41) mmHg and (1.31 ± 0.67) mmHg, which were (3.91 ± 1.22)%, (2.92 ± 1.12)%, (3.33 ± 1.81)%, respectively, which were significantly lower than that of arterial blood gas under the same state, but there was no significant difference between groups. Conclusion: With continuous beat-by-beat arterial blood sampling and ABG analyzing method in three different breathing models, We obtain a clear evidence of the biggest periodic parameters ABG waveform in high breathing models, which followed by normal breathing models, no breathing was the smallest, and the wave variation amplitude of venous oxygen partial pressure was not obvious in the three respiratory states, which implies the oscillatory information of the arterial blood with comes from the gas exchanging in the lung.

Asunto(s)

Respiración , Función Ventricular Izquierda , Análisis de los Gases de la Sangre , Femenino , Humanos , Masculino , Volumen Sistólico , Volumen de Ventilación Pulmonar

RESUMEN

Objective: The fetus has no actual respiration, and the newborn begins to breathe after birth. We assume that the first breath dominantly generated by hypoxia. In this study, the changes and lowest limit of blood oxygen partial pressureof umbilical artery (PuaO2) after chemoreceptor were analyzed to explore the mechanism of neonatal spontaneous breathing. Methods: With signed consent form by all fetal parents before birth, 14 newborns successfully completed the umbilical artery or vein catheterization and drawn blood according to the heartbeat. All blood samples analyzed by blood gas analyzer,calculated and analyzed the similarities and differences between umbilical vein(Puv) and umbilical artery(Pua). Results: Although we completed 14 newborns, there were only 9 cases of umbilical artery samples and 8 cases of umbilical vein samples were collected. Only 3 cases collected both Pua and Puv blood samples at the same time (see serial paper II). PuaO2 in gradually decreased with time (heartbeat frequency), until Pua contracted after spontaneous breathing produced about 8~10 heartbeats, and then could not get enough blood samples. Only 3 newborns were able to take blood samples after spontaneous breathing for 8~10 heartbeats, and their PuaO2 were jumped to 186.0, 137.0 and 93.8 mmHg respectively. The mean value of PuaO2 was (25.94±6.79, 18.04~37.51)mmHg, the highest value was (29.11±6.46, 23.00~45.90)mmHg, and the lowest value was (21.34±5.54, 14.00~33.60)mmHg. Although PuvO2 decreased gradually with time (heartbeat) too, most of them also showed the tendency of alternately rising and falling with the regularity of mother's respiration. The mean value of PuvO2 was (53.35±21.35, 32.56~100.73)mmHg, the highest value was (90.38±48.44, 43.40~153.00)mmHg, and the lowest value was (36.96±14.90, 24.80~73.80)mmHg. Although there were large individual differences, the mean, highest and lowest values of PuvO2 were significantly higher than those of PuaO2 (P<0.05); although PuvCO2 slightly lower than PuaCO2, it was no significant difference (P>0.05). Conclusion: PuaO2 decreases gradually with time before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

Asunto(s)

Dióxido de Carbono , Arterias Umbilicales , China , Humanos , Recién Nacido , Oxígeno , Presión Parcial

RESUMEN

Objective: The arterial blood with the oscillatory information comes from the right heart system after gas exchanging in the lung. However, the evidence of the waveform of venous ABG is lack. The objectives of this article are to compare the different information between arterial and venous beat-by-beat blood sample at the same time. Methods: Six post-operative patients with normal heart function and negative Allen test, had been placed the arterial catheterization and central venous catheterization directly connected to pre-heparin plasticpipes for continuous collecting arterial and venous blood. We twisted the 2 pipes into helix formation. After drawing arterial and venous blood with syringes in one heart beat with one helix at the same time, totally 15 heart beats, clipping the pipes with forceps, we put the helix pipe into icedwater at once and analyses PaO2, PaCO2, pH and SaO2 as soon as possible. We selected two breathscycles of waveform from each patient for data calculations of magnitudes and time interval. Results: The heart beat numbers for drawing blood into pipe were 15~16, and all covered more than 2 breathing cycles. There were significant changes of arterial PaO2(i.e. the highest high values compare to the next lowestvalues, P<0.05), but no significant changes in venous blood(P>0.05). The magnitudes of changing PaO2 in arterial and venous blood sample were (9.96±5.18)mmHg and (1.63±0.41)mmHg with significant variance(P=0.010), and they were (8.09±2.43)% and (3.91±1.22)%from their mean with significant variance(P=0.009) respectively. Conclusion: With continuous beat-by-beat arterial and venous blood sampling and ABG analyzing method at the same time, we obtain a clear evidence of periodic parameters ABG waveform, which following breathing cycle, but no clear ABG waveform of the periodic parameters in the venous blood samples, which implies the oscillatory information of the arterial blood with comes from the gas exchanging in the lung.

Asunto(s)

Arterias , Cuerpo Humano , Análisis de los Gases de la Sangre , Humanos , Respiración , Venas

RESUMEN

Objective: To observe the effect of healthy volunteers different work rate increasing rate cardiopulmonary exercise test (CPET) on the peak exercise core indicators and the changes of respiratory exchange rate (RER) during exercise, to explore the effect of different work rate increasing rate on CPET peak exercise related indicators. Methods: Twelve healthy volunteers were randomly assigned to a moderate (30 W/min), a relatively low (10 W/min) and relatively high (60 W/min) three different work rate increasing rate CPET on different working days in a week. The main peak exercise core indicators of CPET data: VO2, VCO2, work rate (WR), breathe frequency(Bf), tidal volume (VT), ventilation (VE), heart rate (HR), blood pressure (BP), Oxygen pulse(O2P), exercise time and RER for each period of CPET were analyzed using standard methods. The ANOVA test and paired two-two comparison was performed on the difference of each index in the three groups of different work rate increasing rate. Results: Compared with the moderate work rate group, the peak work rate of the lower and higher work rate groups were relatively lower and higher, respectively ((162.04±41.59) W/min vs (132.92±34.55) W/min vs (197.42±46.14) W/min, P<0.01); exercise time was significantly prolonged and shortened ((5.69 ± 1.33) min vs (13.49 ± 3.43) min vs (3.56 ± 0.76) min, P<0.01); peak RER (1.27 ± 0.07 vs 1.18 ± 0.06 vs 1.33 ± 0.08, P<0.01~P<0.05) and the recovery RER maximum (1.72±0.16 vs 1.61±0.11 vs 1.81±0.14, P<0.01~P<0.05) were significantly decreased and increased. Conclusion: Different work rate increasing rate of CPET significantly change the Peak Work Rate, exercise time, Peak RER, and maximum RER during recovery. The CPET operator should choose an individualized work rate increasing rate that is appropriate for the subject, and also does not use a fixed RER value as a basis for ensuring safety, the subject's extreme exercise, and early termination of exercise.

Asunto(s)

Prueba de Esfuerzo , Insuficiencia Cardíaca , Ejercicio Físico , Frecuencia Cardíaca , Humanos , Consumo de Oxígeno

RESUMEN

Objective: To observe the effect of healthy volunteers different work rate increasing rate cardiopulmonary exercise testing (CPET) on the sub-peak parameters . Methods: Twelve healthy volunteers were randomly assigned to a moderate (30 W/min), a relatively low (10 W/min) and relatively high (60 W/min) three different work rate increasing rate CPET on different working days in a week. The core indicators related to CPET sub-peak exercise of 12 volunteers were compared according to standard Methods: anaerobic threshold (AT), oxygen uptake per unit power (ΔVO2/ΔWR), oxygen uptake eficiency plateau,（OUEP), the lowest average of 90 s of carbon dioxide ventilation equivalent (Lowest VE/ VCO2), the slope of carbon dioxide ventilation equivalent (VE/ VCO2 Slope) and intercept and anaerobic threshold oxygen uptake ventilation efficiency value (VO2/ VE@AT) and the anaerobic threshold carbon dioxide ventilation equivalent value (VE/ VCO2@AT). Paired t test was performed on the difference of each parameter in the three groups of different work rate increasing rate. Results: Compared with the relatively low and relatively high work rate increasing rate group, the moderate work rate increasing rate group uptake eficiency plateau, (42.22±4.76 vs 39.54±3.30 vs 39.29±4.29) and the lowest average of 90 s of carbon dioxide ventilation equivalent (24.13±2.88 vs 25.60±2.08 vs 26.06±3.05) was significantly better, and the difference was statistically significant (P<0.05); Compared with the moderate work rate increasing rate group, the oxygen uptake per unit work rate of the relatively low and relatively high work rate increasing rate group increased and decreased significantly ((8.45±0.66 vs 10.04±0.58 vs 7.16±0.60) ml/(min·kg)), difference of which was statistically significant (P<0.05); the anaerobic threshold did not change significantly ((0.87±0.19 vs 0.87±0.19 vs 0.89±0.19) L/min), the difference was not statistically significant (P>0.05). Conclusion: Relatively low and relatively high power increase rate can significantly change the CPET sub-peak sports related indicators such as the effectiveness of oxygen uptake ventilation, the effectiveness of carbon dioxide exhaust ventilation, and the oxygen uptake per unit work rate. Compared with the moderate work rate increasing rate CPET, the lower and higher work rate increasing rate significantly reduces the effectiveness of oxygen uptake ventilation and the effectiveness of carbon dioxide exhaust ventilation in healthy individuals. The standardized operation of CPET requires the selection of a work rate increasing rate suitable for the subject, so that the CPET sub-peak related indicators can best reflect the true functional state of the subject.

Asunto(s)

Prueba de Esfuerzo , Consumo de Oxígeno , Umbral Anaerobio , Humanos , Intercambio Gaseoso Pulmonar , Ventilación Pulmonar

RESUMEN

Objective: The new theory of holistic integrative physiology and medicine, which describes the integrative regulation of respiratory, circulatory and metabolic systems in human body, generates the hypothesis of that breath is the origin of variability of circulatory parameters. We investigated the origin of heart rate variability by analyzing relationship between the breath and heart rate variability (HRV) during sleep. Methods: This retrospective study analyzed 8 normal subjects (NS) and 10 patients of chronic diseases without sleep apnea (CDs-no-SA). After signed the informed consent form, they performed cardiopulmonary exercise testing (CPET) in Fuwai Hospital and monitored polysomnography (PSG) and electrocardiogram (ECG) during sleep since 2014. We dominantly analyzed the correlation between the respiratory cycle during sleep and the heart rate variability cycle of the ECG R-R interval. The HRV cycle included the HR increase from the lowest to the highest and decrease from the highest to the lowest point. The number of HRV (HRV-n), average HRV time and other parameters were calculated. The breath cycle included complete inhalation and subsequent exhalation. The number of breath (B-n), average breath time and other breath parameters were analyzed and calculated. We analyzed each person's relationship between breath and HRV; and the similarities and differences between the NS and CDs-no-SA groups. Independent sample t test was used for statistical analysis, with P<0.05. Results: CPET core parameter such as Peak VO2 (83.8±8.9)% in NS were significantly higher than that (70.1±14.9)% in patients of chronic diseases without sleep apnea (P<0.05), but there was no difference between their AHI (1.7±1.3) in NS and AHI (2.9±1.2) in CDs-no-SA (P>0.05). The B-n and the HRV-n (6581.63±1411.90 vs 6638.38±1459.46), the average B time and the average HRV time (4.19±0.57)s vs (4.16±0.62)s in NS were similar without significant difference (P>0.05). The comparison of the numbers in CDs-no-SA were the number (7354.50±1443.50 vs 7291.20±1399.31) and the average times ((4.20±0.69)s vs (4.23±0.68)s) of B and HRV were similar without significant difference (P>0.05). The ratios of B-n/HRV-n in NS and CDs-no-SA were (0.993±0.027 vs 1.008±0.024) and both were close to 1 and similar without significant difference (P>0.05). The average magnitude of HRV in NS ((5.74±3.21) bpm) was significantly higher than that in CDs-no-SA ((2.88±1.44) bpm) (P<0.05). Conclusion: Regardless of the functional status of NS and CDs-no-SA, there is a similar consistency between B and HRV. The origin of initiating factors of HRV is the respiration.

Asunto(s)

Síndromes de la Apnea del Sueño , Enfermedad Crónica , Frecuencia Cardíaca , Humanos , Estudios Retrospectivos , Sueño

RESUMEN

Objective: Based on the hypothesis that respiration causes variability of circulatory indicators proposed by the holistic integrated physiology and medicine theory, the correlation between respiration and heart rate variability during sleep in chronically ill patients with abnormal sleep breathing is analyzed. Methods: Eleven chronically ill patients with abnormal sleep breathing and apnea-hypopnea index (AHI) ≥15 times/hr are recruited. After signing the informed consent, they completed the standardized symptomatic restrictive extreme exercise cardiopulmonary exercise testing (CPET) and sleep breathing monitoring Calculate and analyze the rules of respiratory nasal airflow and ECG RR interval heart rate variability during the oscillatory breathing (OB) phase and the normal steady breathing phase of the patient during sleep, and use the independent sample t test to compare with normal people and no sleep breathing abnormalities in the same period in this laboratory. Of patients with chronic diseases are more similar and different. Results: The peak oxygen uptake and anaerobic threshold (AT) of CPET in chronic patients with abnormal sleep apnea were (70.8±13.6)% Pred and (71.2±6.1)% Pred; 5 cases of CPET had exercise induced oscillatory breathing (EIOB), 6 An example is unstable breathing, which indicates that the overall functional status is lower than normal. In this group of patients with chronic diseases, AHI (28.8±10.0) beats/h, the ratio of the total time of abnormal sleep breathing to the total time of sleep (0.38±0.25); the length of the OB cycle (51.1±14.4)s. The ratio (Bn/HRV-B-n) of the number of breathing cycles in the normal and steady breathing period to the number of heart rate variability cycles in this group of patients with chronic diseases is 1.00±0.04, and the CV (SD of HRV-B-M/x) is (0.33 ±0.11), blood oxygen saturation (SpO2) did not decrease significantly, the average amplitude of heart rate variability (HRV-B-M) of each respiratory cycle rhythm was (2.64±1.59) bpm, although it was lower than normal people (P<0.05) , But it was similar to chronic patients without sleep apnea (P>0.05). In this group of patients with chronic diseases, the ratio of the number of respiratory cycles to the number of heart rate variability cycles (OB-Bn/OB-HRV-B-n) during OB is (1.22±0.18), and the average amplitude of heart rate variability for each respiratory cycle rhythm in OB (OB -HRV-B-M) is (3.56±1.57)bpm and its variability (OB-CV = SD of OB-HRV-B-M/x) is (0.59±0.28), the average amplitude of heart rate variability in each OB cycle rhythm (OB-HRV-OB-M) is (13.75±4.25)bpm, SpO2 decreases significantly during hypoventilation during OB, and the average decrease in SpO2 during OB (OB-SpO2-OB-M) is (4.79±1.39)%. The OB-Bn/OB-HRV-B-n ratio, OB-HRV-OB-M and OB-SpO2-OB-M in the OB period are all significantly higher than the corresponding indicators in the normal stable breathing period Large (P<0.01). Although OB-HRV-B-M has no statistically significant difference compared with HRV-B-M in normal stable breathing period (P>0.05), its variability OB-CV is significantly increased (P<0.01). Conclusion: The heart rate variability of chronic patients with abnormal sleep breathing in the OB phase is greater than that of the normal stable breathing period. When the breathing pattern changes, the heart rate variability also changes significantly. The number of breathing cycles in the stable breathing period is equal to the number of heart rate variability cycles.The ratio is the same as that of normal people and chronically ill patients without sleep apnea, confirming that heart rate variability is respiratory origin; and the reduction of heart rate variability relative to the respiratory cycle during OB is directly caused by hypopnea or apnea at this time, and heart rate variability is also breathing source.

Asunto(s)

Síndromes de la Apnea del Sueño , Enfermedad Crónica , Frecuencia Cardíaca , Humanos , Polisomnografía , Respiración

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Objective: To verify that the cardiopulmonary exercise testing (CPET) performed by clinical subjects is the maximum extreme exercise, we designed The Max test（Max）during clinical CPET. We used Max to verify the accuracy of the quantitative CPET evaluation result, and whether it is feasible and safe to use the specific value of a certain index as the standard for stopping CPET. Methods: Two hundred and sixteen cases from Fuwai Hospital were selected during June 2017 to January 2019,including 41 healthy person（control group） and 175with cardiovascular diseases（patient group）,The patients had a CPET peak RER ≤ 1.10, or the peak heart rate and peak blood pressure were basically non-responsive.The Max was first attempted in 60 subjects,and this study is further expanded . When the CPET ended, they had a 5-minute break, then the Max, during which, they cycled with a velocity of ≥ 60 r/min, at a constant intensity equivalent to to 130% of peak work,until exhausted.The difference and percentage difference between the peak heart rate and the peak oxygen uptake were calculated. ①If the percentage difference of heart rate and oxygen uptake are all less than -10%,then the Max is defined as failure,otherwise it is succesful. 2 If the percentage difference is between -10%~10%, then the Max is successful, which proved that the CPET is precise.③If the difference is ≥10%, the Max is successful, which proves that the CPET is non-extreme exercise. Results: Patient group's Peak VO2(L/min,ml/(min·kg)),anaerobic threshold (L/min,ml/(min·kg),%pred),Peak VO2/HR(ml/beat, % pred),Peak RER,Peak SBP,Peak WR,peak heart rate,OUEP （ratio,%pred） were lower than those of the control group(P<0.05)．The VE/ VCO2 Slope （ratio,%pred）and Lowest VE/ VCO2（ratio,%pred） were higher in the patient group than in the control group (P<0.05)．No adverse events occurred during the CPET and Max in all cases. Among the 216 cases,Max was successful in 198 cases(91.7%)．CPET was proved to be maximum extreme exercise for 182 cases,non-maximum extreme exercise for 16 cases,and failed in 18 cases(8.3%)．Conclusion: For CPET with a low peak RER and a maximum challenge,the Max can confirm the accuracy of the objective quantitative assessment of CPET. Max is safe and feasible,and that deserved further research and clinical application.

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Prueba de Esfuerzo , Insuficiencia Cardíaca , Umbral Anaerobio , Ejercicio Físico , Humanos , Consumo de Oxígeno

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Objective: Cardiopulmonary exercise testing(CPET)was used to evaluate objectively and quantitatively the holistic function in patients accepted preoperative chemotherapy. Methods: This study investigated reliable objective and quantitative assessment methods of symptom limited maximal incremental CPET before and after chemotherapy in patients with 6 esophageal cancer. We re-analyzed the changes in cardiopulmonary, metabolism, and other functions physiologic parameters of CPET. Results: After patients accepted preoperative chemotherapy,Peak oxygen consumption (Peak VO2)(P<0.05), anaerobic threshold (AT) and peak oxygen pulse (Peak O2 paulse), oxygen uptake efficiency plateau (OUEP)were decreased (P<0.01). The lowest of ventilatory equivalent for carbon dioxide and slope of ventilatory equivalent for carbon dioxide were increased (P<0.05). For individual of all patients, except one patient's Peak VO2 and OUEP slightly increased,all of the above indicators were reduced in the remaining patients. The lowest of ventilatory equivalent for carbon dioxide and slope of ventilatory equivalent for carbon dioxide increased in all the patients,except one patient's slope of ventilatory equivalent for carbon dioxide decreased slightly. The heart rate of 6 patients showed an upward trend in each state, but there was no statistical difference. Three of the 6 patients had blood pressure measurement, and the other 3 patients had a significant decrease in diastolic blood pressure (P<0.05) except at extreme state.The patients had lower oxygen uptake at AT(P<0. 01) and extreme state (P<0. 05) than that before chemotherapy. The oxygen uptake efficiency in a warm-up state(P<0. 01),and an AT state(P<0. 05)after chemotherapy were lower than those before chemotherapy. The ventilator equivalent for carbon dioxide after chemotherapy was in the each states presented an upward trend, but only ventilator equivalent for carbon dioxide after in the warm-up state (P<0.05) and AT(P<0.01) had statistical significance. oxygen pulse in all four states showed a decreasing trend, and only at AT (P<0.05) showed a significant decrease.After chemotherapy,the PETCO2 in a warm-up state after chemotherapy was lower than that before chemotherapy(P<0. 05); the PETO2 in a quiescent state,a warm - up state,and an extreme state after chemotherapy were higher than those before chemotherapy;but there was nosignificant difference. Conclusion: The holistic functional capacity of patients with esophageal significantly decreased after 136 days chemotherapy. The circulatory functionalandentilator functional parameters significantly decreased after chemotherapy.

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Prueba de Esfuerzo , Terapia Neoadyuvante , Umbral Anaerobio , Frecuencia Cardíaca , Humanos , Consumo de Oxígeno

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BACKGROUND: The association between atrial fibrillation (AF) and the prognosis of intravenous thrombolysis (IVT) in patients with Acute Ischemic Stroke (AIS) is debated. Hypokalemia is highly prevalent in patients with AF. We aimed to investigate the effect of hypokalemia and AF on the prognosis of AIS patients following IVT. METHODS: AIS patients undergoing IVT were enrolled and divided into four groups: normokalemia and non-AF, normokalemia and AF, hypokalemia and non-AF, hypokalemia and AF. Logistic regression was applied to analyze the impact of hypokalemia, AF, and their combination on the prognosis of patients. RESULTS: The analysis included 567 patients, 184 with 3-month poor prognosis (modified Rankin Scale score of 3-6). Following adjustment of risk factors, hypokalemia and AF increased the risks for 3-month poor prognosis (adjusted Odds Ratios (aOR) = 4.97; 95% confidence interval (CI), 1.99-12.44, P =.001), early neurological deterioration (END) (aOR=7.98; 95% CI, 3.55-17.95, P <.001), 1-year poor prognosis (aOR=5.05; 95% CI, 1.99-12.81, P =.001), 1-year all-cause death (aOR =6.95; 95% CI, 2.35-20.56, P <.001). Patients with normokalemia and AF merely increased the risk of 1-year all-cause death (aOR=2.69; 95% CI, 1.10-6.61, P=.013). Patients with hypokalemia and non-AF were not associated with any poor prognosis. There were combined and interactive effects of hypokalemia with AF on the 3-month poor prognosis (P for interaction =.039) and END (P for interaction=.005). CONCLUSION: Hypokalemia and AF synergistically increased the risk of near-term poor prognosis, END, long-term poor prognosis, and all-cause death of AIS patients following IVT.

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Fibrilación Atrial , Isquemia Encefálica , Hipopotasemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Humanos , Hipopotasemia/complicaciones , Pronóstico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Resultado del Tratamiento

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Pancreatic tumors are classified into endocrine and exocrine types, and the clinical manifestations in patients are nonspecific. Most patients, especially those with pancreatic ductal adenocarcinoma (PDAC), have lost the opportunity to receive for the best treatment at the time of diagnosis. Although chemotherapy and radiotherapy have shown good therapeutic results in other tumors, their therapeutic effects on pancreatic tumors are minimal. A multifunctional transcription factor, Yin-Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a significant role in diverse tumors. Studies have shown that targeting YY1 can improve the survival time of patients with tumors. In this review, we focused on the mechanism by which YY1 affects the occurrence and development of pancreatic tumors. We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy. In addition, changes in the circadian network are a key causative factor of PDAC. YY1 promotes pancreatic clock progression and induces malignant changes, but YY1 seems to act as a tumor suppressor in PDAC and affects many biological behaviors, such as proliferation, migration, apoptosis and metastasis. Our review summarizes the progress in understanding the role of YY1 in pancreatic endocrine and exocrine tumors and provides a reasonable assessment of the potential for therapeutic targeting of YY1 in pancreatic tumors.

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DUOX2 has been reported to highly express in several types of cancers. However, the prognostic significance and the biological function of DUOX2 expression with pancreatic cancer (PC) still remain unclear. The present study is aimed at investigating whether DUOX2 could act as a novel biomarker of prognosis and evaluating its effect on PC cell progression. The mRNA and protein expression of DUOX2 in PC cells and tissues were assessed by quantitative real-time PCR (RT-qPCR) and immunohistochemistry. The effect of DUOX2 expression on PC cell motility and proliferation was evaluated in vitro. The correlation between DUOX2 mRNA expression and clinicopathological features and its prognostic significance were analyzed according to the Gene Expression Profiling Interactive Analysis (GEPIA) website based on The Cancer Genome Atlas (TCGA) and the GTEx databases combined with our clinical information. According to bioinformatics analysis, we forecasted the upstream transcription factors (TFs) and microRNA (miRNA) regulatory mechanism of DUOX2 in PC. The expression of DUOX2 at transcriptional and protein level was dramatically increased in PC specimens when compared to adjacent nontumor specimens. Functionally, DUOX2 knockdown inhibited cell motility and proliferation activities. Our clinical data revealed that the patients had better postoperative overall survival (OS) with lower expression of DUOX2, which is consistent with GEPIA data. Multivariate analysis revealed that high DUOX2 expression was considered as an independent prognostic indicator for OS (P = 0.031). Based on Cistrome database, the top 5 TFs of each positively and negatively association with DUOX2 were predicted. hsa-miR-5193 and hsa-miR-1343-3p targeting DUOX2 were forecasted from TargetScan, miRDB, and DIANA-TarBase databases, which were negatively correlated with OS (P = 0.043 and P = 0.0088, respectively) and DUOX2 expression (P = 0.0093 and P = 0.0032, respectively) in PC from TCGA data. These findings suggest that DUOX2 acts as a promising predictive biomarker and an oncogene in PC, which could be a therapeutic target for PC.

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Biomarcadores de Tumor/biosíntesis , Movimiento Celular , Proliferación Celular , Oxidasas Duales/biosíntesis , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/biosíntesis , Neoplasias Pancreáticas/enzimología , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Oxidasas Duales/genética , Femenino , Humanos , Masculino , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Pronóstico